Vasu Divi, MD

All Publications

• Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study. The Lancet. Oncology Gross, N. D., Miller, D. M., Khushalani, N. I., Divi, V., Ruiz, E. S., Lipson, E. J., Meier, F., Su, Y. B., Swiecicki, P. L., Atlas, J., Geiger, J. L., Hauschild, A., Choe, J. H., Hughes, B. G., Schadendorf, D., Patel, V. A., Homsi, J., Taube, J. M., Lim, A. M., Ferrarotto, R., Yoo, S. Y., Mathias, M., Han, H., Seebach, F., Lowy, I., Fury, M. G., Rischin, D. 2023

  Abstract

  We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival.This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing.Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths.For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need.Regeneron Pharmaceuticals and Sanofi.

  View details for DOI 10.1016/S1470-2045(23)00459-X

  View details for PubMedID 37875144

• Toll-like Receptor Agonists Are Unlikely to Provide Benefits in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Cancers Maddineni, S., Chen, M., Baik, F., Divi, V., Sunwoo, J. B., Finegersh, A. 2023; 15 (17)

  Abstract

  Recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has poor survival rates. Immunotherapy is the standard of care for R/M HNSCC, but objective responses occur in a minority of patients. Toll-like receptor (TLR) agonists promote antitumor immune responses and have been explored in clinical trials.A search for clinical trials using TLR agonists in HNSCC was performed under PRISMA guidelines. Data on patient characteristics, safety, and efficacy were collected and analyzed.Three phase 1b trials with 40 patients and three phase 2 trials with 352 patients studying TLR8 and TLR9 agonists in combination with other treatment regimens for HNSCC were included. In phase 2 trials, there was no significant change in the objective response rate (RR = 1.13, CI 0.80-1.60) or association with increased grade 3+ adverse events (RR = 0.91, CI 0.76-1.11) associated with TLR agonist use.TLR agonists do not appear to provide additional clinical benefits or increase adverse events in the treatment of HNSCC. Given these results across multiple clinical trials and drug regimens, it is unlikely that additional trials of TLR agonists will demonstrate clinical benefits in HNSCC.

  View details for DOI 10.3390/cancers15174386

  View details for PubMedID 37686661

• Oral cavity cancer in young, non-smoking, and non-drinking patients: a contemporary review. Critical reviews in oncology/hematology Tran, Q., Maddineni, S., Arnaud, E. H., Divi, V., Megwalu, U., Topf, M. C., Sunwoo, J. B. 2023: 104112

  Abstract

  Oral squamous cell carcinoma (OSCC) in non-smoking and non-drinking (NSND) individuals appears to be distinct from the traditional head and neck squamous cell carcinoma (HNSCC). The incidence of this subset is increasing, as are the number of studies examining its characteristics. NSND OSCC individuals tend to be younger (<45 years) compared to traditional HNSCC patients. The proportion of females in the NSND OSCC cohort is also higher. The tongue is the predominantly affected subsite. Studies have revealed several gene mutations and unique epigenomic profiles but no definitive genetic etiology. Transcriptomic analysis has not found any causative viral agents. Other proposed etiologies include chronic dental trauma, microbiome abnormalities, marijuana consumption, and genetic disorders. There are international efforts to determine the relative prognostic outcome of this unique cohort, but no consensus has been reached. Here, we review the incidence, demographics, subsite, possible etiologies, prognosis, and therapy implications of the NSND OSCC cohort.

  View details for DOI 10.1016/j.critrevonc.2023.104112

  View details for PubMedID 37633348

• Head-to-Head Comparison of ChatGPT Versus Google Search for Medical Knowledge Acquisition. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Ayoub, N. F., Lee, Y., Grimm, D., Divi, V. 2023

  Abstract

  OBJECTIVE: Chat Generative Pretrained Transformer (ChatGPT) is the newest iteration of OpenAI's generative artificial intelligence (AI) with the potential to influence many facets of life, including health care. This study sought to assess ChatGPT's capabilities as a source of medical knowledge, using Google Search as a comparison.STUDY DESIGN: Cross-sectional analysis.SETTING: Online using ChatGPT, Google Seach, and Clinical Practice Guidelines (CPG).METHODS: CPG Plain Language Summaries for 6 conditions were obtained. Questions relevant to specific conditions were developed and input into ChatGPT and Google Search. All questions were written from the patient perspective and sought (1) general medical knowledge or (2) medical recommendations, with varying levels of acuity (urgent or emergent vs routine clinical scenarios). Two blinded reviewers scored all passages and compared results from ChatGPT and Google Search, using the Patient Education Material Assessment Tool (PEMAT-P) as the primary outcome. Additional customized questions were developed that assessed the medical content of the passages.RESULTS: The overall average PEMAT-P score for medical advice was 68.2% (standard deviation [SD]: 4.4) for ChatGPT and 89.4% (SD: 5.9) for Google Search (p<.001). There was a statistically significant difference in the PEMAT-P score by source (p<.001) but not by urgency of the clinical situation (p=.613). ChatGPT scored significantly higher than Google Search (87% vs 78%, p=.012) for patient education questions.CONCLUSION: ChatGPT fared better than Google Search when offering general medical knowledge, but it scored worse when providing medical recommendations. Health care providers should strive to understand the potential benefits and ramifications of generative AI to guide patients appropriately.

  View details for DOI 10.1002/ohn.465

  View details for PubMedID 37529853

• Minimally Invasive Surgery in the United States, 2022: Understanding Its Value Using New Datasets. The Journal of surgical research Mattingly, A. S., Chen, M. M., Divi, V., Holsinger, F. C., Saraswathula, A. 2022; 281: 33-36

  Abstract

  INTRODUCTION: While minimally invasive surgery (MIS) has transformed the treatment landscape of surgical care, its utilization is not well understood. The newly released Nationwide Ambulatory Surgery Sample allows for more accurate estimates of MIS volume in the United States-in combination with inpatient datasets.MATERIALS AND METHODS: Multiple nationwide databases from the Healthcare Cost and Utilization Project (HCUP) were used: the Nationwide Ambulatory Surgery Sample and National Inpatient Sample. The volume of MIS and robotic procedures were calculated from 2016 to 2018. An online query system, HCUPNet, was queried for inpatient stays from 1993 to2014.RESULTS: In 2017, 9.8 million inpatient major operating room procedures were analyzed, of which 11.1% were MIS and 2.5% were robotic-assisted, compared with 9.6 million inpatient operating room procedures (11.2% MIS and 2.9% robotic-assisted) in 2018. There were 10.6, 10.6, and 10.7 million ambulatory procedures in 2016, 2017, and 2018, respectively. Ambulatory MIS procedures showed an increasing trend across years, representing 16.9%, 17.4%, and 18%, respectively. HCUPNet data revealed an increase in inpatient MIS cases from 529,811 (8.9%) in 1993 to 1,443,446 (20.7%) in2014.CONCLUSIONS: This study is the first to estimate national MIS volume across specialties in both inpatient and ambulatory hospital settings. We found a trend toward a higher proportion of MIS and robotic cases from 1997 to 2018. These data may help contribute to a more comprehensive understanding of MIS value within surgery and highlight limitations of current databases, especially when categorizing robotic cases on a national scale.

  View details for DOI 10.1016/j.jss.2022.08.006

  View details for PubMedID 36115146

• Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma. The New England journal of medicine Gross, N. D., Miller, D. M., Khushalani, N. I., Divi, V., Ruiz, E. S., Lipson, E. J., Meier, F., Su, Y. B., Swiecicki, P. L., Atlas, J., Geiger, J. L., Hauschild, A., Choe, J. H., Hughes, B. G., Schadendorf, D., Patel, V. A., Homsi, J., Taube, J. M., Lim, A. M., Ferrarotto, R., Kaufman, H. L., Seebach, F., Lowy, I., Yoo, S., Mathias, M., Fenech, K., Han, H., Fury, M. G., Rischin, D. 2022

  Abstract

  BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings.METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events.RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%).CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

  View details for DOI 10.1056/NEJMoa2209813

  View details for PubMedID 36094839

• Practice patterns in transoral robotic surgery: results of an American head and neck society survey. Journal of robotic surgery Holcomb, A. J., Kammer, R., Holman, A., Goldsmith, T., Divi, V., Starmer, H. M., Zenga, J., Li, R., Patel, U. A., Richmon, J. D. 2022

  Abstract

  To understand perioperative practices for transoral robotic surgery (TORS) among academic medical centers. An electronic cross-sectional survey was distributed to fellows and program directors participating in 49 American Head and Neck Society fellowships. Operative decisions, medical and swallowing management, and disposition planning were assessed. Thirty-eight responses were collected (77.6%). Twenty-three centers (60.5%) performed>25 cases annually with the remainder performing fewer. The da Vinci Si was the most commonly used platform (n=28, 73.7%). A majority of institutions advocated tailored resection to adequate margins (n=27, 71.1%) over fixed subunit-based resection (n=11, 28.9%). Most surgeons (n=29, 76.3%) performed neck dissection concurrent with TORS, and 89.5% (n=34) routinely ligated external carotid artery branches. A minority of institutions (n=17, 45.9%) endorsed a standardized TORS care pathway. Antibiotic choices and duration varied, the most common choice being ampicillin/sulbactam (n=21, 55.3%), and the most common duration being 24h or less (n=22, 57.9%). Multimodal analgesia was used at 36 centers (94.7%), steroids at 31 centers (81.6%), and pharmacologic venous thromboembolic prophylaxis at 29 centers (76.3%). Nasogastric feeding tubes were placed during surgery at 20 institutions (54.1%). Speech-language pathologists routinely performed postoperative swallow evaluations at 29 (78.4%) sites. Practice patterns are variable among institutions performing TORS. While certain surgical and postoperative practices were quite common, many institutions reported no standard TORS care pathway. Further understanding of the impact of individual practices on outcomes is necessary to develop evidence-based perioperative protocols for TORS.

  View details for DOI 10.1007/s11701-022-01448-z

  View details for PubMedID 35933632

• Posttreatment FDG-PET/CT Hopkins criteria predict locoregional recurrence after definitive radiotherapy for oropharyngeal squamous cell carcinoma. Head & neck Miller, J. A., Moradi, F., Sundaram, V., Liang, R., Zhang, C., Nguyen, N. K., Akhtar, F., Liu, Y., Ren, Y., Harandi, N., Weng, Y., Pollom, E. L., Colevas, A. D., Divi, V., Holsinger, F. C., Beadle, B. M., Le, Q., Gensheimer, M. F. 2022

  Abstract

  BACKGROUND: Metabolic response assessment for oropharyngeal squamous cell carcinoma (OPSCC) aids in identifying locoregional persistence/recurrence (LRR). The Hopkins Criteria are a standardized qualitative response assessment system using posttreatment FDG-PET/CT.METHODS: We conducted a retrospective cohort study of patients with node-positive OPSCC treated with definitive (chemo)radiotherapy. We assessed Hopkins Criteria performance for LRR, then developed and validated a competing-risks model.RESULTS: Between 2004 and 2018, 259 patients were included with median follow-up of 43months. The Hopkins Criteria sensitivity, specificity, negative predictive value, and accuracy were 68%, 88%, 95%, and 85%. The 36-month cumulative incidence of LRR was greater with positive scores (45% vs. 5%, HR 12.60, p<0.001). PET/CTs performed ≤10weeks after radiotherapy were associated with a four-fold increase in pathologically negative biopsies/surgeries (36% vs. 9%, p=0.03). The AUC for LRR was 0.89 using a model integrating the Hopkins score.CONCLUSIONS: The Hopkins Criteria predict LRR with high accuracy for OPSCC response assessment.

  View details for DOI 10.1002/hed.27160

  View details for PubMedID 35920790

• Impact of Histologic Risk Factors on Recurrence Rates for Oral Cavity Squamous Cell Carcinoma. The Annals of otology, rhinology, and laryngology Kligerman, M. P., Moon, P. K., Tusty, M., Cloutier, J. M., Ma, Y., Holsinger, C. F., Divi, V. 2022: 34894221111223

  Abstract

  This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC).Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence.One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence.TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

  View details for DOI 10.1177/00034894221111223

  View details for PubMedID 35899590

• Head and Neck Oncology Is on the National Quality Sidelines No Longer-Put Me in, Coach. JAMA otolaryngology-- head & neck surgery Graboyes, E. M., Divi, V., Moore, B. A. 2022

  View details for DOI 10.1001/jamaoto.2022.1389

  View details for PubMedID 35708673

• Reducing inpatient mortality in patients with cancer through multidisciplinary review and targeted interventions. Shah, M. P., Garrigues, S. K., Khaki, A., Hansen, J., Divi, V., Blayney, D. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300580

• Cutaneous branch of the nerve to the mylohyoid muscle: potential cause of postoperative sensory alteration in the submental area. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft Iwanaga, J., Ibaragi, S., Okui, T., Divi, V., Ohyama, Y., Watanabe, K., Kusukawa, J., Tubbs, R. S. 2022: 151934

  Abstract

  BACKGROUND: Previous studies suggest that the nerve to the mylohyoid muscle could have a cutaneous branch. However, its clinical relevance has rarely been discussed because there is insufficient evidence for it. Our aim in this study was to investigate the anatomy of the cutaneous branch of the nerve to the mylohyoid muscle and extend the discussion to surgical management.METHODS: Twenty sides from ten embalmed cadaveric heads were dissected to identify the cutaneous branch of the nerve to the mylohyoid muscle. The cutaneous branch was traced up to its termination.RESULTS: The cutaneous branch was observed in 90% and classified into types I and II. In type I, the terminal trunk reached the anterior belly of the digastric muscle. In type II there were two types of terminal trunks, superior and inferior branches, which were identified on all sides. The number of the terminal trunk was one in 23.1% (type I; 6/26) and two in 76.9% (type II; 20/26).The terminal points of the cutaneous branch were all located within a 3cm*2cm rectangular segment in the center of the submental area.CONCLUSIONS: We propose a new dermatome including the nerve to the mylohyoid muscle in the center. Understanding the cutaneous branch of the nerve could help surgeons to prevent iatrogenic sensory loss of the submental area.

  View details for DOI 10.1016/j.aanat.2022.151934

  View details for PubMedID 35307555

• Clinician Attitudes and Beliefs About Deintensifying Head and Neck Cancer Surveillance. JAMA otolaryngology-- head & neck surgery Chen, M. M., Mott, N. M., Miller, J., Kazemi, R., Stover, M., Graboyes, E. M., Divi, V., Malloy, K. M., Wallner, L. P., Pitt, S. C., Dossett, L. A. 2021

  Abstract

  Importance: Surveillance imaging and visits are costly and have not been shown to improve oncologic outcomes for patients with head and neck cancer (HNC). However, the benefit of surveillance visits may extend beyond recurrence detection. To better understand surveillance and potentially develop protocols to tailor current surveillance paradigms, it is important to elicit the perspectives of the clinicians who care for patients with HNC.Objective: To characterize current surveillance practices and explore clinician attitudes and beliefs on deintensifying surveillance for patients with HNC.Design, Setting, and Participants: This qualitative study was performed from January to March 2021. Guided by an interpretive description approach, interviews were analyzed to produce a thematic description. Data analysis was performed from March to April 2021. Otolaryngologists and radiation oncologists were recruited using purposive and snowball sampling strategies.Main Outcomes and Measures: The main outcomes were current practice, attitudes, and beliefs about deintensifying surveillance and survivorship as well as patients' values and perspectives collected from interviews of participating physicians.Results: Twenty-one physicians (17 [81%] men) were interviewed, including 13 otolaryngologists and 8 radiation oncologists with a median of 8 years (IQR, 5-20 years) in practice. Twelve participants (57%) stated their practice comprised more than 75% of patients with HNC. Participants expressed that there was substantial variation in the interpretation of the surveillance guidelines. Participants were open to the potential for deintensification of surveillance or incorporating symptom-based surveillance protocols but had concerns that deintensification may increase patient anxiety and shift some of the burden of recurrence monitoring to patients. Patient and physician peace of mind, the importance of maintaining the patient-physician relationship, and the need for adequate survivorship and management of treatment-associated toxic effects were reported to be important barriers to deintensifying surveillance.Conclusions and Relevance: In this qualitative study, clinicians revealed a willingness to consider altering cancer surveillance but expressed a need to maintain patient and clinician peace of mind, maintain the patient-clinician relationship, and ensure adequate monitoring of treatment-associated toxic effects and other survivorship concerns. These findings may be useful in future research on the management of posttreatment surveillance.

  View details for DOI 10.1001/jamaoto.2021.2824

  View details for PubMedID 34734995

• Timing of postoperative oral feeding after head and neck mucosal free flap reconstruction. Laryngoscope investigative otolaryngology Stramiello, J., Nuyen, B., Saraswathula, A., Blumenfeld, L., Divi, V., Rosenthal, E., Orosco, R., Starmer, H. M. 2021; 6 (5): 1031-1036

  Abstract

  Fistula remains a common complication of upper aerodigestive tract reconstruction. Optimal timing of oral feeding is unknown and the impact of early feeding on swallow function and fistula rates remains controversial. The purpose of this study is to better understand the effects of "early feeding" on fistula rate and swallow in patients with free flap reconstruction of upper aerodigestive tract defects.Retrospective cohort study. One hundred and four patients undergoing free flap reconstruction of mucosalized head and neck defects. Two groups, early feeding (oral intake on or before postoperative day 5) and late-feeding (oral intake after postoperative day 5). Primary outcome was incidence of salivary fistula. Secondary outcomes included Functional Oral Intake Scale scores.Fistula rate was 16.5% in late-feeding group and 0% in early-feeding group (P = .035). Patients who were fed early had an association with progression to a full oral diet by 30 days (P = .027).This cohort analysis suggests that in properly selected patients with free flap reconstruction for mucosal defects, early feeding may not increase risk of salivary fistula and may improve swallow functional outcomes earlier. Level of Evidence: 3.

  View details for DOI 10.1002/lio2.655

  View details for PubMedID 34667846

  View details for PubMedCentralID PMC8513441

• Risk factors for ED visits and admissions during outpatient chemotherapy in head and neck cancer Shukla, N., Saraswathula, A., Khan, S. A., Divi, V. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.223

  View details for Web of Science ID 000707130200219

• Preventing 30-day readmissions for patients with cancer: A root-cause analysis Shah, M. P., Tan, I., Garrigues, S. K., Hansen, J., Blayney, D. W., Divi, V. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.226

  View details for Web of Science ID 000707130200222

• Practice patterns of virtual surgical planning: Survey of the reconstructive section of the American Head and Neck Society. American journal of otolaryngology Miles, B. A., McMullen, C. P., Sweeny, L., Zenga, J., Li, R., Divi, V., Jackson, R., Patel, U. A., Richmon, J. D. 2021; 43 (1): 103225

  Abstract

  PURPOSE: Virtual surgical planning (VSP), with custom made implants and guides represents a recent major advance. Nonetheless, knowledge related to practice patterns is limited. The purpose of this study was to provide data from the AHNS Reconstruction Section related to practice patterns, perceived value of VSP, as well as elucidate specific situations which represent high value for the application of VSP.MATERIALS AND METHODS: A multi-center web-based survey consisting of 30 questions regarding practice patterns related to VSP practices delivered via email to 203 members of the AHNS Reconstructive Surgery Section at institutions across North America.RESULTS: There was a 34% response rate (70/203). A majority of the respondents (96%) used VSP in approximately 50% of their mandibular reconstruction cases, and in 42% of maxillary cases. 46% reported using patient specific implants >75% of cases. Respondents estimated that ~17% of patients received dental implant reconstruction. The majority of respondents (71.0%) did not know the cost of VSP at their institution. The remaining respondents indicated the average cost was $6680 per case. VSP was felt to be necessary as a teaching tool by 55.9%.CONCLUSIONS: Our results demonstrate that a majority of respondents frequently utilize VSP in their practice for head and neck reconstruction. Complex, multi-unit reconstructions were felt to offer the greatest value when utilizing VSP. Future work should focus on increasing the rates of dental implant reconstruction in this population, optimizing value of VSP with careful case selection, and understanding the educational value and costs of these platforms.

  View details for DOI 10.1016/j.amjoto.2021.103225

  View details for PubMedID 34571439

• Timing of postoperative oral feeding after head and neck mucosal free flap reconstruction LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY Stramiello, J., Nuyen, B., Saraswathula, A., Blumenfeld, L., Divi, V., Rosenthal, E., Orosco, R., Starmer, H. M. 2021

  View details for DOI 10.1002/lio2.655

  View details for Web of Science ID 000695542500001

• Development of a Mobile Health App (TOGETHERCare) to Reduce Cancer Care Partner Burden: Product Design Study. JMIR formative research Oakley-Girvan, I., Davis, S. W., Kurian, A., Rosas, L. G., Daniels, J., Palesh, O. G., Mesia, R. J., Kamal, A. H., Longmire, M., Divi, V. 2021; 5 (8): e22608

  Abstract

  Approximately 6.1 million adults in the United States serve as care partners for cancer survivors. Studies have demonstrated that engaging cancer survivors and their care partners through technology-enabled structured symptom collection has several benefits. Given the high utilization of mobile technologies, even among underserved populations and in low resource areas, mobile apps may provide a meaningful access point for all stakeholders for symptom management.We aimed to develop a mobile app incorporating user preferences to enable cancer survivors' care partners to monitor the survivors' health and to provide care partner resources.An iterative information gathering process was conducted that included (1) discussions with 138 stakeholders to identify challenges and gaps in survivor home care; (2) semistructured interviews with clinicians (n=3), cancer survivors (n=3), and care partners (n=3) to identify specific needs; and (3) a 28-day feasibility field test with seven care partners.Health professionals noted the importance of identifying early symptoms of adverse events. Survivors requested modules on medication, diet, self-care, reminders, and a version in Spanish. Care partners preferred to focus primarily on the patient's health and not their own. The app was developed incorporating quality-of-life surveys and symptom reporting, as well as resources on home survivor care. Early user testing demonstrated ease of use and app feasibility.TOGETHERCare, a novel mobile app, was developed with user input to track the care partner's health and report on survivor symptoms during home care. The following two clinical benefits emerged: (1) reduced anxiety among care partners who use the app and (2) the potential for identifying survivor symptoms noted by the care partner, which might prevent adverse events.ClinicalTrials.gov NCT04018677; https://clinicaltrials.gov/ct2/show/NCT04018677.

  View details for DOI 10.2196/22608

  View details for PubMedID 34398787

• Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment. Proceedings of the National Academy of Sciences of the United States of America Moreno-Nieves, U. Y., Tay, J. K., Saumyaa, S., Horowitz, N. B., Shin, J. H., Mohammad, I. A., Luca, B., Mundy, D. C., Gulati, G. S., Bedi, N., Chang, S., Chen, C., Kaplan, M. J., Rosenthal, E. L., Holsinger, F. C., Divi, V., Baik, F. M., Sirjani, D. B., Gentles, A. J., Newman, A. M., Freud, A. G., Sunwoo, J. B. 2021; 118 (28)

  Abstract

  Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

  View details for DOI 10.1073/pnas.2101169118

  View details for PubMedID 34244432

• The effect of reconstruction on positive margin rates in oral cancer: Using length of stay as a proxy measure for flap reconstruction in a national database. American journal of otolaryngology Campbell, D. A., Pipkorn, P., Divi, V., Stadler, M., Massey, B., Campbell, B., Richmon, J. D., Graboyes, E., Puram, S., Zenga, J. 2021; 42 (5): 103012

  Abstract

  PURPOSE: Planned flap reconstruction, allowing aggressive resections of oral cavity squamous cell carcinoma (OCSCC), may decrease positive surgical margins. The purpose of this study was to determine if length of stay (LOS), as a proxy measure for flap reconstruction, is associated with positive margin rates in OCSCC.MATERIALS AND METHODS: Data from the National Cancer Database was retrospectively collected for patients undergoing surgery for previously untreated clinical T1-3 OCSCC. Post-operative LOS was dichotomized between ≤4 and >4days as a proxy measure for whether patients may have received flap reconstruction. Patients with LOS >4days represent a diverse group, but those with a LOS ≤4days are less likely to have undergone an oral cavity flap reconstruction.RESULTS: 10,107 patients were included, of which 5290 (52%) were clinical T1 and 4852 (48%) were clinical T2-3. 771 (8%) patients had a positive surgical margin. On multivariable logistic regression analysis, LOS ≤4days was significantly associated with a positive margin resection in patients with clinical T2-3 tumors (OR 1.68, 95%CI 1.37-2.06) compared to patients with LOS >4days. LOS was not associated with surgical margin status in patients with clinical T1 disease (OR 0.76, 95%CI 0.55-1.06). Patients with positive margin resections demonstrated worse overall survival (cT1: OR 1.35, 95%CI 1.06-1.72; cT2-3: OR 1.52, 95%CI 1.33-1.74).CONCLUSIONS: LOS >4days after oral cavity cancer resection was significantly associated with negative surgical margins in clinical T2-3 oral cavity cancer, suggesting the possibility that patients undergoing flap reconstruction after resection have fewer positive surgical margins.

  View details for DOI 10.1016/j.amjoto.2021.103012

  View details for PubMedID 33857781

• End-of-Life Practice Patterns in Head and Neck Cancer. The Laryngoscope Vukkadala, N., Fardeen, T., Ramchandran, K., Divi, V. 2021

  Abstract

  OBJECTIVE/HYPOTHESIS: Despite the importance of symptom management and end-of-life (EOL) care in head and neck cancers (HNC), there is little literature on care practices in this population. This study examines EOL care practice patterns using nationally established metrics.STUDY DESIGN: Retrospective chart review.METHODS: Review of HNC patients who were actively followed and treated (defined as one clinic note within 90days, two within preceding 9months, and having received treatment at our institution) and died between January 1, 2017 and December 31, 2018. The cohort was reviewed for performance on Quality Oncology Practice Initiative (QOPI) and other metrics.RESULTS: Of 133 patients identified, 52 met inclusion criteria. The average age at death was 69.8years. About 59% had distant metastases, 30% had locoregional disease, 11% were undergoing primary treatment. Twenty-three percentage received chemotherapy within the last 14days of life. Fifty percentage of patients were admitted in the last 30days of life, and 33% died in the hospital. Fifty-four percentage of patients had either Physician Orders for Life-Sustaining Treatment or Advanced Directive on file. Eighty-one percentage of patients had any type of goals of care discussion documented. Sixty-five percentage of all patients received referrals to palliative care and 46% of all patients enrolled in hospice. The median days in hospice was 12. Having a goals of care discussion was significantly associated with utilization of palliative and hospice care.CONCLUSIONS: Provider-documented goals of care discussions were strongly correlated to referrals and enrollment in palliative and hospice care. Areas for improvement include better documentation of treatment directives and reducing low-utility treatments.LEVEL OF EVIDENCE: 4 Laryngoscope, 2021.

  View details for DOI 10.1002/lary.29423

  View details for PubMedID 33491219

• Postoperative Observation Versus Radiotherapy for Pathologic N1 Oral Cavity Squamous Cell Carcinoma. American journal of clinical oncology Xiang, M. n., Holsinger, F. C., Gensheimer, M. F., Divi, V. n., Pollom, E. L., Colevas, A. D., Le, Q. T., Beadle, B. M. 2021; Publish Ahead of Print

  Abstract

  To investigate the benefit of postoperative radiotherapy (PORT) for low-volume (pN1) nodal disease after resection of oral cavity squamous cell carcinoma.The National Cancer Database was queried for adults with nonmetastatic squamous cell carcinoma of the oral cavity treated by surgical resection with pathologic stage T1-2 N0-2 (American Joint Committee on Cancer 7th edition) and with the maximal exclusion of standard indications for PORT. Overall survival was compared within pN1 for observation versus PORT and then compared for pN1 versus pN0 and versus pN2 stratified by receipt of observation or PORT. Multivariable Cox regression was used to adjust for potential confounders between PORT and survival, including comorbidity and age.Overall 5017 pN0, 530 pN1, and 253 pN2 patients were identified, of whom 9%, 35%, and 64% received PORT, respectively. Within the pN1 cohort, PORT was associated with improved survival versus observation (adjusted hazard ratio, 0.66; 95% confidence interval, 0.46-0.97; P=0.03). Among observed patients, the prognosis of pN1 was equivalent to pN2 and inferior to pN0; in contrast, among patients treated with PORT, the prognosis of pN1 was equivalent to pN0 and superior to pN2. Without PORT, pN1 remained an adverse risk factor relative to pN0 regardless of the depth of invasion, lymph node size, lymph node location, and extent of lymph node dissection.PORT was associated with a survival benefit compared with observation. Notably, pN1 was an adverse risk factor relative to pN0 if, and only if, patients did not receive PORT, suggesting pN1 by itself may be an indication for PORT.

  View details for DOI 10.1097/COC.0000000000000792

  View details for PubMedID 33417322

• Development of a Mobile Health App (TOGETHERCare) to Reduce Cancer Care Partner Burden: Product Design Study JMIR Formative Research Oakley-Girvan, I., Davis, S. W., Kurian, A. W., Rosas, L. G., Daniels, J., Palesh, O. G., Mesia, R. J., Kamal, A. H., Longmire, M., Divi, V. 2021; 5 (8)

  View details for DOI 10.2196/22608

• Association Between Immunosuppression and Outcomes in Oral Cavity Squamous Cell Carcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Chang, J., Sunwoo, J. B., Shah, J. L., Hara, W., Hong, J., Colevas, A. D., Divi, V. 2020: 194599820960146

  Abstract

  OBJECTIVE: To assess the effect of immunosuppression on recurrence and mortality outcomes in oral cavity squamous cell carcinoma (SCC) after initial surgical treatment.STUDY DESIGN: Retrospective cohort study.SETTING: A single academic tertiary referral center.METHODS: Patients with oral cavity SCC treated with initial surgery were included. Immunosuppressed versus nonimmunosuppressed groups were compared. Primary end points were 5-year overall recurrence and all-cause mortality. Secondary end points were recurrence subtypes (local, regional, and distant) and disease-specific mortality.RESULTS: Of 803 patients with oral cavity SCC, 71 (9%) were immunosuppressed from therapeutic drug use (n = 48) or systemic disease (n = 23). The immunosuppressed group consisted of patients with a history of transplant (21%), autoimmune or pulmonary disorder (45%), hematologic malignancy or myeloproliferative disorder (30%), and HIV infection (3%). After adjusting for baseline variables of age, sex, comorbidities, pathologic tumor characteristics, and adjuvant treatment, all recurrence and mortality outcomes were worse in the immunosuppressed group. The multivariate-adjusted hazard ratio for overall recurrence was 2.16 (95% CI, 1.50-3.12; P < .01), and all-cause mortality was 1.79 (95% CI, 1.15-2.78; P < .01) in Cox regression analysis. The 2 groups were then matched in a 1:5 ratio according to the same baseline variables. All end points apart from disease-specific mortality were significantly worse in the immunosuppressed group after matching.CONCLUSION: This study demonstrates that immunosuppression is associated with poor outcomes in oral cavity SCC, with an approximate 2-fold increase in rates of recurrence and mortality. Future studies are needed to assess the risks and benefits of adjusting therapeutic immunosuppression in this population.

  View details for DOI 10.1177/0194599820960146

  View details for PubMedID 32957854

• Development and validation of a surgical prioritization and ranking tool and navigation aid for head and neck cancer (SPARTAN-HN) in a scarce resource setting: Response to the COVID-19 pandemic. Cancer de Almeida, J. R., Noel, C. W., Forner, D., Zhang, H., Nichols, A. C., Cohen, M. A., Wong, R. J., McMullen, C., Graboyes, E. M., Divi, V., Shuman, A. G., Rosko, A. J., Lewis, C. M., Hanna, E. Y., Myers, J., Paleri, V., Miles, B., Genden, E., Eskander, A., Enepekides, D. J., Higgins, K. M., Brown, D., Chepeha, D. B., Witterick, I. J., Gullane, P. J., Irish, J. C., Monteiro, E., Goldstein, D. P., Gilbert, R. 2020

  Abstract

  BACKGROUND: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, access to surgical care for patients with head and neck cancer (HNC) is limited and unpredictable. Determining which patients should be prioritized is inherently subjective and difficult to assess. The authors have proposed an algorithm to fairly and consistently triage patients and mitigate the risk of adverse outcomes.METHODS: Two separate expert panels, a consensus panel (11 participants) and a validation panel (15 participants), were constructed among international HNC surgeons. Using a modified Delphi process and RAND Corporation/University of California at Los Angeles methodology with 4 consensus rounds and 2 meetings, groupings of high-priority, intermediate-priority, and low-priority indications for surgery were established and subdivided. A point-based scoring algorithm was developed, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN). Agreement was measured during consensus and for algorithm scoring using the Krippendorff alpha. Rankings from the algorithm were compared with expert rankings of 12 case vignettes using the Spearman rank correlation coefficient.RESULTS: A total of 62 indications for surgical priority were rated. Weights for each indication ranged from -4 to +4 (scale range; -17 to 20). The response rate for the validation exercise was 100%. The SPARTAN-HN demonstrated excellent agreement and correlation with expert rankings (Krippendorff alpha, .91 [95% CI, 0.88-0.93]; and rho, 0.81 [95% CI, 0.45-0.95]).CONCLUSIONS: The SPARTAN-HN surgical prioritization algorithm consistently stratifies patients requiring HNC surgical care in the COVID-19 era. Formal evaluation and implementation are required.LAY SUMMARY: Many countries have enacted strict rules regarding the use of hospital resources during the coronavirus disease 2019 (COVID-19) pandemic. Facing delays in surgery, patients may experience worse functional outcomes, stage migration, and eventual inoperability. Treatment prioritization tools have shown benefit in helping to triage patients equitably with minimal provider cognitive burden. The current study sought to develop what to the authors' knowledge is the first cancer-specific surgical prioritization tool for use in the COVID-19 era, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN). This algorithm consistently stratifies patients requiring head and neck cancer surgery in the COVID-19 era and provides evidence for the initial uptake of the SPARTAN-HN.

  View details for DOI 10.1002/cncr.33114

  View details for PubMedID 32780426

• Significance of Nodal Metastasis in Parotid Gland Acinar Cell Carcinoma. The Laryngoscope Moon, P., Tusty, M., Divi, V., Megwalu, U. C. 2020

  Abstract

  OBJECTIVES: To evaluate the rate of lymph node metastasis in parotid gland acinar cell carcinoma, to identified factors associated with increased risk of metastasis, and to evaluate the effect of nodal metastasis on survival.METHODS: This is a retrospective cohort study utilizing data from a large population-based cancer database. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 database. The study cohort included patients with parotid gland acinar cell carcinoma diagnosed between 2000 and 2015.RESULTS: The overall rate of lymph node metastasis was 6.8%. T3/T4 (OR 6.17, 95% CI, 3.03 to 13.16) disease along with High Grade (OR 15.95) disease were associated with increased risk of nodal metastasis. Non-white, non-Black race was associated with decreased risk. Age and sex were not associated with nodal metastasis. Nodal metastasis was associated with worse OS (HR 6.27, 95% CI, 3.85 to 10.20) and DSS (HR 6.96, 95% CI, 3.81 to 12.73) after adjusting for covariates.CONCLUSION: Parotid gland acinar cell carcinoma carries a low risk of nodal metastasis. Both advanced T stage and high grade are associated with increased risk of nodal metastasis. Nodal metastasis is associated with decreased overall survival.LEVEL OF EVIDENCE: 3 Laryngoscope, 2020.

  View details for DOI 10.1002/lary.28966

  View details for PubMedID 32770798

• Correction to: Compensatory motion scaling for time-delayed robotic surgery. Surgical endoscopy Orosco, R. K., Lurie, B., Matsuzaki, T., Funk, E. K., Divi, V., Holsinger, F. C., Hong, S., Richter, F., Das, N., Yip, M. 2020

  Abstract

  This article was updated to correct Tokio Matsuzaki's name in author listing.

  View details for DOI 10.1007/s00464-020-07825-9

  View details for PubMedID 32696146

• Compensatory motion scaling for time-delayed robotic surgery. Surgical endoscopy Orosco, R. K., Lurie, B., Matsusaki, T., Funk, E. K., Divi, V., Holsinger, F. C., Hong, S., Richter, F., Das, N., Yip, M. 2020

  Abstract

  BACKGROUND: Round trip signal latency, or time delay, is an unavoidable constraint that currently stands as a major barrier to safe and efficient remote telesurgery. While there have been significant technological advancements aimed at reducing the time delay, studies evaluating methods of mitigating the negative effects of time delay are needed. Herein, we explored instrument motion scaling as a method to improve performance in time-delayed robotic surgery.METHODS: This was a robotic surgery user study using the da Vinci Research Kit system. A ring transfer task was performed under normal circumstances (no added time delay), and with 250ms, 500ms, and 750ms delay. Robotic instrument motion scaling was modulated across a range of values (- 0.15, - 0.1, 0,+0.1,+0.15), with negative values indicating less instrument displacement for a given amount of operator movement. The primary outcomes were task completion time and total errors. Three-dimensional instrument movement was compared against different motion scales using dynamic time warping to demonstrate the effects of scaling.RESULTS: Performance declined with increasing time delay. Statistically significant increases in task time and number of errors were seen at 500ms and 750ms delay (p<0.05). Total errors were positively correlated with task time on linear regression (R=0.79, p<0.001). Under 750ms delay, negative instrument motion scaling improved error rates. Negative motion scaling trended toward improving task times toward those seen in non-delayed scenarios. Improvements in instrument path motion were seen with the implementation of negative motion scaling.CONCLUSIONS: Under time-delayed conditions, negative robotic instrument motion scaling yielded fewer surgical errors with slight improvement in task time. Motion scaling is a promising method of improving the safety and efficiency of time-delayed robotic surgery and warrants further investigation.

  View details for DOI 10.1007/s00464-020-07681-7

  View details for PubMedID 32514831

• Tracheostomy Complications in the Emergency Department: A National Analysis of 38,271 Cases. ORL; journal for oto-rhino-laryngology and its related specialties Kligerman, M. P., Saraswathula, A., Sethi, R. K., Divi, V. 2020: 1–8

  Abstract

  BACKGROUND: Greater than 100,000 tracheotomies are performed annually in the USA, yet little is known regarding patients who present to the emergency department (ED) with tracheostomy complications.OBJECTIVES: To characterize patient and hospital characteristics, outcomes, and charges associated with tracheostomy complications and to identify predictors of admission and mortality.METHODS: The 2009-2011 Nationwide Emergency Department Sample (NEDS) was queried for patients with a principle diagnosis of tracheostomy complication. A descriptive analysis was performed and multivariable logistic regression was used to identify predictors of admission and mortality.RESULTS: A total of 69,371 nationwide visits to the ED had tracheostomy complication as an associated ICD-9 diagnosis, of which 55.2% (n = 38,293) carried a primary diagnosis of tracheostomy complication. Unspecified tracheostomy complications were most common (61.4%), followed by mechanical complications (31.3%), and lastly by tracheostomy infections (7.3%). Pediatric patients were significantly more likely to have tracheostomy infections than adults (p < 0.0001). A total of 35.5% of patients with tracheostomy complications were admitted to the hospital, and death occurred with 1.4% of visits. Patients from higher-income ZIP codes had increased odds of admission (adjusted odds ratio [OR]: 1.35; p = 0.0009), as did patients with tracheostomy infections (OR: 4.425; p < 0.0001). Patients with tracheostomy infections (OR: 3.14; p = 0.0062) and unspecified tracheostomy complications (OR: 2.00; p = 0.0076) had increased odds of mortality.CONCLUSION: These findings may help improve overall outcomes amongst patients with tracheostomies by preventing unnecessary ED admissions and improving healthcare provider preparedness and awareness.

  View details for DOI 10.1159/000505130

  View details for PubMedID 32036376

• Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer MOLECULAR IMAGING AND BIOLOGY Nishio, N., van den Berg, N. S., van Keulen, S., Martin, B. A., Fakurnejad, S., Zhou, Q., Lu, G., Chirita, S. U., Kaplan, M. J., Divi, V., Colevas, A. D., Rosenthal, E. L. 2020; 22 (1): 156–64

  View details for DOI 10.1007/s11307-019-01358-x

  View details for Web of Science ID 000513265700021

• The Impact of Hospital Quality on Thyroid Cancer Survival. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Megwalu, U. C., Ma, Y. n., Hernandez-Boussard, T. n., Divi, V. n., Gomez, S. L. 2020: 194599819900760

  Abstract

  To develop a composite measure of thyroid cancer-specific hospital quality and to evaluate the association between hospital quality and survival in patients with well-differentiated thyroid cancer.Retrospective cohort study.Population-based cancer database.Data were extracted from the California Cancer Registry data set linked with discharge records and hospital characteristics from the California Office of Statewide Health Planning and Development. The study cohort comprised adult patients with well-differentiated thyroid cancer diagnosed between January 1, 2004, and December 31, 2015. Principal component analysis, incorporating hospital volume, adherence to national guidelines, and accreditation/certification status, was used to generate a composite thyroid cancer-specific hospital quality score.Treatment in hospitals ranked in the highest quartile of quality was associated with improved overall survival (OS) (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.67-0.98) and disease-specific survival (DSS) (HR, 0.72; 95% CI, 0.54-0.98). Treatment in hospitals meeting the combined metric of 10 or more thyroid cancer cases/year and 80% of patients with high-risk tumors treated with total/near-total thyroidectomy was associated with improved OS (HR, 0.80; 95% CI, 0.70-0.90) and DSS (HR, 0.77; 95% CI, 0.64-0.94).Treatment in high-quality hospitals is associated with improved survival outcomes in patients with thyroid cancer. These findings are important because they help identify hospitals that are better suited to treat patients with thyroid cancer and provide actionable targets for quality improvement.

  View details for DOI 10.1177/0194599819900760

  View details for PubMedID 31961755

• Radiographic surveillance of abdominal free fat graft in complex parotid pleomorphic adenomas: A case series. Heliyon Lee, Y. J., Fischbein, N. J., Megwalu, U. n., Baik, F. M., Divi, V. n., Kaplan, M. J., Sirjani, D. B. 2020; 6 (5): e03894

  Abstract

  Free abdominal fat transfer is commonly used to restore facial volume and improve cosmesis after parotidectomy for pleomorphic adenomas. We describe the radiographic characteristics of these grafts on follow-up imaging.Medical records of four patients who underwent parotidectomy with abdominal fat graft in 2016 and had follow up imaging available were retrospectively analyzed. An otolaryngologist and neuroradiologist reviewed imaging studies, evaluated the fat grafts, and monitored for residual or recurrent disease.The abdominal fat was successfully grafted in all four patients. Post-operative baseline magnetic resonance imaging and additional surveillance imaging showed fat grafts with minimal volume loss. However, there was development of irregular enhancement consistent with fat necrosis in two of the four patients.Radiographic surveillance of free fat graft reconstruction after pleomorphic adenoma resection shows minimal contraction in size but development of fat necrosis. Recognition of expected changes should help avoid confusion with residual or recurrent disease, reassuring both patient and treating physician.

  View details for DOI 10.1016/j.heliyon.2020.e03894

  View details for PubMedID 32395660

  View details for PubMedCentralID PMC7210407

• Physician-Assisted Suicide for Patients with Head and Neck Cancer. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Kligerman, M. P., Divi, V. n. 2020: 194599820923610

  Abstract

  A retrospective observational cohort study was conducted using data from Oregon's Death with Dignity Act (DWDA) to characterize patients with head and neck cancer (HNC) who seek physician-assisted suicide (PAS). Between 1998 and 2018, a total of 57 patients with HNC received DWDA prescriptions, of whom 39 (68.4%) died by administration of the prescribed medication. There were no associated complications with medication administration. The most commonly involved subsites were oral cavity (33.3%) and oropharynx (30.8%), and the most commonly cited end-of-life concerns were loss of ability to engage in activities that make life enjoyable (79.5%) and loss of autonomy (74.4%). There were no differences in age, race, marital status, or hospice enrollment rates between patients with HNC who died by administration and those who were prescribed but did not administer the medication. Patients who died by administration were generally less educated as compared to those who were prescribed but did not administer the medication (P = .015).

  View details for DOI 10.1177/0194599820923610

  View details for PubMedID 32427518

• Abstract 2033: Reducing cancer caregiver burden: A user-centered design approach for an mHealth app American Association for Cancer Research Annual Meeting Oakley-Girvan, I., Divi, V., Palesh, O., Daniels, J., Goldman Rosas, L., O'Brien, D., Davis, S. W., Kamal, A. H., Kurian, A. W., Longmire, M. R. 2020

  View details for DOI 10.1158/1538-7445.AM2020-2033

• Effect of Medical Scribes on Outpatient Oncology Visits at a Multidisciplinary Cancer Center. Journal of oncology practice Gao, R. W., Dugala, A., Maxwell, J., Falconer, P., Birkeland, A. C., Divi, V., Rosenthal, E. L. 2019: JOP1900307

  Abstract

  PURPOSE: The use of medical scribes has emerged as a strategy to increase clinic workflow efficiency and reduce physician burnout. While oncology clinics may be ideally suited to scribe integration because of the high burden of documentation, oncology-specific scribe research has been limited. The objective of this study was to determine the effect of scribe integration on clinic workflow efficiency and physician satisfaction and quality of life in outpatient oncology clinics.METHODS: We conducted a retrospective, concurrent qualitative and quantitative analysis of patient visit durations and survey data for 129 attending physicians affiliated with an academic hospital's cancer center between January 2017 and January 2019. Thirty-three physicians were paired with scribes in each physician's individual clinic or clinics.RESULTS: In terms of clinic efficiency, physicians with scribes had a 12.1% decrease in their overall average patient visit duration compared with their own time before receiving a scribe (P < .0001) and spent significantly less time completing charts at the end of the day (P = .04). Compared with their peers, oncologists with scribes showed a 10%-20% decrease in the duration of all patient visits. Scribes also contributed to patient care, as shown by 90% of physicians surveyed who strongly agreed that they spent less time at the computer and more time with patients; 100% of physicians surveyed strongly agreed that scribes improved their quality of life.CONCLUSION: The integration of medical scribes into oncology clinics across several oncologic disciplines has the potential to reduce burnout through increasing physician satisfaction and quality of life, improving patient care, and streamlining clinic workflow.

  View details for DOI 10.1200/JOP.19.00307

  View details for PubMedID 31804877

• Wound Complications in Head and Neck Squamous Cell Carcinomas After Anti-PD-1 Therapy LARYNGOSCOPE Hwang, V., Mendez, E., Chow, L. M., Futran, N., Andersen, P., Li, R., Divi, V., Rodriguez, C. P. 2019; 129 (12): E428–E433

  View details for DOI 10.1002/lary.27902

  View details for Web of Science ID 000497260600004

• Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer. Nature communications Nishio, N., van den Berg, N. S., van Keulen, S., Martin, B. A., Fakurnejad, S., Teraphongphom, N., Chirita, S. U., Oberhelman, N. J., Lu, G., Horton, C. E., Kaplan, M. J., Divi, V., Colevas, A. D., Rosenthal, E. L. 2019; 10 (1): 5044

  Abstract

  Identification of lymph node (LN) metastasis is essential for staging of solid tumors, and as a result, surgeons focus on harvesting significant numbers of LNs during ablative procedures for pathological evaluation. Isolating those LNs most likely to harbor metastatic disease can allow for a more rigorous evaluation of fewer LNs. Here we evaluate the impact of a systemically injected, near-infrared fluorescently-labeled, tumor-targeting contrast agent, panitumumab-IRDye800CW, to facilitate the identification of metastatic LNs in the ex vivo setting for head and neck cancer patients. Molecular imaging demonstrates a significantly higher mean fluorescence signal in metastatic LNs compared to benign LNs in head and neck cancer patients undergoing an elective neck dissection. Molecular imaging to preselect at-risk LNs may thus allow a more rigorous examination of LNs and subsequently lead to improved prognostication than regular neck dissection.

  View details for DOI 10.1038/s41467-019-13076-7

  View details for PubMedID 31695030

• Impact of mortality reviews on supportive care utilization, end-of-life care, and inpatient mortality. Karimi, Y., Divi, V., Srinivas, S., Smith, A., Hansen, J., Tokareva, I., Tulu, Z., Hedlin, H., Fronk, J., Rosenthal, E., Blayney, D. W. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.31_suppl.45

  View details for Web of Science ID 000518224200044

• Assessing Care Value for Older Patients Receiving Radiotherapy With or Without Cisplatin or Cetuximab for Locoregionally Advanced Head and Neck Cancer. JAMA otolaryngology-- head & neck surgery Saraswathula, A., Chen, M. M., Colevas, A. D., Divi, V. 2019

  Abstract

  Importance: Clinicians frequently use radiotherapy with cetuximab over radiotherapy only or radiotherapy with cisplatin because of a perceived survival and tolerability advantage, but scant data are available to support this perception.Objective: To measure the 3 aspects of value (quality, outcomes, and cost) in older patients receiving radiotherapy only, radiotherapy with cisplatin, or radiotherapy with cetuximab for locoregionally advanced head and neck cancer.Design, Setting, and Participants: For this cohort study, patient records were obtained from the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare outcomes and claims database from January 1, 2004, to December 31, 2014. Participants were 65 years or older; received a diagnosis between 2006 and 2013 of stages III to IVB head and neck cancer; had only 1 cancer on record; and did not undergo surgical intervention. Data analysis was conducted from February 5, 2018, to March 27, 2019.Exposures: Patients were divided into exposure arms on the basis of their first-line therapy or identified chemoradiotherapy and radiotherapy regimen.Main Outcomes and Measures: Overall survival was analyzed by propensity score matching Cox proportional hazards regression models, quality by measuring 90-day emergency department (ED) visit and inpatient admission rates, and costs by assessing 90-day total Medicare spending.Results: The overall cohort included 1091 patients, of whom 815 (74.7%) were male; the mean (SD) age was 73.9 (6.6) years. Patients receiving radiotherapy with cisplatin had higher overall survival compared with those receiving radiotherapy only (adjusted hazard ratio [HR], 0.64; 95% CI, 0.47-0.87). This finding was not seen in patients receiving radiotherapy with cetuximab (adjusted HR, 0.95; 95% CI, 0.75-1.20), compared with the radiotherapy only group, and it persisted after stratifying patients by age. The ED visit (adjusted incidence rate ratio [IRR], 1.72; 95% CI, 1.30-2.30) and inpatient admission (adjusted IRR, 1.48; 95% CI, 1.12-1.98) rates in the 90 days after treatment start were higher in patients receiving radiotherapy with cisplatin compared with those treated with radiotherapy only. Patients receiving radiotherapy with cetuximab had a higher rate of ED visits (adjusted IRR, 1.38; 95% CI, 1.05-1.82) compared with those in the radiotherapy only group. The 90-day after-treatment spending for patients receiving radiotherapy with cetuximab was $48 620 (95% CI, $46 466-$50 775) compared with $33 009 (95% CI, $31 499-$34 519) for radiotherapy with cisplatin and $27 622 (95% CI, $25 118-$30 126) for radiotherapy only.Conclusions and Relevance: In this cohort study, no survival difference, a higher rate of ED visits but not of inpatient admissions, and higher spending were observed in patients receiving radiotherapy with cetuximab compared with patients receiving radiotherapy only. The findings suggest that radiotherapy alone should be maintained as a treatment arm in evaluation of novel therapeutics for locoregionally advanced head and neck cancer in older and sicker patients.

  View details for DOI 10.1001/jamaoto.2019.2381

  View details for PubMedID 31621810

• Lymph node yield, depth of invasion, and survival in node-negative oral cavity cancer. Oral oncology Zenga, J., Divi, V., Stadler, M., Massey, B., Campbell, B., Shukla, M., Awan, M., Schultz, C. J., Shreenivas, A., Wong, S., Jackson, R. S., Pipkorn, P. 2019; 98: 125–31

  Abstract

  OBJECTIVE: To determine the effects of nodal yield on survival in early stage oral cavity squamous cell carcinoma (OCSCC) in the context of primary tumor depth of invasion (DOI).MATERIALS AND METHODS: Patients with early-stage clinically node-negative OCSCC who underwent upfront surgery at the primary site were identified using the National Cancer Database between 2004 and 2015.RESULTS: There were 3384 patients with <4 mm DOI and 1387 patients with ≥4 mm DOI identified. Management of the neck included observation (40%), END with <18 nodes harvested ± postoperative radiation (ND < 18, 16%), and END with ≥18 nodes harvest ± postoperative radiation (ND ≥ 18, 44%). When adjusted for relevant covariates, ND ≥ 18 demonstrated statistically significant improvements in overall survival for both DOI < 4 mm and ≥4 mm (DOI < 4 mm: HR 0.67, 95%CI 0.54-0.85; DOI ≥ 4 mm: HR 0.47, 95%CI 0.34-0.64). However, ND < 18 showed no significant difference from observation of the neck regardless of DOI (DOI < 4 mm: HR 0.82, 95%CI 0.63-1.07; DOI ≥ 4 mm: HR 0.72, 95%CI 0.51-1.03). Of patients undergoing END, the most significant factors associated with obtaining a nodal yield of 18 or more were age less than 40 years (HR 2.58, 95%CI 1.84-3.63) and treatment at an academic facility (HR 2.47, 95%CI 2.06-2.96).CONCLUSIONS: END with 18 or more nodes is associated with improved survival outcomes in patients with early stage OCSCC regardless of DOI. END with less than 18 nodes, however, does not appear significantly different than observation of the neck alone. Achieving a lymph node yield of 18 or more is multifactorial and includes both patient and provider factors.

  View details for DOI 10.1016/j.oraloncology.2019.09.028

  View details for PubMedID 31586894

• Probe-based fluorescence dosimetry of an antibody-dye conjugate to identify head and neck cancer as a first step to fluorescence-guided tissue preselection for pathological assessment. Head & neck Nishio, N., van Keulen, S., van den Berg, N. S., Lu, G., LaRochelle, E. P., Davis, S. C., Martin, B. A., Fakurnejad, S., Zhou, Q., Birkeland, A. C., Kaplan, M. J., Divi, V., Colevas, A. D., Pogue, B. W., Rosenthal, E. L. 2019

  Abstract

  BACKGROUND: Despite the rapid growth of fluorescence imaging, accurate sampling of tissue sections remains challenging. Development of novel technologies to improve intraoperative assessment of tissue is needed.METHODS: A novel contact probe-based fluorescence dosimeter device, optimized for IRDye800CW quantification, was developed. After evaluation of the device in a phantom setup, its clinical value was defined ex vivo in patients with head and neck squamous cell carcinoma who received panitumumab-IRDye800CW.RESULTS: Ten patients were enrolled with a total of 216 data points obtained. Final histopathology showed tumor in 119 spots and normal tissue in 97 spots. Fluorescence-to-excitation ratios in tumor tissue were more than three times higher than those in normal tissue. The area under the curve was 0.86 (95% CI: 0.81-0.91) for tumor detection.CONCLUSIONS: Fluorescence-guided tissue preselection using a fluorescence dosimeter could have substantial impact on tissue sampling for frozen section analysis and potentially reduce sampling errors.

  View details for DOI 10.1002/hed.25964

  View details for PubMedID 31571335

• End-of-Life Costs and Hospice Utilization in Patients with Head and Neck Cancer Chen, M. M., Rosenthal, E. L., Divi, V. SAGE PUBLICATIONS LTD. 2019: 439–41

  View details for DOI 10.1177/0194599819846072

  View details for Web of Science ID 000486228900008

• Impact of lymph node sampling on survival in cN0 major salivary gland adenoid cystic carcinoma HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Qian, Z., Chen, M. M., Divi, V., Megwalu, U. C. 2019; 41 (6): 1903–7

  View details for DOI 10.1002/hed.25628

  View details for Web of Science ID 000468629500045

• Regionalization of head and neck cancer surgery may fragment care and impact overall survival LARYNGOSCOPE Chen, M. M., Megwalu, U. C., Liew, J., Sirjani, D., Rosenthal, E. L., Divi, V. 2019; 129 (6): 1413–19

  View details for DOI 10.1002/lary.27440

  View details for Web of Science ID 000468091400035

• Real-world efficacy of bone modifying agents (BMAs) in patients with breast cancer (BC) treated in an academic health system: Use of the "green button. Karimi, Y., Gombar, S., Dean, L., Hansen, J., Callahan, A., Jung, K., Divi, V., Blayney, D. W. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.e18054

  View details for Web of Science ID 000487345802051

• Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Nishio, N., van den Berg, N. S., van Keulen, S., Martin, B. A., Fakurnejad, S., Zhou, Q., Lu, G., Chirita, S. U., Kaplan, M. J., Divi, V., Colevas, A. D., Rosenthal, E. L. 2019

  Abstract

  PURPOSE: To identify the optimal dosing strategy for fluorescence-guided surgery in patients with head and neck squamous cell carcinoma, we conducted a dose-ranging study evaluating the anti-epidermal growth factor receptor (EGFR) therapeutic antibody, panitumumab, that was fluorescently labeled with the near-infrared dye IRDye800CW.PROCEDURES: Patients (n=24) received either 0.5 or 1.0mg/kg panitumumab-IRDye800CW in the weight-based dosing group or 25 or 50mg panitumumab-IRDye800CW in the fixed dosing group. Following surgery, whole primary specimens were imaged in a closed-field device and the mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were assessed. Clinical variables, including dose, time of infusion-to-surgery, age, unlabeled dose, gender, primary tumor site, and tumor size, were analyzed to evaluate the factors affecting the fluorescence intensity in order to identify the optimal dose for intraoperative fluorescence imaging.RESULTS: A total of 24 primary tumor specimens were imaged and analyzed in this study. Although no correlations between TBR and dose of panitumumab-IRDye800CW were found, there were moderate-strong correlations between the primary tumor MFI and panitumumab-IRDye800CW dose for fixed dose (mg) (R2=0.42) and for dose/weight (mg/kg) (R2=0.54). Results indicated that the optimal MFI was at approximately 50mg for fixed dose and 0.75mg/kg for dose/weight. No significant differences were found for the primary tumor MFI and TBRs between the weight-based dosing and the fixed dosing groups. MFIs significantly increased when the infusion-to-surgery window was reduced to within 2days (vs. 3days or more, p<0.05).CONCLUSIONS: Antibody-based imaging for surgical resection is under investigation in multiple clinical trials. Our data suggests that a fixed dose of 50mg is an appropriate diagnostic dose for successful surgical fluorescence imaging.

  View details for PubMedID 31054001

• Persistent Postoperative Opioid Use in Older Head and Neck Cancer Patients OTOLARYNGOLOGY-HEAD AND NECK SURGERY Saraswathula, A., Chen, M. M., Mudumbai, S. C., Whittemore, A. S., Divi, V. 2019; 160 (3): 380–87

  View details for DOI 10.1177/0194599818778276

  View details for Web of Science ID 000460295100002

• Impact of lymph node sampling on survival in cN0 major salivary gland adenoid cystic carcinoma. Head & neck Qian, Z. J., Chen, M. M., Divi, V., Megwalu, U. C. 2019

  Abstract

  BACKGROUND: The role of elective neck dissection in the management of major salivary gland adenoid cystic carcinoma is unclear.METHODS: Data were retrospectively extracted from the National Cancer Center Database. The study cohort included 1504 patients with adenoid cystic carcinoma of major salivary glands with clinical N0 necks who were treated with surgery between 2004 and 2014. The cohort was divided into four groups based on number of lymph nodes (LNs) examined on pathology: 0, 1-8, 9-17, and ≥18 LNs.RESULTS: The rate of occult nodal metastasis was 9.0%. Number of LNs removed was not associated with survival (Reference, 0 LNs; HR= 0.98, 95% CI 0.73-1.32 for 1-8 LNs; HR= 1.22, 95% CI 0.80-1.88 for 9-17 LNs; HR= 0.94, 95% CI 0.61-1.46 for ≥18 LNs) after adjusting for important covariates.CONCLUSIONS: LN sampling is not associated with survival in cN0 major salivary gland ACC.

  View details for PubMedID 30620437

• Depth of invasion alone as a prognostic factor in low-risk early-stage oral cavity carcinoma. The Laryngoscope Kozak, M. M., Shah, J., Chen, M., Schaberg, K., von Eyben, R., Chen, J. J., Bui, T., Kong, C., Kaplan, M., Divi, V., Hara, W. 2019

  Abstract

  OBJECTIVES: To evaluate the significance of increasing depth of invasion (DOI) as the sole risk factor for recurrence in patients with low-risk early-stage oral cavity squamous cell carcinoma (OCSCC).METHODS: We retrospectively reviewed 560 patients with OCSCC treated at our institution between 2003 and 2013. Patients were included if they had low-risk early-stage OCSCC treated with surgical resection ± neck dissection and no adjuvant therapy. Low risk was defined as absence of positive or close margins, lymphovascular invasion, perineural invasion, and positive lymph nodes. Patients with tumor (T)3-T4 disease were excluded. Pathology specimens were independently re-reviewed by two board-certified pathologists to confirm proper measurement of DOI. Kaplan-Meier and Cox proportional hazards regression analyses were performed to identify factors predictive for recurrence as well as progression-free survival (PFS) and overall survival (OS).RESULTS: A total of 126 patients with low-risk early-stage T1-2N0 OCSCC were included. Median follow-up time was 42.5 months and median DOI was 4 mm. There was no significant difference in incidence of local (P = 0.95), regional (P = 0.81), or distant recurrence (P = 0.96) among patients with DOI < 4 mm versus ≥4 mm. On multivariable analysis, DOI was significant for both PFS (P = 0.03) and OS (P = 0.002).CONCLUSION: In this study, we show that in the absence of other high-risk pathologic features, DOI ≥ 4 mm does not portend for increased incidence of local, regional, or distant relapse in patients treated with surgery alone; however, increasing DOI is a marker for worse PFS and OS in patients with low-risk, early-stage OCSCC.LEVEL OF EVIDENCE: 4. Laryngoscope, 2019.

  View details for DOI 10.1002/lary.27753

  View details for PubMedID 30604435

• Corrigendum to 'Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis'. [Oral Oncol. 85 (2018) 60-67]. Oral oncology Chen, J. J., Harris, J. P., Kong, C. S., Sunwoo, J. B., Divi, V. n., Horst, K. C., Aasi, S. Z., Hollmig, S. T., Hara, W. Y. 2019

  View details for DOI 10.1016/j.oraloncology.2019.05.024

  View details for PubMedID 31174982

• PD-L1 Expression and Tumor-Infiltrating Lymphocytes in High-Risk and Metastatic Cutaneous Squamous Cell Carcinoma OTOLARYNGOLOGY-HEAD AND NECK SURGERY Amoils, M., Kim, J., Lee, C., Sunwoo, J. B., Colevas, A., Aasi, S. Z., Hollmig, S., Ma, Y., Divi, V. 2019; 160 (1): 93–99

  View details for DOI 10.1177/0194599818788057

  View details for Web of Science ID 000454870600012

• Quality Outcome Measures in Neck Dissection NECK DISSECTION Divi, V., Amoils, M., Stack, B., Moreno, M. 2019: 291–94

  View details for Web of Science ID 000562485800030

• Radioactive iodine in differentiated thyroid cancer: a national database perspective. Endocrine-related cancer Orosco, R. n., Hussain, T. n., Noel, J. E., Chang, D. n., Dosiou, C. n., Mittra, E. n., Divi, V. n., Orloff, L. n. 2019

  Abstract

  Radioactive iodine (RAI) is a key component in the treatment of differentiated thyroid cancer. RAI has been recommended more selectively in recent years as guidelines evolve to reflect risks and utility in certain patient subsets. In this study we sought to evaluate the survival impact of radioactive iodine in specific thyroid cancer subgroups. Nationwide retrospective cohort study of patients using the National Cancer Database (NCDB) from 2004-2012 and Surveillance, Epidemiology, and End Results (SEER) database from 1992-2009 examining patients with differentiated thyroid cancer treated with or without RAI. Primary outcomes included all-cause mortality (NCDB and SEER), and cancer-specific mortality (SEER). Cox multivariate survival analyses were applied to each dataset, and in 135 patient subgroups based on clinical and non-clinical parameters. A total of 199,371 NCDB and 77,187 SEER patients were identified. RAI was associated with improved all-cause mortality (NCDB: RAI hazard ratio (HR) 0.55, P<0.001; SEER: HR 0.64, P<0.001); and cancer-specific mortality (SEER: HR 0.82, P=0.029). Iodine therapy showed varied efficacy within each subgroup. Patients with high-risk disease experienced the greatest benefit in all-cause mortality, followed by intermediate-risk, then low-risk subgroups. Regarding cancer-specific mortality, radioactive iodine therapy was protective in high-risk patients, but did not achieve statistical significance in most intermediate-risk subgroups. Low-risk T1a subgroups demonstrated an increased likelihood of cancer-specific mortality with iodine therapy. The efficacy of RAI in patients with differentiated thyroid cancer varies by disease severity. A negative cancer-specific survival association was identified in patients with T1a disease. These findings warrant further evaluation with prospective studies.

  View details for DOI 10.1530/ERC-19-0292

  View details for PubMedID 31443087

• End-of-Life Costs and Hospice Utilization in Patients with Head and Neck Cancer. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Chen, M. M., Rosenthal, E. L., Divi, V. n. 2019: 194599819846072

  Abstract

  The Quality Oncology Practice Initiative has several metrics related to end-of life (EOL) care, including hospice enrollment ≤3 days, with lower scores signaling better performance. Of privately insured patients with head and neck cancer, 3.5% were enrolled in hospice prior to death and 21.3% spent ≤3 days in hospice, indicating aggressive EOL care. Patients with late hospice enrollment had higher spending in the last 30 days of life (DOL). Patients in hospice ≤3 days spent $37,426, while those in hospice >3 days spent $24,418 ( P = .002). The largest portion of this difference was attributable to inpatient services. Patients in hospice ≤3 days spent $22,089 on inpatient services in the last 30 DOL, while those in hospice >3 days spent $8361 ( P < .001). Further research is needed to determine if more high-value care can be provided with earlier hospice enrollment and to ensure that goal concordance is included in defining high-value care.

  View details for PubMedID 31013209

• Wound Complications in Head and Neck Squamous Cell Carcinomas After Anti-PD-1 Therapy. The Laryngoscope Hwang, V. n., Mendez, E. n., Chow, L. Q., Futran, N. D., Andersen, P. n., Li, R. n., Divi, V. n., Rodriguez, C. P. 2019

  Abstract

  Immune checkpoint inhibitors have demonstrated activity in recurrent/metastatic head and neck squamous cell cancer, but less is known regarding their long-term sequelae. We describe four patients who, after complete responses to anti-PD-1 therapy, developed complications requiring surgical intervention. Patient 1 is a 57-year-old female whose marked tumor regression exposed some mandibular hardware. Patient 2 is a 39-year-old male who developed an ulcerated buccal lesion with exposed mandible. Patient 3 is a 66-year-old male with craniofacial osteoradionecrosis. Patient 4 is a 71-year-old male who developed an exposed and fractured mandible. All patients successfully underwent surgical intervention and remain disease free. Laryngoscope, 2019.

  View details for PubMedID 31074843

• UM-HACC-2A: MYB-NFIB fusion-positive human adenoid cystic carcinoma cell line. Oral oncology Warner, K. A., Oklejas, A. E., Pearson, A. T., Zhang, Z., Wu, W., Divi, V., Rodriguez-Ramirez, C., Castilho, R. M., Polverini, P. J., Nor, J. E. 2018; 87: 21–28

  Abstract

  OBJECTIVES: Limited availability of validated human adenoid cystic carcinoma (ACC) cell lines has hindered the mechanistic understanding of the pathobiology of this malignancy and the development of effective therapies. The purpose of this work was to generate and characterize a human ACC cell line.MATERIAL AND METHODS: Immediately after surgery, a tumor fragment from a minor salivary gland from the tongue of a female Caucasian was minced, dissociated, and a single cell suspension was plated in fibronectin-coated flasks. A culture medium containing bovine brain extract and rhEGF was optimized for these cells. Whole exome sequencing was used to evaluate the presence of MYB-NFIB translocation.RESULTS: The University of Michigan-Human Adenoid Cystic Carcinoma (UM-HACC)-2A cells showed continuous growth in monolayers for at least 180 in vitro passages while maintaining epithelial morphology. Short-tandem repeat (STR) profiling confirmed a 100% match to patient DNA. Whole exome sequencing revealed the presence of the MYB-NFIB fusion in UM-HACC-2A cells, which was confirmed by PCR analysis. Western blots revealed high expression of epithelial markers (e.g. E-cadherin, EGFR, pan-cytokeratin) and proteins associated with ACC (e.g. c-Myb, p63). Developmental therapeutic studies showed that UM-HACC-2A cells were resistant to cisplatin (IC50 = 44.7 M) while more responsive to paclitaxel (IC50 = 0.0006 M). In a pilot study, we observed that UM-HACC-2A cells survived orthotopic transplantation into the submandibular gland. Notably, one of the mice injected with UM-HACC-2A cells exhibited lung metastasis after 6 months.CONCLUSION: UM-HACC-2A is a MYB-NFIB fusion-positive ACC cell line that is suitable for mechanistic and developmental therapeutics studies.

  View details for PubMedID 30527239

• Treatment of early-stage laryngeal cancer: A comparison of treatment options ORAL ONCOLOGY Baird, B., Sung, C., Beadle, B. M., Divi, V. 2018; 87: 8–16

  View details for DOI 10.1016/j.oraloncology.2018.09.012

  View details for Web of Science ID 000452540400002

• UM-HACC-2A: MYB-NFIB fusion-positive human adenoid cystic carcinoma cell line ORAL ONCOLOGY Warner, K. A., Oklejas, A. E., Pearson, A. T., Zhang, Z., Wu, W., Divi, V., Rodriguez-Ramirez, C., Castilho, R. M., Polverini, P. J., Nor, J. E. 2018; 87: 21-28

  View details for DOI 10.1016/j.oraloncology.2018.10.012

  View details for Web of Science ID 000452540400004

• Treatment of early-stage laryngeal cancer: A comparison of treatment options. Oral oncology Baird, B. J., Sung, C. K., Beadle, B. M., Divi, V. 2018; 87: 8–16

  Abstract

  Over the course of the last several decades, the treatment options for early laryngeal cancers (T1 and T2) have evolved; however, simultaneously the mortality rate has increased. As larynx preservation approaches have become the standard of care, the selection of the proper treatment modality has become paramount. Radiation therapy or transoral laser microsurgery are the most common options for treatment of these early lesions. Oncologic and functional outcomes are considered equivalent between the two modalities for early glottic cancers; however, no direct comparisons exist for robust analysis. In terms of larynx preservation, there also is not compelling data favoring one treatment option or another. For early stage lesions, the goal for any larynx-sparing technique, either radiation or surgery, should be the intent to cure with single modality treatment and minimal short- and long-term toxicity. This article is designed to create a frame of reference for managing early stage disease with respect to lesions of the glottis and supraglottis while weighing treatment implications from an oncologic, functional, and cost perspective.

  View details for PubMedID 30527248

• Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis. Oral oncology Chen, J. J., Harris, J. P., Kong, C. S., Sunwoo, J. B., Divi, V., Horst, K. C., Aasi, S. Z., Hollmig, S. T., Hara, W. Y. 2018; 85: 60–67

  Abstract

  OBJECTIVES: Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes.MATERIALS AND METHODS: We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM).RESULTS: Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046).CONCLUSION: Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.

  View details for PubMedID 30220321

• Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis ORAL ONCOLOGY Chen, J., Harris, J. P., Kong, C. S., Sunwoo, J. B., Divi, V., Horst, K. C., Aasi, S. Z., Hollmig, S., Hara, W. Y. 2018; 85: 60–67

  View details for DOI 10.1016/j.oraloncology.2018.08.014

  View details for Web of Science ID 000444468900010

• Survival benefit of post-operative chemotherapy for intermediate-risk advanced stage head and neck cancer differs with patient age ORAL ONCOLOGY Chen, M. M., Colevas, A., Megwalu, U., Divi, V. 2018; 84: 71–75

  Abstract

  The National Comprehensive Cancer Network (NCCN) guidelines state that surgical patients with advanced-stage head and neck cancer (HNC) and risk factors other than extranodal extension (ENE) or positive margins should consider post-operative chemoradiation (POCRT). The goal of our study was to determine if POCRT is associated with overall survival (OS) compared with post-operative radiation therapy (PORT) and whether this varies with patient age.We conducted a retrospective study of 5319 adult patients with stage III-IV HNC who received primary surgical treatment with POCRT or PORT in the National Cancer Database (2010-2013). Patients with distant metastases, ENE, and positive margins were excluded. Intermediate risk features included pT3-T4, pN2-N3 disease, and lymphovascular invasion. Our main outcome was overall survival (OS). Statistical analysis included chi-squared tests and Cox proportional hazards regressions.On multivariable analysis for non-oropharyngeal cancer patients <70 years, POCRT was associated with improved OS for T1-4N2-3 disease (hazard ratio [HR], 0.73, 95% confidence interval [CI]; 0.58-0.93) but was not associated with OS for T3-4N0-1 disease (HR, 0.92; 95% CI, 0.71-1.19). For patients ≥70 years, POCRT was not associated with improved OS for patients with T1-4N2-3 disease (HR, 1.21; 95% CI, 0.79-1.86) or T3-4N0-1 disease (HR, 1.08; 95% CI, 0.71-1.65). For oropharyngeal cancer patients with HPV-positive disease, POCRT was associated with decreased OS (HR, 9.52; 95% CI, 2.38-38.08).Chemoradiation may offer a survival benefit for non-oropharyngeal intermediate-risk advanced-stage HNC patients <70 years of age with T1-4N2-3 disease, but may not benefit those ≥70 years of age or those with T3-4N0-1 disease.

  View details for PubMedID 30115479

• Jaw Opening Decreases Window to the Deep Parotid Lobe OTOLARYNGOLOGY-HEAD AND NECK SURGERY Lee, Y., Megwalu, U., Melara, E., Divi, V., Fernandes, V. T., Sirjani, D. 2018; 159 (3): 439–41

  View details for DOI 10.1177/0194599818766317

  View details for Web of Science ID 000443735400005

• Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence CANCER RESEARCH Gao, R. W., Teraphongphom, N. T., van den Berg, N. S., Martin, B. A., Oberhelman, N. J., Divi, V., Kaplan, M. J., Hong, S. S., Lu, G., Ertsey, R., Tummers, W. J., Gomez, A. J., Holsinger, F., Kong, C. S., Colevas, A. D., Warram, J. M., Rosenthal, E. L. 2018; 78 (17): 5144–54

  View details for DOI 10.1158/0008-5472.CAN-18-0878

  View details for Web of Science ID 000443753700029

• Regionalization of Head and Neck Cancer Surgery May Fragment Care and Impact Overall Survival. The Laryngoscope Chen, M. M., Megwalu, U. C., Liew, J., Sirjani, D., Rosenthal, E. L., Divi, V. 2018

  Abstract

  OBJECTIVE: While surgical treatment concentrates in tertiary care centers, an increasing number of patients request postoperative radiation therapy (PORT) at a separate center closer to home. Our goal was to determine whether fragmentation of surgery and PORT were associated with poorer oncologic outcomes.METHODS: We conducted a retrospective cohort study of 32,813 head and neck cancer patients treated with surgery and PORT in the National Cancer Data Base. Our main outcome was overall survival (OS). Statistical analysis included chi2 , t tests, Kaplan-Meier, and Cox regression analysis.RESULTS: Fragmented care was independently associated with increased risk of mortality (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03-1.13), whereas distance to surgical center>30 miles (HR, 0.92; 95% CI, 0.87-0.97) was associated with improved OS. On subgroup analysis, fragmented care was associated with decreased OS only among patients who had surgery at an academic center (HR, 1.10; 95% CI, 1.04-1.17). Within academic centers, greater distance from the surgical center was associated with improved survival only in patients who received PORT at the same facility (HR, 0.85; 95% CI, 0.78-0.93), but this effect was negated among patients who had fragmented care (HR, 0.97; 95% CI, 0.85-1.11).CONCLUSION: When cancer care is fragmented, there is no longer a survival benefit for patients to travel for surgical care at academic medical centers. Fragmented care is independently associated with worse survival, and further research is needed to evaluate the causes of this difference in survival to determine if improving care coordination can mitigate this survival difference.LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

  View details for PubMedID 30152007

• Cost-effectiveness of ibrutinib as first-line therapy for chronic lymphocytic leukemia in older adults without deletion 17p BLOOD ADVANCES Barnes, J., Divi, V., Begaye, A., Wong, R., Coutre, S., Owens, D. K., Goldhaber-Fiebert, J. D. 2018; 2 (15): 1946–56

  Abstract

  Ibrutinib is a novel oral therapy that has shown significant efficacy as initial treatment of chronic lymphocytic leukemia (CLL). It is a high-cost continuous therapy differing from other regimens that are given for much shorter courses. Our objective was to evaluate the cost-effectiveness of ibrutinib for first-line treatment of CLL in patients older than age 65 years without a 17p deletion. We developed a semi-Markov model to analyze the cost-effectiveness of ibrutinib vs a comparator therapy from a US Medicare perspective. No direct comparison between ibrutinib and the best available treatment alternative, obinutuzumab plus chlorambucil (chemoimmunotherapy), exists. Therefore, we compared ibrutinib to a theoretical treatment alternative, which was modeled to confer the effectiveness of an inferior treatment (chlorambucil alone) and the costs and adverse events of chemoimmunotherapy, which would provide ibrutinib with the best chance of being cost-effective. Even so, the incremental cost-effectiveness ratio of ibrutinib vs the modeled comparator was $189 000 per quality-adjusted life-year (QALY) gained. To reach a willingness-to-pay threshold (WTP) of $150 000 per QALY, the monthly cost of ibrutinib would have to be at most $6800, $1700 less than the modeled cost of $8500 per month (a reduction of $20 400 per year). When the comparator efficacy is increased to more closely match that seen in trials evaluating chemoimmunotherapy, ibrutinib costs more than $262 000 per QALY gained, and the monthly cost of ibrutinib would need to be lowered to less than $5000 per month to be cost-effective. Ibrutinib is not cost-effective as initial therapy at a WTP threshold of $150 000 per QALY gained.

  View details for PubMedID 30097461

  View details for PubMedCentralID PMC6093732

• Outcomes in Head and Neck Resections That Require Multiple-Flap Reconstructions A Systematic Review JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Gao, R. W., Nuyen, B. A., Divi, V., Sirjani, D., Rosenthal, E. L. 2018; 144 (8): 746–52

  View details for DOI 10.1001/jamaoto.2018.0835

  View details for Web of Science ID 000441939900018

• Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence. Cancer research Gao, R. W., Teraphongphom, N. T., van den Berg, N. S., Martin, B. A., Oberhelman, N. J., Divi, V., Kaplan, M. J., Hong, S. S., Lu, G., Ertsey, R., Tummers, W. S., Gomez, A. J., Holsinger, F. C., Kong, C. S., Colevas, A. D., Warram, J. M., Rosenthal, E. L. 2018

  Abstract

  For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor-mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. 21 adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 (n=3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A (n=5) received 0.5mg/kg, cohort 2B (n=7) received 1mg/kg, and cohort 3 (n=6) received 50 mg. Patients were followed 30 days post-infusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. In situ imaging demonstrated tumor-to-background ratio (TBR) of 2-3, compared to ex vivo specimen imaging TBR of 5-6. We obtained clear differentiation between tumor and normal tissue, with a three-fold signal difference between positive and negative specimens (p<0.05). We achieved high correlation of fluorescence intensity with tumor location with sensitivities and specificities >89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy which are otherwise less amenable to image guidance.

  View details for PubMedID 29967260

• PD-L1 Expression and Tumor-Infiltrating Lymphocytes in High-Risk and Metastatic Cutaneous Squamous Cell Carcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Amoils, M., Kim, J., Lee, C., Sunwoo, J. B., Colevas, A. D., Aasi, S. Z., Hollmig, S. T., Ma, Y., Divi, A. V. 2018: 194599818788057

  Abstract

  Objective To characterize programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) positivity for locally aggressive or regionally metastatic cutaneous head and neck squamous cell carcinoma (cHNSCC). Study Design Retrospective chart review, followed by immunohistochemical staining of archived tumor specimens. Setting Tertiary academic medical center. Subjects and Methods After identification of 101 patients treated surgically for locally advanced or regionally metastatic cHNSCC, archived tissue was stained and graded for PD-L1 expression in addition to TIL presence. Cross-tabulation was performed to examine the association between either of these variables and clinicopathologic features and outcomes. Results A total of 101 patients met inclusion criteria, but archived tissue was available only for 83 (31 primaries, 52 metastases). The majority of primary tumors demonstrated grade 1 PD-L1 staining, while grade 2 staining was more likely for metastases. Neither high- nor low-grade PD-L1 expression correlated with any clinicopathologic variable for primary tumors. However, for metastases, high-grade staining was significantly associated with regional recurrence (15 of 19, P = .02). TILs were present for 65% of primary tumors and 90% of regional metastases but did not correlate with any clinicopathologic variables. Conclusion Diffuse expression of PD-L1 in this study highlights the possibility of using immunotherapy in the form of programmed death 1/PD-L1 blockade to improve treatment for this devastating disease. However, further studies are needed to clarify the significance of PD-L1 expression and TIL positivity for locally advanced or regionally metastatic cHNSCC.

  View details for PubMedID 30012051

• Reducing the Time from Surgery to Adjuvant Radiation Therapy: An Institutional Quality Improvement Project OTOLARYNGOLOGY-HEAD AND NECK SURGERY Divi, V., Chen, M. M., Hara, W., Shah, D., Narvasa, K., Smith, A., Kelley, J., Rosenthal, E. L., Porter, J. 2018; 159 (1): 158–65

  View details for DOI 10.1177/0194599818768254

  View details for Web of Science ID 000438603000022

• Association of Time between Surgery and Adjuvant Therapy with Survival in Oral Cavity Cancer. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Chen, M. M., Harris, J. P., Orosco, R. K., Sirjani, D., Hara, W., Divi, V. 2018; 158 (6): 1051–56

  Abstract

  Objective The National Cancer Center Network recommends starting radiation therapy within 6 weeks after surgery for oral cavity squamous cell carcinoma (OCSCC), but there is limited evidence of the importance of the total time from surgery to completion of radiation therapy (package time). We set out to determine if there was an association between package time and survival in OCSCC and to evaluate the impact of treatment location on outcomes. Study Design Retrospective cohort study. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of patients with OCSCC who completed postoperative radiation therapy at an academic medical center from 2008 to 2016. The primary endpoints were overall survival and recurrence-free survival. Statistical analysis included chi2 tests and Cox proportional hazards regressions. Results We identified 132 patients with an average package time of 12.6 weeks. On multivariate analysis, package time >11 weeks was independently associated with decreased overall survival (hazard ratio, 6.68; 95% CI, 1.42-31.44) and recurrence-free survival (hazard ratio, 2.94; 95% CI, 1.20-7.18). Patients who received radiation therapy at outside facilities were more likely to have treatment delays (90.2% vs 62.9%, P = .001). Conclusions Prolonged package times are associated with decreased overall and recurrence-free survival among patients with OCSCC. Patients who received radiation therapy at outside facilities are more likely to have prolonged package times.

  View details for PubMedID 29313448

• Association of Time between Surgery and Adjuvant Therapy with Survival in Oral Cavity Cancer OTOLARYNGOLOGY-HEAD AND NECK SURGERY Chen, M. M., Harris, J. P., Orosco, R. K., Sirjani, D., Hara, W., Divi, V. 2018; 158 (6): 1051–56

  View details for DOI 10.1177/0194599817751679

  View details for Web of Science ID 000434026700021

• Standardized Margin Assessment Is Needed Before Implementing Negative Margin as a Quality Measure Reply JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Schoppy, D. W., Divi, V. 2018; 144 (6): 542

  View details for DOI 10.1001/jamaoto.2018.0080

  View details for Web of Science ID 000435868900020

• Association of Survival With Shorter Time to Radiation Therapy After Surgery for US Patients With Head and Neck Cancer JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Harris, J. P., Chen, M. M., Orosco, R. K., Sirjani, D., Divi, V., Hara, W. 2018; 144 (4): 349–59

  Abstract

  Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial.To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry.In this observational cohort study, 25 216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB).Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT.Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation.We identified 25 216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18 968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25 216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation.Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.

  View details for PubMedID 29522072

  View details for PubMedCentralID PMC5876822

• Reducing the Time from Surgery to Adjuvant Radiation Therapy: An Institutional Quality Improvement Project. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Divi, V., Chen, M. M., Hara, W., Shah, D., Narvasa, K., Segura Smith, A., Kelley, J., Rosenthal, E. L., Porter, J. 2018: 194599818768254

  Abstract

  Objective The National Comprehensive Cancer Network guidelines recommend an interval between surgery and adjuvant radiation therapy of less than 6 weeks, but only 44% of patients meet this metric nationally. We sought to identify key components of an improvement process focused on starting adjuvant radiation therapy within 6 weeks of surgery. Methods This project used an A3 model to improve a defined process measure. We studied a consecutive sample of 56 patients with oral cavity carcinoma who were treated at our institution with upfront surgical resection followed by adjuvant radiation therapy. Twelve proposed interventions tested during the study period focused on 3 key drivers of delays: delayed dental evaluation and teeth extraction, delayed radiation oncology consults, and inadequate patient engagement. The primary outcome measure was the number of days from surgery to the start of radiation therapy. Results Prior to the intervention, 62% of patients received adjuvant radiation within 6 weeks of surgery. Following the intervention, 73% of patients achieved this metric. The percentage of patients with avoidable delays decreased from 24% to 9%. The percentage of patients with unavoidable delays was relatively constant before and after the intervention (15% and 18%, respectively). Discussion Defining disease-specific metrics is critical to improving care in our head and neck cancer patient population. We demonstrate several key components to develop and improve self-defined metrics. Implications for Practice As we transition to a system of value-based care, structured quality improvement projects can have a measurable impact on cancer patient process measures.

  View details for PubMedID 29631478

• Standardized Margin Assessment Is Needed Before Implementing Negative Margin as a Quality Measure-Reply. JAMA otolaryngology-- head & neck surgery Schoppy, D. W., Divi, V. 2018

  View details for PubMedID 29596548

• Jaw Opening Decreases Window to the Deep Parotid Lobe. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Lee, Y., Megwalu, U., Melara, E., Divi, V., Fernandes, V. T., Sirjani, D. 2018: 194599818766317

  Abstract

  To describe the relationship between jaw opening and access to the deep parotid window, we identified the following distances in 10 human skulls: symphysis to angle of mandible, mastoid tip to angle of mandible, angle of mandible to condylar process, and mastoid tip to condylar process. With the jaw closed and open, these distances were measured with 1 to 3 wooden blocks, each measuring 1 cm, between the upper and lower incisors. The triangular deep parotid area formed by the last 3 distances was calculated. A repeated measures analysis of variance showed a significant decrease in the deep parotid area with increasing interincisal distance ( P < .01). A generalized estimating equation model demonstrated a statistically significant decreasing area of the deep parotid window with increasing interincisal distance. These results suggest that nasal intubation may improve access to the parotid window.

  View details for PubMedID 29609515

• Outcomes in Head and Neck Resections That Require Multiple-Flap Reconstructions: A Systematic Review. JAMA otolaryngology-- head & neck surgery Gao, R. W., Nuyen, B. A., Divi, V. n., Sirjani, D. n., Rosenthal, E. L. 2018

  Abstract

  Complex head and neck cancer defects that require multiflap reconstructions are technically feasible, but the morbidity and patient outcomes of such large-scale head and neck operations have yet to be systematically reviewed.To systematically review existing literature to characterize the outcomes of large-scale head and neck resections that require multiple-flap reconstructions (defined as defects that require >1 flap [free, pedicled, or combinations thereof]).Two authors independently searched PubMed, Embase, and the Cochrane Review databases for English-only texts published on any date. Included studies examined patients who underwent complex head and neck surgical resections that required multiple simultaneous flaps for reconstruction. Included studies reported results on at least one of the following outcomes: functional and aesthetic, patient survival, or cost (estimated by operating room time, length of stay, and/or complications). Methodological Index for Non-Randomized Studies (MINORS) criteria for bias and modified Oxford Centre for Evidence-Based Medicine recommendations were used to assess study quality.Twenty-four studies published from November 1, 1992, through September 1, 2016, met the final inclusion criteria, with a total of 487 patients (370 male [79.4%]; mean [SD] weighted age, 55.1 [4.1] years). Sixty-two of 250 patients (24.8%) were partially or fully dependent on feeding tubes at follow-up. Twenty-two of 75 patients (29.3%) had poor postoperative oral competence, causing moderate to severe drooling. Nineteen of 108 patients (17.6%) had unintelligible speech. Nine of 64 patients (14.1%) were unsatisfied with their aesthetic outcome. The mean (SD) reported survival was 2.36 (1.39) years. The mean (SD) length of stay was 24.5 (12.2) days in 219 patients. Eighty-eight minor complications (eg, partial flap necrosis, donor site complications) and 185 major complications (eg, surgical reexplorations, flap loss, or cardiopulmonary complications) were reported in 380 patients. Mean (SD) MINORS scores were 16.0 (3.2) for comparison studies and 11.4 (1.8) for noncomparison studies.Because of limited patient life expectancies, modest functional and aesthetic outcomes, and significant associated costs, surgeons should weigh the curative potential and palliative benefits for individual patients with a comprehensive view of the overall outcomes of extensive head and neck resections and reconstructions. Realistic expectations should be emphasized during preoperative discussions with patients.

  View details for PubMedID 29978196

• Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers THERANOSTICS Gao, R. W., Teraphongphom, N., de Boer, E., van den Berg, N. S., Divi, V., Kaplan, M. J., Oberhelman, N. J., Hong, S. S., Capes, E., Colevas, A., Warram, J. M., Rosenthal, E. L. 2018; 8 (9): 2488–95

  Abstract

  Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2, cohort 2 received 25 mg/m2, and cohort 3 received 62.5 mg/m2. For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion. Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-IRDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8). Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.

  View details for PubMedID 29721094

• Persistent Postoperative Opioid Use in Older Head and Neck Cancer Patients. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Saraswathula, A. n., Chen, M. M., Mudumbai, S. C., Whittemore, A. S., Divi, V. n. 2018: 194599818778276

  Abstract

  Objectives Despite the epidemic of opioid overuse among American patients, there are limited data regarding the prevalence of such use among patients with head and neck cancer (HNC). Here, we report on the prevalence of persistent postoperative opioid (PPO) use and its risk factors among older patients with HNC undergoing surgery. Study Design Retrospective cohort study. Setting Surveillance, Epidemiology, and End Results (SEER)-Medicare linked cancer registry-claims database. Subjects and Methods We identified patients aged 66 years or older who were diagnosed with HNC from 2008 to 2013, underwent primary surgical resection for their cancers, and met certain insurance and discharge criteria. The primary outcome was PPO use, defined as new opioid prescriptions 90 to 180 days postoperatively. We used multivariable logistic regression to evaluate associations between PPO use and factors such as demographics and postoperative treatment. Results Of the 1190 eligible patients with HNC, 866 (72.8%) received opioid prescriptions attributable to their surgery. Among these 866 patients, the prevalence of PPO use was 33.3% overall; it was 48.3% among the 428 patients with preoperative opioid use compared to 18.5% among the 438 opioid-naive patients (adjusted odds ratio [OR], 3.96; 95% confidence interval [CI], 2.80-5.59). Other factors associated with PPO use include postoperative radiotherapy (OR, 1.99; 95%, CI 1.33-2.98) and Charlson comorbidity index (OR, 1.20; 95% CI, 1.03-1.41). Postoperative chemotherapy (OR, 1.19; 95% CI, 0.73-1.95) was not significantly associated with PPO use. Conclusions PPO use is a substantial problem in older surgical patients with HNC, one that warrants consideration of alternative treatment strategies and continued examination of prescription guidelines for patients with HNC.

  View details for PubMedID 29807503

• Surrogate for oropharyngeal cancer HPV status in cancer database studies HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Megwalu, U. C., Chen, M. M., Ma, Y., Divi, V. 2017; 39 (12): 2494–2500

  Abstract

  The utility of cancer databases for oropharyngeal cancer studies is limited by lack of information on human papillomavirus (HPV) status. The purpose of this study was to develop a surrogate that can be used to adjust for the effect of HPV status on survival.The study cohort included 6419 patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012, identified in the National Cancer Database (NCDB). The HPV surrogate score was developed using a logistic regression model predicting HPV-positive status.The HPV surrogate score was predictive of HPV status (area under the curve [AUC] 0.73; accuracy of 70.4%). Similar to HPV-positive tumors, HPV surrogate positive tumors were associated with improved overall survival (OS; hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.59-0.91; P = .005), after adjusting for important covariates.The HPV surrogate score is useful for adjusting for the effect of HPV status on survival in studies utilizing cancer databases.

  View details for PubMedID 28963794

• Measuring Institutional Quality in Head and Neck Surgery Using Hospital-Level Data Negative Margin Rates and Neck Dissection Yield Schoppy, D., Rhoads, K. F., Ma, Y., Chen, M. M., Nussenbaum, B., Orosco, R. K., Rosenthal, E. L., Divi, V. AMER MEDICAL ASSOC. 2017: 1111–16

  Abstract

  Negative margins and lymph node yields (LNY) of 18 or more from neck dissections in patients with head and neck squamous cell carcinomas (HNSCC) have been associated with improved patient survival. It is unclear whether these metrics can be used to identify hospitals with improved outcomes.To determine whether 2 patient-level metrics would predict outcomes at the hospital level.A retrospective review of records from the National Cancer Database (NCDB) was used to identify patients who underwent primary surgery and concurrent neck dissection for HNSCC between 2004 and 2013. The percentage of patients at each hospital with negative margins on primary resection and an LNY 18 or more from a neck dissection was quantified. Cox proportional hazard models were used to define the association between hospital performance on these metrics and overall survival.Margin status and lymph node yield at hospital level. Overall survival (OS).We identified 1008 hospitals in the NCDB where 64 738 patients met inclusion criteria. Of the 64 738 participants, 45 170 (69.8%) were men and 19 568 (30.2%) were women. The mean SD age of included patients was 60.5 (12.0) years. Patients treated at hospitals attaining the combined metric of a 90% or higher negative margin rate and 80% or more of cases with LNYs of 18 or more experienced a significant reduction in mortality (hazard ratio [HR] 0.93; 95% CI, 0.89-0.98). This benefit in survival was independent of the patient-level improvement associated with negative margins (HR, 0.73; 95% CI, 0.71-0.76) and LNY of 18 or more (HR, 0.85; 95% CI, 0.83-0.88). Including these metrics in the model neutralized the association of traditional measures of hospital quality (volume and teaching status).Treatment at hospitals that attain a high rate of negative margins and LNY of 18 or more is associated with improved survival in patients undergoing surgery for HNSCC. These surgical outcome measures predicted outcomes independent of traditional, but generally nonmodifiable characteristics. Tracking of these metrics may help identify high-quality centers and provide guidance for institution-level quality improvement.

  View details for PubMedID 28983555

  View details for PubMedCentralID PMC5710350

• Retrograde Parotidectomy and facial nerve outcomes: A case series of 44 patients AMERICAN JOURNAL OF OTOLARYNGOLOGY Kligerman, M. P., Song, Y., Schoppy, D., Divi, V., Megwalu, U. C., Haughey, B. H., Sirjani, D. 2017; 38 (5): 533–36

  Abstract

  The most common surgical method to remove benign parotid tumors remains the prograde approach. We examined if a retrograde surgical technique offers better outcomes than historical prograde controls.A retrospective chart review at Stanford Hospital was conducted to identify retrograde parotidectomies between February 2012 and October 2014 that were staffed by the senior author (DS) with resident involvement. Facial nerve (FN) outcomes and other post-surgical parameters were recorded.We identified 44 consecutive cases and found that 18.2% (n=8) of patients experienced temporary paresis and 2.3% (n=1) experienced minor (HB 2) permanent paresis limited to one branch. The average hospital length of stay was 0.64 days and complication rate was 6.8%.The retrograde technique has complication rates comparable to historical rates for the prograde technique and is amenable to minimally invasive outpatient superficial parotidectomy.

  View details for PubMedID 28647300

• Predictors of readmissions after head and neck cancer surgery: A national perspective ORAL ONCOLOGY Chen, M. M., Orosco, R. K., Harris, J. P., Porter, J. B., Rosenthal, E. L., Hara, W., Divi, V. 2017; 71: 106–12

  Abstract

  Surgical oncology patients have multiple comorbidities and are at high risk of readmission. Prior studies are limited in their ability to capture readmissions outside of the index hospital that performed the surgery. Our goal is to evaluate risk factors for readmission for head and neck cancer patients on a national scale.A retrospective cohort study of head and neck cancer patients in the Nationwide Readmissions Database (2013). Our main outcome was 30-day readmission. Statistical analysis included 2-sided t tests, χ2, and multivariate logistic regression analysis.Within 30days, 16.1% of 11,832 patients were readmitted and 20% of readmissions were at non-index hospitals, costing $31million. Hypopharyngeal cancer patients had the highest readmission rate (29.6%), followed by laryngeal (21.8%), oropharyngeal (18.2%), and oral cavity (11.6%) cancers (P<0.001). Half of readmissions occurred within 10days and were often associated with infections (27%) or wound complications (12%). Patients from lower household income areas were more likely to be readmitted (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.16-2.05). Patients with valvular disease (OR, 2.07; 95% CI, 1.16-3.69), rheumatoid arthritis/collagen vascular disease (OR, 2.05; 95% CI, 1.27-3.31), liver disease (OR, 2.02, 95% CI, 1.37-2.99), and hypothyroidism (OR 1.30; 95% CI, 1.02-1.66) were at highest risk of readmission.The true rate of 30-day readmissions after head and neck cancer surgery is 16%, capturing non-index hospital readmissions which make up 20% of readmissions. Readmissions after head and neck cancer surgery are most commonly associated with infections and wound complications.

  View details for PubMedID 28688676

• Clinical Outcomes in Elderly Patients Treated for Oral Cavity Squamous Cell Carcinoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chen, J., Shah, J. L., Harris, J. P., Bui, T. T., Schaberg, K., Kong, C. S., Kaplan, M. J., Divi, V., Schoppy, D., Quynh-Thu Le, Hara, W. Y. 2017; 98 (4): 775–83

  Abstract

  Oral cavity squamous cell carcinoma (OCSCC) commonly occurs in elderly patients. This study explores the clinical outcomes in elderly patients with OCSCC based on their functional status and clinical comorbidities.We retrospectively reviewed 180 patients aged ≥70 who were treated with definitive intent with surgery followed by adjuvant therapy if indicated for newly diagnosed OCSCC from 1998 to 2013. Pathology review was conducted, and Eastern Cooperative Oncology Group (ECOG) performance status and the Head and Neck Charlson Comorbidity Index (HN-CCI) were assessed. We performed Kaplan-Meier analyses and cumulative incidence estimates to assess overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LRR). Univariate and multivariate analyses were used to test age, adjuvant therapy, adverse pathologic features, ECOG status, and HN-CCI status as predictors.The median age was 80 years (range, 70-95 years), with a median follow-up time of 23 months. The median OS was 18 months and 46 months for patients aged 70 to 84 and ≥85, respectively (P=.0017). The LRR was 24% at 1 year and 30% at 2 years for all patients. On univariate analysis, ECOG score ≥2 (hazard ratio [HR] = 1.96; confidence interval [CI] 1.19-3.21; P=.008) and HN-CCI score ≥2 (HR=1.97; CI 1.17-3.34; P=.011) were predictors of worse OS. On multivariate analysis, HN-CCI score was a better predictor of OS, PFS, and LRR than was ECOG score. Predictors of worse OS were age ≥85 (HR=1.78; CI 1.07-2.96; P=.026), HN-CCI score of ≥2 (HR=2.21; CI 1.20-4.08; P=.011), and adverse features (HR=2.35; CI 1.34-4.13; P=.003). Adjuvant therapy did not have a significant impact on OS or LRR for patients with adverse features even though 48% of them did not receive it.Elderly patients with good health and performance status may live long enough to experience disease progression from OCSCC. ECOG and HN-CCI scores may be useful to evaluate the candidacy of elderly patients for adjuvant therapy. However, the benefit of adjuvant therapy in this population remains elusive and should be investigated prospectively.

  View details for PubMedID 28602409

• Quality Measures in Breast Reconstruction: A Systematic Review. Annals of plastic surgery Nazerali, R. N., Finnegan, M. A., Divi, V., Lee, G. K., Kamal, R. N. 2017

  Abstract

  The importance of providing quality care over quantity of care, and its positive effects on health care expenditure and health, has motivated a transition toward value-based payments. The Centers for Medicare and Medicaid Services and private payers are establishing programs linking financial incentives and penalties to adherence to quality measures. As payment models based on quality measures are transitioned into practice, it is beneficial to identify current quality measures that address breast reconstruction surgery as well as understand gaps to inform future quality measure development.We performed a systematic review of quality measures for breast reconstruction surgery by searching quality measure databases, professional society clinical practice guidelines, and the literature. Measures were categorized as structure, process, or outcome according to the Donabedian domains of quality.We identified a total of 27 measures applicable to breast reconstruction: 5 candidate quality measures specifically for breast reconstruction surgery and 22 quality measures that relate broadly to surgery. Of the breast reconstruction candidate measures, 3 addressed processes and 2 addressed outcomes. Seventeen of the general quality measures were process measures and 5 were outcome measures. We did not identify any structural measures.Currently, an overrepresentation of process measures exists, which addresses breast reconstruction surgery. There is a limited number of candidate measures that specifically address breast reconstruction. Quality measure development efforts on underrepresented domains, such as structure and outcome, and stewarding the measure development process for candidate quality measures can ensure breast reconstruction surgery is appropriately evaluated in value-based payment models.

  View details for DOI 10.1097/SAP.0000000000001088

  View details for PubMedID 28570449

• Association of surgical quality metrics and hospital-level overall survival for patients with head and neck squamous cell carcinoma. Schoppy, D. W., Ma, Y., Rhoads, K., Chen, M. M., Nussenbaum, B., Orosco, R. K., Rosenthal, E., Divi, V. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for Web of Science ID 000443301600205

• Node-positive cutaneous squamous cell carcinoma of the head and neck: Survival, high-risk features, and adjuvant chemoradiotherapy outcomes. Head & neck Amoils, M., Lee, C. S., Sunwoo, J., Aasi, S. Z., Hara, W., Kim, J., Sirjani, D., Colevas, A. D., Chang, A. L., Divi, V. 2017

  Abstract

  Data lacks to guide treatment of regionally metastatic cutaneous head and neck squamous cell carcinoma (HNSCC).We conducted a retrospective review of 80 patients treated for regionally metastatic cutaneous HNSCC. The effect of various clinicopathologic variables on overall survival (OS) was investigated, in addition to outcomes by treatment modality.On multivariate regression, cutaneous primary >2 cm (p = .03) and extracapsular spread (ECS; p = .01) were significantly associated with decreased OS. Location of regional metastasis (neck vs parotid vs both) had no effect on OS (p = .2), nor did the presence of a cutaneous primary at the time of presentation (p = .9). The 3-year survival was 43%, 52%, and 49% for surgery alone, adjuvant radiation, and adjuvant chemoradiation, respectively. Fifty-one percent of patients had a recurrence of their disease.Regionally metastatic cutaneous HNSCC is an aggressive disease associated with high recurrence rates. Patients with tumors >2 cm and ECS have poorer OS despite adjuvant therapy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 881-885, 2017.

  View details for DOI 10.1002/hed.24692

  View details for PubMedID 28252823

• The Multidisciplinary, Function-Oriented Evaluation. International journal of radiation oncology, biology, physics Hara, W. n., Divi, V. n. 2017; 97 (5): 891

  View details for PubMedID 28333007

• Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Porter, J. B. 2017; 13 (8): e673-e682

  Abstract

  Development and implementation of robust reporting processes to systematically provide quality data to care teams in a timely manner is challenging. National cancer quality measures are useful, but the manual data collection required is resource intensive, and reporting is delayed. We designed a largely automated measurement system with our multidisciplinary cancer care programs (CCPs) to identify, measure, and improve quality metrics that were meaningful to the care teams and their patients.Each CCP physician leader collaborated with the cancer quality team to identify metrics, abiding by established guiding principles. Financial incentive was provided to the CCPs if performance at the end of the study period met predetermined targets. Reports were developed and provided to the CCP physician leaders on a monthly or quarterly basis, for dissemination to their CCP teams.A total of 15 distinct quality measures were collected in depth for the first time at this cancer center. Metrics spanned the patient care continuum, from diagnosis through end of life or survivorship care. All metrics improved over the study period, met their targets, and earned a financial incentive for their CCP.Our quality program had three essential elements that led to its success: (1) engaging physicians in choosing the quality measures and prespecifying goals, (2) using automated extraction methods for rapid and timely feedback on improvement and progress toward achieving goals, and (3) offering a financial team-based incentive if prespecified goals were met.

  View details for DOI 10.1200/JOP.2017.021139

  View details for PubMedCentralID PMC5880618

• American Joint Committee on Cancer Eighth Edition Changes in Staging Criteria: Implications for Data Collection. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Saraswathula, A. n., Chen, M. n., Negoita, S. n., Divi, V. n. 2017: 194599817721690

  Abstract

  The American Joint Committee on Cancer, in the eighth edition of its cancer staging manual, makes a number of changes to improve survival predictions in human malignancy. In this commentary, we examine the national collection of data for head and neck cancer. We outline and review the major changes made in head and neck cancer staging, identify the key data elements that will need to be collected with the new edition's criteria, and discuss the institutional adjustments currently being made to data collection under the new guidelines to improve the quality of data in our national cancer databases.

  View details for PubMedID 28741416

• Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Chen, M. M., Harris, J. P., Hara, W., Sirjani, D., Divi, V. 2016; 142 (12): 1224-1230

  Abstract

  The guidelines for head and neck cancer recommend consideration of adjuvant postoperative radiotherapy (PORT) for patients with pT1N1 or pT2N1 disease in the absence of other adverse features. This recommendation was recently changed for oropharyngeal (OP) squamous cell carcinoma (SCC).To examine the use and outcomes of PORT for N1 OP SCC and oral cavity (OC) SCC.This retrospective cohort study identified 1467 adult patients with OC SCC and 790 patients with OP SCC with pT1N1 or pT2N1 disease in the absence of other adverse features from the National Cancer Database from January 1, 2004, to December 31, 2013. Patients who received adjuvant chemotherapy or palliative radiotherapy or who had adverse pathologic features were excluded. Statistical analysis included χ2 tests and Cox proportional hazards regression analysis. Data were analyzed from November 10, 2015, to June 30, 2016.Overall survival.Of the 1467 patients with OC SCC (842 men [57.4%]; 625 women [42.6%]; mean [SD] age, 61.3 [13.8] years), 740 (50.4%) received PORT. Of the 790 patients with OP SCC (584 men [73.9%]; 206 women [26.1%]; mean [SD] age, 58.2 [10.3] years), 449 (56.8%) received PORT. After controlling for patient demographics, pathologic characteristics, and hospital-level variables, PORT was associated with improved overall survival for patients with OC SCC (hazard ratio [HR], 0.76; 95% CI, 0.63-0.92) and OP SCC (HR, 0.62; 95% CI, 0.41-0.92) with pN1 disease without adverse features. On stratified analysis, this association persisted for patients younger than 70 years (OC SCC HR, 0.77; 95% CI, 0.61-0.97; OP SCC HR, 0.48; 95% CI, 0.31-0.75) and those with pT2 disease (OC SCC HR, 0.64; 95% CI, 0.43-0.96; OP SCC HR, 0.56; 95% CI, 0.32-0.95), but there was no association with overall survival among patients 70 years or older (OC SCC HR, 0.78; 95% CI, 0.58-1.06; OP SCC HR, 1.55; 95% CI, 0.63-3.82) and those with pT1 disease (OC SCC HR, 0.80; 95% CI, 0.60-1.07; OP SCC HR, 0.66; 95% CI, 0.35-1.24).PORT may be associated with improved survival in patients with pN1 OC and OP SCC, especially in those younger than 70 years or those with pT2 disease.

  View details for DOI 10.1001/jamaoto.2016.3519

  View details for PubMedID 27832255

• Lymph Node Count From Neck Dissection Predicts Mortality in Head and Neck Cancer JOURNAL OF CLINICAL ONCOLOGY Divi, V., Chen, M. M., Nussenbaum, B., Rhoads, K. F., Sirjani, D. B., Holsinger, F. C., Shah, J. L., Hara, W. 2016; 34 (32): 3892-?

  Abstract

  Multiple smaller studies have demonstrated an association between overall survival and lymph node (LN) count from neck dissection in patients with head and neck cancer. This is a large cohort study to examine these associations by using a national cancer database.The National Cancer Database was used to identify patients who underwent upfront nodal dissection for mucosal head and neck squamous cell carcinoma between 2004 and 2013. Patients were stratified by LN count into those with < 18 nodes and those with ≥ 18 nodes on the basis of prior work. A multivariable Cox proportional hazards regression model was constructed to predict hazard of mortality. Stratified models predicted hazard of mortality both for patients who were both node negative and node positive.There were 45,113 patients with ≥ 18 LNs and 18,865 patients with < 18 LNs examined. The < 18 LN group, compared with the ≥ 18 LN group, had more favorable tumor characteristics, with a lower proportion of T3 and T4 lesions (27.9% v 39.8%), fewer patients with positive nodes (46.6% v 60.5%), and lower rates of extracapsular extension (9.3% v 15.1%). Risk-adjusted Cox models predicting hazard of mortality by LN count showed an 18% increased hazard of death for patients with < 18 nodes examined (hazard ratio [HR] 1.18; 95% CI, 1.13 to 1.22). When stratified by clinical nodal stage, there was an increased hazard of death in both groups (node negative: HR, 1.24; 95% CI, 1.17 to 1.32; node positive: HR, 1.12; 95% CI, 1.05 to 1.19).The results of our study demonstrate a significant overall survival advantage in both patients who are clinically node negative and node positive when ≥ 18 LNs are examined after neck dissection, which suggests that LN count is a potential quality metric for neck dissection.

  View details for DOI 10.1200/JCO.2016.67.3863

  View details for PubMedID 27480149

• Contemporary mandibular reconstruction. Current opinion in otolaryngology & head and neck surgery Divi, V., Schoppy, D. W., Williams, R. A., Sirjani, D. B. 2016; 24 (5): 433-439

  Abstract

  Multiple disease processes, including neoplasia, trauma, and medication side-effects, necessitate segmental resection and subsequent reconstruction of the mandible. As surgical techniques have advanced, several technologies have been developed with the potential to significantly transform a surgeon's approach to the restoration of mandibular continuity. The purpose of this review is to highlight many of these relatively newer tools and discuss their evolving role in mandibular reconstruction.Several contemporary studies have documented the application of different approaches and modifications to mandibular reconstruction - including computer-aided design or computer-aided modeling, contemporary plating systems, osseointegrated implants, and various modifications to existing osseocutaneous free tissue transfer options - and have reported relatively high success rates.In discussing these reports, we present a survey of current and developing technologies in the field of mandibular reconstruction and aim to provide sufficient context for the gradual integration of these techniques into practice.

  View details for DOI 10.1097/MOO.0000000000000284

  View details for PubMedID 27348352

• Geographic variation in Medicare treatment costs and outcomes for advanced head and neck cancer ORAL ONCOLOGY Divi, V., Tao, L., Whittemore, A., Oakley-Girvan, I. 2016; 61: 83-88

  Abstract

  Advanced head and neck cancer (HNC) is a complex group of diseases that requires the input and coordination of multiple providers. While there are general guidelines for treatment, there is also considerable variation in how patients are treated, and how long they survive after treatment. It is unclear how the treatment variations relate to treatment costs and survival.We identified 3678 Medicare patients with advanced HNC treated in 12 US regions between 2004 and 2009 using the linked database containing Medicare and Surveillance Epidemiology and End Results (SEER) data. We calculated average cost per patient during the period three months before to 12months after diagnosis for each region. Costs included inpatient hospital, outpatient, physician, and durable medical equipment charges. We also calculated three-year overall survival for each of the regions.The mean cost-per-patient varied substantially among the regions, ranging from $51,857 for Utah to $82,181 for Detroit. Utah incurred the lowest total costs within one year of advanced HNC diagnosis ($51,857 per patient, 95% CI $42,285-$61,429), whereas Detroit had the highest costs ($82,181 per patient, 95% CI $74,752-$89,610). Overall survival also varied among the regions, ranging from 45months in Kentucky to 58months in Washington. There was little correlation between expenditures and length of survival, with correlation coefficient of 0.0088.Despite significant variation in both expenditures and survival among the regions, we found no correlation between costs and mean survival time, suggesting that more costly care did not lead to improved outcomes.

  View details for DOI 10.1016/j.oraloncology.2016.08.018

  View details for Web of Science ID 000384695400013

  View details for PubMedID 27688109

• Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes (NRG Oncology RTOG 9501 and RTOG 0234). Cancer Divi, V., Harris, J., Harari, P. M., Cooper, J. S., McHugh, J., Bell, D., Sturgis, E. M., Cmelak, A. J., Suntharalingam, M., Raben, D., Kim, H., Spencer, S. A., Laramore, G. E., Trotti, A., Foote, R. L., Schultz, C., Thorstad, W. L., Zhang, Q. E., Le, Q. T., Holsinger, F. C. 2016

  Abstract

  Prospective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study was to investigate the association between lymph node counts from neck dissection, local-regional recurrence, and overall survival.The number of lymph nodes counted from neck dissection in patients treated in 2 NRG Oncology trials (Radiation Therapy Oncology Group [RTOG] 9501 and RTOG 0234) was evaluated for its prognostic impact on overall survival with a multivariate Cox model adjusted for demographic, tumor, and lymph node data and stratified by the postoperative treatment group.Five hundred seventy-two patients were analyzed at a median follow-up of 8 years. Ninety-eight percent of the patients were pathologically N+. The median numbers of lymph nodes recorded on the left and right sides were 24 and 25, respectively. The identification of fewer than 18 nodes was associated with worse overall survival in comparison with 18 or more nodes (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09-1.74; P = .007). The difference appeared to be driven by local-regional failure (HR, 1.46; 95% CI, 1.02-2.08; P = .04) but not by distant metastases (HR, 1.08; 95% CI, 0.77-1.53; P = .65). When the analysis was limited to NRG Oncology RTOG 0234 patients, adding the p16 status to the model did not affect the HR for dissected nodes, and the effect of nodes did not differ with the p16 status.The removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local-regional failure, and this should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma. Cancer 2016. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30204

  View details for PubMedID 27419843

• Third party assessment of resection margin status in head and neck cancer. Oral oncology Ransohoff, A., Wood, D., Solomon Henry, A., Divi, V., Colevas, A. 2016; 57: 27-31

  Abstract

  Definitive assessment of primary site margin status following resection of head and neck cancer is necessary for prognostication, treatment determination and qualification for clinical trials. This retrospective analysis determined how often an independent reviewer can assess primary tumor margin status of head and neck cancer resections based on review of the pathology report, surgical operative report, and first follow-up note alone.We extracted from the electronic medical record pathology reports, operative reports, and follow-up notes from head and neck cancer resections performed at Stanford Hospital. We classified margin status as definitive or not. We labeled any pathology report clearly indicating a positive, negative, or close (<5mm) margin as definitive. For each non-definitive pathology report, we reviewed the operative report and then the first follow-up note in an attempt to clarify margin status. We also looked for associations between non-definitive status and surgeon, year, and primary site.743 unique cases of head and neck cancer resection were extracted. We discarded 255 as non-head and neck cancer cases, or cases that did not involve a definitive resection of a primary tumor site. We could not definitively establish margin status in 20% of resections by independent review of the medical record. There was no correlation between margin determination and surgeon, site, or year of surgery.A substantial fraction (20%) of primary site surgical margins could not be definitively determined via independent EMR review. This could have implications for subsequent patient care decisions and clinical trial options.

  View details for DOI 10.1016/j.oraloncology.2016.03.009

  View details for PubMedID 27208841

• Third party assessment of resection margin status in head and neck cancer ORAL ONCOLOGY Ransohoff, A., Wood, D., Henry, A. S., Divi, V., Colevas, A. 2016; 57: 27-31

  Abstract

  Definitive assessment of primary site margin status following resection of head and neck cancer is necessary for prognostication, treatment determination and qualification for clinical trials. This retrospective analysis determined how often an independent reviewer can assess primary tumor margin status of head and neck cancer resections based on review of the pathology report, surgical operative report, and first follow-up note alone.We extracted from the electronic medical record pathology reports, operative reports, and follow-up notes from head and neck cancer resections performed at Stanford Hospital. We classified margin status as definitive or not. We labeled any pathology report clearly indicating a positive, negative, or close (<5mm) margin as definitive. For each non-definitive pathology report, we reviewed the operative report and then the first follow-up note in an attempt to clarify margin status. We also looked for associations between non-definitive status and surgeon, year, and primary site.743 unique cases of head and neck cancer resection were extracted. We discarded 255 as non-head and neck cancer cases, or cases that did not involve a definitive resection of a primary tumor site. We could not definitively establish margin status in 20% of resections by independent review of the medical record. There was no correlation between margin determination and surgeon, site, or year of surgery.A substantial fraction (20%) of primary site surgical margins could not be definitively determined via independent EMR review. This could have implications for subsequent patient care decisions and clinical trial options.

  View details for DOI 10.1016/j.oraloncology.2016.03.009

  View details for Web of Science ID 000376084500010

  View details for PubMedID 27208841

• Consultation via telemedicine and access to operative care for patients with head and neck cancer in a Veterans Health Administration population HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Beswick, D. M., Vashi, A., Song, Y., Pham, R., Holsinger, F. C., Rayl, J. D., Walker, B., Chardos, J., Yuan, A., Benadam-Lenrow, E., Davis, D., Sung, C. K., Divi, V., Sirjani, D. B. 2016; 38 (6): 925-929

  Abstract

  The purpose of this study was to evaluate a telemedicine model that utilizes an audiovisual teleconference as a preoperative visit.Veterans Health Administration (VHA) patients with head and neck cancer at 2 remote locations were provided access to the Palo Alto Veterans Affairs (PAVA) Health Care System otolaryngology department via the telemedicine protocol: tissue diagnosis and imaging at the patient site; data review at PAVA; and a preoperative teleconference connecting the patient to PAVA. Operative care occurred at PAVA. Follow-up care was provided remotely via teleconference.Fifteen patients were evaluated. Eleven underwent surgery, 4 with high-grade neoplasms (carcinoma). Average time from referral to operation was 28 days (range, 17-36 days) and 72 (range, 31-108 days), respectively, for high-grade and low-grade groups. The average patient was spared 28 hours traveling time and $900/patient was saved on travel-related costs.A telemedicine model enables timely access to surgical care and permits considerable savings among select VHA patients with head and neck cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: 925-929, 2016.

  View details for DOI 10.1002/hed.24386

  View details for PubMedID 26899939

• Number of positive nodes is superior to the lymph node ratio and American Joint Committee on Cancer N staging for the prognosis of surgically treated head and neck squamous cell carcinomas CANCER Roberts, T. J., Colevas, A. D., Hara, W., Holsinger, F. C., Oakley-Girvan, I., Divi, V. 2016; 122 (9): 1388-1397

  Abstract

  Recent changes in head and neck cancer epidemiology have created a need for improved lymph node prognostics. This article compares the prognostic value of the number of positive nodes (pN) with the value of the lymph node ratio (LNR) and American Joint Committee on Cancer (AJCC) N staging in surgical patients.The Surveillance, Epidemiology, and End Results database was used to identify cases of head and neck squamous cell carcinomas from 2004 to 2012. The sample was grouped by the AJCC N stage, LNR, and pN and was analyzed with Kaplan-Meier and multivariate Cox proportional hazards models. The sample was also analyzed by the site of the primary tumor.This study identified 12,437 patients. Kaplan-Meier survival curves showed superior prognostic ability for LNR and pN staging in comparison with AJCC staging. Patients with a pN value > 5 had the worst overall survival (5-year survival rate, 16%). Patients with oropharyngeal tumors had better outcomes for all groupings, and a pN value > 5 for oropharyngeal cancers was associated with decreased survival. Multivariate regressions demonstrated larger hazard ratios (HRs) and a lower Akaike information criterion for the pN model versus the AJCC stage and LNR models. The HRs were 1.78 (95% confidence interval, 1.62-1.95) for a pN value of 1, 2.53 (95% confidence interval, 2.32-2.75) for a pN value of 2 to 5, and 4.64 (95% confidence interval, 4.18-5.14) for a pN value > 5.The pN models demonstrated superior prognostic value in comparison with the LNR and AJCC N staging. Future modifications of the nodal staging system should be based on the pN with a separate system for oropharyngeal cancers. Future trials should consider examining adjuvant treatment escalation in patients with >5 lymph nodes. Cancer 2016;122:1388-1397. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.29932

  View details for Web of Science ID 000374706500010

  View details for PubMedID 26969807

• Use of Pedicled Nasoseptal Flap for Pathologic Oroantral Fistula Closure JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY Noel, J. E., Teo, N. W., Divi, V., Nayak, J. V. 2016; 74 (4)

  View details for DOI 10.1016/j.joms.2015.11.010

  View details for Web of Science ID 000373090400006

• Regional variation in head and neck cancer mortality: Role of patient and hospital characteristics HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Divi, V., Ma, Y., Rhoads, K. F. 2016; 38: E1896-E1902

  Abstract

  The purpose of this study was to determine whether outcomes in head and neck cancer would vary based on geographic location of patients.A dataset from the California Cancer Registry was linked to publicly available discharge abstracts. Patients were separated into geographic areas based on health service areas (HSAs). Multilevel logistic regression models were constructed to include geographic, patient, and hospital-level characteristics.There was significant variation in 5-year survival hazard ratios (HRs) among the majority of the 14 HSAs in the unadjusted model. After adjusting for patient and hospital characteristics, the differences between regions were not significant except for Orange County (HR = 0.75). Commission on Cancer certification (HR = 0.82; p < .01) and hospital volume (HR = 0.975; p < .01) were each independently associated with differences in survival.Geographic variation in 5-year survival outcomes is seen in head and neck cancer. Patient characteristics and treating hospitals explain much of this variation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1896-E1902, 2016.

  View details for DOI 10.1002/hed.24343

  View details for Web of Science ID 000375116400247

  View details for PubMedID 26713544

• Use of Pedicled Nasoseptal Flap for Pathologic Oroantral Fistula Closure. Journal of oral and maxillofacial surgery Noel, J. E., Teo, N. W., Divi, V., Nayak, J. V. 2016; 74 (4): 704 e1-6

  Abstract

  Oroantral fistula (OAF) is a pathologic, epithelialized communication between the oral cavity and the maxillary sinus. OAF most commonly results from posterior maxillary tooth or molar extraction owing to proximity of the dental roots to the maxillary antrum and the thinness of the adjacent antral floor. It also can arise secondary to implant and orthognathic surgeries, cyst and tumor removal, dental infection, trauma, or as a sequela of radiation therapy. Communications larger than 5 mm are less likely to heal spontaneously and can epithelialize, forming an OAF. When locoregional flaps and grafts are not ideal or have failed, but primary OAF closure is mandated, surgical options are unclear. This report describes a novel method for autologous tissue flap coverage from the nasal septum, pedicled off the posterior septal artery, for successful extension to, and closure of, OAFs.

  View details for DOI 10.1016/j.joms.2015.11.010

  View details for PubMedID 26704432

• A prospective study of electronic quality of life assessment using tablet devices during and after treatment of head and neck cancers. Oral oncology Pollom, E. L., Wang, E., Bui, T. T., Ognibene, G., von Eyben, R., Divi, V., Sunwoo, J., Kaplan, M., Dimitri Colevas, A., Le, Q., Hara, W. Y. 2015; 51 (12): 1132-1137

  Abstract

  Electronic data collection is increasingly used for quality of life (QOL) assessments in the field of oncology. It is important to assess the feasibility of these new data capture technologies.Patients at our institution who were 18years or older with a pathological diagnosis of head and neck cancer were prospectively enrolled. Each patient completed two questionnaires [EORTC-QLQ-C30 and EORTC-QLQ-H&N35] administered on a touch-screen tablet device (iPad™) at initial consult, during treatment, at the completion of treatment and at each subsequent follow up visit for one year after treatment.A total of 50 patients were included in this study. Although all patients completed the surveys at the initial consult, 86% of initially enrolled patients completed surveys at the end of radiation treatment, and 48% of initially enrolled patients completed surveys by the fourth follow-up visit. Average time to complete the survey for all patients over all time points was 9.8min (standard deviation 6.1). Age as a continuous variable was significantly associated with time for survey completion (p<0.001), with older age associated with longer survey completion times.QOL assessment using tablet devices in head and neck cancer patients is feasible, but may be more challenging in elderly patients. Patients ⩾70years old may benefit from more assistance with electronic forms and should be allotted more time for completing tablet-based QOL surveys.

  View details for DOI 10.1016/j.oraloncology.2015.10.003

  View details for PubMedID 26475062

• Anterolateral approach to the upper cervical spine: Case report and operative technique HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Song, Y., Tharin, S., Divi, V., Prolo, L. M., Sirjani, D. B. 2015; 37 (9): E115-E119

  Abstract

  Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. © 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.

  View details for DOI 10.1002/hed.23951

  View details for Web of Science ID 000359605700004

  View details for PubMedID 25522016

• Effect of the extent of lymph node dissection on overall survival in patients treated for oral cavity squamous cell carcinoma Shah, J., Kaplan, M., Divi, V., Quynh-Thu Le, Hara, W. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for Web of Science ID 000358036901392

• Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes, NRG Oncology/RTOG 9501-0234. Divi, V., Harris, J., Harari, P. M., Cooper, J., McHugh, J. B., Bell, D., Sturgis, E. M., Cmelak, A., Suntharalingam, M., Raben, D., Kim, H. E., Spencer, S., Laramore, G. E., Trotti, A., Foote, R., Schultz, C. J., Thorstad, W. L., Zhang, Q., Quynh-Thu Le, Holsinger, F. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for DOI 10.1200/jco.2015.33.15_suppl.6011

  View details for Web of Science ID 000358036901323

• Third party assessment of resection margin status in head and neck cancer. Ransohoff, A., Wood, D., Henry, S., Divi, V., Colevas, A. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for DOI 10.1200/jco.2015.33.15_suppl.e17011

  View details for Web of Science ID 000358036903396

• CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma. Oncotarget Murillo-Sauca, O., Chung, M. K., Shin, J. H., Karamboulas, C., Kwok, S., Jung, Y. H., Oakley, R., Tysome, J. R., Farnebo, L. O., Kaplan, M. J., Sirjani, D., Divi, V., Holsinger, F. C., Tomeh, C., Nichols, A., Le, Q. T., Colevas, A. D., Kong, C. S., Uppaluri, R., Lewis, J. S., Ailles, L. E., Sunwoo, J. B. 2014; 5 (16): 6854-6866

  Abstract

  Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.

  View details for PubMedID 25149537

• EVALUATION OF CD44 VARIANT EXPRESSION IN ORAL, HEAD AND NECK SQUAMOUS CELL CARCINOMAS USING A TRIPLE APPROACH AND ITS CLINICAL SIGNIFICANCE INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY Athanassiou-Papaefthymiou, M., Shkeir, O., Kim, D., Divi, V., MATOSSIAN, M., Owen, J. H., CZERWINSKI, M. J., PAPAGERAKIS, P., McHugh, J., Bradford, C. R., Carey, T. E., Wolf, G. T., Prince, M. E., Papagerakis, S. 2014; 27 (3): 337-349

  Abstract

  Cancer stem cells possess the qualities of self-renewal, tumorigenesis and the ability to recapitulate a heterogeneous tumor. Our group was the first to isolate head and neck squamous cell carcinoma (HNSCC) stem cells using the cell surface marker CD44. CD44 is a trans-membrane glycoprotein with a multitude of key-functions that regulate cancer cell proliferation and metastasis. The variety of CD44 functions is due to tissue-specific patterns of glycosylation of the extracellular portion, and to the multiple protein isoforms (CD44 variants, CD44v) generated by alternative splicing. This study investigates the expression pattern of CD44 variants in HNSCC. Ten cell lines from the most common HNSCC locations and representative of various clinical outcomes were assayed by quantitative realtime PCR, flow cytometry and immunofluorescence comparatively with normal oral keratinocytes. The CD44 v4 and v6 were exclusively abundant in HNSCC while the isoform v1,2 was expressed in normal oral keratinocytes. Of interest, the highest level of CD44v6 expression was detected in advanced metastatic HNSCC, suggesting a link between CD44v6 expression and HNSCC metastasis, while the highest CD44v4 was detected in a stage IV HNSCC refractory to chemotherapy which developed recurrence. Oral-derived HNSCC expressed the highest CD44v4 and v6, and levels corresponded with staging, showing also an increasing tendency with recurrence and metastasis. CD44v were detected predominantly in smaller cells (a characteristic that has been associated with stem cell properties) or cells with mesenchymal morphology (a characteristic that has been associated with the migratory and invasive potential of epithelial tumor cells), suggesting that CD44v differential expression in HNSCC may be representative of the morphological changes inherent during tumor progression towards a more aggressive potential, and thus contributing to the individual tumor biology. The mechanism of CD44 variant involvement in HNSCC progression and metastasis is under investigation.

  View details for Web of Science ID 000342397100004

  View details for PubMedID 25280025

• Characterization of tumorigenic cell lines from the recurrence and lymph node metastasis of a human salivary mucoepidermoid carcinoma ORAL ONCOLOGY Warner, K. A., Adams, A., Bernardi, L., Nor, C., Finkel, K. A., Zhang, Z., McLean, S. A., Helman, J., Wolf, G. T., Divi, V., Queimado, L., Kaye, F. J., Castilho, R. M., Noer, J. E. 2013; 49 (11): 1059-1066

  Abstract

  The long-term outcome of patients with mucoepidermoid carcinoma is poor. Limited availability of cell lines and lack of xenograft models is considered a major barrier to improved mechanistic understanding of this disease and development of effective therapies.To generate and characterize human mucoepidermoid carcinoma cell lines and xenograft models suitable for mechanistic and translational studies.Five human mucoepidermoid carcinoma specimens were available for generation of cell lines. Cell line tumorigenic potential was assessed by transplantation and serial in vivo passaging in immunodeficient mice, and cell line authenticity verified by short tandem repeat (STR) profiling.A unique pair of mucoepidermoid carcinoma cell lines was established from a local recurrence (UM-HMC-3A) and from the metastatic lymph node (UM-HMC-3B) of the same patient, 4years after surgical removal of the primary tumor. These cell lines retained epithelial-like morphology through 100 passages in vitro, contain the Crtc1-Maml2 fusion oncogene (characteristic of mucoepidermoid carcinomas), and express the prototypic target of this fusion (NR4A2). Both cell lines generated xenograft tumors when transplanted into immunodeficient mice. Notably, the xenografts exhibited histological features and Periodic Acid Schiff (PAS) staining patterns that closely resembled those found in human tumors. STR profiling confirmed the origin and authenticity of these cell lines.These data demonstrate the generation and characterization of a pair of tumorigenic salivary mucoepidermoid carcinoma cell lines representative of recurrence and lymph node metastasis. Such models are useful for mechanistic and translational studies that might contribute to the discovery of new therapies for mucoepidermoid carcinoma.

  View details for DOI 10.1016/j.oraloncology.2013.08.004

  View details for Web of Science ID 000325461200004

  View details for PubMedID 24035723

  View details for PubMedCentralID PMC3821871

• Transoral robotic biopsy of the tongue base: A novel paradigm in the evaluation of unknown primary tumors of the head and neck HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Abuzeid, W. M., Bradford, C. R., Divi, V. 2013; 35 (4): E126-E130

  Abstract

  Squamous cell carcinoma of the head and neck can present as a cervical metastasis from an unknown primary site. The standard diagnostic workup includes panendoscopy and directed biopsies but this will fail to identify a portion of unknown primary tumors.Herein, we present a case report of a male patient with an unknown primary tumor in which the da Vinci surgical robot was used to evaluate the tongue base.Clinical evaluation, imaging, and panendoscopy with directed biopsies failed to detect the primary tumor site. Robot-assisted biopsy of a broad area of the tongue base, incorporating submucosal tissue, identified the primary tumor with minimal postoperative morbidity.Failure to localize an unknown primary tumor often results in widespread irradiation of the upper aerodigestive tract, inducing significant morbidity. Robot-assisted biopsies of the tongue base may identify unknown primaries that would otherwise have been missed through standard directed biopsy techniques.

  View details for DOI 10.1002/hed.21968

  View details for Web of Science ID 000316575900007

  View details for PubMedID 22180229

• Diagnostic modalities for distant metastasis in head and neck squamous cell carcinoma: Are we changing life expectancy? LARYNGOSCOPE Spector, M. E., Chinn, S. B., Rosko, A. J., Worden, F. P., Ward, P. D., Divi, V., McLean, S. A., Moyer, J. S., Prince, M. E., Wolf, G. T., Chepeha, D. B., Bradford, C. R. 2012; 122 (7): 1507-1511

  Abstract

  To determine if the various imaging modalities for distant metastasis (DM) diagnosis alters life expectancy in head and neck squamous cell carcinoma (HNSCC).Retrospective.One hundred seventy patients (mean age, 59.1 years; male:female, 135:35) with HNSCC who developed DM were reviewed. The main outcome measures were the method of DM diagnosis and time from DM diagnosis to death while controlling for clinical parameters (age, gender, tobacco status, primary tumor site, initial TNM classification, number and site of DM, administration of palliative chemotherapy).Tumor subsites were: 40 oral cavity, 75 oropharynx, 36 larynx, 10 hypopharynx, one nasopharynx, and eight unknown primary. Of the patients, 16.5% (28/170) had distant metastasis at presentation; the remaining 142 patients were diagnosed with DM at a median of 324 days from diagnosis. Although patients diagnosed with DM by positron-emission tomography (PET) scan were more likely to have multiple DM sites (P = .0001), there were no differences in life expectancy in patients who were diagnosed with or without PET scan (median, 185 vs. 165 days, P = .833). There were no differences in life expectancy based on age, gender, site of primary tumor, or number/site of DM. The use of palliative chemotherapy resulted in a significantly longer life expectancy (median, 285 vs. 70 days; P = .001).Although a PET scan is more likely to diagnose multiple DM sites, there was no difference in life expectancy based on imaging modality. Patients who are symptomatic from their distant metastasis have a worse life expectancy, and palliative chemotherapy was able to increase life expectancy, even in patients who were symptomatic from the distant metastasis.

  View details for DOI 10.1002/lary.23264

  View details for Web of Science ID 000305577400015

  View details for PubMedID 22460441

  View details for PubMedCentralID PMC3470851

• Re-animation and rehabilitation of the paralyzed face in head and neck cancer patients CLINICAL ANATOMY Divi, V., Deschler, D. G. 2012; 25 (1): 99-107

  Abstract

  Facial nerve paralysis can occasionally result from the treatment of head and neck cancer. The treatment of paralysis is patient specific, and requires an assessment of the remaining nerve segments, musculature, functional deficits, anticipated recovery, and patient factors. When feasible, reinnervation of the remaining musculature can provide the most natural outcome. However, the complex and topographic nature of facial innervation often prevents complete and meaningful movement. In these instances, a wide variety of procedures can be used to combat the functional and cosmetic sequella of facial paralysis.

  View details for DOI 10.1002/ca.21286

  View details for Web of Science ID 000298302200010

  View details for PubMedID 22025410

• Primary TEP Placement in Patients with Laryngopharyngeal Free Tissue Reconstruction and Salivary Bypass Tube Placement OTOLARYNGOLOGY-HEAD AND NECK SURGERY Divi, V., Lin, D. T., Emerick, K., Rocco, J., Deschler, D. G. 2011; 144 (3): 474-476

  Abstract

  The authors examined the feasibility and advantages of primary tracheoesophageal puncture (TEP) with intraoperative placement of the voice prosthesis for patients undergoing laryngopharyngectomy requiring free tissue reconstruction and salivary bypass tube placement. Six patients were identified; 4 underwent total laryngopharyngectomy, and 2 underwent total laryngectomy with partial pharyngectomy. All 6 required free tissue reconstruction, and a salivary bypass tube was placed in all cases. All patients had a 20F Indwelling Blom-Singer prosthesis (InHealth Technologies, Carpinteria, California) placed. No complications were noted with intraoperative prosthesis placement. No prostheses were dislodged in the postoperative period. At 6 months, 4 patients available for evaluation had successful voice outcomes, and 3 were disease free. This study demonstrates the effectiveness of voice prosthesis placement at the time of primary TEP associated with free tissue reconstruction of a laryngopharyngeal defect with salivary bypass tube placement.

  View details for DOI 10.1177/0194599810391960

  View details for Web of Science ID 000293997400025

  View details for PubMedID 21493216

• Metastatic Potential of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Davis, S. J., Divi, V., Owen, J. H., Bradford, C. R., Carey, T. E., Papagerakis, S., Prince, M. E. 2010; 136 (12): 1260-1266

  Abstract

  to design in vitro and in vivo models of metastasis to study the behavior of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC).cells were sorted for CD44 expression using flow cytometry. Sorted cells were used in an in vitro invasion assay. For in vivo studies, CSCs and non-CSCs were injected into the tail veins of mice, and lungs were either harvested or imaged to evaluate for lesions.in vitro, CD44(high) cells were more motile but not more invasive than CD44(low) cells. In vivo, 8 of 17 mice injected with CD44(high) cells and 0 of 17 mice injected with CD44(low) cells developed lung lesions. Two of the lesions arose from CSCs from a primary tumor and 6 from CSCs from HNSCC cell lines.in vitro, CSCs do not have an increased ability to invade through basement membrane, but they migrate more efficiently through a porous barrier. In contrast, CSCs efficiently formed lung lesions in vivo, whereas non-CSCs did not give rise to any distant disease. This phenomenon could be due to the enhanced migratory capacity of CSCs, which may be more important than basement membrane degradation in vivo.

  View details for Web of Science ID 000285323000014

  View details for PubMedID 21173377

• CHEMOTHERAPY ALONE FOR ORGAN PRESERVATION IN ADVANCED LARYNGEAL CANCER HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Divi, V., Worden, F. P., Prince, M. E., Eisbruch, A., Lee, J. S., Bradford, C. R., Chepeha, D. B., Teknos, T. N., Hogikyan, N. D., Moyer, J. S., Tsien, C. I., Urba, S. G., Wolf, G. T. 2010; 32 (8): 1040-1055

  Abstract

  For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy.Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response.A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively.Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site.

  View details for DOI 10.1002/hed.21285

  View details for Web of Science ID 000280539500009

  View details for PubMedID 19953609

  View details for PubMedCentralID PMC2891819

• Use-of cross-sectional imaging in predicting surgical location of parotid neoplasms JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Divi, V., Fatt, M. A., Teknos, T. N., Mukherji, S. K. 2005; 29 (3): 315-319

  Abstract

  The purpose of this study was to determine the diagnostic accuracy of using the retromandibular vein as seen on cross-sectional imaging to help differentiate superficial lobe from deep lobe tumors.Of the patients who had parotid neoplasms between January 1997 and July 2002, we were able to identify 44 patients with preoperative imaging studies that were available for evaluation. The films were reviewed by a single head and neck radiologist to determine whether the neoplasms involved the superficial, deep, or both lobes of the parotid gland (total). The lateral margin of the retromandibular vein was used as a marker for the facial nerve, since the nerve is not always visible on CT and MRI scans. The radiologist's findings were then compared with the findings during surgery. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of predicting the location of neoplasms were then calculated.For lesions in the superficial lobe, cross-sectional imaging was able to predict the location of the neoplasm with a sensitivity of 0.91 (95% CI, 0.70-0.98), specificity of 0.86 (95% CI, 0.63-0.96), PPV of 0.88 (95% CI, 0.67-0.97), and NPV of 0.90 (95% CI, 0.67-0.98). For lesions in both lobes (total), cross-sectional imaging was able to predict the location of the neoplasm with a sensitivity of 0.94 (95% CI, 0.68-0.99), specificity of 0.89 (95% CI, 0.71-0.97), PPV of 0.83 (95% CI, 0.58-0.96), and NPV of 0.96 (95% CI, 0.78-0.99).Use of the retromandibular vein as a marker for the facial nerve is a sensitive method for identifying the location of parotid gland neoplasms on cross-sectional imaging. This supports the accuracy of using preoperative imaging to detect the position of parotid neoplasms with respect to the facial nerve.

  View details for Web of Science ID 000229458400006

  View details for PubMedID 15891497