Michelle M. Chen, MD, MHS

All Publications

• Surgical Oncology Care for Patients With Frailty-Is the Juice Worth the Squeeze? JAMA otolaryngology-- head & neck surgery Chen, M. M., Sethi, R. K. 2024

  View details for DOI 10.1001/jamaoto.2024.3745

  View details for PubMedID 39509104

• Factors Associated With Psychological Distress Among Thyroid Cancer Patients. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Lin, M. E., Wei, E. X., Finegersh, A., Orloff, L. A., Noel, J. E., Chen, M. M. 2024

  Abstract

  OBJECTIVE: To assess the prevalence of psychological distress (PD) among thyroid cancer patients (TCPs) and identify clinical, demographic, and socioeconomic factors associated with PD.STUDY DESIGN: Retrospective population-based cohort study.SETTING: 2016 to 2018 National Health Interview Survey.METHODS: Adults with cancer were included. The primary outcome measure was moderate-to-severe psychological distress (MSPD), defined as a respondent score ≥5 on the validated K6 Psychological Distress Scale. chi2 tests were used to assess differences in MSPD by cancer type. Weighted multivariable logistic regression was used to elucidate factors associated with MSPD among TCPs.RESULTS: The majority of TCPs (n=684,674) were white (75.4%), female (78.5%), and on average 55.65 years old (SD=13.2). 28.4% reported MSPD. On weighted analysis, TCPs were more likely to have MSPD than prostate (14.9%, P<.001), bladder (16.4%, P=.011), and nonmelanoma skin cancer (16.3%, P<.001) patients but less likely than pancreatic cancer (30.0%, P=.030) patients. TCPs who were older when surveyed (odds ratio [OR], 0.93; 95% confidence interval [CI, 0.88-0.98), previously drank alcohol (OR, 0.23; 95% CI, 0.06-0.91), and saw a general physician (GP) in the past year (OR, 0.14; 95% CI, 0.03-0.56) were less likely to have MSPD. Female sex (OR, 8.12; 95% CI, 1.61-40.89), increased number of medical comorbidities (OR, 1.46; 95% CI, 1.00-2.14), and functional limitations (OR, 4.55; 95% CI, 1.33-15.74) were associated with increased likelihood of MSPD.CONCLUSION: Nearly 30% of TCPs have MSPD, especially younger patients who do not regularly see GPs. Future work to identify the most at-risk patients is needed to improve prevention and develop meaningful psychosocial interventions.

  View details for DOI 10.1002/ohn.1051

  View details for PubMedID 39501654

• Oropharyngeal cancer: Lack of human papillomavirus awareness and economic burden in the United States. Clinical and translational medicine Lechner, M., Masterson, L., Mermelstein, S., Liu, J., Rehman, U., Chen, M., O'Mahoney, J., Holsinger, F. C. 2024; 14 (11): e70062

  View details for DOI 10.1002/ctm2.70062

  View details for PubMedID 39558538

  View details for PubMedCentralID PMC11573731

• Comorbid Depression in Patients With Head and Neck Cancer Compared With Other Cancers. JAMA otolaryngology-- head & neck surgery Martinez, M. C., Finegersh, A., Baik, F. M., Holsinger, F. C., Starmer, H. M., Orloff, L. A., Sunwoo, J. B., Sirjani, D., Divi, V., Chen, M. M. 2024

  Abstract

  Depression is more prevalent among individuals with cancer than in the general population and is correlated with increased mortality in patients with head and neck cancer (HNC) in particular.To compare the prevalence of depression between patients with HNC and patients with other cancers.This retrospective cohort study used population-level data on patients aged 18 years or older with cancer who participated in the 2019 National Health Interview Survey and had completed the Personal Health Questionnaire-8 (PHQ-8). The analysis was performed between August 7, 2023, and April 5, 2024.Any cancer diagnosis.The main outcome was prevalence and severity of depression based on the PHQ-8. The magnitude of the difference in baseline characteristics was measured between patients with HNC and those with other cancer types, and 95% CIs were used to measure the precision of these estimates. Multivariable logistic regressions were used to evaluate the association of demographic, socioeconomic, anxiety, and clinical variables with depression.From a weighted cohort of 23 496 725 adult patients with cancer, 377 080 were diagnosed with HNC (87.5% aged 51-84 years; 77.9% male). The prevalence of any depression on the PHQ-8 (mild, moderate, or severe) was 40.1% in patients with HNC vs 22.3% in patients with other cancers. Compared with patients with other cancers, patients with HNC were equally likely to screen positive for anxiety (23.6% vs 16.0%; difference, 7.6%; 95% CI, -5.9% to 21.1%), take medication for depression (10.1% vs 13.9%; difference, -3.8%; 95% CI, -11.9% to 4.4%), and state that they never feel depressed (59.7% vs 53.7%; difference, 6.0%; 95% CI, -9.1% to 21.0%). On multivariable logistic regression analysis, having HNC was associated with an increased likelihood of depression (odds ratio [OR], 2.94; 95% CI, 1.39-6.22). Other factors associated with depression were being unmarried or not living with a partner (OR, 1.94; 95% CI, 1.55-2.43) and having anxiety (OR, 23.14; 95% CI, 17.62-30.37).This cohort study found that patients with HNC were twice as likely to screen positive for depression on a validated survey than those with other cancers, despite having similar rates of self-reported depression and depression medication use. These findings suggest that self-reporting of depression may result in underreporting and undertreatment in this population and, thus, a need for further work in developing interventions to improve identification of and optimize treatment for patients with HNC and comorbid depression.

  View details for DOI 10.1001/jamaoto.2024.3233

  View details for PubMedID 39446380

• Timely Treatment and No Change in Thyroid Cancer Mortality During COVID-19 Pandemic. Reply to Nocini et al. No Impact of COVID-19 Pandemic on Early Mortality for Thyroid Cancer in the US. Comment on "Lee et al. Impact of the COVID-19 Pandemic on Thyroid Cancer Surgery. Curr. Oncol. 2024, 31, 3579-3590". Current oncology (Toronto, Ont.) Lee, M. L., Chen, M. M. 2024; 31 (10): 6270-6271

  Abstract

  We thank Nocini et al [...].

  View details for DOI 10.3390/curroncol31100467

  View details for PubMedID 39451771

• Patient perceptions underlying ctDNA molecular surveillance for HPV(+) oropharyngeal squamous cell carcinoma. Oral oncology Bastien, A. J., Ng, J., Cong, I., Garcia, J., Walgama, E. S., Luu, M., Jang, J. K., Mita, A. C., Scher, K. S., Moyers, J. T., Clair, J. M., Maghami, E., Chen, M. M., Zumsteg, Z. S., Ho, A. S. 2024; 156: 106894

  Abstract

  Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC).Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay.Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety.ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines.

  View details for DOI 10.1016/j.oraloncology.2024.106894

  View details for PubMedID 38909394

• Impact of the COVID-19 Pandemic on Thyroid Cancer Surgery. Current oncology (Toronto, Ont.) Lee, M. L., Megwalu, U. C., Finegersh, A., Noel, J. E., Chen, M. M. 2024; 31 (6): 3579-3590

  Abstract

  The COVID-19 pandemic caused major disruptions to healthcare services in 2020, delaying cancer diagnosis and treatment. While early-stage thyroid cancer often progresses slowly, it is crucial to determine whether treatment delays associated with the pandemic have impacted the clinical presentation and management of advanced-stage thyroid cancer. The purpose of our study was to determine the impact of the early COVID-19 pandemic on thyroid cancer presentation and treatment times. Utilizing the National Cancer Database, chi-squared tests and regression analyses were performed to compare patient demographic and clinical characteristics over time for 56,011 patients diagnosed with primary thyroid cancer who were treated at the Commission on Cancer-accredited sites in 2019 and 2020. We found that thyroid cancer diagnoses decreased between 2019 and 2020, with the biggest drop among patients with cT1 disease relative to other T stages. We also found that patients diagnosed with thyroid cancer in 2020 had similar treatment times to patients diagnosed in 2019, as measured by both the time between diagnosis and start of treatment and the time between surgery and start of radioactive iodine therapy. Overall, our study suggests that resources during the pandemic were allocated to patients with advanced thyroid disease, despite a decrease in diagnoses.

  View details for DOI 10.3390/curroncol31060263

  View details for PubMedID 38920746

• A Novel Gene Fusion YLPM1::PRKD1 Identified in a Cribriform Subtype of Polymorphous Adenocarcinoma. Head and neck pathology Miyakawa-Liu, M., Ozawa, M. G., Chen, M., Rahman, M. 2024; 18 (1): 43

  Abstract

  Cribriform adenocarcinoma of the salivary gland (CASG) is an entity that is currently classified under polymorphous adenocarcinoma (PAC), cribriform subtype per the 2022 WHO classification of head and neck tumours. There is debate about whether CASG should be considered a separate diagnostic entity, as CASG differs from conventional PAC in anatomic site, clinical behaviors, and molecular patterns. Herein we describe a challenging and unique case which shares histologic and behavioral features between CASG and conventional PAC with a YLPM1::PRKD1 rearrangement not previously reported in the literature.

  View details for DOI 10.1007/s12105-024-01648-z

  View details for PubMedID 38735907

  View details for PubMedCentralID 7863585

• Sinonasal Tumors Masquerading as Invasive Fungal Sinusitis (IFS). The Annals of otology, rhinology, and laryngology Pak, K. Y., Hsue, V. B., Lee, M. K., Chen, M. M., Balzer, B., Wu, A. W., Tang, D. M. 2024: 34894241238864

  Abstract

  Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma.Here, we describe 3 cases of carcinoma mimicking IFS from a single institution.Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality.We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma.

  View details for DOI 10.1177/00034894241238864

  View details for PubMedID 38491860

• 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

• Global Epidemiologic Patterns of Oropharyngeal Cancer Incidence Trends. Journal of the National Cancer Institute Zumsteg, Z. S., Luu, M., Rosenberg, P. S., Elrod, J. K., Bray, F., Vaccarella, S., Gay, C., Lu, D. J., Chen, M. M., Chaturvedi, A. K., Goodman, M. T. 2023

  Abstract

  The emergence of HPV-positive oropharyngeal cancer (OPC) and evolving tobacco use patterns have changed the landscape of head and neck cancer epidemiology internationally. We investigated updated trends in OPC incidence worldwide.We analyzed cancer incidence data during 1993-2012 from 42 countries using the Cancer Incidence in Five Continents database Volumes V-XI. Trends in OPC incidence were compared to oral cavity cancers (OCC) and lung squamous cell carcinoma (SCC) using log-linear regression and age-period-cohort modeling.156,567 OPC, 146,693 OCC, and 621,947 lung SCC cases were included. OPC incidence significantly increased in 19 and 23 countries in men and women, respectively. In countries with increasing male OPC incidence, all but one had significantly decreasing lung SCC incidence, and all but two had decreasing or non-significant net drifts for OCC. Increased OPC incidence was observed both in middle (40-59 years old) and older (≥60 years old) age male cohorts, with strong non-linear birth cohort effects. In 20 countries where OPC incidence increased for women and age-period-cohort analysis was possible, 13 had negative or non-significant lung SCC net drifts, including 4 with significantly higher OPC net drift increases vs both lung SCC and OCC.Increasing OPC incidence is seen among an expanding array of countries worldwide. In men, increased OPC is extending to older age groups, likely driven by HPV-related birth-cohort effects. In women, more diverse patterns were observed, suggesting complex interplay of risks factors varying by country, including several countries where female OPC increases may be driven by HPV.

  View details for DOI 10.1093/jnci/djad169

  View details for PubMedID 37603716

• Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system. Head & neck Ho, A. S., Luu, M., Balzer, B. L., Aro, K., Jang, J. K., Mita, A. C., Scher, K. S., Mallen-St Clair, J., Vasquez, M., Bastien, A. J., Epstein, J. B., Lin, D., Chen, M. M., Zumsteg, Z. S. 2023

  Abstract

  BACKGROUND: The comparative impact of histologic variants and grade has not been well described.METHODS: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival.RESULTS: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p<0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p<0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM+G schema (c-index 0.75) superior to the existing system (c-index 0.73).CONCLUSION: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

  View details for DOI 10.1002/hed.27429

  View details for PubMedID 37345665

• The influence of grade on mortality risk in salivary gland malignancy Bastien, A. J., Luu, M., Balzer, B., Aro, K., Jang, J., Mita, A. C., Scher, K., Mallen-St. Clair, J., Vasquez, M., Epstein, J., Lin, D. J., Chen, M., Zumsteg, Z., Ho, A. S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772004098

• Diagnostic Assessment (Imaging) and Staging of Laryngeal Cancer. Otolaryngologic clinics of North America Itamura, K., Hsue, V. B., Barbu, A. M., Chen, M. M. 2023; 56 (2): 215-231

  Abstract

  Diagnosis of larynx cancer relies on a detailed history and physical and objective assessment with endoscopy and imaging. Endoscopy is needed to assess for vocal fold function that directly affects staging. Computed tomography and MRI can be used to assess for tumor extent in relation to intra- and extra-laryngeal structures, especially paraglottic and pre-epiglottic space involvement as well as cartilage invasion. Accurate staging is critical for subsequent treatment decision-making regarding larynx preservation.

  View details for DOI 10.1016/j.otc.2022.12.006

  View details for PubMedID 37030936

• Impact of monoclonal antibody therapy for head and neck cancer on end-of-life care utilization and costs. Head & neck Benjamin, W. J., Yalamanchi, P., Taylor, J. M., Lenze, N., Worden, F. P., Chinn, S. B., Chen, M. M. 2023

  Abstract

  The impact of monoclonal antibody therapy (mAB) for advanced head and neck cancer on end-of-life health care utilization and costs has yet to be adequately studied.Retrospective cohort study of patients aged 65 and over with a diagnosis of head and neck cancer between 2007 and 2017 within the SEER-Medicare registry assessing the impact of mAB therapy (i.e., cetuximab, nivolumab, or pembrolizumab) on end-of-life health care utilization (ED visits, inpatient admissions, ICU admissions, and hospice claims) and costs.Of 12 544 patients with HNC, 270 (2.2%) utilized mAB therapy at the end-of-life period. On multivariable analyses adjusting for demographic and clinicopathologic characteristics, there was a significant association between mAB therapy and emergency department visits (OR: 1.38, 95% CI: 1.1-1.8, p = 0.01) and healthcare costs (β: $9760, 95% CI: 5062-14 458, p < 0.01).mAB use is associated with higher emergency department utilization and health care costs potentially due to infusion-related and drug toxicity expenses.

  View details for DOI 10.1002/hed.27359

  View details for PubMedID 36976786

• Expanded Parameters in Active Surveillance for Low-risk Papillary Thyroid Carcinoma: A Nonrandomized Controlled Trial. JAMA oncology Ho, A. S., Kim, S., Zalt, C., Melany, M. L., Chen, I. E., Vasquez, J., Mallen-St Clair, J., Chen, M. M., Vasquez, M., Fan, X., van Deen, W. K., Haile, R. W., Daskivich, T. J., Zumsteg, Z. S., Braunstein, G. D., Sacks, W. L. 2022

  Abstract

  Unlike for prostate cancer, active surveillance for thyroid cancer has not achieved wide adoption. The parameters by which this approach is feasible are also not well defined, nor is the effect of patient anxiety.To determine if expanded size/growth parameters for patients with low-risk thyroid cancer are viable, as well as to assess for cohort differences in anxiety.This prospective nonrandomized controlled trial was conducted at a US academic medical center from 2014 to 2021, with mean [SD] 37.1 [23.3]-month follow-up. Of 257 patients with 20-mm or smaller Bethesda 5 to 6 thyroid nodules, 222 (86.3%) enrolled and selected treatment with either active surveillance or immediate surgery. Delayed surgery was recommended for size growth larger than 5 mm or more than 100% volume growth. Patients completed the 18-item Thyroid Cancer Modified Anxiety Scale over time.Active surveillance.Cumulative incidence and rate of size/volume growth.Of the 222 patients enrolled, the median (IQR) age for the study population was 46.8 (36.6-58) years, and 76.1% were female. Overall, 112 patients (50.5%) underwent treatment with active surveillance. Median tumor size was 11.0 mm (IQR, 9-15), and larger tumors (10.1-20.0 mm) comprised 67 cases (59.8%). One hundred one (90.1%) continued to receive treatment with active surveillance, 46 (41.0%) had their tumors shrink, and 0 developed regional/distant metastases. Size growth of more than 5 mm was observed in 3.6% of cases, with cumulative incidence of 1.2% at 2 years and 10.8% at 5 years. Volumetric growth of more than 100% was observed in 7.1% of cases, with cumulative incidence of 2.2% at 2 years and 13.7% at 5 years. Of 110 patients who elected to undergo immediate surgery, 21 (19.1%) had equivocal-risk features discovered on final pathology. Disease severity for all such patients remained classified as stage I. Disease-specific and overall survival rates in both cohorts were 100%. On multivariable analysis, immediate surgery patients exhibited significantly higher baseline anxiety levels compared with active surveillance patients (estimated difference in anxiety scores between groups at baseline, 0.39; 95% CI, 0.22-0.55; P < .001). This difference endured over time, even after intervention (estimated difference at 4-year follow-up, 0.50; 95% CI, 0.21-0.79; P = .001).The results of this nonrandomized controlled trial suggest that a more permissive active surveillance strategy encompassing most diagnosed thyroid cancers appears viable. Equivocal-risk pathologic features exist in a subset of cases that can be safely treated, but suggest the need for more granular risk stratification. Surgery and surveillance cohorts possess oppositional levels of worry, elevating the importance of shared decision-making when patients face treatment equivalence.ClinicalTrials.gov Identifier: NCT02609685.

  View details for DOI 10.1001/jamaoncol.2022.3875

  View details for PubMedID 36107411

  View details for PubMedCentralID PMC9478884

• 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

• Impact of Nodal Metastases in HPV-Negative Oropharyngeal Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Chang, C. M., Chen, M. M., Bellile, E. L., Rozek, L. S., Carey, T. E., Spector, M. E., Wolf, G. T., Taylor, J. M., Chinn, S. B. 2022; 31 (8): 1554-1563

  Abstract

  The updated American Joint Committee on Cancer (AJCC) 8th Edition staging manual restructured nodal classification and staging by placing less prognostic emphasis on nodal metastases for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). However, there was no change for HPV-negative OPSCC. The purpose of our study is to examine the impact of nodal metastases on survival in HPV-negative OPSCC.HPV-negative OPSCC was queried from the National Cancer Database (NCDB) and Surveillance, Epidemiology and End Results program (SEER) databases. Univariable and multivariable models were utilized to determine the impact of nodal status on overall survival. These patients were reclassified according to AJCC 8 HPV-positive criteria (TNM8+) and risk stratification was quantified with C-statistic.There were 11,147 cases of HPV-negative OPSCC in the NCDB and 3,613 cases in SEER that were included in the nodal classification analysis. Unlike nonoropharyngeal malignancies, increased nodal stage is not clearly associated with survival for patients with OPSCC independent of HPV status. When the TNM8+ was applied to HPV-negative patients, there was improved concordance in the NCDB cohort, 0.561 (plus minus) 0.004 to 0.624 (plus minus) 0.004 (difference +0.063) and the SEER cohort, 0.561 (plus minus) 0.008 to 0.625 (plus minus) 0.008 (difference +0.065).We demonstrated a reduced impact of nodal metastasis on OPSCC survival, independent of HPV status and specific to OPSCC.We demonstrate, for the first time that when nodal staging is deemphasized as a part of overall staging, we see improved concordance and risk stratification for HPV-negative OPSCC. The exact mechanism of this differential impact remains unknown but offers a novel area of study.

  View details for DOI 10.1158/1055-9965.EPI-21-0776

  View details for PubMedID 35579907

• Nodal Metastasis Count and Oncologic Outcomes in Head and Neck Cancer: A Secondary Analysis of NRG/RTOG 9501, NRG/RTOG 0234, and EORTC 22931 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lu, D. J., Luu, M., Gay, C., Nguyen, A. T., Anderson, E. M., Bernier, J., Cooper, J. S., Harari, P. M., Torres-Saavedra, P. A., Le, Q., Chen, M. M., Mallen-St Clair, J., Ho, A. S., Zumsteg, Z. S. 2022; 113 (4): 787-795

  View details for DOI 10.1016/j.ijrobp.2021.03.033

  View details for Web of Science ID 000832133200015

• Quantitative Nodal Burden and Mortality Across Solid Cancers. Journal of the National Cancer Institute Nguyen, A. T., Luu, M., Nguyen, V. P., Lu, D. J., Shiao, S. L., Kamrava, M., Atkins, K. M., Mita, A. C., Scher, K. S., Spratt, D. E., Faries, M. B., Daskivich, T. J., Lin, D. C., Chen, M. M., Clair, J. M., Sandler, H. M., Ho, A. S., Zumsteg, Z. S. 2022; 114 (7): 1003-1011

  Abstract

  Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors.We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites. Multivariable Cox regression analyses were constructed using restricted cubic splines to model the association between nodal number and mortality. Recursive partitioning analysis (RPA) was used to derive nodal classification systems for each solid cancer based on metastatic LN count. The reproducibility of these findings was assessed in 1 969 727 patients from the Surveillance, Epidemiology, and End Results registry. Two-sided tests were used for all statistical analyses.Consistently across disease sites, mortality risk increased continuously with increasing number of metastatic LNs (P < .001 for all spline segments). Each RPA-derived nodal classification system produced multiple prognostic groups spanning a wide spectrum of mortality risk (P < .001). Multivariable models using these RPA-derived nodal classifications demonstrated improved concordance with mortality compared with models using American Joint Committee on Cancer staging in sites where nodal classification is not based on metastatic LN count. Each RPA-derived nodal classification system was reproducible in a large validation cohort for all-cause and cause-specific mortality (P < .001). High quantitative nodal burden was the single strongest tumor-intrinsic variable associated with mortality in 12 of 16 disease sites.Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers and should serve as a foundation for pathologic nodal staging across solid tumors.

  View details for DOI 10.1093/jnci/djac059

  View details for PubMedID 35311991

  View details for PubMedCentralID PMC9275768

• Financial Hardship in Patients With Head and Neck Cancer. JCO oncology practice Mott, N. M., Mierzwa, M. L., Casper, K. A., Shah, J. L., Mallen-St Clair, J., Ho, A. S., Zumsteg, Z. S., Prince, M. E., Dossett, L. A., Chen, M. M. 2022; 18 (6): e925-e937

  Abstract

  Financial hardship is a growing concern for patients with cancer. Patients with head and neck cancer (HNC) are particularly vulnerable, given that a third leave the workforce following treatment. The goal of our study was to characterize financial hardship in the psychologic response (response to increased expenses) and coping behaviors (behaviors patients adopt to manage their care in the setting of increased expenses) domains in patients with HNC compared with patients with other cancers.This was a retrospective cohort study of nationally representative public survey data from 2013 to 2018 in the National Health Interviews Survey, an annual cross-sectional household survey. We included respondents age ≥ 18 years who reported a diagnosis of cancer and identified a subset of patients with HNC. Our main outcomes were financial hardship in the psychologic response and coping behaviors domains.Our sample included a weighted population of 357,052 patients with HNC and 21.4 million patients with other cancers. Compared with patients with other cancers, patients with HNC reported greater levels of coping behaviors hardship (31% v 23%, P = .015), but similar levels of psychologic financial hardship (73% v 72%, P = .787). Medicaid or uninsured patients more often reported coping behaviors hardship. On multivariable analysis, HNC (odds ratio, 1.51; 95% CI, 1.01 to 2.24) was independently associated with coping behaviors hardship.To our knowledge, this is the first study to evaluate financial hardship in patients with HNC compared with patients with other cancers that includes Medicaid and uninsured patients, who are more often to have financial hardship. Patients with HNC have greater levels of hardship in the coping behaviors domain compared with patients with other cancers, but similar levels in the psychologic response domain.

  View details for DOI 10.1200/OP.21.00683

  View details for PubMedID 35167324

• A Consideration for Surgical Management in Select T4b Oral Cavity Squamous Cell Carcinoma. The Annals of otology, rhinology, and laryngology Chen, M. M., Chang, C. M., Dermody, S., Rosko, A. J., Mierzwa, M. L., Swiecicki, P. L., Spector, M. E., Worden, F. P., Prince, M. E., Chinn, S. B. 2022; 131 (6): 609-616

  Abstract

  The role of surgery for conventionally "unresectable" (cT4b) oral cavity squamous cell carcinoma is unclear. We analyzed factors associated with overall survival in cT4b relative to cT4a oral cavity squamous cell carcinoma.We identified 6830 cT4a and 522 cT4b oral cavity squamous cell carcinoma chemoradiation or surgery + adjuvant therapy patients in the National Cancer Data Base from 2004 to 2016. The main outcome was overall survival. Statistical analysis was performed using chi-squared tests, univariable and multivariable regression analysis.The cT4b group had a higher rate of positive margins (30.4% vs 21.3%, P = .009) and downstaging (41.2% vs 13.1%; P < .001) compared to cT4a, while only 1.7% were upstaged. cT4b surgery + chemoradiation patients had similar survival to cT4a surgery + radiation (HR 0.93; 95% CI, 0.70-1.25) and cT4a surgery + chemoradiation patients (HR, 0.92; 95% CI, 0.69-1.23), while cT4b surgery + radiation patients had worse OS (HR, 1.55; 95% CI, 1.05-1.47).Clinical T4b staging is a poor predictor of pathologic staging given a high rate of downstaging on final pathology. Surgical resection with adjuvant chemoradiation is an option in select cT4b oral cavity squamous cell carcinoma patients.

  View details for DOI 10.1177/00034894211038213

  View details for PubMedID 34365858

• Nodal Metastasis Count and Oncologic Outcomes in Head and Neck Cancer: A Secondary Analysis of NRG/RTOG 9501, NRG/RTOG 0234, and EORTC 22931. International journal of radiation oncology, biology, physics Lu, D. J., Luu, M., Gay, C., Nguyen, A. T., Anderson, E. M., Bernier, J., Cooper, J. S., Harari, P. M., Torres-Saaverdra, P. A., Le, Q. T., Chen, M., Mallen-St Clair, J., Ho, A. S., Zumsteg, Z. S. 2022

  Abstract

  Better understanding of the relationship between spread of head and neck squamous cell carcinoma (HNSCC) to regional lymph nodes (LN) and the frequency and manner of treatment failure should help design better treatment intensification strategies. In this study, we evaluate the relationship between recurrence patterns, mortality, and number of pathologically positive (+) LN in HNSCC in three prospective randomized controlled trials.Secondary analysis of 947 HNSCC patients enrolled on XXX (N=410), XXX (N=203), and XXX (N=334) undergoing surgery and post-operative radiation +/- systemic therapy.   Multivariable models were constructed for overall survival (OS), disease-free survival (DFS), local-regional relapse (LRR), and distant metastases (DM). Restricted cubic splines were used to model the nonlinear relationship between +LN and outcomes.In multivariable analysis, OS and DFS decreased with each +LN without plateau, most pronounced up to 5 (OS: hazard ratio [HR], 1.19 per +LN; 95% confidence interval [CI], 1.10-1.29; P<0.001; DFS: HR per +LN 1.17, 95% CI 1.08-1.26; P<0.001), and more gradually beyond this (OS: HR per +LN, 1.03; 95% CI, 1.01-1.05; P<0.001; DFS: HR per +LN, 1.03; 95% CI, 1.02-1.05; P<0.001). In contrast to LRR risk, which increased sharply up to 5 +LNs (HR per +LN, 1.25; 95% CI, 1.11-1.39, P<0.001) but plateaued beyond this (HR per +LN, 1.00; 95% CI, 0.967-1.04; P=0.91), DM risk increased continuously with increasing +LN (≤5 +LN: HR per +LN, 1.14; 95% CI, 1.01-1.28; P=0.04; >5 +LN, HR per +LN, 1.05; 95% CI, 1.02-1.07; P=0.002).In high-risk resected HNSCC, increased mortality was associated with increased +LN count. LRR and DM risk both increased in parallel up to 5 +LN, but only DM continued to increase for further +LN increases. These differing recurrence patterns can help inform design of future treatments.

  View details for DOI 10.1016/j.ijrobp.2022.03.033

  View details for PubMedID 35395358

• Leveraging Molecular Assays to Aid Decision-making in Large Indeterminate Thyroid Nodules-A Minimalist Approach. JAMA otolaryngology-- head & neck surgery Chen, M. M., Ho, A. S. 2022; 148 (4): 383

  View details for DOI 10.1001/jamaoto.2021.4433

  View details for PubMedID 35175281

• Peace of Mind: A Role in Unnecessary Care? Journal of clinical oncology : official journal of the American Society of Clinical Oncology Chen, M. M., Hughes, T. M., Dossett, L. A., Pitt, S. C. 2022; 40 (5): 433-437

  View details for DOI 10.1200/JCO.21.01895

  View details for PubMedID 34882501

  View details for PubMedCentralID PMC8824400

• Comparative Proteomic Analysis of HPV(+) Oropharyngeal Squamous Cell Carcinoma Recurrence JOURNAL OF PROTEOME RESEARCH Ho, A. S., Robinson, A., Shon, W., Laury, A., Raedschelders, K., Venkatraman, V., Holewinski, R., Zhang, Y., Shiao, S. L., Chen, M. M., Clair, J., Lin, D., Zumsteg, Z. S., Van Eyk, J. E. 2022; 21 (1): 200-208

  Abstract

  Deintensification therapy for human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV(+) OPSCC) is under active investigation. An adaptive treatment approach based on molecular stratification could identify high-risk patients predisposed to recurrence and better select for appropriate treatment regimens. Collectively, 40 HPV(+) OPSCC FFPE samples (20 disease-free, 20 recurrent) were surveyed using mass spectrometry-based proteomic analysis via data-independent acquisition to obtain fold change and false discovery differences. Ten-year overall survival was 100.0 and 27.7% for HPV(+) disease-free and recurrent cohorts, respectively. Of 1414 quantified proteins, 77 demonstrated significant differential expression. Top enriched functional pathways included those involved in programmed cell death (73 proteins, p = 7.43 × 10-30), apoptosis (73 proteins, p = 5.56 × 10-9), β-catenin independent WNT signaling (47 proteins, p = 1.45 × 10-15), and Rho GTPase signaling (69 proteins, p = 1.09 × 10-5). PFN1 (p = 1.0 × 10-3), RAD23B (p = 2.9 × 10-4), LDHB (p = 1.0 × 10-3), and HINT1 (p = 3.8 × 10-3) pathways were significantly downregulated in the recurrent cohort. On functional validation via immunohistochemistry (IHC) staining, 46.9% (PFN1), 71.9% (RAD23B), 59.4% (LDHB), and 84.4% (HINT1) of cases were corroborated with mass spectrometry findings. Development of a multilateral molecular signature incorporating these targets may characterize high-risk disease, predict treatment response, and augment current management paradigms in head and neck cancer.

  View details for DOI 10.1021/acs.jproteome.1c00757

  View details for Web of Science ID 000744097700019

  View details for PubMedID 34846153

• 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

• Predictive Impact of Metastatic Lymph Node Burden on Distant Metastasis Across Papillary Thyroid Cancer Variants. Thyroid : official journal of the American Thyroid Association Ho, A. S., Luu, M., Shafqat, I., Mallen-St Clair, J., Chen, M. M., Chen, Y., Jain, M., Ali, N., Patio, C., Filarski, C. F., Lin, D. C., Bankston, H., Braunstein, G. D., Sacks, W. L., Zumsteg, Z. S. 2021; 31 (10): 1549-1557

  Abstract

  Background: While numerous factors determine prognosis in papillary thyroid carcinoma (PTC), distant metastasis (M1) represents one of the most dire. Escalating nodal burden and aggressive histology may contribute to higher metastatic risk, but this relationship is poorly defined and challenging to anticipate. We evaluate the predictive impact of these histological features on predicting distant metastases at initial presentation. Methods: Univariate and multivariable logistic regression models of conventional and aggressive thyroid cancer variants (well-differentiated papillary thyroid carcinoma [WDPTC], diffuse sclerosing variant [DSV], tall cell variant [TCV], poorly differentiated thyroid cancer [PDTC], and anaplastic thyroid carcinoma [ATC]) identified via U.S. cancer registry data were constructed to determine associations between M1 status and quantitative nodal burden. Associations between metastatic lymph node (LN) number and M1 disease were modeled using univariate and multivariable logistic regression with interaction terms, as well as a linear continuous probability model. Results: Overall, M1 prevalence at disease presentation was 3.6% (n = 1717). When stratified by subtype, M1 prevalence varied significantly by histology (WDPTC [1.0%], DSV [2.3%], TCV [4.1%], PDTC [17.4%], ATC [38.4%] [p < 0.001]). For WDPTC, M1 prevalence escalated with metastatic LN number (0 LN+ [0.5%], 1-5 LN+ [2.0%], 6-10 LN+ [3.4%], >10 LN+ [5.5%] [p < 0.001]) and LN ratio (p < 0.001). A statistically significant interaction was observed between histology and increasing nodal burden for M1 risk. On multivariable analysis, each successive metastatic LN conferred increased M1 risk for WDPTC (odds ratio [OR] 1.06 [1.05-1.08], p < 0.001) and TCVs (OR 1.04 [1.02-1.07], p < 0.001). In contrast, other aggressive variants had a higher baseline M1 risk, but this did not vary based on the number of positive LN (DSV, OR 1.02 [0.95-1.10], p = 0.52; PDTC, OR 1.00 [0.98-1.02], p = 0.66; ATC, 1.00 [0.98-1.02], p = 0.97). Conclusions: Progressive nodal burden independently escalates the risk of distant metastasis in WDPTC and TCVs of PTC. Conversely, aggressive variants such as PDTC and ATC have substantial M1 risk at baseline and appear to be minimally affected by metastatic nodal burden. Consideration of these factors after surgery may help tailor clinical decision-making for treatment and surveillance. Further studies are warranted to calibrate the ideal management approach for these higher risk patient groups.

  View details for DOI 10.1089/thy.2021.0131

  View details for PubMedID 34470466

• Patient Burden with Current Surveillance Paradigm and Factors Associated with Interest in Altered Surveillance for Early Stage HPV-Related Oropharyngeal Cancer. The oncologist Gharzai, L. A., Burger, N., Li, P., Jaworski, E. M., Henderson, C., Spector, M., Rosko, A., Chen, M. M., Prince, M. E., Bradford, C. R., Malloy, K. M., Stucken, C. L., Swiecicki, P., Worden, F., Schipper, M. J., Schonewolf, C. A., Shah, J., Jagsi, R., Chinn, S., Shuman, A., Casper, K., Mierzwa, M. L. 2021; 26 (8): 676-684

  Abstract

  Optimal surveillance paradigms for survivors of early stage human papillomavirus (HPV)-related oropharyngeal cancer are not well defined. This study aimed to characterize patient interest in and factors associated with an altered surveillance paradigm.We surveyed patients with Stage I or II HPV-related oropharyngeal cancer treated at a tertiary care institution from 2016 to 2019. Primary outcomes were descriptive assessment of patient knowledge, interest in altered surveillance, burdens of in-person appointments, and priorities for surveillance visits. Ordinal regression was used to identify correlates of interest in altered surveillance.Sixty-seven patients completed surveys from February to April 2020 at a median of 21 months since completing definitive treatment. A majority (61%) of patients were interested in a surveillance approach that decreased in-person clinic visits. Patients who self-identified as medical maximizers, had higher worry of cancer recurrence, or were in long-term relationships were less likely to be interested. Patients reported significant burdens associated with surveillance visits, including driving distance, time off work, and nonmedical costs. Patients were most concerned with discussing cancer recurrence (76%), physical quality of life (70%), mortality (61%), and mental quality of life (52%) with their providers at follow-up visits.Patients with early stage HPV-related oropharyngeal cancers are interested in altered surveillance approaches, experience significant burdens related to surveillance visits, and have concerns that are not well addressed with current surveillance approaches, including physical and mental quality of life. Optimized surveillance approaches should incorporate patient priorities and minimize associated burdens.The number of patients with HPV-related oropharyngeal cancers is increasing, and numerous clinical trials are investigating novel approaches to treating these good-prognosis patients. There has been limited work assessing optimal surveillance paradigms in these patients. Patients experience significant appointment-related burdens and have concerns such as physical and mental quality of life. Additionally, patients with early stage HPV-related oropharyngeal cancers express interest in altered surveillance approaches that decrease in-person clinic visits. Optimization of surveillance paradigms to promote broader survivorship care in clinical practice is needed.

  View details for DOI 10.1002/onco.13784

  View details for PubMedID 33823077

  View details for PubMedCentralID PMC8342565

• HPV Vaccination Among Young Adults in the US. JAMA Chen, M. M., Mott, N., Clark, S. J., Harper, D. M., Shuman, A. G., Prince, M. E., Dossett, L. A. 2021; 325 (16): 1673-1674

  View details for DOI 10.1001/jama.2021.0725

  View details for PubMedID 33904878

  View details for PubMedCentralID PMC8080227

• Complications of Transoral Robotic Surgery. Otolaryngologic clinics of North America Sethi, R. K., Chen, M. M., Malloy, K. M. 2020; 53 (6): 1109-1115

  Abstract

  This article summarizes major and minor complications following transoral robotic surgery in the head and neck. Overall, transoral robotic surgery is extremely safe; however, surgeons must recognize inherent risks associated with major and severe bleeding, dysphagia, and minor complications, including injury to nerves, mucosal surfaces, teeth, and the eyes. This article briefly discusses prevention and management strategies for common complications.

  View details for DOI 10.1016/j.otc.2020.07.017

  View details for PubMedID 32917420

• The Difficult Airway and Aerosol-Generating Procedures in COVID-19: Timeless Principles for Uncertain Times. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Smith, J. D., Chen, M. M., Balakrishnan, K., Sidell, D. R., di Stadio, A., Schechtman, S. A., Brody, R. M., Kupfer, R. A., Rassekh, C. H., Brenner, M. J. 2020: 194599820936615

  Abstract

  The impact of the COVID-19 pandemic on otolaryngology practice is nowhere more evident than in acute airway management. Considerations of preventing SARS-CoV-2 transmission, conserving personal protective equipment, and prioritizing care delivery based on acuity have dictated clinical decision making in the acute phase of the pandemic. With transition to a more chronic state of pandemic, heightened vigilance is necessary to recognize how deferral of care in patients with tenuous airways and COVID-19 infection may lead to acute airway compromise. Furthermore, it is critical to respect the continuing importance of flexible laryngoscopy in diagnosis. Safely managing airways during the pandemic requires thoughtful multidisciplinary planning. Teams should consider trade-offs among aerosol-generating procedures involving direct laryngoscopy, supraglottic airway use, fiberoptic intubation, and tracheostomy. We share clinical cases that illustrate enduring principles of acute airway management. As algorithms evolve, time-honored approaches for diagnosis and management of acute airway pathology remain essential in ensuring patient safety.

  View details for DOI 10.1177/0194599820936615

  View details for PubMedID 32571147

• 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

• 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

• 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

• 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

• Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis CANCER Xiang, M., Holsinger, F., Colevas, A., Chen, M. M., Quynh-Thu Le, Beadle, B. M. 2018; 124 (23): 4486–94

  View details for DOI 10.1002/cncr.31708

  View details for Web of Science ID 000452622400012

• Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis. Cancer Xiang, M., Holsinger, F. C., Colevas, A. D., Chen, M. M., Le, Q., Beadle, B. M. 2018

  Abstract

  BACKGROUND: Cisplatin and cetuximab are both systemic therapies commonly used in combination with radiation (RT) for the definitive treatment of head and neck cancers, but their comparative efficacy is unclear.METHODS: Patients with locoregionally advanced (American Joint Committee on Cancer stage III-IVB) squamous cell carcinomas of the oropharynx, larynx, or hypopharynx were identified in the Surveillance, Epidemiology, and End Results-Medicare database. Patients received either cisplatin or cetuximab concurrent with RT, as determined by Medicare claims. The primary study outcome was head and neck cancer-specific mortality (CSM) analyzed with competing risks. Filtering, propensity score matching, and multivariable Fine-Gray regression were used to adjust for differences between the cisplatin and cetuximab cohorts, including age, comorbidity, and cycles of systemic therapy received.RESULTS: The total cohort consisted of 1395 patients, of whom 786 (56%) received cisplatin and 609 (44%) received cetuximab; the median follow-up was 3.5 years in the patients who remained alive. In the cetuximab cohort, CSM was significantly higher than in the cisplatin cohort (39% vs 25% at 3 years; P < .0001). In the matched cohorts (n = 414), the adjusted hazard ratio of CSM for cetuximab was 1.65 (95% confidence interval, 1.30-2.09; P < .0001) relative to cisplatin, corresponding to an absolute difference of approximately 10% in both CSM and overall survival at 3 years. Cetuximab was associated with less dysphagia, more dermatitis, and a similar incidence of mucositis.CONCLUSIONS: In this sizeable, national patient population, treatment with cetuximab was associated with significantly higher CSM than cisplatin. These results suggest that cisplatin may be the preferred chemotherapeutic agent in this setting. Cancer 2018;124:000-000.

  View details for PubMedID 30332498

• 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

• 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

• 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

• Comparative Effectiveness and Toxicity of Cetuximab or Cisplatin With Concurrent Radiation for Locoregionally Advanced Squamous Cell Carcinoma of The Head And Neck: A Population-Based Analysis Xiang, M., Holsinger, F., Chen, M., Colevas, A., Beadle, B. ELSEVIER SCIENCE INC. 2018: E16

  View details for Web of Science ID 000432447200037

• 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

• 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

• 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

• Improved transoral dissection of the tongue base with a next-generation robotic surgical system LARYNGOSCOPE Chen, M. M., Orosco, R. K., Lim, G., Holsinger, F. 2018; 128 (1): 78–83

  Abstract

  To describe the application of a novel, flexible, single-port robotic surgical system for transoral tongue base resection, and compare it to the current multiport, rigid-arm robotic surgical system.Preclinical anatomic study using four human cadavers.Transoral resection of the tongue base using the da Vinci Sp and the Si robotic surgical systems. A standardized operative procedure is outlined, and operative parameters were compared between robotic systems.Successful completion of tongue base resection was achieved in all cadavers using both the Sp and the Si systems. The optimal entry guide and instrument position for the Sp system was with the cannula rotated 180° from the standard position so that the camera was in the most inferior (caudal) channel. In the optimal configuration, no instrument exchanges were needed with the Sp system, but use of the Si system required one instrument exchange.This is the first preclinical anatomic study of robotic tongue base resection that compares a novel single-port robotic system to the current multiarm system. Surgical workflow was more streamlined with the da Vinci Sp system, and the new capabilities of simultaneous dissection, traction, and counter traction allowed for improved dissection and vessel control.NA. Laryngoscope, 128:78-83, 2018.

  View details for PubMedID 28681924

• 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

• 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

• 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

• 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

• A Tracheal Mass. JAMA otolaryngology-- head & neck surgery Chen, M. M., Jeffery, C., Damrose, E. J. 2017; 143 (1): 87-88

  View details for DOI 10.1001/jamaoto.2016.1544

  View details for PubMedID 27356210

• Indolent thyroid cancer: knowns and unknowns. Cancers of the head & neck Hahn, L. D., Kunder, C. A., Chen, M. M., Orloff, L. A., Desser, T. S. 2017; 2: 1

  Abstract

  Thyroid cancer incidence is rapidly increasing due to increased detection and diagnosis of indolent thyroid cancer, i.e. cancer that is likely to be clinically insignificant. Clinical, radiologic, and pathologic features predicting indolent behavior of thyroid cancer are still largely unknown and unstudied. Existing clinicopathologic staging systems are useful for providing prognosis in the context of treated thyroid cancer but are not designed for and are inadequate for predicting indolent behavior. Ultrasound studies have primarily focused on discrimination between malignant and benign nodules; some studies show promising data on using sonographic features for predicting indolence but are still in their early stages. Similarly, molecular studies are being developed to better characterize thyroid cancer and improve the yield of fine needle aspiration biopsy, but definite markers of indolent thyroid cancer have yet to be identified. Nonetheless, active surveillance has been introduced as an alternative to surgery in the case of indolent thyroid microcarcinoma, and protocols for safe surveillance are in development. As increased detection of thyroid cancer is all but inevitable, increased research on predicting indolent behavior is needed to avoid an epidemic of overtreatment.

  View details for PubMedID 31093348

  View details for PubMedCentralID PMC6460732

• 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

• Hospital readmission and 30-day mortality after surgery for oral cavity cancer: Analysis of 21,681 cases HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Luryi, A. L., Chen, M. M., Mehra, S., Roman, S. A., Sosa, J. A., Judson, B. L. 2016; 38: E221–E226

  Abstract

  Oral cavity squamous cell cancer (SCC) is treated primarily with surgery. Rates of 30-day hospital readmission and mortality after surgery for oral cavity SCC are unknown.We conducted a retrospective analysis of postoperative 30-day unplanned readmission and mortality in patients with oral cavity SCC in the National Cancer Data Base (NCDB).Among 21,681 cases, the 30-day unplanned readmission rate was 3.2%, and the 30-day mortality rate was 1.0%. Male sex (odds ratio [OR] = 1.23; p = .02), stage T3 (OR = 1.55; p = .007), or T4 (OR = 1.52; p = .002), and neck dissection (OR = 1.37; p = .04) were independently associated with readmission. Age 76 to 85 years (OR = 4.80; p < .001), age >85 years (OR = 10.24; p < .001), comorbidity index ≥1 (OR = 2.31; p < .001), and stage T3 (OR = 3.02; p < .001) or T4 (OR = 3.24; p < .001) were associated with 30-day mortality.Interventions aimed at decreasing hospital readmissions should target high-risk patients identified here. Factors associated with 30-day mortality reflect risk factors for overall mortality. © 2015 Wiley Periodicals, Inc. Head Neck 38: E221-E226, 2016.

  View details for PubMedID 25537226

• Morbidity and Mortality Associated With Robotic Head and Neck Surgery: An Inquiry of the Food and Drug Administration Manufacturer and User Facility Device Experience Database. JAMA otolaryngology-- head & neck surgery Chen, M. M., Holsinger, F. C. 2016; 142 (4): 405–6

  View details for PubMedID 26939860

• Salvage Conservation Laryngeal Surgery After Radiation Therapy Failure OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Chen, M. M., Holsinger, F. C., Laccourreye, O. 2015; 48 (4): 667-?

  Abstract

  Conservation laryngeal surgery (CLS) includes time-honored approaches such as the vertical partial laryngectomy and the open horizontal supraglottic laryngectomy, as well as the supracricoid partial laryngectomy and transoral laser microsurgery. Carefully selected patients can undergo transoral endoscopic or open CLS for early to intermediate stage recurrent tumors of the glottic and supraglottic larynx. Patient factors, such as comorbid pulmonary disease, are essential in selecting patients for CLS, especially after previous radiation therapy. This article reviews the preoperative indications and postoperative management of salvage CLS after radiation therapy for laryngeal cancer.

  View details for DOI 10.1016/j.otc.2015.04.011

  View details for PubMedID 26233791

• Predictors of Survival in Sinonasal Adenocarcinoma JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE Chen, M. M., Roman, S. A., Sosa, J. A., Judson, B. L. 2015; 76 (3): 208-213

  Abstract

  Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15-0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26-0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis.

  View details for DOI 10.1055/s-0034-1543995

  View details for Web of Science ID 000354613800008

  View details for PubMedCentralID PMC4433397

• Predictors of Survival in Sinonasal Adenocarcinoma. Journal of neurological surgery. Part B, Skull base Chen, M. M., Roman, S. A., Sosa, J. A., Judson, B. L. 2015; 76 (3): 208-13

  Abstract

  Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15-0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26-0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis.

  View details for DOI 10.1055/s-0034-1543995

  View details for PubMedID 26225303

  View details for PubMedCentralID PMC4433397

• The Role of Adjuvant Therapy in the Management of Head and Neck Merkel Cell Carcinoma An Analysis of 4815 Patients JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Chen, M. M., Roman, S. A., Sosa, J. A., Judson, B. L. 2015; 141 (2): 137-141

  Abstract

  Merkel cell carcinoma (MCC) is a rare neuroendocrine malignant neoplasm that most commonly occurs in the head and neck and is rapidly increasing in incidence. The role of adjuvant chemoradiotherapy (CRT) in the management of head and neck MCC remains controversial.To evaluate the association between different adjuvant therapies and survival in head and neck MCC.Retrospective review of adult patients with head and neck MCC who had surgery recorded in the National Cancer Data Base from 1998 to 2011.Surgical excision, adjuvant radiation therapy (RT), or adjuvant CRT.Our main outcome was overall survival (OS). Statistical analysis included χ2, t tests, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis.We identified 4815 patients; 92.0% underwent standard surgical excision, and 8.0% underwent Mohs surgery. On multivariate analysis, age at least 75 years (hazard ratio [HR], 2.83 [95% CI, 1.82-4.41]), larger tumor size, positive margins (HR, 1.52 [95% CI, 1.25-1.85]), and metastatic lymph nodes (HR, 2.29 [95% CI, 1.84-2.85]) were independently associated with decreased OS. Postoperative CRT (HR, 0.62 [95% CI, 0.47-0.81]) and RT (HR, 0.80 [95% CI, 0.70-0.92]) provided a survival benefit over surgery alone. Adjuvant CRT was associated with improved OS over adjuvant RT in patients with positive margins (HR, 0.48 [95% CI, 0.25-0.93]), tumor size at least 3 cm (HR, 0.52 [95% CI, 0.30-0.90]), and male sex (HR, 0.69 [95% CI, 0.50-0.94]).To our knowledge, this the first study examining the role of adjuvant CRT in head and neck MCC. Results suggest that adjuvant CRT may help improve survival in high-risk patients, such as males and those with positive margins and larger tumors.

  View details for DOI 10.1001/jamaoto.2014.3052

  View details for PubMedID 25474617

• Trends and Variations in the Use of Adjuvant Therapy for Patients With Head and Neck Cancer CANCER Chen, M. M., Roman, S. A., Yarbrough, W. G., Burtness, B. A., Sosa, J. A., Judson, B. L. 2014; 120 (21): 3353-3360

  Abstract

  The National Comprehensive Cancer Network guidelines recommend that patients with surgically resected head and neck cancers that have adverse pathologic features should receive adjuvant therapy in the form of radiotherapy (RT) or chemoradiation (CRT). To the authors' knowledge, the current study is the first analysis of temporal trends and use patterns of adjuvant therapy for these patients.Patients with head and neck cancer and adverse pathologic features were identified in the National Cancer Data Base (1998-2011). Data were analyzed using chi-square, Student t, and log-rank tests; multivariate logistic regression; and Cox multivariate regression.A total of 73,088 patients were identified: 41.5% had received adjuvant RT, 33.5% had received adjuvant CRT, and 25.0% did not receive any adjuvant therapy. From 1998 to 2011, the increase in the use of adjuvant CRT was greatest for patients with oral cavity (6-fold) and laryngeal (5-fold) cancers. Multivariate analysis demonstrated that Medicare/Medicaid insurance (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.01-1.11), distance ≥34 miles from the cancer center (OR, 1.66; 95% CI, 1.59-1.74), and academic (OR, 1.26; 95% CI, 1.20-1.31) and high-volume (OR, 1.10; 95% CI, 1.05-1.15) centers were independently associated with patients not receiving adjuvant therapy. Receipt of adjuvant therapy was found to be independently associated with improved overall survival (hazard ratio, 0.84; 95% CI, 0.81-0.86).Approximately 25% of patients are not receiving National Comprehensive Cancer Network guideline-directed adjuvant therapy. Patient-level and hospital-level factors are associated with variations in the receipt of adjuvant therapy. Further evaluation of these differences in practice patterns is needed to standardize practice and potentially improve the quality of care. Cancer 2014;120:3353-3360. © 2014 American Cancer Society.

  View details for DOI 10.1002/cncr.28870

  View details for PubMedID 25042524