Maxwell Lee

All Publications

• Single-cell spatial transcriptomics uncovers niches that govern response to PD-1/PD-L1 blockade in cutaneous squamous cell carcinoma. Journal for immunotherapy of cancer Lee, M. Y., Sherman, A. R., Martinez Ramirez, L., Rahman, M., Zdravkovic, S., Shin, J. H., Stepanek, I., Colevas, A. D., Sunwoo, J. B., Divi, V. 2026; 14 (1)

  Abstract

  Neoadjuvant PD-1/PD-L1 blockade yields robust efficacy in advanced cutaneous squamous cell carcinoma (cSCC), yet many patients fail to achieve a complete or major pathologic response. The reasons why some patients experience response but others do not are unclear.We profiled cSCC specimens before, after 1 dose, and after 3-4 doses of PD-1/PD-L1 blockade to uncover resistance mechanisms and predict therapeutic response. In total, 27 patients across three cohorts, including two phase II trials, were studied. We created 1.7 mm tissue-core microarrays and performed single-cell spatial transcriptomics, including spatial clustering, gene-set enrichment, and spatial correlation analyses.After profiling all samples, six distinct spatial niches emerged, each differentially enriched in responders versus non-responders. A high antigen presentation niche, B/plasma cell enriched niche, and inflammatory keratinocyte niche were more frequent in responders, whereas proliferative keratinocyte, low antigen presentation myeloid, and fibroblast-rich epithelial-mesenchymal transition niches prevailed in non-responders. Notably, spatial niche profiling on pretreatment samples outperformed PD-L1 status in predicting pathologic response. Each niche displayed unique gene coexpression modules, suggesting niche-specific resistance mechanisms. Individual tumor analyses revealed varied immune evasion strategies, including defective interferon-induced antigen presentation, immunosuppressive myeloid environments, and epithelial-mesenchymal transition.Our single-cell spatial transcriptomic approach identifies six spatial niches that predict immunotherapy response better than PD-L1 status using only 1.7 mm tissue cores and may inform the development of biomarkers. Our results further underscore the heterogeneity of resistance mechanisms among cSCC patients, highlighting the need for tailored therapeutic strategies.

  View details for DOI 10.1136/jitc-2025-014067

  View details for PubMedID 41617396

• Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis. NPJ vaccines Lee, M. Y., Metenou, S., Brough, D. E., Sabzevari, H., Bai, K., Jochems, C., Schlom, J., Allen, C. T. 2021; 6 (1): 86

  Abstract

  Activation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of a novel gorilla adenovirus vaccine expressing a protein designed to elicit immune responses directed against HPV6 and HPV11, PRGN-2012, was studied using in vitro stimulation of T lymphocytes from patients with recurrent respiratory papillomatosis, in vivo vaccination studies, and therapeutic studies in mice bearing tumors expressing lrHPV antigen. PRGN-2012 treatment induces lrHPV antigen-specific responses in patient T lymphocytes. Vaccination of wild-type mice induces E6-specific T-lymphocyte responses without toxicity. In vivo therapeutic vaccination of mice bearing established HPV6 E6 expressing tumors results in HPV6 E6-specific CD8+ T-lymphocyte immunity of sufficient magnitude to induce tumor growth delay. The clinical study of PRGN-2012 in patients with disorders caused by chronic infection with lrHPV is warranted.

  View details for DOI 10.1038/s41541-021-00348-x

  View details for PubMedID 34145272

  View details for PubMedCentralID PMC8213691

• Chimeric antigen receptor engineered NK cellular immunotherapy overcomes the selection of T-cell escape variant cancer cells. Journal for immunotherapy of cancer Lee, M. Y., Robbins, Y., Sievers, C., Friedman, J., Abdul Sater, H., Clavijo, P. E., Judd, N., Tsong, E., Silvin, C., Soon-Shiong, P., Padget, M. R., Schlom, J., Hodge, J., Hinrichs, C., Allen, C. 2021; 9 (3)

  Abstract

  As heterogeneous tumors develop in the face of intact immunity, tumor cells harboring genomic or expression defects that favor evasion from T-cell detection or elimination are selected. For patients with such tumors, T cell-based immunotherapy alone infrequently results in durable tumor control.Here, we developed experimental models to study mechanisms of T-cell escape and demonstrated that resistance to T-cell killing can be overcome by the addition of natural killer (NK) cells engineered to express a chimeric antigen receptor (CAR) targeting programmed death ligand-1 (PD-L1).In engineered models of tumor heterogeneity, PD-L1 CAR-engineered NK cells (PD-L1 t-haNKs) prevented the clonal selection of T cell-resistant tumor cells observed with T-cell treatment alone in multiple models. Treatment of heterogenous cancer cell populations with T cells resulted in interferon gamma (IFN-γ) release and subsequent upregulation of PD-L1 on tumor cells that escaped T-cell killing through defects in antigen processing and presentation, priming escape cell populations for PD-L1 dependent killing by PD-L1 t-haNKs in vitro and in vivo.These results describe the underlying mechanisms governing synergistic antitumor activity between T cell-based immunotherapy that results in IFN-γ production, upregulation of PD-L1 on T-cell escape cells, and the use of PD-L1 CAR-engineered NK cells to target and eliminate resistant tumor cell populations.

  View details for DOI 10.1136/jitc-2020-002128

  View details for PubMedID 33741731

  View details for PubMedCentralID PMC7986659

• Mechanisms of resistance to T cell-based immunotherapy in head and neck cancer. Head & neck Lee, M. Y., Allen, C. T. 2020; 42 (9): 2722-2733

  Abstract

  Most current approved or investigational immunotherapeutic approaches for head and neck squamous cell carcinoma are aimed at activating T cells. The majority of patients receiving such immunotherapy do not demonstrate durable tumor remission.Original articles covering tumor heterogeneity, immunoediting, immune escape, and local tumor immunosuppression were reviewed.In the face of immune pressure, subclones susceptible to T cell killing are eliminated, leaving behind resistant tumor clones in a process known as immunoediting. Such subclones of tumor cells that are resistant to T cell killing may remain sensitive to natural killer (NK) cell detection and elimination, suggesting that patients harboring such tumors may benefit from combination of T and NK cell-based immunotherapy. Even in the setting of optimal immunotherapy, the immunosuppressive tumor microenvironment may arrogate effector immune responses through a number of distinct mechanisms.Highly effective immunotherapy will likely require multimodality approaches targeting independent mechanisms of immune activation.

  View details for DOI 10.1002/hed.26158

  View details for PubMedID 32275098

• Patterns of Influenza Vaccination in Head and Neck Cancer Patients in the United States. Laryngoscope investigative otolaryngology Lee, M. Y., Sunwoo, J. B., Chen, M. M. 2026; 11 (1): e70358

  Abstract

  The American Society of Clinical Oncology recommends routine influenza vaccination for cancer patients. Lack of influenza vaccination may lead to increased infection incidence, increased infection severity, and delays in cancer care. Vaccine uptake among head and neck patients is unknown.We performed a retrospective cohort analysis using the SEER-Medicare database for patients above age 65 with head and neck cancer diagnosed between 2013 and 2018.Among 32,155 patients, 32.5% received vaccination in the year before diagnosis and 32.1% in the year after diagnosis. Analyses revealed a significant increase in vaccination at the time of diagnosis and fewer vaccinations in the 3 months afterward. Various factors were associated with decreased odds of receiving vaccination, including Black and AAPI race/ethnicity, male gender, and regional and distant metastasis.Vaccination uptake is suboptimal in patients with head and neck cancer, underscoring the need for targeted interventions to enhance preventive care to improve outcomes in high-risk patients.

  View details for DOI 10.1002/lio2.70358

  View details for PubMedID 41727983

  View details for PubMedCentralID PMC12919370

• Effects of diagnostic delays in head and neck cancer patients presenting to the emergency department. Oral oncology Lee, M. Y., Huynh, J. D., Kim, D. D., Sunwoo, J. B., Chen, M. M. 2025; 168: 107467

  Abstract

  Delayed diagnosis of head and neck cancer leads to poorer survival, and whether initial presentation to the Emergency Department (ED) expedites or delays diagnosis is unclear. We retrospectively studied patients aged 65 or older, diagnosed with head and neck cancer between 2011 and 2015 using SEER Medicare data, comparing those who received first imaging in the ED with those who received it as outpatients. Both overall and disease-specific survival were assessed using Cox Proportional Hazards analysis, and bootstrapping was performed to determine an ideal interval between imaging and biopsy. Of 2282 included patients, 211 received initial imaging in the ED and were propensity score matched to 633 outpatients. ED patients had longer intervals between imaging and biopsy (44.6 % vs 11.7 % with an interval > 34 days, p < 0.001) and poorer two-year overall (47.8 % vs 60.3 %, p < 0.01) and cancer-specific (56.2 % vs 67.3 %, p < 0.01) survival compared to outpatients. Those biopsied within 34 days of imaging had statistically similar survival compared to those biopsied prior to imaging (HR = 1.13, 95 % CI 0.90-1.43), and those biopsied 34 or more days after imaging demonstrated worse survival (HR = 1.32, 95 % CI 1.01-1.72). These findings suggest that patients presenting to the ED for initial imaging may experience delays in biopsy leading to inferior survival, underscoring the importance of ensuring timely tissue diagnosis.

  View details for DOI 10.1016/j.oraloncology.2025.107467

  View details for PubMedID 40669441

• Newborn hearing screening methodology impacts the timing of diagnosis for auditory neuropathy spectrum disorder. American journal of otolaryngology Bennett, C., Yoon, P., Lee, M. Y., Wolfe, M., Anne, S., Carvalho, D. S. 2023; 44 (4): 103920

  Abstract

  Auditory Neuropathy Spectrum Disorder (ANSD) accounts for 10 % to 15 % of pediatric hearing loss. In most cases, otoacoustic emissions (OAE) are present as the outer hair cell function is normal, and the auditory brainstem response (ABR) is abnormal. Newborn hearing screen (NBHS) is completed using OAE or ABR depending on the institution. Because OAEs are often present in ANSD, NBHS done solely with OAE can miss and delay diagnosis of patients with ANSD.To assess whether NBHS methodology impacts the age of diagnosis of ANSD.This is a retrospective study of patients, 0-18 years of age, diagnosed with ANSD at two tertiary pediatric hospitals from 1/01/2010 to 12/31/2018 after referral from NBHS performed in the community. Data recorded included patient demographics, method of NBHS, NICU stay, and age at ANSD diagnosis.264 patients were diagnosed with ANSD. Of those, 123 (46.6 %) were female, and 141 (53.4 %) were male. Ninety-seven (36.8 %) were admitted to NICU and the mean stay was 6.98 weeks (STD = 10.7; CI = 4.8-9.1). The majority (244, 92.4 %) of patients had NBHS with ABR, and 20 (7.5 %) had NBHS with OAE. Patients screened with ABR were diagnosed with ANSD earlier than those who screened with OAE, with a mean age of 14.1 versus 27.3 weeks (p = 0.0397, CI = 15.2-39.3). Among those screened with ABR, median age at diagnosis was 4 months for NICU infants and 2.5 months for infants with no history of NICU stay over 5 days. In comparison, median diagnosis age was 8 months for non-NICU infants screened with OAEs.Patients with ANSD who had NBHS with ABR were diagnosed earlier than those with OAE. Our data suggest that universal screening with ABR may facilitate earlier diagnosis of ANSD and earlier evaluation for aural rehabilitation, especially in high-risk cohorts such as NICU patients. Further research is needed into factors that contribute to earlier diagnosis among patients screened with ABR.

  View details for DOI 10.1016/j.amjoto.2023.103920

  View details for PubMedID 37207575

• Primary Total Laryngectomy versus Organ Preservation for Locally Advanced T3/T4a Laryngeal Cancer. The Laryngoscope Lee, M. Y., Belfiglio, M., Zeng, J., Fleming, C. W., Koyfman, S., Joshi, N. P., Lamarre, E., Prendes, B., Scharpf, J., Lorenz, R. R., Woody, N. M., Adelstein, D. J., Geiger, J. L., Chute, D. J., Ku, J. A. 2023; 133 (5): 1122-1131

  Abstract

  Organ preservation (OP) treatment for advanced laryngeal cancer has increased compared to primary total laryngectomy. Our study compares oncologic and functional outcomes between these approaches.Retrospective cohort study.Single tertiary care institution.Retrospective review of patients receiving primary total laryngectomy or OP for laryngeal cancer between 1/1/2000 and 12/31/2018.A total of 118 patients received primary total laryngectomy and 119 received OP. Overall survival was similar between total laryngectomy and OP. When stratified by T stage, disease-free survival was worse among T3 patients receiving OP versus total laryngectomy. In T3 patients, 28 OP patients experienced local recurrence (28.9%) compared to 3 total laryngectomy patients (7.1%; p < 0.01). In total, 20 OP patients with local recurrence received salvage surgery. These patients had similar overall survival to patients who underwent initial total laryngectomy (TL). About 14 OP patients with local recurrence did not receive salvage surgery. About 89 (75.4%) TL patients achieved normal diet as compared to 64 (53.8%) OP patients (p < 0.001). In TL patients, 106 (89.8%) received primary or secondary tracheoesophageal-prosthesis, 82 (77.4%) of whom achieved completely understandable speech.There was no difference in survival by treatment in T4 patients, possibly because of strict patient selection. However, disease-free survival was worse in T3 patients receiving OP, likely due to a high local recurrence rate. Approximately 40% of patients with local recurrence were not eligible for salvage laryngectomy. TL patients had comparable swallowing and speech outcomes with OP patients.3 Laryngoscope, 133:1122-1131, 2023.

  View details for DOI 10.1002/lary.30254

  View details for PubMedID 35754153

• Prognostic value of computed tomography scan detection of cartilage invasion in advanced laryngeal cancer treated with primary total laryngectomy HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Lee, M. Y., Lee, J., Stock, S., Belfiglio, M., Matia, B., Koyfman, S., Joshi, N. P., Burkey, B. B., Lamarre, E., Prendes, B., Scharpf, J., Lorenz, R. R., Woody, N. M., Adelstein, D. J., Geiger, J. L., Chute, D. J., Ku, J. A. 2022; 44 (10): 2220-2227

  Abstract

  We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy.Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis.Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease-free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS.Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity.

  View details for DOI 10.1002/hed.27133

  View details for Web of Science ID 000821803300001

  View details for PubMedID 35801556

  View details for PubMedCentralID PMC9544100

• Determining if T cell antigens are naturally processed and presented on HLA class I molecules BMC IMMUNOLOGY Friedman, J., Gunti, S., Lee, M., Bai, K., Hinrichs, C., Allen, C. T. 2022; 23 (1): 5

  Abstract

  Determining T cell responses to naturally processed and presented antigens is a critical immune correlate to determine efficacy of an investigational immunotherapeutic in clinical trials. In most cases, minimal epitopes and HLA restriction elements are unknown.Here, we detail the experimental use of ex vivo expanded autologous B cells as antigen presenting cells to overcome the limitation of unknown HLA restriction, and the use of electroporated full length mRNA encoding full length parental proteins to ensure that any observed T cell responses are specific for antigens that are naturally processed and presented.This technique can serve as useful experimental approach to determine the induction or enhancement of specific responses to naturally processed and presented antigens on HLA class I molecules in peripheral blood or tumor infiltrating T cells.

  View details for DOI 10.1186/s12865-022-00478-4

  View details for Web of Science ID 000754195100001

  View details for PubMedID 35148673

  View details for PubMedCentralID PMC8832792

• A Volumetric Dosimetry Analysis of Vertebral Body Fracture Risk After Single Fraction Spine Stereotactic Body Radiation Therapy PRACTICAL RADIATION ONCOLOGY Lee, M. Y., Ouyang, Z., LaHurd, D., Xia, P., Chao, S. T., Suh, J. H., Angelov, L., Magnelli, A., Balik, S., Balagamwala, E. H. 2021; 11 (6): 480-487

  Abstract

  Vertebral compression fractures (VCF) are a common and severe complication of spine stereotactic body radiation therapy (SBRT). We sought to analyze how volumetric dosimetry and clinical factors were associated with the risk of VCF.We evaluated 173 spinal segments that underwent single fraction SBRT in 85 patients from a retrospective database. Vertebral bodies were contoured and dosimetric values were calculated. Competing risk models were used to evaluate the effect of clinical and dosimetry variables on the risk of VCF.Our primary endpoint was development of a post-SBRT VCF. New or progressive fractures were noted in 21/173 vertebrae (12.1%); the median time to fracture was 322 days. Median follow-up time was 426 days. Upon multivariable analysis, the percentages of vertebral body volume receiving >20 Gy and >24 Gy were significantly associated with increased risk of VCF (hazard ratio, 1.036, 1.104; P = .029, .044, respectively). No other patient or treatment factors were found to be significant on multivariable analysis. Sensitivity analysis revealed that the percentages of vertebral body volume receiving >20 Gy and >24 Gy required to obtain 90% sensitivity for predicting vertebral body fracture were 24% and 0%, respectively.VCF is a common complication after SBRT, with a crude incidence of 12.1%. Treatment plans that permit higher volumes receiving doses >20 Gy and >24 Gy to the vertebral body are associated with increased risk of VCF. To achieve 90% sensitivity for predicting VCF post-SBRT, the percentage of vertebral volume receiving >20 Gy should be <24% and maximum point dose should be <24 Gy. These results may help guide clinicians when evaluating spine SBRT treatment plans to minimize the risk of developing posttreatment VCF.

  View details for DOI 10.1016/j.prro.2021.07.004

  View details for Web of Science ID 000719409300010

  View details for PubMedID 34303836

• Immunotherapy for HPV Malignancies. Seminars in radiation oncology Lee, M. Y., Allen, C. T. 2021; 31 (4): 361-370

  Abstract

  Owing to the presence of known tumor-specific viral antigens, human papillomavirus (HPV)-associated cancers are well suited for treatment with immunotherapy designed to unleash, amplify or replace the T cell arm of the adaptive immune system. Immune checkpoint blockade designed to unleash existing T cell immunity is currently Food and Drug Administration approved for certain HPV-associated cancers. More specific immunotherapies such as therapeutic vaccines and T cell receptor-engineered cellular therapy are currently in clinical development. Such therapies may offer more specific immune activation against viral tumor antigens and decrease the risk of immune-related adverse events. Current and planned clinical study of these treatments will determine their utility in the treatment of patients with newly diagnosed advanced stage or relapsed HPV-associated cancer.

  View details for DOI 10.1016/j.semradonc.2021.02.008

  View details for PubMedID 34455991

  View details for PubMedCentralID PMC8409092

• Predictors of second-sided deep brain stimulation for Parkinson's disease JOURNAL OF NEUROSURGERY Golubovsky, J. L., Li, H., Momin, A., Shao, J., Lee, M. Y., Frizon, L. A., Hogue, O., Walter, B., Machado, A. G., Nagel, S. J. 2021; 134 (2): 386-392

  Abstract

  Parkinson's disease (PD) is a progressive neurological movement disorder that is commonly treated with deep brain stimulation (DBS) surgery in advanced stages. The purpose of this study was to investigate factors that affect time to placement of a second-sided DBS lead for PD when a unilateral lead is initially placed for asymmetrical presentation. The decision whether to initially perform unilateral or bilateral DBS is largely based on physician and/or patient preference.This study was a retrospective cohort analysis of patients with PD undergoing initial unilateral DBS for asymmetrical disease between January 1999 and December 2017 at the authors' institution. Patients treated with DBS for essential tremor or other conditions were excluded. Variables collected included demographics at surgery, time since diagnosis, Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III), patient-reported quality-of-life outcomes, side of operation, DBS target, intraoperative complications, and date of follow-up. Paired t-tests were used to assess mean changes in UPDRS-III. Cox proportional hazards analysis and the Kaplan-Meier method were used to determine factors associated with time to second lead insertion over 5 years.The final cohort included 105 patients who underwent initial unilateral DBS for asymmetrical PD; 59% of patients had a second-sided lead placed within 5 years with a median time of 34 months. Factors found to be significantly associated with early second-sided DBS included patient age 65 years or younger, globus pallidus internus (GPi) target, and greater off-medication reduction in UPDRS-III score following initial surgery. Older age was also found to be associated with a smaller preoperative UPDRS-III levodopa responsiveness score and with a smaller preoperative to postoperative medication-off UPDRS-III change.Younger patients, those undergoing GPi-targeted unilateral DBS, and patients who responded better to the initial DBS were more likely to undergo early second-sided lead placement. Therefore, these patients, and patients who are more responsive to medication preoperatively (as a proxy for DBS responsiveness), may benefit from consideration of initial bilateral DBS.

  View details for DOI 10.3171/2019.12.JNS19638

  View details for Web of Science ID 000646411300001

  View details for PubMedID 32059181

• Comparative Effectiveness Between Primary and Revision Foraminotomy for the Treatment of Lumbar Foraminal Stenosis INTERNATIONAL JOURNAL OF SPINE SURGERY Hu, E., Shao, J., Momin, A., Lee, M. Y., Gould, H. P., Xiao, R., Haines, C. M., Moore, D. K., Mroz, T. E., Steinmetz, M. P. 2020; 14 (4): 511-517

  Abstract

  Foraminotomy has demonstrated clinical benefit in patients with lumbar foraminal stenosis (LFS), as evidenced by several small retrospective investigations. However, there is a subset of patients who have recurrent symptoms following the operation and therefore require revision surgery. Yet, despite this phenomenon, the relative efficacy of revision foraminotomy (RF) is not well elucidated due to limited literature on the quality of life (QOL) outcomes and cost associated with primary foraminotomy (PF) and RF.To compare the effectiveness of PF and RF in terms of QOL outcomes and relative costs.This is a retrospective cohort study conducted at a single tertiary-care institution. The patient sample consisted of patients undergoing foraminotomy for the treatment of LFS between 2008 and 2016. The primary outcome measure was improvement in postoperative QOL, as measured by EuroQol 5-Dimensions (EQ-5D), and secondary outcome measures included Pain Disability Questionnaire (PDQ) and Patient Health Questionnaire-9 (PHQ-9) perioperative cost as well as minimum clinically important difference (MCID).A retrospective chart review was conducted to identify individuals who underwent PF or RF for LFS and to collect clinical, operative, and demographic data. QOL scores (EQ-5D, PDQ, and PHQ-9) were collected between 2008 and 2016, and perioperative financial data were extracted via the institution's cost utilization engine. Paired t tests were used to assess changes within treatment groups, and Fisher exact tests were used for intercohort comparisons.Five hundred seventy-nine procedures were eligible: 476 (82%) PF and 103 (18%) RF. A significantly higher proportion of males underwent RF than PF (71% versus 59%, P = .03), and PF was done on a significantly higher number of vertebral levels (2.2 versus 2.0, P = .04). There were no other significant differences in demographics. Preoperatively, mean PDQ-Functional scores (50 versus 54, P = .04) demonstrated significantly poorer QOL in the RF cohort. Postoperatively, EQ-5D index showed significant improvement in both the PF (0.547→0.648, P < .0001) and the RF (0.507→0.648, P < .0001) cohorts. Similarly, total PHQ-9 improved significantly in the PF cohort (7.84→5.91, P < .001) and in the RF cohort (8.55→5.53, P = .02), as did total PDQ (PF: 77→63, P < .0001; RF: 85→70, P = .04). QOL scores were also compared between groups preoperatively and postoperatively, and the only significant difference between PF and RF was observed in the preoperative PDQ-Functional score (49.7 versus 54.3, P = .04). The proportion of patients achieving MCID was not significantly associated with cohort. Finally, perioperative cost did not differ significantly between cohorts (PF: $13,383 versus RF: $13,595, P = .82).Both PF and RF produced significant improvement in nearly all measures in patients with LFS. There was no significant difference in cost between PF and RF, but both PF and RF showed postoperative QOL improvements as compared with preoperative scores, indicating that RF remains a reasonable treatment option for patients with recurrent symptoms of LFS.

  View details for DOI 10.14444/7067

  View details for Web of Science ID 000564185800008

  View details for PubMedID 32986571

  View details for PubMedCentralID PMC7478060

• Antigen processing and presentation in cancer immunotherapy. Journal for immunotherapy of cancer Lee, M. Y., Jeon, J. W., Sievers, C., Allen, C. T. 2020; 8 (2)

  Abstract

  Knowledge about and identification of T cell tumor antigens may inform the development of T cell receptor-engineered adoptive cell transfer or personalized cancer vaccine immunotherapy. Here, we review antigen processing and presentation and discuss limitations in tumor antigen prediction approaches.Original articles covering antigen processing and presentation, epitope discovery, and in silico T cell epitope prediction were reviewed.Natural processing and presentation of antigens is a complex process that involves proteasomal proteolysis of parental proteins, transportation of digested peptides into the endoplasmic reticulum, loading of peptides onto major histocompatibility complex (MHC) class I molecules, and shuttling of peptide:MHC complexes to the cell surface. A number of T cell tumor antigens have been experimentally validated in patients with cancer. Assessment of predicted MHC class I binding and total score for these validated T cell antigens demonstrated a wide range of values, with nearly one-third of validated antigens carrying an IC50 of greater than 500 nM.Antigen processing and presentation is a complex, multistep process. In silico epitope prediction techniques can be a useful tool, but comprehensive experimental testing and validation on a patient-by-patient basis may be required to reliably identify T cell tumor antigens.

  View details for DOI 10.1136/jitc-2020-001111

  View details for PubMedID 32859742

  View details for PubMedCentralID PMC7454179

• Detection and Oncologic Outcomes of Head and Neck Squamous Cell Carcinoma of Unknown Primary Origin ANTICANCER RESEARCH Lee, M. Y., Fowler, N., Adelstein, D., Koyfman, S., Prendes, B., Burkey, B. B. 2020; 40 (8): 4207-4214

  Abstract

  To assess factors that predict detection of tumors and oncologic outcomes in head and neck squamous cell carcinoma of unknown primary (SCCUP).This was a retrospective cohort study at a single tertiary care institution.The primary site was detected at examination under anesthesia (EUA) in 92 (51.1%) patients. The primary site was detected by directed biopsies in 60 (65%), palatine tonsillectomy in 28 (30.4%), and lingual tonsillectomy in 4 patients (4.3%). Four of eight lingual tonsillectomies were positive (50%). Primary locations included: palatine tonsils (51, 28.3%), base of tongue (37, 20.6%), larynx (4, 2.2%), oral cavity (3, 1.67%) and nasopharynx (1, 0.6%). Human papillomavirus (HPV) positive status (HR=0.26, p=0.004) and treatment with chemoradiation (CRT) (HR=0.38, p=0.004) were associated with better disease free survival (DFS).A primary site was located after aggressive investigation in approximately half of the patients. More research is warranted towards the use of lingual tonsillectomy. Predictors of favorable prognosis included HPV positive status and treatment with CRT.

  View details for DOI 10.21873/anticanres.14421

  View details for Web of Science ID 000554884600001

  View details for PubMedID 32727746

• A cough that won't go away: Evaluation and treatment in 2 patients CLEVELAND CLINIC JOURNAL OF MEDICINE Lee, M. Y., Taliercio, R. M., Adessa, M., Milstein, C., Bryson, P. C. 2020; 87 (2): 83-89

  View details for DOI 10.3949/ccjm.87a.19010

  View details for Web of Science ID 000512391800007

  View details for PubMedID 32015061

• Outcomes of audiometric testing in children with auditory neuropathy spectrum disorder INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY Meleca, J. B., Stillitano, G., Lee, M. Y., Lyle, W., Liu, Y., Anne, S. 2020; 129: 109757

  Abstract

  Auditory Neuropathy Spectrum Disorder (ANSD) is characterized by hearing loss ranging from normal to profound. Additionally, results are confounded by commonly fluctuating hearing thresholds in ANSD. As such, we sought to evaluate results of audiometric testing on children with ANSD and the impact of age and time on testing results.Retrospective chart review on children <18 years of age diagnosed with ANSD at two tertiary care academic institutions. Data analyzed included initial audiogram with speech detection thresholds (SDT) and pure tone averages (PTA) as well as most recent unaided audiogram SDT and PTA.75 ANSD patients were analyzed, of which 32 (42.7%) were female. Bilateral and unilateral ANSD was seen in 55 (73.3%) and 20 (26.7%), respectively. A total of 130 ears with ANSD were assessed with 80 (61.5%) meeting inclusion criteria. Of these patients, the median age in years at first audiogram and most recent audiogram were 1.94 (0.45-13.68) and 4.22 (0.97-14.61), respectively. The median ages at which an SDT and PTA could first be acquired on the audiogram in ANSD patients were 1.94 (0.50-13.68) and 2.86 (0.45-13.68), respectively. The average SDT/PTA at the initial and most recent audiogram were 47.5/45.7 and 49.4/53.0 dB, respectively. SDT to PTA within the same audiogram exhibited strong correlation (r = 0.82, p < 0.001). Similarly, comparison of initial SDT to SDT at a later time interval showed strong correlation (r = 0.73, p < 0.001). SDT and PTA at initial audiogram and PTA at later time demonstrated lower correlation but was still statistically significant (r = 0.49, p < 0.009 and r = 0.51, p < 0.044, respectively). Individual PTA was associated with age (r = -0.56, p < 0.001).SDT and PTA within the same audiogram and initial SDT to SDT acquired at a later time correlate strongly in audiometric testing in children with ANSD. Although not as strong, initial SDT and PTA still correlate with PTA at a later time interval. These findings suggest that audiometric results yielding a reliable SDT and frequency specific information necessary to calculate the PTA is not typically obtained until 2-3 years old. However, once this information is obtained, the child's hearing is fairly stable but may fluctuate over time.

  View details for DOI 10.1016/j.ijporl.2019.109757

  View details for Web of Science ID 000509613300009

  View details for PubMedID 31704576

• The efficacy of intraoperative multimodal monitoring in pedicle subtraction osteotomies of the lumbar spine Shao, J., Lee, M. Y., Louis, S., Knusel, K., Lee, B. S., Pelle, D. W., Savage, J., Tanenbaum, J. E., Mroz, T. E., Steinmetz, M. P. AMER ASSOC NEUROLOGICAL SURGEONS. 2019: 683-690

  Abstract

  Iatrogenic spine injury remains one of the most dreaded complications of pedicle subtraction osteotomies (PSOs) and spine deformity surgeries. Thus, intraoperative multimodal monitoring (IOM), which has the potential to provide real-time feedback on spinal cord signal transmission, has become the gold standard in such operations. However, while the benefits of IOM are well established in PSOs of the thoracic spine and scoliosis surgery, its utility in PSOs of the lumbar spine has not been robustly documented. The authors' aim was to determine the impact of IOM on outcomes in patients undergoing PSO of the lumbar spine.All patients older than 18 years who underwent lumbar PSOs at the authors' institution from 2007 to 2017 were analyzed via retrospective chart review and categorized into one of two groups: those who had IOM guidance and those who did not. Perioperative complications were designated as the primary outcome measure and postoperative quality of life (QOL) scores, specifically the Parkinson's Disease Questionnaire-39 (PDQ-39) and Patient Health Questionnaire-9 (PHQ-9), were designated as secondary outcome measures. Data on patient demographics, surgical and monitoring parameters, and outcomes were gathered, and statistical analysis was performed to compare the development of perioperative complications and QOL scores between the two cohorts. In addition, the proportion of patients who reached minimal clinically important difference (MCID), defined as an increase of 4.72 points in the PDQ-39 score or a decrease of 5 points in the PHQ-9 score, in the two cohorts was also determined.A total of 95 patients were included in the final analysis. IOM was not found to significantly impact the development of new postoperative deficits (p = 0.107). However, the presence of preoperative neurological comorbidities was found to significantly correlate with postoperative neurological complications (p = 0.009). Univariate analysis showed that age was positively correlated with MCID achievement 3 months after surgery (p = 0.018), but this significance disappeared at the 12-month postoperative time point (p = 0.858). IOM was not found to significantly impact MCID achievement at either the 3- or 12-month postoperative period as measured by PDQ-39 (p = 0.398 and p = 0.156, respectively). Similarly, IOM was not found to significantly impact MCID achievement at either the 3- or 12-month postoperative period, as measured by PHQ-9 (p = 0.230 and p = 0.542, respectively). Multivariate analysis showed that female sex was significantly correlated with MCID achievement (p = 0.024), but this significance disappeared at the 12-month postoperative time point (p = 0.064). IOM was not found to independently correlate with MCID achievement in PDQ-39 scores at either the 3- or 12-month postoperative time points (p = 0.220 and p = 0.097, respectively).In this particular cohort, IOM did not lead to statistically significant improvement in outcomes in patients undergoing PSOs of the lumbar spine (p = 0.220). The existing clinical equipoise, however, indicates that future studies in this arena are necessary to achieve systematic guidelines on IOM usage in PSOs of the lumbar spine.

  View details for DOI 10.3171/2019.5.SPINE19125

  View details for Web of Science ID 000493980000008

  View details for PubMedID 31349220

• Predictive value of the ACS NSQIP calculator for head and neck reconstruction free tissue transfer LARYNGOSCOPE Tierney, W., Shah, J., Clancy, K., Lee, M. Y., Ciolek, P. J., Fritz, M. A., Lamarre, E. D. 2020; 130 (3): 679-684

  Abstract

  Predictive models to forecast the likelihood of specific outcomes after surgical intervention allow informed shared decision-making by surgeons and patients. Previous studies have suggested that existing general surgical risk calculators poorly forecast head and neck surgical outcomes. However, no large study has addressed this question while subdividing subjects by surgery performed.To determine the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator in estimating length of hospital stay and risk of postoperative complications after free tissue transfer surgery.A retrospective chart review of patients at one institution was performed using Current Procedural Terminology codes for anterolateral thigh (ALT) flap, fibula free flap (FFF), and radial forearm free flap (RFFF) reconstruction. Output data from the ACS NSQIP surgical risk calculator were compared with the observed rates in our patients.Incidences of cardiac complications, pneumonia, venous thromboembolism, return to the operating room, and discharge to skilled nursing facility (SNF) were compared to predicted incidences. Length of stay was also compared to the predicted length of stay.Three hundred thirty-six free flap reconstructions with 197 ALT flaps, 85 RFFFs, and 54 FFFFs were included. Brier scores were calculated using ACS NSQIP forecast and actual incidences. No Brier score was <0.01 for the entire sample or any subgroup, which indicates that the NSQIP risk calculator does not accurately forecast outcomes after free tissue reconstruction.The ACS NSQIP failed to accurately forecast postoperative outcomes after head and neck free flap reconstruction for the entire sample or subgroup analyses.4 Laryngoscope, 130:679-684, 2020.

  View details for DOI 10.1002/lary.28195

  View details for Web of Science ID 000479787400001

  View details for PubMedID 31361334

• Intraoperative Multimodal Monitoring in Pedicle Subtraction Osteotomies of the Lumbar Spine A Narrative Literature Review CLINICAL SPINE SURGERY Shao, J., Lee, B. S., Pelle, D., Lee, M. Y., Savage, J., Tanenbaum, J. E., Mroz, T. E., Steinmetz, M. P. 2019; 32 (4): 137-142

  Abstract

  The use of intraoperative multimodal monitoring (IOM) in spinal deformity surgeries is well documented. In particular, pedicle subtraction osteotomy (PSO), a corrective procedure for sagittal deformity of the spine, often involves IOM usage. By providing immediate feedback to the operating surgeon, IOM has the potential to eliminate or at least minimize the risk of iatrogenic neurological injury. However, despite the widespread usage of IOM, there is currently no standardization of IOM usage in complex spine surgeries, including lumbar PSOs, and decisions concerning IOM utilization are often driven by surgeon experience and preference. This creates a state of clinical equipoise, which is further complicated by the varying degrees of benefit that IOM has on patient outcomes depending on the operation and spinal levels involved. For instance, while IOM use in thoracic PSOs has been shown to be effective, there is no established consensus on the net impact of IOM use in PSOs of the lumbar spine. Although IOM has the potential to mitigate neurological damage, it also increases operation time and cost; thus, it should only be used in operations where it will have a net positive impact on patient outcomes. The question thus becomes whether PSO of the lumbar spine is one such operation. To address this, we examine the most frequently used IOM modalities and evaluate their current usage and efficacy in lumbar PSOs. Furthermore, we will also examine the utility of IOM for other surgeries of the lumbar spine, including corrective procedures for idiopathic scoliosis and degenerative scoliosis, and routine lumbar procedures, such as discectomies and decompression surgeries for foraminal and canal stenosis.

  View details for DOI 10.1097/BSD.0000000000000740

  View details for Web of Science ID 000467739700002

  View details for PubMedID 30407261

  View details for PubMedCentralID PMC6499651