Allergy History and Immunotherapy Response in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: This study examines the association between patient-reported allergy history and immune checkpoint inhibition (ICI) response in patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary care hospital. METHODS: Data were collected from the electronic medical records on baseline age, sex, allergy history, human papillomavirus status, T-stage, N-stage, smoking status, and survival for patients with and without an allergy history. The primary outcome was ICI response defined as complete or partial response by the RECIST criteria. Chi-square and logistic regression analyses were conducted to compare rates and odds of ICI response. Kaplan-Meier analyses were used to compare survival between groups. RESULTS: Our study included 52 patients with an allergy history and 36 patients without an allergy history. The groups were similar in age, sex, HPV status, smoking status, and T- and N-stage. Patients with an allergy history (17/52, 32.1%) had a greater ICI response rate than patients without allergy history (4/36, 11.1%) (P = .02). After adjusting for HPV, patients with allergies had 3.93 (1.19-13.00) times increased odds of ICI response compared to patients without allergies. The median progression-free survival was 6.0 and 4.2 months for patients with and without an allergy history respectively (log-rank, P = .04). The median overall survival was 25.0 and 11.1 months for patients with and without an allergy history respectively (log-rank, P = .002). CONCLUSION: Patient-reported allergy history was associated with ICI response in patients with RMHNSCC, underscoring the potential clinical utility of allergy history in estimating ICI response.

The association of a scholarly concentrations program with medical students' matched residencies.

PURPOSE: Many medical school curricula include Scholarly Concentrations (SC) programs. While studies have examined how these programs affect students' future research involvement, the association of SC programs with students' specialty choices is uncertain. This study examines the SC program factors associated with congruence between the specialty focus of students' SC projects and the clinical specialty they matched into for residency. METHODS: The authors conducted a retrospective cohort study of all students participating in the SC program at Johns Hopkins University School of Medicine for graduating classes 2013-2020. They used data from program questionnaires to categorize students' specialty interests (baseline) and SC program experiences (post-program). The authors categorized each student's project into specialties according to their faculty mentors' primary appointments, abstracted student publications from SCOPUS, and abstracted residency program rankings from Doximity Residency Navigator. The authors used multivariable logistic regression to calculate adjusted odds ratios (aOR) for specialty-congruent matching (same specialty as SC project) and for matching into a Doximity-ranked top 20 or top 10 program. RESULTS: Overall, 35.3% of the 771 students matched into the same specialty as their SC projects. Increased odds of specialty-congruent matching occurred with 'definite' interest in the specialty at baseline [aOR (95% CI): 1.76 (0.98-3.15)] (P = 0.06) and with increasing publications with SC mentors [aOR (95% CI): 1.16 (1.03-1.30)] (P = 0.01). Congruence between SC specialty focus and matched specialty conferred no significant difference in odds of matching to a Doximity-ranked top 20 or top 10 program. CONCLUSIONS: Baseline certainty of specialty interest and research productivity were associated with specialty congruence. However, as completing an SC project in a given specialty was not associated with increased odds of matching into that specialty nor into a higher Doximity-ranked program, SC program directors should advise students to pursue SC projects in any topic of personal interest.

Tumor Histological Grade and Immunotherapy Response in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Importance: Tumor histological factors that predict immunotherapy response in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are not well defined. Objective: To investigate the association between tumor grade and immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. Design, Setting, and Participants: In this retrospective cohort study, the medical records of 60 patients with recurrent or metastatic mucosal HNSCC treated with immune checkpoint inhibitors at Johns Hopkins Hospital between July 1, 2015, and January 22, 2020, were reviewed. Exposures: High-grade tumors (HGTs) vs low-grade tumors (LGTs) in recurrent or metastatic HNSCC. Main Outcomes and Measures: Patients were divided into 2 groups: those with LGTs (well differentiated and moderately differentiated) and those with HGTs (poorly differentiated). The main outcome was a clinically beneficial immunotherapy response, defined as complete response or partial response. Univariable and multivariable logistic regressions were conducted to calculate odds ratios for each variable's association with immunotherapy response. Survival differences were evaluated using Kaplan-Meier survival curves with multivariable Cox proportional hazards regression models. Results: The 60 patients (35 with HGTs and 25 with LGTs) had a mean (SD) age of 64.6 (8.88) years; 51 were male (85%); and 38 were current or former smokers (63%). The oropharynx was the most common primary tumor site both in patients with HGTs (22 of 35; 63%) and those with LGTs (12 of 25; 48%). Bivariate analysis showed the proportion of patients having a beneficial response to immunotherapy was greater for patients with HGTs (12 of 35; 34.3%) than those with LGTs (2 of 25, 8.0%) (difference, 26.3%; 95% CI, 7.3%-45.3%). Upon multivariable analysis, patients with HGTs had 5.35-fold increased odds (95% CI, 1.04-27.37) of having a clinically beneficial response to immunotherapy. Among patients with available tumor genomic profiling data, the mean tumor mutational burden was greater for patients with HGTs (mean [SD], 8.6 [5.4] mut/Mb; n = 8) than patients with LGTs (mean [SD], 3.6 [1.1] mut/Mb; n = 4) (difference = 5.0 mut/Mb; 95% CI -1.4 to 11.4 mut/Mb; Cohen d = 1.2). Conclusions and Relevance: In this cohort study, tumor grade was independently associated with immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. These findings highlight the potential role of tumor grade in predicting immunotherapy response in mucosal HNSCC.

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review.

Given the recent successes of anti-PD-1 immunotherapy, many clinical trials have sought to assess the safety and efficacy of this treatment modality in the neoadjuvant setting. This systematic review provides a comprehensive summary of findings from neoadjuvant head and neck cancer immunotherapy clinical trials with a focus on PD-1/PD-L1 axis blockade. Pubmed, Embase, Cochrane Library, Web of Science, Google Scholar, and clinicaltrials.gov were systematically searched for all eligible neoadjuvant head and neck cancer immunotherapy clinical trials. Eight clinical trials met the inclusion criteria comprising a total of 260 patients. Study drugs included nivolumab, pembrolizumab, ipilimumab, durvalumab, and tremelimumab. The overall mean objective response rate (ORR) was 45.9 ± 5.7% with a 41.5 ± 5.6% single agent mean ORR. There were no deaths due to immune-related toxicities. Neoadjuvant immunotherapy for mucosal head and neck squamous cell cancer has demonstrated favorable response rates with no unexpected immune-related toxicities in phase I/II clinical trials.