The association between pretreatment nutritional status and immunotherapy response in patients with advanced head and neck cancer is unclear. We retrospectively analyzed a cohort of 99 patients who ...underwent treatment with anti-PD-1 or anti-CTLA-4 antibodies (or both) for stage IV HNSCC between 2014 and 2020 at the Johns Hopkins Hospital. Patient demographics and clinical characteristics were retrieved from electronic medical records. Baseline prognostic nutritional index (PNI) scores and pretreatment body mass index (BMI) trends were calculated. Associations between PNI and BMI were correlated with overall survival (OS), progression-free survival (PFS), and immunotherapy response. In univariate analysis, there was a significant correlation between OS and PFS with baseline PNI (OS: HR: 0.464; 95% CI: 0.265–0.814; PFS: p = 0.007 and HR: 0.525; 95% CI: 0.341–0.808; p = 0.003). Poor OS was also associated with a greater decrease in pretreatment BMI trend (HR: 0.42; 95% CI: 0.229–0.77; p = 0.005). In multivariate analysis, baseline PNI but not BMI trend was significantly associated with OS and PFS (OS: log (HR) = −0.79, CI: −1.6, −0.03, p = 0.041; PFS: log (HR) = −0.78, CI: −1.4, −0.18, p = 0.011). In conclusion, poor pretreatment nutritional status is associated with negative post-immunotherapy outcomes.
BackgroundLeiomyosarcoma (LMS) is one of the most common types of soft tissue sarcoma arising from the smooth muscle cells. Despite the current treatment regimens, many LMS patients experience ...progression and poor survival and might benefit from Immune Checkpoint Blockade (ICB). Yet LMS tumors have responded mildly to ICB. Deep immunogenomic profiling of LMS tumors might help in improving ICB outcomes by deconstructing the immune landscape to discover biomarkers of response and identify novel targets which might potentiate ICB outcomes in LMS.MethodsLMS tumors from The Cancer Genome Atlas (TCGA) Sarcoma cohort were classified into molecular subtypes based on previously identified gene signatures.1 We then examined the relationship of the subtypes with expression of various immune related genes. We comprehensively profiled the LMS immune landscape by performing Immunohistochemistry (IHC) (n = 65) for CD3, CD8, PDL1, CD163, TIM3, CD20, CD21 and CD31 on archived formalin fixed paraffin embedded blocks and multi-parameter flow cytometry (n = 22) on single cell suspensions isolated from LMS tumors resected at Johns Hopkins Hospital (JHH). We used HALO Digital Pathology Suite for further analysis.ResultsLMS tumors from the TCGA cohort were classified into 4 major subtypes which associated with expression levels of the immune genes and survival outcomes. Based on the tissue slides available for the TCGA data, we observed presence of lymphoid aggregates predominantly in one subtype. IHC from the JHH cohort showed higher density of CD163 and PDL1 cells as compared to lymphoid cells and were associated with poor survival. We also observed aggregates of CD3 and CD8 cells and Tertiary Lymphoid Structures (TLS), as seen by CD21, CD20, CD3 IHC in a subset of specimens. Upon merging the different IHC for each specimen (n = 52) we saw a marked colocalization of PDL1 with the lymphoid aggregates hinting at the possibility of Interferon Gamma induced PDL1 expression. We noted high expression of PDL1 and TIM3 on myeloid cells which was correlated with poor survival outcomes.ConclusionsDeep immune profiling of the LMS specimens suggests that the TIM3 expressing myeloid cells could be a potential target to augment immunotherapy in LMS. Through spatial analysis, we observed a higher density of PDL1 cells around lymphoid aggregates as compared to the rest of the tumor pointing to evidence of immune related activity. Coupling our discoveries vis-à-vis the immune landscape to the molecular subtypes of LMS will be crucial to identify patients who will most benefit from ICB.ReferenceML Hemming, et al, Mol Cancer Res 2020;18(9):1302–1314Ethics ApprovalThis study was conducted in accordance with the ethical principles and was approved by the Johns Hopkins Institutional Review Board and all samples were obtained in accordance with the Health Insurance and Accountability Act.
Introduction
The underlying factors that contribute to early radiotherapy (RT) termination are understudied, especially in the era of hypofractionated treatment regimens. In this retrospective ...investigation, we examined the characteristics and causes of premature RT terminations in senior adults (>70 years old) with oral cavity (OC) and laryngeal carcinomas.
Methods
Hundred and eighty‐eight patients treated with RT ± systemic therapy for OC and laryngeal cancer from 2017 to 2022 were identified. Premature termination was defined as completion of less than 95% of the prescribed RT. Logistic regression analysis was performed to examine factors predictive of premature termination, and survival was determined using the Kaplan–Meier method.
Results
Twenty patients (10.6%) experienced premature RT terminations. On regression analysis, ECOG score at initiation of RT was the only covariate studied to be independently associated with premature termination (OR 2.00, 95%CI: 1.21, 3.30, p = 0.007). Three‐year overall survival (49.1% vs. 77.3%) was significantly reduced in the termination cohort (p < 0.0001).
Conclusions
This analysis demonstrated over 1 in 10 patients had premature RT termination, which prognosticated inferior survival outcomes. Poor performance status may highlight patients at risk for premature termination and thus identify good candidates for hypofractionated protocols.
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.
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).
Retrospective cohort study.
Academic tertiary care hospital.
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.
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).
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.
Abstract
Objectives
To explore the impact of pre‐existing comorbidities on immunotherapy response, overall and progression‐free survival, and immune‐related adverse events (irAEs) of patients with ...advanced head and neck cancer (HNC) treated with immunotherapy.
Patients and methods
Ninety‐three patients treated with immunotherapy were identified and stratified into comorbidity absent or present (CCI < 1 and CCI ≥ 1, respectively) cohorts, and clinical outcomes were compared between these two groups.
Results
Patients with no comorbidities had longer overall survival (aHR = 2.74, 95% CI 1.18, 6.40,
p
= 0.02) and progression‐free survival (aHR = 2.07, 95% CI 1.03, 4.16,
p
= 0.04) and a higher tumor response rate (32% in CCI < 1 vs. 14% in CC ≥ 1,
p
= 0.05). Risk for irAEs was higher in the comorbidity absent group (
p
= 0.05).
Conclusion
Comorbidity should be considered as a significant prognostic factor in clinical decision‐making for patients with advanced HNC undergoing immunotherapy.
Human papillomavirus (HPV)-positive status in patients with oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved survival compared with HPV-negative status. However, it remains ...controversial whether HPV is associated with improved survival among patients with nonoropharyngeal and cervical squamous cell tumors.
To investigate differences in the immunogenomic landscapes of HPV-associated tumors across anatomical sites (the head and neck and the cervix) and their association with survival.
This cohort study used genomic and transcriptomic data from the Cancer Genome Atlas (TCGA) for 79 patients with OPSCC, 435 with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC), and 254 with cervical squamous cell carcinoma and/or endocervical adenocarcinoma (CESC) along with matched clinical data from TCGA. The data were analyzed from November 2020 to March 2021.
Positivity for HPV was classified by RNA-sequencing reads aligned with the HPV reference genome. Gene expression profiles, immune cell phenotypes, cytolytic activity scores, and overall survival were compared by HPV tumor status across multiple anatomical sites.
The study comprised 768 patients, including 514 (66.9%) with HNSCC (380 male 73.9%; mean SD age, 59.5 10.8 years) and 254 (33.1%) with CESC (mean SD age, 48.7 14.1 years). Human papillomavirus positivity was associated with a statistically significant improvement in overall survival for patients with OPSCC (adjusted hazard ratio aHR, 0.06; 95% CI, 0.02-0.17; P < .001) but not for those with non-OP HNSCC (aHR, 0.64; 95% CI, 0.31-1.27; P = .20) or CESC (aHR, 0.50; 95% CI, 0.15-1.67; P = .30). The HPV-positive OPSCCs had increased tumor immune infiltration and immunomodulatory receptor expression compared with HPV-negative OPSCCs. Compared with HPV-positive non-OP HNSCCs, HPV-positive OPSCCs showed greater expression of immune-related metrics including B cells, T cells, CD8+ T cells, T-cell receptor diversity, B-cell receptor diversity, and cytolytic activity scores, independent of tumor variant burden. The immune-related metrics were similar when comparing HPV-positive non-OP HNSCCs and HPV-positive CESCs with their HPV-negative counterparts. The 2-year overall survival rate was significantly higher for patients with HPV-positive OPSCC compared with patients with HPV-negative OPSCC (92.0% 95% CI, 84.8%-99.9% vs 45.8% 95% CI, 28.3%-74.1%; HR, 0.10 95% CI, 0.03-0.30; P = .009).
In this cohort study, tumor site was associated with the immune landscape and survival among patients with HPV-related tumors despite presumed similar biologic characteristics. These tumor site-related findings provide insight on possible outcomes of HPV positivity for tumors in oropharyngeal and nonoropharyngeal sites and a rationale for the stratification of HPV-associated tumors by site and the subsequent development of strategies targeting immune exclusion in HPV-positive nonoropharyngeal cancer.
Tumor histological factors that predict immunotherapy response in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are not well defined.
To investigate the ...association between tumor grade and immunotherapy response in patients with recurrent or metastatic mucosal HNSCC.
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.
High-grade tumors (HGTs) vs low-grade tumors (LGTs) in recurrent or metastatic HNSCC.
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.
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).
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.
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