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.
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.
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.
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.
Due to the sanctions imposed on Syria on an ongoing basis, the most recent of which is the “Caesar Act,” which has affected Syria in general and in particular the information sector, and whose ...effects included the ban on the use of digital certificates (SSL Certificate); it has become impossible to use locally generated digital certificates granted by the National Authority for Information Technology Services in Syria, because browsers will not support the use of these certificates specific to this country. Syria has previously obtained, through the Ministry of Communications and Technology, in cooperation with a friendly country, the authority to issue national digital certificates and a national digital certificate generator. However, after the issuance of the “Caesar Act,” which stipulates in one of its paragraphs the imposition of information sanctions on Syria, the authentication of the Syrian digital certificate issuance authority has been prevented by international authentication authorities, including (VeriSign, Thawte, Geotrust, Comodo, Entrust, DigiCert, and others). Consequently, the authority to issue Syrian digital certificates becomes unreliable because international browsers will not accept their use except after obtaining electronic permission to certify their authenticity and reliability by international authentication authorities, and the latter will not grant acceptance due to sanctions. This research presents a proposed technique for addressing the aforementioned ban problem, by building an open-source web browser that does not depend on international authentication authorities to authenticate nationally generated digital certificates, but rather it breaks the connection with those international authentication authorities and ensures correct operation of using these national certificates.
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