Recurrent Squamous Cell Carcinoma Research Articles

Considerable interlaboratory variation in PD-L1 positivity forhead and neck squamous cell carcinoma in the Netherlands- A nationwide evaluation study.

Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are eligible for first-line immune checkpoint inhibition if their tumour is positive for programmed death ligand 1 (PD-L1) determined by the combined positive score (CPS). This nationwide study, using real-world data, investigated the developing PD-L1 testing landscape in the first 3 years after introduction of the test in HNSCC and examined interlaboratory variation in PD-L1 positivity rates. Pathology reports of HNSCC patients mentioning PD-L1 were extracted from the Dutch Pathology Registry (Palga). Tumour and PD-L1 testing characteristics were analysed per year and interlaboratory variation in PD-L1 positivity rates was assessed using funnel plots with 95% confidence limits around the overall mean. A total of 817 PD-L1 tests were reported in 702 patients among 19 laboratories; 85.2% of the tests on histological material were stated to be positive. The national PD-L1 positivity rate differed significantly per year during the study period (79.7-89.9%). The use of the recommended 22C3 antibody increased from 59.9 to 74.3%. A total of 673 PD-L1 tests on histological material from 12 laboratories were analysed to investigate interlaboratory variation. Four (33%) deviated significantly from the national mean of PD-L1-positive cases using CPS ≥ 1 cut-off, while two (17%) deviated significantly for CPS ≥ 20 cut-off. In the first 3 years of PD-L1 assessment in HNSCC, the testing landscape became more uniform. However, interlaboratory variation in PD-L1 positivity rates between Dutch laboratories was substantial. This implies that there is a need for further test standardisation to reduce this variation.

Is Perineural Invasion an Independent Prognostic Factor for Local Recurrence in Oral Squamous Cell Carcinoma?

Is Perineural Invasion an Independent Prognostic Factor for Local Recurrence in Oral Squamous Cell Carcinoma?

The relationship between the treatment course and prognosis of oligometastasis after esophageal squamous cell carcinoma resection.

The concept of oligometastasis, which represents limited metastatic disease, has recently gained interest, accompanied by a more detailed classification. This study aims to investigate the relationship between the treatment course and prognosis in patients with a recurrence of esophageal squamous cell carcinoma (ESCC) after curative esophagectomy. 126 patients with ESCC recurrence after curative resection were enrolled in this study. Oligometastasis was defined as fewer than five recurrences in a single organ. Patients were classified as having oligometastatic recurrence (OLR) or polymetastatic recurrence (PLR). Patients were further classified into four subgroups according to lesion progression: persistent oligorecurrence (PER-OLR), converted polyrecurrence (CON-PLR), induced oligorecurrence (IND-OLR), and persistent polyrecurrence (PER-PLR). We analyzed the relationship between the recurrence patterns and prognosis according to the progression of oligometastatic lesions. OLR was identified in 58 (46%) of 126 patients with recurrence. Patients with OLR had a significantly better prognosis than those with PLR (P < 0.0001). A further subgroup analysis revealed that patients who underwent IND-OLR had a similar prognosis to those who underwent PER-OLR. This study suggests that OLR is a prognostic factor after recurrence following resection of ESCC and that PLR can be converted to OLR by therapeutic intervention to achieve a long-term survival.

Clinical Results and Prognostic Factors in BNCT for Recurrent Squamous Cell Carcinoma of the Head and Neck under the Japan National Health Insurance System: A Retrospective Study of the Initial 47 Patients

PurposeRecurrent head and neck cancer presents a therapeutic challenge due to cumulative toxicity from initial radiation therapy, limiting re-irradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck. Materials and MethodsThis retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiotherapy with a median dose of 70 Gy (range, 44–176) prior to BNCT. Median tumor size was 11 cm3 (range, 1–117 cm3), with 23% of tumors larger than 30 cm3, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3–45.2). In 23 patients, 18F-FBPA-PET was performed within 1 week before BNCT, tumor to blood 10B ratio was 3.5 (range, 2.0–8.7). ResultsEfficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant impact on achieving complete response. ConclusionsThis study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer.

Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive. Clinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment-related adverse events (trAEs), grade three or more trAEs, treatment-related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted. Twenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment-related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%-65.02%), 13.82% (95% CI, 11.23%-16.62%), 0.39% (95% CI, 0.15%-0.71%), 3.99% (95% CI, 2.36%-5.95%), respectively. Programmed cell death protein 1 (PD-1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05-1.49 and 1.36, 95% CI, 1.15-1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08-1.84 and 1.79, 95% CI, 1.39-2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06-7.70 and 10.14, 95% CI, 5.49-18.70, respectively) compared with programmed death-ligand 1 (PD-L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD-1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03-1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different. Our study suggests that the incidences of grade three or more trAEs, treatment-related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD-L1 inhibitors monotherapy may be safer compared with PD-1 inhibitors monotherapy and ICIs combination therapy.

Survival impact of sequential chemotherapy following pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma.

Pembrolizumab alone or combined with chemotherapy is the standard of care for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with positive programmed death-ligand 1 combined positive scores. However, data on second-line chemotherapy following pembrolizumab are scarce. A single-center, retrospective study was conducted to determine the efficacies of pembrolizumab and pembrolizumab plus chemotherapy as first-line treatments and the efficacy of second-line chemotherapy for patients with R/M HNSCC who were refractory or intolerant to first-line treatment. Fifty-four patients were treated with pembrolizumab, and 29 received second-line therapy, with 27 opting for cetuximab-containing regimens. The median progression-free survival (PFS), overall survival (OS), and PFS on next-line therapy for first-line treatment were 4.7 (95% confidence interval [CI], 2.1-8.7), 22.1 (95% CI, 12.6-not reached), and 15.6months (95% CI, 9.7-not reached) in the pembrolizumab group and 5.4 (95% CI, 3.3-6.8), 15.8 (95% CI, 8.6-not reached), and 13.7months (95% CI, 8.1-not reached) in the pembrolizumab plus chemotherapy group, respectively. The overall response rate and median PFS for second-line treatment were 48.3% (95% CI, 30.4-67.0) and 6.1months (95% CI, 2.30-8.84). The median OS for patients who received second-line treatment was 18.4months, which was superior to the median OS of 6.0months for patients who received the best supportive care (log-rank p = 0.10). This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance.

Validation and comparison of prognostic scoring systems in patients with head and neck squamous cell carcinoma treated with nivolumab.

Several scoring systems have been developed to predict prognosis in patients with refractory cancer. We aimed to validate eight scoring systems and determine the best method for predicting the prognosis of head and neck squamous cell carcinoma treated with nivolumab. This multicentre retrospective study involved 154 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with nivolumab between 2017 and 2020. Oncological outcomes were assessed according to the scoring systems, including MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scores. Objective response, overall survival and progression-free survival were evaluated using logistic regression and Cox proportional hazards analyses. Receiver operating curve analysis was used to calculate the area under the curve and estimate the efficacy of each score. No significant associations were found between the responses and any score. Seven of the eight scoring systems were associated with disease control (odds ratio, 0.26-0.70). Amongst the eight scoring systems, MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio showed the highest area under the curve for predicting response and disease control. Seven scoring systems were prognostic factors for progression-free survival (hazard ratio, 1.22-1.95). All eight scoring systems were prognostic factors for overall survival (hazard ratio, 1.62-3.83). According to the time-dependent receiver operating characteristics analysis for overall survival, the Hammersmith scoring system had the best predictive ability at 3months, and the MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio scoring system had the highest area under the curve between 6 and 24months. MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scoring systems were better predictors of prognosis in patients with head and neck squamous cell carcinoma treated with nivolumab.

Salvage transoral robotic surgery in recurrent oropharyngeal carcinoma: a single-center retrospective study.

Salvage surgery is still the best therapeutic option for resectable recurrent oropharyngeal squamous cell carcinoma (rOPSCC). Transoral robotic surgery may potentially reduce the morbidity of standard open approaches. The aim of the study is to present oncological and functional outcomes of a monocentric experience in salvage transoral robotic surgery. We performed a single-center retrospective analysis of patients submitted to transoral robotic salvage surgery with or without neck dissection for cT1-3 rOPSCC. We investigated complication rate, survival outcomes (Overall Survival, Disease Specific Survival, Loco-Regional Recurrence Free Survival) and functional outcomes (tracheal tube and/or gastrostomy dependence). Sixty-one patients were included in the analysis. No major complications or perioperative deaths were recorded. The estimated 2-year OS was 76.7%, DSS 81.8% and LRRFS 50.5%. In multivariable analysis rpT, PNI (perineural infiltration) and HPV-positivity were significantly associated with LRRFS (Hazard Ratios: T3 vs T1 6.43, PNI yes vs no 4.19, HPV+ yes vs no 2.63). At last follow up, 97% of patients were tracheal tube-free, while 93% were gastrostomy-free. Transoral robotic salvage surgery is a successful treatment in selected patients affected by rOPSCC because it grants good oncologic and functional outcomes.

Surgical Reconstruction of a Large Defect after Excision of Infiltrative Squamous Cell Carcinoma in the Scalp and Occipital Region: A Case Report

Squamous cell carcinoma (SCC) of the scalp is the second most prevalent skin cancer, following basal cell carcinoma. Notably, it has the capability to infiltrate the skull, dura mater, and even brain tissue. The cornerstone of treatment is the surgical removal of the lesion, with a particular focus on the depth of invasion, which is directly correlated with recurrence rates. Post-surgical strategies may involve immediate or delayed cranial bone reconstruction and repair of scalp defects using either artificial dermis or skin grafts. In the case presented, a substantial defect necessitated more than a single flap for primary repair. Hence, a single pedicle double-island flap was designed for reconstructing the occipital area. Due to increased tension on the flap following cranial bone repair, the bone repair was temporarily deferred. Postoperative care included adjuvant chemotherapy and radiotherapy to mitigate the risk of SCC recurrence.

Abstract 7658: Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a prognostic biomarker for pembrolizumab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma

Abstract Background: Programmed cell death ligand 1 (PD-L1) expression alone has limited predictive value for pembrolizumab plus 5-fluorouracil and platinum (PFP) therapy in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). An artificial intelligence (AI)-powered spatial tumor-infiltrating lymphocyte (TIL) analyzer may provide independent prognostic information. Methods: This study included 63 patients with locally incurable HNSCC who received first-line PFP at Samsung Medical Center. Patients were classified into inflamed phenotype (IP) or non-inflamed phenotype (NIP) based on the 5% proportion threshold of inflamed 1 mm2-sized grids over total grids within hematoxylin and eosin-stained whole-slide images (WSIs) analyzed using Lunit SCOPE IO. We evaluated the prognostic value of inflamed status and densities of intratumoral TILs (iTILs), stromal TILs (sTILs), and tumor microenvironment TILs (tTILs). Results: Patients were predominantly male (78%). The median age at PFP initiation was 57 years. The most common primary tumor site was oral cavity (49.2%), followed by oropharynx (16%) and hypopharynx (10%). Of the 37 patients with available PD-L1 combined positive score (CPS), 2 (5%), 23 (62%), and 12 (32%) had CPS values of &amp;lt;1, 1-19, and ≥20, respectively. The overall response rate was 54%, with 67% in the CPS ≥20 subgroup and 48% in the CPS &amp;lt;20 subgroup. The median progression-free survival (PFS) was 7.2 months, with 10.8 months for patients with CPS ≥20 and 5.5 months for patients with CPS &amp;lt;20. The median overall survival (OS) was 18.6 months. Among 62 patients with available WSIs, 47 (74%) and 15 (26%) patients were categorized as having an IP and NIP, respectively. Oral cavity cancer was enriched with IP (57.4% of all IP cases vs 26.7% of all NIP cases), while all four paranasal sinus tumors had NIP. The overall response rate was 57% in the IP group and 44% in the NIP group. Patients with IP had significantly longer PFS and OS than patients with NIP, both in unadjusted (hazard ratio [HR] for PFS, 0.4; 95% confidence interval [CI], 0.21-0.78; P = 0.007; HR for OS, 0.43; 95% CI, 0.2-0.95; P = 0.036) and PD-L1 CPS-adjusted analyses (HR for PFS, 0.41; 95% CI, 0.21-0.79; P = 0.008; HR for OS, 0.4; 95% CI, 0.18-0.89; P = 0.025). High densities (≥25th percentile) of iTILs, sTILs, and tTILs were all significantly associated with prolonged PFS after CPS adjustment (P = 0.001, 0.001, and 0.012). High density of iTILs was also significantly associated with improved OS (P = 0.001 after CPS adjustment), while there was no significant association between OS and high density of sTILs or tTILs (0.077 and 0.085, respectively, after CPS adjustment). Conclusion: An AI-driven spatial TIL analyzer might serve as a simple and independent prognostic biomarker in HNSCC patients receiving pembrolizumab plus chemotherapy. Citation Format: Sehhoon Park, Junghoon Shin, Chan-Young Ock, Chang Ho Ahn, Hyun Ae Jung, Se-Hoon Lee, Myung-Ju Ahn. Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a prognostic biomarker for pembrolizumab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7658.

Abstract 222: Establishment of patient-derived tumor organoids from head and neck cancers for predicting response to treatments

Abstract The risk of relapse or recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) is high despite the combination of surgery and radiochemotherapy, responsible for high toxicity. It is crucial to develop new therapeutic strategies and to identify patients likely to benefit from these treatments. Patient-Derived Tumor Organoids (PDTO) are three-dimensional multicellular structures derived from patient tumor samples and faithfully reproduce the histological and molecular characteristics of the original tumor. A growing body of research indicates that PDTO may predict the clinical response, representing a major opportunity for the development of new therapeutic strategies and precision medicine. The purpose of this translational study is to generate PDTO from HNSCC patients to evaluate their predictive value. PDTO were obtained after dissociation of tumor specimen of HNSCC patients through the setup of the clinical study ORGAVADS (NCT04261192). Tumor cells were embedded in extracellular matrix and cultured in specific medium. Histological and immunohistochemical characterizations were performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovative therapies were evaluated by live-cell imaging and viability assays. The culture conditions were optimized to improve the success rate of PDTO establishment which now exceeded 50%. Twenty-one PDTO lines have been established and showed histological characteristics close to the original tumor. Expression of immunohistochemical tumor markers p53, p40, p63, and p16 were similar in tumors and paired PDTO. Functional assays were performed on 15 PDTO to analyze the response to treatments (cisplatin, olaparib, X-Rays) and heterogeneity of response was observed between the models. When clinical response was available, PDTO derived from good responders showed high sensitivity to treatments while PDTO from bad responders showed low sensitivity to treatments. Interestingly, two PDTO lines derived from HPV+ oropharyngeal tumors displayed very high sensitivity to cisplatin, matching with the patient's profile and response. Our results showed feasibility to derive PDTO from HNSCC and to perform functional assay to assess their response to different treatments. The first studies of correlation between PDTO and patient responses are promising and will be further investigated in more patients. This will allow to demonstrate the predictive value of PDTO from HNSCC with the purpose to develop a clinically compatible predictive functional assay. Citation Format: Marion Perréard, Vianney Bastit, Lucie Lecouflet, Guillaume Desmartin, Romane Florent, Corinne Jeanne, Juliette Thariat, Emmanuel Babin, Laurent Poulain, Louis-Bastien Weiswald. Establishment of patient-derived tumor organoids from head and neck cancers for predicting response to treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 222.

Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.

Abstract 1195: Prospective study for the identification of nivolumab biomarkers via analyses of pre-treatment plasma exosome mRNAs from head and neck cancer patients (BIONEXT)

Abstract Nivolumab paved a new way in the treatment of recurrent or metastatic (RM) head and neck squamous cell carcinoma of (HNSCC). However, the limited rates of long-term survivors (&amp;lt; 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and as well provides a biological clue to develop effective therapies for a majority of non-survivors. Pre-treatment plasmas (N = 104) were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment naïve tumor and plasma samples (N = 20) were assayed to elucidate biological implications of the PEX mRNA signature. A combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely (P = 0.000124) distinguished non-survivors from &amp;gt;2-yr survivor (0% vs 57.7%) with a high hazard ratio (2.878; 95% confidence interval 1.639-5.055; P = 0.0002348). In paired samples, high PEX HLA-E mRNA (a non-survivor-predicting marker) reflected the increased HLA-E protein expression (P = 0.0191) and the dense population of tumor-infiltrating NK cells (P = 0.024) in the corresponding tumor. It is estimated that the effects of PD-1blockade is canceled by the HLA-E-NKG2A immune checkpoint in patients with high PEX HLA-E mRNA. The combination of NKG2A antibody (i.e., monalizumab) and nivolumab may be a promising strategy for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs. A candidate companion diagnostic of nivolumab that indicates a possible treatment option is identified. Citation Format: Muneyuki Masuda, Satoshi Toh, Mioko Matsuo, Masashi Sugasawa, Keisuke Yamazaki, Ueki Yushi, Torahiko Nakashima, Hideoki Uryu, Takeharu Ono, Tsutomu Ueda, Hirohito Umeno, Satoshi Kano, Kiyoaki Tsukahara. Prospective study for the identification of nivolumab biomarkers via analyses of pre-treatment plasma exosome mRNAs from head and neck cancer patients (BIONEXT) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1195.

Abstract 3852: Comprehensive genomic profiling of recurrent or metastatic head and neck cancer presenting with combined positive score 90 or more

Abstract Background. Biomarkers that predict response to immune checkpoint inhibitor (ICI) in recurrent metastatic squamous cell carcinoma of the head and neck (RMHNSCC) are not well known. Previously, we have found that Combined positive score (CPS) ≥90 and albumin &amp;gt;3.5 respond well to ICI treatment in patients with RMHNSCC treated with ICI irrespective of addition of chemotherapy. In the present study, we investigated whether RMHNSCC with CPS ≥90 has a characteristic genomic mutational profile. Methods. CPS measurements were performed on a single tumor specimen at the time of diagnosis of RMHNSCC, as approved by Japanese health insurance. Tumor specimens were obtained from the primary tumor as much as possible, and sections that best reflected anti-tumor immunity were decided by a pathologist. We retrospectively reviewed the results obtained from comprehensive genomic profiling (CGP) testing of RMHNSCC cases with CPS ≥90 who were treated by ICI experienced at our institution. Results. There were 117 eligible RMHNSCC cases. The number of primary lesions were oral cavity in 28 cases (23.9%), nasopharynx in 10 cases (8.5%), oropharynx in 21 cases (17.9%), hypopharynx in 33 cases (28.2%), and others in 18 cases (15.4%). Of 117 patients, 28 patients (23.9%) had a CPS ≥90. Of the 28 cases, the number of primary lesions were oral cavity in 12 cases (42.9%), nasopharynx in 4 cases (14.3%), oropharynx in 0 cases (0%), hypopharynx in 8 cases (28.6%), and others in 3 cases (10.7%). When ICI was administered, CPS ≥90 had a statistically significantly better prognosis than CPS &amp;lt;90 for OS and PFS. Of the 28 cases with CPS ≥90, CGP test was performed in 6 cases. The primary lesions in the 6 cases consisted of 3 oral cavity, 2 nasopharynx, 1 hypopharynx, and 1 maxillary sinus. All three oral primary cases had co-mutations in the TERT promoter and HRAS. Two of the nasopharyngeal primary cases had mutations in JAK3 and STAT, respectively. One of the hypopharyngeal primary cases had mutations in FGFR3. Conclusion. RMHNSCC with CPS ≥90 had unique mutations that could account the enhanced PD-L1 expression, such as TERT/HRAS co-mutation, JAK-STAT pathway mutation, and FGFR pathway mutation. The above findings may be useful for predicting the efficacy of ICI for RMHNSCC. Citation Format: Yuki Saito, Kage Hidenori, Kenya Kobayashi, Osamu Fukuoka, Koji Yamamura, Aya Shinozaki-Ushiku, Katsutoshi Oda, Kenji Kondo. Comprehensive genomic profiling of recurrent or metastatic head and neck cancer presenting with combined positive score 90 or more [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3852.

Abstract 6413: Biomarkers of response and progression to Pembrolizumab and Vorinostat combination in late-stage squamous cell carcinoma patients of different locations included in the PEVOsq basket trial

Abstract Background: Epigenetic modulation plays a major role in escaping tumor immunosurveillance. PEVOsq (NCT04357873) was an open-label, non-randomized, multi-center, basket phase II trial evaluating the efficacy of pembrolizumab (P) and the vorinostat (V) HDAC inhibitor in 112 patients (pts) with recurrent and/or metastatic squamous cell carcinoma (SCC) of the cervix, head and neck, anus, vulva/vagina, penis, and lung. Results showed an objective response rate (ORR) of 25%, the highest being in anal (31%) and cervical (39%) (ASCO #397612). We report here early biomarkers of response and progression to P+V. Patients and Methods: Pts had to undergo a tumor biopsy at baseline, and optional biopsies on-treatment (after cycle 2), and at progression for translational analyses. PD-L1 expression (n=102), tumor-infiltrating lymphocytes quantification (n=39), HPV typing (n=111), WES (n=83), RNAseq (n=82) and liquid chromatography-mass spectrometry (LC-MS) quantitative analysis of histone post-translational modifications (PTMs) (n=44) were performed on baseline samples.SNVs, CNVs, TMB, MSI status (by MSI sensor), aneuploidy score (AS), mutational signatures, immune signatures, and histone modifications were correlated with response and progression. Results: Sixty-six pts were HPV+ (59%). Most frequently altered genes were PIK3CA (30%), TP53 (30%), KMT2D/C (18 and 17%), and FGF3/4 (17%). MSI was detected in 4 pts (5%), and TMB-high (&amp;gt;10mut/Mb) in 13 pts (16%). High AS (&amp;gt;10) was detected in 34 pts (40%), and was significantly associated with HPV- status (p=0.03). TMB high and MSI were associated with MMR mutational signatures (p&amp;lt;0.01). TMB high was also associated with APOBEC (p=0.02) and DNA polymerase (POL) signatures (p &amp;lt;0.01). Biomarkers associated with improved overall survival (OS) included HPV positivity (7.8 months versus 17.4 months, p&amp;lt;0.01), high TMB (not reached versus 10.3 months, p=0.01), and high PD-L1 CPS score (13.2 months versus 7.0 months, p=0.06).Deconvolution of immune cell infiltration showed an expected trend for increased CD8 and decreased neutrophil infiltration in non progressor pts.Interestingly, LC-MS histone PTMs profiling showed a significant decrease in H4K5K8K12K16-4ac (p=0.05) and increase in H3K27me2K36me1 in non progressor pts (p=0.03). At the transcriptomic level, although not statistically significant, we observed modulation in the expression of genes associated with H3K36me1 (KDM2A, SETD3, SMYD2), and H3K27me3 (KDM6A) regulation, as well as HDAC genes. Conclusions: HPV+ status was associated with improved OS, together with a high TMB and PD-L1 expression. CD8, macrophages and neutrophil signatures at baseline were associated with response. Promising epigenetic biomarkers were identified using LC/MS and will be correlated to transcriptomic and genomic data. Citation Format: Christophe Le Tourneau, Luca Mazzarella, Bastien Cabarrou, Miguel Francisco, Célia Dupain, Maral Halladjian, Gianmaria Frige, Bruno Duso, Yinxiu Zhan, Elena Guerini-Rocco, Roberta Noberini, Tiziana Bonaldi, Maria Manuela Tonini, Grégoire Marret, Clélia Coutzac, Elodie Coquan, Mathilde Saint-Ghislain, Olivia Le Saux, Laetitia Chanas, François Legrand, Daria Maria Filippini, Emmanuelle Jeannot, Stephan Bernhart, Gabor Balogh, Marta Jimenez, Thomas Filleron, Nicolas Servant, Maud Kamal. Biomarkers of response and progression to Pembrolizumab and Vorinostat combination in late-stage squamous cell carcinoma patients of different locations included in the PEVOsq basket trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6413.

Nivolumab plus ipilimumab versus the EXTREME regimen in recurrent/metastatic squamous cell carcinoma of the head and neck: a cost-effectiveness analysis

In the CheckMate 651 study, nivolumab plus ipilimumab versus EXTREME (cisplatin/carboplatin + cetuximab + fluorouracil) regimen was compared for effectiveness. It is not known whether these immunotherapy agents are cost-effective for recurrent or metastatic squamous cell carcinomas of the head and neck (R/M SCCHN). The purpose of this study was to compare the cost-effectiveness of nivolumab plus ipilimumab with EXTREME in the first-line setting from the standpoint of third-party payers in the United States. The projecting of costs and outcomes over 15 years was done using a three-state partitioned survival model discounted by 3% per year. Long-term extrapolation of CheckMate 651 was used to model progression-free survival and overall survival (OS). The incremental net health benefit (INHB), incremental net monetary benefit (INMB), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. The uncertainty and stability of the model were accounted for via one-way and probabilistic sensitivity analyses. As compared with nivolumab plus ipilimumab, EXTREME was associated with an increase of 0.154 life-years and 0.076 QALYs, as well as a cost increase of $572 per patient. The corresponding ICERs were $7545/QALY along with the values of INMB and INHB were $113,267 and 0.076 QALYs, respectively, at a willingness to pay (WTP) threshold of $150,000/QALY. The probability of nivolumab plus ipilimumab being cost-effective was > 99% in patients with combined positive score (CPS) ≥ 1, CPS 1–19, or CPS ≥ 20. Moreover, hazard ratio for OS and body weight were the most sensitive parameters for the model. According to sensitivity analyses, these results were generally robust. In overall populations with R/M SCCHN, the EXTREME regimen is cost-effective compared with nivolumab plus ipilimumab. Given a WTP threshold of $150,000 per QALY, the probability of the EXTREME regiment being cost-effective compared with nivolumab and ipilimumab, was 64%. Importantly, there was heterogeneity in the cost-effectiveness probabilities, based on primary sites and expression levels of PD-L1. Therefore, tailored treatment based on individual patient and clinical characteristics, remains important, and may impact the cost-effectiveness of the regimens under study.

Real-world 2-year long-term outcomes and prognostic factors in patients receiving nivolumab therapy for recurrent or metastatic squamous cell carcinoma of the head and neck

Real-world 2-year long-term outcomes and prognostic factors in patients receiving nivolumab therapy for recurrent or metastatic squamous cell carcinoma of the head and neck

"Diffuse Hot Pleura" in a Case of Recurrent Squamous Cell Carcinoma of the Foot: 18 F-FDG PET/CT Findings.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer. Unlike basal cell carcinoma, regional lymph nodal metastases and subsequent distant site metastases are more common. Up to approximately 2% to 5% of cSCCs can result in distant metastases. Prognosis is dismal, and median survival is distinctly shortened in case of distant metastatic disease. Diffuse pleural metastases with distinctive overarching unilateral involvement are uncommon. Cutaneous SCC commonly metastasizes to lymph nodes, lungs, liver, bones, and skin. Diffuse unilateral pleural metastasis of cSCC of the foot is extremely rare. We report the case of a 54-year-old man with recurrent cSCC. On follow up restaging, 18 F-FDG PET/CT revealed diffuse nodular bipleural (visceral and parietal) hypermetabolic right pleural thickening, which was later biopsied and turned out to be diffuse pleural metastases from cSCC giving appearance of "hot pleura."

A Phase 2 Clinical Trial of Pembrolizumab with Radiation Following Progression on anti-PD-1 Therapy in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

A Phase 2 Clinical Trial of Pembrolizumab with Radiation Following Progression on anti-PD-1 Therapy in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

A Phase II Trial of Personalized Immunotherapy in Patients (pts) with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC) That Have Progressed on Prior Immunotherapy.

A Phase II Trial of Personalized Immunotherapy in Patients (pts) with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC) That Have Progressed on Prior Immunotherapy.