scholarly journals Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Nir Hirshoren ◽  
Issa Al-Kharouf ◽  
Jeffrey M. Weinberger ◽  
Ron Eliashar ◽  
Aron Popovtzer ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Progression Free Survival ◽  
Antigen Expression ◽  
Neck Squamous Cell Carcinoma ◽  
Tissue Specimens

<b><i>Introduction:</i></b> Immune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study’s main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings. <b><i>Materials and Methods:</i></b> This is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies. <b><i>Results:</i></b> We analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (<i>p</i> = 0.45, <i>p</i> = 0.31, and <i>p</i> = 0.88, respectively). There was a significant (18%, 95% CI 0.65–0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity. <b><i>Discussion and Conclusions:</i></b> Our data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.

scholarly journals On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy

2021 ◽  
Vol 9 (6) ◽  
pp. e002718
Author(s):  
Pablo Nenclares ◽  
Lucinda Gunn ◽  
Heba Soliman ◽  
Mateo Bover ◽  
Amy Trinh ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Scoring System ◽  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
External Validation ◽  
Progression Free Survival ◽  
Neck Squamous Cell Carcinoma

BackgroundPrevious studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy.MethodsAnalysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics.ResultsLow baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0–2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell’s C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell’s C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model.ConclusionsNLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC.

scholarly journals Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Arutha Kulasinghe ◽  
Touraj Taheri ◽  
Ken O’Byrne ◽  
Brett G. M. Hughes ◽  
Liz Kenny ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Neck Squamous Cell Carcinoma ◽  
Protein Markers ◽  
Spatial Profiling

BackgroundImmune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) patients. To identify patient-responders from non-responders, biomarkers are needed which are predictive of outcome to ICI therapy. Cues in the tumor microenvironment (TME) have been informative in understanding the tumor-immune contexture.MethodsIn this preliminary study, the NanoString GeoMx™ Digital Spatial Profiling (DSP) technology was used to determine the immune marker and compartment specific measurements in a cohort of HNSCC tumors from patients receiving ICI therapy.ResultsOur data revealed that markers involved with immune cell infiltration (CD8 T-cells) were not predictive of outcome to ICI therapy. Rather, a number of immune cell types and protein markers (CD4, CD68, CD45, CD44, CD66b) were found to correlate with progressive disease. Cross platform comparison with the Opal Vectra (Perkin Elmer) for a number of markers across similar regions of interest demonstrated concordance for pan-cytokeratin, CD8, and PD-L1.ConclusionThis study, to our knowledge, represents the first digital spatial analysis of HNSCC tumors. A larger cohort of HNSCC will be required to orthogonally validate the findings.

scholarly journals Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2299 ◽  
Author(s):  
Takahiro Wakasaki ◽  
Ryuji Yasumatsu ◽  
Muneyuki Masuda ◽  
Toranoshin Takeuchi ◽  
Tomomi Manako ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Neck Squamous Cell Carcinoma ◽  
Prognostic Biomarkers ◽  
Free Survival ◽  
Reactive Protein

Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1%) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9%) received tegafur-gimestat-otastat potassium (S1), an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2%, 85.7%, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (<1.2 mg/dL) or low NLR (<7.0) values at the time of SCT induction, which was significantly associated with an improved OS (p = 0.0440, p = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS (p = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR. This is the first report on biomarkers of SCT in R/M HNSCC.

Phase II trial of combined durvalumab plus tremelimumab with proton therapy to boost the abscopal effect for recurrent or metastatic head and neck squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6034-6034
Author(s):  
Hana Kim ◽  
Myung-Ju Ahn ◽  
Dongryul Oh ◽  
Sehhoon Park ◽  
Hyun Ae Jung ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Proton Therapy ◽  
Medical Center ◽  
Objective Response ◽  
Neck Squamous Cell Carcinoma ◽  
Electrolyte Imbalance ◽  
Abscopal Effect

6034 Background: This phase 2 study investigated whether durvalumab plus tremelimumab with proton therapy improves objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) via boosting abscopal effect. Methods: Thirty-one patients who have previously received more than one chemotherapy regimen, including at least one platinum-based regimen and have at least two measurable lesions enrolled at Samsung medical center. Patients received durvalumab 1500mg intravenously (IV) in combined with tremelimumab 75 mg IV every four weeks for four cycles followed by durvalumab 1500mg every four weeks. After one cycle of durvalumab and tremelimumab combination, proton therapy was performed with a total dose of 25 Gy in 5-Gy daily fractions to one of the measurable lesions. We assessed the target lesion response outside the radiation field by RECIST criteria 1.1 to evaluate the abscopal effect. Results: Between March 2018 and July 2020, 31 patients were enrolled. The median age was 59 years, and median two prior chemotherapy regimens were administered. With 24.8 months of follow-up, the median number of cycles of immunotherapy was three. The ORR was 27.3%, including one complete response and five partial responses. Median OS was 6.4 months (95% CI, 1.0 to 11.8), and median PFS was 2.4 months (95% CI, 0.6 to 4.2). Median duration of response was 15.9 months (range 3.7 – 21.2). Grade 3 or higher adverse events were observed in 6 (27.3%) patients; anemia (n = 1), constipation (n = 1), electrolyte imbalance (n = 2), hyperglycemia (n = 1), pneumonia (n = 1). Conclusions: Combination of durvalumab/tremelimuab with proton therapy is well tolerable and shows encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients. These results suggest that the combination of immunotherapy with proton therapy might enhance the abscopal effect. Clinical trial information: NCT03450967.

scholarly journals Immunotherapy in head and neck squamous cell carcinoma and rare head and neck malignancies

2021 ◽  
Vol 2 (6) ◽  
Author(s):  
Stefano Cavalieri ◽  
Daria Maria Filippini ◽  
Arianna Ottini ◽  
Cristiana Bergamini ◽  
Carlo Resteghini ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Approaches ◽  
Dismal Prognosis ◽  
Genomic Landscape

The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In recent years, the deeper and increasing knowledge on the genomic landscape and the upcoming new data on immunotherapy enacted by HNSCCs have led to successful therapeutic targeting of the immune system. Immune checkpoint inhibitors (ICIs) have changed state of the art in R/M patients and could have a potential role even in early disease. The purpose of this work is to summarize the role of immunotherapy for R/M HNSCC in clinical practice, with insights about future perspectives. Updated immunotherapy results in other R/M head and neck cancers such as thyroid, salivary glands, nasopharynx, sinonasal cancers, and nuclear protein in testis (NUT) are presented.

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