Dataset Information

Intratumor heterogeneity could inform the use and type of postoperative adjuvant therapy in patients with head and neck squamous cell carcinoma.

ABSTRACT:

Background

After surgery for head and neck squamous cell carcinoma (HNSCC), decisions regarding adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) are based on staging and the presence of high-risk pathology. Because higher mutant allele tumor heterogeneity (MATH; a measure of intratumor genetic heterogeneity) is associated with shorter overall survival (OS) in patients with HNSCC, the authors sought to determine whether MATH analysis might further inform these decisions.

Methods

Adjuvant therapy-associated relationships between MATH and OS were analyzed for 389 patients with HNSCC who were treated surgically. Data were obtained from The Cancer Genome Atlas and analyzed with Cox proportional hazards multiple regression accounting for 7 other patient characteristics.

Results

The relationship between MATH and OS differed with adjuvant therapy in a way that could inform therapy decisions. Adjuvant RT alone was found to provide substantial benefit for patients having high-MATH tumors (RT vs no adjuvant therapy: hazard ratio, 0.29 [95% CI, 0.17-0.51]) but no benefit for those having low-MATH tumors. In contrast, adjuvant CRT provided no benefit beyond that of adjuvant RT for patients with high-MATH tumors but substantially improved OS among patients with low-MATH tumors (CRT vs no adjuvant therapy: hazard ratio, 0.34 [95% CI, 0.15-0.78]).

Conclusions

The results of the current analysis suggested that patients with HNSCC with high-MATH tumors who underwent surgical treatment could benefit from adjuvant RT, even when current clinical guidelines indicate otherwise. The addition of adjuvant chemotherapy for patients with high-MATH tumors would not be indicated. Adding chemotherapy might be necessary to radiosensitize low-MATH tumors to adjuvant RT. This potential predictive role of tumor MATH analysis should be evaluated in prospective clinical trials.

SUBMITTER: Mroz EA

PROVIDER: S-EPMC7160035 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Intratumor heterogeneity could inform the use and type of postoperative adjuvant therapy in patients with head and neck squamous cell carcinoma.

Mroz Edmund A EA Patel Krupal B KB Rocco James W JW

Cancer 20200101 9

<h4>Background</h4>After surgery for head and neck squamous cell carcinoma (HNSCC), decisions regarding adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) are based on staging and the presence of high-risk pathology. Because higher mutant allele tumor heterogeneity (MATH; a measure of intratumor genetic heterogeneity) is associated with shorter overall survival (OS) in patients with HNSCC, the authors sought to determine whether MATH analysis might further inform these decisions.<h4>Methods</ ...[more]

PMID: 32083741

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Project description:The literature contains numerous references describing heterogeneity for tumor phenotypes including cell proliferation, invasiveness, metastatic potential, and response to therapies. However, data regarding angiogenic heterogeneity are limited. In this study, we investigated the degree of intertumoral angiogenic heterogeneity present in head and neck squamous cell carcinomas (HNSCC). In addition, we investigated the biological relevance that this heterogeneity may have in the context of cytokine directed antiangiogenic therapy. Keratinocytes were harvested from HNSCC specimens using laser capture microdissection (LCM). Gene expression profiling of the RNA extracted from these specimens demonstrated variability in the expression of angiogenesis-related genes. Hierarchical clustering and principal component analyses (PCA) demonstrated the presence of unique patient clusters, suggesting that there may be two potentially distinct pathways by which HNSCC induce angiogenesis. Immunohistochemistry for VEGF, IL-8/CXCL8, HGF, and FGF-2, cytokines that play functional roles in HNSCC angiogenesis was performed on the original patient samples as well as a larger panel of normal, dysplastic and HNSCC specimens to validate the heterogeneous expression observed in the gene expression profiling studies. Finally, the therapeutic response of HNSCC tumor xenografts to anti-VEGF therapy was found to be dependent on the amount of VEGF produced by the tumor cells. These findings support the hypothesis of intertumoral angiogenic heterogeneity. They imply that there are differences with regard to the specific molecular mechanisms by which individual tumors within the same histological type induce angiogenesis. Moreover, they demonstrate the need for a more in-depth understanding of the variability of the angiogenic phenotype within a given type of neoplasm when designing cytokine targeted antiangiogenic therapies. Finally, they suggest that studies in conjunction with the ongoing clinical trials that explore the correlation between target expression and clinical outcome are warranted.

Project description:IntroductionImmune-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.Materials and methodsThis 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.ResultsWe 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 (p = 0.45, p = 0.31, and p = 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.Discussion and conclusionsOur 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.

Dataset Information

Intratumor heterogeneity could inform the use and type of postoperative adjuvant therapy in patients with head and neck squamous cell carcinoma.

Background

Methods

Results

Conclusions

Publications

Intratumor heterogeneity could inform the use and type of postoperative adjuvant therapy in patients with head and neck squamous cell carcinoma.

Similar Datasets

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