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A Rational Approach to Unilateral Neck RT for Head and Neck Cancers in the Era of Immunotherapy.

ABSTRACT: Radiotherapy plays an important role in the definitive and adjuvant treatment of head and neck squamous cell carcinoma (HNSCC). However, standard courses of radiation therapy may contribute to the depletion of circulating lymphocytes and potentially attenuate optimal tumor antigen presentation that may be detrimental to the efficacy of novel immunotherapeutic agents. This review explores the advantages of restricting radiation to the primary tumor/tumor bed and ipsilateral elective neck as it pertains to the evolving field of immunotherapy.

SUBMITTER: Chin RI

PROVIDER: S-EPMC8582444 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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A Rational Approach to Unilateral Neck RT for Head and Neck Cancers in the Era of Immunotherapy.

Chin Re-I RI Schiff Joshua P JP Brenneman Randall J RJ Gay Hiram A HA Thorstad Wade L WL Lin Alexander J AJ

Cancers 20211020 21

Radiotherapy plays an important role in the definitive and adjuvant treatment of head and neck squamous cell carcinoma (HNSCC). However, standard courses of radiation therapy may contribute to the depletion of circulating lymphocytes and potentially attenuate optimal tumor antigen presentation that may be detrimental to the efficacy of novel immunotherapeutic agents. This review explores the advantages of restricting radiation to the primary tumor/tumor bed and ipsilateral elective neck as it pe ...[more]

PMID: 34771432

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Project description:Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy characterized by tumor-driven immune-system abnormalities that contribute to disease progression. For patients with surgically resectable HNSCC, treatment is often curative surgery followed by irradiation or chemoradiation in high-risk settings to reduce the risk of recurrence. Poor survival and considerable morbidity of current treatments suggest the need for new therapeutic modalities that can improve outcomes. Defects in antitumor immunity of HNSCC patients include suppressed dendritic cell (DC) maturation, deficient antigen-presenting cell function, compromised natural killer (NK)-cell cytotoxicity, increased apoptosis of activated T lymphocytes, and impaired immune-cell migration to tumor sites. Strategies for relieving immunosuppression and restoring antitumor immune functions could benefit HNSCC patients. IRX-2 is a primary cell-derived biologic consisting of physiologic levels of T-helper type 1 cytokines produced by stimulating peripheral blood mononuclear cells of normal donors with phytohemagglutinin. The primary active components in IRX-2 are IL2, IL1β, IFNγ, and TNFα. In vitro, IRX-2 acts on multiple immune-system cell types, including DCs, T cells, and NK cells, to overcome tumor-mediated immunosuppression. In clinical settings, IRX-2 is administered as part of a 21-day neoadjuvant regimen, which includes additional pharmacologic agents (low-dose cyclophosphamide, indomethacin, and zinc) to promote anticancer immunoresponses. In a Phase IIA trial in 27 patients with surgically resectable, previously untreated HNSCC, neoadjuvant IRX-2 increased infiltration of T cells, B cells, and DCs into tumors and was associated with radiological reductions in tumor size. Event-free survival was 64% at 2 years, and overall 5-year survival was 65%. Follow-up and data analysis are under way in the multicenter, randomized, Phase IIB INSPIRE trial evaluating the IRX-2 regimen as a stand-alone therapy for activating the immune system to recognize and attack tumors.

Dataset Information

A Rational Approach to Unilateral Neck RT for Head and Neck Cancers in the Era of Immunotherapy.

Publications

A Rational Approach to Unilateral Neck RT for Head and Neck Cancers in the Era of Immunotherapy.

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