AI Article Synopsis

  • The study investigates the impact of tumor hypoxia on the treatment of HPV-related oropharyngeal carcinoma to potentially reduce toxicity from standard chemoradiotherapy by de-escalating dosages for nonhypoxic tumors.
  • In a phase II trial, patients underwent surgery and were evaluated for hypoxia using PET scans, with 128 nonhypoxic patients receiving 30 Gy and 24 hypoxic patients receiving the standard 70 Gy treatment.
  • Results showed a 2-year locoregional control rate of 94.7%, with lower adverse effects in the 30 Gy group, suggesting that targeting treatment based on tumor hypoxia may improve patient outcomes and reduce side effects.

Article Abstract

Purpose: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy.

Methods: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin.

Results: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% 32%; = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia.

Conclusion: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10927322PMC
http://dx.doi.org/10.1200/JCO.23.01308DOI Listing

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