Synapse - Hypoxia-directed treatment of human papillomavirus-related oropharyngeal carcinoma

Hypoxia-directed treatment of human papillomavirus-related oropharyngeal carcinoma Journal Article

Authors:	Lee, N. Y.; Sherman, E. J.; Schöder, H.; Wray, R.; Boyle, J. O.; Singh, B.; Grkovski, M.; Paudyal, R.; Cunningham, L.; Zhang, Z.; Hatzoglou, V.; Katabi, N.; Diplas, B. H.; Han, J.; Imber, B. S.; Pham, K.; Yu, Y.; Zakeri, K.; McBride, S. M.; Kang, J. J.; Tsai, C. J.; Chen, L. C.; Gelblum, D. Y.; Shah, J. P.; Ganly, I.; Cohen, M. A.; Cracchiolo, J. R.; Morris, L. G. T.; Dunn, L. A.; Michel, L. S.; Fetten, J. V.; Kripani, A.; Pfister, D. G.; Ho, A. L.; Shukla-Dave, A.; Humm, J. L.; Powell, S. N.; Li, B. T.; Reis-Filho, J. S.; Diaz, L. A.; Wong, R. J.; Riaz, N.
Article Title:	Hypoxia-directed treatment of human papillomavirus-related oropharyngeal carcinoma
Abstract:	PURPOSEStandard 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.METHODSWe 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 18F-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.RESULTSOne 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% v 32%; P =.02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia.CONCLUSIONTumor 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. © American Society of Clinical Oncology.
Keywords:	clinical trial; phase 2 clinical trial; hypoxia; carcinoma; chemoradiotherapy; oropharyngeal neoplasms; wart virus; papillomavirus infections; complication; oropharynx tumor; papillomavirus infection; procedures; humans; human; human papillomavirus viruses
Journal Title:	Journal of Clinical Oncology
Volume:	42
Issue:	8
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2024-03-10
Start Page:	940
End Page:	950
Language:	English
DOI:	10.1200/jco.23.01308
PUBMED:	38241600
PROVIDER:	scopus
PMCID:	PMC10927322
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85187203911&doi=10.1200%2fJCO.23.01308&partnerID=40&md5=bcd675cfb4caefa16222d64f53a29a1a
Notes:	Article -- MSK author Anuja Kriplani's last name is misspelled on the original publication -- Source: Scopus