Synapse - Precision radiotherapy: Reduction in radiation for oropharyngeal cancer in the 30 ROC trial

Precision radiotherapy: Reduction in radiation for oropharyngeal cancer in the 30 ROC trial Journal Article

Authors:	Riaz, N.; Sherman, E.; Pei, X.; Schöder, H.; Grkovski, M.; Paudyal, R.; Katabi, N.; Selenica, P.; Yamaguchi, T. N.; Ma, D.; Lee, S. K.; Shah, R.; Kumar, R.; Kuo, F.; Ratnakumar, A.; Aleynick, N.; Brown, D.; Zhang, Z.; Hatzoglou, V.; Liu, L. Y.; Salcedo, A.; Tsai, C. J.; McBride, S.; Morris, L. G. T.; Boyle, J.; Singh, B.; Higginson, D. S.; Damerla, R. R.; da Cruz Paula, A.; Price, K.; Moore, E. J.; Garcia, J. J.; Foote, R.; Ho, A.; Wong, R. J.; Chan, T. A.; Powell, S. N.; Boutros, P. C.; Humm, J. L.; Shukla-Dave, A.; Pfister, D.; Reis-Filho, J. S.; Lee, N.
Article Title:	Precision radiotherapy: Reduction in radiation for oropharyngeal cancer in the 30 ROC trial
Abstract:	Background: Patients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods: In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results: Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation-related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions: Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.
Keywords:	chemotherapy; hypoxia; chemoradiation; chemoradiotherapy; squamous-cell carcinoma; neck-cancer; dna-repair; hpv; human-papillomavirus; locally advanced head
Journal Title:	JNCI: Journal of the National Cancer Institute
Volume:	113
Issue:	6
ISSN:	0027-8874
Publisher:	Oxford University Press
Date Published:	2021-06-01
Start Page:	742
End Page:	751
Language:	English
ACCESSION:	WOS:000734337200018
DOI:	10.1093/jnci/djaa184
PROVIDER:	wos
PMCID:	PMC8168141
PUBMED:	33429428
Notes:	Article -- djaa184 -- Source: Wos