Patient Reported Toxicity with Radiation Deintensification in HPV-Associated Oropharynx Cancer: ECOG-ACRIN E2399 and E1308.

Authors

Anthony J Cmelak, Yael Flamand, Shanthi Marur, Shuli Li, Barbara A Murphy, Thomas J Galloway, Weiqiang J Zhao, William H Westra, Christine H Chung, Maura Gillison, Jill Gilbert, Robert L Ferris, Julie E Bauman, David R Trevarthen, A Dijmitrios Colevas, Balkrishna N Jahagirdar, Nishant Agrawal, Lynne I Wagner, Barbara A Burtness

Published in

JCO oncology advances. Volume 3. Issue 3. Epub Sep 29, 2026.

Abstract

E2399 showed higher response rates and survival for human papillomavirus-associated (HPV+) oropharynx (OP) cancer than for HPV-negative OP cancer. E1308, a follow-up prospective phase II trial in HPV+ OP patients, hypothesized that reduced radiation (54Gy) may achieve comparable tumor control in patients who achieve a complete clinical response to induction chemotherapy, and that toxicities would be ameliorated.
Acute and late toxicities for both E2399 and E1308 were recorded prospectively using a battery of patient reported outcomes (PROs). General QOL PROs utilized on E1308 included KATZ -ADL, BFI, IADL, Baecke, CHAMPS; HHC specific PROs were FACT-HN, and the VHNSSv2. E2399 used the FACT-HN. Toxicities were correlated with both IMRT dose (69.3Gy vs. 54Gy) used on E1308, and with IMRT technique utilized on E1308 versus 3D conformal RT used on E2399.
Radiation dose reduction resulted in significant decreased toxicities as detected with VHNNSv2 and FACT-HN PRO instruments. The VHNSSv2 showed late symptoms are significantly reduced by lowering IMRT to 54Gy: eating solids (p = 0.011), liquids (p = 0.004), voice changes (p = 0.026), dry mouth (p=0.02), and neck and shoulder movements (p=0.03). FACT-HN showed less difficulty in eating solids at 6 months (p = 0.054), as well as voice strength and quality (p = 0.038). Comparing IMRT 69.3Gy to 3D RT 70Gy, the FACT-HN showed eating solids at 12 months (p = 0.0067) and greater ability to eat foods the patient liked (p = 0.0103).
Both radiation dose reduction and utilizing IMRT decreased toxicities in a variety of QOL PROs. Head and neck specific PROs are more sensitive than qeneral PROs. Inter-instrument corroboration validates the FACT-HN and VHNSSv2 utility for treatment deintensification evaluation.

PMID:
42820118
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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