DOI: 10.1200/oa-25-00134 ISSN: 2994-9750

Patient-Reported Toxicity With Radiation Deintensification in Human Papillomavirus–Associated Oropharynx Cancer: ECOG-ACRIN E2399 and E1308

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 L. Gillison, Jill Gilbert, Robert L. Ferris, Julie E. Bauman, A. Dimitrios Colevas, Balkrishna N. Jahagirdar, Nishant Agrawal, Lynne I. Wagner, Barbara A. Burtness
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PURPOSE

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 patients with HPV+ OP, 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.

METHODS

Acute and late toxicities for both E2399 and E1308 were recorded prospectively using a battery of patient-reported outcomes (PROs). General quality of life (QOL) PROs used on E1308 included KATZ-Index of Independence in Activities of Daily Living (ADL), Brief Fatigue Index, Instrumental Activities of Daily Living, Baecke, and Community Health Activities Model Program for Seniors Physical Activity Questionnaire; head and neck cancer-specific PROs were Functional Assessment of Cancer Therapy – Head & Neck (FACT-HN) and the Vanderbilt Head and Neck Symptom Survey Version 2 (VHNSSv2). E2399 used the FACT-HN. Toxicities were correlated with both intensity-modulated radiation therapy (IMRT) dose (69.3Gy v 54Gy) used on E1308 and with the IMRT technique used on E1308 versus three-dimensional conformal radiation therapy (3DRT) used on E2399.

RESULTS

Radiation dose reduction resulted in significantly decreased toxicities as detected with VHNNSv2 and FACT-HN PRO instruments. The VHNSSv2 showed that late symptoms are significantly reduced by lowering IMRT to 54Gy: eating solids ( P = .011), liquids ( P = .004), voice changes ( P = .026), dry mouth ( P = .02), and neck and shoulder movements ( P = .03). FACT-HN showed less difficulty in eating solids at 6 months ( P = .054), as well as voice strength and quality ( P = .038). Comparing IMRT 69.3Gy with 3DRT 70Gy, the FACT-HN showed eating solids at 12 months ( P = .0067) and greater ability to eat foods the patient liked ( P = .0103) favored IMRT.

CONCLUSION

Both radiation dose reduction and using IMRT decreased toxicities in a variety of QOL PROs. Head and neck–specific PROs are more sensitive than general PROs. Interinstrument corroboration validates the FACT-HN and VHNSSv2 utility for treatment deintensification evaluation.

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