TOPLINE

Among patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) who had a complete response to induction chemotherapy, those who received reduced-dose intensity-modulated radiation therapy (IMRT) reported significantly less difficulty swallowing and less voice impairment than those who received standard-dose IMRT, per the phase 2 E1308 trial. Disease-specific patient-reported outcome (PRO) tools detected these differences more reliably than general quality-of-life measures. A historical comparison with the earlier E2399 trial supported similar reductions in toxicity with IMRT vs three-dimensional conformal radiation therapy (3DRT).

METHODOLOGY

• A phase 2 trial, E2399, showed that HPV-positive oropharynx cancer responds well to chemoradiation, raising the possibility of reducing treatment intensity without compromising cure rates. Because high-dose radiation drives most acute and long-term toxicity, the follow-up E1308 trial tested whether a response to induction chemotherapy could guide the use of lower-dose IMRT.
• This prospective phase 2 trial (ECOG-ACRIN E1308) evaluated reduced-dose IMRT of 54 Gy against standard-dose IMRT of 69.3 Gy in patients with HPV-associated OPSCC who achieved a complete clinical response to induction chemotherapy.
• A total of 80 patients were treated in E1308; 62 of 80 (78%) achieved a complete response to induction chemotherapy with paclitaxel, cisplatin, and cetuximab and received 54 Gy, while the remainder received 69.3 Gy. Fifty-one patients who remained progression-free at 12 months (42 patients who received 54 Gy and nine patients who received 69.3 Gy) were evaluated for PROs.
• Researchers assessed disease-specific symptom burden using the Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) and the Vanderbilt Head and Neck Symptom Survey Version 2 (VHNSSv2) and general quality of life using the Katz Index of Independence in Activities of Daily Living (ADL), Brief Fatigue Index (BFI), Instrumental Activities of Daily Living (IADL), Baecke physical activity scale, and Community Health Activities Model Program for Seniors (CHAMPS) questionnaire. All measures were administered at baseline and at 6, 12, 24, and 30 months post-treatment.
• Toxicity outcomes in E1308 were compared historically with those of 69 patients treated in the earlier E2399 trial who received induction chemotherapy followed by 3DRT at 70 Gy over 7 weeks with concurrent weekly paclitaxel.

TAKEAWAY

• At 6 months, VHNSSv2 scores indicated that reduced-dose IMRT eased swallowing of solids (P = .011) and liquids (P = .004), voice impairment (P = .026), dry mouth (P = .02), and neck/shoulder movement limitations (P = .03) compared with standard-dose IMRT.
• FACT-HN scores indicated that the reduced-dose IMRT group had less difficulty eating solid foods at 6 months (P = .054) and better voice strength and quality (P = .038) than the standard-dose group.
• Comparing reduced-dose IMRT (54 Gy) in E1308 with 3DRT (70 Gy) in E2399, FACT-HN scores showed that IMRT was associated with better ability to eat solid food at 12 months (P = .0103) and greater ability to eat preferred foods (P = .0067). Additionally, patients who received 3DRT had higher rates of grade ≥ 3 oral mucositis (58% vs 29%; P = .0003), dysphagia (39% vs 15%; P = .001), and esophagitis (8% vs 0%; P = .023) than those who received reduced-dose IMRT.
• General quality-of-life tools — CHAMPS, Katz ADL, BFI, IADL, and Baecke — did not detect significant reductions in toxicity or differences in function or fatigue between the dose groups.

IN PRACTICE

"Our data from the first prospective study of radiation dose reduction in treatment responsive HPV-associated oropharynx cancer demonstrate a statistically significantly less worsening of swallowing dysfunction and voice impairment for patients treated with reduced-dose IMRT based on disease-specific VHNSSv2 and FACT-HN instruments at 6 months post-treatment. This supports our initial hypothesis that reducing radiation dose and duration will reduce chronic symptom burden and has spawned a plethora of additional deintensification paradigms in ongoing clinical trials," the authors concluded.

SOURCE

The study, led by Anthony J. Cmelak, MD, Vanderbilt University/Ingram Cancer Center in Nashville, Tennessee, was published online in JCO Oncology Advances.

LIMITATIONS

Small standard-dose cohorts and declining PRO completion at later time points limited statistical power. Comparisons were not randomized, with E2399 including both HPV-positive and HPV-negative patients, introducing heterogeneity. Historical 3DRT-vs-IMRT comparisons also reflected inherent technical differences between the two radiation approaches beyond dose alone.

DISCLOSURES

This study was supported by the ECOG-ACRIN Cancer Research Group and grants from the National Cancer Institute of the National Institutes of Health. Several authors reported consulting, research funding, employment, leadership, or ownership ties to pharmaceutical and biotechnology companies, including Merck, AstraZeneca, Regeneron, Takeda, and others. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.