Radiotherapy De-Escalation Improves Toxicity in p16+ Oropharyngeal Squamous Cell Carcinoma

A presentation from the 2022 ASTRO Multidisciplinary Head and Neck Cancers Symposium showed a de-escalated radiotherapy dose to 54 Gy vs 70 Gy led to better measures of toxicity in those with p16+ oropharyngeal squamous cell carcinoma.

A de-escalated dose of radiotherapy was found to alleviate weight loss, feeding tube placement, and swallow function in the short-term for patients with human papillomavirus (HPV)–associated p16-positive oropharyngeal squamous cell carcinoma (OPSCC), according to results from a phase 2 trial presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

In the de-escalation cohort, there was a statistically significant benefit vs standard therapy in terms of weight loss (P <.001) and feeding tube placement (P = .037). Similarly, swallowing function on the Penetration-Aspiration Scale was improved with de-escalated therapy (P = .023).

“About half of early-stage HPV-associated [OPSCCs] were able to be de-escalated to 54 Gy and 27 fractions. This is not a re-plan or change in volume, but stopping treatment after 27 fractions,” Steven Allen, MD, PhD, a radiation oncology resident at the University of Michigan, said during the presentation.

Investigators enrolled 59 patients with fluorodeoxyglucose (FDG)–avid stage I to II p16-positive OPSCC with any smoking history. Those with any prior surgery such as tonsillectomy, excisional biopsy, or neck dissection; FDG contraindications; prior radiation to the head and neck; or matted lymph nodes were excluded.

All patients enrolled underwent pre-treatment PET/CT imaging as well as radiotherapy at 70 Gy in 35 fractions with weekly concurrent carboplatin and paclitaxel. Those who had metabolic tumor volume (MTV)50% of more than 22 cc were not eligible for de-escalation therapy. After 2 weeks, patients underwent mid-treatment PET/CT at fraction 10, and those with both a pre-treatment MTV50% of SUVmax 22cc or less and a 50% or greater decrease in MTV above SUV 2.5 were eligible for de-escalation treatment at 54 Gy in 27 fractions. Standard radiation was administered to patients who did not meet these criteria, at 70 Gy in 35 fractions.

The primary end points included noninferior and locoregional control with de-escalation vs historical controls as well as prognostic significance of mid-treatment MTV 2.5 with a decrease of 50%. The current analysis focused on the secondary end point of acute and late toxicities found with de-escalation of chemoradiotherapy.

At baseline, the standard (n = 31) and de-escalated radiotherapy (n = 28) arms had similar characteristics and pathology. It was noted that smoking status by pack-year history was more significant for the de-escalated radiation arm at 20.0 pack-years (95% CI, 6.0-35.0) vs 15.0 pack-years (95% CI, 9.2-22.5) for standard therapy (P >.9).

Primary gross tumor volume (GTV) was 14.1 cc (95% CI, 7.6-18.1) in the standard radiotherapy cohort and 12.4 cc (95% CI, 7.8-18.1) in the de-escalated cohort (P >.09). The GTV with the primary tumor and lymph nodes was 29.0 cc (95% CI, 20.6-40.7) in the standard radiotherapy cohort and 31.8 cc (95% CI, 19.6-37.7) in the de-escalated radiotherapy cohort (P = .07).

De-escalation resulted in a 20% to 30% reduction in doses to organs at risk known to succumb to head and neck toxicities, such as the larynx (P <.001), superior constrictors (P <.001), ipsilateral parotid gland (P <.001), and contralateral parotid gland (P <.001). Additionally, 8 patients in the 70 Gy cohort had an increased number of aspirations vs only 2 in the 54 Gy cohort (P = .03); feeding tube placement occurred in 7 and 1 patients, respectively.

After 1 month of treatment, patient reported outcomes in both cohorts were worse than at baseline. Although numerical patient-reported outcomes in the de-escalated cohort were better, none were statistically significant.


Allen S, Rosen B, Aryal M, et al. Early toxicity and patient reported outcomes from a phase II trial of FDG-PET response-based de-escalated definitive radiotherapy for p16+ oropharynx cancer. 2022 Multidisciplinary Head and Neck Symposium; February 24-26, 2022; Phoenix, AZ. Abstract 1. Accessed February 24, 2022.

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