Initial Feasibility and Acute Toxicity Outcomes From a Phase 2 Trial of 18F-Fluorodeoxyglucose Positron Emission Tomography Response-Based De-escalated Definitive Chemoradiotherapy for p16+ Oropharynx Cancer: A Planned Interim Analysis

Abstract

Purpose: ¹⁸F-Fluorodeoxyglucose positron emission tomography (FDG-PET) parameters are prognostic of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). We used FDG-PET imaging biomarkers to select patients for de-escalated chemoradiotherapy (CRT), hypothesizing that acute toxicity will be improved with de-escalation.

Methods and materials: This is a planned interim initial feasibility and acute toxicity report from a phase 2, prospective, nonrandomized study, which enrolled patients with stage I-II p16+ OPSCC. All patients started definitive CRT to 70 Gy in 35 fractions, and those who met de-escalation criteria on midtreatment FDG-PET at fraction 10 completed treatment at 54 Gy in 27 fractions. We report the acute toxicity and patient-reported outcomes for 59 patients with a minimum follow-up of 3 months.

Results: There were no statistically significant differences between baseline patient characteristics in the standard and de-escalated cohorts. There were 28 of 59 (47.5%) patients who met FDG-PET de-escalation criteria and collectively received 20% to 30% less dose to critical organs at risk known to affect toxicity. At 3 months posttreatment, patients who received de-escalated CRT lost significantly less weight (median, 5.8% vs 13.0%; P < .001), had significantly less change from baseline in penetration-aspiration scale score (median, 0 vs 1; P = .018), and had significantly fewer aspiration events on repeat swallow study (8.0% vs 33.3%, P = .037) compared with patients receiving standard CRT.

Conclusions: Approximately half of patients with early-stage p16+ OPSCC are selected for de-escalation of definitive CRT using midtreatment FDG-PET biomarkers, which resulted in significantly improved rates of observed acute toxicity. Further follow-up is ongoing and will be required to determine whether this de-escalation approach preserves the favorable oncologic outcomes for patients with p16+ OPSCC before adoption.

Fig. 1.

Trial schema. Abbreviations: AJCC = American Joint Committee on Cancer; CRT = chemoradiotherapy; FDG-PET/CT = ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography; Fx = fraction; HN = head and neck; MTV = metabolic tumor volume; PTV = planning treatment volume (high = gross disease; low = at-risk regional lymph node basins); SCC = squamous cell carcinoma; Tx = treatment.

Fig. 2.

Mean doses (Gy) to selected organs at risk from final “as treated” radiation therapy plans. Box and whisker plots of mean doses of selected organs at risk best characterized to affect toxicity: (A) larynx, (B) superior constrictors, (C) ipsilateral parotid gland, and (D) contralateral parotid gland. Data shown are for each cohort in aggregate and represent dose from final “as treated” standard and de-escalated RT plans, with vertical dash at the institutional mean dose constraint and P values from 1-sided Wilcoxon rank sum tests between cohorts (N = 59 patients).

Fig. 3.

Short-term weight loss. Box and whisker plots of percent weight loss from baseline at (A) 1 month and (B) 3 months after chemoradiotherapy. Negative percent weight loss reflects weight gain from baseline. Vertical dashed line at limit where institutional policy recommends feeding tube placement and P values represent 1-sided Wilcoxon rank sum tests between cohorts (N = 59 patients).

Fig. 4.

Short-term objective swallowing toxicity. Box and whisker plots of change from baseline videofluoroscopic swallow study penetration-aspiration scale 3 months after chemoradiotherapy. Positive change reflects a worse score, and negative change reflects improvement. Vertical dashed line at no change and P value represents 1-sided Wilcoxon rank sum tests between cohorts. N = 49 patients with evaluable baseline and 3-month videofluoroscopic swallow study.