Phase II Trial of Proton Re-Irradiation+/-Chemotherapy in Previously Irradiated Recurrent Head/Neck Cancer

Purpose/Objective(s)

To report the results of a multi-center phase II trial of using proton re-irradiation (re-RT) for previously irradiated recurrent head/neck cancer (HNC).

Materials/Methods

Recurrent HNC patients who received >/= 40 Gy of prior head/neck radiation were enrolled. Patients received fractionated re-RT (F-Re-RT to 70 Gy) or QUAD Shot re-RT (QS-Re-RT, 4 cycles to 59.2 Gy) at physician discretion. The primary endpoints (Clopper-Pearson Confidence Intervals method) were to determine the 12-months, 6-months locoregional recurrence-free (LRRF) rates for F-Re-RT and QS-Re-RT, respectively. Secondary endpoints were to determine: overall survival (OS), progression-free survival (PFS) [both estimated using the Kaplan-Meier method]; distant metastasis (DM), locoregional recurrence (LRR) rates [both calculated from using the Cumulative Incidence Function with death as a competing event]. Patient reported outcomes (PROs) included EORTC QLQ-HN35, PRO-CTCAE, Skindex-16, OMWQ-HM mucositis, EQ-5D. Median follow-up was calculated using the Reverse Kaplan-Meier method.

Results

From July 2017 to November 2022, 88 patients were enrolled (85 analyzable): F-Re-RT (n = 57) versus QS-Re-RT (n = 28). F-Re-RT patients were young with better performance status versus QS-Re-RT patients. Median follow-up was 35 months (all patients); F-Re-RT (38 months); QS-Re-RT (23 months). The 1-year LRRF rate for F-Re-RT was 71% (90% CI = 59%, 81%); 6-month LRRF rate for QS-Re-RT was 76% (90% CI = 58%, 89%) [See table for treatment factors, other endpoints] 36% of the patients had acute grade 3-4 toxicities, most notably dermatitis, dysphagia, dysgeusia. Late grade 3 complications were 20% (see the Table below). Nine patients had grade 4 and 3 had grade 5 complications. The Baseline, 1-year post re-RT mean score of EORTC QLQ-HN35 for F-Re-RT versus QS-Re-RT were 31.05 to 39.09 versus 35.43 to 14.85. Other PROs will be presented at the meeting.

Conclusion

In this largest and first multi-center phase II trial for recurrent HNC patients, proton therapy achieved remarkable locoregional control and survival. Although long-term survivors (> 5 years) were observed which compares very favorably to other treatment modalities, especially when multiple therapies were done prior to re-RT with proton, these patients remain at risk for late complications.