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

N. Y. Lee¹, N. S. Kalman², C. A. Barker³, C. White⁴, Z. Zhang⁵, D. Gelblum¹, Y. Yu¹, L. Chen¹, S. McBride³, N. Riaz¹, A. Shamseddine¹, L. Michel⁶, T. Hung³, D. G. Pfister⁶, B. Singh⁷, I. Ganly⁷, J. O. Boyle⁷, R. J. Wong⁷, P. B. Romesser³, and E. Sherman⁶; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, ³Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Memorial Sloan-Kettering Cancer Center, New York, NY, ⁵Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, ⁶Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁷Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

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 >/=40Gy of prior head/neck radiation were enrolled. Patients received fractionated re-RT (F-Re-RT to 70Gy) 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 7/17-11/22, 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% (table below). 9 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. Abstract 144 – Table 1

Analyzable(N=85)	F-Re-RT(N=57)	QS-Re-RT(n=28)	All(n=85)
Median Age	66	73
Median Performance Status	90	80
Surgery prior to re-RT	n=44	n=20
Systemic therapies prior to re-RT (cisplatin/cetuximab/ carboplatin/taxanes/PD1)	n=41	n=28
Concurrent (majority platinum-based)	n=45	n=20
Median Re-RT Dose	70Gy (63-78Gy)	44.4Gy (14.8-59.2Gy)
2-year LRR	24%	59%
2-year DM	19%	42%
2- year PFS	52%	8.5%
2-year OS	59%	29%
5-year LRR, OS			38%, 32%
Most common late Grade 3(patient can have multiple)	Dysphagia(11) Voice changes 7) Necrosis(Osteo-, soft tissue-brain)[7]	Repeated wound Infections(3) Chronic Pain(3) Necrosis(brain with CSF leak; soft tissue)[2]