3457 - Survival and Toxicity Outcomes of Twice-Daily (BID) Accelerated Hyperfractionated Reirradiation in Head and Neck Cancers (HNC)

Purpose/Objective(s): Salvage reirradiation (reRT) for HNC carries competing risks of locoregional failure (LRF) and severe late toxicity. Accelerated hyperfractionated BID reRT is guideline-supported and may have radiobiologic advantages in radioresistant recurrent disease, yet concerns remain regarding durable control, tolerability, and late toxicity with prior data suggesting elevated risk of osteoradionecrosis (ORN). We evaluated survival, failure patterns, toxicity, and whether baseline patient-reported dysphagia predicts long-term feeding tube (FT) use after modern BID reRT.

Materials/Methods: All BID HNC reRT cases (< 180 cGy/fraction = 6 hrs apart) since 2012 were retrospectively reviewed. Patients completing prescribed reRT with complete prior records were included. Overall and progression free survival (OS & PFS) were estimated from reRT completion using Kaplan Meier. Cumulative incidence (CI) of LRF and distant failure (DF) was calculated with death as a competing risk. Maximum toxicity was graded for ORN, CNS necrosis, and carotid blowout. FT status and Sydney Swallow Questionnaire (SSQ) were assessed longitudinally.

Results: Among 106 patients prescribed BID reRT, 98 (92.5%) completed treatment. Seventy-eight met inclusion criteria (82.4% treated for LRF; 16.7% for a new primary). Median time between RT courses was 24.9 months. Median reRT dose was 64.8 Gy (EQD2, a/ß = 3) at median PTV 56.4 cc (IQR 25.2 - 126 cc). A low-dose PTV was used in 75.6% of plans (median EQD2 45.8 Gy; median volume 265.1cc [IQR 163.6 - 350.6 cc]). Median follow-up was 31.4 months.

Median OS was 40.7 months (1- & 3-yr OS: 79.5%, 53.9%). Median PFS was 16.9 months (1- & 3-yr PFS: 61.5%, 38.9%). The 1- & 3-yr CI of LRF was 24.4% and 36.7%, and DF was 18.8% and 41.7%. Among patients with prior LRF, 58.5% did not have subsequent LRF.

Nineteen patients (24.4%) had a FT prior to reRT, and 24 (30.8%) had one placed after reRT start. Of 62 patients evaluable beyond 12 months, 30 (48.4%) remained FT-dependent. Persistent FT use was associated with higher baseline SSQ (median 624.3 [IQR 183 – 1062] vs 147.2 [IQR 78.1 – 227.2]; Wilcoxon p = 0.0003); but longitudinal SSQ change did not differ between groups (p = 0.98). Low-dose PTV volume did not differ for FT dependence (p = 0.67).

Severe toxicity occurred in nine patients (11.5%): six (7.7%) with G3-4 ORN, two with G3 CNS necrosis, and two with carotid blowout. Composite dosimetric analysis is ongoing.

Conclusion: Modern BID reRT achieved high completion rates, durable outcomes, and acceptable late toxicities, challenging prior concerns of tolerability and prohibitive late effects. Baseline dysphagia severity, not post-reRT decline, was associated with long-term FT use, supporting incorporation of patient-reported measures into reRT selection and counseling. These findings provide contemporary benchmarks for BID reRT and support prospective validation.