Palliative Quadshot Radiation Therapy with or without Concurrent Immune Checkpoint Inhibition for Head and Neck Cancer

Purpose: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. Quad-shot (QS), a hypofractionated palliative radiotherapy regimen (14.8 Gy in four twice-daily fractions), can provide symptomatic relief and local control and may potentiate the effects of immune-checkpoint inhibitors (ICI). We compared outcomes of QS +/- concurrent ICI in the palliative treatment of HNC.

Methodology: We identified patients treated with QS in our department from January 2017 to December 2022, who received atleast 3 cycles of QS and completed atleast 3 months of follow-up. Concurrent ICI was defined as receipt of ICI within 4 weeks of QS. Outcomes for patients who received ICI concurrent with QS were compared to those treated with QS alone. The primary endpoint was local progression-free survival (LPFS), defined as time interval from the end date of cycle 1 QS radiation to date of local progression or death. Secondary endpoints included adverse events, distant progression-free survival(dPFS), and overall survival(OS). Kaplan-Meier method was used for survival analyses and Cox-proportional hazards models was used for univariate analysis of factors affecting outcomes.

Results: 131 patients received QS radiation, 70 of whom completed 3 QS cycles with ≥3 months follow-up. 40 (57%) patients received concurrent ICI (28 Pembrolizumab, 11 Nivolumab and 1 Cemiplimab) with QS, and 30 (43%) received QS radiation alone. Median age was 65.5 years (IQR 57.9-77.8y) and the most common primary tumor sites were oropharynx (33%), oral cavity (24%), and larynx (16%). Age, gender, primary site, smoking history, and performance status were well balanced between the two groups. Patients who received concurrent ICI had significantly higher N2/N3 patients (80% vs 47%, p = 0.019). Median follow-up was 8.8 months. Incidence of highest CTCAE grade 1, 2 and 3 toxicities were 36%, 37% and 23% respectively, and were similar in the two groups. No patient experienced grade ≥4 toxicity. Overall, 71% patients had a complete or partial response (70% vs 73%, p = 0.487). LPFS was significantly higher in the QS+ICI group (12-month: 85% vs 63%, p = 0.038). Median OS was 9.4 months, and similar between the two groups (9.0m vs 10.0m, p = 0.850). dPFS was also similar between the two groups (12-month: 56% vs 63%, 0.629). On univariate analysis, concurrent ICI+QS was a significant predictor of LPFS (HR: 0.019; 95% CI: 0.002-0.248).

Conclusions: The combination of QS with concurrent ICI was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with recurrent and metastatic HNC. This approach represents a novel treatment option for patients with HNC who are not a candidate for curative-intent treatment and warrants further prospective evaluation.

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