Novel Enhancement of Checkpoint Inhibition Using Pulsing Radiotherapy with Concurrent and Adjuvant CPI for LAHNSCC in Elderly Patients Considered Ineligible for Curative Intent Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Elderly patients with NON-METASTATIC HNSCC represent an unmet and growing need population that would benefit for more novel, less toxic approaches. With the success of immunotherapy in metastatic LAHNSCC, understanding how to best utilize palliative radiotherapy (RT) with immunotherapy remains a challenge. We sought to combine a pulsing RT strategy (QUAD shot x 3) directed only to gross LAHNSCC non-metastatic, to enhance response to immunotherapy. <h3>Materials/Methods</h3> 25 pts (16 males/9 females), median age of 82, were seen in our HN-MDC and determined to be ineligible for curative intent treatment. 23 were evaluable for this analysis. Pts were treated with the QUAD shot regimen (3,7 Gy x 4 BID) x 3 (TD 44.4 Gy) spaced 3 weeks apart with inclusion of an approved CPI at the discretion of the Medical Oncologist. ERT was directed to ONLY Gross disease, determined by clinical and diagnostic PET/CT scan. CPI was administered in the majority of patients AFTER the 1^st QUAD shot within the 1^st five days. CPI continued until assessment of response, or AE/tolerance or POD. Sites treated included oropharynx (43%), LA/or recurrent cutaneous SCC (30%), Nasopharynx (8%), OC (8%) and Larynx (4%). AJCC 8^th edition stage included Stage 1 (4%), stage II (8%), stage III (8%) and stage IVa-c (56%). The median cycles of CPI were 5 (range: 2-24). <h3>Results</h3> The median Follow-up time was 5 months, (range 3-36). 16/23pts (70%) achieved a cCR at the completion of their QUAD regimen +CPI, while 1 pt achieved a cCR after 2 Quad shots. 2 pts were not evaluable due to death from intercurrent disease or covid after completion of the QUAD regimen. The overall infield LRC control rate was 65%. The infield LC and RC rates were 65% and 71% respectively. The regional failure rate in the untreated elective neck was only 8% (2/21). 2 patients died immediately after completing radiation from Covid and FTT. Of the patients treated for LA-cSCC, the infield and out of field LRC was 100% and 100% respectively. 3 pts developed distant failure. 2/3 experienced Local and/or regional failure as well. QUAD regimen was well tolerated when combined with CPI, with only 1/23 pts requiring treatment interruption and admission for FTT, but completed therapy. Gr 3 mucositis occurred in 1 patient on the lower lip that resolved. Gr 1 fatigue, xerostomia, and anorexia were noted in 1 patient. Gr 3/ 4 IMAR's were observed in 3 patients and included infusion reaction, colitis, and fatigue/FTT and were discontinued. 4 pts (23%) required post QUAD PEG's unrelated to radiation toxicity and due to POD or intercurrent illness. <h3>Conclusion</h3> This represents the first reported experience utilizing a pulsing radiotherapy approach in elderly patients with LAHNSCC combined with a CPI unable to undergo conventional radiotherapy. The regimen was well tolerated with surprisingly low local/regional toxicity and very encouraging response rates. The low failure rate observed in the untreated neck was encouraging and reduces toxicity.