Short-Course Palliative Radiotherapy Combined With Immunotherapy for Recurrent/Advanced/Metastatic Head and Neck Cancer

Abstract

To evaluate tumor response rates in patients treated with a combination of palliative short-course radiotherapy (SCRT) and immune checkpoint inhibitor immunotherapy (IO) in patients with recurrent, advanced or metastatic (R/A/M) head and neck cancer (HNC).We reviewed the medical records of patients treated with short-course palliative intent radiation therapy (RT) (hypofractionated RT in 4-5 fractions) for R/A/M HNC between 2014-2020. Patient, disease, and treatment factors were abstracted from the medical record. Patients were categorized as having been treated with combined immunotherapy and radiotherapy (IO+RT) if the RT was given after at least 1 cycle of IO with at least 1 cycle of IO afterward. Treated gross tumor volume (GTV) was measured prior to and after RT and percent change in GTV volume from baseline to best overall response (BOR) was calculated. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.In total, 19 patients were treated with SCRT, 7 of whom were treated with combined IO+RT. Primary site included oral cavity (n = 6), larynx/hypopharynx (5), oropharynx (3), sinonasal (2), cutaneous (2), and thyroid (1). Squamous cell histology was most frequent (16/19) with the other 3 comprised of sinonasal intestinal-type adenocarcinoma, mucosal melanoma, and Hürthle cell carcinoma. Disease status included 6 patients with a recurrence, 6 were metastatic, 3 locally advanced/incurable, and 3 recurrent/metastatic. Prior treatments included RT (n = 9) and chemotherapy (6); ECOG performance status was 1-2 in 13 patients and 3-4 in 6 patients. Seventeen patients were treated with "quad-shot" radiotherapy (14.4-14.8 Gy in 4 fractions delivered twice daily) and 2 were treated with 20 Gy in 5 fractions. Median (range) number of IO cycles given pre- and post-RT were 7 (1-11) and 2 (1-21), respectively. Of the 17 evaluable patients for treatment response, 13 patients responded or were stable while 4 had progression. Median pre-RT target volume in the RT cohort was 37.2 (6.14-486.21) cc and 145.28 (24.21-219.51) cc in the IO+RT cohort. Median post-RT target volume in the RT cohort was 28.00 (17.23, 57.630 cc and 58.44 (0.00, 246.56) cc in the IO+RT cohort. Median change in target volume in RT cohort was -42% (range: -100, 259) cc and -54% (-100, 12) cc in the IO+RT cohort. 1-year PFS and OS were 5% and 21%, respectively. 1-year OS was numerically higher for IO+RT patients (43% v. 8%, P = 0.13).In this select cohort of patients with R/A/M HNC, combined IO+SCRT was feasible and showed an improved tumor response as evidenced by greater decrement in post-treatment tumor volume. An ongoing clinical trial (NCT04454489) aims to prospectively evaluate the potential benefit of combined quad-shot radiotherapy with Pembrolizumab to improve response rates to IO alone.