Brachial Plexus Tolerance to Standard Fractionation Re-Irradiation: The Ohio State University Experience

Abstract

Factors contributing to brachial plexopathy (BPP) in the re-irradiation setting need further assessment. Preliminary work revealed that higher the doses and the use of concurrent cisplatin were associated with higher risk of BPP. Here, we expand our cohort and increase our follow-up duration, given the late nature of BPP development. Sixty-two BP sites with 41 patients (pts), treated between 2015 and 2020 for recurrent H&N cancer, were assessed. Contours and plans were reviewed via a prospective multidisciplinary chart rounds prior to treatment delivery and re-verified by two authors prior to this analysis. Kaplan-Meier and logistic regression were used to test the correlation between variables and outcomes. ROC was used to evaluate the cutoff values. Common terminology criteria of adverse events were used to define BPP. The median age of pts was 63 (29-78) and 65% were males. Median prescription dose was 70 Gy (60-70) for the 1st course and 66 Gy (44-70) for the 2nd course. 13% received intraoperative radiotherapy (IORT) during salvage treatment ranging from 10-15 Gy. 30% of pts in the 1st course and 80% in the 2nd course of pts had surgery. Concurrent chemotherapy was delivered to 71% of pts in the 1st course (Cisplatin 34%, Cetuximab 22%, Carboplatin +/- Paclitaxel 15%) and 76% in the 2nd course (Carboplatin/Paclitaxel 41%, Cisplatin 19%, Cetuximab 12%, Nivolumab 4%). The median interval between courses was 26.5 months (8-221). The median cumulative Dmax (0.03cc) and mean dose to the BP were 96.5 Gy (51-144) and 61.5 Gy (15-110), respectively. The median V60, V70, V80, V90, and V100 were 3.6cc (0.03-10.4), 2.4cc (0-9.9), 1.3cc (0-9.3), 0.6cc (0-8.4), and 0.0015cc (0-7.2), respectively. The median follow-up after the completion of the 2nd RT course was 19 months (1.4-71.5). The 1-yr incidence of BPP was 17%, with a median time to onset of 8.9 months (1-16.6). Factors associated with development of BPP were cumulative Dmax > 100 Gy (HR 1.06, [CI 1.014-1.1], p = 0.009), cumulative mean dose >70 Gy (HR 1.05, [CI 1.01-1.09], p = 0.03), V80 > 1.6cc (HR 1.2. [CI 0.99- 1.52], p = 0.06), V90 > 1cc (HR 1.3, [CI 1.013-1.58], p = 0.038), V100 > 0.3cc (HR 1.33, [1.044-1.69], p = 0.021) and the usage of concurrent cisplatin during the 2nd course (HR 8.9, [CI 2.36-33.75], p = 0.001). Other factors including gender, age, surgery, treatment interval between the two courses, IORT, V60, and V70 were not associated with increased risk of BPP. The incidence of grade 1, grade 2, and grade 3 BPP were 9.6%, 3% and 2.4%, respectively. The 1-yr OS was 70% and LC was 60%. At a median follow up of 19 months, the 1-yr incidence of grade 2 and 3 BPP was approximately 5%. Cisplatin during the 2nd course, cumulative metrics of Dmax 100 Gy, mean 70 Gy, V80 1.6cc, V90 1cc and V100 0.3cc were associated with development of BPP. Prospective study, longer follow up, and higher numbers are warranted. To our knowledge, this represents the largest cohort and longest follow up yet reported for BPP in the re-irradiation setting.