Brachial Plexus Tolerance to High-Dose Radiation in the Re-Irradiation Setting

Abstract

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) is a cornerstone modality in treating head and neck cancers in the primary and salvage settings. Maximum tolerated dose to the brachial plexus and other factors contributing to brachial plexus injury in the re-irradiation setting are poorly understood. To define radiation dose and other clinical factors associated with the brachial plexus injury in patients treated with re-irradiation for recurrent head and neck cancers. <h3>Materials/Methods</h3> We analyzed 47 brachial plexus re-irradiation between 2015 and 2020. A first course of radiation for head and neck cancer, developed recurrent disease, and then underwent salvage re-irradiation. DICOM plans and contours for all patients were reviewed by two authors and via a prospective multidisciplinary chart rounds. Common terminology criteria for adverse events (CTCAE) was used to define the brachial plexus injury after the second course of radiation. We used ROC curves to evaluate the cutoff values. Kaplan-Meier and logistic regression were used to test the correlation between the variables and the outcome. <h3>Results</h3> Median prescription dose from the 1st course was 70 Gy (range: 60-70) and from the 2nd course was 66 Gy (46-70) in 2 Gy per fraction. All patients received photon volumetric modulated arc therapy; 74% received concurrent chemotherapy (CRT) during the 1st course (Cisplatin 30%, Carboplatin +/- Paclitaxel 23% and Cetuximab 21%), 74% received CRT during the 2nd course (Carboplatin/Paclitaxel 40%, Cetuximab 17%, Cisplatin 13% and Nivolumab 4%) and 53% received CRT twice. The median time interval between the two RT courses was 24 months (range, 8-221 months). The median cumulative maximum dose (Dmax) to brachial plexus was 97 Gy (range, 64-144 Gy). At a median follow-up of 9 months (range, 1-47 months), the cumulative incidence of brachial plexopathy (CIBPP) was 17% at 1 year. This consisted of two cases with pain alone, one case with numbness alone, two cases with weakness alone and one case with combination of pain and numbness. The median time to development of symptoms was 8.2 months (range, 1-15 months). Among patients with a Dmax greater than vs less than 106 Gy, the 1-year cumulative incidence of BPP was 42% vs 4% <i>P</i> = 0.005. V80 > 1cc (1-yr CIBPP 34% vs 4% <i>P</i> = 0.03) and V90 > 0.3cc (32% vs 4%, <i>P</i> = 0.046) associated with increased risk of BPP. The use of concurrent cisplatin during re-irradiation was associated with increased risk of BPP (OR 39 CI 4.263-356.81, <i>P</i> = 0.001). Other variables like gender, history of neck surgery, use of other kind of systemic therapy, use of cisplatin during the first course of RT, mean cumulative dose, V60, V70, V100 and the interval between the first and the second courses of radiation were not associated with increased risk of BPP. The 1-year OS was 78% and the 1-year PFS was 52%. <h3>Conclusion</h3> Cumulative incidence of radiation-induced BPP after re-irradiation was 17% at 1 year. Dmax > 106 Gy, higher V80/V90, and the use of concurrent cisplatin during re-irradiation, were associated with increased risk of BPP.