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Purpose/Objective(s) 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. Materials/Methods 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. Results 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% P = 0.005. V80 > 1cc (1-yr CIBPP 34% vs 4% P = 0.03) and V90 > 0.3cc (32% vs 4%, P = 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, P = 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%. Conclusion 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.

Purpose/Objective(s) Pediatric patients with metastatic solid tumors historically have a poor overall survival. Some pediatric patients may still be potentially curable with aggressive local therapy to metastatic disease, and adult trials have defined a group of oligometastatic patients, where the use of stereotactic body radiation therapy (SBRT) has an overall survival benefit. The purpose of this study is to report results of the use of SBRT in the treatment of pediatric metastatic disease. Materials/Methods All pediatric and adolescents and young adult (AYA) patients age 3-40 years who received SBRT were included between the years 2000-2020. SBRT included radiation treatments with 3-5 fractions and ablative doses above conventional palliative radiation. Study endpoints included local control (LC), progression free survival (PFS), overall survival (OS), cumulative incidence (CI) of death or local failure and toxicity. The endpoints with respect to survival and LC were calculated using the Kaplan-Meier estimate. The cumulative incidence of local failure was calculated using death as a competing risk. Toxicity was scored using CTCAE v5.0. Results Thirty-six lesions in 16 patients were treated with SBRT and comprised the overall cohort. The most common pediatric solid tumors treated were Ewing's Sarcoma (n = 3), Osteosarcoma (n = 3), and Rhabdomyosarcoma (n = 2). The majority of lesions irradiated were in the spine (n = 11), lung (n = 8), pelvis (n = 7), and brain (n = 5). The median follow up was 12 months. The median OS and PFS for the entire cohort were 17 months and 15.7 months, respectively. Patients were treated to a median dose of 25 Gy in 5 fractions. The 1-year OS for the entire cohort was 75%. The 6- and 12-month local control was 85% and 78%, respectively. There were no local failures in irradiated lesions for patients who received a BED10≥100 Gy. Patients treated with SBRT who had ≤5 metastatic lesions at first recurrence had a superior 1-year OS of 100% versus 50% for those with > 5 lesions. No patients experienced a grade 4 or 5 toxicity in our cohort. One patient (6.3%) experienced a CTCAE grade 3 toxicity (seizure) which resolved after anti-epileptic medications. Conclusion Local control was excellent with SBRT delivered to metastatic disease, particularly for lesions receiving a BED10≥100 Gy. High-grade toxicity was rare in our patient population. Patients with 5 or fewer metastatic sites have a significantly better OS compared to > 5 sites. Future prospective trials with multi-institutional collaboration will be necessary to evaluate appropriate patient selection and the optimal radiation dose regimen.

Purpose Despite high response rates, there has been reluctance to use radiation therapy for patients with relapsed/refractory (r/r) Hodgkin (HL) or aggressive non-Hodgkin lymphoma (NHL) given concerns for subacute and late toxicities. Symptomatic pneumonitis, a subacute toxicity, has an incidence of 17% to 24% (≥grade 2) even with intensity modulated radiation therapy. Proton therapy (PT), which has no exit radiation dose, is associated with a lower dose to lung compared with other radiation techniques. As risk of radiation pneumonitis is associated with lung dose, we evaluated whether pneumonitis rates are lower with PT. Methods and Materials Within an international, multi-institutional cohort, we retrospectively evaluated the incidence and grade of radiation pneumonitis (National Cancer Institute Common Terminology Criteria for Adverse Events v4) among patients with r/r HL or NHL treated with PT. Results A total of 85 patients with r/r lymphoma (66% HL, 34% NHL; 46% primary chemorefractory) received thoracic PT from 2009 to 2017 in the consolidation (45%) or salvage (54%) setting. Median dose was 36 Gy(RBE). Before PT, patients underwent a median of 1 salvage systemic therapy (range, 0-4); 40% received PT within 4 months of transplant. With a median follow-up of 26.3 months among living patients, 11 patients developed symptomatic (grade 2) pneumonitis (12.8%). No grade 3 or higher pneumonitis was observed. Dose to lung, including mean lung dose, lung V5, and V20, significantly predicted risk of symptomatic pneumonitis, but not receipt of brentuximab, history of bleomycin toxicity, sex, or peritransplant radiation. Conclusions PT for relapsed/refractory lymphoma was associated with favorable rates of pneumonitis compared with historical controls. We confirm that among patients treated with PT, pneumonitis risk is associated with mean lung and lung V20 dose. These findings highlight how advancements in radiation delivery may improve the therapeutic ratio for patients with relapsed/refractory lymphoma. PT may be considered as a treatment modality for patients with relapsed/refractory lymphoma in the consolidation or salvage setting.