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Purpose: In patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), the standard of care is concurrent chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab. Pneumonitis is a known adverse event of both radiation therapy and immune checkpoint inhibitors such as durvalumab. We sought to characterize pneumonitis rates and dosimetric predictors of pneumonitis in a real-world population of patients with NSCLC treated with definitive CRT followed by consolidative durvalumab. Methods and Materials: Patients with NSCLC from a single institution who were treated with definitive CRT followed by consolidative durvalumab were identified. Outcomes of interest included pneumonitis incidence, type of pneumonitis, progression-free survival, and overall survival. Results: Sixty-two patients were included in our data set treated from 2018 to 2021 with a median follow-up of 17 months. The rate of grade 2+ pneumonitis in our cohort was 32.3%, and the rate of grade 3+ pneumonitis was 9.7%. Lung dosimetry parameters including V20 ≥30% and mean lung dose (MLD) >18 Gy were found to be correlated with increased rates of grade 2+ and grade 3+ pneumonitis. Patients with a lung V20 ≥30% had a grade 2+ pneumonitis rate at 1 year of 49.8% compared with 17.8% in patients with a lung V20 18 Gy had a grade 2+ pneumonitis rate at 1 year of 52.4% compared with 25.8% in patients with an MLD ≤18 Gy (P = .01). Moreover, heart dosimetry parameters including mean heart dose ≥10 Gy were found to be correlated with increased rates of grade 2+ pneumonitis. The estimated 1-year overall survival and progression-free survival of our cohort were 86.8% and 64.1%, respectively. Conclusions: The modern management of locally advanced, unresectable NSCLC involves definitive chemoradiation followed by consolidative durvalumab. Pneumonitis rates were higher than expected in this cohort, particularly for patients with a lung V20 ≥30%, MLD >18 Gy, and mean heart dose ≥10 Gy, suggesting that more stringent radiation planning dose constraints may be needed.

Purpose: Single-fraction radiation surgery for spine metastases is highly effective. However, a high rate (20-39%) of vertebral body fracture (VBF) has been associated with large, single-fraction doses. We report our experience using multifraction stereotactic body radiation therapy (SBRT). Methods and materials: All patients who were treated with multifraction SBRT for spine metastases at our institution between 2009 and 2017 were retrospectively analyzed. SBRT was delivered in 2 to 5 fractions using the Cyberknife System (Accuray, Sunnyvale, CA). Patients were followed clinically and with magnetic resonance imaging every 3 to 6 months. Local control, complications (including VBF), and overall survival were evaluated. Patient, disease, and treatment variables were analyzed for a statistical association with outcomes. Results: A total of 83 patients were treated to 98 spine lesions with a median follow-up of 7.6 months. Histologies included non-small cell lung cancer (NSCLC; 24%), renal cell carcinoma (RCC; 18%), and breast cancer (12%). Surgery or vertebroplasty were performed before SBRT in 21% of cases. Patients received a median SBRT dose of 24 Gy in a median of 3 fractions. Local control was 93% at 6 months and 84% at 1 year. Higher prescribed dose, higher biologic effective dose, higher minimum dose to 90% of the planning target volume, tumor histology, and smaller tumor volume predicted improved local control. The cumulative dose was 23 Gy versus 26 Gy for patients with and without failure (P = .02), higher biologic effective dose 39 Gy versus 46 Gy, (P = .01), and higher minimum dose to 90% of the planning target volume 23 Gy versus 26 Gy (P = .03). VBF occurred in 4.2% of all cases and 5.3% of those without surgery or vertebroplasty prior to SBRT. Only preexisting VBF predicted risk of post-SBRT VBF (P

Purpose: Many patients treated with stereotactic radiosurgery (SRS) alone as initial treatment require 1 or more subsequent salvage therapies. This study aimed to determine if commonly used salvage strategies are associated with differing risks of radiation necrosis (RN). Methods and materials: All patients treated with upfront SRS alone for brain metastases at our institution were retrospectively analyzed. Salvage treatment details were obtained for brain failures. Patients who underwent repeat SRS to the same lesion were excluded. RN was determined based on pathological confirmation or advanced brain imaging consistent with RN in a symptomatic patient. Patients were grouped according to salvage treatment and rates of RN were compared via Fisher's exact tests. Results: Of 284 patients treated with upfront SRS alone, 132 received salvage therapy and 44 received multiple salvage treatments. This included 31 repeat SRS alone, 58 whole brain radiation therapy (WBRT) alone, 28 SRS and WBRT, 7 surgery alone, and 8 surgery with adjuvant radiation. With a median follow-up of 10 months, the rate of RN among all patients was 3.17% (9/284), salvaged patients 4.55% (6/132), and never salvaged patients 1.97% (3/152). Receiving salvage therapy did not significantly increase RN risk (P = .31). Of the patients requiring salvage treatments, the highest RN rate was among patients that had both salvage SRS and WBRT (delivered as separate salvage therapies) (6/28, 21.42%). RN rate in this group was significantly higher than in those treated with repeat SRS alone (0/31), WBRT alone (0/58), surgery alone (0/7), and surgery with adjuvant radiation (0/8). Comparing salvage WBRT doses

Abstract:Purpose: Standard chemoradiation therapy for Stage III non-small cell lung cancer results in suboptimal outcomes with a high rate of local failure and poor overall survival. We hypothesize that dose escalation using stereotactic body radiotherapy (SBRT) boost could improve upon these results. We present here a study evaluating the dosimetric feasibility of such an approach.Methods: Anonymized CT data sets from 3 randomly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected. 3D-CRT plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels, 16 Gy in 2 fractions and 28 Gy in 2 fractions. SBRT plans and total composite (3D-CRT and SBRT) were optimized and evaluated for target coverage and dose to critical structures; lung, esophagus, cord, and heart.Results: All three plans met predetermined target coverage and normal tissue dose constraints. PTV V95 was equal to or greater than 95% in all cases. The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30% and 55%, respectively. The 5cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans. The cumulative dose to the esophagus was also acceptable with less than 10% of the esophagus receiving doses in excess of 50 Gy. The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5%.Conclusion: The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study. A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken.

Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach. Material and Methods: Patients with brain metastases treated with SRS from 2001-2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky Performance Status ≥70, and life expectancy ≥3 mo. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-yr WBRT-free survival (N=104), and those who died or required salvage WBRT within 3 mo of SRS (N=56). Differences between these groups were assessed by univariate and multivariate analyses.Results: Median survival for all patients was 11 mo. Among patients with ≥1-yr WBRT-free survival, median survival was 33 mo [12-107 mo] with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p