To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO).Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose [BED10] ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%).Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression.Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.

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Objectives To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy. Patients and Methods Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression‐free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan–Meier curves and log‐rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT‐induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03. Results Fifty‐three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2–21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1–5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40–129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035–0.528) and PFS (P = 0.004; 95% CI 0.165–0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG‐PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001–0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed. Conclusion Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full‐dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG‐PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.

Background: Renal cell carcinoma (RCC) is traditionally considered to be radioresistant. Radiotherapy response rates are believed to improve with hypofractionated, high dose stereotactic body radiotherapy (SBRT).However, limited data exist regarding the role of SBRT in the treatment of pulmonary metastases. Methods: The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology analyzed its multi-institutional database of more than 700 patients who received SBRT for pulmonary metastases. Treatment was performed at 10 centers between 2001 and 2016. Patients with metastatic RCC were included in the study. Tumor characteristics, treatment details, and follow-up data including survival, local control (LC), distant metastases, and toxicity were evaluated. Results: A total of 46 RCC patients treated with SBRT for 67 lung metastases were identified, who received a median total biologically effective dose (BED iso ) at planning target volume (PTV) isocenter of 117.0 Gy (range, 48.0-189.0 Gy). A median fractional dose of 20.8 Gy at isocenter (range, 6.0-37.9 Gy) was administered in a median number of 3 fractions (1-8 fractions). After a median follow-up time of 28.3 months for all patients, 1-and 3-year LC rates were 98.1% and 91.9%, with corresponding 1-and 3-year overall survival (OS) of 84.3% and 43.8%, respectively. Pulmonary metastases treated with BEDiso ≥130 Gy showed a trend for superior LC (P=0.054). OS was significantly improved in both uni-and multivariate analysis for patients with higher Karnofsky performance scale, lower maximum pulmonary metastasis diameter and lack of post-SBRT systemic therapy due to progression (P=0.014; P=0.049; P=0.006). Only mild acute and late toxicity was reported.

Purpose External-beam radiotherapy (EBRT) is the predominant method for localized brain radiotherapy (LBRT) after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50-kV x‑rays is an alternative way to focally irradiate the resection cavity after BM surgery, with the option of shortening the overall treatment time and limiting normal tissue irradiation. Methods We retrospectively analyzed the outcomes of all patients who underwent neurosurgical resection of BM and 50-kV x‑ray IORT between 2013 and 2020 at Augsburg University Medical Center. Results We identified 40 patients with 44 resected BM treated with 50-kV x‑ray IORT. Median diameter of the resected metastases was 2.8 cm (range 1.5–5.9 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including 3‑monthly MRI of the brain. Mean FU was 14.4 months, with a median MRI FU for alive patients of 12.2 months. Median overall survival (OS) of all treated patients was 26.4 months (estimated 1‑year OS 61.6%). The observed local control (LC) rate of the resection cavity was 88.6% (estimated 1‑year LC 84.3%). Distant brain control (DC) was 47.5% (estimated 1‑year DC 33.5%). Only 25% of all patients needed WBI in the further course of disease. The observed radionecrosis rate was 2.5%. Conclusion IORT with 50-kV x‑rays is a safe and appealing way to apply LBRT after neurosurgical resection of BM, with low toxicity and excellent LC. Close MRI FU is paramount to detect distant brain failure (DBF) early.

Background Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients. Methods A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan–Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis. Results MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30–3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05–2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10–3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09–5.89). Death was never therapy-related. Conclusions Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation. Trial registration: retrospectively registered

Purpose External beam radiotherapy (EBRT) is the predominant method for localized brain radiotherapy (LBRT) after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50kV x-rays is an alternative way to irradiate the resection cavity focally after BM surgery with the option to shorten the overall treatment time and limit normal tissue irradiation.Methods We retrospectively analyzed the outcomes of all patients who underwent neurosurgical resection of BM and 50kV x-ray IORT between 2013 and 2020 at Augsburg University Medical Center.Results We identified 40 patients with 44 resected BM treated with 50kV x-ray IORT. Median diameter of the resected metastases was 2.8 cm (range 1.5–5.9 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including 3-monthly MRI of the brain. Mean FU was 14.4 months, with a median MRI FU for patients alive of 12.2 months. Median overall survival (OS) of all treated patients was 26.4 months (estimated 1-year OS 61.6%). The observed local control (LC) rate of the resection cavity was 88.6% (estimated 1-year LC 84.3%). Distant brain control (DC) was 47.5% (estimated 1-year DC 33.5%). Only 25% of all patients needed WBI in the further course of disease. The observed radionecrosis rate was 2.5%.Conclusion IORT with 50kV x-rays is a safe and appealing way to apply LBRT after neurosurgical resection of BM with low toxicity and excellent LC. Close MRI FU is paramount to detect distant brain failure (DBF) early.