This review gives a best-possible overview of current knowledge and its limitations and underlines the need for a timely generation of stronger evidence in this rapidly expanding field.

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.

Only a small number of studies have examined the relationship between medical students and burnout syndrome. In Salzburg, Paracelsus Private Medical University (PMU) offers a 5-year medical program instead of the regular 6 years of medical studies. Due to the tight schedule and heavy workload, the stress level of students is high. The purpose of this study was to determine whether PMU students show burnout symptoms. Three surveys were conducted: at the beginning of the academic year (T1, December 2009), at the end of the academic year (T2, June 2010), and at the beginning of the following academic year (T3, December 2010). For the assessment of burnout, the Maslach Burnout Inventory (emotional exhaustion, depersonalization or cynicism, and low personal accomplishment) was used, as well as the Six Factors Theory of Burnout (workload, control, reward, community, fairness, and values) and for comparison, the Austrian norms developed by Unterholzer. Burnout rate was calculated by a combined measure of the three components. The results show a significant difference from the norm means in emotional exhaustion, depersonalization/cynicism, and low personal

Purpose: Stereotactic radiosurgery (SRS) is the preferred primary treatment option for patients with a limited number of asymptomatic brain metastases. In case of relapse after initial SRS the optimal salvage treatment is not well defined. Within this retrospective analysis, we investigated the feasibility of repeated courses of SRS to defer Whole-Brain Radiation Therapy (WBRT) and aimed to derive prognostic factors for patient selection.Materials and Methods: From 2014 until 2017, 42 patients with 197 brain metastases have been treated with multiple courses of SRS at our institution. Treatment was delivered as single fraction (18 or 20 Gy) or hypo-fractionated (6 fractions with 5 Gy) radiosurgery. Regular follow-up included clinical examination and contrast-enhanced cMRI at 3–4 months' intervals. Besides clinical and treatment related factors, brain metastasis velocity (BMV) as a newly described clinical prognostic metric was included and calculated between first and second treatment.Results: A median number of 1 lesion (range: 1–13) per course and a median of 2 courses (range: 2–6) per patient were administered resulting in a median of 4 (range: 2–14) metastases treated over time per patient. The median interval between SRS courses was 5.8 months (range: 0.9–35 months). With a median follow-up of 17.4 months (range: 4.6–45.5 months) after the first course of treatment, a local control rate of 84% was observed after 1 year and 67% after 2 years. Median time to out-of-field-brain-failure (OOFBF) was 7 months (95%CI 4–8 months). WBRT as a salvage treatment was eventually required in 7 patients (16.6%). Median overall survival (OS) has not been reached. Grouped by ds-GPA (≤ 2 vs. >2) the survival curves showed a significant split (p = 0.039). OS differed also significantly between BMV-risk groups when grouped into low vs. intermediate/high risk groups (p = 0.025). No grade 4 or 5 acute or late toxicity was observed.Conclusion: In selected patients with relapse after SRS for brain metastases, repeat courses of SRS were safe and minimized the need for rescue WBRT. The innovative, yet easy to calculate metric BMV may facilitate treatment decisions as a prognostic factor for OS.

No abstract

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

The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan–Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1–102 mo); 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11–40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1–42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi (p = 0.016) or BRAF/MEKi (p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or PFS. Overall, severe toxicity of combined treatment was rare; a potentially increased toxicity after SRT and continuous treatment with EGFR inhibitors or BRAF(±MEK) inhibitors requires further evaluation.

BackgroundMetastasis 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.MethodsA 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.ResultsMDT 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.ConclusionsMetastases-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 registrationretrospectively registered