In the era of personalized medicine, individualized prognostic models with tumor characteristics are needed to inform patients about survival. Before clinical use, external validation of such models by an independent group is needed. An updated version of the graded prognostic assessment (GPA) estimates survival in patients with brain metastases (BMs) of non-small cell lung cancer (NSCLC). This is the first external validation of the updated Lung-molGPA in patients treated with stereotactic radiotherapy (SRT) for one or more BMs. Patients treated with SRT for BMs from NSCLC adenocarcinoma were retrospectively included. GPA score was calculated for each patient based on six prognostic factors including age, Karnofsky Performance Status, number of BMs, extracranial metastases, EGFR/ALK status and PD-L1 expression. Kaplan-Meier analysis evaluated survival probability. Impact of individual prognostic factors on survival was assessed by univariate and multivariate analyses using the Cox proportional hazard model. Predictive performance was evaluated using discrimination (C-statistic) and calibration (Brier test). The cohort (n = 241) was divided into four prognostic groups. Overall median survival was 15 months. Predicted and observed median survival were similar between the original and validation cohorts, apart from the most favorable prognostic group. With adequate C-statistics and Brier scores, the Lung-molGPA provided accurate survival predictions. The Lung-molGPA accurately predicted survival in our European population, except for an overestimation of survival in the small most favorable prognostic group. This prognostic model was externally validated and is therefore useful for counseling of patients with BMs of NSCLC adenocarcinoma.

Background and purpose: During radiotherapy treatment planning, avoidance of organs at risk (OARs) is important. An international consensus-based delineation guideline was recently published with 34 OARs in the brain. We developed an MR-based OAR autosegmentation atlas and evaluated its performance compared to manual delineation. Materials and methods: Anonymized cerebral T1-weighted MR scans (voxel size 0.9 x 0.9 x 0.9 mm(3)) were available. OARs were manually delineated according to international consensus. Fifty MR scans were used to develop the autosegmentation atlas in a commercially available treatment planning system (Raystation (R)). The performance of this atlas was tested on another 40 MR scans by automatically delin-eating 34 OARs, as defined by the 2018 EPTN consensus. Spatial overlap between manual and automated delineations was determined by calculating the Dice similarity coefficient (DSC). Two radiation oncolo-gists determined the quality of each automatically delineated OAR. The time needed to delineate all OARs manually or to adjust automatically delineated OARs was determined. Results: DSC was >= 0.75 in 31 (91 %) out of 34 automated OAR delineations. Delineations were rated by radiation oncologists as excellent or good in 29 (85 %) out 34 OAR delineations, while 4 were rated fair (12 %) and 1 was rated poor (3 %). Interobserver agreement between the radiation oncologists ranged from 77-100 % per OAR. The time to manually delineate all OARs was 88.5 minutes, while the time needed to adjust automatically delineated OARs was 15.8 minutes. Conclusion: Autosegmentation of OARs enables high-quality contouring within a limited time. Accurate OAR delineation helps to define OAR constraints to mitigate serious complications and helps with the development of NTCP models. (C) 2022 The Author(s). Published by Elsevier B.V.

Background/Objectives: Neurosurgical resection is the standard treatment for large brain metastases (BMs). Postoperative stereotactic radiotherapy (SRT) is used to reduce local recurrence (LR) but does not always prevent leptomeningeal disease (LMD). This study aims to analyze patterns of tumor recurrence and to identify opportunities for the further improvement of treatment efficacy. Methods: We included 147 patients who underwent resection and SRT for BMs. The distance between the resection cavity target volume and the new tumor growth was calculated. Cox regression analyses were used to assess associations of LMD with various patient characteristics. Results: Median survival after postoperative SRT was 14 months (IQR 6–30) with a 3-year actuarial survival rate of 21%. LR occurred in 20/147 patients (14%). After total resection, LR occurred in 21% of patients after 3 years of follow-up compared to 36% after subtotal resection. Marginal LR occurred in 5/147 patients (3%). LMD was found in 21/147 patients (14%; 3-year actuarial rate, 26%), and it was found more commonly in patients with resected cerebellar metastases (23%; 3-year actuarial rate, 46%) compared to those with cerebral metastases (11%; 3-year actuarial rate 17%) (HR 2.54, 95% CI 1.07–6.04, p = 0.034). Conclusions: This study examined patterns of recurrence after postoperative radiotherapy and its implications for radiation dose, radiation field size, and treatment sequence. Local control was high after total resection. Radiation field size appeared adequate given the low incidence of marginal recurrences. Patients with cerebellar metastases showed an increased risk of LMD, underscoring the need for preventive measures, particularly preoperative SRT.

Stereotactic radiation therapy (SRT) is a frequently used and effective treatment for patients who received diagnosis for brain metastases (BMs). Radionecrosis (RN) is a severe complication of SRT which may cause neurologic symptoms. A normal tissue complication probability (NTCP) model has previously been established to predict the risk of RN based on the volume of healthy brain receiving ≥12 Gy. The aim of this study is to externally validate this prediction model. A total of 162 patients treated with SRT for solitary BMs were retrospectively included. The NTCP models for all (asymptomatic and symptomatic) RN and symptomatic RN cases were evaluated using discrimination (C-statistic) and calibration (Brier scores). Overall survival was determined using the Kaplan-Meier method. Median overall survival was 10 months. Asymptomatic or symptomatic RN was found in 44 (27%) of patients. Of these, 26 (16%) RN cases were symptomatic, with actuarial rates of 11% and 22% after 6 and 12 months, respectively. The C-statistics of the “any RN” and the “symptomatic RN” models were identical (0.61). Brier scores were 0.201 and 0.217, respectively. Univariable logistic regression analysis showed a significant correlation between both tumor volume and volume of healthy brain receiving ≥12 Gy with symptomatic RN. These effects did not hold up in the multivariable analysis. A nomogram was established and internally validated. The accuracy of the tested NTCP models in assessing the risk of RN in patients with BM after SRT was insufficient for clinical practice. A novel multifactorial nomogram was developed to predict symptomatic RN. This model needs to be externally validated.

Background: Stereotactic radiotherapy (SRT) is a promising treatment option for patients with multiple brain metastases (BMs). Using one isocenter instead of a separate isocenter for each BM can reduce the treatment time. This work compares the calculated dose in the treatment planning system with the measured dose using film dosimetry of single-isocenter multi-target (SIMT) SRT for multiple BM. Methods: Fifty patients with 4 to 18 BMs (median = 6, in total 356 BMs) were treated with a single-isocenter non-coplanar LINAC-based treatment with six VMAT arcs. Treatment was performed using RayStation and Elekta Versa HD with Agility multileaf collimator, including a 6D robotic couch. Patient-specific QA measurements were performed with an in-house developed phantom using three layers of GafChromic EBT3 film. Film measurements were analyzed in DoseLab using global gamma with 3% and 1 mm distance-to-agreement criteria. Additionally, secondary dose calculations in Mobius3D were performed with similar gamma criteria. Results: The mean total Paddick conformity index and gradient index were 0.7 ± 0.10 and 5.2 ± 1.9, respectively. Monitor units used were 6321 ± 2510, and mean irradiation time was 600 ± 90 s. The mean global gamma passing rate for all measured films was 94.5 ± 4.6% with 3% and 1 mm criteria, while that of the dose calculations in Mobius3D was 98.2 ± 1.2% with the same criteria. A dependence of gamma passing rates of film measurements on the total PTV volume was observed, whereas such dependence was minimal for Mobius3D. Conclusions: The results demonstrate good agreement between the TPS, film measurements, and independent dose calculations, supporting the dosimetric accuracy of single-isocenter multi-target SRT for treating multiple BMs.