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Background: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk., Methods: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of BMs (AURORA) retrospective study (training cohort: 253 patients from 2 centers; external test cohort: 99 patients from 5 centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (T2-FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set., Results: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (P < .001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively., Conclusions: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Postoperative stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hFSRT) to tumor cavities is emerging as a new standard of care after resection of brain metastases. Both Gamma Knife (GK) and CyberKnife (CK) are modalities commonly used for stereotactic radiotherapy, but fractional schemes are not consistent. The objective of this study was to evaluate outcomes in patients receiving postoperative stereotactic radiotherapy of resected brain metastases (BM) using different fractionation schedules and modalities in two large centers., Methods: Patients with newly diagnosed BM who underwent postoperative SRS or hFSRT with either GK or CK at two large cancer centers were retrospectively evaluated. We analyzed local control (LC), regional control (RC) and overall survival (OS)., Results: From April 14 th to May 18 th , 2020, 79 patients with 81 resection cavities were treated. Forty-seven patients (59.5%) received GK and 32 patients (40.5%) received CK treatment. Fifty-four cavities (66.7%) were treated with hFSRT and 27 (33.3%) with SRS. The most common hFSRT and SRS scheme was 3x10 Gy and 1x16 Gy, respectively. Median OS was 11.7 months with survival rates of 44.7% at 1 year and 18.5% at 2 years. LC was 83.3% after 1 year. Median time to regional progression was 12.0 months with RC rates of 61.1% at 6 months and 41.0% at 12 months. There was no difference in OS, LC or RC between GK and CK treatments or SRS and hFSRT., Conclusions: Both SRS and hFSRT provide high local control rates in resected BM regardless of the applied modality.

Background: Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability., Methods: We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers., Results: Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07)., Conclusion: Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aim: Very elderly patients may benefit from individualized treatment. A survival score was created for patients aged 80+ receiving radiosurgery or fractionated stereotactic radiotherapy for 1-2 brain metastases., Patients and Methods: Thirteen patients were retrospectively evaluated. Characteristics showing significant associations with survival or trends were used for analysis. Prognostic groups were calculated from scoring points of these characteristics (0=worse, 1=better survival) added for each patient., Results: Survival was significantly associated with performance score (p=0.010). Trends were found for histology (p=0.066) and diameter of lesions (p=0.071). Three groups were created (0, 1-2, 3 points) with 6-month survival rates of 0%, 56%, and 100% (p=0.025). Positive predictive values (PPVs) to predict death ≤6 months were 100% with the new score vs. not available and 50% with previous scores; PPVs regarding survival ≥6 were 100% vs. 75% and 67%., Conclusion: Given its limitations, the score was more precise than previous tools and can serve for orientation in patients aged 80+., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Preoperative stereotactic radiosurgery (SRS) of brain metastases may achieve similar local control and better leptomeningeal control rates than postoperative fractionated stereotactic radiotherapy (FSRT) in patients treated with elective metastasectomy. To plan a multicentre trial of preoperative SRS compared with postoperative FSRT, a survey of experts was conducted to determine current practice., Methods: A survey with 15 questions was distributed to the DEGRO Radiosurgery and Stereotactic Radiotherapy Working Group. Participants were asked under what circumstances they offered SRS, FSRT, partial and/or whole brain radiotherapy before or after resection of a brain metastasis, as well as the feasibility of preoperative stereotactic radiosurgery and neurosurgical resection within 6 days., Results: Of 25 participants from 24 centres, 22 completed 100% of the questions. 24 respondents were radiation oncologists and 1 was a neurosurgeon. All 24 centres have one or more dedicated radiosurgery platform and all offer postoperative FSRT. Preoperative SRS is offered by 4/24 (16.7%) centres, and 9/24 (37.5%) sometimes recommend single-fraction postoperative SRS. Partial brain irradiation is offered by 8/24 (33.3%) centres and 12/24 (50%) occasionally recommend whole-brain irradiation. Two centres are participating in clinical trials of preoperative SRS. SRS techniques and fractionation varied between centres., Conclusion: All responding centres currently offer postoperative FSRT after brain metastasectomy. Approximately one third offer single-fraction postoperative SRS and four already perform preoperative SRS. With regard to potential co-investigators, 18 were identified for the PREOP‑2 multicentre trial, which will randomise between preoperative SRS and postoperative FSRT., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: For step-and-shoot robotic stereotactic radiosurgery (SRS) the dose delivered over time, called local tumor-dose-rate (TDR), may strongly vary during treatment of multiple lesions. The authors sought to evaluate technical parameters influencing TDR and correlate TDR to clinical outcome., Material and Methods: A total of 23 patients with 162 oligo (1-3) and multiple (>3) brain metastases (OBM/MBM) treated in 33 SRS sessions were retrospectively analyzed. Median PTV were 0.11 cc (0.01-6.36 cc) and 0.50 cc (0.12-3.68 cc) for OBM and MBM, respectively. Prescription dose ranged from 16 to 20 Gy prescribed to the median 70% isodose line. The maximum dose-rate for planning target volume (PTV) percentage p in time span s during treatment (TDR s,p ) was calculated for various p and s based on treatment log files and in-house software., Results: TDR 60min,98% was 0.30 Gy/min (0.23-0.87 Gy/min) for OBM and 0.22 Gy/min (0.12-0.63 Gy/min) for MBM, respectively, and increased by 0.03 Gy/min per prescribed Gy. TDR 60min,98% strongly correlated with treatment time (ρ = -0.717, p < 0.001), monitor units (MU) (ρ = -0.767, p < 0.001), number of beams (ρ = -0.755, p < 0.001) and beam directions (ρ = -0.685, p < 0.001) as well as lesions treated per collimator (ρ = -0.708, P < 0.001). Median overall survival (OS) was 20 months and 1‑ and 2‑year local control (LC) was 98.8% and 90.3%, respectively. LC did not correlate with any TDR, but tumor response (partial response [PR] or complete response [CR]) correlated with all TDR in univariate analysis (e.g., TDR 60min,98% : hazard ration [HR] = 0.974, confidence interval [CI] = 0.952-0.996, p = 0.019). In multivariate analysis only concomitant targeted therapy or immunotherapy and breast cancer tumor histology remained a significant factor for tumor response. Local grade ≥2 radiation-induced tissue reactions were noted in 26.3% (OBM) and 5.2% (MBM), respectively, mainly influenced by tumor volume (p < 0.001)., Conclusions: Large TDR variations are noted during MBM-SRS which mainly arise from prolonged treatment times. Clinically, low TDR corresponded with decreased local tumor responses, although the main influencing factor was concomitant medication.

Introduction: Combination therapy for melanoma brain metastases (MM) using stereotactic radiosurgery (SRS) and immune checkpoint-inhibition (ICI) or targeted therapy (TT) is currently of high interest. In this collective, time evolution and incidence of imaging findings indicative of pseudoprogression is sparsely researched. We therefore investigated time-course of MRI characteristics in these patients., Methods: Data were obtained retrospectively from 27 patients (12 female, 15 male; mean 61 years, total of 169 MMs). Single lesion volumes, total MM burden and edema volumes were analyzed at baseline and follow-up MRIs in 2 months intervals after SRS up to 24 months. The occurrence of intralesional hemorrhages was recorded., Results: 17 patients (80 MM) received ICI, 8 (62 MM) TT and 2 (27 MM) ICI + TT concomitantly to SRS. MM-localization was frontal (n = 89), temporal (n = 23), parietal (n = 20), occipital (n = 10), basal ganglia/thalamus/insula (n = 10) and cerebellar (n = 10). A volumetric progression of MM 2-4 months after SRS was observed in combined treatment with ICI (p = 0.028) and ICI + TT (p = 0.043), whereas MMs treated with TT showed an early volumetric regression (p = 0.004). Edema volumes moderately correlated with total MM volumes (r = 0.57; p < 0.0001). Volumetric behavior did not differ significantly over time regarding lesions' initial sizes or localizations. No significant differences between groups were observed regarding rates of post-SRS intralesional hemorrhages., Conclusion: Reversible volumetric increases in terms of pseudoprogression are observed 2-4 months after SRS in patients with MM concomitantly treated with ICI and ICI + TT, rarely after TT. Edema volumes mirror total MM volumes. Medical treatment type does not significantly affect rates of intralesional hemorrhage.

Background/aim: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have gained popularity especially for treating 1-3 cerebral metastases. Elderly patients benefit from treatment personalisation. A specific survival score was created to facilitate this approach., Patients and Methods: Ten characteristics were retrospectively analysed for survival in 104 elderly patients with 1-3 cerebral metastases receiving SRS or FSRT alone using a linear accelerator or Cyberknife®., Results: On multivariate analysis, better survival was significantly associated with KPS of 90-100 (p=0.049), single lesion (p=0.036), maximum cumulative diameter of all lesions <16 mm (p=0.026) and supratentorial involvement only (p=0.047). Three groups were formed with 12-14 points (n=22), 15-16 points (n=33) and 17-19 points (n=49) with 12-month survival rates of 7%, 34% and 58% (p<0.0001), respectively. Positive predictive values for predicting death ≤12 months and survival ≥12 months were 95% and 54%., Conclusion: The new score showed very high accuracy in predicting death ≤12 months, but not in predicting survival ≥12 months., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Treatment for elderly patients with few brain metastases is controversial. A score was generated to predict distant brain metastases (DBMs) after stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT)., Patients and Methods: Ten characteristics were retrospectively analyzed for freedom from new DBMs in 104 elderly patients receiving SRS or FSRT alone for 1-3 brain metastases. Characteristics that were significant or showed a trend on multivariate analysis were used for the score., Results: On multivariate analysis, favorable histology (p=0.026) and single brain metastasis (p=0.006) showed significant associations with freedom from DBMs. A trend was found for supra-tentorial location only (p=0.065). Three groups were designed, 10-14, 16-20 and 21-25 points, with 6-month rates of freedom from DBMs of 10%, 54% and 95%, respectively (p<0.0001). Positive predictive values to predict DBMs and freedom from DBMs at 6 months were 91% and 94%., Conclusion: This new score provided high accuracy in predicting DBMs and freedom from DBMs., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT)., Methods: This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS., Results: One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0-40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03)., Conclusion: The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.

The aim was to evaluate toxicity and oncological outcome of combined stereotactic radiosurgery (SRS) and immunotherapy or targeted therapy in patients with multiple brain metastases originating from malignant melanoma. Despite the fact that both SRS and kinase inhibitors or immune checkpoint inhibitors are considered standard treatment options for this indication, the optimal combination and sequence of these modalities remains largely unknown, especially for patients with a high number of brain metastases. For this retrospective analysis, conducted in two large SRS dedicated centers, we identified patients with brain metastases from malignant melanoma and simultaneous application of immunotherapy or targeted therapy within 30 days of SRS. Forty-eight patients with a total of 250 lesions (median: 3) were treated in 65 single fraction SRS sessions from 2012 to 2018. After a median follow-up of 8.3 months (range: 1.2-43.6 months), the 6-month and 1-year overall survival rates were 75.3 and 50.8%, respectively. The local control rate at one year was 89.5%. Immunotherapy and the application of systemic treatment directly before or concomitant to SRS were both associated with improved overall survival (P=0.037 and 0.045, respectively). We observed four grade III toxicities, of which only two can be clearly attributed to the combined treatment. Various combinations of SRS and kinase inhibitors or immune checkpoint inhibitors appear feasible and provide promising oncological results and safety profiles for treating few (n=1-4) and also multiple (n≥5) melanoma brain metastases.

Purpose: Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain metastases with high local control rates. However, data about local re-irradiation in case of local failure after SRS (re-SRS) are rare. We evaluated the feasibility, efficacy and patient selection characteristics in treating locally recurrent metastases with a second course of SRS., Methods: We retrospectively evaluated patients with brain metastases treated with re-SRS for local tumor progression between 2011 and 2017. Patient and treatment characteristics as well as rates of tumor control, survival and toxicity were analyzed., Results: Overall, 32 locally recurrent brain metastases in 31 patients were irradiated with re-SRS. Median age at re-SRS was 64.9 years. The primary histology was breast cancer and non-small-cellular lung cancer (NSCLC) in respectively 10 cases (31.3%), in 5 cases malignant melanoma (15.6%). In the first SRS-course 19 metastases (59.4%) and in the re-SRS-course 29 metastases (90.6%) were treated with CyberKnife® and the others with Gamma Knife. Median planning target volume (PTV) for re-SRS was 2.5 cm3 (range, 0.1-37.5 cm3) and median dose prescribed to the PTV was 19 Gy (range, 12-28 Gy) in 1-5 fractions to the median 69% isodose (range, 53-80%). The 1-year overall survival rate was 61.7% and the 1-year local control rate was 79.5%. The overall rate of radiological radio-necrosis was 16.1% and four patients (12.9%) experienced grade ≥ 3 toxicities., Conclusions: A second course of SRS for locally recurrent brain metastases after prior local SRS appears to be feasible with acceptable toxicity and can be considered as salvage treatment option for selected patients with high performance status. Furthermore, this is the first study utilizing robotic radiosurgery for this indication, as an additional option for frameless fractionated treatment., Competing Interests: The authors have declared that no competing interests exist.

Aim: To create an instrument for estimating the risk of new brain metastases after stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) alone in patients with renal cell carcinoma (RCC)., Patients and Methods: In 45 patients with 1-3 brain metastases, seven characteristics were analyzed for association with freedom from new brain metastases (age, gender, performance score, number and sites of brain metastases, extra-cerebral metastasis, interval from RCC diagnosis to SRS/FSRT)., Results: Lower risk of subsequent brain lesions after RT was associated with single metastasis (p=0.043) and supratentorial involvement only (p=0.018). Scoring points were: One metastasis=1, 2-3 metastases=0, supratentorial alone=1, infratentorial with/without supratentorial=0. Scores of 0, 1 and 2 points were associated with 6-month rates of freedom from subsequent brain lesions of 25%, 74% and 92% (p=0.008). After combining groups with 1 and 2 points, 6-month rates were 25% for those with 0 points and 83% for those with 1-2 points (p=0.002)., Conclusion: Two groups were identified with different risks of new brain metastases after SRS or FSRT alone. High-risk patients may benefit from additional whole-brain irradiation., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To design a tool to predict the probability of new cerebral lesions after stereotactic radiosurgery/radiotherapy for patients with 1-3 brain metastases from colorectal cancer., Patients and Methods: In 21 patients, nine factors were evaluated for freedom from new brain metastases, namely age, gender, Karnofsky performance score (KPS), tumor type, number, maximum total diameter of all lesions and sites of cerebral lesions, extra-cranial metastases, and time from cancer diagnosis to irradiation., Results: Freedom from new lesions was positively associated with KPS of 90-100 (p=0.013); maximum total diameter ≤15 mm showed a trend for positive association (p=0.09). Points were assigned as: KPS 70-80=1 point, KPS 90-100=2 points, maximum diameter ≤15 mm=2 points and maximum diameter >15 mm=1 point. Six-month rates of freedom from new lesions were 29%, 45% and 100% for those with total scores of 2, 3 and 4 points, respectively, with corresponding 12-month rates of 0%, 45% and 100% (p=0.027)., Conclusion: This study identified three risk groups regarding new brain metastases after stereotactic irradiation. Patients with 2 points could benefit from additional whole-brain radiotherapy., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We developed a scoring system to predict 1-year survival after radiosurgery for 1-3 brain metastases. This study aimed to validate this system., Patients and Methods: Seventy-six new patients were included in this validation study. Like in the original scoring-system, three factors (age, performance status, extra-cranial metastases) were used. For each factor, 1-year survival rates in % were divided by 10, and the three scoring-points were added for each patient., Results: Patient's scores were 10, 11, 13, 14, 16 or 17 points with 1-year survival rates ranging between 31% and 80%. Two groups, 10-14 and 16-17 points were formed. In the 14-16 points group, 1-year survival was 47% (versus 33% in the preceding study, p=0.060). In the 16-17 points group, 1-year survival rates were 75% versus 77% (p=0.79)., Conclusion: In the more favorable group, the scoring-system was very reproducible. In the less favorable group, the difference was larger, but also not signficant., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases., Methods: One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS)., Results: On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001)., Conclusion: In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

Aim: To generate a survival score for patients with breast cancer treated with stereotactic radiosurgery (SRS) alone for brain metastases., Patients and Methods: Seven factors were evaluated in 34 patients, namely age, performance score, number of brain metastases, maximum diameter of all brain metastases, location of brain metastases, extracerebral metastases and time between breast cancer diagnosis and SRS. The score was created from factors having a significant impact on survival. Points of 0 (worse survival) or 1 (better survival) were assigned. Factor scores were added to total prognostic scores for each patient., Results: A significant impact on survival was found for performance score (p<0.001), maximum diameter of cerebral lesions (p=0.002), and extracerebral metastases (p=0.026). Three groups were designated by score: 0-1, 2 and 3 points. One-year survival rates were 48%, 71% and 100%, respectively (p<0.001)., Conclusion: This score contributes to appropriate selection of personalized treatment in patients with breast cancer with few cerebral metastases., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To generate a tool that estimates the probability of developing new cerebral metastases after stereotactic radiosurgery (SRS) in breast cancer patients., Patients and Methods: SRS dose plus seven characteristics (age, performance score, number of cerebral metastases, maximum diameter of all metastases, location of metastases, extra-cerebral spread and time from breast cancer diagnosis until SRS) were analyzed regarding their ability to predict the probability of new cerebral metastases development following SRS. For those characteristics deemed significant, points of 0 (higher risk of new lesions) or 1 (lower risk) were given. Scores were generated by adding the points of significant characteristics., Results: Performance score (p=0.013) and maximum diameter of all metastases (p=0.022) were associated with development of subsequent brain metastases. Two groups were created, 0-1 and 2 points. Freedom from new cerebral metastases rates were 27% and 92%, respectively, at 15 months (p=0.003)., Conclusion: This tool helps select breast cancer with few cerebral metastases receiving SRS who may benefit from additional whole-brain irradiation., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Many patients with few cerebral metastases receive radiosurgery alone. The goal of this study was to create a tool to estimate the survival of such patients. To identify characteristics associated with survival, nine variables including radiosurgery dose, age, gender, Eastern cooperative oncology group performance score (ECOG-PS), primary tumor type, number/size of cerebral metastases, location of cerebral metastases, extra-cerebral metastases and time between cancer diagnosis and radiosurgery were analyzed in 214 patients. On multivariate analysis, age (p=0.03), ECOG-PS (p=0.02) and extra-cerebral metastases (p<0.01) had significant impacts on survival. Scoring points for each patient were obtained from 12-month survival rates (in %) related to the significant variables divided by 10. Addition of the scoring points of the three variables resulted in a patient's total predictive score. Two groups were designed, A (10-14 points) and B (16-17 points). Twelve-month survival rates were 33% and 77%, respectively (p<0.001). Median survival times were 8 and 20 months, respectively. Because most patients of group A died from extra-cerebral disease and/or new cerebral lesions, early systemic treatment and additional WBI should be considered. As cause of death in group B was mostly new cerebral metastases, additional WBI appears even more important for this group.

Aim: To determine the optimal dose of radiosurgery-alone for patients with 1-3 cerebral metastases from breast cancer., Patients and Methods: Patients receiving 20 Gy (n=20) were compared to those receiving 16-18.5 Gy (n=10) for local control, distant brain control and overall survival. Seven other variables were also evaluated., Results: Radiosurgery dose achieved significance on univariate (p=0.002; log-rank and Wilcoxon test) and multivariate analysis (p=0.004) of local control. Twelve-month local control rates were 94% after 20 Gy and 48% after 16-18.5 Gy. On univariate analysis of distant brain control, radiosurgery dose was not a significant factor, with 12-month rates of 73% and 60%, respectively. Regarding overall survival, radiosurgery dose was of borderline significance (p=0.059; Wilcoxon test). Twelve-month overall survival rates were 75% and 40%, respectively. On Cox regression analysis, radiosurgery dose exhibited a trend for improving survival (p=0.10)., Conclusion: Radiosurgery with 20 Gy resulted in significantly better local control and led to a trend towards improved overall survival compared to treatment with 16-18.5 Gy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: It is unclear whether patients with few cerebral metastases benefit from whole-brain irradiation added to radiosurgery. Since primary tumors disseminating to the brain show different behavior, this question should be answered separately for each tumor type. This study compared both treatments in patients with 1-3 cerebral metastases from lung cancer., Methods: Ninety-eight patients receiving radiosurgery alone were retrospectively compared to 50 patients receiving radiosurgery plus whole-brain irradiation for local control, distant cerebral control and overall survival. Ten other characteristics were additionally considered including radiosurgery dose, age, gender, Eastern Cooperative Oncology Group (ECOG) performance score, histology, number of cerebral metastases, maximum diameter of all cerebral metastases, site of cerebral metastases, extra-cerebral metastases, and interval from lung cancer diagnosis to irradiation., Results: The treatment approach had no significant impact on local control (p = 0.61). On multivariate analysis of local control, ECOG performance score was significant (risk ratio [RR]: 2.10; p < 0.001). The multivariate analysis of distant brain control revealed significant positive associations with radiosurgery plus whole-brain irradiation (RR: 4.67; p < 0.001) and one cerebral metastasis (RR: 2.62; p < 0.001). Treatment approach was not significantly associated with overall survival (p = 0.32). On multivariate analysis, significant associations with overall survival were found for maximum diameter of all cerebral metastases (RR: 1.81; p = 0.008), extra-cerebral metastases (RR: 2.98; p < 0.001), and interval from lung cancer diagnosis to irradiation (RR: 1.19; p < 0.001)., Conclusion: Addition of whole-brain irradiation to radiosurgery significantly improved distant brain control in patients with few cerebral metastases from lung cancer. This improvement did not translate into better overall survival.

Background: An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients., Methods: Fifty-eight patients with 1-3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy., Results: The treatment regimen had no significant impact on local control in the univariate analysis (p=0.59). Age ≤59 years showed a trend towards improved local control on univariate (p=0.066) and multivariate analysis (p=0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p=0.040) and ECOG 0-1 (p=0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p=0.039) and performance status (p=0.028) maintained significance on multivariate analysis. ECOG 0-1 was positively correlated with survival on univariate analysis (p<0.001); age ≤59 years showed a strong trend (p=0.054). On multivariate analysis, performance status (p<0.001) and age (p=0.041) were significant., Conclusions: In breast cancer patients with few brain metastases, radiosurgery plus whole-brain radiotherapy resulted in significantly better freedom from new brain metastases than radiosurgery alone. However, this advantage did not lead to significantly better survival.

Aim: Two dose groups of patients treated with stereotactic radiosurgery (SRS) alone for 1-3 brain metastases from non-small cell lung cancer (NSCLC) were compared for outcomes., Patients and Methods: Based on the SRS dose administered to the margins of the brain lesions, 46 patients were assigned to groups treated with 15-18 Gy (n=13) or with 20 Gy (n=33). Seven additional factors were investigated: age (≤ 58 vs. ≥ 59 years), gender, Karnofsky performance score (KPS 70-80 vs. 90-100), number of brain metastases (1 vs. 2-3), histology (adenocarcinoma vs. other) extracerebral metastases and interval from NSCLC diagnosis to SRS (≤ 6 vs. >6 months)., Results: Local control rates for 15-18-Gy and 20-Gy groups were 75% and 92% at one year (p=0.043). SRS dose was significant on multivariate analysis (p=0.030). SRS dose was not associated with freedom from new brain metastases (p=0.24) or survival (p=0.37)., Conclusion: SRS with 20 Gy resulted in better control of the irradiated metastases than 15-18 Gy did., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Addition of whole-brain irradiation (WBI) to radiosurgery for treatment of few cerebral metastases is controversial. This study aimed to create an instrument that estimates the probability of developing new cerebral metastases after radiosurgery to facilitate the decision regarding additional WBI., Methods: Nine characteristics were investigated for associations with the development of new cerebral metastases including radiosurgery dose (dose equivalent to <20 Gy vs. 20 Gy vs. >20 Gy for tumor cell kill, prescribed to the 73-90% isodose level), age (≤60 vs. ≥61 years), gender, Eastern Cooperative Oncology Group performance score (0-1 vs. 2), primary tumor type (breast cancer vs. non-small lung cancer vs. malignant melanoma vs. others), number/size of cerebral metastases (1 lesion <15 mm vs. 1 lesion ≥15 mm vs. 2 or 3 lesions), location of the cerebral metastases (supratentorial alone vs. infratentorial ± supratentorial), extra-cerebra metastases (no vs. yes) and time between first diagnosis of the primary tumor and radiosurgery (≤15 vs. >15 months)., Results: Number of cerebral metastases (p = 0.002), primary tumor type (p = 0.10) and extra-cerebral metastases (p = 0.06) showed significant associations with development of new cerebral metastases or a trend, and were integrated into the predictive instrument. Scoring points were calculated from 6-months freedom from new cerebral metastases rates. Three groups were formed, group I (16-17 points, N = 47), group II (18-20 points, N = 120) and group III (21-22 points, N = 47). Six-month rates of freedom from new cerebral metastases were 36%, 65% and 80%, respectively (p < 0.001). Corresponding rates at 12 months were 27%, 44% and 71%, respectively., Conclusion: This new instrument enables the physician to estimate the probability of developing new cerebral metastases after radiosurgery alone. Patients of groups I and II appear good candidates for additional WBI in addition to radiosurgery, whereas patients of group III may not require WBI in addition to radiosurgery.

Background and Purpose: Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases., Patients and Methods: In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size (< 15 vs. ≥ 15 mm), extracranial metastases (no vs. yes), RPA class (1 vs. 2), and interval of cancer diagnosis to SRS (≤ 24 vs. > 24 months)., Results: For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79%, respectively (p < 0.001). The SRS dose maintained significance on multivariate analysis (risk ratio: 2.25; 95% confidence interval: 1.56-3.29; p < 0.001). On intergroup comparisons of local control, 20 Gy was superior to 13-16 Gy (p < 0.001) but not to 18 Gy (p = 0.12); 18 Gy showed a strong trend toward better local control when compared with 13-16 Gy (p = 0.059). Freedom from new brain metastases (p = 0.57) and survival (p = 0.15) were not associated with SRS dose in the univariate analysis., Conclusion: SRS doses of 18 Gy and 20 Gy resulted in better local control than 13-16 Gy. However, 20 Gy and 18 Gy must be compared again in a larger cohort of patients. Freedom from new brain metastases and survival were not associated with SRS dose.