Search

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm., (© 2024. The Author(s).)

Stereotactic radiosurgery (SRS) is an option for brain metastases (BM) not eligible for surgical resection, however, predictors of SRS outcomes are poorly known. The aim of this study is to investigate predictors of SRS outcome in patients with BM secondary to non-small cell lung cancer (NSCLC). The secondary objective is to analyze the value of volumetric criteria in identifying BM progression. This retrospective cohort study included patients >18 years of age with a single untreated BM secondary to NSCLC. Demographic, clinical, and radiological data were assessed. The primary outcome was treatment failure, defined as a BM volumetric increase 12 months after SRS. The unidimensional measurement of the BM at follow-up was also assessed. One hundred thirty-five patients were included, with a median BM volume at baseline of 1.1 cm 3 (IQR 0.4-2.3). Fifty-two (38.5%) patients had SRS failure at follow-up. Only right BM laterality was associated with SRS failure (p=0.039). Using the volumetric definition of SRS failure, the unidimensional criteria demonstrated a sensibility of 60.78% (46.11%-74.16%), specificity of 89.02% (80.18%-94.86%), positive LR of 5.54 (2.88-10.66) and negative LR of 0.44 (0.31-0.63). SRS demonstrated a 61.5% local control rate 12 months after treatment. Among the potential predictors of treatment outcome analyzed, only the right BM laterality had a significant association with SRS failure. The volumetric criteria were able to identify more subtle signs of BM increase than the unidimensional criteria, which may allow earlier diagnosis of disease progression and use of appropriate therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Stereotactic radiosurgery (SRS) presents as a good treatment option for smaller, deep-seated brain metastases (BMs). This study aims to determine predictors of SRS failure for patients with non-small cell lung cancer BMs., Methods: This was a retrospective study of single non-small cell lung cancer BMs treated using SRS. We included patients >18 years with a single, previously untreated lesion. Primary outcome was treatment failure, defined as BMs dimension increase above the initial values. Demographic, clinical, and radiological data were collected to study potential predictors of treatment failure., Results: Worse rates of progression-free survival (PFS) were associated with heterogeneous contrast enhancement (18.1 ± 4.1 vs. 41.9 ± 4 months; P < 0.001). Better rates of PFS were associated with volumes <1.06 cm 3 (log-rank; P = 0.001). Graded prognostic assessment was significantly associated with survival at 120 months (log-rank; P < 0.001). Karnofsky Performance Scale was evaluated in 3 strata: 90-100, 80, and ≤70. Mean survival rates for these strata were 31.8 ± 3.9, 10.6 ± 2.2, and 9.8 ± 2.3 months, respectively (log-rank; P < 0.001). There were no differences regarding presence of extracranial metastases, age, or lesion location. A multivariable logistic regression found that volume <1.06 cm 3 was associated with higher survival rates at 10 years (odds ratio: 3.2, 95% confidence interval: 1.3-8.0)., Conclusions: Contrast-homogeneous metastases and lesions <1.06 cm 3 are associated with better rates of PFS. Karnofsky Performance Scale and graded prognostic assessment were associated with more favorable survival rates after 10 years. Volume <1.06 cm 3 was the only significant predictor of survival in the multivariable analysis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We analyzed volumetric response of metastatic brain tumors that progressed despite treatment with stereotactic radiosurgery (SRS) after treatment with laser interstitial thermal therapy (LITT). We retrospectively reviewed consecutive patients treated from 1/2012 to 10/2015 with LITT for metastatic brain tumors demonstrating progression after SRS. Volumes were quantified using MRI with contrast-enhanced T1-weighted (T1W) and fluid-attenuated inversion recovery (FLAIR). Fifty lesions from 36 patients were studied. Lesions were assessed prior to LITT, immediately after LITT, 0-90 days after LITT, 90-180 days after LITT, 180-270 days after LITT, and 270-360 days after LITT. The median T1W volume was 5.05 cc (range 0.54-23.31 cc) before LITT treatment (n = 50), 7.70 cc (range 1.72-38.76 cc) 0-90 days after LITT (n = 47), and 3.68 cc (range 1.282-48.31 cc) 180-270 days after LITT (n = 21). The median FLAIR volume was 43.36 cc (range 3.09-233.01 cc) before LITT treatment (n = 50), 37.13 cc (range 3.48-244.23 cc) 0-90 days after LITT (n = 43), 31.68 cc (range 1.6-248.75 cc) 180-270 days after LITT (n = 18). The 6-month FLAIR volume showed a statistically significant reduction compared to pretreatment (p = 0.04). After selecting for cases where patients had two or more post-operative MRIs, we found that 24 lesions (63%) demonstrated an overall downward trend and 14 lesions (37%) demonstrated an upward trend. The median pre-treatment T1W volume for the patients whose lesions demonstrated volumetric reduction after LITT was 3.54 cc (range 0.539-10.06 cc) and for those who did not demonstrate volumetric reduction after LITT it was 8.81 cc (range 0.926-23.313 cc). The pre-treatment tumor volume plays a significant role in determining response to LITT with smaller tumor volumes responding better to LITT than tumors with larger volumes.

Background: After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone., Methods: In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants., Findings: Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group., Interpretation: SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy., Funding: National Institutes of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Object: The authors' institution previously reported a 69% rate of crude local control for surgical management of lateral ventricle metastases at the University of Texas MD Anderson Cancer Center. For comparison, the authors here report their institutional experience with use of stereotactic radiosurgery (SRS) to treat intraventricular metastases., Methods: To identify patients with intraventricular metastases for this retrospective review, the authors queried an institutional SRS database containing the medical records of 1962 patients with 5800 brain metastases who consecutively underwent SRS from June 2009 through October 2013. End points assessed were local control (crude and locoregional), distant failure-free survival, progression-free survival, and overall survival., Results: Of the 1962 records examined, those for 25 (1.3%) patients with 30 (0.52%) intraventricular metastases were identified. Median patient age at SRS was 55.8 years. The most common primary malignancy was renal cell carcinoma (n = 13), followed by melanoma (n = 7) and breast adenocarcinoma (n = 5). Median tumor volume was 0.75 cm(3) (range 0.01-5.6 cm(3)). Most lesions were located in the lateral ventricles (n = 25, 83.3%) and were treated to a median dose of 20 Gy (range 14-20 Gy). A total of 12 (48%) patients received whole-brain radiation therapy, most (n = 10) before SRS. With a median follow-up of 11.4 months (range 1.6-39.2 months), the rate of crude local control was 93.3%, and the rates of 6-month and 1-year actuarial locoregional control were 85.2% and 56.2%, respectively. The median overall survival time after SRS was 11.6 months (range 1.3-38.9 months), and the 6-month and 1-year actuarial rates were 87.1% and 46.7%, respectively. Disease dissemination developed in 7 (28%) patients as a second intraventricular metastatic lesion (n = 3, 12%), leptomeningeal disease (n = 3, 12%), or both (n = 1, 4%). Radiographic changes developed in 5 (20%) patients and included necrosis (n = 2, 8%) and hemorrhage (n = 3, 12%). A primary diagnosis of renal cell carcinoma was associated with an improved rate of distant failure-free survival (p = 0.05) and progression-free survival (p = 0.08)., Conclusions: SRS provides excellent local control for intraventricular metastases, with acceptable treatment-related toxicity, thereby supporting nonsurgical treatment for these lesions. The propensity for intraventricular dissemination among intraventricular metastases seems to be histologically dependent.

Purpose: The number of brain metastases (BM) is a major consideration in determining patient eligibility for stereotactic radiosurgery (SRS), but the evidence for this popular practice is equivocal. The purpose of this study was to determine whether, following multivariate adjustment, the number and volume of BM held prognostic significance in a cohort of patients initially treated with SRS alone., Methods and Materials: A total of 251 patients with primary malignancies, including non-small cell lung cancer (34%), melanoma (30%), and breast carcinoma (16%), underwent SRS for initial treatment of BM. SRS was used as the sole management (62% of patients) or was combined with salvage treatment with SRS (22%), whole-brain radiation therapy (WBRT; 13%), or resection (3%). Median follow-up time was 9.4 months. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on distant brain failure (DBF), local control (LC), and overall survival (OS)., Results: LC at 1 year was 94.6%, and median time to DBF was 10 months. Median OS was 11.1 months. On multivariate analysis, statistically significant predictors of OS were presence of extracranial disease (hazard ratio [HR], 4.2, P<.001), total tumor volume greater than 2 cm(3) (HR, 1.98; P<.001), age ≥60 years (HR, 1.67; P=.002), and diagnosis-specific graded prognostic assessment (HR, 0.71; P<.001). The presence of extracranial disease was a statistically significant predictor of DBF (HR, 2.15), and tumor volume was predictive of LC (HR, 4.56 for total volume >2 cm(3)). The number of BM was not predictive of DBF, LC, or OS., Conclusions: The number of BM is not a strong predictor for clinical outcomes following initial SRS for newly diagnosed BM. Other factors including total treatment volume and systemic disease status are better determinants of outcome and may facilitate appropriate use of SRS or WBRT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Object: Brain metastases present a therapeutic challenge because patients with metastatic cancers live longer now than in the recent past due to systemic therapies that, while effective, may not penetrate the blood-brain barrier. In the present study the authors sought to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), a new prognostic index that takes into account the histological characteristics of the primary tumor, and the Radiation Therapy Ontology Group Recursive Partitioning Analysis (RPA) system by using a single-institution database of patients who were treated initially with stereotactic radiosurgery (SRS) alone for brain metastases., Methods: Investigators retrospectively identified adult patients who had undergone SRS at a single institution, MD Anderson Cancer Center, for initial treatment of brain metastases between 2003 and 2010 but excluded those who had undergone craniotomy and/or whole-brain radiation therapy at an earlier time; the final number was 251. The Leksell Gamma Knife was used to treat 223 patients, and a linear accelerator was used to treat 28 patients. The patient population was grouped according to DS-GPA scores as follows: 0-0.5 (7 patients), 1 (33 patients), 1.5 (25 patients), 2 (63 patients), 2.5 (14 patients), 3 (68 patients), and 3.5-4 (41 patients). The same patients were also grouped according to RPA classes: 1 (24 patients), 2 (216 patients), and 3 (11 patients). The most common histological diagnoses were non-small cell lung cancer (34%), melanoma (29%), and breast carcinoma (16%). The median number of lesions was 2 (range 1-9) and the median total tumor volume was 0.9 cm(3) (range 0.3-22.9 cm(3)). The median radiation dose was 20 Gy (range 14-24 Gy). Stereotactic radiosurgery was performed as the sole treatment (62% of patients) or combined with a salvage treatment consisting of SRS (22%), whole-brain radiation therapy (12%), or resection (4%). The median duration of follow-up was 9.4 months., Results: In this patient group the median overall survival was 11.1 months. The DS-GPA prognostic index divided patients into prognostically significant groups. Median survival times were 2.8 months for DS-GPA Scores 0-0.5, 3.9 months for Score 1, 6.6 months for Score 1.5, 12.9 months for Score 2, 11.9 months for Score 2.5, 12.2 months for Score 3, and 31.4 months for Scores 3.5-4 (p < 0.0001). In the RPA groups, the median overall survival times were 38.8 months for Class 1, 9.4 months for Class 2, and 2.8 months for Class 3 (p < 0.0001). Neither the RPA class nor the DS-GPA score was prognostic for local tumor control or new lesion-free survival. A multivariate analysis revealed that patient age > 60 years, Karnofsky Performance Scale score ≤ 80%, and total lesion volume > 2 cm(3) were significant adverse prognostic factors for overall survival., Conclusions: Application of the DS-GPA to a database of patients with brain metastases who were treated with SRS appears to be valid and offers additional prognostic refinement over that provided by the RPA. The DS-GPA may also allow for improved selection of patients to undergo initial SRS alone and should be studied further.

Purpose: Determine whether EGFR and KRAS mutations carry prognostic significance in non-small cell lung cancer (NSCLC) patients with brain metastases treated with stereotactic radiosurgery. Methods and Materials: Ninety-four NSCLC patients with brain metastases initially treated with stereotactic radiosurgery were retrospectively reviewed. Both EGFR and KRAS mutation status were recorded in 67 patients: EGFR+/KRAS- status in 9 patients, EGFR-/KRAS+ in 15 patients, and EGFR-/KRAS- in 43 patients. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on overall survival, local control, and distant brain control - all from time of brain metastasis diagnosis. Results: Median overall survival from time of brain metastasis diagnosis was 30.6 months for EGFR+/KRAS-patients, 9.8 months for EGFR-/KRAS+ patients, and 19.1 months for EGFR-/KRAS- patients (p=0.094). Local control at 2 years was 100% for EGFR+/KRAS- patients, 66.7% for EGFR-/KRAS+ patients, and 97.2% for EGFR-/KRAS-patients (p=0.399). Distant brain control at 12 months was achieved in 66.7% of EGFR+/KRAS- patients, 30.0% of EGFR-/KRAS+ patients, and 73.7% of EGFR-/KRAS- patients (p=0.039). On multivariate analysis, the most important predictors of mortality were baseline DS-GPA>2 (HR=0.27; p=0.001), EGFR mutation positivity (HR=0.30; p=0.054), and KRAS mutation positivity (HR=2.12; p=0.056); the most important predictors of distant brain failure were KRAS status (HR=4.44; p=0.004) and extracranial disease (HR=3.28; p=0.058); there was no statistically significant multivariate model identified for local control. Conclusions: In NSCLC patients with brain metastases, KRAS mutations portend higher rates of distant brain failure. Our data also suggests that EGFR portends better overall survival and KRAS portends worse overall survival, though this still needs to be verified by a larger study. [ABSTRACT FROM AUTHOR]

Stereotactic Radiosurgery has become the main treatment for patients with limited number of brain metastases (BM). Recently, with the increasing use of this modality, there is a growth in recurrence cases. Recurrence after radiation therapy can be divided in changes favoring either tumor recurrence or radiation necrosis (RN). Laser Interstitial Thermal Therapy (LITT) is minimally invasive treatment modality that has been used to treat primary and metastatic brain tumors. When associated with real-time thermometry using Magnetic Resonance Imaging, the extent of ablation can be controlled to provide maximum coverage and avoid eloquent areas. The objective of this study was to investigate the use of LITT in the treatment of BM. An extensive review of the relevant literature was conducted and the outcome results are discussed. There is an emphasis on safety and local control rate of patients treated with this modality. The findings of our study suggest that LITT is a viable safe technique to treat recurrent BM, especially in patients with deep-seated lesions where surgical resection is not an option. [ABSTRACT FROM AUTHOR]