Radiotherapy For Brain Metastases Research Articles

Radiotherapy for brain metastases near the end of life in an integrated health care system.

To examine radiotherapy (RT) patterns-of-care and utilization at the end of life (EOL) among non-small cell lung cancer (NSCLC) patients with brain metastasis (BrM) in an integrated health care system. Central tumor registry identified 5,133 patients diagnosed with NSCLC from 2007-2011. BrM were determined by imaging. Patient and clinical characteristics were obtained by chart abstraction. In addition to abstracted variables, graded prognostic assessment (GPA) score of 0-1 was derived by collected data and tested as a predictor of death within 14 or 30 days of RT. On NSCLC presentation, 10% harbored BrM while 7% developed BrM thereafter. Of 900 BrM patients, 15% were not referred for RT, with median time to death of 21 days. Median time to death for 5% not recommended RT was 48 days. Among those receiving brain RT, 11.9% died within 14 days and 23.3% (cumulatively) died within 30 days of treatment. Over 50% with GPA score 0-1 received RT, 11% within 14 days and 21% within 30 days of death; median survival of GPA score 0-1 patients was 49 days. GPA score 0-1 independently predicted for death within 30 days of RT receipt. BrM are common in NSCLC, and most patients are referred for brain RT. A surprising proportion of patients received treatment near the EOL, as 23% died within 30 days of RT. GPA score of 0-1 predicted for death within 30 days of treatment. RT referral, recommendation, and timing should be better tailored to life expectancy, and additional benchmarks for quality of care are needed.

A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis.

This study was conducted to compare the effects of whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRS) in treatment of brain metastasis.A systematical retrieval in PubMed and Embase databases was performed for relative literatures on the effects of WBRT and SRS in treatment of brain metastasis. A Bayesian network meta-analysis was performed by using the ADDIS software. The effect sizes included odds ratio (OR) and 95% confidence interval (CI). A random effects model was used for the pooled analysis for all the outcome measures, including 1-year distant control rate, 1-year local control rate, 1-year survival rate, and complication. The consistency was tested by using node-splitting analysis and inconsistency standard deviation. The convergence was estimated according to the Brooks–Gelman–Rubin method.A total of 12 literatures were included in this meta-analysis. WBRT + SRS showed higher 1-year distant control rate than SRS. WBRT + SRS was better for the 1-year local control rate than WBRT. SRS and WBRT + SRS had higher 1-year survival rate than the WBRT. In addition, there was no difference in complication among the three therapies.Comprehensively, WBRT + SRS might be the choice of treatment for brain metastasis.

Pseudoprogression in Non-Small Cell Lung Cancer Brain Metastases Attributable to the Anti-PD-1 Antibody Nivolumab

Pseudoprogression is a challenging obstacle in the interpretation of therapeutic response to radiation and chemotherapies for metastatic brain lesions. Combination of stereotactic radio surgery post-treatment effects and anti-PD-1 antibody therapy may cause benign edematous enhancements in treated brain metastases which mimic tumor progression. Herein we report a case of a patient who experienced pseudoprogression in previously irradiated brain metastases after systemic therapy with immune checkpoint inhibitors targeting PD-1.

TEP/tomodensitométrie et imagerie spectroscopique par résonance magnétique tridmensionnelle pour le diagnostic différentiel entre radionécrose cérébrale et rechute tumorale après irradiation en conditions stéréotaxiques de métastases cérébrales : place dans l’arbre décisionnel

PurposeAfter stereotactic radiation therapy for brain metastases, one of the complications is radionecrosis. Differential diagnosis with tumour recurrence can be helped by different methods of imaging, although histology remains the gold standard. According to the treatment centres, practice diverges. The objective of this single-centre retrospective study was to define the power of MRI, PET scan and NMR spectroscopy to establish a decision tree. Material and methodsThis study included patients who underwent stereotactic radiation therapy for brain metastases, and required, during follow-up, both a PET scan and NMR spectroscopy in order to differentiate a radiation necrosis and tumour recurrence. From 2010 to 2015, 25 patients were consistent with these criteria. ResultsConventional MRI technique, with the T1/T2 mismatch criterion, had a specificity of 75% and a sensitivity of only 44%. A lesion quotient greater than 0.3 diagnosed a recurrence with a sensitivity of 92%. PET scan combined the best sensitivity and specificity, respectively of 92% and 69%. Whatever the thresholds used in NMR spectroscopy for choline/N-acetylaspartate and choline/creatin ratios, the power of this imaging modality did not exceed that of PET scan. ConclusionThe criteria described in conventional MRI cannot by themselves establish the differential diagnosis. In first intention in case of doubt, PET scan should be done, combining the best sensitivity and specificity, whereas NMR spectroscopy used in combination does not improve these factors.

Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases

AimsStereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments. Materials and methodsA Markov model was constructed for patients treated with SRS alone or SRS plus upfront WBRT based on largely randomised clinical trials. Costs were based on 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) and effectiveness was measured in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were carried out. Strategies were evaluated from the healthcare payer's perspective with a willingness-to-pay threshold of $100 000 per QALY gained. ResultsIn the base case analysis, the median survival was 9 months for both arms. SRS alone resulted in an ICER of $9917 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation in cognitive decline rates for both groups and median survival rates, but the SRS alone remained cost-effective for most parameter ranges. ConclusionsBased on the current available evidence, SRS alone was found to be cost-effective for patients with one to three brain metastases compared with upfront WBRT plus SRS.

Study of the impact of cytomegalovirus-encephalopathy on survival of brain cancer patients undergoing treatment with radio(chemo)therapy.

2036 Background: As recently demonstrated (Neurooncology, 2016), neurological decline of patients with brain cancer (high grade glioma, brain metastases) during radio(chemo)therapy (RCT) of the brain is oftentimes caused by CMV-encephalopathy but not disease progression or therapeutic complications. We examined the impact of clinical and serological CMV-status on the survival one year after the onset of radio(chemo)therapy of the brain. Methods: 118 patients requiring whole-brain radiotherapy for brain metastases (n = 55) or local RCT of the brain for high-grade gliomas (n = 63) were observed in the prospective GLIO-CMV-01 study. MRIs and blood samples were obtained before, halfway through, and at the end of radiotherapy. MRIs were screened for disease progression or increased intracranial pressure. Blood was tested for anti-CMV immunoglobulin (Ig)M, anti-CMV IgG, and CMV DNA. Results: 68 of 118 (58%) patients were positive for anti-CMV IgG before radio(chemo)therapy. 28 of those 68 (41%) developed CMV-viremia during or up to 28 days after the end of irradiation. 21 of those 28 (75%) required treatment for symptomatic CMV-associated encephalopathy. One year after the start of RCT, survival was 72% (34/47) (no encephalopathy, anti-CMV-IgG+) or 68% (34/50) (no encephalopathy, anti-CMV-IgG-) versus 38% (8/21) (encephalopathy) (p = 0.0034). Conclusions: Symptomatic CMV-encephalopathy all but doubles the mortality of brain cancer patients within one year of RCT, despite antiviral treatment with ganciclovir. These findings heavily underline the importance to identify patients with increased risk profile for developing CMV-encephalopathy before initiating RCT.

(P098) A Treatment Planning Comparison Between Novel Cobalt-60 With a Ring Type Gantry and Robotic Linear Accelerator Based Stereotactic Radiosurgery / Radiotherapy for Brain Metastases

(P098) A Treatment Planning Comparison Between Novel Cobalt-60 With a Ring Type Gantry and Robotic Linear Accelerator Based Stereotactic Radiosurgery / Radiotherapy for Brain Metastases

Stereotactic radiation therapy of brain metastases from colorectal cancer: A single institution cohort

PurposeThe brain remains an uncommon site of colorectal cancer metastases. Due to the improvement of overall colorectal cancer patient survival, the incidence of brain metastases will likely rise. We report the efficacy and safety of hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery, and its role in colorectal cancer brain metastasis management. Methods and materialBetween June 2010 and December 2014, fifteen consecutive patients received hypofractionnated stereotactic radiation therapy or stereotactic radiosurgery as first local therapy or following surgical removal for colorectal cancer brain metastases. The primary endpoint was overall survival. Secondary endpoints were brain progression free survival, in field control rates and safety. ResultsMedian follow-up was 41 months (95% confidence interval [CI]: [8.9–73.1 months]), median overall survival was 8 months (95% CI [4.7–11.3 months]), and median brain progression-free survival was 5 months (95% CI [3.9–6.1 months]). Five in field recurrences were observed, which makes a control rate per metastases at 6 and 12 months of 77.8% (95% CI [74.34%–81.26%]), 51.9% (95% CI [44.21%–59.59%]) respectively. Over the 19 treatment sequences, five in field recurences were observed: 6, 12 and 18 months control rate per treatment sequence were 93.3% (95% CI [90.42%–96.18%]), 68.1% (95% CI [62.03%–74.17%]) and 45.4% (95% CI [36.14%–54.66%]) respectively. Immediate tolerance was good with no toxicity grade III or more. Long-term toxicity included two radionecrosis among which, one was symptomatic. DiscussionThe results of this retrospective analysis suggest that hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery are effective and safe treatment modalities for single and multiple small brain metastases from colorectal cancer. However, results need to be confirmed by multicenter, collected data.

PV-0457: Delay between planning and stereotactic radiotherapy for brain metastases: margins still accurate?

PV-0457: Delay between planning and stereotactic radiotherapy for brain metastases: margins still accurate?

EP-1103: Are hippocampi considered organs at risks during stereotactic radiotherapy for brain metastases?

EP-1103: Are hippocampi considered organs at risks during stereotactic radiotherapy for brain metastases?

EP-1101: Leptomeningeal spread after stereotactic radiation for brain metastases from breast cancer

EP-1101: Leptomeningeal spread after stereotactic radiation for brain metastases from breast cancer

Stereotactic ablative radiation therapy for brain metastases with volumetric modulated arc therapy and flattening filter free delivery: feasibility and early clinical results.

For selected patients with brain metastases (BMs), the role of stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) is well recognized. The recent introduction of flattening filter free (FFF) delivery during linac-based SRS or SFRT allows shorter beam-on-time, improving patients' comfort and facility workflow. Nevertheless, limited experiences evaluated the impact of FFF linac-based SRS and SFRT in BMs treatment. Aim of the current study was to analyze SRS/SFRT linac-based FFF delivery for BMs in terms of dosimetric and early clinical results. Patients with life expectancy >3months, number of BMs <5, diameter <3cm, and controlled or synchronous primary tumor received SRS/SFRT. The prescribed total dose and fractionation, based on BMs size and proximity to organs at risk, ranged from 15Gy in 1 fraction to 30Gy in 5 fractions. A FFF volumetric modulated arc therapy (VMAT) plan was generated with one or two coplanar partial arcs. Toxicity was assessed according to CTCAE v4.0. From April 2014 to February 2016, 45 patients (89 BMs) were treated with SRS/SFRT linac-based FFF delivery. The mean beam-on-time was 140s for each lesion (range 90-290s) and the average brain Dmean was 1Gy (range 0.1-4.8Gy). At the time of analysis, local control was reported in 93.2% (83/89BMs). With a median follow-up time of 12months (range 1-27months), the median overall survival was 14months and the 6-month overall survival was 77%. Finally, the median intracranial disease control was 11months. Acute and late toxicities were acceptable without severe events (no adverse events ≥G2 were recorded). These preliminary results highlighted the feasibility and safety of linac-based SRS/SFRT with FFF mode for BMs patients. A longer follow-up is necessary to confirm the efficacy of this treatment modality in BM patients.

P18.16 Changes in health-related quality of life and neurocognitive functioning in individual patients treated with stereotactic radiotherapy for brain metastases

Abstract Background: Stereotactic radiotherapy (SRT) is believed to result in a similar survival rate as whole-brain radiotherapy for treatment of brain metastases, with a less profound impact on cognition and health-related quality of life (HRQoL). Recently it has been shown that, on group level, brain metastases patients treated with SRT maintain their pre-treatment levels of cognition and HRQoL. Although stable on group level, this may not hold true for individual patients. Objective: We sought to evaluate changes in cognition and HRQoL on the individual patient level three and six months after SRT. Methods: A total of 55 patients completed HRQoL questionnaires and underwent neurocognitive testing prior to SRT and 3 and/or 6 months after SRT. The EORTC QLQ-C30 and BN20 questionnaires were used to assess HRQoL and a standardized test battery to assess neurocognitive functioning. Changes in HRQoL and cognition were evaluated on (1) a scale/domain level and (2) patient level. First, percentage of patients showing a clinically relevant improvement, stable score or deterioration on each of 8 predetermined HRQoL scales and 7 cognitive domains were calculated. Next, patients were categorized into 4 groups, separately for HRQoL and cognition: decline (only worsening of HRQoL or cognition), both (decline and improvement), stable (no detectable change in any scale/domain) and improvement (only improvement). Results: Three months after SRT, a decline in the 8 different HRQOL scales was observed in 16-61% of the patients, while 20-71% remained stable and 16-40% improved. Six months after SRT, 8-47% of the patients had worse scores on the 8 HRQoL scales, 18-75% the same scores and 11-34% better scores. On the 7 different neurocognitive functioning domains, only 3-8% of the patients worsened, 78-100% remained stable, while 3-17% showed an improvement three months after SRT. These percentages were similar six months after SRT; 8-20% of the patients deteriorated on the 7 domains, 73-100% remained stable and 4-8% improved. Changes in HRQoL and cognition on patient level were evaluated for two different time periods (0-3 months and 3-6 months). For HRQoL, 22% and 21% of the patients worsened in the period 0-3 and 3-6 months respectively, 64% and 58% both improved and deteriorated, 2% and 3% were stable and 12% and 18% showed improvement only. For cognition, the percentages were as follows: 14% and 33% showed a decline only, 6% and 4% both a decline and improvement, 67% and 50% stable scores and 14% and 13% an improvement only. Conclusion: In line with the results at group level, most brain metastases patients treated with SRT maintained their pre-treatment levels of cognition for at least 6 months. In contrast, changes in HRQoL scores for the different scales differed considerably on an individual patient level, and most patients showed both deterioration and improvement in various HRQoL scales in the first 6 months after SRT.

Clinical outcomes of gastrointestinal brain metastases treated with radiotherapy

BackgroundBrain metastases of gastrointestinal origin are a rare occurrence. Radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is an effective established treatment modality in either the definitive or adjuvant setting. The aim of this study is to assess the long-term clinical outcomes of patients with gastrointestinal (GI) brain metastases treated with SRS or WBRT.MethodsIn this single institutional retrospective review, we detail the outcomes of patients diagnosed with metastatic brain tumors from an adenocarcinoma gastrointestinal primary. Patients were treated using stereotactic radiosurgery or whole brain radiation therapy. Initial site control (defined as lesions visualized on imaging at time of treatment), new site control (defined as new intracranial lesions visualized on follow-up imaging), and overall survival were calculated using the Kaplan-Meier method.ResultsThirty-three patients were treated from August 2008 to December 2015. Primary malignancy locations were as follows: 18 colon, 6 esophagus, 4 rectum, 5 other. Median total dose delivered was 25 Gy (18–35 Gy) in a median of 4 fractions for SRS and 30 Gy (10.8–40 Gy) in 10 fractions for WBRT. Crude initial site control at last radiographic follow-up was 64.3% after SRS and 41.7% after WBRT. Eleven of the 28 brain lesions (39.3%) treated with SRS had resection of the SRS-treated lesion prior to radiation therapy. Five of the twelve patients (41.7%) undergoing WBRT underwent cranial resection prior to radiation therapy. Crude new site control at last radiographic follow-up was 46.4% after SRS and 83.3% after WBRT. Kaplan-Meier analysis of overall survival did not show any statistically significant difference between WBRT and SRS (p = 0.424). Median overall survival for SRS patients was 5.2 months (0.5–57.5) and for WBRT patients 4.4 months (0–15). Kaplan-Meier analysis of new site control was significantly improved with WBRT versus SRS (p = 0.017). Total dose, treatment with WBRT, and active extracranial disease were statistically significant on multivariate analysis for new site control (p < 0.05).ConclusionsSurvival and intracranial disease control are poor following RT for brain metastases from GI primaries. In this small series, outcomes are worse than published series for other primary malignancies metastatic to the brain and further research into methods of local control improvement is warranted. Future studies should explore the utility of dose escalation or radiosensitization in this patient population.

Use of Systemic Therapy Concurrent With Cranial Radiotherapy for Cerebral Metastases of Solid Tumors.

The incidence of brain metastases of solid tumors is increasing. Local treatment of brain metastases is generally straightforward: cranial radiotherapy (e.g., whole-brain radiotherapy or stereotactic radiosurgery) or resection when feasible. However, treatment becomes more complex when brain metastases occur while other metastases, outside of the central nervous system, are being controlled with systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies). It is known that some anticancer agents can increase the risk for neurotoxicity when used concurrently with radiotherapy. Increased neurotoxicity decreases quality of life, which is undesirable in this predominantly palliative patient group. Therefore, it is of utmost importance to identify the compounds that should be temporarily discontinued when cranial radiotherapy is needed.This review summarizes the (neuro)toxicity data for combining systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies) with concurrent radiotherapy of brain metastases. Because only a limited amount of high-level data has been published, a risk assessment of each agent was done, taking into account the characteristics of each compound (e.g., lipophilicity) and the microenvironment of brain metastasis. The available trials suggest that only gemcitabine, erlotinib, and vemurafenib induce significant neurotoxicity when used concurrently with cranial radiotherapy. We conclude that for most systemic therapies, the currently available literature does not show an increase in neurotoxicity when these therapies are used concurrently with cranial radiotherapy. However, further studies are needed to confirm safety because there is no high-level evidence to permit definitive conclusions. The Oncologist 2017;22:222-235Implications for Practice: The treatment of symptomatic brain metastases diagnosed while patients are receiving systemic therapy continues to pose a dilemma to clinicians. Will concurrent treatment with cranial radiotherapy and systemic therapy (chemotherapeutics, molecular targeted agents, and monoclonal antibodies), used to control intra- and extracranial tumor load, increase the risk for neurotoxicity? This review addresses this clinically relevant question and evaluates the toxicity of combining systemic therapies with cranial radiotherapy, based on currently available literature, in order to determine the need to and interval to interrupt systemic treatment.

Radiotherapy for Brain Metastases from Renal Cancer and Utility of Prognostic Indices: Real Life Experience from The Beatson West of Scotland Cancer Centre

Radiotherapy for Brain Metastases from Renal Cancer and Utility of Prognostic Indices: Real Life Experience from The Beatson West of Scotland Cancer Centre

Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling.

Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen. We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan-Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT. 10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3-12 fractions (BED range: 29-100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10 yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10 yield 2-year LC rates of 62%, 69% and 81%, respectively. FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose-response relationship that should be explored in prospective trials. Advances in knowledge: This review identified a dose-response relationship for LC in patients treated with FSRT for brain metastases.

Clinical outcome of tyrosine kinase inhibitors alone or combined with radiotherapy for brain metastases from epidermal growth factor receptor (EGFR) mutant non small cell lung cancer (NSCLC).

This study compared treatment outcomes between TKI monotherapy and TKI administration combined with brain radiotherapy (TKI + RT) in 133 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). We also evaluated the association of different epidermal growth factor receptor (EGFR) mutation subtypes with treatment outcome. To screen for potential variables affecting cranial progression free survival (PFS) and overall survival (OS), we performed univariate and multivariate analysis based on Cox proportional-hazards models. Median cranial PFS and OS were longer for the TKI + RT group (n = 67) than TKI alone group (n = 66). Intracranial metastasis correlated with a better median OS than extracranial metastasis. For patients with exon 21 mutations, TKI + RT yielded a better median OS and cranial PFS than TKI alone. However, there were no significant differences in median OS and cranial PFS between the two treatment groups for patients with exon 19 deletions. Thus EGFR-mutant NSCLC patients with BM could benefit more from TKI + RT than from TKI monotherapy, especially when they suffer from exon 21 mutations. However, TKI + RT confers no advantage over TKI treatment alone for patients with exon 19 deletions. These results underscore the urgent need to develop individualized disease management strategies in clinical practice.

Radiosurgery vs radiation therapy for brain metastases: A waning controversy.

Radiosurgery vs radiation therapy for brain metastases: A waning controversy.

Patterns of failure after brain metastases radiotherapy: reflections on the importance for treatment and clinical trials reporting.

In many ongoing clinical trials, new strategies for radiotherapy of brain metastases are currently being investigated. A post surgical focal cavity stereotactic radiosurgery and the developing role of a hippocampal-sparing whole brain radiotherapy are of the highest importance. The evaluation of spatial patterns of metastases failure after radiotherapy is a powerful tool for assessing the potential benefit of new different radiotherapy approaches, which enables to identify possible directions leading to better radiotherapy techniques and to modify general management for newly diagnosed brain metastases. The purpose of this article is to present a mix between trial data and philosophical point of view for discussion about the importance of systematic evaluation of spatial patterns of failure in all ongoing trials investigating new approaches in local brain metastases treatment.