Novel risk stratification score for predicting early distant brain failure and salvage whole-brain radiotherapy after stereotactic radiosurgery for brain metastases.
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ABSTRACT:
SUBMITTER: Press RH
PROVIDER: S-EPMC4618074 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
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Novel risk stratification score for predicting early distant brain failure and salvage whole-brain radiotherapy after stereotactic radiosurgery for brain metastases.
Press Robert H RH Prabhu Roshan S RS Nickleach Dana C DC Liu Yuan Y Shu Hui-Kuo G HK Kandula Shravan S Patel Kirtesh R KR Curran Walter J WJ Crocker Ian I
Cancer 20150804 21
<h4>Background</h4>The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole-brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score to stratify patients' risk for these events.<h4>Methods</h4>The records of 270 patients with brain metastases who were treated with SRS between 2003 and 2012 were reviewed. Pretreatment patient and tumor characteristics were anal ...[more]
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Project description:Stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HFSRT) have become important treatment modalities for brain metastases. While effective, there are still areas of extensive debate on its appropriate use in patients with life-limiting diseases. This review provides an overview of the indications and challenges of SRS and HFSRT in the management of brain metastases.
| S-EPMC3656557 | biostudies-literature
Project description:Introduction:Due to the neurocognitive side effects of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) is being used with increasing frequency. The use of SRS is expanding for patients with multiple (>4) brain metastases (BM). This study summarizes our institutional experience with single-fraction, linear-accelerator-based SRS for multiple BM. Methods and materials:All patients who were treated between January 1, 2013, and September 30, 2015, with single-fraction SRS for ?4 BM were included in this institutional review board-approved, retrospective, single-institution study. Patients were treated with linear accelerator-based image guided SRS. Results:A total of 59 patients with ?4 BM were treated with single-fraction SRS. The median follow-up was 15.2 months, and the median overall survival for the entire cohort was 5.8 months. The median number of treated lesions per patient was 5 (range, 4-23). Per patient, the median planning target volume (PTV) was 4.8?cc (range, 0.7-28.8?cc). The prescribed dose across all 380 BM for the 59 patients ranged from 7 to 20?Gy. The median of the mean dose to the total PTV was 19.5?Gy. Although the number of treated lesions (4-5 vs ?6) did not influence survival, better survival was noted for a total PTV <10?cc versus ?10?cc (7.1 vs 4.2 months, respectively; P?=?.0001). A mean dose of ?19?Gy to the entire PTV was also associated with increased survival (6.6 vs 5.0 months, respectively; P?=?.0172). Patients receiving a dose of >12?Gy to ?10?cc of normal brain had worse survival (5.1 vs 8.6 months, respectively; P?=?.0028). Conclusion:In single-fraction SRS for patients with multiple BM, smaller total tumor volume, higher total dose, and lower volume of normal brain receiving >12?Gy were associated with increased survival. These data suggest that using SRS for the treatment of multiple BM is efficacious and that outcomes may be affected more by total tumor volume than by the number of lesions.
| S-EPMC5707418 | biostudies-literature
Project description:BackgroundUntil 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS).MethodsBetween 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data.ResultsAfter a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65-2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively.ConclusionFractionation does not decrease LPFS. Even for small radioresistant brain metastases (< 3 cm), HFSRT, with 3 or 6 fractions, leads to an excellent local control rate of 72% at 1 year with a rate of 7.1% of radionecrosis. HFSRT is a safe and efficient alternative treatment to SRS.
| S-EPMC6064124 | biostudies-literature
Project description:Maintenance of quality of life is the primary goal during treatment of brain metastases (BM). This is a protocol of an ongoing phase III randomised multicentre study. This study aims to determine the exact additional palliative value of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with 4-10 BM.The study will include patients with 4-10 BM from solid primary tumours diagnosed on a high-resolution contrast-enhanced MRI scan with a maximum lesional diameter of 2.5 cm in any direction and a maximum cumulative lesional volume of 30 cm3. Patients will be randomised between WBRT in five fractions of 4 Gy to a total dose of 20 Gy (standard arm) and single dose SRS to the BMs (study arm) in the range of 15-24 Gy. The largest BM or a localisation in the brainstem will determine the prescribed SRS dose. The primary endpoint is difference in quality of life (EQ5D EUROQOL score) at 3 months after radiotherapy with regard to baseline. Secondary endpoints are difference in quality of life (EQ5D EUROQOL questionnaire) at 6, 9 and 12 months after radiotherapy with regard to baseline. Other secondary endpoints are at 3, 6, 9 and 12 months after radiotherapy survival, Karnofsky ? 70, WHO performance status, steroid use (mg), toxicity according to CTCAE V4.0 including hair loss, fatigue, brain salvage during follow-up, type of salvage, time to salvage after randomisation and Barthel index. Facultative secondary endpoints are neurocognition with the Hopkins verbal learning test revised, quality of life EORTC QLQ-C30, quality of life EORTC BN20 brain module and fatigue scale EORTC QLQ-FA13.Worldwide, most patients with more than 4 BM will be treated with WBRT. Considering the potential advantages of SRS over WBRT, i.e. limiting radiation doses to uninvolved brain and a high rate of local tumour control by just a single treatment with fewer side effects, such as hair loss and fatigue, compared to WBRT, SRS might be a suitable alternative for patients with 4-10 BM.Trial registration number: NCT02353000 , trial registration date 15th January 2015, open for accrual 1st July 2016, nine patients were enrolled in this trial on 14th April 2017.
| S-EPMC5526250 | biostudies-literature
Project description:Brain metastases (BM) affect approximately a third of all cancer patients with systemic disease. Treatment options include surgery, whole-brain radiotherapy, or stereotactic radiosurgery (SRS) while chemotherapy has only limited activity. In cases where patients undergo resection before irradiation, intraoperative radiotherapy (IORT) to the tumor bed may be an alternative modality, which would eliminate the repopulation of residual tumor cells between surgery and postoperative radiotherapy. Accumulating evidence has shown that high single doses of ionizing radiation can be highly efficient in eliciting a broad spectrum of local, regional, and systemic tumor-directed immune reactions. Furthermore, immune checkpoint blockade (ICB) has proven effective in treating antigenic BM and, thus, combining IORT with ICB might be a promising approach. However, it is not known if a low number of residual tumor cells in the tumor bed after resection is sufficient to act as an immunizing event opening the gate for ICB therapies in the brain. Because immunological data on tumor bed irradiation after resection are lacking, a rationale for combining IORT with ICB must be based on mechanistic insight from experimental models and clinical studies on unresected tumors. The purpose of the present review is to examine the mechanisms by which large radiation doses as applied in SRS and IORT enhance antitumor immune activity. Clinical studies on IORT for brain tumors, and on combined treatment of SRS and ICB for unresected BM, are used to assess the safety, efficacy, and immunogenicity of IORT plus ICB and to suggest an optimal treatment sequence.
| S-EPMC5522878 | biostudies-literature
Project description:PurposeThis retrospective study aimed to determine the prognostic factors associated with overall survival after intracranial local and distant recurrence in patients undergoing stereotactic radiosurgery (SRS) for brain metastases.Patients and methodsClinical characteristics and therapeutic parameters of 251 patients, who were treated with initial stereotactic radiosurgery for brain metastases and later experienced intracranial recurrence, were analyzed to identify prognostic factors of post-recurrence overall survival (PROS). A Cox proportional hazard model was applied for univariate and multivariate analyses.ResultsAmong the 251 patients, the median post-recurrence overall survival was 8 months, and the six-month PROS rate was 60.2%. The interval from initial radiosurgery treatment to intracranial recurrence (hazard ratio [HR]:0.970), the number of brain recurrent tumors (HR:1.245), the number of extracranial metastatic organs (HR:1.183), recursive partition analysis (RPA) (HR:1.778), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (HR:2.442) were identified as independent prognostic factors. The patients who received local treatment for solitary brain recurrence achieved better survival (the median survival time after recurrence was 22 months). In patients without extracranial metastasis, the median post-recurrence overall survival of the local treatment group was longer than that in the whole brain radiation therapy (WBRT) group (P<0.001) and the systemic therapy group (P<0.001).ConclusionA shorter interval from initial stereotactic radiosurgery to recurrence, an increasing number of brain recurrences and extracranial metastatic organs, and poor RPA and ECOG PS values are associated with poor post-recurrence prognosis. When the number of brain recurrent tumors and extracranial metastatic organs was limited, local treatment including stereotactic radiosurgery, surgery or intensity-modulated radiation therapy (IMRT) improved the post-recurrence overall survival.
| S-EPMC7276324 | biostudies-literature
Project description: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.
| S-EPMC7268472 | biostudies-literature
Project description:Purpose:Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS?+?IMT, and SRS?+?targeted therapy. Methods and materials:Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results:A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS?+?IMT: 48; and SRS?+?targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS?+?IMT, and SRS?+?targeted therapy were 11.5%, 60%, and 10%, respectively (P?<?.001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS?+?IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P?=?.003) and compared with SRS?+?targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P?=?.001).One-year local control for SRS, SRS?+?IMT, and SRS?+?targeted therapy was 66%, 85%, and 72%, respectively (P?=?.044). On multivariate analysis, after adjusting for dose, SRS?+?IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P?=?.04). Conclusions:SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result.
| S-EPMC5707419 | biostudies-literature
Project description:Brain metastasis (BM) represents a common complication of cancer, and in the modern era requires multi-modal management approaches and multi-disciplinary care. Traditionally, due to the limited efficacy of cytotoxic chemotherapy, treatment strategies are focused on local treatments alone, such as whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and resection. However, the increased availability of molecular-based therapies with central nervous system (CNS) penetration now permits the individualized selection of tailored systemic therapies to be used alongside local treatments. Moreover, the introduction of immune checkpoint inhibitors (ICIs), with demonstrated CNS activity has further revolutionized the management of BM patients. The rapid introduction of these cancer therapeutics into clinical practice, however, has led to a significant dearth in the published literature about the optimal timing, sequencing, and combination of these systemic therapies along with SRS. This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis.
| S-EPMC8345095 | biostudies-literature
Project description:BackgroundBrain metastases (BM) pose a significant problem in patients with metastatic renal-cell carcinoma (mRCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.Patients and methodsThe mRCC patients with BM treated with SRS were reviewed. Patient demographics, clinical history, and SRS treatment parameters were identified.ResultsAmong 268 patients with mRCC treated between 2006 and 2015, 38 patients were identified with BM. A total of 243 BM were treated with SRS with 1 to 26 BMs treated per SRS session (median, 2 BMs). The median (range) BM size was 0.6 (0.2-3.1) cm and median (range) SRS treatment dose was 18 (12-24) Gy. Treated BM local control rates at 1 and 2 years were 91.8% (95% confidence interval, 85.7-95.4) and 86.1% (95% confidence interval, 77.1-91.7), respectively. BM control declined for larger tumors. Survival after 1-year was 57.5% (95% CI 40.2-71.4) for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM. Survival was prognostic based on International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups in patients with < 5 BM. Two patients experienced grade 3 radiation necrosis requiring surgical intervention.ConclusionSRS is effective in controlling BM in patients with mRCC. Over half of treated patients survive past a year, and no differences in survival were noted in patients with > 5 metastases. Prognostic risk categories based on systemic disease (IMDC) are predictive of survival in this BM population, with limited rates of symptomatic radiation necrosis.
| S-EPMC6563340 | biostudies-literature