Hypofractionated and single-fraction radiosurgery for brain metastases with sex as a key predictor of overall survival.
Ontology highlight
ABSTRACT:
SUBMITTER: Mangesius J
PROVIDER: S-EPMC8060341 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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:BACKGROUND:Hypofractionated-SRS (HF-SRS) may allow for improved local control and a reduced risk of radiation necrosis compared to single-fraction-SRS (SF-SRS). However, data comparing these two treatment approaches are limited. The purpose of this study was to compare clinical outcomes between SF-SRS versus HF-SRS across our multi-center academic network. METHODS:Patients treated with SF-SRS or HF-SRS for brain metastasis from 2013 to 2018 across 5 radiation oncology centers were retrospectively reviewed. SF-SRS dosing was standardized, whereas HF-SRS dosing regimens were variable. The co-primary endpoints of local control and radiation necrosis were estimated using the Kaplan Meier method. Multivariate analysis using Cox proportional hazards modeling was performed to evaluate the impact of select independent variables on the outcomes of interest. Propensity score adjustments were used to reduce the effects confounding variables. To assess dose response for HF-SRS, Biologic Effective Dose (BED) assuming an ?/? of 10 (BED10) was used as a surrogate for total dose. RESULTS:One-hundred and fifty six patients with 335 brain metastasis treated with SF-SRS (n?=?222 lesions) or HF-SRS (n?=?113 lesions) were included. Prior whole brain radiation was given in 33% (n?=?74) and 34% (n?=?38) of lesions treated with SF-SRS and HF-SRS, respectively (p?=?0.30). After a median follow up time of 12?months in each cohort, the adjusted 1-year rate of local control and incidence of radiation necrosis was 91% (95% CI 86-96%) and 85% (95% CI 75-95%) (p?=?0.26) and 10% (95% CI 5-15%) and 7% (95% CI 0.1-14%) (p?=?0.73) for SF-SRS and HF-SRS, respectively. For lesions >?2?cm, the adjusted 1?year local control was 97% (95% CI 84-100%) for SF-SRS and 64% (95% CI 43-85%) for HF-SRS (p?=?0.06). On multivariate analysis, SRS fractionation was not associated with local control and only size ?2?cm was associated with a decreased risk of developing radiation necrosis (HR 0.21; 95% CI 0.07-0.58, p?<?0.01). For HF-SRS, 1?year local control was 100% for lesions treated with a BED10???50 compared to 77% (95% CI 65-88%) for lesions that received a BED10?<?50 (p?=?0.09). CONCLUSIONS:In this comparison study of dose fractionation for the treatment of brain metastases, there was no difference in local control or radiation necrosis between HF-SRS and SF-SRS. For HF-SRS, a BED10 ??50 may improve local control.
| S-EPMC7257186 | biostudies-literature
Project description:BackgroundThe benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear.ObjectivesTo compare the efficacy and safety of surgery or SRS plus WBRT with that of surgery or SRS alone for treatment of brain metastases in patients with systemic cancer.Search methodsWe searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL) up to May 2013 and annual meeting proceedings of ASCO and ASTRO up to September 2012 for relevant studies.Selection criteriaRandomised controlled trials (RCTs) comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases.Data collection and analysisTwo review authors undertook the quality assessment and data extraction. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), health related quality of life (HRQL) and neurological adverse events. Hazard ratios (HR), risk ratio (RR), confidence intervals (CI), P-values (P) were estimated with random effects models using Revman 5.1 MAIN RESULTS: We identified five RCTs including 663 patients with one to four brain metastases. The risk of bias associated with lack of blinding was high and impacted to a greater or lesser extent on the quality of evidence for all of the outcomes. Adding upfront WBRT decreased the relative risk of any intracranial disease progression at one year by 53% (RR 0.47, 95% CI 0.34 to 0.66, P value < 0.0001, I(2) =34%, Chi(2) P value = 0.21, low quality evidence) but there was no clear evidence of a difference in OS (HR 1.11, 95% CI 0.83 to 1.48, P value = 0.47, I(2) = 52%, Chi(2) P value = 0.08, low quality evidence) and PFS (HR 0.76, 95% CI 0.53 to 1.10, P value = 0.14, I(2) = 16%, Chi(2) P value = 0.28, low quality evidence). Subgroup analyses showed that the effects on overall survival were similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The evaluation of the impact of upfront WBRT on NF, HRQL and neurological adverse events was limited by the unclear and high risk of reporting, performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.Authors' conclusionsThere is low quality evidence that adding upfront WBRT to surgery or SRS decreases any intracranial disease progression at one year. There was no clear evidence of an effect on overall and progression free survival. The impact of upfront WBRT on neurocognitive function, health related quality of life and neurological adverse events was undetermined due to the high risk of performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.
| S-EPMC6457788 | biostudies-literature
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:PURPOSE:Since the introduction of ipilimumab (IPI) for the treatment of patients with metastatic malignant melanoma, we have observed remarkable responses after hypofractionated whole brain irradiation (WBRT) or stereotactic radiotherapy (STX) for brain metastases of malignant melanoma. We sought to investigate the impact of the sequence of these treatment modalities. METHODS:We retrospectively evaluated the survival of melanoma patients with brain metastases who were treated with WBRT or STX and received IPI in close temporal relation between October 2010 and March 2015. Follow-up was obtained until November 2016. A total of 27 patients with advanced melanoma and brain metastases who were treated with WBRT before 2010, and who had not received IPI, served as historical controls. RESULTS:We identified a total of 41 patients of whom 15 were treated with STX, 7 with a combination of STX and WBRT and 19 with WBRT alone. All patients received at least 2 doses of IPI. The median time interval between radiotherapy and IPI was 2 months. Patients treated with IPI after radiotherapy had a censored median survival of 11 months, compared with 3 months for the patients who received IPI prior to radiotherapy. Patients who received IPI before radiotherapy showed a similar survival as historical controls, who had not received IPI. We observed long-term survivors after radiotherapy of brain metastases followed by IPI. CONCLUSIONS:These data suggest that the sequence of RT and immune checkpoint inhibition with IPI may be crucial for the success of combined modality treatment of melanoma brain metastases.
| S-EPMC6267133 | biostudies-literature
Project description:Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole-brain radiotherapy (WBRT) improved local control rates compared with WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to a greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents, and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.
| S-EPMC6165316 | biostudies-other
Project description:PurposeThe latest version of the Gamma Knife, the Icon, allows for immobilization with a mask in lieu of the traditional frame during stereotactic radiosurgery. There have been some concerns regarding extent of immobilization during single fraction frameless treatment and potential effect on outcomes. As such, we reviewed outcomes in patients with brain metastases treated in a single fraction using either a frame or mask on the Gamma Knife Icon at our institution.Methods and materialsWe reviewed the records of 95 patients with a total of 374 metastases treated between May 2019 and January 2021. Thirty-nine patients (41%) were treated using the Leksell frame with the remainder being immobilized with a mask. The median number of metastatic lesions was 2 (1-20). The median prescription dose was 20 Gy (11.5-24 Gy). Odds ratios were generated to identify predictors of mask use. Kaplan-Meier analysis was used to calculate survival, local failure, and distant failure rates. Cox regression was used to identify predictors of survival. Propensity matching was used to account for indication bias.ResultsOf the 95 patients treated, 88 (93%) had follow-up with a median duration of 5 months (1-18). Frame utilization was more likely with 6 to 10 brain metastases. Median overall survival was not reached and was 70% and 60% at 6 and 12 months for the entire cohort, respectively. There was no significant difference in survival by immobilization method (P = .12). Six patients had local failure in 10 total lesions (3 patients in each group). After propensity matching the 12 month tumor local control was 96% and 85% for framed and frameless cases, respectively (P = .07).ConclusionsFrameless mask-based stereotactic radiosurgery using the Gamma Knife Icon is feasible and maintains the excellent local control seen with the use of the headframe.
| S-EPMC8498737 | biostudies-literature
Project description:First-line stereotactic radiosurgery (SRS) is now considered the preferred treatment over whole brain radiation therapy (WBRT) for limited brain metastases arising from most tumor histologies. This standard was reached following the consistent results of multiple phase III studies which demonstrated that, despite improved CNS control, the addition of WBRT to SRS does not improve overall survival (OS) and is associated with a reduction in cognitive function. Thus, it may be reasonable to consider the benchmark necessary to favor a paradigm of SRS alone over strategies incorporating WBRT as the demonstration of comparable OS in the context of decreased treatment-related side effects. However, patients with small-cell lung cancer (SCLC) brain metastases were excluded from the landmark trials that established SRS alone for limited brain metastases, largely due to concerns for short-interval CNS progression in SCLC as well the historic role of prophylactic cranial irradiation (PCI) in SCLC in the absence of known brain metastases. As a result, WBRT has remained the standard for SCLC for limited and even solitary brain lesions. With shifting SCLC care patterns including increased MRI surveillance, decreased PCI delivery, and emerging systemic agents, interest in first-line SRS for SCLC is likely to continue to increase over time. Herein we will review the emerging data for first-line SRS in the management of SCLC brain metastases and the potential for its increasing role in the setting of a greater utilization of MRI surveillance and improving systemic therapies.
| S-EPMC7656430 | 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