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Identification of Patients with Brain Metastases with Favorable Prognosis After Local and Distant Recurrence Following Stereotactic Radiosurgery.

ABSTRACT: Purpose:This 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 Methods:Clinical 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. Results:Among 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). Conclusion:A 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.

SUBMITTER: Jiang X

PROVIDER: S-EPMC7276324 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of Patients with Brain Metastases with Favorable Prognosis After Local and Distant Recurrence Following Stereotactic Radiosurgery.

Jiang Xuechao X

Cancer management and research 20200603

<h4>Purpose</h4>This 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.<h4>Patients and methods</h4>Clinical 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 f ...[more]

PMID: 32581585

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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.

Project description:BackgroundStereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases.MethodsPatients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life.DiscussionCurrently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure.Trial registrationClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

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.

Dataset Information

Identification of Patients with Brain Metastases with Favorable Prognosis After Local and Distant Recurrence Following Stereotactic Radiosurgery.

Publications

Identification of Patients with Brain Metastases with Favorable Prognosis After Local and Distant Recurrence Following Stereotactic Radiosurgery.

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