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Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

ABSTRACT: PURPOSE:To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis. METHODS AND MATERIALS:In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (?2.0 vs <2.0 and ?2.5 vs <2.5). RESULTS:A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ?2.0, and 23.0% of patients had DS-GPA scores ?2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ?2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ?2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53). CONCLUSIONS:We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases.

SUBMITTER: Churilla TM

PROVIDER: S-EPMC5699951 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

Churilla Thomas M TM Ballman Karla V KV Brown Paul D PD Twohy Erin L EL Jaeckle Kurt K Farace Elana E Cerhan Jane H JH Anderson S Keith SK Carrero Xiomara W XW Garces Yolanda I YI Barker Fred G FG Deming Richard R Dixon Jesse G JG Burri Stuart H SH Chung Caroline C Ménard Cynthia C Stieber Volker W VW Pollock Bruce E BE Galanis Evanthia E Buckner Jan C JC Asher Anthony L AL

International journal of radiation oncology, biology, physics 20170805 5

<h4>Purpose</h4>To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis.<h4>Methods and materials</h4>In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment ( ...[more]

PMID: 28939223

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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:PurposeUtilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has increased, prompting reassessment of whole brain radiation therapy (WBRT). A pattern of care analysis of SRS and WBRT dose-fractionations was performed in patients presenting with BM at the time of cancer diagnosis.Methods and materialsAdults with BM at cancer diagnosis between 2010 to 2015 and no prior malignancy were identified in the National Cancer Database. SRS was defined using published thresholds. Short (ShWBRT), standard (StWBRT), and extended (ExWBRT) dose-fractionations were defined as 4 to 9, 10 to 15, and >15 fractions. Radioresistant histology was defined as melanoma, renal cell carcinoma, sarcoma or spindle cell, or gastrointestinal primary.ResultsOf 4,087,967 adults with their first lifetime cancer, 90,388 (2.2%) had BM at initial diagnosis. Of these, 11,486 (12.7%) received SRS and 24,262 (26.8%) WBRT as first-course radiation therapy. The proportion of annual WBRT use decreased from 27.8% to 23.5% of newly diagnosed patients, and SRS increased from 8.7% to 17.9%. Common dose-fractionations were 30 Gy in 10 fractions (56.8%) for WBRT and 20 Gy in 1 fraction (13.0%) for SRS. On multivariate analysis, factors significantly associated with SRS versus WBRT included later year of diagnosis (2015 vs 2010, adjusted odds ratio [aOR] = 2.4), radioresistance (aOR = 2.0), academic facility (aOR = 1.9), highest income quartile (aOR = 1.6), chemotherapy administration (aOR = 1.4), and longer travel distance (>15 vs < 5 miles, aOR = 1.4). Linear regression revealed significant ExWBRT reductions (-22.4%/y, R2 = 0.97, P < .001) and no significant change for ShWBRT or StWBRT. Patients were significantly more likely to receive ShWBRT than StWBRT if not treated with chemotherapy (aOR = 3.5).ConclusionsUtilization of WBRT, particularly ExWBRT, decreased while SRS utilization doubled as the first radiation therapy course in patients with BM at diagnosis. Patients with radioresistant histologies were more likely to receive SRS. Those not receiving chemotherapy, potentially owing to poor performance status, were less likely to receive SRS and more likely to receive ShWBRT.

Dataset Information

Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

Publications

Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

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