Project description:IntroductionDue 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 materialsAll 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.ResultsA 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).ConclusionIn 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:OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6-50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7-86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2-70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

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:ObjectiveFor patients with surgically accessible solitary metastases or oligometastatic disease, treatment often involves resection followed by postoperative stereotactic radiosurgery (SRS). This strategy has several potential drawbacks, including irregular target delineation for SRS and potential tumor "seeding" away from the resection cavity during surgery. A neoadjuvant (preoperative) approach to radiation therapy avoids these limitations and offers improved patient convenience. This study assessed the efficacy of neoadjuvant SRS as a new treatment paradigm for patients with brain metastases.MethodsA retrospective review was performed at a single institution to identify patients who had undergone neoadjuvant SRS (specifically, Gamma Knife radiosurgery) followed by resection of a brain metastasis. Kaplan-Meier survival and log-rank analyses were used to evaluate risks of progression and death. Assessments were made of local recurrence and leptomeningeal spread. Additionally, an analysis of the contemporary literature of postoperative and neoadjuvant SRS for metastatic disease was performed.ResultsTwenty-four patients who had undergone neoadjuvant SRS followed by resection of a brain metastasis were identified in the single-institution cohort. The median age was 64 years (range 32-84 years), and the median follow-up time was 16.5 months (range 1 month to 5.7 years). The median radiation dose was 17 Gy prescribed to the 50% isodose. Rates of local disease control were 100% at 6 months, 87.6% at 12 months, and 73.5% at 24 months. In 4 patients who had local treatment failure, salvage therapy included repeat resection, laser interstitial thermal therapy, or repeat SRS. One hundred thirty patients (including the current cohort) were identified in the literature who had been treated with neoadjuvant SRS prior to resection. Overall rates of local control at 1 year after neoadjuvant SRS treatment ranged from 49% to 91%, and rates of leptomeningeal dissemination from 0% to 16%. In comparison, rates of local control 1 year after postoperative SRS ranged from 27% to 91%, with 7% to 28% developing leptomeningeal disease.ConclusionsNeoadjuvant SRS for the treatment of brain metastases is a novel approach that mitigates the shortcomings of postoperative SRS. While additional prospective studies are needed, the current study of 130 patients including the summary of 106 previously published cases supports the safety and potential efficacy of preoperative SRS with potential for improved outcomes compared with postoperative SRS.

Project description:PurposeTo report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity.Methods and materialsA total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity.ResultsThe median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm(3) (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm(3) (RR 13, P=.0013), V20 = 0.11 cm(3) (RR 6, P=0.01), and V22 = 0.0 cm(3) (RR 13, P=.0013). The median split for D2.5 cm(3) (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm(3). One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus.ConclusionsHigh-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are associated with development of grade ≥4 toxicity.

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Single versus multiple fraction stereotactic radiosurgery for medium-sized brain metastases (4-14 cc in volume): reducing or fractionating the radiosurgery dose?

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