Purpose The treatment standard for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection followed by postoperative stereotactic radiosurgery (SRS). Preoperative SRS may lead to a reduced incidence of radiation necrosis (RN), local failure (LF), and nodular meningeal disease (nMD). Fractionated treatments may reduce the incidence of LF and nMD. We hypothesize that preoperative fractionated stereotactic radiation therapy will reduce the incidence rate of RN, LD, and nMD compared to patients receiving preoperative SRS. Methods and Materials Patients who had surgical resection and preoperative radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by (1) LF; (2) nMD; and/or (3) grade 2 or higher (symptomatic) RN. Results 299 resected brain metastases from 260 patients were eligible for analysis. Two hundred thirty-five metastases received fractionated stereotactic radiation therapy (FSRT) and 64 received SRS. Thirty-eight patients had multiple metastases resected preoperatively. Overall, 4 (6.3%) SRS and 6 (2.6%) FSRT metastases experienced LF. Four (6.2%) SRS and 21 (9.1%) FSRT metastases experienced grade 2 or higher RN. Three (4.7%) SRS and 11 (4.7%) FSRT metastases were diagnosed with leptomeningeal disease. Additionally, 3 (4.6%) and 0 (0%) of SRS, and 8 (3.4%) and 4 (1.7%) of FSRT patients experienced classical or nodular meningeal disease, respectively. Eleven percent and 12% of SRS and FSRT metastases experienced the composite endpoint. Conclusions In our study, preoperative SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. It is important to prospectively compare preoperative SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.

BACKGROUND/OBJECTIVES:Stereotactic body radiation therapy (SBRT) provides improved pain response and local control for spinal metastases. However, management of local failure after initial SBRT is challenging. We report institutional outcomes, dosimetry, and toxicity for reSBRT following SBRT. METHODS:We retrospectively reviewed 61 lesions (55 patients) treated with reSBRT after prior SBRT. Both SBRT courses delivered a median dose of 27 Gy. Patients underwent clinical and radiological evaluation every three months. Toxicity was graded using CTCAE v5.0. Dosimetric parameters for the spinal cord (SC), cauda equina (CE), planning organ-at-risk volumes (PRV), and thecal sac were converted to equivalent dose in 2 Gy fractions (EQD2) using the linear-quadratic model (α/β = 2). RESULTS:Median follow-up was 10.3 months. Forty lesions (65%) were cervicothoracic and 21 (35%) were lumbosacral. One- and two-year overall survival (OS) were 45% and 29%, respectively, and one- and two-year local control (LC) were 89% and 88%, respectively. Gastrointestinal primary tumors were associated with inferior LC (HR 2.41, 95% CI 1.11-5.23, p = 0.026). Fifteen patients (27%) reported myelitis/neuropathic symptoms during follow-up; four (7%) developed new post-radiation myelitis or neuropathy (RMN) without radiologic progression. Five patients (9%) developed vertebral compression fractures (VCF). Cumulative EQD2 was not significantly associated with RMN (p = 0.344); all affected patients had thecal sac EQD2 > 95.5 Gy and relevant nerve roots EQD2 > 108 Gy. CONCLUSIONS:ReSBRT provided a favorable LC with acceptable toxicity. High cumulative dose to the thecal sac and nerve roots may contribute to neurologic toxicity as peripheral nerve injury.

PURPOSE:Patients with large or symptomatic brain metastases typically have surgery followed by postoperative (post-op) stereotactic radiosurgery. However, post-op stereotactic radiosurgery leads to elevated rates of radiation necrosis (RN), nodular meningeal disease (nMD), and local failure (LF) when compared with whole brain radiation therapy. Fractionated stereotactic radiation therapy (FSRT) can deliver a higher biological effective dose and may reduce the risk of LF, and preoperative (pre-op) treatments may reduce the risk of RN and nMD through treating smaller volumes and tumor sterilization. METHODS AND MATERIALS:This single institution cohort study included patients who had surgical resection and FSRT to at least one brain metastasis. Pre-op or post-op FSRT was delivered with a dose of 27 Gy in 3 fractions or 30 Gy in 5 fractions. The primary endpoint was a composite endpoint defined by (1) LF, (2) nMD, and/or (3) grade 2 or higher (symptomatic) RN. RESULTS:Of the 534 resected brain metastases from 458 patients were eligible for analysis, 235 and 299 metastases received pre-op and post-op FSRT, respectively. Notably, 4 (1.7%) pre-op and 14 (4.7%) post-op metastases were diagnosed with nMD (P = .088). Notably, 28 (12%) and 59 (20%) metastases that received pre-op and post-op FSRT, respectively, experienced the composite endpoint (P = .018). The 3-year composite endpoint for pre-op and post-op FSRT was 15% (95% CI, 10%-20%) and 20% (95% CI, 15%-25%), respectively. CONCLUSIONS:In our study, pre-op FSRT compares favorably to post-op FSRT primarily because of a lower incidence of nMD. Differences between treatment groups for symptomatic RN or LF endpoints were comparatively smaller. Prospective validation of pre-op FSRT is needed.

Melanoma remains a formidable challenge in oncology, causing the majority of skin cancer deaths in the United States, with brain metastases contributing substantially to this mortality. This paper reviews the current therapeutic strategies for melanoma brain metastases, with a focus on delayed and concurrent stereotactic radiosurgery (SRS). While surgery and traditional chemotherapy offer limited efficacy, recent advances in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have played a major role in the advancement and improved efficacy of the treatment of cancers, including brain metastases. Recent studies indicate that monotherapy with ICIs may lead to a higher median overall survival compared to historical benchmarks, potentially allowing patients to delay radiosurgery. Other studies have found that combining SRS with ICIs demonstrates promise, with results indicating improved intracranial control. Ongoing clinical trials explore novel combinations of immunotherapies and radiotherapies, aiming to optimize treatment outcomes while minimizing adverse effects. As treatment options expand, future studies will be necessary to understand the interplay between therapies and their optimal sequencing to improve patient outcomes.

Background: Current standard of care treatment for patients with ≥15 brain metastases (BM) is whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery (SRS), with the aim of evaluating safety, cognitive outcomes, and survival metrics. Methods: Patients who received SRS for ≥15 BMs in 1 to 5 fractions from 2014 to 2022 were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS) scores. The Kaplan-Meier method was used for survival analysis and log-rank test for intergroup comparisons. Results: Overall, 118 patients underwent 124 courses of LINAC-based SRS. The median number of lesions treated per course was 20 (range, 15-94). Most patients received fractionated SRS to a dose of 24 Gy in 3 fractions (81.5%). At the time of SRS, 19.4% patients had received prior WBRT, and 24.2% had received prior SRS. The rate of any grade radiation necrosis (RN) and grade ≥3 RN were 15.3% and 3.2%, respectively. When evaluating longitudinal PROMIS score trends, 25 of 31 patients had a stable/improved PROMIS score. Patients who did not receive prior brain RT had a longer median survival (7.4 months vs 4.6 months, P = .034). The 12m local control was 97.6%, and the cumulative incidence of distant intracranial failure, with death as a competing event, was 46% (95% CI, 36%, 55%). One year freedom from neurologic death, leptomeningeal disease, and salvage WBRT were 89%, 94.6%, and 84%, respectively. Conclusion: We present here one of the largest studies evaluating SRS for patients with ≥15 BMs. SRS was safe, had favorable cognitive outcomes, and had comparable survival outcomes to contemporary studies evaluating WBRT in this population. Treatment-naïve patients had a median survival of >6 months, long enough to benefit from cognitive sparing with SRS. Our study supports randomized studies comparing SRS and hippocampal avoidance WBRT approaches for these patients.

Abstract The treatment standard for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection followed by post-operative (post-op) stereotactic radiosurgery (SRS). The multicenter PROPS-BM cohort showed how pre-operative (pre-op) SRS may lead to a reduced incidence of radiation necrosis (RN), local failure (LF), and meningeal disease (MD) compared to historical controls. Fractionated treatments can deliver a higher biological effective dose and may reduce the incidence of LF and MD. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive pre-op SRS. Patients who had surgical resection and pre-operative radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. 260 patients with 299 resected brain metastases were eligible for analysis. 64 metastases received SRS and 235 metastases received FSRT. 38 patients had multiple metastases resected pre-operatively. The median gross tumor volume was 4 ccs for SRS and 10 ccs for FSRT (p<0.001). Overall, 4 (6.3%) SRS and 6 (2.6%) FSRT patients experienced LF. 4 (6%) SRS and 21 (8.9%) FSRT patients experienced Grade 2 or higher RN. 3 (4.7%) SRS and 11 (4.7%) FSRT patients were diagnosed with MD. 14% of both SRS and FSRT patients experienced the composite endpoint. There were no statistically significant differences in outcome between these two treatment groups. In our study, pre-op SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. It is important to prospectively compare pre-op SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.

Abstract Patients with large or symptomatic brain metastases and limited intracranial disease typically have surgery followed by post-operative (post-op) stereotactic radiosurgery (SRS). However, SRS can lead to elevated rates of radiation necrosis (RN), meningeal disease (MD), and local failure (LF). Fractionated treatments can deliver a higher biological effective dose and may reduce the risk of LF, and pre-operative (pre-op) treatments may reduce the risk of RN and MD through treating smaller volumes and tumor sterilization. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive post-op FSRT. A retrospective analysis was performed at a single institution and included patients who had surgical resection and radiation to at least one brain metastasis. Patients with multiple metastases resected, either during the same surgery or at different times in the disease course, were eligible for inclusion. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. 458 patients with 534 resected brain metastases were eligible for analysis. 235 metastases received pre-op FSRT, and 299 metastases received post-op FSRT. Overall, 15% of patients had multiple brain metastases resected. Overall, 6 (2.6%) pre-op and 13 (4.3%) post-op patients experienced LF. 21 (8.9%) pre-op and 38 (12.7%) post-op patients experienced symptomatic RN. 11 (4.7%) pre-op and 29 (9.7%) post-op patients were diagnosed with MD (p=0.031). 14% and 24% of metastases that received pre-op and post-op FSRT, respectively, experienced the composite endpoint (p=0.005). In our study, pre-op FSRT compares favorably to post-op FSRT primarily due to a 50% reduction in the incidence of MD. Differences in symptomatic RN or LF were small on adjusted analyses. Prospective validation of pre-op FSRT is needed.

Abstract The treatment standard for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection followed by post-operative (post-op) stereotactic radiosurgery (SRS). The multicenter PROPS-BM cohort showed how pre-operative (pre-op) SRS may lead to a reduced incidence of radiation necrosis (RN), local failure (LF), and meningeal disease (MD) compared to historical controls. Fractionated treatments can deliver a higher biological effective dose and may reduce the incidence of LF and MD. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive pre-op SRS. Patients who had surgical resection and pre-operative radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. 260 patients with 299 resected brain metastases were eligible for analysis. 64 metastases received SRS and 235 metastases received FSRT. 38 patients had multiple metastases resected pre-operatively. The median gross tumor volume was 4 ccs for SRS and 10 ccs for FSRT (p<0.001). Overall, 4 (6.3%) SRS and 6 (2.6%) FSRT patients experienced LF. 4 (6%) SRS and 21 (8.9%) FSRT patients experienced Grade 2 or higher RN. 3 (4.7%) SRS and 11 (4.7%) FSRT patients were diagnosed with MD. 14% of both SRS and FSRT patients experienced the composite endpoint. There were no statistically significant differences in outcome between these two treatment groups. In our study, pre-op SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. It is important to prospectively compare pre-op SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.

Carbon-fiber reinforced (CFR) polyetheretherketone hardware is an alternative to traditional metal hardware used for spinal fixation surgeries before postoperative radiation therapy for patients with spinal metastases. CFR hardware's radiolucency decreases metal artifact, improving visualization and accuracy of treatment planning. We present the first clinical use and proof of principle of CFR spinal hardware with tantalum markers used for successful tracking of intrafraction motion (IM) using Varian TrueBeam IMR (Intrafraction Motion Review) software module during postoperative spine stereotactic radiation. A 63-year-old woman with history of endometrial cancer presented with acute back pain. Imaging demonstrated pathologic T12 vertebral fracture with cord compression. She underwent T12 vertebrectomy with circumferential decompression and posterior instrumented T10-L2 fusion at our facility using CFR-polyetheretherketone hardware with tantalum screw markers followed by postoperative stereotactic body radiation therapy to 3000 cGy in 5 fractions delivered to T11-T12. Tantalum screw markers were used for IMR tracking. During irradiation, 260 kV images were acquired, and IMR software was able to identify and track markers. During the entire treatment, the IM motions were less than 3 mm. This is the first presented case of CFR spinal hardware with tantalum markers used for successful IMR tracking of IM during daily spine stereotactic treatment. Future work will be needed to improve workflow and create a spine-specific IMR protocol.

IntroductionWe sought to determine the influence of primary tumor histology and metastatic tumor location on the frequency of seizures among patients with brain metastases. A secondary aim was to determine if surgery reduced the occurrence and frequency of seizures.MethodsWe retrospectively reviewed patients with cerebral metastasis at a single institution from 2006 to 2016.ResultsAmong 1949 patients identified as having had cerebral metastasis, 168 (8.6%) had documentation of one or more seizures. The incidence of seizures was highest among patients with metastases from melanoma (19.8%), followed by those with colon cancer (9.7%), renal cell carcinoma (RCC; 8.3%), and lung cancer (7.0%). Among 1581 patients with melanoma, colon cancer, RCC, non-small cell lung cancer, or breast cancer, having metastases in the frontal lobe seemed to confer the greatest risk of seizures (n = 100), followed by foci in the temporal lobe (n = 20) and elsewhere (n = 16).ConclusionPatients with cerebral metastasis are at increased risk for seizures. Seizure rates seem to be higher for certain primary tumors, such as melanoma, colon cancer, and RCC, and for lesions located in the frontal lobe.

BackgroundWith survival improving in many metastatic malignancies, spine metastases have increasingly become a source of significant morbidity; achieving durable local control (LC) is critical. Stereotactic body radiotherapy (SBRT) may offer improved LC and/or symptom palliation. However, due to setup concerns, SBRT is infrequently offered to patients with ≥3 contiguous involved levels. Because data are limited, we sought to evaluate the feasibility, toxicity, and cancer control outcomes of spine SBRT delivered to ≥3 contiguous levels.MethodsWe retrospectively identified all SBRT courses delivered between 2013 and 2019 at a tertiary care institution for postoperative or intact spine metastases. Radiotherapy was delivered to 14–35 Gy in 1–5 fractions. Patients were stratified by whether they received SBRT to 1–2 or ≥3 contiguous levels. The primary endpoint was 1-year LC and was compared between groups. Factors associated with increased likelihood of local failure (LF) were explored. Acute and chronic toxicity was assessed. In-depth dosimetric data were collected.ResultsOverall, 165 patients with 194 SBRT courses were identified [54% were men, median age was 61 years, 93% had Karnofsky Performance Status (KPS) ≥70, and median follow-up was 15 months]. One hundred thirteen patients (68%) received treatment to 1–2 and 52 to 3–7 (32%) levels. The 1-year LC was 88% (89% for 1–2 levels vs. 84% for ≥3 levels, p = 0.747). On multivariate analysis, uncontrolled systemic disease was associated with inferior LC for patients with ≥3 treated levels. No other demographic, disease, treatment, or dosimetric variables achieved significance. Rates of new/progressive fracture were equivalent (8% vs. 9.5%, p = 0.839). There were no radiation-induced myelopathy or grade 3+ acute or late toxicities in either group. Coverage of ≥95% of the planning target volume with ≥95% prescription dose was similar between groups (96% 1–2 levels vs. 89% ≥3 levels, p = 0.078).ConclusionsFor patients with ≥3 contiguous involved levels, spine SBRT is feasible and may offer excellent LC without significant toxicity. Prospective evaluation is warranted.

Abstract BACKGROUND Pre-operative stereotactic radiosurgery (SRS) has emerged as a recent treatment option to treat large or symptomatic brain metastases. Compared to post-operative SRS, pre-operative treatment may reduce rates of radiation necrosis (RN) and meningeal disease through treating a smaller treatment volume and by preventing post-operative tumor seeding. We hypothesize that pre-operative radiation volumes will be smaller than post-operative volumes, which in turn may lead to a decreased treatment morbidity. METHODS A retrospective analysis was conducted and patients who had surgical resection and post-operative SRS or fractionated stereotactic radiosurgery (FSRT) for a posterior fossa brain metastasis were eligible for inclusion. Both pre-operative and post-operative MRIs were required to allow for accurate radiation target delineation. A pre-operative tumor volume was added for each patient, and the post-operative clinical treatment volume (CTV) used for radiation treatment was included. Pre-operative tumor and post-operative cavity volumes were compared using Wilcoxon signed rank test. RESULTS 28 patients who received post-operative SRS or FSRT from 1/1/2016-12/31/2020 were included in this analysis. The mean pre-operative tumor volume was 14.9 ccs, and the mean post-operative CTV was 21.0 ccs (p < 0.01). 75% of patients had a smaller initial tumor size compared to the post-operative CTV used for radiation treatment planning. For patients with at least 4 follow up MRIs (n = 8), the size of the post-operative cavity progressively decreased with a mean initial cavity volume of 18.9 ccs and mean follow up volumes of 8.1, 7.1, 6.9, and 6.2 ccs. CONCLUSIONS In this study evaluating patients who received post-operative SRS, the pre-operative tumor volume was lower than the post-operative CTV for most patients. Previous studies including PROPS-BM have shown how pre-operative treatment may reduce the risk of RN because smaller radiation volumes are used. Pre-operative radiosurgery for patients with brain metastases requires prospective validation.

Background With advances in systemic therapy translating to improved survival in metastatic malignancies, spine metastases have become an increasingly common source of morbidity. Achieving durable local control (LC) for patients with circumferential epidural disease can be particularly challenging. Circumferential stereotactic body radiotherapy (SBRT) may offer improved LC for circumferential vertebral and/or epidural metastatic spinal disease, but prospective (and retrospective) data are extremely limited. We sought to evaluate the feasibility, toxicity, and cancer control outcomes with this novel approach to circumferential spinal disease. Methods We retrospectively identified all circumferential SBRT courses delivered between 2013 and 2019 at a tertiary care institution for post-operative or intact spine metastases. Radiotherapy was delivered to 14–27.5 Gy in one to five fractions. Feasibility was assessed by determining the proportion of plans for which ≥95% planning target volume (PTV) was coverable by ≥95% prescription dose. The primary endpoint was 1-year LC. Factors associated with increased likelihood of local failure (LF) were explored. Acute and chronic toxicity were assessed. Detailed dosimetric data were collected. Results Fifty-eight patients receiving 64 circumferential SBRT courses were identified (median age 61, KPS ≥70, 57% men). With a median follow-up of 15 months, the 12-month local control was 85% (eight events). Five and three recurrences were in the epidural space and bone, respectively. On multivariate analysis, increased PTV and uncontrolled systemic disease were significantly associated with an increased likelihood of LF; ≥95% PTV was covered by ≥95% prescription dose in 94% of the cases. The rate of new or progressive vertebral compression fracture was 8%. There were no myelitis events or any grade 3+ acute or late toxicities. Conclusions For patients with circumferential disease, circumferential spine SBRT is feasible and may offer excellent LC without significant toxicity. A prospective evaluation of this approach is warranted.

Background: The standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT. Methods: A multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined as patients with one of the following adverse events: 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results: 279 patients were eligible for analysis. The median follow-up time was 9 months. 87 % of patients received fractionated treatment. 29 % of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0 %, 17 %, 15 %, and 7.5 %, respectively. Conclusions: In our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.

The standard of care for elderly glioblastoma patients is 40 Gy in 15 fraction radiotherapy with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions. Elderly patients (≥ 65 years old) who received hypofractionated radiation with TMZ from 2010 to 2020 were included in this analysis. Overall survival (OS) and progression free survival were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared between patients who received 40 and 52.5 Gy. Univariable and multivariable analyses were performed. Sixty-six newly diagnosed patients were eligible for analysis. Thirty-nine patients were treated with 40 Gy in 15 fractions while twenty-seven were treated with 52.5 Gy in 15 fractions. Patients had no significant differences in age, sex, methylation status, or performance status. OS was superior in the 52.5 Gy group (14.1 months) when compared to the 40 Gy group (7.9 months, p = 0.011). Isoeffective dosing to 52.5 Gy was shown to be an independent prognostic factor for improved OS on multivariable analysis. Isoeffective dosing to 52.5 Gy in 15 fractions was associated with superior OS compared to standard of care 40 Gy in 15 fractions. These hypothesis generating data support accelerated hypofractionation in future prospective trials.

BACKGROUND Spine surgery is indicated for select patients with mechanical instability, pain, and/or malignant epidural spinal cord compression, with or without neurological compromise. Stereotactic body radiotherapy (SBRT) is an option for durable local control (LC) for metastatic spine disease. OBJECTIVE To determine factors associated with LC and progression-free survival (PFS) for patients receiving postoperative stereotactic spine radiosurgery. METHODS We analyzed consecutive patients from 2013 to 2019 treated with surgical intervention followed by SBRT. Surgical interventions included laminectomy and vertebrectomy. SBRT included patients treated with 1 to 5 fractions of radiosurgery. We analyzed LC, PFS, overall survival (OS), and toxicity. Univariate and multivariate analyses were performed. RESULTS A total of 63 patients were treated with a median follow-up of 12.5 mo. Approximately 75% of patients underwent vertebrectomy and 25% underwent laminectomy. One-year cumulative incidence of local failure was 19%. LC was significantly improved for patients receiving radiosurgery ≤40 d from surgery compared to that for patients receiving radiosurgery ≥40 d from surgery, 94% vs 75%, respectively, at 1 yr (P = .03). Patients who received preoperative embolization had improved LC with 1-yr LC of 88% vs 76% for those who did not receive preoperative embolization (P = .037). Significant predictors for LC on multivariate analysis were time from surgery to radiosurgery, higher radiotherapy dose, and preoperative embolization. The 1-yr PFS and OS was 56% and 60%, respectively. CONCLUSION Postoperative radiosurgery has excellent and durable LC for spine metastasis. An important consideration when planning postoperative radiosurgery is minimizing delay from surgery to radiosurgery. Preoperative embolization and higher radiotherapy dose were associated with improved LC warranting further study.

OBJECTIVE:Gliosarcomas (GS) comprise ~ 2 - 8% of glioblastomas and are associated with a similar poor prognosis. GS have rarely been found with a primitive neuroectodermal component (PNET). We present a case of gliosarcoma with PNET features (GS-PNET) that mimicked a neuroendocrine carcinoma on initial biopsy.MATERIALS AND METHODS:A 68-year-old male presented with 2 weeks of increasing headaches and difficulties with reading, writing, and word-finding. He was found to have a left-sided parieto-occipital heterogeneously enhancing mass.RESULTS:Pathologic analysis after surgical resection initially diagnosed a poorly differentiated carcinoma with neuroendocrine features, and adjuvant therapy was guided by this diagnosis as well as systemic imaging, which was suggestive of gastrointestinal primary malignancy with central nervous system (CNS) metastasis. Subsequent progression and re-resection established a diagnosis of GS with PNET component. Genomic profiling showed shared PTEN, TERT promotor, and TP53 mutations in the original and recurrent tumors.CONCLUSION:There have only been 5 previously reported cases of GS-PNET, to our knowledge, with this case representing the first with comprehensive molecular profiling. The case also highlights the importance of further work-up of presumed metastatic carcinoma with indeterminate immunostaining and/or suspected non-epithelioid component.

Background: The standard of care for elderly glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions. Methods: Elderly patients (≥ 65 years old) who received hypofractionated radiation with TMZ from 2010-2020 were included in this analysis. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared between patients who received 40 Gy and 52.5 Gy. Univariable and multivariable analyses were performed. Results: Sixty-six newly diagnosed patients were eligible for analysis. Thirty-nine patients were treated with 40 Gy in 15 fractions while twenty-seven were treated with 52.5 Gy in 15 fractions. Patients had no significant differences in age, sex, methylation status, or performance status. Overall survival (OS) was superior in the 52.5 Gy group (14.1 months) when compared to the 40 Gy group (7.9 months, p = 0.011). Isoeffective dosing to 52.5 Gy was shown to be an independent prognostic factor for improved OS on multivariable analysis. Conclusions: Isoeffective dosing to 52.5 Gy in 15 fractions was associated with superior OS compared to standard of care 40 Gy in 15 fractions. These hypothesis generating data support accelerated hypofractionation in future prospective trials.

BACKGROUND:Ossifying fibromyxoid tumor (OFMT) is a rare musculoskeletal soft-tissue neoplasm of uncertain histogenesis most frequently occurring in the lower extremities. Conventionally, considered benign, these tumors are often managed by surgical resection followed by surveillance. However, malignant OFMTs with an increased propensity for local recurrence and distant metastasis have been recently identified, and the role of adjuvant therapy in these more aggressive cases is unclear.CASE DESCRIPTION:We present, to the best of our knowledge, the first reported case of a primary, malignant, and intracranial OFMT. A 29-year-old female presented with recurrent headaches secondary to a large mass in her right frontal lobe. She underwent gross total resection of the brain mass with final pathology consistent with malignant OFMT demonstrating high-risk features including increased cellularity, grade, and mitotic activity. Due to these high-risk features, she received postoperative fractionated stereotactic radiation therapy (FSRT) to the resection cavity, and to the best of our knowledge, she represents the only known patient with OFMT to be treated with adjuvant FSRT. She tolerated the adjuvant treatment well with no acute or late toxicities and remains disease-free over 5 ½ years after resection.CONCLUSION:Adjuvant FSRT appears to be a safe and efficacious approach for managing this rare intracranial disease presentation. We review this patient's clinical course in the context of the literature to demonstrate the difficulties associated with accurate diagnosis of this rare tumor and the controversial role of adjuvant therapy in preventing disease recurrence in this patient population.

Background: Gamma knife (GK) and linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) both offer excellent local control in the management of multiple brain metastases. The efficacy and toxicity of LINAC and GK SRS have not been directly compared in the modern era. We studied outcomes in patients treated with LINAC SRS and GK at two separate institutions. Methods: We identified patients treated with either LINAC or GK who were treated to >2 lesions and had available follow up. LINAC patients were treated using single-isocenter multitarget technique. We used Cox regression, Fine and Gray competing risks regression, and nearest neighbor propensity score matching to account for confounders and imbalance between cohorts. Kaplan-Meier curves were used to estimate overall survival and rates of radionecrosis. Results: We identified 391 patients who were treated in 537 courses to a total 2699 lesions (LINAC: 1014, GK: 1685). After propensity score matching, GK was associated with similar overall survival (HR = 0.86; 95% CI 0.59-1.24; p = 0.41) and higher rate of radionecrosis (HR = 3.83; 95% CI 1.66-8.84; p = 0.002) compared to LINAC. In a secondary propensity score matched analysis comparing radionecrosis in singlefraction LINAC and GK, GK remained associated with higher incidence of radionecrosis (HR = 4.42; 95% CI 1.28-15.29; p = 0.019). Conclusions: In this multi-institutional study, we found similar overall survival with lower incidence of radionecrosis in patients treated with LINAC compared to GK SRS. These findings are hypothesis generating and should be validated in an independent cohort. (c) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 147 (2020) 136-143