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.

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.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections. METHODS: Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (>= 2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan-Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism. RESULTS: Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone >= 2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P-value = .004). CONCLUSION: For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection.

Purpose: There is marked variability in treatment fields for glioblastoma. We performed a retrospective study comparing outcomes of patients treated according to MD Anderson Cancer Center (MDACC) or Radiation Therapy Oncology Group (RTOG) guidelines and identified differences in treatment-related toxicity. Methods and Materials: Adult patients with glioblastoma treated with surgery and adjuvant radiation treatment were included in this study. Primary outcomes were local control, progression-free survival (PFS), overall survival (OS), and radiation-related toxicity. PFS and OS were estimated using the Kaplan-Meier estimator. Univariate and multivariate analyses were conducted using Cox regression models. Results: In total, 257 patients met the inclusion criteria with a median age of 60.1 years at diagnosis. There were 162 and 95 patients treated according to the MDACC or RTOG guidelines, respectively. Despite having similar gross tumor volumes, the RTOG cohort had a larger median planning target volume (303.2 cm³ vs 430.7 cm³, P < .001) and worse PFS (6 months vs 9 months, P = .031). There was no difference in OS between treatment techniques. Patients treated according to RTOG guidelines experienced higher rates of radionecrosis (34% vs 21%, P = .024) and severe lymphopenia (15% vs 7%, P = .044). Conclusions: Patients treated according to MDACC guidelines had smaller treatment volumes, improved PFS, and lower rates of radionecrosis and severe lymphopenia. However, when adjusting for prognostic factors, treatment type was not associated with PFS in multivariate analysis. Prospective investigation is warranted to confirm these differences in outcomes.

Purpose: Single fraction preoperative stereotactic radiosurgery (SRS) has historically used a 10% to 20% dose reduction standard dosing. However, the effects of this dose reduction are not well characterized. The goal of this study was to compare outcomes and toxicity of standard dose (SD) with reduced dose (RD) single fraction preoperative SRS. Methods and Materials: Patients with brain metastases from solid cancers, of which at least 1 lesion measuring ≤ 4 cm was treated with single fraction preoperative SRS and underwent planned resection were included from the Preoperative Radiosurgery for Brain Metastases (PROPS-BM international multicenter combined prospective and retrospective registries from 8 institutions. SD was a priori defined as ≥20 Gy for lesions ≤2 cm, ≥17 Gy for >2 to 3 cm, and ≥14 Gy for >3 to 4 cm based on institutional dosing practices. Multivariable and propensity score matched analyses were performed. Results: The cohort consisted of 307 patients with 307 preoperative SRS treated index lesions. SD was used in 124 patients (40%) and RD was used in 183 patients (60%). Median dose for lesions 0 to 2 cm (n = 73), >2 to 3 cm (n = 152), and >3 to 4 cm (n = 82) was 20, 18, and 15 Gy in the SD cohort and 16, 15, and 13 Gy in the RD cohort, respectively. There was no difference in 2-year cavity local recurrence (LR, 16% vs 15%, P = .69), adverse radiation effect (ARE, 8% vs 6%, P = .77), meningeal disease (2% vs 8%, P = .07), composite endpoint of cavity LR, ARE, or nodular meningeal disease (23% vs 22%, P = .86), or overall survival (49% vs 36%, P = .15). Results were similar within each specific lesion diameter subgroup and within the propensity score matched cohorts (n = 168). Conclusions: Both SD and RD single fraction preoperative SRS demonstrate excellent rates of cavity LR and ARE. Cavity LR risk increased with larger lesion size, regardless of SRS dose category. There does not seem to be an advantage in efficacy or toxicity for RD over SD single fraction preoperative SRS. Additional studies are warranted to optimize preoperative SRS dose and fractionation.

Over recent decades, significant advancements have been made in the treatment and imaging of gliomas. Conventional imaging techniques, such as MRI and CT, play critical roles in glioma diagnosis and treatment but often fail to distinguish between tumor pseudoprogression (Psp) and radiation necrosis (RN) versus true progression (TP). Emerging fields like radiomics and radiogenomics are addressing these challenges by extracting quantitative features from medical images and correlating them with genomic data, respectively. This article will discuss several studies that show how radiomic features (RFs) can aid in better patient stratification and prognosis. Radiogenomics, particularly in predicting biomarkers such as MGMT promoter methylation and 1p/19q codeletion, shows potential in non-invasive diagnostics. Radiomics also offers tools for predicting tumor recurrence (rBT), essential for treatment management. Further research is needed to standardize these methods and integrate them into clinical practice. This review underscores radiomics and radiogenomics’ potential to revolutionize glioma management, marking a significant shift towards precision neuro-oncology.

Purpose/Objective(s) 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. However, most patients in this cohort were treated with single fraction radiosurgery. 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. Materials/Methods Patients who had surgical resection and radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Only patients who received pre-op radiation were eligible for inclusion. Patients with multiple metastases resected pre-operatively, 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. Relevant demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results 260 patients with 299 resected brain metastases were eligible for analysis. The median follow up was 10 months. 64 metastases received SRS and 235 metastases received FSRT. 38 patients had multiple metastases resected pre-operatively. Resected metastases were commonly located in the frontal lobe (35%), parietal lobe (23%), and cerebellum (16%). The median gross tumor volume was 4 ccs for SRS and 10 ccs for FSRT (P<0.001). The median planning target volume was 6 ccs for SRS and 16 ccs for FSRT (P<0.0001). The median SRS dose was 18 Gy, and the median FSRT dose was 24 Gy. 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. Conclusion In our study, pre-op SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. Comparing SRS and FSRT in our cohort is challenging due to differences in tumor size; larger tumors more frequently received FSRT, and these tumors may have a higher risk for adverse events. Therefore, the selection bias in this cohort may disguise any potential benefit of FSRT. It is important to prospectively compare pre-op SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.

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.

OBJECTIVE:Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS:This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS:There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS:SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Introduction Craniospinal irradiation (CSI) is indicated for adult patients diagnosed with leptomeningeal disease (LMD). Proton-based vertebral body sparing (VBS) CSI has been explored with pediatric patients to minimize hematologic toxicity; however, utilization of VBS in an adult population is limited. A recent phase II trial has shown efficacy of proton-based CSI to treat non-small cell lung and breast cancer with LMD. We hypothesize that VBS CSI using volumetric modulated arc therapy (VMAT) could also effectively reduce dose to vertebral bodies and surrounding organs at risk, minimizing toxicity for adult patients with LMD and comparing favorably to proton-based CSI. Methods and Materials Consecutive patients with LMD received VMAT VBS CSI, 30 Gy in 10 fractions, as a part of a prospective registry. Full VMAT arcs for the brain fields matched to 2 spine isocenters for the upper and lower spine were created using limited posterior arcs. To further decrease the vertebral body dose, an avoid entry and exit contour was created. Acute toxicity data were collected using Common Terminology Criteria for Adverse Events v5. Results Ten adult patients were treated in this cohort. One patient experienced grade 2 neutropenia with the remaining 9 experiencing grade 1 hematologic toxicity. Three patients experienced grade 2 gastrointestinal toxicity with the remaining 7 experiencing grade 1 nausea. No patient experienced grade 3+ toxicities in this cohort. One patient experienced a 5-day delay in systemic therapy initiation due to neutropenia; otherwise, all patients planned for systemic therapy started without delay. Conclusions In this study, VMAT VBS CSI led to acceptable toxicity compared with patients treated with proton CSI on a phase 2 clinical trial. Given its promising early results, future prospective evaluation of the technique is warranted.

Purpose/Objective(s) There is marked variability defining treatment fields for the treatment of glioblastoma (GBM). We performed a retrospective study comparing outcomes of patients treated according to the MD Anderson Cancer Center (MDACC) or Radiation Therapy Oncology Group (RTOG) guidelines and identified differences in treatment-related toxicity. Materials/Methods Adult patients with GBM treated with surgery and adjuvant radiation treatment (RT) between 2013–2016 were included in this study. Patients were treated according to institutional preference. Primary outcomes were local control rates, survival outcomes, and radiation-related toxicity. Radionecrosis was characterized through either surgical pathology or MRI, utilizing available perfusion and diffusion techniques. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator. Univariate and multivariate analyses were conducted using the Cox regression models. Results In our study, 257 patients met inclusion criteria with a median age of 60.1 at the time of diagnosis. There were 162 and 95 patients treated according to the MDACC and RTOG guidelines, respectively. Although the gross tumor volumes were similar between the groups, the RTOG cohort had a larger median planning target volume (303.2 cc vs 430.7 cc, P = < 0.001) and worse PFS (P = 0.031). There was not a statistically significant difference in OS between treatment strata. Patients treated according to the RTOG protocol experienced higher rates of radionecrosis (34% vs 21%, P = 0.024) and grade 3+ lymphopenia (15% vs 7%, P = 0.044). Conclusion Patients treated according to the MDACC protocol had smaller treatment volumes, improved PFS, and lower rates of radiation-related toxicity. Prospective investigation is warranted to confirm the differences in outcomes.

BACKGROUND:Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS:Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS:A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS:SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

Background: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. Methods: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan–Meier estimates in R v4.2.3. Results: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14–23 y) and the median follow-up was 18.1 months (IQR: 7.7–29.1). The median SABR dose was 30 Gy (IQR 25–35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). Conclusions: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

PurposeThe role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM, a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas.Methods and MaterialsData on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from eight academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than two lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes including progression-free survival (PFS) and overall survival (OS) as well as toxicity outcomes were reported at the patient level.ResultsFrom 2000-2022, 108 patients were identified (94% grade 2, 6.0% grade 3). 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiotherapy (RT). Median time to first progression was 2.5 years (IQR 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of two lesions (87% received single fraction SRS). Median follow-up time after SRS was 2.6 years. 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively after treatment with SRS. 1-, 2-, and 3-year OS was 97%, 94%, and 92%, respectively. On multivariable analysis, grade 3 disease (HR 6.80; 95% CI 1.61-28.6), male sex (HR 3.48; 95% CI 1.47-8.26), and receipt of prior RT (HR 2.69; 95% CI 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well-tolerated, with a 3.0% incidence of grade 2+ radiation necrosis.ConclusionsThis is the largest multi-center study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation.

Purpose: Palliative radiotherapy (RT) plays a crucial role in alleviating symptoms associated with metastatic sarcoma. However, there is a lack of consensus on the optimal palliative radiation dose and fractionation for metastatic sarcomas. We analyzed the association between biologically effective radiation dose and symptom response for patients who underwent palliative RT for metastatic sarcomas Methods and materials: We retrospectively identified patients with metastatic sarcoma treated with palliative RT between 1999 and 2021 at our institution. We assessed the association between equivalent dose in 2 Gy fractions (EQD2) with an alpha/beta of three and symptom relief or overall survival (OS) using univariable and multivariable analyses. Results: Of the 198 metastatic sites treated, the most common indications for palliative radiation were pain (n = 181, 91 %) and compression of adjacent structures (n = 16, 8 %). In our analysis, an EQD2 of > 20 Gy was associated with greater rates of short-term symptom relief (n = 143, 85 %) at the RT site compared to an EQD2 of <= 20 Gy (n = 14, 54 %, P = 0.001) with no reports of grade 3 or higher toxicity. However, there was no significant improvement in short-term symptom relief for higher radiation doses. Patients treated with an EQD2 of <= 20 Gy had a significantly worse performance status, but there was no significant difference in overall survival based on EQD2 on multivariable analysis. Conclusions: An EQD2 <= 20 Gy (e.g., 8 Gy in 1 fraction) provided inadequate palliative benefit in this series. An EQD2 > 20 Gy resulted in greater rates of symptom palliation in metastatic sarcomas, but further dose escalation did not improve symptom response or durability. These findings suggest standard palliative regimens such as 20 Gy in 5 fractions (EQD2 of 28 Gy) are effective for patients with metastatic sarcomas.

Purpose/Objective(s) The standard treatment for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection 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. Materials/Methods 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 who received pre-op or post-op radiation were eligible for inclusion. Patients with multiple metastases resected, either during the same surgery or at different times in the disease course, were eligible for inclusion. All included patients received FSRT. Outcomes were evaluated on a per-lesion basis. Relevant demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results 458 patients with 534 resected brain metastases were eligible for analysis. The median follow up was 11 months. 235 metastases received pre-op FSRT, and 299 metastases received post-op FSRT. Overall, 15% of patients had multiple brain metastases resected. The most common metastasis locations were frontal (33%), parietal (22%), and cerebellar (19%) with no significant differences between groups. The median planning target volumes were 16 ccs and 36ccs for pre-op and post-op FSRT, respectively (p <0.001). 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). Overall, 14% of metastases that received pre-op FSRT experienced the composite endpoint, and 24% of metastases receiving post-op FSRT experienced the composite endpoint (p=0.005). Conclusion 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.

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.

OBJECTIVE: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT. - METHODS: This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures. - RESULTS: Median age was 44 years (range, 19-79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1-268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control ( P = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STRRT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P = 0.03) or stereotactic radiosurgery (P = 0.04). - CONCLUSIONS: Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. Firstline treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity.