Pleomorphic Xanthoastrocytoma: Multi-Institutional Evaluation of Stereotactic Radiosurgery.

BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.

Differences in Patterns of Care and Referral Between Proton and Photon Therapy.

Purpose: To report demographic and clinical characteristics of patients who were more likely to receive proton beam therapy (PBT) than photon therapy from facilities with access to proton centers. Materials and Methods: We utilized the national cancer database to identify the facilities with access to PBT between 2004 and 2015 and compared the relative usage of photons and PBT for demographic and clinical scenarios in breast, prostate, and nonsmall cell cancer. Results: In total, 231 facilities with access to proton centers accounted for 168 323 breast, 39 975 lung, and 77 297 prostate cancer patients treated definitively. Proton beam therapy was used in 0.5%, 1.5%, and 8.9% of breast, lung, and prostate cases. Proton beam therapy was correlated with a farther distance traveled and longer start time from diagnosis for each site (P < .05).For breast, demographic correlates of PBT were treatment in the west coast (odds ratio [OR] = 4.81), age <60 (OR = 1.25), white race (OR = 1.94), and metropolitan area (OR = 1.58). Left-sided cancers (OR = 1.28), N2 (OR = 1.71), non-ER+/PR+/Her2Neu- cancers (OR = 1.24), accelerated partial breast irradiation (OR = 1.98), and hypofractionation (OR = 2.35) were predictors of PBT.For nonsmall cell cancer, demographic correlates of PBT were treatment in the south (OR = 2.6), metropolitan area (OR = 1.72), and Medicare insurance (OR = 1.64). Higher comorbid score (OR = 1.36), later year treated (OR = 3.16), and hypofractionation (not SBRT) (OR = 3.7) were predictors of PBT.For prostate, correlates of PBT were treatment in the west coast (OR = 2.48), age <70 (OR = 1.19), white race (OR = 1.41), metropolitan area (OR = 1.25), higher income/education (OR = 1.25), and treatment at an academic center (OR = 33.94). Lower comorbidity score (OR = 1.42), later year treated (OR = 1.37), low-risk disease (OR = 1.45), definitive compared to postoperative (OR = 6.10), and conventional fractionation (OR = 1.64) were predictors of PBT. Conclusion: Even for facilities with established referrals to proton centers, PBT utilization was low; socioeconomic status was potentially a factor. Proton beam therapy was more often used with left-sided breast and low-risk prostate cancers, without a clear clinical pattern in lung cancer.

Cost of Treatment for Brain Metastases Using Data From a National Health Insurance.

Purpose: In the United States, brain metastases (BMs) affect 10% to 20% of patients with cancer, presenting a significant health care challenge and necessitating intricate, high-cost treatments. Few studies have explored the comprehensive care cost for BMs, and none have used real insurance claims data. Partnering with a northeastern health care insurer, we investigated the true costs of various brain-directed radiation methods, aiming to shed light on treatment expenses, modalities, and their efficacy. Methods and Materials: We analyzed medical claims from Highmark Health-insured patients in Pennsylvania, Delware, West Virginia, and New York diagnosed with BMs (ICD-10 code C79.31) and treated with radiation from January 1, 2020 to July 1, 2022. Costs for radiation techniques were grouped by specific current procedural terminology claim codes. We subdivided costs into technical and physician components and separated hospital from freestanding costs for some modalities. Results: From January 1, 2020 to July 1, 2022, 1048 Highmark Health members underwent treatment for BMs. Females (n = 592) significantly outnumbered males (n = 456), with an average age of 64.4 years. Each member had, on average, 5.309 claims costing $2015 per claim. Total cost totaled $10,697,749. Per-treatment analysis showed that hippocampal avoidance intensity modulated radiation therapy was the costliest treatment at $47,748, followed by stereotactic radiation therapy at $37,230, linear accelerator stereotactic radiosurgery (SRS) at $30,737, Gamma Knife SRS at $30,711, and whole-brain radiation therapy at $5225. Conclusions: Whole-brain radiation therapy was the least costly radiation technique. Similar per-treatment prices for Gamma Knife and linear accelerator SRS support their use in treating BMs. Stereotactic radiation therapy in general was costlier on a per-use basis than SRS, prompting further scrutiny on its frequent use. Hippocampal avoidance intensity modulated radiation therapy was the costliest radiation therapy on a per-use basis by a moderate amount, prompting further discussion about its comparative cost effectiveness against other radiation modalities. This study underscores the importance of multiple considerations in treating BMs, such as tumor control, survival, side effects, and costs.

National trends in the treatment of adult diffuse midline gliomas: a rare clinical scenario.

PURPOSE: Diffuse midline gliomas (DMG) include all midline gliomas with a point mutation to the histone H3 gene resulting in the substitution of a lysine with a methionine (K27M). These tumors are classified as World Health Organization grade 4 with a mean survival between 9- and 19-months following diagnosis. There is currently no standard of care for DMG, and palliative radiation therapy has been proven to only extend survival by months. Our current study aims to report current treatment trends and predictors of the overall survival of DMG. METHODS: We searched the National Cancer Database for adult patients treated for DMG from 2016 to 2020. Patients were required to have been treated with primary radiation directed at the brain with or without concurrent chemotherapy. Univariable and multivariable Cox regressions were used to determine predictors of overall survival. RESULTS: Of the 131 patients meeting the inclusion criteria, 113 (86%) received radiation and chemotherapy. Based on multivariable Cox regression, significant predictors of survival were Charlson-Deyo comorbidity index and race. Patients with a Charlson-Deyo score of 1 had 2.72 times higher odds of mortality than those with a score of 0. Patients not identifying as White or Black had 2.67 times higher odds of mortality than those identifying as White. The median survival for all patients was 19 months. CONCLUSIONS: Despite being considered ineffective, chemotherapy is still administered in most adult patients diagnosed with DMG. Significant predictors of survival were Charlson-Deyo comorbidity index and race.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

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.

Intratumoral Hemorrhage in Vestibular Schwannomas After Stereotactic Radiosurgery: Multi-Institutional Study.

BACKGROUND AND OBJECTIVES: Intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is exceedingly rare. The aim of this study was to define its incidence and describe its management and outcomes in this subset of patients. METHODS: A retrospective multi-institutional study was conducted, screening 9565 patients with VS managed with SRS at 10 centers affiliated with the International Radiosurgery Research Foundation. RESULTS: A total of 25 patients developed ITH (cumulative incidence of 0.26%) after SRS management, with a median ITH size of 1.2 cm 3 . Most of the patients had Koos grade II-IV VS, and the median age was 62 years. After ITH development, 21 patients were observed, 2 had urgent surgical intervention, and 2 were initially observed and had late resection because of delayed hemorrhagic expansion and/or clinical deterioration. The histopathology of the resected tumors showed typical, benign VS histology without sclerosis, along with chronic inflammatory cells and multiple fragments of hemorrhage. At the last follow-up, 17 patients improved and 8 remained clinically stable. CONCLUSION: ITH after SRS for VS is extremely rare but has various clinical manifestations and severity. The management paradigm should be individualized based on patient-specific factors, rapidity of clinical and/or radiographic progression, ITH expansion, and overall patient condition.

Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency.

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.

The 5-factor modified frailty index as a prognostic factor of stereotactic radiosurgery for metastatic disease to the brain.

OBJECTIVE: Frailty, a state of increased vulnerability to adverse health outcomes, is associated with poor neurosurgical outcomes. The relationship between frailty and stereotactic radiosurgery (SRS) for brain metastases (BMs), however, has not been adequately described. In this study, the authors attempted to examine the connection between frailty and outcomes for patients receiving SRS for BMs. METHODS: A single-center retrospective cohort study was performed. The 5-factor modified frailty index (mFI-5) was used to stratify patients into pre-frail (mFI-5 score 0-1), frail (mFI-5 score 2), and severely frail (mFI-5 score ≥ 3) cohorts at the time of SRS treatment. Both overall survival (OS) and progression-free survival (PFS) were evaluated. Factors associated with OS/PFS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS: Two hundred three patients met the inclusion criteria and received SRS to one or more BMs. Fifty-six patients (27.6%) received SRS as an adjuvant treatment. The 12-month OS and PFS rates were 58.6% and 45.5%, respectively. One hundred twenty-six patients (62.1%) were classified as pre-frail, 58 (28.6%) as frail, and 19 (9.4%) as severely frail. Significantly less OS was demonstrated in frailer groups (frail hazard ratio [HR] 3.14, p < 0.005; severely frail HR 3.13, p < 0.005). Compared with pre-frail patients, frail patients had shorter intervals of PFS (frail HR 2.05, p < 0.005). Five patients (2.5%) had symptomatic radiation necrosis (RN) and 60 (29.6%) required repeat radiation. CONCLUSIONS: Higher frailty scores at the time of SRS treatment were predictive of shorter OS and PFS intervals.

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis.

BACKGROUND AND OBJECTIVES: Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS: We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS: Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS ( P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence ( P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION: This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

Selected-Lesion Stereotactic Radiosurgery (SL-SRS) as a Novel Strategy in the Treatment of Patients With Multiple Brain Metastases.

INTRODUCTION: With the diminishing use of whole-brain radiotherapy (WBRT), there is increasing debate regarding the maximum number of brain metastases that should be treated with stereotactic radiosurgery (SRS). In patients with >10-15 lesions, some groups are proposing a new approach - selected-lesion SRS (SL-SRS) - where only a subset of intracranial lesions are chosen for irradiation. This study is an initial look into this practice. METHODS: This is a cross-sectional exploratory survey study. A survey of 19 questions was created by the International Radiosurgery Research Foundation (IRRF) using open-ended and multiple-choice style questions on SL-SRS practices and indications with the goal of qualitatively understanding how SL-SRS is being implemented worldwide. The survey was distributed to physicians in the United States (US) and internationally who are members of the IRRF and who perform SRS frequently. Ten out of 50 IRRF institutions provided responses reflecting the practices of 16 physicians. RESULTS: SL-SRS is being performed at 8/10 institutions. The most common reasons for using SL-SRS included patients with prior WBRT, patients with progressing systemic disease with central nervous system (CNS)-penetrating or immunotherapies available, specific requests from medical oncology, and cooperative studies using this approach. Lesion size was cited as the most important factor when choosing to irradiate any single lesion. The majority of respondents reported 30 mm and 40 mm as size cutoffs (by largest dimension) for treatment of a lesion in eloquent and non-eloquent locations, respectively. Eloquence of lesion location and attributable symptoms were also considered important. Progression of untreated lesions was the most common reason reported for bringing patients back for additional treatment. CONCLUSION: The responses to this survey show that SL-SRS is being used, allowing for small/asymptomatic brain metastases to be left safely unirradiated. It is currently used in patients who have >10-15 lesions with prior WBRT, those with progression of extracranial disease but with acceptable systemic treatment options, and those with poor functional status. The incorporation of this new approach into clinical trials should be considered for the safe study of the efficacy of new CNS-penetrating systemic therapies.

A target definition based on electroanatomic maps for stereotactic arrhythmia radioablation.

PURPOSE: Identifying the target region is critical for successfully treating ventricular tachycardia (VT) with single fraction stereotactic arrhythmia radioablation (STAR). We report the feasibility of target definition based on direct co-registration of electroanatomic maps (EAM) and radioablation planning images. MATERIALS AND METHODS: The EAM consists of 3D cardiac anatomy representation with electrical activity at endocardium and is acquired by a cardiac electrophysiologist (CEP) during electrophysiology study. The CEP generates an EAM using a 3D cardiac mapping system anticipating radioablation planning. Our in-house software read these non-DICOM EAMs, registered them to a planning image set, and converted them to DICOM structure files. The EAM based target volume was finalized based on a consensus of CEPs, radiation oncologists and medical physicists, then expanded to ITV and PTV. The simulation, planning, and treatment is performed with a standard STAR technique: a single fraction of 25 Gy using volumetric-modulated arc therapy or dynamic conformal arc therapy depending on the target shape. RESULTS: Seven patients with refractory VT were treated by defining the target based on registering EAMs on the planning images. Dice similarity indices between reference map and reference contours after registration were 0.814 ± 0.053 and 0.575 ± 0.199 for LV and LA/RV, respectively. CONCLUSIONS: The quality of the transferred EAMs on the MR/CT images was sufficient to localize the treatment region. Five of 7 patients demonstrated a dramatic reduction in VT events after 6 weeks. Longer follow-up is required to determine the true safety and efficacy of this therapy using EAM-based direct registration method.

Treatment trends in brain metastases from testicular cancer in the United States.

Aim: We utilized the National Cancer Database to describe the treatment trends in brain metastases from primary testicular cancers. Methods: We analyzed data from the NCDB from 2010 to 2015 for patients with both primary testicular cancers and brain metastases who were treated with brain-directed radiation. We performed multivariable logistic and cox regressions to identify predictors of treatment type and overall survival respectively. Results: Most patients meeting the above criteria received whole brain radiation therapy as opposed to stereotactic radiosurgery (SRS). Predictors of improved survival were age, private insurance coverage, receipt of chemotherapy, and receipt of SRS. The 5-year survival rate was highest for patients who received SRS. Conclusion: This study confirms significantly improved overall survival with the use of SRS.

Testicular cancer is quite rare, making up just 1% of solid cancers found in men every year. Even rarer is the situation where this cancer spreads to the brain. When this happens, it can be treated in a few different ways: surgery, radiation to the entire brain, a focused type of radiation called stereotactic radiosurgery, or a combination of these methods. Due to its rarity, there isn't a clear-cut best approach for treating these brain tumors. In our research, we used a massive database, the National Cancer Database (NCDB), to get a clearer picture of this issue. We looked at patients diagnosed with testicular cancer between 2004 and 2015 who also had at least one tumor in the brain. By analyzing this information, we could compare the survival outcomes of patients based on the type of treatment they received and other factors. We found that brain tumors from testicular cancer are very rare, found in just 0.4% of the patients we studied. We also found that treatment with either focused radiation, whole brain radiation, or chemotherapy significantly improves survival rates compared with no treatment. In addition, focused radiation, called stereotactic radiosurgery, might result in even better survival results than radiation to the entire brain. Receiving this focused radiation was more common in patients who also had tumors in other parts of their body. While our study gives essential insights, it does have some limitations. The database we used doesn't provide specific details like the size of the brain tumors, the exact treatment doses, and some other crucial patient information. This means that while we now have a better overall picture, more research is needed to give patients and doctors a complete understanding.

Survival Benefit with Re-resection and Optimal Time to Re-resection in Gallbladder Cancer: a National Cancer Database Study.

PURPOSE: Gallbladder cancer is often diagnosed incidentally after cholecystectomy. Most patients will then undergo re-resection for potential residual disease; however, overall survival (OS) benefit data in this scenario is variable. This National Cancer Database analysis (NCDB) compared OS in patients with T1b-T3 gallbladder cancer who underwent re-resection and evaluated if time to resection impacts OS. METHODS: We reviewed the NCDB for patients who received initial cholecystectomy for gallbladder cancer and were subsequently eligible for re-resection based on tumor stage (T1b-T3 disease). Patients with re-resection were subdivided into four cohorts based on time to re-resection: 0-4 weeks, 5-8 weeks, 9-12 weeks, and > 12 weeks. We used a Cox proportional hazards ratio to identify factors associated with worse survival and logistic regression to evaluate characteristics associated with re-resection. OS was calculated using Kaplan Meier curves. RESULTS: A total of 791 (5.82%) patients received re-resection. Cox proportional hazards analysis showed a comorbidity score of 1 was associated with worse survival. Patients with higher comorbidity scores and treatment at comprehensive community, integrated, or academic cancer programs were less likely to undergo re-resection. Re-resection showed significantly improved OS [HR 0.87; 95 CI 0.77-0.98; p = 0.0203]. Improved survival was appreciated when re-resection was completed at 5-8 weeks [HR 0.67; CI 0.57-0.81], 9-12 weeks [HR 0.64; CI 0.52-0.79], or > 12 weeks [HR 0.61; CI 0.47-0.78] compared to 0-4 weeks. CONCLUSION: Optimal timing to re-resection in gallbladder cancer supports previous data showing benefit at > 4 weeks. However, there was no significant survival difference as to whether re-resection was completed at 5-8 weeks, 9-12 weeks, or > 12 weeks post initial cholecystectomy.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Treatment Selection and Survival in Patients with Gray Zone Lymphoma: A Comprehensive Population-Based Analysis.

BACKGROUND AND OBJECTIVES: There are no treatment guidelines for gray-zone lymphoma (GZL), given the disease's rarity and being a relatively new entity. Our objective was to assess factors affecting treatment selection in GZL and its effect on survival, focusing on combined modality treatment (CMT) versus chemotherapy alone. PATIENTS AND METHODS: We identified 1047 patients with GZL treated with CMT or chemotherapy alone between 2004 and 2016 from the National Cancer Database (NCDB). We excluded patients without histologic confirmation of the diagnosis, those who did not receive chemotherapy, and those who started chemotherapy >120 days or radiation >365 days from diagnosis to account for immortal time bias. Factors affecting treatment selection were investigated using a logistic regression model. A propensity score-matched methodology was used to compare survival outcomes. RESULTS: Only 164 patients (15.7%) received CMT, while 883 (84.3%) received chemotherapy alone. Treatment selection was affected by clinical factors (age, odds ratio [OR] 0.99, 95% confidence interval [CI] 0.98-0.997, p-value 0.01 and advanced stage, OR for stage 4: 0.21, 95% CI 0.13-0.34, p-value < 0.001) but not socioeconomic factors. Higher median income was associated with better survival, while increased age, higher comorbidity score, and B symptoms were associated with worse survival. The use of CMT had a survival advantage over chemotherapy alone (hazard ratio [HR] 0.54, 95% CI 0.351-0.833, p-value 0.005). CONCLUSION: CMT is associated with survival advantage in our analysis. Careful selection of patients is essential to achieve the best outcomes with minimal toxicity. Socioeconomic factors affect treatment selection in patients with GZL that can alter outcomes. Future work should focus on strategies that access disparities without compromising survival.

A Comparison of Single Fraction and Multi Fraction Radiosurgery on the Gamma Knife ICON: A Single Institution Review.

Purpose: Brain metastases are a common development in patients with malignant solid tumors. Stereotactic radiosurgery (SRS) has a long track record of effectively and safely treating these patients, with some limitations to the use of single fraction SRS based on size and volume. In this study, we reviewed outcomes of patients treated using SRS and fractionated SRS (fSRS) to compare predictors and outcomes of those treatments. Methods and Materials: Two hundred patients treated with SRS or fSRS for intact brain metastases were included. We tabulated baseline characteristics and performed a logistic regression to identify predictors of fSRS. Cox regression was used to identify predictors of survival. Kaplan-Meier analysis was used to calculate survival, local failure, and distant failure rates. A receiver operating characteristic curve was generated to determine timepoint from planning to treatment associated with local failure. Results: The only predictor of fSRS was tumor volume >2.061 cm3. There was no difference in local failure, toxicity, or survival by fractionation of biologically effective dose. Predictors of worse survival were age, extracranial disease, history of whole brain radiation therapy, and volume. Receiver operating characteristic analysis identified 10 days as potential factor in local failure. At 1 year, local control was 96.48 and 76.92% for those patients treated before or after that interval, respectively (P = .0005). Conclusions: Fractionated SRS is a safe and effective alternative for patients with larger volume tumors not suitable for single fraction SRS. Care should be taken to treat these patients expeditiously as a delay was shown to affect local control in this study.

Utilization Patterns of Single-Fraction and Short-Course Radiotherapeutic Schedules in the Management of Bone Metastases.

Purpose: Bone metastases are common, occurring in 60% to 70% of patients with advanced malignancies. Historically, bone-directed radiation therapy regimens of 30 Gy over 10 fractions were used. However, prospective randomized data suggest equivalent pain relief with shorter-course regimens. The American Society for Radiation Oncology Choosing Wisely Campaign encourages clinicians to consider shorter-course palliative regimens in patients with limited prognosis. A retrospective analysis was performed to assess patterns of short-course and single-fraction radiation therapy during the past 5 years. Methods and Materials: We queried our electronic medical record (MOSAIQ) from 2016 to 2020 for patients with bone metastases who received palliative radiation therapy. Patients receiving >10 fractions or Medicare-approved palliative courses of radiation (30 Gy/10 fractions, 24 Gy/6 fractions, 20 Gy/5 fractions, 8 Gy/1 fraction) were included. Treatment department was defined as academic (n = 2) versus community (n = 12). Short-course treatment was defined as <6 fractions, whereas long-course included patients receiving >10 fractions. Patients were subdivided based on age and disease site. Physicians were grouped according to their year of residency completion. Multivariable logistic regression analysis identified predictors of short-course and single-fraction treatment. Results: We identified 1004 patients with 1768 bony metastases meeting inclusion criteria. The spine was the most common site, followed by pelvis/hip, extremity, and other site. Use of short-course treatment increased from 40% in 2016 to 50% in 2020. Single-fraction treatment increased from 7% in 2016 to 11% in 2020. Predictors of shorter courses included treatment at academic centers, more recent treatment, patient age >76 years, and nonspine anatomic site. Predictors of single-fraction treatment included treatment at academic centers, treating physician residency completion after 2010, patient age >76 years, and treatment to extremity or other site. Conclusions: Rates of short-course and single-fraction bone-directed radiation therapy increased within our health system over time. Treatment receipt at academic centers was associated with both short-course and single-fraction regimens. Physicians completing residency after 2010 were more likely to deliver single-fraction therapy.

Effects of Neuroanatomic Structural Distances on Pituitary Function After Stereotactic Radiosurgery: A Multicenter Study.

BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

Stereotactic Radiosurgery for Intraventricular Metastases: A Multicenter Study.

BACKGROUND: Intraventricular metastases (IVMs) are uncommon, and their optimal management remains debatable. OBJECTIVE: To define the safety and efficacy of stereotactic radiosurgery (SRS) in the treatment of IVMs. METHODS: This retrospective, multicenter study included patients managed with SRS for IVMs. SRS-induced adverse events, local tumor or intracranial progression, and the frequency of new-onset hydrocephalus or leptomeningeal spread were documented. Analyses of variables related to patient neuroimaging or clinical outcomes were also performed. RESULTS: The cohort included 160 patients from 11 centers who underwent SRS for treatment of 1045 intracranial metastases, of which 196 were IVMs. The median survival from SRS was 10 months. Of the 154 patients and 190 IVMs with imaging follow-up, 94 patients (61%) experienced distant intracranial disease progression and 16 IVMs (8.4%) progressed locally. The 12- and 24-month local IVM control rates were 91.4% and 86.1%, respectively. Sixteen (10%) and 27 (17.5%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Adverse radiation effects were documented in 24 patients (15%). Eleven patients (6.9%) died because of intracranial disease progression. CONCLUSION: SRS is an effective treatment option for IVMs, with a local IVM control rate comparable with SRS for parenchymal brain metastases. Leptomeningeal spread and hydrocephalus in patients with IVM occur in a minority of patients, but these patients warrant careful follow-up to detect these changes.