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.

Trends in radiation dose for low grade gliomas across the United States.

PURPOSE: Adjuvant radiation is often used in patients with low grade gliomas with high-risk characteristics with a recommended dose of 45-54 Gy. We used the National Cancer Database (NCDB) to see which doses were being used, and if any difference was seen in outcome. METHODS: We queried the NCDB for patients with WHO Grade 2 primary brain tumors treated with surgery and adjuvant radiotherapy. We divided the cohort into dose groups: 45-50 Gy, 50.4-54 Gy, and > 54 Gy. Multivariable logistic regression was used to identify predictors of low and high dose radiation. Propensity matching was used to account for indication bias. RESULTS: We identified 1437 patients meeting inclusion criteria. Median age was 45 years and 62% of patients were > 40 years old. Nearly half of patients (48%) had astrocytoma subtype and 70% had subtotal resection. The majority of patients (69%) were treated to doses between 50.4 and 54 Gy. Predictors of high dose radiation (> 54 Gy) were increased income, astrocytoma subtype, chemotherapy receipt, and treatment in later year (2014). The main predictors of survival were age > 40, astrocytoma subtype, and insurance type. Patients treated to a dose of > 54 Gy had a median survival of 73.5 months and was not reached in those treated to a lower dose (p = 0.0041). CONCLUSIONS: This analysis shows that 50.4-54 Gy is the most widely used radiation regimen for the adjuvant treatment of low-grade gliomas. There appeared to be no benefit to higher doses, although unreported factors may impact interpretation of the results.

Management of brain metastases from large cell neuroendocrine carcinoma of the lung: improved outcomes with radiosurgery.

OBJECTIVES: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare pulmonary tumor, having similar natural history and management strategy as small cell lung cancer. Therefore, the management of brain metastases in these patients has mirrored that of SCLC through the use of whole brain radiation therapy (WBRT). We used the National Cancer Database (NCDB) to look at predictors of stereotactic radiosurgery (SRS) and any potential differences in outcomes for patients with brain metastases from LCNEC. MATERIAL AND METHODS: We queried the NCDB from 2004 to 2015 for patients with LCNEC of the lung with brain metastases that received brain radiation. Univariable and multivariable analyses were performed to identify factors predictive of SRS use and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Out of 9970 patients with LCNEC of the lung we identified 348 with brain metastases. Sixty-eight patients were treated with upfront SRS and 280 were treated with WBRT. Patients that were treated at an academic facility or received chemotherapy as part of upfront treatment were more likely to receive SRS. Univariable analysis revealed improved outcomes with SRS compared to WBRT, with a median OS of 11 months compared to 6 months, respectively (p = .007). Multivariable Cox regression with propensity score confirmed SRS to have improved survival (HR: 0.68, 95%CI: 0.51-0.91, p = .0093). Multivariable Cox regression with propensity score also identified younger age, receipt of chemotherapy, absence of extracranial disease and non-rural locations as additional predictors of improved OS. CONCLUSIONS: Treatment of brain metastases from LCNEC of the lung with SRS was associated with improved survival. For the appropriate patients, upfront treatment of limited brain metastases with SRS may be appropriate.

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era.

OBJECTIVE: The aim of this study was to evaluate the efficacy of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) as salvage therapy for recurrent high-grade glioma and to look at the overall efficacy of treatment with linear accelerator (LINAC)-based radiosurgery and fractionated radiotherapy. METHODS: From 2010 to 2017, a total of 25 patients aged 23-74 years were re-irradiated with LINAC-based SRS and fSRT. Patients were treated to a median dose of 25 Gy in 5 fractions. RESULTS: The median overall survival (OS) after (initial) diagnosis was 39 months with an actuarial 1-, 3-, and 5-year OS rate of 88, 56, and 30%, respectively. After treatment with SRS or fSRT, the median OS was 9 months with an actuarial 1-year OS rate of 29%. Local control, assessed for 28 tumors, after 6 months was 57%, while local control after 1 year was 39%. Three patients experienced local failure. There was no evidence of toxicity noted after SRS or fSRT throughout the follow-up period. CONCLUSION: SRS and fSRT remain a safe, reasonable, effective treatment option for re-irradiation following recurrent glioblastoma. Additionally, treatment volume may predict local control in the salvage setting.

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.

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.

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.

Trends in the use of radiation for meningioma across the United States.

PURPOSE: Meningiomas are tumors originating from arachnoid cap cells on the surface of the brain or spinal cord. Treatment differs by grade but can consist of observation, surgery, radiation therapy or both. We utilized the National Cancer Database (NCDB) to compare trends in the use stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) in the management of meningioma. MATERIALS AND METHODS: We queried the NCDB from 2004-2015 for meningioma patients (grade 1-3) treated with radiation therapy, either SRS or EBRT. Multivariable logistic regression was used to identify predictors of each treatment and to generate a propensity score. Propensity adjusted Kaplan-Meier survival curve analysis and multivariable Cox hazards ratios were used to identify predictors of survival. RESULTS: We identified 5,406 patients with meningioma meeting above criteria with 45%, 44%, and 11% having World Health Organization (WHO) grade 1, 2, and 3 disease, respectively. Median follow up was 43 months. Predictors for SRS were grade 1 disease, distance from treatment facility, and histology. The only predictor of EBRT was grade 3 disease. Treatment year, histology, race and female sex were associated with improved survival. Five- and 10-year survival rates were 89.2% versus 72.6% (p < 0.0001) and 80.3% versus 61.4% (p = 0.29) for SRS and EBRT respectively. After propensity matching 226 pairs were generated. For SRS, 5-year survival was not significantly improved at 88.2% compared with EBRT (p = 0.056). CONCLUSION: In the present analysis, predictors of SRS utilization in management of meningioma include WHO grade 1 disease, distance from treatment facility and histology whereas conventional EBRT utilization was associated with grade 2 and 3 disease. Future studies need to be performed in order to optimize management of atypical and malignant meningioma.

Resection cavity dynamics and optimal timing of adjuvant stereotactic radiosurgery for resected brain metastases.

Purpose: Optimal timing of SRS after surgical resection of brain metastases (BMs) remains debated but is generally advocated to occur within 4 weeks of surgery to account for cavity remodeling. Our study assesses this recommendation by examining cavity dynamics and any downstream effects on outcome. Methods: Post-operative MRIs were used to compare target lesion volumes to target volume at time of SRS. Spearman's analysis identified a relationship between the time to SRS (ttSRS) and target remodeling. The Mann-Whitney-U test compared median remodeling between groups receiving standard (≤4 weeks) and late (>4 weeks) adjuvant SRS. Kaplan Meier functions estimated probabilities of local recurrence (LR) and survival (OS). A Cox proportional hazards model (CPH) identified predictors of OS, LR, and leptomeningeal disease (LMD). Results: Median ttSRS was 32 days (3-72). A positive correlation exists when comparing ttSRS to reduction in cavity volume (0-10 weeks; p = 0.01) with no difference in median cavity remodeling between standard and late SRS groups. OS and LR rates were respectively 53.3% and 70.2% at 12 months with no difference in OS (p = 0.16) or LR (p = 0.54) between standard and late SRS groups. Subtotal resection predicted LMD (HR: 6.37; p = 0.03). No grade 3 or higher toxicity was seen in follow-up. Conclusion: Resection cavities may continue to shrink well after resection. There is no significant difference in OS or LR based on ttSRS, however, treatment factors such as the extent of resection may account for outcomes such as LMD.

A volume-independent conformity index for stereotactic radiosurgery.

PURPOSE: To develop a volume-independent conformity metric called the Gaussian Weighted Conformity Index (GWCI) to evaluate stereotactic radiosurgery/radiotherapy (SRS/SRT) plans for small brain tumors. METHODS: A signed bi-directional local distance (BLD) between the prescription isodose line and the target contour is determined for each point along the tumor contour (positive distance represents under-coverage). A similarity score function (SF) is derived from Gaussian function, penalizing under- and over-coverage at each point by assigning standard deviations of the Gaussian function. Each point along the dose line contour is scored with this SF. The average of the similarity scores determines the GWCI. A total of 40 targets from 18 patients who received Gamma-Knife SRS/SRT treatments were analyzed to determine appropriate penalty criteria. The resulting GWCIs for test cases already deemed clinically acceptable are presented and compared to the same cases scored with the New Conformity Index to determine the influence of tumor volumes on the two conformity indices (CIs). RESULTS: A total of four penalty combinations were tested based on the signed BLDs from the 40 targets. A GWCI of 0.9 is proposed as a cutoff for plan acceptability. The GWCI exhibits no target volume dependency as designed. CONCLUSION: A limitation of current CIs, volume dependency, becomes apparent when applied to SRS/SRT plans. The GWCI appears to be a more robust index, which penalizes over- and under-coverage of tumors and is not skewed by the tumor volume.

Single Fraction Frameless Stereotactic Radiosurgery on the Gamma Knife Icon for Patients With Brain Metastases: Time to Abandon the Frame?

PURPOSE: The latest version of the Gamma Knife, the Icon, allows for immobilization with a mask in lieu of the traditional frame during stereotactic radiosurgery. There have been some concerns regarding extent of immobilization during single fraction frameless treatment and potential effect on outcomes. As such, we reviewed outcomes in patients with brain metastases treated in a single fraction using either a frame or mask on the Gamma Knife Icon at our institution. METHODS AND MATERIALS: We reviewed the records of 95 patients with a total of 374 metastases treated between May 2019 and January 2021. Thirty-nine patients (41%) were treated using the Leksell frame with the remainder being immobilized with a mask. The median number of metastatic lesions was 2 (1-20). The median prescription dose was 20 Gy (11.5-24 Gy). Odds ratios were generated to identify predictors of mask use. Kaplan-Meier analysis was used to calculate survival, local failure, and distant failure rates. Cox regression was used to identify predictors of survival. Propensity matching was used to account for indication bias. RESULTS: Of the 95 patients treated, 88 (93%) had follow-up with a median duration of 5 months (1-18). Frame utilization was more likely with 6 to 10 brain metastases. Median overall survival was not reached and was 70% and 60% at 6 and 12 months for the entire cohort, respectively. There was no significant difference in survival by immobilization method (P = .12). Six patients had local failure in 10 total lesions (3 patients in each group). After propensity matching the 12 month tumor local control was 96% and 85% for framed and frameless cases, respectively (P = .07). CONCLUSIONS: Frameless mask-based stereotactic radiosurgery using the Gamma Knife Icon is feasible and maintains the excellent local control seen with the use of the headframe.

Radiotherapeutic treatment of brain metastases in patients with gynecologic malignancies: A nationwide analysis.

Objectives: Brain metastases are a rare finding in patients with primary gynecologic malignancies having a poor outcome despite treatment. We sought to use the National Cancer Database (NCDB) to characterize the incidence of brain metastases and types of treatment administered. Methods: We queried the NCDB from 2010-16 for patients with endometrial, cervical, and ovarian primaries with brain metastases at diagnosis treated with radiation-whole brain radiation (WBRT) or stereotactic radiosurgery (SRS). We tabulated baseline characteristics and performed a multivariable logistic regression to identify predictors of SRS. Multivariable Cox regression was used to identify predictors of death. Propensity matching was done to account for indication bias. Results: We identified 765 patients meeting above criteria, representing <1% of patients. Of patients with brain metastases, 287 received radiation to the brain. The median age was 60 (40-90). The majority of patients (80%) received WBRT. On multivariable logistic regression the only predictor of SRS was receipt of chemotherapy. Median follow up was 4.9 months. The overall survival for the entire cohort was 5.2 months. On Cox regression predictors of improved survival were receipt of chemotherapy, no extracranial disease, and SRS. After propensity matching, median survival was 8.3 months compared to 6.3 months in favor of SRS. Conclusions: This study represents the largest series to date of patients with brain metastases from gynecologic malignancies, confirming an incidence of <1% and overall poor prognosis. Radiation remains a viable treatment option.

Predictors of Treatment Interruption During Frameless Gamma Knife Icon Stereotactic Radiosurgery.

PURPOSE: The Gamma Knife (GK) Icon allows for the delivery of stereotactic radiosurgery using a thermoplastic mask in combination with intrafraction motion monitoring using high definition motion management. The system pauses treatment if the magnitude of motion in all directions exceeds 1 to 1.5 mm, causing a break in treatment and prolongation of the session. We reviewed the records of patients treated in a frameless manner on our GK Icon system to determine predictors for treatment interruption. METHODS AND MATERIALS: We reviewed the records of patients treated between May 2019 and May 2020 on the GK Icon using a frameless technique for brain metastases, gliomas, schwannomas, and meningiomas. We recorded treatment time as noted in the plan document, actual treatment delivery time, and any pauses in treatment. We tabulated baseline characteristics including age, gender, diagnosis, performance status, and shifts at time of treatment. We used a receiver operating curve analysis to determine a timepoint corresponding with treatment interruption. We then conducted a logistic regression analysis to generate odds ratios for likelihood of treatment. RESULTS: We identified 150 patients meeting inclusion criteria. The majority (82%) were patients with brain metastases. The median age was 63 and the median dose was 27 Gy (16-30 Gy) in 3 fractions (1-5 fractions). The median treatment time was 23 minutes (4-108 minutes). Sixty-nine patients (46%) had at least 1 pause in treatment (range, 1-7). Receiver operating curve analysis revealed treatment time >19 minutes and rotation >0.47 degrees to be associated with interruption. Multivariable logistic regression revealed rotation >0.47 degrees and treatment time >19 minutes as predictive of interruption. CONCLUSIONS: For patients with rotations exceeding 0.47 degrees or an extended treatment time, physicians should expect treatment interruptions, consider fractionation to lessen table time, or use a frame-based approach.

Adaptation of a Gamma Knife Icon stereotactic radiosurgery program in the face of the COVID-19 pandemic.

Objective: The COVID-19 pandemic necessitated drastic and rapid changes throughout the field of radiation oncology, some of which were unique to the discipline of radiosurgery. Guidelines called for reduced frame use and reducing the number of fractions. Our institution implemented these guidelines, and herein we show the resultant effect on patient treatments on our Gamma Knife Icon program. Methods: In early March 2020 we rapidly implemented suggested changes according to ASTRO and other consensus guidelines as they relate to stereotactic radiosurgery in the COVID-19 era. We reviewed the GK Icon schedule at our institution between January 01 and April 30, 2020. We documented age, condition treated, technique (frame vs. mask), and number of fractions. We then tabulated and graphed the number of patients, framed cases, and fractions delivered. Results: Seventy-seven patients were treated on the GK Icon over that period, for a total of 231 fractions. The number of unique patients varied from 18 (April) to 22 (January). Of the 77 patients only 5 were treated using a frame. The number of fractions per month decreased significantly over time, from 70 in January to 36 in April. Likewise, the percentage of single fraction cases increased from 4.5% per month in January to 67% in April. Conclusions: The results presented here show that it is possible to quickly and efficiently change work flows to allow for reduced fractionation and frame use in the time of a global pandemic. Multidisciplinary cooperation and ongoing communication are integral to the success of such programs.

Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series.

BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21-63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0-10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. IMPORTANCE OF THE STUDY: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp's protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient's derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1-10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies.

Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy.

OBJECT: Whole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up. METHODS: The authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (< or = 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage. RESULTS: From November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800-1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm(3) (range 0.08-22 cm(3)). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2-43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT. CONCLUSIONS: Adjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

Unforeseen Computed Tomography Resimulation for Initial Radiation Planning: Associated Factors and Clinical Impact.

PURPOSE: Repeat computed tomography (CT) simulation is problematic because of additional expense of clinic resources, patient inconvenience, additional radiation exposure, and treatment delay. We investigated the factors and clinical impact of unplanned CT resimulations in our network. METHODS AND MATERIALS: We used the billing records of 18,170 patients treated at 5 clinics. A total of 213 patients were resimulated before their first treatment. The disease site, location, use of 4-dimensional CT (4DCT), contrast, image fusion, and cause for resimulation were recorded. Odds ratios determined statistical significance. RESULTS: Our total rate of resimulation was 1.2%. Anal/colorectal (P < .001) and head and neck (P < .001) disease sites had higher rates of resimulation. Brain (P = .001) and lung/thorax (P = .008) had lower rates of resimulation. The most common causes for resimulation were setup change (11.7%), change in patient anatomy (9.8%), and rectal filling (8.5%). The resimulation rate for 4DCTs was 3.03% compared with 1.0% for non-4DCTs (P < .001). Median time between simulations was 7 days. CONCLUSIONS: The most common sites for resimulation were anal/colorectal and head and neck, largely because of change in setup or changes in anatomy. The 4DCT technique correlated with higher resimulation rates. The resimulation rate was 1.2%, and median treatment delay was 7 days. Further studies are warranted to limit the rate of resimulation.

National trends in radiation dose escalation for glioblastoma.

PURPOSE: Glioblastoma (GBM) carries a high propensity for in-field failure despite trimodality management. Past studies have failed to show outcome improvements with dose-escalation. Herein, we examined trends and outcomes associated with dose-escalation for GBM. MATERIALS AND METHODS: The National Cancer Database was queried for GBM patients who underwent surgical resection and external-beam radiation with chemotherapy. Patients were excluded if doses were less than 59.4 Gy; dose-escalation referred to doses ≥66 Gy. Odds ratios identified predictors of dose-escalation. Univariable and multivariable Cox regressions determined potential predictors of overall survival (OS). Propensity-adjusted multivariable analysis better accounted for indication biases. RESULTS: Of 33,991 patients, 1,223 patients received dose-escalation. Median dose in the escalation group was 70 Gy (range, 66 to 89.4 Gy). The use of dose-escalation decreased from 8% in 2004 to 2% in 2014. Predictors of escalated dose were African American race, lower comorbidity score, treatment at community centers, decreased income, and more remote treatment year. Median OS was 16.2 months and 15.8 months for the standard and dose-escalated cohorts, respectively (p = 0.35). On multivariable analysis, age >60 years, higher comorbidity score, treatment at community centers, decreased education, lower income, government insurance, Caucasian race, male gender, and more remote year of treatment predicted for worse OS. On propensity-adjusted multivariable analysis, age >60 years, distance from center >12 miles, decreased education, government insurance, and male gender predicted for worse outcome. CONCLUSION: Dose-escalated radiotherapy for GBM has decreased over time across the United States, in concordance with guidelines and the available evidence. Similarly, this large study did not discern survival improvements with dose-escalation.

Linear Accelerator-Based Stereotactic Radiotherapy for Low-Grade Meningiomas: Improved Local Control With Hypofractionation.

BACKGROUND AND PURPOSE: Meningioma is a common type of benign tumor that can be managed in several ways, ranging from close observation, surgical resection, and various types of radiation. We present here results from a 10-year experience treating meningiomas with a hypofractionated approach. MATERIALS AND METHODS: We reviewed the charts of 56 patients treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (SRT) from 2008 to 2017. A total of 46 (82%) patients had WHO Grade 1 disease and 10 (18%) had Grade 2. Outcomes that were analyzed included local control rates and the rate and grade of any reported toxicity. RESULTS: A total of 38 women and 18 men underwent SRS to a median dose of 15 Gy (n = 24) or hypofractionated SRT with a median dose of 25 Gy in five fractions (n = 34). Of the 56 patients, 22 had surgery before receiving treatment. The median follow-up was 36 (6-110) months. Local control at 2 and 5 years for all patients was 90% and 88%, respectively. Comparing fractionated to single-fraction treatment, there was improved local control with fractionation (91% vs 80% local control at 2 years, P = .009). There was one episode of late radionecrosis on imaging with associated symptoms after single-fraction treatment and one patient requiring resection of meningioma related to worsening symptoms (and local recurrence) after five-fraction SRT. CONCLUSIONS: This study provides further evidence for high rates of local control and minimal toxicity using a hypofractionated SRT approach, with improvement in local control through use of hypofractionation.

Short-Term Follow-Up Mammography in Breast Conservation Therapy Likely Leads to Unnecessary Downstream Workup: A Longitudinal Study.

PURPOSE: To analyze the effect of post-radiation therapy (XRT) mammographic timing and radiation technique in relation to additional downstream workup for 569 breast conservation therapy patients treated with adjuvant XRT after their initial surveillance mammogram (MMG). METHODS AND MATERIALS: From January 2011 to December 2014, 569 breast cancer patients treated with breast conservation surgery and adjuvant XRT with a follow-up MMG were reviewed. Patients were stratified by the time interval until their first post-XRT MMG, and by XRT technique-whole breast (472), accelerated partial breast (96), conventional fractionation (373), hypofractionation (94), surgical cavity boosts (407), or no boost (66). The primary endpoint was further imaging after the initial MMG. RESULTS: Additional workup for those receiving an MMG within 3 months of completing XRT was 51% (73 of 143), compared with 40% (84 of 210) with MMG between 3 and 6 months and 34.5% (75 of 216) with MMG after 6 months (P=.04). Radiation boost to the postoperative bed was associated with further downstream imaging, whereas accelerated partial-breast irradiation and hypofractionated treatment were not. CONCLUSIONS: Breast conservation therapy patients who underwent screening MMG before 6 months after completion of XRT were more likely to undergo downstream workup, including additional biopsies. Accelerated and hypofractionated radiation techniques were not associated with supplementary workup. Further study is needed to assess appropriate selection of high-risk patients and possible negative implications of earlier post-XRT screening MMG.