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Background: Pleomorphic Xanthoastrocytoma (PXA) is a low-grade central nervous system (CNS) tumor with a generally favorable prognosis. However, due to its rarity, optimal adjuvant treatment guidelines have not been established by large scale studies. In this study, we investigated the effect of adjuvant radiation therapy (RT) on overall survival (OS) in adult patients with PXA to help address this unanswered question., Methods: The National Cancer Database (NCDB) was used to identify adult patients (age ≥ 18 years old) diagnosed with histologically confirmed grade II PXA (2004-2016). Patient demographics, tumor characteristics, and treatment information were collected. Kaplan-Meier curves were generated to study OS, and factors that affected OS were identified using a multivariate Cox proportional hazards (CPH) model., Results: A total of 546 patients were identified. The average age of patients at diagnosis was 36.6 years old, and overall median survival was 128.6 months. RT was used to treat 179 (33.3 %) patients. Those who received RT had a shorter median OS (33.3 months) compared to those who did not (>128.6 months, p < 0.001). Our multivariate model demonstrated receiving RT was independently associated with a significantly higher risk of death (hazard ratio [HR] = 4.28, 95 % confidence interval [CI] = 1.77-10.38, p = .0013). Patients ≥65 years of age also demonstrated significantly higher risk of death (HR = 2.20, CI = 1.54-4.16, p = .006) and had a decreased median OS (26.0 months)., Conclusion: In adults with PXA, treatment with RT is independently associated with a significantly higher risk of mortality. The routine use of this modality in treating PXA warrants further study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

New Zealand has one of the highest rates of melanoma in the world. In up to 10% of cases, the disease is metastatic at diagnosis. Cerebral metastatic involvement carries a particularly poor prognosis. 110 patients were included in the analysis. A retrospective consecutive series of patients treated surgically at Auckland City Hospital were studied, with parameters of demographics, tumour characteristics, surgery, pathology, systemic therapy and survival analysed. Mean age was 59.9 years (range 22-81 years). Median survival from date of surgery was 8.1 months (95% CI 6.9-9.4 months). Of the 58 patients tested for BRAF mutation, 28 were positive, similar to previously published data. This conferred a better prognosis with median overall survival of 12.3 months (95% CI 7.2-17.3 months) compared to 7.8 months (95% CI 5.6-10 months) for those who were negative (p < 0.05). Survival correlated positively with extent of surgical resection. Both BRAF positive status and targeted and/or immunotherapy were significant predictors of improved survival. In this cohort, radiation therapy did not show a statistically significant improvement in overall survival. Survival from resection of cerebral metastases from melanoma is improving. Survival benefit is conferred by BRAF mutation, solitary metastasis and gross total resection of lesion., (Copyright © 2019. Published by Elsevier Ltd.)

Background and Objective: A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed., Methods: Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2 Gy-equivalent doses assuming α/β = 10 (EQD2 [10] ). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05., Results: There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm 3 (range 2.4-149.2). Median EQD2 [10] was 38.4 Gy (range 22.3-59.7) and 24 Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215 days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2 [10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location., Conclusion: This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.

Background: We sought to evaluate the impact of adjuvant radiotherapy dose on overall survival (OS) after surgical resection for localized intracranial ependymoma., Procedure: The National Cancer Database (NCDB) was queried from 2004 to 2015 for patients of all ages with intracranial WHO grade II to III ependymoma treated with surgery and 4500 to 7000 cGy of adjuvant radiotherapy. Pearson χ 2 test and multivariate logistic regression analyses were used to assess clinicodemographic factors and patterns of care. After propensity-score matching, OS was assessed with Kaplan-Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling., Results: Of the 1153 patients meeting criteria, 529 (46%) received ≤ 5400 cGy and 624 (54%) received > 5400 cGy. At a median follow-up of 54.5 months, an OS benefit was observed for > 5400 cGy in pediatric patients aged 2-18 years (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.28-0.99, P = 0.047). No OS difference was found between ≤ 5400 cGy and > 5400 cGy in pediatric patients aged < 2 years (P = 0.819) or in adults (P = 0.180). Increasing age, WHO grade III, subtotal resection, and receipt of chemotherapy portended worse OS. Age 2 to 18 years, WHO III grade, supratentorial location, and receipt of chemotherapy were associated with receiving > 5400 cGy., Conclusion: Adjuvant radiotherapy dose > 5400 cGy was associated with improved OS for children aged 2-18 years with WHO grade II-III intracranial ependymoma. No OS benefit was found with > 5400 cGy in adults or children less than two years of age., (© 2019 Wiley Periodicals, Inc.)

Aim: To share a single center experience with 27 atypical teratoid/rhabdoid tumor (AT/RT) cases, and to determine the effect of gross total tumor resection and other clinical characteristics on the overall survival rate of AT/RT., Material and Methods: We included 27 patients-with a histopathologically confirmed primary intracranial childhood AT/ RT-who were operated in our clinic between January 2000 and December 2017. Age, sex, tumor location, disseminated disease, the presence of hydrocephalus, symptom duration till diagnosis, the extent of resection, and adjuvant radiotherapy were evaluated for their influence on overall survival., Results: Median age at diagnosis for 27 patients was 19.1 months (7.2 months-5 years). Gross total resection was possible in 13 (48.72%) patients. Except for three patients who died of perioperative complications, all patients received chemotherapy and 11 received radiotherapy. In univariate analysis, male sex, older age at diagnosis (≥24 months), gross total resection, and radiotherapy were associated with overall longer survival; however, radiotherapy remained the only significant parameter in multivariate analysis., Conclusion: AT/RT is a rare and dreadful brain tumor that has low survival rates despite contemporary treatment. Radiotherapy seems to prolong survival; however, large-scale studies are needed to establish prognostic factors.

It is unclear whether there is a survival benefit with postoperative radiation for low-grade gliomas deemed to be high-risk. We sought to analyze patterns of care and outcomes of radiation use. We accessed the National Cancer Database to identify patients with WHO grade II oligodendroglioma or astrocytoma between 2010 and 2012. Multivariable logistic regression was used to identify predictors of radiation use and multivariable Cox regression was used to identify covariables associated with differences in survival. There were 1952 patients included in this study, of which 518 (26.5%) received postoperative radiation. The majority had oligodendroglioma histology (n = 1121, 57.4%) compared to astrocytoma (n = 831, 42.6%). There were 1626 patients who were either ≥40 years old or underwent a subtotal resection ("high-risk"), and from these 495 (30.4%) received postoperative radiation. On multivariable logistic regression treatment at an academic facility (OR 0.72) was associated with a lower likelihood of receiving postoperative radiation. Astrocytoma histology (OR 2.08), age ≥40 years (OR 2.23), tumor size ≥6 cm (OR 1.64), subtotal resection (OR 1.55), and chemotherapy use (OR 3.93) were associated with an increased likelihood of postoperative radiation. On multivariable analysis, astrocytoma histology (HR 3.49, p < 0.001) and receipt of radiation (HR 2.06, p < 0.001) were associated with worse overall survival. GTR (HR 0.51, p = 0.001) was associated with improved overall survival. Patients treated in United States hospitals are not routinely referred for postoperative radiation for high-risk, low-grade gliomas. Patients who received radiation did not do better than those who did not receive radiation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Generally, re-irradiation (Re-RT) is offered to patients with glioma recurrences with macroscopic lesions. Results are discussed controversially, and some centers postulate limited benefit of Re-RT. Re-RT is generally offered to tumors up to 4 cm in diameter. Re-resection is also discussed controversially; however, recent studies have shown significant benefit., Objective: To combine proactive re-resection and early Re-RT in patients with recurrent glioma., Methods: We included 108 patients treated between 2002 and 2016 for recurrent glioma. All patients underwent surgical resection for recurrence; Re-RT was applied with a median dose of 37.5 Gy (range 25 Gy-57Gy/equivalent dose in 2Gy fractions [EQD2]) with high-precision techniques. All patients were followed prospectively in an interdisciplinary follow-up program., Results: Median follow-up after Re-RT was 7 mo. Median survival after surgery and Re-RT was 12 mo (range 1-102 mo). Complete resection had a significant impact on the outcome (P = .03). The strongest predictors of outcome were MGMT-promotor methylation and Karnofsky Performance Score and time interval between primary and second RT., Conclusion: Proactive resection of tumor recurrences combined with early Re-RT conveys into promising outcome in recurrent glioma. Complete resection and early Re-RT lead to improved survival. Thus, moving Re-RT to an earlier timepoint during the treatment of recurrent glioma, eg after complete macroscopic removal of the tumor, may be crucial for treatment optimization. Using advanced RT techniques, side effects are low. Currently, this concept is evaluated in the GLIOCAVE/NOA 17 trial.

Background: Glioblastoma relapses in the vast majority of cases within 1 year. Maximum safe resection of the recurrent glioblastoma can be offered in some cases. Re-irradiation has been established for the treatment of recurrent glioblastoma, too. In both cases, adjuvant treatment, mostly using temozolomide, can improve PFS and OS after these interventions. However, combining gross tumor resection and adjuvant re-radiotherapy to the resection cavity has not been tested so far., Methods/design: In the multicenter two-armed randomized Phase II GlioCave Study, fractionated stereotactic radiotherapy to the resection cavity, after gross tumor resection of recurrent glioblastoma, will be compared to observation. Depending on the size of the target volume, a total dose of 46 Gy in 2 Gy per fraction or a total dose if 36 Gy in 3 Gy per fraction will be applied. Progression free survival will be the primary endpoint of the study., Discussion: Adjuvant treatment after gross tumor resection of recurrent glioblastoma is currently deemed to be limited to chemotherapy. However, re-irradiation has proven safety and tolerability in the treatment of macroscopic disease. Performing re-irradiation as an adjuvant measure after gross tumor resection has not been tested so far. The GlioCave Study will investigate the efficacy and the safety profile of this approach., Trial Registration: The trial was prospectively registered at clinicaltrials.gov ( NCT02715297 , registration date February 29th, 2016). The protocol presented hereby refers to the version 1.2 of the protocol (January 11 th , 2017).

Objective: Central neurocytoma (CN) is a rare central nervous system tumor the optimal management strategy of which remains controversial because of their rarity. Detailed information on CN is necessary to establish optimal management strategies. The purpose of this study was to show the clinical features, treatments, and long-term clinical outcomes of CN., Methods: A total of 63 patients with CN were surgically treated between 1995 and 2016 at West China Hospital. All pathologically proven CN cases were identified. Epidemiologic characteristics, clinical features, imaging features, functional outcomes, overall survival, and progression-free survival according to multimodal treatments were reviewed retrospectively., Results: There were 29 males and 34 females, with a median age of 29 years (range, 15-58 years). Thirty-four patients underwent gross total resection (GTR) and 29 patients underwent subtotal resection (STR). The surgical approaches to CNs in this study included a transcortical approach (39 cases) and an interhemispheric transcallosal approach (24 cases). There were no differences in functional outcomes or initial extent of resection according to the surgical approach used. The extent of resection was GTR in 34 patients (54.0%), and STR in 29 patients (46.0%). At the median follow-up of 74 months (range, 6-205 months), the actuarial 5-year and 10-year overall survival were 93.3% and 85.4%. At the last follow-up, 8 patients had experienced tumor progression. The 5-year and 10-year progression-free rate was 73.4% and 57.5%. The initial extent of resection and multimodal treatment was not related to overall survival; however, the actuarial local control rate differed significantly according to the initial extent of resection and multimodal treatment., Conclusions: CN is a rare type of World Health Organization grade II primary brain tumor with a tendency to recur. Complete resection of CNs with maximal safety remains the primary treatment to minimize local progression. Adjuvant radiotherapy should be considered in patients receiving incomplete resection. The long-term clinical outcomes of CN after multimodal treatment seem to be satisfactory., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis., Methods and Materials: In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs <2.0 and ≥2.5 vs <2.5)., Results: A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53)., Conclusions: We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Multiple regimens for stereotactic radiosurgery (SRS) at the postoperative bed have shown a high local control rate and a low toxicity profile with no decrease in overall survival with the omission of whole-brain radiation therapy., Methods: In this retrospective analysis, we evaluate our experience with postoperative SRS using a uniform regimen of 25 Gy in 5 sessions., Results: Between April 2011 and May 2014, 75 patients were treated for 77 metastatic brain lesions with postoperative SRS in 5 sessions. The median planning target volume was 13.8 cm(3) (1.93-128.43 cm(3)) with a median follow-up for all lesions of 9.5 months (range, 1.2-38.2 months). Kaplan-Meier estimates of local control at 1 and 2 years were 88.8% and 83.9%, respectively. On univariate analysis, a trend in decreased survival with multiple brain lesions was noted (hazard ratio [HR] = 2; 95% confidence interval [CI], 0.87-4.53; P = 0.10). There was a trend towards decreased local control with radioresistant tumors (HR = 3.23; 95% CI, 0.7-22.6; P = 0.14) and planning target volume ≥17 cm(3) (HR = 3.07; 95% CI, 0.73-15.23; P = 0.12). Two (3%) patients developed radionecrosis, one of whom required craniotomy., Conclusions: SRS with a dose of 25 Gy in 5 sessions is associated with excellent local control at the resection site with minimal toxicity in the postoperative settings in our patient population. Further investigation is required to determine if dose escalation to the postoperative cavity of radioresistant tumors improves outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Aim of this single center, retrospective study was to assess the efficacy and safety of linear accelerator-based hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity of brain metastases after surgical resection. Local control (LC), locoregional control (LRC = new brain metastases outside of the treatment volume), overall survival (OS) as well as acute and late toxicity were evaluated., Patients and Methods: 46 patients with large (> 3 cm) or symptomatic brain metastases were treated with HFSRT. Median resection cavity volume was 14.16 cm(3) (range 1.44-38.68 cm(3)) and median planning target volume (PTV) was 26.19 cm(3) (range 3.45-63.97 cm(3)). Patients were treated with 35 Gy in 7 fractions prescribed to the 95-100 % isodose line in a stereotactic treatment setup. LC and LRC were assessed by follow-up magnetic resonance imaging., Results: The 1-year LC rate was 88 % and LRC was 48 %; 57% of all patients showed cranial progression after HFSRT (4% local, 44% locoregional, 9% local and locoregional). The median follow-up was 19 months; median OS for the whole cohort was 25 months. Tumor histology and recursive partitioning analysis score were significant predictors for OS. HFSRT was tolerated well without any severe acute side effects > grade 2 according to CTCAE criteria., Conclusion: HFSRT after surgical resection of brain metastases was tolerated well without any severe acute side effects and led to excellent LC and a favorable OS. Since more than half of the patients showed cranial progression after local irradiation of the resection cavity, close patient follow-up is warranted. A prospective evaluation in clinical trials is currently being performed.

Aims: To determine pathological features that predict survival in patients having repeat craniotomy within 6 months of radiotherapy for high-grade glioma (HGG)., Materials and Methods: HGG patients (World Health Organization grade 3/4) managed with repeat craniotomy within 6 months of completing radiotherapy between 2008 and 2012 were included. Based on the presence of residual tumour cells, the pathology was reported as pathological progression or pathological pseudoprogression. The proliferation index (Ki67) was reported and compared with initial pathology as a percentage change. Tumour necrosis was estimated as a percentage of the specimen. Overall survival was calculated in months., Results: Of 327 patients managed with HGG, 27 patients underwent repeat craniotomy within 6 months of radiotherapy. The median survival after reoperation was 11 months (95% confidence interval 1-22). Ki67 at reoperation of 0%, 1-9% and >10% was associated with survival with a median survival of 13, 13 and 3 months, respectively (P = 0.007). Change in Ki67 was also associated with median survival, with <50% reduction median survival 3 months, 50-80% median survival 7 months and >80% reduction median survival 13 months, P = 0.02. Widespread treatment-related necrosis improved outcome, with >80% necrosis having a median survival of 13 months versus 3 months in those with <80% necrosis (P = 0.003)., Conclusion: The presence of residual tumour at repeat craniotomy within 6 months of radiotherapy is not an independent indicator of prognosis. Patients with residual tumour that had a low Ki67 had a similar median survival as those with only treatment necrosis. Reduced proliferation of residual tumour cells and widespread necrosis may be more important indicators for future outcome., (Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Because of the rarity of intracranial hemangiopericytomas (HPCs), the role of postoperative radiation therapy (PORT) in the management of HPC remains unclear. This study therefore analyzed the effects of PORT on patterns of failure and survival improvement in patients with HPC. Fifty-two patients surgically treated for intracranial HPC at our institution between 1992 and 2013 were retrospectively analyzed. Patterns of failure were subdivided into local recurrence, regional metastasis, and distant metastasis. Multivariate Cox proportional hazards models were used to assess factors prognostic of treatment failure and survival, and a time-dependent Cox proportional hazards models were used to investigate the correlations between patterns of failure and death. Of the 52 patients, 45 (87 %) underwent gross total resection, and 39 (75 %) received PORT. PORT significantly lengthened local control (LC) and overall survival (OS), by 14 and 13 months, respectively, independent of the extent of resection. Patients who did and did not receive PORT had 5 year LC rates of 97 and 44 %, respectively (HR .05, P = .002); and 10 year OS rates of 83 and 25 %, respectively (hazard ratio (HR) .20, P = .008). PORT, however, did not show preventive effects on regional and distant metastases. The main patterns of failure were local recurrence in patients who did not receive PORT and distant metastasis in those who received PORT. Regional metastasis was a main immediate cause of death (P < .001), and tended to occur more frequently and earlier in patients not receiving PORT.

Importance: It remains uncertain whether treatment with stereotactic radiosurgery (SRS) alone can be safely applied to all patient populations with 1 to 4 brain metastases (BMs) exhibiting heterogeneous prognoses., Objective: To investigate the feasibility of SRS alone for patients with different prognoses determined by the diagnosis-specific Graded Prognostic Assessment (DS-GPA)., Design, Setting, and Participants: A secondary analysis (performed in September 2014) of the Japanese Radiation Oncology Study Group (JROSG) 99-1, a phase 3 randomized trial, comparing SRS alone and whole-brain radiotherapy (WBRT) + SRS conducted in 1999 to 2003. Among a total of 132 patients, 88 with non-small-cell lung cancer (NSCLC) and 1 to 4 BMs were included and poststratified by DS-GPA scores to avoid potential bias from BMs from different primary cancer types. The median follow-up time was 8.05 months., Interventions: The WBRT schedule was 30 Gy in 10 fractions over 2 to 2.5 weeks. The mean SRS dose was 21.9 Gy in SRS alone and 16.6 Gy in WBRT + SRS., Main Outcomes and Measures: The primary end point was overall survival (OS), and the secondary end points included brain tumor recurrence (BTR), salvage treatment, and radiation toxic effects., Results: Forty-seven patients had a favorable prognosis, with DS-GPA scores of 2.5 to 4.0 (26 SRS-alone and 21 WBRT + SRS [DS-GPA 2.5-4.0 group]), and 41 had an unfavorable prognosis, with DS-GPA scores of 0.5 to 2.0 (19 SRS-alone and 22 WBRT + SRS [DS-GPA 0.5-2.0 group]). Significantly better OS was observed in the DS-GPA 2.5-4.0 group in WBRT + SRS vs the SRS alone, with a median survival time of 16.7 (95% CI, 7.5-72.9) months vs 10.6 (95% CI, 7.7-15.5) months (P = .04) (hazard ratio [HR], 1.92; 95% CI, 1.01-3.78). However, no such difference was observed in the DS-GPA 0.5-2.0 group (HR, 1.05; 95% CI, 0.55-1.99) (P = .86). This benefit could be explained by the differing BTR rates, in that the prevention against BTR by WBRT had a more significant impact in the DS-GPA 2.5-4.0 group (HR, 8.31; 95% CI, 3.05-29.13) (P < .001) vs the DS-GPA 0.5-2.0 group (HR, 3.57; 95% CI, 1.02-16.49) (P = .04)., Conclusions and Relevance: Despite the current trend of using SRS alone, the important role of WBRT for patients with BMs from NSCLC with a favorable prognosis should be considered. Our findings should be validated through appropriately designed prospective studies., Trial Registration: umin.ac.jp/ctr Identifier: C000000412.

Background: The purpose of this study was to evaluate the prognostic significance of Ki-67 and subjective microvascular density (SMVD) indexes together with other factors in patients with oligodendroglioma., Materials and Methods: In this retrospective study, oligodendroglioma specimens obtained from twenty-five consecutive patients were evaluated for Ki-67 and SMVD indices to help determine histological grading and investigate the fidelity of these markers in clinical prognosis. Other potentially prognostic factors were Karnofsky performance scale, tumor histological grade, and adjuvant radiotherapy., Results: The Ki-67 proliferation index appeared to have a strong correlation with the grade of the tumor and the survival. Age, gender, adjuvant radiotherapy, surgical resection type (complete versus incomplete) did not have any influence on recurrence. The SMVD index correlated significantly with the 3 to 5-year survival., Conclusions: Ki-67 and MVD indexes are important and useful markers in estimating the prognosis of oligodendrogliomas.

Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology., Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT., Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses., Conclusions: In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The benefit of whole-brain radiation therapy (WBRT) following stereotactic radiation surgery (SRS) for brain metastases is controversial. We conducted a systematic analysis of published literature to explore the outcome of brain metastases treated with SRS and WBRT versus SRS alone using PubMed and MEDLINE. Outcomes including survival, control, salvage therapy, and other quality of life measures were reported. Three randomized controlled trials involving 389 patients with 1 to 4 brain metastases were selected. In 2 of these trials (n = 190), the mean 1-year survival was 33.2% for SRS + WBRT and 38.7% for SRS alone (P = .5233); 1-year local control was 89% for SRS + WBRT and 71% for SRS alone (P < .001). Mean crude distant recurrence rate for SRS + WBRT was 36.6% and 54% for SRS alone (P < .001). Patients without WBRT were over 3 times more likely to require salvage therapy (P < .001). The addition of WBRT was associated with a decreased health-related quality of life assessment, mini mental status exam, and Hopkins Verbal Learning Test (P < .05). Five retrospective studies (n = 1122) were also included in a separate analysis and yielded findings that supported results from the randomized trials. Our systematic analysis demonstrates that adjuvant WBRT following SRS for the treatment of oligometastases in the brain is more effective at controlling local and distant recurrence than SRS alone, but there is no apparent benefit for survival or symptomology. The proven cognitive decline and neurotoxicity present with WBRT should be weighed against the benefit of local control. Prognosis of brain metastasis is poor regardless of current treatment and further exploration for alternative adjuvant treatment for SRS is warranted., (© 2014. Published by Elsevier Inc. All rights reserved.)

Background: Several trials incorporating adjuvant focal RT for treatment of young children with ependymoma have demonstrated improved survival with acceptable adverse effects. The optimal timing of RT administration is, however, unknown., Procedure: A retrospective review of territory-wide database was performed to identify pediatric patients with ependymoma diagnosed between 1995 and 2011. OS and EFS were compared between patients receiving upfront RT (<150 days of diagnosis), delayed RT (≥150 days of diagnosis), or no RT., Results: Thirty-one patients with intracranial ependymoma were identified. Median age was 3.5 years and 14 (45%) were male. Primary tumor was supratentorial in 10 (32%) and infratentorial in 21 (68%). All patients underwent initial surgery, with gross-total resection (GTR) in 27 (87%). Twelve (39%) received upfront RT, 10 (32%) had delayed RT and 9 (29%) had no RT. During the study period, there were 11 relapses (35%) and 10 deaths (32%). Five-year OS was 69.9% and 5yr-EFS was 49.3%. In univariate analysis, GTR led to improved OS (P < 0.001) and EFS (P = 0.004); superior OS and EFS was observed in patients who received RT when compared with those without (P = 0.018 and 0.011, respectively). Upfront RT also resulted in better OS and EFS than delayed RT (P = 0.049 and 0.014, respectively). No significant effect on survival was observed with age, sex, tumor location, RT dosage, and protocol used. In multivariate analysis, GTR significantly improved OS (P = 0.002) and EFS (P = 0.004)., Conclusions: Our results support the early initiation of adjuvant RT in the multi-modal management of pediatric ependymomas., (© 2013 Wiley Periodicals, Inc.)

Background: Tumor bed stereotactic radiosurgery (SRS) after resection of brain metastases is a new strategy to delay or avoid whole-brain irradiation (WBRT) and its associated toxicities. This retrospective study analyzes results of frameless image-guided linear accelerator (LINAC)-based SRS and stereotactic hypofractionated radiotherapy (SHRT) as adjuvant treatment without WBRT., Materials and Methods: Between March 2009 and February 2012, 44 resection cavities in 42 patients were treated with SRS (23 cavities) or SHRT (21 cavities). All treatments were delivered using a stereotactic LINAC. All cavities were expanded by ≥ 2 mm in all directions to create the clinical target volume (CTV)., Results: The median planning target volume (PTV) for SRS was 11.1 cm(3). The median dose prescribed to the PTV margin for SRS was 17 Gy. Median PTV for SHRT was 22.3 cm(3). The fractionation schemes applied were: 4 fractions of 6 Gy (5 patients), 6 fractions of 4 Gy (6 patients) and 10 fractions of 4 Gy (10 patients). Median follow-up was 9.6 months. Local control (LC) rates after 6 and 12 months were 91 and 77 %, respectively. No statistically significant differences in LC rates between SRS and SHRT treatments were observed. Distant brain control (DBC) rates at 6 and 12 months were 61 and 33 %, respectively. Overall survival (OS) at 6 and 12 months was 87 and 63.5 %, respectively, with a median OS of 15.9 months. One patient treated by SRS showed symptoms of radionecrosis, which was confirmed histologically., Conclusion: Frameless image-guided LINAC-based adjuvant SRS and SHRT are effective and well tolerated local treatment strategies after resection of brain metastases in patients with oligometastatic disease.

Concerns regarding long-term toxicities have led to the avoidance of post-operative radiation (PORT) in young children with intracranial ependymoma. We investigated the association between post-operative radiation therapy and overall survival (OS) in children younger than 3 years and compared their survival to other age groups. The study sample from the SEER database included 804 patients with intracranial ependymoma, grades 2-3, and diagnosed between 1988 and 2005. OS was estimated using the Kaplan-Meier method, and hazard ratios (HR) and 95% confidence limits (CL) were calculated based on multivariable Cox proportional hazards models. A total of 804 patients were selected and PORT was administered to 35% of patients younger than 3 years. With a median follow-up of 3 years (range 0.1-18 years), the 3 year OS was 61% for children younger than 3 years, 83% for those ages 3-20 years, and 69% for patients older than 20 years (P < 0.001). In multivariable analysis, OS was significantly improved for patients receiving PORT (HR 0.8, 95% CL 0.6-0.9), and gross total resection (HR 0.6, 95% CL 0.5-0.8). Among children younger than 3 years, the 3 year OS was significantly greater among those who received PORT compared to those who did not (81% vs. 56%, respectively, P = 0.005). The majority of children younger than 3 years with intracranial ependymoma did not receive PORT. Children younger than 3 years who did not receive PORT had a relatively poor outcome, while those who received radiation therapy had a survival similar to older patients.

Objective: Despite the published information on cranial chordoma, most of the data regarding survival in these patients has come from a single institution. Here, we perform a systematic review of the literature to evaluate across multiple institutions the overall survival after treatment for intracranial chordoma., Materials and Methods: We systematically analysed every study published in English and found a total of over 2000 patients being treated for intracranial chordoma. The overall 5-year and 10-year survivals in these patients were stratified according to the age (<5 years vs. >5 years and  <40 years vs. >40 years), treatment (surgery and radiation vs. surgery alone) and histological findings (chondroid vs. typical). Data were analysed via Pearson chi-square test and student t-test when appropriate., Results: A total of 560 non-duplicated patients treated for cranial chordoma met inclusion criteria for this systematic analysis. The survival rate among these patients was 63% (299 patients) and 16% (176 patients) for 5-year and 10-year survivals, respectively. There was no difference in overall survival between the two groups when a cut-off age of 40 years was used (<40 years = 50% vs.  >40 years = 51% at 5-year survival; p = 0.1), but when 5 years was used as the cut-off age, then survival was better for patients in the group older than 5 years of age (<5 years = 14% vs.  >5 years = 66%; p = 0.001). There was no difference between 5-year survival in patients with chordoma with histological chondroid features and those with chordoma possessing typical histology (45% vs. 67%; p = 0.06). When patients who only received surgery were compared to those patients who were treated with surgical intervention in combination with adjuvant radiation treatment, no difference in survival rate was found (54% vs. 56% at 5 years; p = 0.8)., Conclusion: The results of our systematic study provide data to predict the survival of intracranial chordoma patients across multiple institutions. Our data suggest that patients younger than 5 years of age may be associated with a worse prognosis, and adjuvant radiation therapy and histological type were not associated with the improvement of survival rates.

Object: Intracranial hemangiopericytoma (HPC) is a rare and malignant extraaxial tumor with a high proclivity toward recurrence and metastasis. Given this lesion's rarity, little information exists on prognostic factors influencing mortality rates following treatment with surgery or radiation or both. A systematic review of the published literature was performed to ascertain predictors of death following treatment for intracranial HPC., Methods: The authors identified 563 patients with intracranial HPC in the published literature, 277 of whom had information on the duration of follow-up. Statistical analysis of survival was performed using Kaplan-Meier and Cox regression analysis., Results: Hemangiopericytoma was diagnosed in 246 males and 204 females, ranging in age from 1 month to 80 years. Among patients treated for HPC, overall median survival was 13 years, with 1-, 5-, 10-, and 20-year survival rates of 95%, 82%, 60%, and 23%, respectively. Gross-total resection alone (105 patients) was associated with superior survival rates overall, with a median survival of 13 years, whereas subtotal resection alone (23 patients) resulted in a median survival of 9.75 years. Subtotal resection plus adjuvant radiotherapy led to a median survival of 6 years. Gross-total resection was associated with a superior survival benefit to patients regardless of the addition or absence of radiation, and patients receiving > 50 Gy of radiation had worse survival outcomes (median survival 4 vs 18.6 years, p < 0.01, log-rank test). Patients with tumors of the posterior fossa had a median survival of 10.75 versus 15.6 years for those with non-posterior fossa tumors (p < 0.05, log-rank test)., Conclusions: Treatment with gross-total resection provides the greatest survival advantage and should be pursued aggressively as an initial therapy. The addition of postoperative adjuvant radiation does not seem to confer a survival benefit.

Purpose: To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma., Methods and Materials: Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months., Results: The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT -- three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106)., Conclusions: The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients., Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured., Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months., Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients.