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PURPOSE This study sought to determine the prognostic significance of the WHO-defined glioma molecular subgroups along with additional alterations, including MGMT promoter methylation and mutations in ATRX, CIC, FUBP1, TERT, and TP53, in NRG/RTOG 0424 using long-term follow-up data. METHODS Mutations were determined using an Ion Torrent sequencing panel. 1p/19q co-deletion and MGMT promoter methylation were determined by Affymetrix OncoScan and Illumina 450K arrays. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios were calculated using the Cox proportional hazard model. Multivariable analyses (MVAs) included patient pretreatment characteristics. RESULTS We obtained complete molecular data to categorize 80/129 eligible patients within the WHO subgroups. Of these, 26 (32.5%) were IDHmutant/co-deleted, 28 (35%) were IDHmutant/non-co-deleted, and 26 (32.5%) were IDHwild-type. Upon single-marker MVA, both IDHmutant subgroups were associated with significantly better OS and PFS ( P values < .001), compared with the IDHwild-type subgroup. MGMT promoter methylation was obtained on 76 patients, where 58 (76%) were methylated and 18 (24%) were unmethylated. Single-marker MVAs demonstrated that MGMT promoter methylation was statistically significant for OS ( P value < .001) and PFS ( P value = .003). In a multimarker MVA, one WHO subgroup comparison ( IDHmutant/co-deleted v IDHwild-type) was significant for OS ( P value = .045), whereas MGMT methylation did not retain significance. CONCLUSION This study reports the long-term prognostic effect of the WHO molecular subgroups, MGMT promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and MGMT both serve as strong prognostic indicators, but that MGMT does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond IDH and 1p/19q status.

Background: Myxopapillary ependymomas (MPE) are intradural spinal tumors with a predilection to the filum terminale. Damage to conus medullaris during surgery can result in sphincteric and sexual dysfunction. The purpose of this study is to determine how myxopapillary ependymoma proximity to the conus impacts patient presentation, extent of resection, and clinical outcomes. Methods: Fifty-one patients who underwent surgical resection of pathologically confirmed myxopapillary ependymoma with at least 1 year of follow-up were included in the study. We collected initial presenting symptoms, distance of the tumor from the conus, extent of resection, and postoperative clinical outcomes including bladder dysfunction. Results: Average age was 38 years (range 7–75 years) with a male to female ratio of 1.43:1. Patients most commonly presented with pain symptoms (88%), and 12 patients (23.5%) had urologic symptoms on presentation. The mean tumor distance from the tip of the conus was 1.60 cm (10 cm above to 21 cm below the tip of the conus). Patients with tumors in contact with the conus had a significantly higher rate of preoperative urinary symptoms and were more likely (32% vs. 14%) to suffer postoperative urinary sphincteric disturbances. Tumors with direct invasion of the conus medullaris were more likely to require intralesional resection and fail to achieve a gross total resection (GTR). Conclusion: Patients with MPE in close proximity to the conus were more likely to suffer from long-term morbidity related to urologic issues following surgical resection. Adjuvant radiotherapy may be a viable option for patients who fail to achieve GTR.

Abstract Ewing sarcoma is a rare tumor that requires complex multidisciplinary management. This report describes the general management and standard radiotherapy guidelines in both North America (Children's Oncology Group) and Europe (International Society of Pediatric Oncology). Standard treatment involves multiagent induction chemotherapy followed by local treatment with surgery, definitive radiation, or a combination of surgery and radiation followed by additional chemotherapy and consolidation local treatment to metastatic sites. The data supporting the role of chemotherapy, surgery, and radiation and specific radiation therapy guidelines are presented.

Abstract Background To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity. Methods Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed. Results Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively. Conclusions Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

Abstract PURPOSE We investigated the long term impact of SRS and WBRT in two large prospective phase III trials. METHODS Patients with 1–4 BMs +/- resection were randomized to SRS or WBRT. Cognitive deterioration was a drop of &gt;1 standard deviation from baseline in &gt;2/6 cognitive measures (CM). Quality of life (QOL) scores were scored 0–100 point scale. CM and QOL scores were modeled using baseline adjusted Linear Mixed Models (LMM) with uncorrelated random intercept for subject and random slopes for time. Differences over time between groups and the effect of &gt;2 cognitive scores with &gt;2 SD change from baseline were assessed. RESULTS 88 patients were included with median follow up of 24 months. We observed decreasing CM over time (SRS: 4/6; WBRT: 5/6). Mean CM was significantly higher in SRS for Total recall and Delayed Recall at 3, 6, 9, 12 months. More patients in WBRT arm declined 1 SD in &gt;1 and &gt;2 CM at the 3, 6, 9, and 12 months. A 1 SD decline in &gt;3 CM at 1 year was 21% SRS vs 47% WBRT (p=0.02). SRS had fewer patients with a 2 SD decline in &gt;1 CM at every time point. SRS had fewer patients with a 2 SD decline at &gt;2 and &gt;3 CM. WBRT had lower QOL at 3 months, but switched to SRS having lower QOL at 24 months for PWB, EWB, FWB, FactG, BR, and FactBR (p&lt; 0.05). A 2 SD decline in cognition decreased mean FWB by 6.4 units (95% CI: -11, -1.75; p=0.007) and decreased QOL by 5.1 units (95% CI: -7.7, -2.5; p&lt; 0.001). CONCLUSIONS We report the first pooled prospective study demonstrating the long term outcomes of patients with BMs after cranial radiation. WBRT was associated with worse cognitive outcomes. Impaired cognition is associated with worse QOL.

Abstract Introduction Coronary artery calcification (CAC) is associated with and identifies patients at higher risk of major adverse cardiovascular events (MACE). However, the prevalence, characteristics, and outcomes of cancer patients with CAC on CT before or after chest radiation therapy (RT) are not well addressed. Methods Retrospective cohort study of all breast cancer patients who underwent chest RT at Mayo Clinic Rochester in 2010. All pre-RT CTs were reviewed and the extent of CAC was recorded in addition to history of pre-RT atherosclerotic risk factors (hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and smoking), history of pre-RT cardiovascular disease (CVD), and RT dosage. MACE (sudden cardiac death (SCD), acute coronary syndrome (ACS), and stroke), and CAC progression in follow-up were recorded. CAC extent was quantified before and on 5-year follow-up CT scan in all patients, and a positive change was considered progression. Patients were divided into 2 groups based on the presence of CAC before RT: present (group 1) or absent (group 2). Results Our cohort was comprised of 244 breast cancer patients who received chest RT. A total of 39 patients (16.9%) had evidence of CAC on CT prior to RT. Compared with patients without CAC before RT (n=205), those with CAC before RT were found to be older (71.8±7.7 vs 58.9±11.3, p&lt;0.01), had higher pre-RT history of HTN (84.6% vs 47.8%); p&lt;0.01), DM (20.5% vs 4.4%; p&lt;0.01), dyslipidemia (74.2% vs 40%; p&lt;0.01), CAD (23.1% vs 3.9%; p&lt;0.01), and stroke (7.69% vs 1.45%; p=0.04). Following RT, patients in group 1 were more likely to exhibit ACS (33.3% vs 2.9%; p&lt;0.01), and stroke (22.6% vs 5.2%; p&lt;0.01). Multinomial logistic regression identified pre-RT CAD pre-RT CAC (β=1.01 (0.33–1.69), OR=7.60 (1.93–29.93); p=0.02) pre-RT CAD (β=0.78 (0.06–1.49), OR=4.74 (1.14–19.74); p=0.03) as independent predictors for the development of MACE after RT. Progression in CAC after RT was found in 61.9% of all patients (13/21) who developed MACE. Conclusion MACE in breast cancer patients undergoing RT can be predicted before RT based on the CV risk factor and disease profile. The strongest predictor for MACE, however, is evidence of CAC before RT. These data provide a unique window for the identification and follow-up of breast cancer RT patients who have a risk of MACE. Funding Acknowledgement Type of funding source: None

Background Metastasectomy is standard of care for pediatric patients with metastatic sarcoma with limited disease. For patients with unresectable disease, stereotactic body radiotherapy (SBRT) may serve as an alternative. Herein, the authors report the results of a prospective, multi‐institutional phase 2 trial of SBRT in children and young adults with metastatic sarcoma. Methods Patients aged >3 years and ≤40 years with unresected, osseous metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone were eligible. Patients received SBRT to a dose of 40 Gray (Gy) in 5 fractions. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were calculated using the Kaplan‐Meier method. Results Fourteen patients with a median age of 17 years (range, 4‐25 years) were treated to 37 distinct metastatic lesions. With a median follow‐up of 6.8 months (30.5 months in surviving patients), the Kaplan‐Meier patient‐specific and lesion‐specific LC rates at 6 months were 89% and 95%, respectively. The median PFS was 6 months and the median OS was 24 months. In a post hoc analysis, PFS (median, 9.3 months vs 3.7 months; log‐rank P = .03) and OS (median not reached vs 12.7 months; log‐rank P = .02) were improved when all known sites of metastatic disease were consolidated with SBRT compared with partial consolidation. SBRT was well tolerated, with 2 patients experiencing grade 3 toxicities. Conclusions SBRT achieved high rates of LC in pediatric patients with inoperable metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone. These results suggest that the ability to achieve total consolidation of metastatic disease with SBRT is associated with improved PFS and OS.

Abstract Background Patterns of recurrence and survival with different surgical and radiotherapy (RT) techniques were evaluated to guide RT target volumes for patients with temporal lobe glioma. Methods and Materials This retrospective cohort study included patients with World Health Organization grades II to IV temporal lobe glioma treated with either partial (PTL) or complete temporal lobectomy (CTL) followed by RT covering both the parenchymal and dural resection bed (whole-cavity radiotherapy [WCRT]) or the parenchymal resection bed only (partial-cavity radiotherapy [PCRT]). Patterns of recurrence, progression-free survival (PFS) and overall survival (OS) were evaluated. Results Fifty-one patients were included and 84.3% of patients had high-grade glioma (HGG). CTL and PTL were performed for 11 (21.6%) and 40 (78.4%) patients, respectively. Median RT dose was 60 Gy (range, 40-76 Gy). There were 82.4% and 17.6% of patients who received WCRT and PCRT, respectively. Median follow-up time was 18.4 months (range, 4-161 months). Forty-six patients (90.2%) experienced disease recurrence, most commonly at the parenchymal resection bed (76.5%). No patients experienced an isolated dural recurrence. The median PFS and OS for the PCRT and WCRT cohorts were 8.6 vs 10.8 months (P = .979) and 19.9 vs 18.6 months (P = .859), respectively. PCRT was associated with a lower RT dose to the brainstem, optic, and ocular structures, hippocampus, and pituitary. Conclusion We identified no isolated dural recurrence and similar PFS and OS regardless of postoperative RT volume, whereas PCRT was associated with dose reduction to critical structures. Omission of dural RT may be considered a reasonable alternative approach. Further validation with larger comparative studies is warranted.

Abstract Osteosarcoma is a rare tumor that requires complex multidisciplinary management. This paper reviews the general management and standard radiotherapy guidelines for osteosarcoma in both North America and Europe in a joined effort between the Children's Oncology Group and International Society of Pediatric Oncology. Standard treatment involves multiagent induction chemotherapy followed by surgical resection for local tumor control and consolidation local control to metastatic sites. Radiotherapy is reserved for cases with a marginal or incomplete resection or for definitive treatment in the case of unresectable disease. We present supporting data for the role of chemotherapy, surgery, and radiation therapy.