BACKGROUND Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00003375.)

There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

PURPOSE NRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375 ) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802. METHODS IDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates. RESULTS Of the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup. CONCLUSION This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.

Purpose To determine the effect of adjunctive epidural local anesthetic and opioid infusion on disease recurrence following radical prostatectomy for adenocarcinoma under general anesthesia. Methods This article describes a secondary analysis of subjects undergoing radical prostatectomy who had participated previously in a randomized controlled trial evaluating pain control, blood loss, and the need for perioperative allogeneic blood transfusion. The patients were randomly allocated to receive either general anesthesia alone (control group; n = 50) or combined general/ epidural anesthesia (study group; n = 49). A long-term follow-up chart review was undertaken to determine clinically evident or biochemical (Prostate Specific Antigen [0.2 ng Á mL -1 ) recurrence of prostate cancer. Comparison by group was undertaken using survival analysis.Results Median disease-free survival for the study as a whole was 1644 days, and the longest recorded survival was 3403 days. Biochemical recurrence of prostate cancer was observed in 11/49 study subjects and 17/50 control subjects. There was one death from prostate cancer in each group and a total of five deaths in the study group and six deaths in the control group. The hazard ratio for recurrence in the study group compared with the control group was 1.33 (95% confidence intervals 0.64-2.77; P = 0.44 by log-rank test). Conclusion No difference was observed between the epidural and control groups in disease-free survival at a median follow-up time of 4.5 years. There is a need for large randomized controlled trials to determine the ability of epidural analgesia to alter disease recurrence rates following radical prostatectomy. RésuméObjectif De´terminer l'effet d'une the´rapie adjuvante d'anesthe´sique local pe´ridural et perfusion d'opioı¨des sur la re´currence de la maladie apre`s une prostatectomie radicale pour ade´nocarcinome sous anesthe´sie ge´ne´rale. Méthode Cet article de´crit une analyse secondaire de patients ayant subi une prostatectomie radicale, lesquels avaient pre´ce´demment participe´a`une e´tude randomise´e contrôle´e e´valuant le contrôle de la douleur, les pertes sanguines et le besoin de transfusions sanguines alloge`nes en pe´riode pe´riope´ratoire. Les patients ont e´te´randomise´s a`recevoir soit une anesthe´sie ge´ne´rale seule (groupe te´moin; n = 50) ou une combinaison d'anesthe´sie ge´ne´rale et pe´ridurale (groupe a`l'e´tude; n = 49). Une re´vision des dossiers de suivi a`long terme a e´te´entreprise afin de

Gliomas are primary brain tumours arising from the glial cells of the nervous system. The diffuse nature of spread, coupled with proximity to critical brain structures, makes treatment a challenge. Pathological analysis confirms that the extent of glioma spread exceeds the extent of the grossly visible mass, seen on conventional magnetic resonance imaging (MRI) scans. Gliomas show faster spread along white matter tracts than in grey matter, leading to irregular patterns of spread. We propose a mathematical model based on Diffusion Tensor Imaging, a new MRI imaging technique that offers a methodology to delineate the major white matter tracts in the brain. We apply the anisotropic diffusion model of Painter and Hillen (J Thoer Biol 323:25-39, 2013) to data from 10 patients with gliomas. Moreover, we compare the anisotropic model to the state-of-the-art Proliferation-Infiltration (PI) model of Swanson et al. (Cell Prolif 33:317-329, 2000). We find that the anisotropic model offers a slight improvement over the standard PI model. For tumours with low anisotropy, the predictions of the two models are virtually identical, but for patients whose tumours show higher anisotropy, the results differ. We also suggest using the data from the contralateral hemisphere to further improve the model fit. Finally, we discuss the potential use of this model in clinical treatment planning.

Abstract

IntroductionCancer care has expanded from a disease-focused, survival-oriented model to an approach that now considers how survivors can live well in the aftermath of intensive therapy, where they may deal with significant changes to their bodies, mental health or emotional well-being. Research evidence supports the benefit of exercise during and following cancer treatments for cancer-related symptoms, physical functioning and fitness, and health-related quality of life. To move this efficacy evidence into practice, we designed and launched a 5-year study to evaluate the relative benefit from implementing a clinic-to-community-based cancer and exercise model of care.Methods and analysisA hybrid effectiveness and implementation trial design is being used to evaluate the effectiveness of delivery of community-based exercise and to collect data on implementation of the programme. The study opened in January 2017, with estimated completion by January 2022. The programme will be delivered in seven cities across the province of Alberta, Canada, with sites including three academic institutions, six YMCA locations, Wellspring Edmonton and Calgary, and six municipal fitness centres. Participants are adult cancer survivors (n=2500) from all tumour groups and stages and at any time point along their cancer treatment trajectory, up to 3 years post treatment completion. Survivors take part in a minimum of 60 min of mild-to-moderate intensity full body exercise twice weekly for a 12-week period. The primary effectiveness outcome is the proportion of participants meeting or exceeding 150 min of moderate intensity exercise per week at 1-year follow-up. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework will be utilised to capture individual-level and organizational-level impact of the exercise programme at 12 and 24 weeks and 1-year follow-up. The cohort of survivors participating in the study will allow for long-term (>5-year) evaluation of rates of cancer recurrence and secondary cancers beyond the funding period.Ethics and disseminationThe study was approved by the Health Research Ethics Board of Alberta. The study is funded by Alberta Innovates and the Alberta Cancer Foundation. The study will help to answer critical questions on the effectiveness of cancer-specific community-based exercise programming in both the short-term and the long-term. Collectively, the findings will help to inform the acceptability, adoption, feasibility, reach and sustainability of community-based exercise.Trial registration numberNCT02984163; Pre-results.

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