Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known

Origins and genetic legacy of prehistoric dogs

Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry

A phase i study of tomotherapy in patients with primary benign and low-grade brain tumors: Late toxicity and quality of life

Objectives: To evaluate longitudinal quality of life and late neurotoxicity (\u3e 12 mo) of tomotherapy in patients with primary benign and low-grade brain tumors. Methods: Between January 2006 and October 2009, 49 patients with brain tumors were treated with tomotherapy at 2 radiotherapy centers in Canada. The median age of the patients was 51.0 years (range, 21 to 74 y); there were 21 men (42.86%) and 28 women (57.14%). All 49 patients had an initial Karnofsky performance score Z70. One patient (2.04%) received 45 Gy in 25 fractions, 27 patients (55.10%) received 50.4 Gy in 28 fractions, 15 patients (30.6%) received 54 Gy in 30 fractions, and 5 patients (10.2%) received 60 Gy in 30 fractions. A total of 47 patients were analyzed for late toxicity and outcomes. Results: Changes in the Karnofsky Performance Status of the patients did not reach statistical significance (P \u3e 0.05). The majority of the quality of life parameters that reached a statistically significant level (P \u3c 0.05) of change at 2 years were changes toward improvement (drowsiness, itchy skin, emotional functioning, fatigue, nausea, and appetite). Statistically significant (P \u3c 0.05) interval deterioration in physical, role, and social functioning was observed. Actuarial overall survival at 5 years was 91.6%; disease-free survival at 5 years was 86.6%. Conclusions: IMRT helical tomotherapy is well tolerated, without statistically significant constitutional and late neurotoxicity up to the 2-year mark