Treatment outcomes in 1p19q co-deleted/partially deleted gliomasa

AbstractBackground:Radiotherapy with procarbazine, lomustine, and vincristine improves overall survival (OS) in patients with 1p19q co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma.Methods:This retrospective analysis investigated outcomes in patients with 1p19q co-deleted/partially deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and prognostic factors using the Cox proportional hazard model.Results:A total of 106 patients (between December 1997 and December 2013) were included. Median age was 40 years (19-66), 58 were male (55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients (75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27 (25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients, respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85 patients with sufficient material. Upfront treatment was given in 72 (68%) patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47 patients (44%) was 34.7 months and 41.2 months in 9 patients with co-deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma who received upfront temozolomide alone. Median OS was not reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On multivariable analysis for all patients, receipt of therapy upfront versus none (p=0.04), PS 1 versus 0 (p&lt;0.001) and 1p19q co-deletion/incomplete deletion versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate dehydrogenase-1 status was not prognostic for PFS.Conclusions:With similar survival patterns in low-grade/anaplastic gliomas, molecular characteristics may be more important than histological grade. Longer follow-up and results of prospective trials are needed for definitive guidance on treatment of these patients.</jats:p

Prostate Cancer Brain Metastasis: Review of a Rare Complication with Limited Treatment Options and Poor Prognosis

Brain metastases (BM) are perceived as a rare complication of prostate cancer associated with poor outcome. Due to limited published data, we conducted a literature review regarding incidence, clinical characteristics, treatment options, and outcomes of patients with prostate cancer BM. A literature analysis of the PubMed, MEDLINE, and EMBASE databases was performed for full-text published articles on patients diagnosed with BM from prostate cancer. Eligible studies included four or more patients. Twenty-seven publications were selected and analyzed. The sources of published patient cohorts were retrospective chart reviews, administrative healthcare databases, autopsy records, and case series. BM are rare, with an incidence of 1.14% across publications that mainly focus on intraparenchymal metastases. Synchronous visceral metastasis and rare histological prostate cancer subtypes are associated with an increased rate of BM. Many patients do not receive brain metastasis-directed local therapy and the median survival after BM diagnosis is poor, notably in patients with multiple BM, dural-based metastases, or leptomeningeal dissemination. Overall, prostate cancer BM are rare and associated with poor prognosis. Future research is needed to study the impact of novel prostate cancer therapeutics on BM incidence, to identify patients at risk of BM, and to characterize molecular treatment targets

Clinical utility of targeted next-generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making

International audienceBackground: Targeted gene NGS testing is available through many academic institutions and commercial entities and is increasingly incorporated in practice guidelines for glioblastoma (GBM). This single-center retrospective study aimed to evaluate the clinical utility of incorporating NGS results in the management of GBM patients at a clinical trials-focused academic center.Methods: We identified 1011 consecutive adult patients with pathologically confirmed GBM (IDHwt or IDHmut) who had somatic tumor sequencing (Oncopanel, ~500 cancer gene panel) at DFCI from 2013-2019. Clinical records of all IDHwt GBM patients were reviewed to capture clinical trial enrollment and off-label targeted therapy use based on NGS results.Results: Of the 557 IDHwt GBM patients with sequencing, 182 entered clinical trials at diagnosis (32.7%) and 213 (38.2%) entered after recurrence. Sequencing results for 130 patients (23.3%) were utilized for clinical trial enrollment for either targeted therapy indications (6.9 % upfront and 27.7% at recurrent clinical trials and 3.1% for off-label targeted therapy) or exploratory studies (55.4% upfront and 6.9% recurrent clinical trials). Median overall survival was 20.1 months with no survival difference seen between patients enrolled in clinical trials compared to those who were not, in a posthoc analysis.Conclusions: While NGS testing has become essential for improved molecular diagnostics, our study illustrates that targeted gene panels remain underutilized for selecting therapy in GBM-IDHwt. Targeted therapy and clinical trial design remain to be improved to help leverage the potential of NGS in clinical care