Deborah Forst

First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)—a systematic review and individual patient data meta-analysis

BACKGROUND To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients. PATIENTS AND METHODS A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out. RESULTS We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS ≥ 70% was the strongest prognostic factor for mortality [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74). CONCLUSIONS Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted.

Low-Grade Gliomas

Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with longer-term survival in comparison with high-grade gliomas. Treatment options include observation, surgery, radiation, chemotherapy, or a combined approach, and management is individualized based on tumor location, histology, molecular profile, and patient characteristics. Moreover, in this type of brain tumor with a relatively good prognosis and prolonged survival, the potential benefits of treatment must be carefully weighed against potential treatment-related risks. We review in this article current management strategies for LGG, including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated.

Hospice utilization in patients with malignant gliomas

Background Despite recommendations from professional organizations supporting early hospice enrollment for patients with cancer, little research exists regarding end-of-life (EOL) practices for patients with malignant glioma (MG). We evaluated rates and correlates of hospice enrollment and hospice length of stay (LOS) among patients with MG. Methods Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, we identified adult patients who were diagnosed with MG from January 1, 2002 to December 31, 2011 and who died before December 31, 2012. We extracted sociodemographic and clinical data and used univariate logistic regression analyses to compare characteristics of hospice recipients versus nonrecipients. We performed multivariable logistic regression analyses to examine predictors of hospice enrollment >3 or >7 days prior to death. Results We identified 12437 eligible patients (46% female), of whom 7849 (63%) were enrolled in hospice before death. On multivariable regression analysis, older age, female sex, higher level of education, white race, and lower median household income predicted hospice enrollment. Of those enrolled in hospice, 6996 (89%) were enrolled for >3 days, and 6047 (77%) were enrolled for >7 days. Older age, female sex, and urban residence were predictors of longer LOS (3- or 7-day minimum) on multivariable analysis. Median LOS on hospice for all enrolled patients was 21 days (interquartile range, 8-45 days). Conclusions We identified important disparities in hospice utilization among patients with MG, with differences by race, sex, age, level of education, and rural versus urban residence. Further investigation of these barriers to earlier and more widespread hospice utilization is needed.

Neurological Complications of Targeted Therapies

Drug development in oncology has increasingly shifted from a focus on cytotoxic chemotherapy to the production of targeted agents designed to address specific molecular drivers of tumor growth. These targeted agents include antiangiogenic agents, small molecule inhibitors, monoclonal antibodies and antibody-drug conjugates. Overall, these agents are better tolerated than their cytotoxic counterparts, but they carry the risk of specific neurologic toxicities. Headache is often reported in association with targeted agents. Neuropathy is a common feature of proteasome inhibitors and also frequently described with the use of thalidomide and its analogs. Antiangiogenic agents carry an increased risk of thrombotic and hemorrhagic complications. The Reversible Posterior Leukoencephalopathy Syndrome (RPLS) or Posterior Reversible Encephalopathy Syndrome (PRES) is a rare but serious complication seen with the use of various targeted therapies, including antiangiogenic agents and monoclonal antibodies. Neurologic complications of targeted therapies are generally mild to moderate in severity, but may rarely result in dose modification or necessitate drug discontinuation.