Background: Leptomeningeal disease (LMD), also known as neoplastic meningitis, leptomeningeal carcinomatosis, or carcinomatous meningitis, is a rare cancer complication occurring in ~5% of cases and ultimately leads to significant morbidity and mortality. In the modern era, incidence of this condition continues to rise with longer survival of patients with advanced and even metastatic disease due to continued improvements in systemic therapies that are providing prolonged control of distant disease, but with limited effect in the central nervous system (CNS). Typical treatment strategies include optimal systemic therapy for the primary disease, as well as neuroaxis directed therapies, which may include intrathecal chemotherapy (ITC) or radiotherapy (RT).Methods: A systematic review of radiotherapy for LMD was performed. Medline, EMBASE, and Cochrane databases were searched from 1946 to 2018 for clinical trials, retrospective/prospective reviews, and case series with ≥2 human subjects that used radiation therapy techniques in the treatment of LMD. The outcome measures of interest included: characteristics of trial participants, inclusion/exclusion criteria, study type, number of participants, primary cancer histology, type of intervention for LMD, survival results if reported, length of follow up, and study conclusion.Results: Of 547 unique citations, 62 studies met the pre-specified eligibility criteria. These studies included 36 retrospective cohorts, 11 prospective series, 12 case series, and a single citation of guidelines, NCDB analysis, and a randomized control trial. Owing to study heterogeneity, meta-analyses of the endpoint data could not be performed.Conclusions: LMD is a devastating complication of cancer with reported survivals ranging from 2 to 4 months. Based on this systematic review, the recommendation for the treatment of LMD is for multimodality discussion of cases and treatment, including the use of radiotherapy, for LMD. However, with continued advances in systemic therapy as well as imaging advances, the landscape of LMD is evolving rapidly and the role of RT will likely also continue to evolve and advance. There is limited high-quality evidence to guide the optimal use of RT for the treatment of LMD, and there is a great need for prospective, histology specific investigation of the role of radiotherapy for LMD in the era of modern systemic therapies.
Hesham elhalawani, neil chevli, pamela K. Allen * & caroline chung * treatment for glioblastoma (GBM) includes surgical resection and adjuvant radiotherapy (Rt) and chemotherapy. the optimal time interval between surgery and Rt remains unclear. the national cancer Database (ncDB) was queried for patients with GBM. overall survival (oS) was estimated using Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariable cox regression (MVA) modeling was used to determine predictors of OS. A total of 45,942 patients were included. On MVA: younger age, female gender, black ethnicity, higher KpS, obtaining a gross total resection (GtR), MGMt promotermethylated gene status, unifocal disease, higher RT dose, and RT delay of 4-8 weeks had improved oS. patients who underwent a subtotal resection (StR) had worsened survival with Rt delay ≤4 weeks and patients with GtR had worsened survival when Rt was delayed >8 weeks. This analysis suggests that an interval of 4-8 weeks between resection and RT results in better survival. Delays >8 weeks in patients with a GtR and delays <4 weeks in patients with a STR/biopsy resulted in worse survival. This impact of time delay from surgery to Rt, in conjunction with extent of resection, should be considered in the clinical management of patients and future designs of clinical trials. Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Current standard of care treatment for patients 70 years or younger and with good performance status, per the National Comprehensive Cancer Network (NCCN), includes maximal safe surgical resection with image-verified complete resection, followed by adjuvant radiotherapy (RT) and chemotherapy 1. Several prior studies have demonstrated an improved progression-free survival with more complete surgical resections 2-6. Under the same assumption that maximum cytoreductive treatment provides benefit to patients and, given the aggressive and rapidly progressive nature of this disease, many clinicians seek to minimize the time delay between surgery and initiation of RT. However, in the modern era, there are potentially numerous factors that could delay time to initiation of RT, including: evolution of practice that incorporates molecular/genetic testing and consideration of enrollment to clinical trials that requires additional testing and even central pathology review. This study provides information about the possible clinical impact of time delays for these various reasons between surgical resection and the start of adjuvant radiation therapy for patients with GBM. The optimal time interval between surgery and the initiation of adjuvant therapy; however, remains unclear. Cancer in several non-central nervous system (CNS) sites, including head and neck cancer and breast cancer, have increased local-regional recurrence rates when adjuvant RT is delayed 7. To our knowledge, in patients with GBM, two retrospective series have indicated that a delay in initiating adjuvant therapy worsened survival 8,9 ; nine series, including a SEER ana...
Background This retrospective study investigated the impact of Karnofsky performance status (KPS), in addition to age, on the management and outcomes of elderly patients with glioblastoma (GBM). Methods The National Cancer Database was queried between 2004–2015 for GBM patients with age ≥60. Three age groups were created: 60-69, 70-79, and ≥ 80 years old, and four age/KPS groups: ‘Age≥ 60/ KPS<70’ (group 1), ‘Age 60-69/KPS≥ 70’ (group 2), ‘age 70-79/KPS≥ 70’ (group 3), ‘age≥ 80/KPS≥ 70’ (group 4). Multivariable (MVA) modeling with Cox regression determined predictors of survival (OS), and estimated average treatment effects analysis was performed. Results A total of 48,540 patients with median age of 70 (range 60-90) at diagnosis, and median follow-up of 6.8 months (range 0-151) were included. Median survivals were 5.0, 15.2, 9.6 and 6.8 months in groups 1, 2, 3 and 4, respectively (p<0.001). On treatment effects analysis, all groups survived longer with combined chemotherapy (ChT) and radiation therapy (RT), except group 1 which survived longer with ChT alone (p<0.001). RT alone was associated with the worst OS in all groups (p<0.01). Across all groups, predictors of worse OS on MVA were older age, lower KPS, Caucasian, higher comorbidity score, worse socioeconomic status, community treatment, tumor multifocality, subtotal resection, and no adjuvant treatment (all p<0.01). Conclusions In elderly patients with newly diagnosed GBM, those with good KPS fared best with combined ChT and RT across all age groups. Performance status is a key prognostic factor that should be considered for management decisions in these patients.
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