Primary central nervous system lymphomas (PCNSLs) are rare cancers of the central nervous system (CNS) and are predominantly diffuse large B-cell lymphomas of the activated B-cell (ABC) subtype. They typically present in the sixth and seventh decade of life, with the highest incidence among patients aged >75 years. Although many different regimens have demonstrated efficacy in newly diagnosed and relapsed or refractory PCNSL, there have been few randomized prospective trials, and most recommendations and treatment decisions are based on single-arm phase II trials or even retrospective studies. High-dose methotrexate (HD-MTX; 3–8 g/m2) is the backbone of preferred standard induction regimens. Various effective regimens with different toxicity profiles can be considered that combine other chemotherapies and/or rituximab with HD-MTX, but there is currently no consensus for a single preferred regimen. There is controversy about the role of various consolidation therapies for patients who respond to HD-MTX–based induction therapy. For patients with relapsed or refractory PCNSL who previously experienced response to HD-MTX, repeat treatment with HD-MTX–based therapy can be considered depending on the timing of recurrence. Other more novel and less toxic regimens have been developed that show efficacy in recurrent disease, including ibrutinib, or lenalidomide ± rituximab. There is uniform agreement to delay or avoid whole-brain radiation therapy due to concerns for significant neurotoxicity if a reasonable systemic treatment option exists. This article aims to provide a clinically practical approach to PCNSL, including special considerations for older patients and those with impaired renal function. The benefits and risks of HD-MTX or high-dose chemotherapy with autologous stem cell transplantation versus other, better tolerated strategies are also discussed. In all settings, the preferred treatment is always enrollment in a clinical trial if one is available.
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Matthias Holdhoff, Maciej M. Mrugala, Christian Grommes, Thomas J. Kaley, Lode J. Swinnen, Carlos Perez-Heydrich and Lakshmi Nayak
Bin Wu and Lizheng Shi
Background: Maintenance therapy with the PARP inhibitor olaparib for metastatic pancreatic cancer (MPC) with a germline BRCA1 or BRCA2 mutation has been shown to be effective. We aimed to evaluate the cost-effectiveness of maintenance olaparib for MPC from the US payer perspective. Materials and Methods: A partitioned survival model was adopted to project the disease course of MPC. Efficacy and toxicity data were gathered from the Pancreas Cancer Olaparib Ongoing (POLO) trial. Transition probabilities were estimated from the reported survival probabilities in each POLO group. Cost and health preference data were derived from the literature. The incremental cost-utility ratio, incremental net-health benefit, and incremental monetary benefit were measured. Subgroup analysis, one-way analysis, and probabilistic sensitivity analysis were performed to explore the model uncertainties. Results: Maintenance olaparib had an incremental cost-utility ratio of $191,596 per additional progression-free survival (PFS) quality-adjusted life-year (QALY) gained, with a high cost of $132,287 and 0.691 PFS QALY gained, compared with results for a placebo. Subgroup analysis indicated that maintenance olaparib achieved at least a 16.8% probability of cost-effectiveness at the threshold of $200,000/QALY. One-way sensitivity analyses revealed that the results were sensitive to the hazard ratio of PFS and the cost of olaparib. When overall survival was considered, maintenance olaparib had an incremental cost-utility ratio of $265,290 per additional QALY gained, with a high cost of $128,266 and 0.483 QALY gained, compared with results for a placebo. Conclusions: Maintenance olaparib is potentially cost-effective compared with placebo for patients with a germline BRCA mutation and MPC. Economic outcomes could be improved by tailoring treatment based on individual patient factors.
Edward Christopher Dee, Vinayak Muralidhar, Santino S. Butler, Zizi Yu, Sybil T. Sha, Brandon A. Mahal, Paul L. Nguyen and Nina N. Sanford
Background: A significant proportion of cancer survivors endorse ongoing health information needs and may use the internet to access information. We assessed patterns and predictors of general and health-specific internet use among cancer survivors. Methods: Using data from the National Health Interview Survey (NHIS), which was administered in 2013 through 2018, for adults reporting a cancer diagnosis, sample weight-adjusted estimates defined prevalence and multivariable logistic regressions defined adjusted odds ratios (aORs) of general and health-specific internet use, adjusting for relevant sociodemographic covariates, including healthcare satisfaction as the primary independent variable. The analysis for health-specific internet use was also repeated including a sex (female vs male)*healthcare satisfaction (very satisfied/somewhat satisfied vs somewhat dissatisfied/very dissatisfied) interaction term. Results: Among 12,970 survivors of cancer, general and health-specific internet use increased from 2013 to 2018 (from 63.2% to 70.8% and from 46.8% to 52.2%, respectively; P<.05 for both). Survivors who were very dissatisfied with healthcare were more likely to use the internet for health information compared with those who were very satisfied (59.5% vs 48.0%; aOR, 1.78; 95% CI, 1.20–2.64; P=.004). Younger age, female sex, higher educational attainment, and higher socioeconomic status were all associated with increased reported use of the internet for both general and health-specific purposes (P<.001 for all). There was a significant sex*healthcare satisfaction interaction (P=.009) such that for female survivors, healthcare dissatisfaction was associated with higher odds of health-specific internet use (61.4% vs 52.5%; P<.001; men, P=.97). No association was found between healthcare satisfaction and general internet use (P=.42). Conclusions: The increasing proportion of survivors of cancer using the internet for health-specific information may be associated with self-reported dissatisfaction with healthcare. Efforts are needed to improve both access to the internet and the quality of cancer-relevant online health information, and to enhance patients’ online health literacy.
Bishal Gyawali and Saroj Niraula
Chloe E. Atreya, Eric A. Collisson, Meyeon Park, James P. Grenert, Spencer C. Behr, Amalia Gonzalez, Jonathan Chou, Samantha Maisel, Terence W. Friedlander, Chris E. Freise, Jun Shoji, Thomas J. Semrad, Jessica Van Ziffle and Peter Chin-Hong
Organ donors are systematically screened for infection, whereas screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to a lack of universal tumor testing in the posttransplant setting. Donor-transmitted malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. We describe the detection of a gastrointestinal adenocarcinoma transmitted from a young donor to 4 transplant recipients. Multidimensional histopathologic and genomic profiling showed a CDH1 mutation and MET amplification, consistent with gastric origin. At the time of writing, one patient in this series remains alive and without evidence of cancer after prompt organ explant after cancer was reported in other recipients. Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.
Featured Updates to the NCCN Guidelines
Steven M. Horwitz, Stephen Ansell, Weiyun Z. Ai, Jeffrey Barnes, Stefan K. Barta, Mark W. Clemens, Ahmet Dogan, Aaron M. Goodman, Gaurav Goyal, Joan Guitart, Ahmad Halwani, Bradley M. Haverkos, Richard T. Hoppe, Eric Jacobsen, Deepa Jagadeesh, Allison Jones, Youn H. Kim, Neha Mehta-Shah, Elise A. Olsen, Barbara Pro, Saurabh A. Rajguru, Sima Rozati, Jonathan Said, Aaron Shaver, Andrei Shustov, Lubomir Sokol, Pallawi Torka, Carlos Torres-Cabala, Ryan Wilcox, Basem M. William, Jasmine Zain, Mary A. Dwyer and Hema Sundar
Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.