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NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

Featured Updates to the NCCN Guidelines

Shaji K. Kumar, Natalie S. Callander, Jens Hillengass, Michaela Liedtke, Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Jason C. Chandler, Robert F. Cornell, Caitlin Costello, Yvonne Efebera, Matthew Faiman, Alfred Garfall, Kelly Godby, Leona Holmberg, Myo Htut, Carol Ann Huff, Yubin Kang, Ola Landgren, Ehsan Malek, Thomas Martin, James Omel, Noopur Raje, Douglas Sborov, Seema Singhal, Keith Stockerl-Goldstein, Carlyn Tan, Donna Weber, Alyse Johnson-Chilla, Jennifer Keller and Rashmi Kumar

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates and changes in the 1.2020 version of the NCCN Guidelines for Multiple Myeloma.

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Scott F. Huntington, Jessica R. Hoag, Rong Wang, Amer M. Zeidan, Smith Giri, Steven D. Gore, Xiaomei Ma, Cary P. Gross and Amy J. Davidoff

Background: Provider experience, or clinical volume, is associated with improved outcomes in many complex healthcare settings. Despite increased complexity of anticancer therapies, studies evaluating physician-level experience and cancer treatment outcomes are lacking. Methods: A population-based study was conducted of older adults (aged ≥66 years) diagnosed with B-cell non-Hodgkin’s lymphoma in 2004 through 2011 using SEER-Medicare data. Analysis focused on outcomes in patients receiving rituximab, the first approved monoclonal anticancer immunotherapy. We hypothesized that lower physician experience using rituximab and managing its infusion-related reactions would be associated with early treatment discontinuation. A 12-month look-back from each initiation of rituximab was used to categorize physician volume (0, 1–2, or ≥3 initiations per year). Modified Poisson regression was used to account for provider-level correlation and estimated relative risk (RR) of early rituximab discontinuation (<3 cycles within 180 days of rituximab initiation). Cox proportional hazards were used to measure the impact of rituximab discontinuation on survival. Results: Among 15,110 patients who initiated rituximab with 2,684 physicians, 7.6% experienced early rituximab discontinuation. Approximately one-fourth of patients (26.1%) initiated rituximab with a physician who had no rituximab initiations during the preceding 12 months. Compared with patients treated by physicians who had ≥3 rituximab initiations in the prior year, those treated by physicians without initiations were 57% more likely to experience early discontinuation (adjusted RR [aRR], 1.57; 95% CI, 1.35–1.82; P<.001 for 0 vs ≥3, and aRR, 1.19; 95% CI, 1.03–1.37; P=.02 for 1–2 vs ≥3). Additionally, rituximab discontinuation was associated with higher risk of death (adjusted hazard ratio, 1.39; 95% CI, 1.28–1.52; P<.001). Conclusions: Lower oncologist experience with rituximab was associated with increased risk of early rituximab discontinuation in Medicare beneficiaries with non-Hodgkin’s lymphoma. Physician-level volume may be an important factor in providing high-quality cancer care in the modern era.

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Dennis R. Taaffe, Robert U. Newton, Nigel Spry, David J. Joseph and Daniel A. Galvão

Background: Androgen deprivation therapy (ADT) in the management of prostate cancer (PCa) results in an array of adverse effects, and exercise is one strategy to counter treatment-related musculoskeletal toxicities. This study assessed the prevalence of exercise responsiveness in men with PCa undergoing ADT in terms of body composition, muscle strength, and physical function. Methods: Prospective analyses were performed in 152 men (aged 43–90 years) with PCa receiving ADT who were engaged in resistance exercise combined with aerobic or impact training for 3 to 6 months. Whole-body lean mass and fat mass (FM), trunk FM, and appendicular skeletal muscle were assessed with dual x-ray absorptiometry; upper and lower body muscle strength were assessed with the one-repetition maximum; and physical function was assessed with a battery of tests (6-m usual, fast, and backward walk; 400-m walk; repeated chair rise; stair climb). Results: Significant improvements were seen (P<.01) in lean mass (0.4±1.4 kg [range, −2.8 to +4.1 kg]), appendicular skeletal muscle (0.2±0.8 kg [range, −1.9 to +1.9 kg]), and all measures of muscle strength (chest press, 2.9±5.8 kg [range, −12.5 to +37.5 kg]; leg press, 29.2±27.6 kg [range, −50.0 to +140.0 kg]) and physical function (from −0.1±0.5 s [range, +1.3 to −2.1 s] for the 6-m walk; to −8.6±15.2 s [range, +25.2 to −69.7 s] for the 400-m walk). An increase in FM was also noted (0.6±1.8 kg [range, −3.6 to +7.3 kg]; P<.01). A total of 21 men did not exhibit a favorable response in at least one body composition component, 10 did not experience improved muscle strength, and 2 did not have improved physical function. However, all patients responded in at least one of the areas, and 120 (79%) favorably responded in all 3 areas. Conclusions: Despite considerable heterogeneity, most men with PCa receiving ADT responded to resistance-based multimodal exercise, and therefore our findings indicate that this form of exercise can be confidently prescribed to produce beneficial effects during active treatment.

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Justin Famoso, Gerald Lemole, Srinath Sundararajan and Baldassarre Stea

Primary melanoma of the pineal gland is a rare disease entity with an overall poor prognosis. Limited data exist to appropriately guide treatment decisions. Historical case reports have showed some success using a combination of surgical resection, radiotherapy, and chemotherapy, but long-term survival has been exceedingly rare. This report presents a female patient with a primary pineal melanoma who underwent subtotal resection followed by adjuvant focal radiation to the residual tumor. Immunohistochemistry identified a strong positivity for PD-L1 (70%). After radiation, systemic therapy with pembrolizumab was initiated with the plan to treat until progression. She has now completed 33 cycles of pembrolizumab without interruptions, complications, or disease progression. At the time of writing, the patient has had an excellent clinical outcome, with a durable near-complete response of >138 weeks. To our knowledge, this is the first patient with a pineal melanoma to be managed by targeting PD-L1. Furthermore, she has achieved the second longest overall survival and the longest progression-free survival reported in the literature.

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Kristine A. Donovan, Teresa L. Deshields, Cheyenne Corbett and Michelle B. Riba

The first NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Distress Management were published in 1999. Since then, a number of other organizations have advocated for distress screening. Previous surveys of distress screening showed modest progress in implementation of the NCCN Guidelines for Distress Management by NCCN Member Institutions (MIs); this review examined whether further progress has been made. Representatives appointed to the NCCN Distress Management Panel or their designee were asked to complete an online survey in the summer of 2018. The survey was developed based on similar surveys performed in 2005 and 2012 and a survey of psychosocial staffing conducted in NCCN MIs in 2012. New items solicited details about triaging, rescreening, formal screening protocols, and tracking of distressed patients. The survey was completed by representatives from 23 of 27 NCCN MIs (85%). Among the responding institutions, 20 (87%) currently conduct routine screening for distress and 3 are piloting routine screening. All respondents reported use of a self-report measure to screen for distress, with the Distress Thermometer most often used. A total of 70% of respondents rescreen patients for distress and 83% reported having a formal distress screening protocol in place. Once triaged, 65% of institutions who routinely screen for distress track clinical contacts and referrals; 70% track rates of adherence to screening protocols. Findings suggest wide acceptance and implementation of the NCCN Guidelines. Most respondents reported the existence of a formal distress screening protocol, with routine tracking of clinical contacts and referrals and rates of protocol adherence. Clinical experience and the American College of Surgeons Commission on Cancer accreditation standard for cancer centers appear to have resulted in greater adoption and implementation of the guidelines, but considerable opportunities for improvement remain.

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James McCanney, Terrell Johnson, Lindsey A.M. Bandini, Shonta Chambers, Lynette Bonar and Robert W. Carlson

Demographic factors such as race, socioeconomic status, gender identity, area of residence, native language, and cultural barriers have an effect on outcomes in cancer care. To identify unmet needs, challenges, and opportunities in achieving high-quality, patient-centered cancer care for all, NCCN conducted a yearlong environmental scan, which involved stakeholder meetings with patients and patient advocacy groups to discuss these topics. The findings from this scan informed the corresponding NCCN Patient Advocacy Summit: Advocating for Equity in Cancer Care, held in Washington, DC, on December 10, 2018. In addition to the many patient advocacy groups, the summit featured a number of other stakeholders that advocate for equity in cancer care. This article encapsulates the findings of the environmental scan and the discussion from the NCCN Patient Advocacy Summit.

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Marcin Chwistek