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Daniel A. Pollyea, Jessica K. Altman, Rita Assi, Dale Bixby, Amir T. Fathi, James M. Foran, Ivana Gojo, Aric C. Hall, Brian A. Jonas, Ashwin Kishtagari, Jeffrey Lancet, Lori Maness, James Mangan, Gabriel Mannis, Guido Marcucci, Alice Mims, Kelsey Moriarty, Moaath Mustafa Ali, Jadee Neff, Reza Nejati, Rebecca Olin, Mary-Elizabeth Percival, Alexander Perl, Amanda Przespolewski, Dinesh Rao, Farhad Ravandi, Rory Shallis, Paul J. Shami, Eytan Stein, Richard M. Stone, Kendra Sweet, Swapna Thota, Geoffrey Uy, Pankit Vachhani, Carly J. Cassara, Deborah A. Freedman-Cass, and Katie Stehman

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths from leukemias in the United States. Like AML, blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a myeloid malignancy. It is a rare malignancy characterized by the aggressive proliferation of precursors of plasmacytoid dendritic cells that frequently involves the bone marrow, skin, central nervous system, and other organs and tissues. This discussion section focuses on the diagnosis and management of BPDCN as outlined in the NCCN Guidelines for AML.

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Narhari Timilshina, Antonio Finelli, George Tomlinson, Beate Sander, and Shabbir M.H. Alibhai

Background: Although a few studies have reported wide variations in quality of care in active surveillance (AS), there is a lack of research using validated quality indicators (QIs). The aim of this study was to apply evidence-based QIs to examine the quality of AS care at the population level. Methods: QIs were measured using a population-based retrospective cohort of patients with low-risk prostate cancer diagnosed between 2002 and 2014. We developed 20 QIs through a modified Delphi approach with clinicians targeting the quality of AS care at the population level. QIs included structure (n=1), process of care (n=13), and outcome indicators (n=6). Abstracted pathology data were linked to cancer registry and administrative databases in Ontario, Canada. A total of 17 of 20 QIs could be applied based on available information in administrative databases. Variations in QI performance were explored according to patient age, year of diagnosis, and physician volume. Results: The cohort included 33,454 men with low-risk prostate cancer, with a median age of 65 years (IQR, 59–71 years) and a median prostate-specific antigen level of 6.2 ng/mL. Compliance varied widely for 10 process QIs (range, 36.6%–100.0%, with 6 [60%] QIs >80%). Initial AS uptake was 36.6% and increased over time. Among outcome indicators, significant variations were observed by patient age group (10-year metastasis-free survival was 95.0% for age 65–74 years and 97.5% in age <55 years) and physician average annual AS volume (10-year metastasis-free survival was 94.5% for physicians with 1–2 patients with AS and 95.8% for those with ≥6 patients with AS annually). Conclusions: This study establishes a foundation for quality-of-care assessments and monitoring during AS implementation at a population level. Considerable variations appeared with QIs related to process of care by physician volume and QIs related to outcome by patient age group. These findings may represent areas for targeted quality improvement initiatives.

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Katherine Daunov, Michael Daunov, Kara Noskoff, Hilary Gan, Simon Davies, Megan Farrell, Whitney Hadley, Amelia Baffa, Jennifer Giesel, Rachel Egler, Alex Y. Huang, John J. Letterio, and Richard T. Lee

Background: This study sought to evaluate the current services and delivery models of adolescent and young adult oncology (AYAO)–specific programs at NCI-designated Cancer Centers (NCI-CCs). Patients and Methods: NCI, academic, and community cancer centers were electronically sent surveys from October to December 2020 and administered via REDCap. Results: Survey responses were received from 50 of 64 (78%) NCI-CCs, primarily completed by pediatric oncologists (53%), adult oncologists (11%), and social workers (11%). Half (51%) reported an existing AYAO program, with most (66%) started within the past 5 years. Although most programs combined medical and pediatric oncology (59%), 24% were embedded within pediatrics alone. Most programs saw patients aged 15 (55%) to 39 years (66%) mainly via outpatient clinic consultation (93%). Most centers reported access to a range of medical oncology and supportive services, but dedicated services specifically for adolescent and young adults (AYAs) were available at a much lower extent, such as social work (98% vs 58%) and psychology (95% vs 54%). Although fertility preservation was offered by all programs (100%), only two-thirds of NCI centers (64%) reported providing sexual health services to AYAs. Most NCI-CCs (98%) were affiliated with a research consortium, and a lesser extent (73%) reported collaboration between adult and pediatric researchers. Nearly two-thirds (60%) reported that AYA oncology care was important/very important to their respective institution and reported providing good/excellent care to AYAs with cancer (59%), but to a lesser extent reported good/excellent research (36%), sexual health (23%), and education of staff (21%). Conclusions: Results of this first-ever national survey to assess AYAO programs showed that only half of NCI-CCs report having a dedicated AYAO program, and that areas of improvement include staff education, research, and sexual health services for patients.

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Akriti Jain and Kendra Sweet

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with an aggressive clinical course and poor prognosis. BPDCN is most often characterized by its presentation with distinct cutaneous lesions. Bone marrow involvement, lymphadenopathy, splenomegaly, and/or cytopenias are also seen to varying degrees. BPDCN presents with diffuse, monomorphous blasts with irregular nuclei, fine chromatin, and scant, agranular cytoplasm. Expression of CD4, CD56, and CD123 is the hallmark of BPDCN. The presence of ≥4 of CD4, CD56, CD123, TCL1, TCF4, and CD303 is necessary for the diagnosis of BPDCN. Prior to December 2018, management of BPDCN revolved around intensive chemotherapy using acute myeloid leukemia or acute lymphoblastic leukemia regimens. However, responses were transient with poor overall survival (OS). Allogeneic stem cell transplantation (alloSCT) is the only potentially curative treatment for BPDCN. Even so, only a minority of patients are candidates for alloSCT given the preponderance of disease in older individuals. For the few fit patients who are candidates for alloSCT, the aim is to achieve complete remission prior to alloSCT. Tagraxofusp (SL-401), a recombinant fusion protein containing interleukin-3 fused to truncated diphtheria toxin, was the first approved CD123-targeted therapy for BPDCN based on a phase I/II clinical trial showing a 90% overall response rate. It was approved by the FDA on December 21, 2018. Capillary leak syndrome is an important adverse effect of tagraxofusp that requires close monitoring. Several clinical trials are underway to study other regimens for the treatment of BPDCN, including IMGN632 (pivekimab sunirine), venetoclax (alone and in combination with hypomethylating agents), CAR-T cells, and bispecific monoclonal antibodies.

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Margaret Tempero

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Justine Lequesne, Florence Joly, Julien Peron, Isabelle Ray-Coquard, Anne-Claire Hardy-Bessard, Frédéric Selle, Dominique Berton, Philippe Follana, Michel Fabbro, Alain Lortholary, Eric Pujade-Lauraine, Sophie Lefèvre-Arbogast, and Elodie Coquan

Background: Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients’ quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation. Methods: Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab. Global and physical functioning QoL were issued from the EORTC QoL Questionnaire-Core 30 (QLQ-C30), collected at baseline and 8/9 and 16/18 weeks after treatment initiation. Four toxicity scores were computed: the total number of AEs, multiplied by their grade and not, and the cumulative duration of AEs, weighted by their grade and not. Each score included all AEs or only grade 3/4 nonlaboratory or treatment-related AEs. The relationship between toxicity scores and QoL was assessed through linear mixed regression. Results: We found that 171 (47.5%) and 43 (11.9%) patients experienced at least one grade 3 or 4 AE, respectively, whereas 113 (31.4%) experienced grade 2 AEs only. Physical QoL was negatively associated with all toxicity scores when computed with all grades of AEs (all P<.01), with a weaker association when treatment-related AEs were considered. Global QoL was negatively associated with toxicity scores computed with nonlaboratory all-grade AEs only (β, –3.42 to –3.13; all P<.01). Degrees of association were lower when considering the AE duration. Conclusions: In this analysis of patients with platinum-resistant ovarian cancer, toxicity scores based on the cumulative number of AEs, modulated or not by grade, were more effective at predicting QoL changes than those based on AE duration. Toxicity impact on QoL was better reflected when grade 2 AEs were taken into account together with grade 3/4 AEs, whatever their treatment imputability, and when laboratory AEs were excluded.

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NCCN Guidelines® Insights: Distress Management, Version 2.2023

Featured Updates to the NCCN Guidelines

Michelle B. Riba, Kristine A. Donovan, Kauser Ahmed, Barbara Andersen, IIana Braun, William S. Breitbart, Benjamin W. Brewer, Cheyenne Corbett, Jesse Fann, Stewart Fleishman, Sofia Garcia, Donna B. Greenberg, George F. Handzo Rev., Laura Herald Hoofring, Chao-Hui Huang, Sean Hutchinson, Shelley Johns, Jennifer Keller, Pallavi Kumar, Sheila Lahijani, Sara Martin, Shehzad K. Niazi, Megan Pailler, Francine Parnes, Vinay Rao, Jaroslava Salman, Eli Scher, Jessica Schuster, Melissa Teply, Angela Usher, Alan D. Valentine, Jessica Vanderlan, Megan S. Lyons, Nicole R. McMillian, and Susan D. Darlow

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. All patients experience some level of distress associated with a cancer diagnosis and the effects of the disease and its treatment regardless of the stage of disease. Clinically significant levels of distress occur in a subset of patients, and identification and treatment of distress are of utmost importance. The NCCN Distress Management Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights describe updates to the NCCN Distress Thermometer (DT) and Problem List, and to the treatment algorithms for patients with trauma- and stressor-related disorders.

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