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Hereditary Cancer Clinics Improve Adherence to NCCN Germline Testing Guidelines for Pancreatic Cancer

Claudia Rosso, Naomie Devico Marciano, Deepika Nathan, Wen-Pin Chen, Christine E. McLaren, Kathryn E. Osann, Pamela L. Flodman, May T. Cho, Fa-Chyi Lee, Farshid Dayyani, Jason A. Zell, and Jennifer B. Valerin

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year overall survival rate of 10%. In November 2018, NCCN recommended that all patients with PDAC receive genetic counseling (GC) and germline testing regardless of family history. We hypothesized that patients with PDAC were more likely to be referred for testing after this change to the guidelines, regardless of presumed predictive factors, and that compliance would be further improved following the implementation of a hereditary cancer clinic (HCC). Methods: We conducted a single-institution retrospective analysis of patients diagnosed with PDAC from June 2017 through December 2021 at University of California, Irvine. We compared rates of genetics referral among patients in different diagnostic eras: the 18-month period before the NCCN Guideline change (pre-NCCN era: June 2017 through November 2018), 14 months following the change (post-NCCN era: December 2018 through January 2020), and 18 months after the creation of an HCC (HCC era: June 2020 through December 2021). Family and personal cancer history, genetics referral patterns, and results of GC were recorded. Data were compared using chi-square, Fisher exact, and multivariate analyses. Results: A total of 335 patients were treated for PDAC (123 pre-NCCN, 109 post-NCCN, and 103 HCC) at University of California, Irvine. Demographics across groups were comparable. Prior to the guideline changes, 30% were referred to GC compared with 54.7% in the post-NCCN era. After the implementation of the HCC, 77.4% were referred to GC (P<.0001). The odds ratio (OR) for referral to GC among patients with a positive family history of cancer progressively decreased following the change (pre-NCCN era: OR, 11.90 [95% CI, 3.00–80.14]; post-NCCN era: OR, 3.39 [95% CI, 1.13–10.76]; HCC era: OR, 3.11 [95% CI, 0.95–10.16]). Conclusions: The 2018 updates to the NCCN Guidelines for PDAC recommending germline testing for all patients with PDAC significantly increased GC referral rates at our academic medical center. Implementation of an HCC further boosted compliance with guidelines.

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Therapy for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma in Children, Adolescents, and Young Adults

Aliza Gardenswartz and Mitchell S. Cairo

Despite excellent cure rates among children, adolescents, and young adults (CAYAs) with mature B-cell non-Hodgkin lymphomas (B-NHLs) treated with chemoimmunotherapy, CAYAs with relapsed/refractory B-NHL remain difficult to treat, with a dismal prognosis. Reinduction and subsequent therapeutic management are not standardized. The armamentarium of active agents against B-NHL, including antibody–drug conjugates, monoclonal antibodies, checkpoint inhibitors, T-cell engagers, CAR T cells, CAR-natural killer (CAR-NK) cells, and cell signaling inhibitors, continues to expand. This article reviews current management practices and novel therapies in this difficult to treat population.

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Cancer Rehabilitation: Impact on Breast Cancer Survivors’ Work Ability and Health-Related Quality of Life

Mackenzi Pergolotti, Kelley C. Wood, Tiffany Kendig, Kim Love, and Stacye Mayo

Background: Breast cancer survivors (BCSs) report persistent, diminished ability to work, and decreased health-related quality of life (HRQoL). Cancer rehabilitation interventions (physical therapy or occupational therapy [PT/OT]) aim to improve these outcomes, but little is known about their impact in the community. Methods: This retrospective, pre-post, uncontrolled study examined cases of younger BCSs (age <65 years) who attended cancer-specialized PT/OT over a 2-year period. Outcomes and covariates (age, race, US region, payer type, number of visits, length of care [weeks]) were extracted from electronic medical records. Patient-reported outcomes were overall-Work Ability Score (WASoverall), physical-WAS (WASphysical), and mental-WAS (WASmental) and PROMIS Global Physical Health (GPH), Global Mental Health (GMH), Physical Function (PF), and Ability to Participate in Social Roles and Activities (SRA). We used linear mixed effect models to examine pre- to post-rehabilitation change overall, and separately, while controlling for covariates. Results: PT/OT cases (NPT=758; NOT=140) had a mean [SD] age of 51.39 [8.49] years and attended approximately 12 visits (IQR, 8.0–19.0) over 10.71 weeks (IQR, 6.14–17.00). Overall, work ability outcomes (WASoverall: +1.79; WASphysical: +0.78; WASmental: +0.47; all P<.001) and HRQoL outcomes improved significantly (GPH: +5.38; GMH: +2.90; PF: +5.17; SRA: +5.83; all P<.001), and average change on each HRQoL outcome exceeded the minimal important change (2 points). Outcome scores were similar at each timepoint for both PT and OT cases (all P>.05) and both groups improved significantly (all P<.01). Conclusions: In this large study of the impact of cancer-specialized, community-based PT and OT, younger BCSs reported significant improvement in ability to work and HRQoL. Although more research is needed, these findings suggest improved access to PT/OT could improve work ability and HRQoL for younger BCSs.

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Improved Survival in Contemporary Community-Based Patients With Metastatic Clear-Cell Renal Cell Carcinoma Undergoing Active Treatment

Reha-Baris Incesu, Simone Morra, Lukas Scheipner, Andrea Baudo, Letizia Maria Ippolita Jannello, Mario de Angelis, Carolin Siech, Anis Assad, Zhe Tian, Fred Saad, Shahrokh F. Shariat, Felix K. H. Chun, Alberto Briganti, Ottavio de Cobelli, Luca Carmignani, Sascha Ahyai, Nicola Longo, Derya Tilki, Markus Graefen, and Pierre I. Karakiewicz

Background: We hypothesized that the evolving treatment paradigms recommended based on phase III trials may have translated into improved overall survival (OS) in contemporary community-based patients with clear-cell metastatic renal cell carcinoma (ccmRCC) undergoing active treatment. Patients and Methods: Within the SEER database, contemporary (2017–2020) and historical (2010–2016) patients with ccmRCC treated with either systemic therapy (ST), cytoreductive nephrectomy (CN), or both (ST+CN) were identified. Univariable and multivariable Cox-regression models were used. Results: Overall, 993 (32%) contemporary versus 2,106 (68%) historical patients with ccmRCC were identified. Median OS was 41 months in contemporary versus 25 months in historical patients (Δ=16 months; P<.001). In multivariable Cox-regression analyses, contemporary membership was independently associated with lower overall mortality (hazard ratio [HR], 0.7; 95% CI, 0.6–0.8; P<.001). In patients treated with ST alone, median OS was 17 months in contemporary versus 10 months in historical patients (Δ=7 months; P<.001; multivariable HR, 0.7; P=.005). In patients treated with CN alone, median OS was not reached in contemporary versus 33 months in historical patients (Δ=not available; P<.001; multivariable HR, 0.7; P<.001). In patients treated with ST+CN, median OS was 38 months in contemporary versus 26 months in historical patients (Δ=12 months; P<.001; multivariable HR, 0.7; P=.003). Conclusions: Contemporary community-based patients with ccmRCC receiving active treatment clearly exhibited better survival than their historical counterparts, when examined as one group, as well as when examined as separate subgroups according to treatment type. Treatment advancements of phase III trials seem to be applied appropriately outside of centers of excellence.

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Demographic Disparities in Lung Cancer Mortality and Trends in the United States From 1999 Through 2020: A Population-Based CDC Database Analysis

Alexander J. Didier, Logan Roof, and James Stevenson

Background: Lung cancer is the leading cause of cancer-related mortality in the United States and is projected to account for 127,070 deaths in 2023. Although the lung cancer mortality rate has been decreasing over the last decade, demographic disparities in mortality still exist. We sought to determine the impact of demographic factors on lung cancer mortality and trends in the United States. Patients and Methods: We queried the Centers for Disease Control and Prevention (CDC) database for mortality statistics with an underlying cause of death of lung and bronchus cancer from 1999 through 2020. Age-adjusted mortality rates (AAMR) were calculated per 100,000 people. We assessed the AAMR by demographic variables, including race, geographic density, sex, age, and US census region. Temporal trends were evaluated using Joinpoint regression software, and average annual percent change (APC) was calculated. Results: From 1999 through 2020, lung cancer led to 3,380,830 deaths. The AAMR decreased by 55.1 to 31.8, with an associated average APC of −2.6%. In 1999, men had an AAMR almost twice as high as women, but these differences became less pronounced over time. Rural populations experienced the highest AAMR and the slowest rate of decrease compared with urban populations, who experienced the lowest AAMR and fastest decrease. Non-Hispanic Black individuals experienced the highest AAMR, with an annual decrease of −3.0%. The West experienced the fastest decrease at −3.1% annually, whereas the Midwest experienced the slowest decrease at −2.0% annually. Conclusions: Although the mortality rate of lung cancer has been decreasing since 1999, not all demographic groups have experienced the same rates of decrease, and disparities in outcomes are still prevalent. Vulnerable subgroups need targeted interventions, such as the incorporation of patient navigators, improved screening chest CT scan access and follow-up, and telehealth expansion, which will improve the likelihood of earlier-stage diagnoses and the potential for curative treatments.

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Volume 22 (2024): Issue 2D (Jun 2024)

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Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology

Al B. Benson III, Alan P. Venook, Mohamed Adam, George Chang, Yi-Jen Chen, Kristen K. Ciombor, Stacey A. Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Paul Haste, J. Randolph Hecht, Sarah Hoffe, Steven Hunt, Hisham Hussan, Kimberly L. Johung, Nora Joseph, Natalie Kirilcuk, Smitha Krishnamurthi, Midhun Malla, Jennifer K. Maratt, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, Benjamin Shogan, John M. Skibber, Constantinos T. Sofocleous, Anna Tavakkoli, Christopher G. Willett, Christina Wu, Lisa A. Gurski, Jenna Snedeker, and Frankie Jones

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

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Hello JNCCN Readers

Daniel M. Geynisman

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Highlights of the NCCN Oncology Research Program