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Value of Size and Malignant Features of Lateral Lymph Nodes in Risk Stratification at Lateral Local Recurrence of Rectal Cancer: A National Cohort Study

Eline G.M. van Geffen, Tania C. Sluckin, Sanne-Marije J.A. Hazen, Karin Horsthuis, Regina G.H. Beets-Tan, Susan van Dieren, Corrie A.M. Marijnen, Pieter J. Tanis, and Miranda Kusters

Background: Patients with rectal cancer who have enlarged lateral lymph nodes (LLNs) have an increased risk of lateral local recurrence (LLR). However, little is known about prognostic implications of malignant features (internal heterogeneity, irregular margins, loss of fatty hilum, and round shape) on MRI and number of enlarged LLNs, in addition to LLN size. Methods: Of the 3,057 patients with rectal cancer included in this national, retrospective, cross-sectional cohort study, 284 with a cT3–4 tumor located ≤8 cm from the anorectal junction who received neoadjuvant treatment and who had visible LLNs on MRI were selected. Imaging was reassessed by trained radiologists. LLNs were categorized based on size. Influence of malignant features and the number of LLNs on LLR was investigated. Results: Of 284 patients with at least 1 visible LLN, 122 (43%) had an enlarged node (≥7.0 mm) and 157 (55%) had malignant features. Of the 122 patients with enlarged nodes, 25 had multiple (≥2). In patients with a single enlarged node (n=97), a single malignant feature was associated with a 4-year LLR rate of 0% and multiple malignant features was associated with a rate of 17% (P=.060). In the group with multiple malignant features, their disappearance on restaging was associated with an LLR rate of 13% compared with an LLR rate of 20% for persistent malignant features (P=.532). The presence of intermediate-size LLNs (5.0–6.9 mm) with at least 1 malignant feature was associated with a 4-year LLR rate of 8%; the 4-year LLR rate was 13% when the malignant features persisted on restaging MRI (P=.409). Patients with multiple enlarged LLNs had a 4-year LLR rate of 28% compared with 11% for those with a single enlarged LLN (P=.059). Conclusions: The presence of multiple enlarged LLNs (≥7.0 mm), as well as multiple malignant features in an enlarged node contribute to the risk of developing an LLR. These radiologic features can be used for clinical decision-making regarding the potential benefit of LLN dissection.

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Associations Among Optimal Lung Cancer Treatment, Clinical Outcomes, and Health Care Utilization in Patients Who Underwent Comprehensive Genomic Profiling

Adam C. Powell, Elifnur Yay Donderici, Nicole J. Zhang, Shaun P. Forbes, Julie Wiedower, Amy C. McNeal, and Mark D. Hiatt

Background: Although immune checkpoint inhibitor immunotherapies are contraindicated as first-line treatment of advanced non–small cell lung cancer (NSCLC) in patients with ALK rearrangement and EGFR mutation, many receive them. The purpose of this study was to examine the association between optimal first-line treatment in this population and clinical outcomes. Methods: Claims and genomic data from patients with advanced or metastatic NSCLC were extracted from a nationally representative GuardantINFORM dataset. Patients who had their first claim mentioning advanced or metastatic NSCLC between March 2019 and February 2020 and had ALK rearrangement or EGFR mutation detected by comprehensive genomic profiling were included in this study. Patients were classified as having received optimal or suboptimal first-line treatment. Claims were reviewed to determine real-world time to next treatment, real-world time to discontinuation, and health services utilization (emergency department, inpatient, and outpatient) in the 12 months following first-line treatment initiation. Survival analyses were conducted using Kaplan-Meier plots and Cox proportional hazard models. Health services utilization was compared between the groups using t tests and negative binomial models. Results: Of the 359 patients included, 280 (78.0%) received optimal first-line treatment. Optimally treated patients had longer median real-world time to next treatment (11.2 vs 4.4 months; P<.01) and real-world time to discontinuation (10.4 vs 1.9 months; P<.01). The optimal group had significantly fewer emergency department presentations (0.76 vs 1.27; P<.01) and outpatient visits (22.9 vs 42.7; P<.01) than the suboptimal group but did not significantly differ in inpatient utilization. Adjusted utilization analysis yielded similar findings. Conclusions: Patients with NSCLC who received optimal treatment, as determined by comprehensive genomic profiling using next-generation sequencing–based circulating tumor DNA testing (Guardant360), had significantly superior clinical and utilization outcomes, reinforcing existing guidelines recommending profiling at the onset of treatment.

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Development of a Strategic Initiative at MD Anderson Cancer Center to Improve Outcomes in Immune-Related Adverse Events

Sarah E. Fayle, Nicolas L. Palaskas, Bilal A. Siddiqui, Jennifer L. McQuade, Jamie S. Lin, Sumit K. Subudhi, Anisha B. Patel, Robert R. Jenq, Amishi Y. Shah, Amy R. Spelman, Mianen Sun, Bettina H. Marble, and Yinghong Wang

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for many cancer types. The clinical use of ICIs is increasing rapidly, including in combinations associated with increased risk of toxicities, termed “immune-related adverse events” (irAEs). Therefore, MD Anderson Cancer Center (MDACC) in Houston, Texas has proactively responded by developing a priority endeavor known as the Immuno-Oncology Toxicity (IOTOX) initiative. This strategic initiative aims to facilitate the seamless integration of key domains: (1) standardized clinical practice and innovative decision toolsets; (2) patient and provider education; and (3) a comprehensive clinical and translational research platform. The ultimate goal of this initiative is to develop and disseminate clinical best practices and biologic insights into irAEs to improve outcomes of patients with irAEs at MDACC and in the wider oncology community.

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Reduction in Breast Cancer Death With Adjuvant Chemotherapy Among US Women According to Race, Ethnicity, and the 21-Gene Recurrence Score

Hsiao-Ching Huang, Gregory S. Calip, Jennifer Weiss, Yael Simons, V.K. Gadi, Oana C. Danciu, Garth H. Rauscher, and Kent F. Hoskins

Background: We previously showed the 21-gene breast recurrence score (RS) has lower prognostic accuracy for non-Hispanic Black (NHB) compared with non-Hispanic White (NHW) women with estrogen receptor (ER)–positive/HER2-negative breast cancer. The purpose of this study was to determine the clinical validity of the RS for predicting chemotherapy benefit as recommended in the current NCCN Guidelines for Breast Cancer among women from diverse racial/ethnic groups. Methods: Using the SEER Oncotype database, we estimated propensity score–weighted hazard ratios (HRs) and 95% confidence intervals for breast cancer death with chemotherapy for women with ER-positive/HER2-negative, AJCC stages I–II, axillary node–negative, invasive breast cancer according to race/ethnicity. Results: We included 6,033 (8.2%) Asian/Pacific Islander (API), 5,697 (7.8%) NHB, 6,688 (9.1%) Hispanic, and 54,945 (74.9%) NHW women. Breast cancer death was reduced with chemotherapy for NHB (HR, 0.48, 95% CI, 0.28–0.81), Hispanic (HR, 0.48; 95% CI, 0.25–0.94), and NHW (HR, 0.80; 95% CI, 0.65–0.99) women with an RS of 26 to 100. There was a nonsignificant reduction for API women (HR, 0.59; 95% CI, 0.28–1.24). For women with an RS of 11 to 25, there was no reduction in death for any racial/ethnic group. Among women aged ≤50 years, the reduction in breast cancer death with chemotherapy differed according to race (NHB: HR, 0.37 [95% CI, 0.20–0.67]; NHW: HR, 0.56 [95% CI, 0.44–0.74]; P interaction for chemotherapy * race <.0499). An exploratory subgroup analysis found that young NHB women may benefit from chemotherapy at a lower RS cutoff than other women. Conclusions: The RS was clinically validated as a predictive biomarker for NHB, Hispanic, and NHW women with ER-positive, axillary node-negative breast cancer, but it may underestimate the benefit of chemotherapy for young NHB women. If this finding is confirmed, the RS cutoff for recommending adjuvant chemotherapy for young NHB women with ER-positive, axillary node-negative breast cancer may need to be lower than for other women.

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Molecular Targets and Therapies for Ampullary Cancer

Monica Arun Patel, Jeremy D. Kratz, Alexander S. Carlson, Ysaith Orellana Ascencio, Broc S. Kelley, and Noelle K. LoConte

Ampullary carcinomas are rare but increasing in incidence. Ampullary cancers have molecular alterations that guide choice of therapy, particularly in nonresectable cases. These alterations can be more common by subtype (intestinal, pancreaticobiliary, or mixed), and next-generation sequencing is recommended for all patients who cannot undergo surgery. In this article, we review the approach to tissue acquisition and consideration for molecular testing. Common molecular targets of interest in ampullary cancer are also discussed in this review, including HER2/ERBB2, HER3, tumor mutational burden, microsatellite instability, KRAS, and germline BRCA and ATM mutations, along with emerging and rarer alterations.

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Lung Cancer Survivorship: Physical, Social, Emotional, and Medical Needs of NSCLC Survivors

Melinda L. Hsu, Matthew Z. Guo, Sarah Olson, Cyd Eaton, Mary Boulanger, Michelle Turner, Mattea E. Miller, Anna Nguyen, Karol Szczepanek, Rahul Shenolikar, and Josephine L. Feliciano

Background: Newer therapies prolong survival for patients with lung cancer. Beyond extending survival, the needs of lung cancer (LC) survivors are poorly described. Methods: We conducted a single-institution needs assessment survey of LC survivors alive ≥1 year from diagnosis. Needs were rated on a 5-point Likert scale for 4 domains (physical, social, emotional, and medical). Multiple regression models identified demographic or treatment characteristics associated with more needs in each category. A subset analysis of survivors with metastatic LC was performed. Results: Of 360 patients approached, 235 surveys were completed. Among completed survey respondents, the median age was 69 years; most were female (62%), married (71%), and White (74%); and 41% had stage IV cancer. Finding support resources (34%) was the most common medical need. Fatigue (70%), sleep disturbance (60%), memory and concentration (57.5%), weakness (54%), and trouble breathing (51%) were physical needs affecting more than half of respondents. The most common social need was managing daily activities (42%). Emotional needs were highly prevalent, with 79% of respondents reporting a fear of recurrence and 74.5% reporting living with uncertainty. Multiple regression analysis identified that receipt of multiple lines of systemic therapy and lower household income were associated with higher physical and social needs. Younger age was associated with having a greater number of social and emotional needs. Similar results were found in the subset of survivors with metastatic disease at diagnosis. Conclusions: The needs of LC survivors are diverse across multiple domains. Several clinical and demographic factors are independently associated with higher numbers of patient-reported needs. Our study identifies critical gaps in survivorship care for LC survivors with all stages of disease and highlights areas of future intervention.

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Volume 22 (2024): Issue 1D (Jan 2024)

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Highlights of the NCCN Oncology Research Program

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NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024

Featured Updates to the NCCN Guidelines

Chrysalyne D. Schmults, Rachel Blitzblau, Sumaira Z. Aasi, Murad Alam, Arya Amini, Kristin Bibee, Diana Bolotin, Jeremy Bordeaux, Pei-Ling Chen, Carlo M. Contreras, Dominick DiMaio, Jessica M. Donigan, Jeffrey M. Farma, Karthik Ghosh, Kelly Harms, Alan L. Ho, John Nicholas Lukens, Susan Manber, Lawrence Mark, Theresa Medina, Kishwer S. Nehal, Paul Nghiem, Kelly Olino, Soo Park, Tejesh Patel, Igor Puzanov, Jason Rich, Aleksandar Sekulic, Ashok R. Shaha, Divya Srivastava, Valencia Thomas, Courtney Tomblinson, Puja Venkat, Yaohui Gloria Xu, Siegrid Yu, Mehran Yusuf, Beth McCullough, and Sara Espinosa

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled “Clinical N0 Disease, Locally Advanced MCC.” This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term “nonsurgical” by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.