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Health-Related Quality of Life in Patients With Metastatic Colorectal Cancer Undergoing Systemic Therapy With or Without Maximal Tumor Debulking

Lotte Bakkerus, Laurien M. Buffart, Tineke E. Buffart, Yannick M. Meyer, Barbara M. Zonderhuis, Cornelis J.A. Haasbeek, Kathelijn S. Versteeg, Olaf J.L. Loosveld, Jan Willem B. de Groot, Mathijs P. Hendriks, Cornelis Verhoef, Hendrik M.W. Verheul, and Elske C. Gootjes

Background: Maintaining a sufficient health-related quality of life (HRQoL) is important in the palliative treatment of patients with metastatic colorectal cancer (mCRC). The ORCHESTRA trial ( identifier: NCT01792934) is designed to prospectively evaluate overall survival benefit and impact on HRQoL of tumor debulking when added to first-line palliative systemic therapy in patients with multiorgan mCRC. In the present study, we report the HRQoL associated with this combination treatment compared with standard systemic therapy. Methods: Patients included in the ORCHESTRA trial with clinical benefit after 3 or 4 cycles of first-line palliative systemic therapy with fluoropyrimidines and oxaliplatin with or without bevacizumab were randomly assigned to maximal tumor debulking followed by systemic therapy versus systemic therapy alone. Patients completed the EORTC Quality of Life Questionnaire-Core 30 and the Multidimensional Fatigue Inventory questionnaire at prespecified time points during treatment. Between-group differences in HRQoL over time were evaluated with linear mixed model analyses. A pattern mixture approach was applied to correct for missing questionnaires due to progressive disease. Results: A total of 300 patients were randomized to the intervention arm (n=148) or the standard arm (n=152). No statistically significant or clinically relevant differences in HRQoL and fatigue were observed when tumor debulking was added to systemic therapy. In patients of both study arms, HRQoL after 1 year of treatment was not significantly different from HRQoL at the time of randomization. Patients in the intervention arm experienced serious adverse events (SAEs) twice as often as patients in the standard arm (P≤.001). Conclusions: Maximal tumor debulking in combination with palliative systemic therapy in patients with multiorgan mCRC was significantly associated with more SAEs resulting from local therapy but no difference in HRQoL compared with palliative systemic therapy alone. There is a remarkable lack of association between the occurrence of SAEs and impact on HRQoL.

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Highlights of the NCCN Oncology Research Program

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Identification and Characterization of Avoidable Hospital Admissions in Patients With Lung Cancer

Eric M. Lander, Xuanyi Li, Li-Ching Huang, Amanda S. Cass, Wade T. Iams, Emily A. Skotte, Jennifer G. Whisenant, Robert A. Ramirez, Sally J. York, Travis J. Osterman, Jennifer A. Lewis, Christine M. Lovly, Yu Shyr, and Leora Horn

Background: More than 50% of patients with lung cancer are admitted to the hospital while receiving treatment, which is a burden to patients and the healthcare system. This study characterizes the risk factors and outcomes of patients with lung cancer who were admitted to the hospital. Methods: A multidisciplinary oncology care team conducted a retrospective medical record review of patients with lung cancer admitted in 2018. Demographics, disease and admission characteristics, and end-of-life care utilization were recorded. Following a multidisciplinary consensus review process, admissions were determined to be either “avoidable” or “unavoidable.” Generalized estimating equation logistic regression models assessed risks and outcomes associated with avoidable admissions. Results: In all, 319 admissions for 188 patients with a median age of 66 years (IQR, 59–74 years) were included. Cancer-related symptoms accounted for 65% of hospitalizations. Common causes of unavoidable hospitalizations were unexpected disease progression causing symptoms, chronic obstructive pulmonary disease exacerbation, and infection. Of the 47 hospitalizations identified as avoidable (15%), the median overall survival was 1.6 months compared with 9.7 months (hazard ratio, 2.07; 95% CI, 1.34–3.19; P<.001) for unavoidable hospitalizations. Significant reasons for avoidable admissions included cancer-related pain (P=.02), hypervolemia (P=.03), patient desire to initiate hospice services (P=.01), and errors in medication reconciliation or distribution (P<.001). Errors in medication management caused 26% of the avoidable hospitalizations. Of admissions in patients receiving immunotherapy (n=102) or targeted therapy (n=44), 9% were due to adverse effects of treatment. Patients receiving immunotherapy and targeted therapy were at similar risk of avoidable hospitalizations compared with patients not receiving treatment (P=.3 and P=.1, respectively). Conclusions: We found that 15% of hospitalizations among patients with lung cancer were potentially avoidable. Uncontrolled symptoms, delayed implementation of end-of-life care, and errors in medication reconciliation were associated with avoidable inpatient admissions. Symptom management tools, palliative care integration, and medication reconciliations may mitigate hospitalization risk.

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It Just Keeps Getting Better!

Margaret Tempero

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Letter to the Editor: Inclusive and Adequate Care Overcoming All Health Care Gaps: The Need to Specifically Look to the LGBTQI+ Population

Massimo De Martinis and Lia Ginaldi

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Letter to the Editor Re: Influence of Food With Different Fat Concentrations on Alectinib Exposure: A Randomized Crossover Pharmacokinetic Trial

Andrew D. Frugé, Kristen S. Smith, Sylvia L. Crowder, and Wendy Demark-Wahnefried

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Machine Learning–Based Early Warning Systems for Acute Care Utilization During Systemic Therapy for Cancer

Robert C. Grant, Jiang Chen He, Ferhana Khan, Ning Liu, Sho Podolsky, Yosuf Kaliwal, Melanie Powis, Faiyaz Notta, Kelvin K.W. Chan, Marzyeh Ghassemi, Steven Gallinger, and Monika K. Krzyzanowska

Background: Emergency department visits and hospitalizations frequently occur during systemic therapy for cancer. We developed and evaluated a longitudinal warning system for acute care use. Methods: Using a retrospective population-based cohort of patients who started intravenous systemic therapy for nonhematologic cancers between July 1, 2014, and June 30, 2020, we randomly separated patients into cohorts for model training, hyperparameter tuning and model selection, and system testing. Predictive features included static features, such as demographics, cancer type, and treatment regimens, and dynamic features, such as patient-reported symptoms and laboratory values. The longitudinal warning system predicted the probability of acute care utilization within 30 days after each treatment session. Machine learning systems were developed in the training and tuning cohorts and evaluated in the testing cohort. Sensitivity analyses considered feature importance, other acute care endpoints, and performance within subgroups. Results: The cohort included 105,129 patients who received 1,216,385 treatment sessions. Acute care followed 182,444 (15.0%) treatments within 30 days. The ensemble model achieved an area under the receiver operating characteristic curve of 0.742 (95% CI, 0.739–0.745) and was well calibrated in the test cohort. Important predictive features included prior acute care use, treatment regimen, and laboratory tests. If the system was set to alarm approximately once every 15 treatments, 25.5% of acute care events would be preceded by an alarm, and 47.4% of patients would experience acute care after an alarm. The system underestimated risk for some treatment regimens and potentially underserved populations such as females and non-English speakers. Conclusions: Machine learning warning systems can detect patients at risk for acute care utilization, which can aid in preventive intervention and facilitate tailored treatment. Future research should address potential biases and prospectively evaluate impact after system deployment.

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NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024

Featured Updates to the NCCN Guidelines

Mary B. Daly, Tuya Pal, Kara N. Maxwell, Jane Churpek, Wendy Kohlmann, Zahraa AlHilli, Banu Arun, Saundra S. Buys, Heather Cheng, Susan M. Domchek, Susan Friedman, Veda Giri, Michael Goggins, Andrea Hagemann, Ashley Hendrix, Mollie L. Hutton, Beth Y. Karlan, Nawal Kassem, Seema Khan, Katia Khoury, Allison W. Kurian, Christine Laronga, Julie S. Mak, John Mansour, Kevin McDonnell, Carolyn S. Menendez, Sofia D. Merajver, Barbara S. Norquist, Kenneth Offit, Dominique Rash, Gwen Reiser, Leigha Senter-Jamieson, Kristen Mahoney Shannon, Kala Visvanathan, Jeanna Welborn, Myra J. Wick, Marie Wood, Matthew B. Yurgelun, Mary A. Dwyer, and Susan D. Darlow

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.

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Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology

Edward M. Schaeffer, Sandy Srinivas, Nabil Adra, Yi An, Daniel Barocas, Rhonda Bitting, Alan Bryce, Brian Chapin, Heather H. Cheng, Anthony Victor D’Amico, Neil Desai, Tanya Dorff, James A. Eastham, Thomas A. Farrington, Xin Gao, Shilpa Gupta, Thomas Guzzo, Joseph E. Ippolito, Michael R. Kuettel, Joshua M. Lang, Tamara Lotan, Rana R. McKay, Todd Morgan, George Netto, Julio M. Pow-Sang, Robert Reiter, Mack Roach III, Tyler Robin, Stan Rosenfeld, Ahmad Shabsigh, Daniel Spratt, Benjamin A. Teply, Jonathan Tward, Richard Valicenti, Jessica Karen Wong, Dorothy A. Shead, Jenna Snedeker, and Deborah A. Freedman-Cass

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer. For patients with nonmetastatic CRPC, ADT is continued with or without the addition of certain secondary hormone therapies depending on prostate-specific antigen doubling time. In the mCRPC setting, ADT is continued with the sequential addition of certain secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, the presence or absence of visceral disease, symptoms, and potential side effects.