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Management of EGFR Mutation–Positive Non–Small Cell Lung Cancer

Rogerio A. Lilenbaum and Leora A. Horn

For appropriate treatment selection, the updated NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) recommend broad molecular profiling for all patients with nonsquamous disease. Three different tyrosine kinase inhibitors (TKIs) are recommended as first-line treatment of EGFR mutation–positive NSCLC: gefitinib, erlotinib, and afatinib. Most patients whose disease responds will still experience progression, and the type of disease progression drives management. Systemic progression requires switching TKI treatment, whereas patients with oligoprogression and central nervous system progression may have their new lesions treated but continue on their TKI. A new third-generation TKI has been approved and others are currently under development, and new combinations of these drugs with a VEGFR inhibitor offer promise to improve outcomes.

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Making the Grade: The Impact of Low-Grade Toxicities on Patient Preference for Treatment With Novel Agents

Emily H. Castellanos, Sheau-chiann Chen, Hillary Drexler, and Leora Horn

Background: Targeted therapies have shown clinical benefit in the treatment of solid tumors. The toxicity profiles and treatment duration and schedule of these agents differ considerably from those of traditional chemotherapy. Many studies of targeted therapies report sizeable numbers of grade 1 or 2 toxicities. We sought to determine whether anticipation of low-grade toxicities and treatment logistics impact patient willingness to undergo therapy. Patients and Methods: A total of 209 patients with cancer (101 lung and 108 breast) were surveyed at the Vanderbilt-Ingram Cancer Center regarding willingness to comply with treatment based on anticipated efficacy, dosing convenience, and toxicity profiles. All toxicities were Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 1 and 2. Willingness to comply with treatment depending on toxicity, anticipated benefit, cancer type, and dosing convenience was compared. Results: A substantial number of patients (2.9%–48.8%, depending on the toxicity described) professed unwillingness to undergo treatment because of anticipated grade 1 and 2 toxicities. Gastrointestinal and constitutional toxicities had a stronger negative impact on patient willingness to undergo therapy than dermatologic toxicity. Patients with lung cancer were significantly more likely to accept dermatologic and gastrointestinal toxicities than those with breast cancer. Willingness to tolerate toxicities correlated with expected benefit in terms of life expectancy and chance of cure. Lengthy travel distance for treatment negatively impacted willingness to undergo treatment. Conclusions: Anticipation of low-grade toxicities and dosing inconvenience negatively impacts patient willingness to be treated, which may affect adherence and therapeutic outcomes from therapy. Long-term tolerability should be considered when developing and assessing the impact of novel agents.

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Low Provider Knowledge Is Associated With Less Evidence-Based Lung Cancer Screening

Jennifer A. Lewis, Heidi Chen, Kathryn E. Weaver, Lucy B. Spalluto, Kim L. Sandler, Leora Horn, Robert S. Dittus, Pierre P. Massion, Christianne L. Roumie, and Hilary A. Tindle

Background: Despite widespread recommendation and supportive policies, screening with low-dose CT (LDCT) is incompletely implemented in the US healthcare system. Low provider knowledge of the lung cancer screening (LCS) guidelines represents a potential barrier to implementation. Therefore, we tested the hypothesis that low provider knowledge of guidelines is associated with less provider-reported screening with LDCT. Patients and Methods: A cross-sectional survey was performed in a large academic medical center and affiliated Veterans Health Administration in the Mid-South United States that comprises hospital and community-based practices. Participants included general medicine providers and specialists who treat patients aged >50 years. The primary exposure was LCS guideline knowledge (US Preventive Services Task Force/Centers for Medicare & Medicaid Services). High knowledge was defined as identifying 3 major screening eligibility criteria (55 years as initial age of screening eligibility, smoking status as current or former smoker, and smoking history of ≥30 pack-years), and low knowledge was defined as not identifying these 3 criteria. The primary outcome was self-reported LDCT order/referral within the past year, and the secondary outcome was screening chest radiograph. Multivariable logistic regression evaluated the adjusted odds ratio (aOR) of screening by knowledge. Results: Of 625 providers recruited, 407 (65%) responded, and 378 (60.5%) were analyzed. Overall, 233 providers (62%) demonstrated low LCS knowledge, and 224 (59%) reported ordering/referring for LDCT. The aOR of ordering/referring LDCT was less among providers with low knowledge (0.41; 95% CI, 0.24–0.71) than among those with high knowledge. More providers with low knowledge reported ordering screening chest radiographs (aOR, 2.7; 95% CI, 1.4–5.0) within the past year. Conclusions: Referring provider knowledge of LCS guidelines is low and directly proportional to the ordering rate for LDCT in an at-risk US population. Strategies to advance evidence-based LCS should incorporate provider education and system-level interventions to address gaps in provider knowledge.

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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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Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica Bauman, Lucian R. Chirieac, Thomas A. D'Amico, Malcolm M. DeCamp, Thomas J. Dilling, Michael Dobelbower, Robert C. Doebele, Ramaswamy Govindan, Matthew A. Gubens, Mark Hennon, Leora Horn, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Leah J. Leisch, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

This selection from the NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 5.2018

David S. Ettinger, Dara L. Aisner, Douglas E. Wood, Wallace Akerley, Jessica Bauman, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D'Amico, Thomas J. Dilling, Michael Dobelbower, Ramaswamy Govindan, Matthew A. Gubens, Mark Hennon, Leora Horn, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Sandip P. Patel, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 4.2016

David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas J. Dilling, M. Chris Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr., Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC; Versions 1–4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

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Non–Small Cell Lung Cancer, Version 1.2015

David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Thomas J. Dilling, Ramaswamy Govindan, Frederic W. Grannis Jr, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Mark G. Kris, Lee M. Krug, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Steven Schild, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

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NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016

David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas Dilling, Michael Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, Scott J. Swanson, James Stevenson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

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Small Cell Lung Cancer

Gregory P. Kalemkerian, Wallace Akerley, Paul Bogner, Hossein Borghaei, Laura QM Chow, Robert J. Downey, Leena Gandhi, Apar Kishor P. Ganti, Ramaswamy Govindan, John C. Grecula, James Hayman, Rebecca Suk Heist, Leora Horn, Thierry Jahan, Marianna Koczywas, Billy W. Loo Jr, Robert E. Merritt, Cesar A. Moran, Harvey B. Niell, Janis O’Malley, Jyoti D. Patel, Neal Ready, Charles M. Rudin, Charles C. Williams Jr, Kristina Gregory, and Miranda Hughes

Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.