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Optimize Local Therapy for Oligometastatic and Oligoprogressive Non–Small Cell Lung Cancer to Enhance Survival

Joe Y. Chang and Vivek Verma

Metastatic non–small cell lung cancer (NSCLC) is highly heterogeneous, and there are patients with limited areas of metastases (oligometastases) or progression (oligoprogression) whose natural history and prognosis can be considerably more favorable. As a result, local therapy may offer these patients a chance at clinically meaningful disease control and/or cure. This review begins by describing the current status of the existing prospective data, including evidence of overall survival improvements from multiple randomized trials. Given the nascence of this realm, the review then examines ongoing controversies and unresolved issues regarding local therapy for oligometastatic and oligoprogression. First, the role of local therapy in the setting of targeted therapies and immunotherapy is discussed, because most published randomized trials of local therapy have been performed in the context of chemotherapy, which is no longer the standard of care for most patients with metastatic NSCLC. Refining patient selection for local therapy is then reviewed, including clinical factors (such as control of the primary and regional lymph node sites, the heterogeneous definitions of oligometastases/oligoprogression, and the underrepresentation of brain metastases in existing randomized data) and novel pathologic/molecular biomarkers. Next, because there also remains no consensus regarding the optimal modality of local therapy, the advantages and disadvantages of stereotactic radiotherapy, surgery, and other ablative techniques are discussed. Subsequently, methods to optimize radiotherapy are examined, including controversies regarding the optimal dose/fractionation and timing/sequencing scheme. A discussion regarding potentially extending the existing data to polymetastatic NSCLC follows. The review concludes with remarks regarding prudently designing randomized trials of local therapy going forward, including the benefits and drawbacks of specific endpoints meriting further testing in this unique population.

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Early and Midtreatment Mortality in Palliative Radiotherapy: Emphasizing Patient Selection in High-Quality End-of-Life Care

Matthew S. Ning, Prajnan Das, David I. Rosenthal, Bouthaina S. Dabaja, Zhongxing Liao, Joe Y. Chang, Daniel R. Gomez, Ann H. Klopp, G. Brandon Gunn, Pamela K. Allen, Paige L. Nitsch, Rachel B. Natter, Tina M. Briere, Joseph M. Herman, Rebecca Wells, Albert C. Koong, and Mary Frances McAleer

Background: Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. Materials and Methods: All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. Results: In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41–45) and varied by site (P<.001), ranging from 36 (head and neck) to 53 days (dermal/soft tissue). On multivariable analysis, earlier time-to-death was associated with osseous (hazard ratio [HR], 1.33; P<.001) and head and neck (HR, 1.45; P<.001) sites, multiple RT courses ≤6 months (HR, 1.65; P<.001), and multisite treatments (HR, 1.40; P=.008), whereas stereotactic technique (HR, 0.77; P<.001) and more recent treatment year (HR, 0.82; P<.001) were associated with longer survival. No difference in time to death was noted among patients prescribed conventional RT in 1 to 10 versus >10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; P<.001), and performance status of 3 to 4 (OR, 1.63; P=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). Conclusions: Earlier referrals and hypofractionated courses (≤5–10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

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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 2.2023

Featured Updates to the NCCN Guidelines

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aparna Hegde, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Gregory J. Riely, Jonathan Riess, Steven E. Schild, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina M. Gregory, and Miranda Hughes

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

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Non–Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D’Amico, Malcolm DeCamp, Thomas J. Dilling, Jonathan Dowell, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aparna Hegde, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr., Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Thomas Ng, Gregory A. Otterson, Jose M. Pacheco, Sandip P. Patel, Gregory J. Riely, Jonathan Riess, Steven E. Schild, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina Gregory, and Miranda Hughes

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 2.2021

Featured Updates to the NCCN Guidelines

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D’Amico, Thomas J. Dilling, Jonathan Dowell, Scott Gettinger, Matthew A. Gubens, Aparna Hegde, Mark Hennon, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Renato G. Martins, Erminia Massarelli, Daniel Morgensztern, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Jane Yanagawa, Stephen C. Yang, Kristina M. Gregory, and Miranda Hughes

The NCCN Clinical Practice Guidelines in Oncology (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 NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 1.2020

Featured Updates to the NCCN Guidelines

David S. Ettinger, Douglas E. Wood, Charu Aggarwal, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D’Amico, Thomas J. Dilling, Michael Dobelbower, Scott Gettinger, Ramaswamy Govindan, Matthew A. Gubens, Mark Hennon, Leora Horn, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Jules Lin, Billy W. Loo Jr, Renato G. Martins, Gregory A. Otterson, Sandip P. Patel, Karen L. Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, James Stevenson, Scott J. Swanson, Kurt W. Tauer, Stephen C. Yang, Kristina Gregory, OCN, 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 in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as “preferred interventions,” whereas others are categorized as either “other recommended interventions” or “useful under certain circumstances.”

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Mesothelioma: Pleural, Version 1.2024

Featured Updates to the NCCN Guidelines

James Stevenson, David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Aakash Desai, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Marina C. Garassino, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Trey C. Mullikin, Thomas Ng, Gregory A. Otterson, Dawn Owen, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Gregory J. Riely, Jonathan Riess, Theresa A. Shapiro, Aditi P. Singh, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina Gregory, and Lisa Hang

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

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Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology

David S. Ettinger, Douglas E. Wood, James Stevenson, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aparna Hegde, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Trey C. Mullikin, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Gregory J. Riely, Jonathan Riess, Theresa A. Shapiro, Aditi P. Singh, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina M. Gregory, and Miranda Hughes

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term “malignant” is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.