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Omission of Adjuvant Therapy After Gastric Cancer Resection: Development of a Validated Risk Model

Jashodeep Datta, Matthew T. McMillan, Eric K. Shang, Ronac Mamtani, Russell S. Lewis Jr, Rachel R. Kelz, Ursina Teitelbaum, John P. Plastaras, Jeffrey A. Drebin, Douglas L. Fraker, Giorgos C. Karakousis, and Robert E. Roses

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer recommend adjuvant chemotherapy with or without radiotherapy following after resection of gastric adenocarcinoma (GA) for patients who have not received neoadjuvant therapy. Despite frequent noncompliance with NCCN Guidelines nationally, risk factors underlying adjuvant therapy omission (ATom) have not been well characterized. We developed an internally validated preoperative instrument stratifying patients by incremental risk of ATom. The National Cancer Data Base was queried for patients with stage IB–III GA undergoing gastrectomy; those receiving neoadjuvant therapy were excluded. Multivariable models identified factors associated with ATom between 2006 and 2011. Internal validation was performed using bootstrap analysis; model discrimination and calibration were assessed using k-fold cross-validation and Hosmer-Lemeshow procedures, respectively. Using weighted β-coefficients, a simplified Omission Risk Score (ORS) was created to stratify ATom risk. The impact of ATom on overall survival (OS) was examined in ORS risk-stratified cohorts. In 4,728 patients (median age, 70 years; 64.8% male), 53.7% had ATom. The bootstrap-validated model identified advancing age, comorbidity, underinsured/uninsured status, proximal tumor location, and clinical T1/2 and N0 tumors as independent ATom predictors, demonstrating good discrimination. The simplified ORS, stratifying patients into low-, moderate-, and high-risk categories, predicted incremental risk of ATom (30% vs 53% vs 80%, respectively) and progressive delay to adjuvant therapy initiation (median time, 51 vs 55 vs 61 days, respectively). Patients at moderate/high-risk of ATom demonstrated worsening risk-adjusted mortality compared with low-risk patients (median OS, 26.4 vs 29.2 months). This ORS may aid in rational selection of multimodality treatment sequence in GA.

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NCCN Guidelines Insights: Bone Cancer, Version 2.2017

J. Sybil Biermann, Warren Chow, Damon R. Reed, David Lucas, Douglas R. Adkins, Mark Agulnik, Robert S. Benjamin, Brian Brigman, G. Thomas Budd, William T. Curry, Aarati Didwania, Nicola Fabbri, Francis J. Hornicek, Joseph B. Kuechle, Dieter Lindskog, Joel Mayerson, Sean V. McGarry, Lynn Million, Carol D. Morris, Sujana Movva, Richard J. O'Donnell, R. Lor Randall, Peter Rose, Victor M. Santana, Robert L. Satcher, Herbert Schwartz, Herrick J. Siegel, Katherine Thornton, Victor Villalobos, Mary Anne Bergman, and Jillian L. Scavone

The NCCN Guidelines for Bone Cancer provide interdisciplinary recommendations for treating chordoma, chondrosarcoma, giant cell tumor of bone, Ewing sarcoma, and osteosarcoma. These NCCN Guidelines Insights summarize the NCCN Bone Cancer Panel's guideline recommendations for treating Ewing sarcoma. The data underlying these treatment recommendations are also discussed.

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Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology

Robert J. Morgan Jr, Deborah K. Armstrong, Ronald D. Alvarez, Jamie N. Bakkum-Gamez, Kian Behbakht, Lee-may Chen, Larry Copeland, Marta Ann Crispens, Maria DeRosa, Oliver Dorigo, David M. Gershenson, Heidi J. Gray, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Lainie Martin, Ursula A. Matulonis, David M. O'Malley, Richard T. Penson, Sanja Percac-Lima, Mario Pineda, Steven C. Plaxe, Matthew A. Powell, Elena Ratner, Steven W. Remmenga, Peter G. Rose, Paul Sabbatini, Joseph T. Santoso, Theresa L. Werner, Jennifer Burns, and Miranda Hughes

This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors.

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Chronic Myeloid Leukemia, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

Neil P. Shah, Ravi Bhatia, Jessica K. Altman, Maria Amaya, Kebede H. Begna, Ellin Berman, Onyee Chan, Joan Clements, Robert H. Collins Jr, Peter T. Curtin, Daniel J. DeAngelo, Michael Drazer, Lori Maness, Leland Metheny, Sanjay Mohan, Joseph O. Moore, Vivian Oehler, Keith Pratz, Iskra Pusic, Michal G. Rose, William Shomali, B. Douglas Smith, Michael Styler, Moshe Talpaz, Tiffany N. Tanaka, Srinivas Tantravahi, James Thompson, Steven Tsai, Jennifer Vaughn, Jeanna Welborn, David T. Yang, Hema Sundar, and Kristina Gregory

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome resulting from a reciprocal translocation between chromosomes 9 and 22 [t9;22] that gives rise to a BCR::ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase in developed countries. Tyrosine kinase inhibitor (TKI) therapy is a highly effective treatment option for patients with chronic phase–CML. The primary goal of TKI therapy in patients with chronic phase–CML is to prevent disease progression to accelerated phase–CML or blast phase–CML. Discontinuation of TKI therapy with careful monitoring is feasible in selected patients. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase–CML.

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Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

Jaffer A. Ajani, Thomas A. D’Amico, David J. Bentrem, Joseph Chao, Carlos Corvera, Prajnan Das, Crystal S. Denlinger, Peter C. Enzinger, Paul Fanta, Farhood Farjah, Hans Gerdes, Michael Gibson, Robert E. Glasgow, James A. Hayman, Steven Hochwald, Wayne L. Hofstetter, David H. Ilson, Dawn Jaroszewski, Kimberly L. Johung, Rajesh N. Keswani, Lawrence R. Kleinberg, Stephen Leong, Quan P. Ly, Kristina A. Matkowskyj, Michael McNamara, Mary F. Mulcahy, Ravi K. Paluri, Haeseong Park, Kyle A. Perry, Jose Pimiento, George A. Poultsides, Robert Roses, Vivian E. Strong, Georgia Wiesner, Christopher G. Willett, Cameron D. Wright, Nicole R. McMillian, and Lenora A. Pluchino

Abstract

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

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Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology

Jaffer A. Ajani, Thomas A. D’Amico, David J. Bentrem, David Cooke, Carlos Corvera, Prajnan Das, Peter C. Enzinger, Thomas Enzler, Farhood Farjah, Hans Gerdes, Michael Gibson, Patrick Grierson, Wayne L. Hofstetter, David H. Ilson, Shadia Jalal, Rajesh N. Keswani, Sunnie Kim, Lawrence R. Kleinberg, Samuel Klempner, Jill Lacy, Frank Licciardi, Quan P. Ly, Kristina A. Matkowskyj, Michael McNamara, Aaron Miller, Sarbajit Mukherjee, Mary F. Mulcahy, Darryl Outlaw, Kyle A. Perry, Jose Pimiento, George A. Poultsides, Scott Reznik, Robert E. Roses, Vivian E. Strong, Stacey Su, Hanlin L. Wang, Georgia Wiesner, Christopher G. Willett, Danny Yakoub, Harry Yoon, Nicole R. McMillian, and Lenora A. Pluchino

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

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Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Jaffer A. Ajani, Thomas A. D’Amico, David J. Bentrem, Joseph Chao, David Cooke, Carlos Corvera, Prajnan Das, Peter C. Enzinger, Thomas Enzler, Paul Fanta, Farhood Farjah, Hans Gerdes, Michael K. Gibson, Steven Hochwald, Wayne L. Hofstetter, David H. Ilson, Rajesh N. Keswani, Sunnie Kim, Lawrence R. Kleinberg, Samuel J. Klempner, Jill Lacy, Quan P. Ly, Kristina A. Matkowskyj, Michael McNamara, Mary F. Mulcahy, Darryl Outlaw, Haeseong Park, Kyle A. Perry, Jose Pimiento, George A. Poultsides, Scott Reznik, Robert E. Roses, Vivian E. Strong, Stacey Su, Hanlin L. Wang, Georgia Wiesner, Christopher G. Willett, Danny Yakoub, Harry Yoon, Nicole McMillian, and Lenora A. Pluchino

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.