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Ju Dong Yang, Michael Luu, Amit G. Singal, Mazen Noureddin, Alexander Kuo, Walid S. Ayoub, Vinay Sundaram, Honore Kotler, Irene K. Kim, Tsuyoshi Todo, Georgios Voidonikolas, Todd V. Brennan, Kambiz Kosari, Andrew S. Klein, Andrew Hendifar, Shelly C. Lu, Nicholas N. Nissen and Jun Gong

Background: It remains unknown to what extent hepatocellular carcinomas (HCCs) are detected very early (T1 stage; ie, unifocal <2 cm) in the United States. The aim of this study was to investigate the trends and factors associated with very early detection of HCC and resultant outcomes. Methods: Patients with HCC diagnosed from 2004 through 2014 were identified from the National Cancer Database. Logistic regression was used to identify factors associated with T1 HCC detection, and Cox proportional hazard analyses identified factors associated with overall survival among patients with T1 HCC. Results: Of 110,182 eligible patients, the proportion with T1 HCC increased from 2.6% in 2004 to 6.8% in 2014 (P<.01). The strongest correlate of T1 HCC detection was receipt of care at an academic institution (odds ratio, 3.51; 95% CI, 2.31–5.34). Older age, lack of insurance, high Model for End-Stage Liver Disease (MELD) score, high alpha-fetoprotein, increased Charlson-Deyo comorbidity score, and nonsurgical treatment were associated with increased mortality, and care at an academic center (hazard ratio [HR], 0.27; 95% CI, 0.15–0.48) was associated with reduced mortality in patients with T1 HCC. Liver transplantation (HR, 0.27; 95% CI, 0.20–0.37) and surgical resection (HR, 0.67; 95% CI, 0.48–0.93) were independently associated with improved survival compared with ablation. This is the first study to examine the trend of T1 HCC using the National Cancer Database, which covers approximately 70% of all cancer diagnoses in the United States, using robust statistical analyses. Limitations of the study include a retrospective study design using administrative data and some pertinent data that were not available. Conclusions: Despite increases over time, <10% of HCCs are detected at T1 stage. The strongest correlates of survival among patients with T1 HCC are receiving care at an academic institution and surgical treatment.

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Nanruoyi Zhou, Maria A. Velez, Dwight Owen and Aaron E. Lisberg

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Ganessan Kichenadasse, John O. Miners, Arduino A. Mangoni, Andrew Rowland, Ashley M. Hopkins and Michael J. Sorich

Background: Immune-related adverse events (irAEs) are known to occur in patients with cancer who are treated with immune checkpoint inhibitors. However, limited literature exists on the incidence, time of onset, and risk factors for irAEs, particularly those affecting multiple organs, associated with anti–PD-L1 inhibitors. Methods: A post hoc pooled analysis was conducted using individual patient data from atezolizumab monotherapy arms of 4 non–small cell lung cancer clinical trials. Incidence, clinical patterns, outcomes, and risk factors were investigated of selected organ-specific and multiorgan irAEs during treatment using the anti–PD-L1 inhibitor atezolizumab. Results: From a total of 1,548 patients, 730 irAE episodes were reported in 424 patients (27%). Skin irAEs were the most common (42%), followed by laboratory abnormalities (27%) and endocrine (11.6%), neurologic (7.6%), and pulmonary (6.2%) irAEs. A total of 84 patients (5.4%) had multiorgan irAEs, 70 had 2, 13 had 3, and 1 had 4 different organs affected. “Skin plus” or “laboratory plus” were the most common irAE multiorgan clusters. Patients with multiorgan irAEs were more likely to be white and have a good performance status, a lower baseline neutrophil-lymphocyte ratio, and a good or intermediate lung immune prognostic index score. Multiorgan irAEs were also associated with improved overall survival (hazard ratio, 0.47; 95% CI, 0.28–0.78; P<.0001) but not with progression-free survival (hazard ratio, 0.92; 95% CI, 0.62–1.35; P=.74) compared with the cohort with no irAEs. Conclusions: Multiorgan irAEs occurred in 5.4% of patients treated with atezolizumab in non–small cell lung cancer trials. Future trials should consider routine reporting of data on multiorgan toxicities in addition to organ-specific toxicities.

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Aaron T. Gerds, Jason Gotlib, Prithviraj Bose, Michael W. Deininger, Andrew Dunbar, Amro Elshoury, Tracy I. George, Ivana Gojo, Krishna Gundabolu, Elizabeth Hexner, Gabriela Hobbs, Tania Jain, Catriona Jamieson, Andrew T. Kuykendall, Brandon McMahon, Sanjay R. Mohan, Vivian Oehler, Stephen Oh, Animesh Pardanani, Nikolai Podoltsev, Erik Ranheim, Lindsay Rein, Rachel Salit, David S. Snyder, Brady L. Stein, Moshe Talpaz, Swapna Thota, Pankit Vachhani, Martha Wadleigh, Katherine Walsh, Dawn C. Ward, Mary Anne Bergman and Hema Sundar

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.

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NCCN Guidelines Insights: Kidney Cancer, Version 1.2021

Featured Updates to the NCCN Guidelines

Robert J. Motzer, Eric Jonasch, Shawna Boyle, Maria I. Carlo, Brandon Manley, Neeraj Agarwal, Ajjai Alva, Katy Beckermann, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Arpita Desai, Saby George, John L. Gore, Naomi Haas, Steven L. Hancock, Christos Kyriakopoulos, Elaine T. Lam, Clayton Lau, Bryan Lewis, David C. Madoff, Brittany McCreery, M. Dror Michaelson, Amir Mortazavi, Lakshminarayanan Nandagopal, Phillip M. Pierorazio, Elizabeth R. Plimack, Lee Ponsky, Sundhar Ramalingam, Brian Shuch, Zachary L. Smith, Bradley Somer, Jeffrey Sosman, Mary A. Dwyer and Angela D. Motter

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.

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Terrell Johnson, Lindsey A.M. Bandini, Darryl Mitteldorf, Elizabeth Franklin, Justin E. Bekelman and Robert W. Carlson

As the oncology ecosystem shifts from service-based care to outcomes and value-based care, stakeholders cite concerns regarding the lack of patient experience data that are important to the patient community. To address the patient perspective and highlight the challenges and opportunities within policy and clinical decision-making to improve patient-centered care, NCCN hosted the NCCN Patient Advocacy Summit: Delivering Value for Patients Across the Oncology Ecosystem on December 11, 2019, in Washington, DC. The summit featured multidisciplinary panel discussions, keynote speakers, and patient advocate presentations exploring the implications for patient-centered care within a shifting health policy landscape. This article encapsulates and expounds upon the discussions and presentations from the summit.

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Joan How and Gabriela S. Hobbs

Primary myelofibrosis (PMF) has the least favorable prognosis of the Philadelphia chromosome–negative myeloproliferative neoplasms, which also include essential thrombocythemia (ET) and polycythemia vera (PV). However, clinical presentations and outcomes of PMF vary widely, with median overall survival ranging from years to decades. Given the heterogeneity of PMF, there has been considerable effort to develop discriminatory prognostic models to help with management decisions, particularly for the consideration of hematopoietic stem cell transplantation in patients at higher risk. Although earlier models incorporated only clinical features in risk stratification, contemporary models increasingly use molecular and cytogenetic features, leading to more comprehensive prognostication. This article reviews the most widely adopted prognostic models used for PMF, including the International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS)/DIPSS+, mutation-enhanced IPSS for transplant-age patients (MIPSS70)/MIPSS70+/MIPSS70+ version 2.0, genetically inspired prognostic scoring system, and Myelofibrosis Secondary to PV and ET-Prognostic Model in patients with post-ET/PV myelofibrosis. We also discuss newly emerging prognostic models and provide a practical approach to risk stratification in patients with PMF and post-ET/PV myelofibrosis.

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Andrew T. Kuykendall and Rami Komrokji

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by clonal overproduction of platelets and an increased risk of thrombohemorrhagic complications. Patients are risk stratified by driver mutation, age, and thrombotic history and treated to reduce the risk of thrombotic and hemorrhagic events. The significance of platelet number as a risk factor or treatment goal is unclear. Despite the preponderance of data failing to demonstrate an association, there exists a pervasive belief that higher platelet counts correlate with an increased thrombotic risk. In fact, the association between thrombocytosis and bleeding is more clearly supported. Variability in regional consensus guidelines contributes to the uncertainty. This article reviews the data that shed light on the importance of platelet count in patients with ET.