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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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Yong Li, Xian Chen, Yanchun Qu, Jia-Ming Fan, Yan Li, Hui Peng, Yaojie Zheng, Yihong Zhang and Hai-Bo Zhang

Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, there is no standard treatment for recurrence or unresectable tumors. Almost 50% of IMTs carry ALK gene rearrangement that can be treated using ALK inhibitors, but therapeutic options for ALK-negative tumors are limited. This report describes a woman aged 22 years with unresectable ALK-negative IMT. Next-generation sequencing revealed a TFG-ROS1 fusion, and she had a partial response to the ROS1 inhibitor ceritinib. This report provides the first published demonstration of a patient with IMT with ROS1 fusion successfully treated using ceritinib. Our study suggests that targeting ROS1 fusions using the small molecule inhibitor shows promise as an effective therapy in patients with IMT carrying this genetic alteration, but this requires further investigation in large clinical trials.

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Katherine E. Hersberger, Mishal Mendiratta-Lala, Rocky Fischer, Ravi K. Kaza, Isaac R. Francis, Mirabella S. Olszewski, John F. Harju, Wei Shi, Frank J. Manion, Mahmoud M. Al-Hawary and Vaibhav Sahai

Background: Objective radiographic assessment is crucial for accurately evaluating therapeutic efficacy and patient outcomes in oncology clinical trials. Imaging assessment workflow can be complex; can vary with institution; may burden medical oncologists, who are often inadequately trained in radiology and response criteria; and can lead to high interobserver variability and investigator bias. This article reviews the development of a tumor response assessment core (TRAC) at a comprehensive cancer center with the goal of providing standardized, objective, unbiased tumor imaging assessments, and highlights the web-based platform and overall workflow. In addition, quantitative response assessments by the medical oncologists, radiologist, and TRAC are compared in a retrospective cohort of patients to determine concordance. Patients and Methods: The TRAC workflow includes an image analyst who pre-reviews scans before review with a board-certified radiologist and then manually uploads annotated data on the proprietary TRAC web portal. Patients previously enrolled in 10 lung cancer clinical trials between January 2005 and December 2015 were identified, and the prospectively collected quantitative response assessments by the medical oncologists were compared with retrospective analysis of the same dataset by a radiologist and TRAC. Results: This study enlisted 49 consecutive patients (53% female) with a median age of 60 years (range, 29–78 years); 2 patients did not meet study criteria and were excluded. A linearly weighted kappa test for concordance for TRAC versus radiologist was substantial at 0.65 (95% CI, 0.46–0.85; standard error [SE], 0.10). The kappa value was moderate at 0.42 (95% CI, 0.20–0.64; SE, 0.11) for TRAC versus oncologists and only fair at 0.34 (95% CI, 0.12–0.55; SE, 0.11) for oncologists versus radiologist. Conclusions: Medical oncologists burdened with the task of tumor measurements in patients on clinical trials may introduce significant variability and investigator bias, with the potential to affect therapeutic response and clinical trial outcomes. Institutional imaging cores may help bridge the gap by providing unbiased and reproducible measurements and enable a leaner workflow.

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Margaret Tempero

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Caijin Lin, Jiayi Wu, Shuning Ding, Chihwan Goh, Lisa Andriani, Shuangshuang Lu, Kunwei Shen and Li Zhu

Background: Patients with de novo metastatic breast cancer (MBC) constitute a heterogeneous group with different clinicopathologic characteristics and survival outcomes. Despite controversy regarding its prognostic value, primary tumor surgery may improve survival for selected patients. Patients and Methods: Patients with de novo MBC were identified using the SEER database and were then divided randomly into training and validation sets. A Fine-Gray competing risks model was developed to identify the variables associated with increased cancer-specific mortality in the training set. The M1 subdivision system was established based on the independent prognostic factors. Cumulative incidence curves were estimated and compared using Gray’s test. Results: Involvement of brain or liver and number of metastatic sites were identified as independent prognostic factors in multivariate analysis. The M1 category was subdivided into 3 subcategories: M1a, single site involvement except brain and liver; M1b, liver involvement only, or multiple site involvement except brain and liver; and M1c, brain involvement regardless of number of metastatic sites, or liver and other sites involvement except brain (M1b vs M1a: subdistribution hazard ratio [SHR], 1.48; 95% CI, 1.29–1.68; M1c vs M1a: SHR, 2.45; 95% CI, 2.18–2.75). Patients with the M1a subtype benefited most from primary tumor surgery in the adjusted competing risks model (M1a: SHR, 0.57; 95% CI, 0.48–0.67, M1b: SHR, 0.62; 95% CI, 0.47–0.83, and M1c: SHR, 0.59; 95% CI, 0.44–0.80), whereas benefits conferred by treatment with chemotherapy alone increased with the upstaging of metastatic disease (M1a: SHR, 0.72; 95% CI, 0.62–0.83, M1b: SHR, 0.54; 95% CI, 0.44–0.68, and M1c: SHR, 0.53; 95% CI, 0.45–0.61). Conclusions: Subdivision of M1 stage facilitates prognosis prediction and treatment planning for patients with de novo MBC. Treatment offered should be decided in a coordinated multidisciplinary setting. Primary tumor surgery may play an important role in the management of selected patients.

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Chunkit Fung, Paul C. Dinh Jr, Sophie D. Fossa and Lois B. Travis

Testicular cancer (TC) is the most common cancer among men aged 18 to 39 years. It is highly curable, with a 10-year relative survival approaching 95% due to effective cisplatin-based chemotherapy. Given the increasing incidence of TC and improved survival, TC survivors (TCS) now account for approximately 4% of all US male cancer survivors. They have also become a valuable cohort for adult-onset cancer survivorship research, given their prolonged survival. Commensurately, long-term treatment-related complications have emerged as important survivorship issues. These late effects include life-threatening conditions, such as second malignant neoplasms and cardiovascular disease. Moreover, TCS can also experience hearing loss, tinnitus, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, infertility, anxiety, depression, cognitive impairment, and chronic cancer-related fatigue. Characterization of the number and severity of long-term adverse health outcomes among TCS remains critical to develop risk-stratified, evidence-based follow-up guidelines and to inform the development of preventive measures and interventions. In addition, an improved understanding of the long-term effects of TC treatment on mortality due to noncancer causes and second malignant neoplasms remains paramount. Future research should focus on the continued development of large, well-characterized clinical cohorts of TCS for lifelong follow-up. These systematic, comprehensive approaches can provide the needed infrastructure for further investigation of long-term latency patterns of various medical and psychosocial morbidities and for more in-depth studies investigating associated etiopathogenetic pathways. Studies examining premature physiologic aging may also serve as new frontiers in TC survivorship research.

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Timothy Gilligan, Daniel W. Lin, Rahul Aggarwal, David Chism, Nicholas Cost, Ithaar H. Derweesh, Hamid Emamekhoo, Darren R. Feldman, Daniel M. Geynisman, Steven L. Hancock, Chad LaGrange, Ellis G. Levine, Thomas Longo, Will Lowrance, Bradley McGregor, Paul Monk, Joel Picus, Phillip Pierorazio, Soroush Rais-Bahrami, Philip Saylor, Kanishka Sircar, David C. Smith, Katherine Tzou, Daniel Vaena, David Vaughn, Kosj Yamoah, Jonathan Yamzon, Alyse Johnson-Chilla, Jennifer Keller and Lenora A. Pluchino

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.