For decades physicians have attempted to accurately predict post-treatment outcomes before performing prostate cancer interventions. Use of basic clinical factors, such as clinical T-stage, biopsy Gleason sum, and pretreatment prostate specific antigen, has allowed some level of prediction of pathologic and clinical outcomes. However, these basic tables and risk stratification schema provide a broad range of potential outcomes. The rapid growth of retrospective research in prostate cancer has yielded an abundance of additional potential prognostic factors that may influence outcomes of interest; however, incorporating and understanding the significance of these ever-expanding factors is difficult for even the most experienced physicians. Nomograms incorporate these factors (including treatment-specific) and assign them relative weights to provide a probability of the outcome of interest on a graphical scale. They distill large numbers of data into a manageable format and provide the probability of outcomes on a continuous scale rather than in categoric groups. However, because they require a computation to generate a probability, they are not amenable to memorization, which decreases ease of use. Furthermore, these numbers still have associated confidence intervals and the models are largely derived from retrospective data, which have inherent drawbacks. Clinicians and patients should still exercise due diligence when interpreting the results of these nomograms, and these prediction tools should not serve as a stand-alone substitute for clinical decision-making.
Andrew K. Lee and Christopher L. Amling
Yan Hiu Athena Lee, Jiandong Zhou, Jeremy Man Ho Hui, Xuejin Liu, Teddy Tai Loy Lee, Kyle Hui, Jeffrey Shi Kai Chan, Abraham Ka Chung Wai, Wing Tak Wong, Tong Liu, Kenrick Ng, Sharen Lee, Edward Christopher Dee, Qingpeng Zhang, and Gary Tse
Background: The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM). Methods: This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation therapy were performed. Results: The final study cohort consisted of 25,695 metformin users (mean [SD] age, 65.2 [11.8] years) and 25,695 matched sulfonylurea users (mean [SD] age, 65.3 [11.8] years) with a median follow-up duration of 119.6 months (interquartile range, 91.7–139.6 months) after 1:1 propensity score matching of 66,411 patients. Metformin users had lower risks of new-onset prostate cancer (hazard ratio, 0.80; 95% CI, 0.69–0.93; P=.0031) and all-cause mortality (hazard ratio, 0.89; 95% CI, 0.86–0.92; P<.0001) than sulfonylurea users. Metformin use was more protective against prostate cancer but less protective against all-cause mortality in patients aged <65 years (P for trend <.0001 for both) compared with patients aged ≥65 years. Metformin users had lower risk of all-cause mortality than sulfonylurea users, regardless of the use of androgen deprivation therapy (P for trend <.0001) among patients who developed prostate cancer. Conclusions: Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.
Yan Hiu Athena Lee, Jiandong Zhou, Jeremy Man Ho Hui, Xuejin Liu, Teddy Tai Loy Lee, Kyle Hui, Abraham Ka Chung Wai, Wing Tak Wong, Tong Liu, Kenrich Ng, Sharen Lee, Edward Christopher Dee, Jeffrey Shi Kai Chan, Qingpeng Zhang, and Gary Tse
Lydia T. Madsen, Deborah A. Kuban, Seungtaek Choi, John W. Davis, Jeri Kim, Andrew K. Lee, Delora Domain, Larry Levy, Louis L. Pisters, Curtis A. Pettaway, John F. Ward, Christopher Logothetis, and Karen E. Hoffman
Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative.
Justin Lee, Jennifer Axilbund, W. Brian Dalton, Daniel Laheru, Stanley Watkins, David Chu, Karen Cravero, Berry Button, Kelly Kyker-Snowman, Ian Waters, Christopher D. Gocke, Josh Lauring, and Ben Ho Park
Next-generation sequencing (NGS) is increasingly being used in cancer care to identify both somatic tumor driver mutations that can be targeted for therapy, and heritable mutations in the germline associated with increased cancer risk. This report presents a case of a JAK2 V617F mutation falsely identified as a duodenal cancer mutation via NGS. The patient was found to have a history of polycythemia vera, a disorder with a high incidence of JAK2 somatic mutations. Buccal cell DNA showed heterozygosity for the mutation, suggesting that it was potentially germline. However, subsequent resequencing of tumor, adjacent normal tissue, and fingernail DNA confirmed the mutation was somatic, and its presence in tumor and buccal cells resulted from contaminating blood cells. This report highlights important nuances of NGS that can lead to misinterpretation of results with potential clinical implications.
Annette M. Lim, Graham R. Taylor, Andrew Fellowes, Laird Cameron, Belinda Lee, Rodney J. Hicks, Grant A. McArthur, Christopher Angel, Benjamin Solomon, and Danny Rischin
The efficacy of targeted monotherapy for BRAF V600E-positive anaplastic thyroid carcinomas (ATC) is not established. We report 2 cases of BRAF V600E-positive ATC treated with a BRAF inhibitor. A 49-year-old woman with a T4bN1bM0 ATC manifested symptomatic metastatic disease 8 weeks after radical chemoradiotherapy. Within 1 month of BRAF inhibitor monotherapy, a complete symptomatic response was observed, with FDG-PET scan confirming metabolic and radiologic response. Treatment was terminated after 3 months because of disease progression. The patient died 11 months after primary diagnosis. A 67-year-old man received first-line BRAF inhibitor for a T4aN1bM0 ATC. Within 10 days of treatment his pain had stabilized and his tumor had clinically halved in size. Stable disease was achieved for 11 weeks but the patient died 11 months after diagnosis because of disease progression. BRAF inhibitor monotherapy in ATC may obtain clinical benefit of short duration. Upfront combination therapy should be investigated in this patient subgroup.
Luxi Chen, John Davelaar, Srinivas Gaddam, Kambiz Kosari, Nicholas Nissen, George Chaux, Christopher Lee, Eric Vail, Andrew Hendifar, Jun Gong, Karen Reckamp, and Arsen Osipov
Pancreatic metastasis of primary lung adenocarcinoma is a rare occurrence, accounting for <0.3% of all pancreatic malignancies. Given that the prognosis and treatment options for primary pancreatic cancer differ greatly from pancreatic metastases from a primary site, an accurate diagnosis is critical. This report presents a unique case of a 65-year-old man who was admitted with significant unintentional weight loss, fatigue, abdominal pain, and jaundice, and found to have a pancreatic mass initially thought to be primary pancreatic adenocarcinoma and subsequently diagnosed as an EGFR-mutated lung adenocarcinoma with metastases to the pancreas via early application of next-generation sequencing (NGS). The use of NGS early in the patient’s clinical course not only changed the treatment strategy but also drastically altered the prognosis. Although metastatic pancreatic adenocarcinoma has a poor prognosis and survival rate, treatment of EGFR-mutated non–small cell lung cancer with EGFR tyrosine kinase inhibitors is associated with high response rates. Importantly, our case demonstrates that timely application of NGS very early in the disease course is paramount to the diagnosis, management, and prognosis of solid malignancies.
Razelle Kurzrock, A. Dimitrios Colevas, Anthony Olszanski, Wallace Akerley, Carlos L. Arteaga, William E. Carson III, Jeffrey W. Clark, John F. DiPersio, David S. Ettinger, Robert J. Morgan Jr, Lee S. Schwartzberg, Alan P. Venook, Christopher D. Gocke, Jonathan Tait, and F. Marc Stewart
Background: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. Methods: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. Results: A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, “molecular profiling/diagnostics” was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)–certified laboratory. Conclusions: Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care.
Shoko Mori, Cristian Navarrete-Dechent, Tatyana A. Petukhova, Erica H. Lee, Anthony M. Rossi, Michael A. Postow, Lara A. Dunn, Benjamin R. Roman, Vivian T. Yin, Daniel G. Coit, Travis J. Hollmann, Klaus J. Busam, Kishwer S. Nehal, and Christopher A. Barker
Background: Tumor board conferences (TBCs) are used by oncologic specialists to review patient cases, exchange knowledge, and discuss options for cancer management. These multidisciplinary meetings are often a cornerstone of treatment at leading cancer centers and are required for accreditation by certain groups, such as the American College of Surgeons' Commission on Cancer. Little is known regarding skin cancer TBCs. The objective of this study was to characterize the structure, function, and impact of existing skin cancer TBCs in the United States. Methods: A cross-sectional online survey was administered to physician leaders of skin cancer TBCs at NCI-designated Comprehensive and Clinical Cancer Centers. Results: Of the 59 centers successfully contacted, 14 (24%) reported not having a conference where skin cancer cases were discussed, and 45 (76%) identified 53 physician leaders. A total of 38 physicians (72%) completed the survey. Half of the meeting leaders were medical and/or surgical oncologists, and dermatologists led one-third of meetings. TBCs had a moderate to significant impact on patient care according to 97% of respondents. All respondents indicated that the meetings enhanced communication among physicians and provided an opportunity for involved specialists and professionals to discuss cases. The most frequently cited barrier to organizing TBCs was determining a common available date and time for attendees (62%). The most common suggestion for improvement was to increase attendance, specialists, and/or motivation. Conclusions: Results showed overall consistency in meeting structure but variability in function, which may be a reflection of institutional resources and investment in the conference. Future directions include defining metrics to evaluate changes in diagnosis or management plan after tumor board discussion, attendance, clinical trial enrollment, and cost analysis. Results of this survey may aid other institutions striving to develop and refine skin cancer TBCs.