Background: Editorials accompanying the publication of trials in major oncology journals can have a substantial influence on clinical practice. We describe the prevalence of financial conflicts of interest (FCOIs) of authors writing such editorials and the extent to which FCOIs may shape the interpretation of clinical trials. Methods: We examined editorials published in 2018 alongside trial reports in the top 5 journals that publish cancer drug trials (New England Journal of Medicine, Lancet, Lancet Oncology, JAMA Oncology, and Journal of Clinical Oncology). An editorial was considered to have an FCOI if at least one of the editorialists had any disclosed FCOI. An FCOI with the same company whose drug was being discussed in the editorial was classified as a direct FCOI. Editorials were reviewed for their content and classified as being unduly favorable (defined as the presence of a positive spin without discussion of limitations) or not. Association of an FCOI and a direct FCOI with writing an unduly favorable editorial was assessed. Results: Of the 90 editorials assessed, 74% (n=67) were classified as having an FCOI with the pharmaceutical industry, and 39% (n=35) had an FCOI with the same company whose product was being discussed in the editorial (direct FCOI). Editorials were classified as being unduly favorable toward the study drug in 12% (8 of 67) and 13% (3 of 23) (P=1.0) of those with and without FCOIs, respectively; corresponding rates with and without direct FCOI were 23% (8 of 35) and 5% (3 of 55), respectively (P=.009). Conclusions: Editorials in top oncology journals were frequently authored by experts with FCOIs, including direct FCOIs. Authoring an unduly favorable editorial for a new cancer drug was significantly associated with the author having a direct FCOI with the same company. These findings support the call for journals to ensure that authors of editorials have no direct FCOIs.
Shubham Sharma, Christopher M. Booth, Elizabeth A. Eisenhauer, and Bishal Gyawali
Kelsey C. Stoltzfus, Biyi Shen, Leila Tchelebi, Daniel M. Trifiletti, Niraj J. Gusani, Vonn Walter, Ming Wang, and Nicholas G. Zaorsky
Eva Battaglini, David Goldstein, Peter Grimison, Susan McCullough, Phil Mendoza-Jones, and Susanna B. Park
Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major adverse effect of cancer treatment. However, its impact remains poorly understood. This study aimed to investigate the impact associated with CIPN on the lives of cancer survivors. Patients and Methods: A volunteer sample of 986 individuals who had received neurotoxic chemotherapy completed an anonymous, cross-sectional survey. Outcomes assessed included CIPN symptoms, pain, neuropathic pain, quality of life (QoL), physical activity, and comorbid health conditions via the Self-Administered Comorbidity Questionnaire. Results: Respondents had a mean age of 58 years (SD, 10.7), and 83.2% were female. Most were treated for breast (58.9%) or colorectal cancer (13.5%); had received docetaxel (32.7%), paclitaxel (31.6%), or oxaliplatin (12.5%); and had completed treatment 3.6 ± 3.5 years previously. We found that 76.5% of respondents reported current CIPN. Respondents reporting severe CIPN had poorer QoL, more comorbidities, and higher body mass index, and more often received multiple neurotoxic chemotherapies than those with mild CIPN. Respondents who completed the survey ≤1 year after completing chemotherapy did not differ in reported CIPN or pain compared with respondents who completed chemotherapy ≥6 years earlier. However, respondents who completed chemotherapy ≥6 years earlier reported better QoL. Multivariable linear regression analyses revealed predictors of CIPN severity as follows: F(7, 874) = 64.67; P<.001; R 2 = 0.34, including pain (β = −0.36; P<.001), burning pain (β = 0.25; P<.001), sex (male sex associated with greater CIPN: β = 0.14; P<.001), years since completing chemotherapy (shorter time associated with greater CIPN; β = −0.10; P<.001), age (β = 0.80; P=.006), number of comorbid conditions (β = 0.07; P=.02), and body mass index (β = 0.07; P=.02). Conclusions: Respondents with a high CIPN symptom burden experienced poorer general health and QoL. Improvements in CIPN may be more likely soon after treatment. However, improvements in QoL may occur over time in those with chronic symptoms. CIPN seems to have lasting impacts on cancer survivors, and understanding risk factors is important to enable the design of further preventive and therapeutic management strategies.
Ying L. Liu and Zsofia K. Stadler
Under the traditional paradigm of genetic testing in cancer, the role of germline testing was to assess for the inherited risk of cancer, whereas the role of tumor testing was to determine therapeutic selection. Parallel tumor-normal genetic testing uses simultaneous genetic testing of the tumor and normal tissue to identify mutations and allows their classification as either germline or somatic. The increasing adoption of parallel testing has revealed a greater number of germline findings in patients who otherwise would not have met clinical criteria for testing. This result has widespread implications for the screening and further testing of at-risk relatives and for gene discovery. It has also revealed the importance of germline testing in therapeutic actionability. Herein, we describe the pros and cons of tumor-only versus parallel tumor-normal testing and summarize the data on the prevalence of incidental actionable germline findings. Because germline testing in patients with cancer continues to expand, it is imperative that systems be in place for the proper interpretation, dissemination, and counseling for patients and at-risk relatives. We also review new therapeutic approvals with germline indications and highlight the increasing importance of germline testing in selecting therapies. Because recommendations for universal genetic testing are increasing in multiple cancer types and the number of approved therapies with germline indications is also increasing, a gradual transition toward parallel tumor-normal genetic testing in all patients with cancer is foreseeable.
Anisley Valenciaga, O. Hans Iwenofu, and Gabriel Tinoco
Pleomorphic liposarcoma of the uterus (PLU) is an extremely rare disease with poor prognosis. Limited treatment options exist for these patients, and disease recurrence usually occurs rapidly within months of initial diagnosis. Few case reports of metastatic PLU are available in the literature. We describe a 70-year-old woman who presented with a large uterus and ovarian mass on imaging and negative serum tumor markers and endometrial biopsy. Staging revealed localized disease. Surgical resection revealed PLU on pathology. Immunohistochemistry was negative for smooth muscle actin (SMA), S100, and MDM2, and positive for CD10 and cyclin-D1. She was treated with adjuvant therapy and experienced disease recurrence in the liver at 15 months from surgery. Genetic testing of the metastasis showed IQGAP-NTRK3 gene fusion. She was given entrectinib but continued to show progression in the liver. Right partial hepatectomy was performed, showing positivity for CD10, BCL-1, MDM2, and SMA on tumor staining. Treatment was switched to pazopanib with disease progression in the neck. She was treated with larotrectinib last, showing no disease progression and adequate tolerance of therapy after 18 months of this treatment. This is the first case in the literature of metastatic PLU with NRTK3 fusion treated with sequential first-generation NRTK inhibitors. More case reports are needed to identify commonalities and therapeutic options. Genetic testing in all PLU cases is needed for targeted therapy approaches.
Featured Updates to the NCCN Guidelines
Maria Dans, Jean S. Kutner, Rajiv Agarwal, Justin N. Baker, Jessica R. Bauman, Anna C. Beck, Toby C. Campbell, Elise C. Carey, Amy A. Case, Shalini Dalal, Danielle J. Doberman, Andrew S. Epstein, Leslie Fecher, Joshua Jones, Jennifer Kapo, Richard T. Lee, Elizabeth T. Loggers, Susan McCammon, William Mitchell, Adeboye B. Ogunseitan, Diane G. Portman, Kavitha Ramchandran, Linda Sutton, Jennifer Temel, Melissa L. Teply, Stephanie Y. Terauchi, Jane Thomas, Anne M. Walling, Finly Zachariah, Mary Anne Bergman, Ndiya Ogba, and Mallory Campbell
Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members’ clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel’s recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.
Manisha H. Shah, Whitney S. Goldner, Al B. Benson III, Emily Bergsland, Lawrence S. Blaszkowsky, Pamela Brock, Jennifer Chan, Satya Das, Paxton V. Dickson, Paul Fanta, Thomas Giordano, Thorvardur R. Halfdanarson, Daniel Halperin, Jin He, Anthony Heaney, Martin J. Heslin, Fouad Kandeel, Arash Kardan, Sajid A. Khan, Boris W. Kuvshinoff II, Christopher Lieu, Kimberly Miller, Venu G. Pillarisetty, Diane Reidy, Sarimar Agosto Salgado, Shagufta Shaheen, Heloisa P. Soares, Michael C. Soulen, Jonathan R. Strosberg, Craig R. Sussman, Nikolaos A. Trikalinos, Nataliya A. Uboha, Namrata Vijayvergia, Terence Wong, Beth Lynn, and Cindy Hochstetler
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.