Historically, genetic testing (and billing) for hereditary cancer risk was essentially performed gene by gene, with clinicians ordering testing only for the genes most likely to explain a patient’s or family’s cancer presentation, with laboratories typically charging $1,000 to $1,500 for each gene that was sequenced. Given the expense, only patients at high risk of having a hereditary syndrome were offered testing. With the introduction of next-generation sequencing technologies, however, laboratories are able to test for multiple genes at the same time with greater efficiency, significantly decreased costs, and relatively little increased expense when adding additional genes. This has drastically altered clinical practice so that clinicians now typically order testing for a panel of multiple genes for most patients. Although this approach has streamlined the diagnostic odyssey, it has introduced several problems, as well, including difficulties in choosing the appropriate panel test for a given patient, assessing the significance of identified genetic variants (including variants of uncertain significance [VUS]), and understanding the disease risks and management associated with pathogenic variants in a given gene. Many laboratories offer testing for genes that have limited data supporting their associated cancer risks, which then leads to an inability to set management guidelines based on that gene. In addition, testing larger numbers of genes increases the likelihood of finding one or more VUS, which introduce their own management issues. Thus, although panel testing has certainly moved clinical practice forward in many ways, it has also raised its own set of problems that increase the complexity of genetic counseling and highlight the need for education of community practitioners on the complexities and nuances of this testing. Whenever possible, testing should be performed by, or in consultation with, cancer genetics professionals.
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James Sun, Brittany J. Mathias, Christine Laronga, Weihong Sun, Jun-Min Zhou, William J. Fulp, John V. Kiluk and M. Catherine Lee
Background: Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. Materials and Methods: A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). Results: Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46–62 years). The median number of SLNs sampled was 3 (IQR, 2–4), and the median number of positive SLNs was 1 (IQR, 1–2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29–83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). Conclusions: CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.
Donglai Chen, Xiaofan Wang, Qifeng Ding and Yongbing Chen
Featured Updates to the NCCN Guidelines
Daniel A. Pollyea, Dale Bixby, Alexander Perl, Vijaya Raj Bhatt, Jessica K. Altman, Frederick R. Appelbaum, Marcos de Lima, Amir T. Fathi, James M. Foran, Ivana Gojo, Aric C. Hall, Meagan Jacoby, Jeffrey Lancet, Gabriel Mannis, Guido Marcucci, Michael G. Martin, Alice Mims, Jadee Neff, Reza Nejati, Rebecca Olin, Mary-Elizabeth Percival, Thomas Prebet, Amanda Przespolewski, Dinesh Rao, Farhad Ravandi-Kashani, Paul J. Shami, Richard M. Stone, Stephen A. Strickland, Kendra Sweet, Pankit Vachhani, Matthew Wieduwilt, Kristina M. Gregory, Ndiya Ogba and Martin S. Tallman
The NCCN Guidelines for Acute Myeloid Leukemia (AML) provide recommendations for the diagnosis and treatment of adults with AML based on clinical trials that have led to significant improvements in treatment, or have yielded new information regarding factors with prognostic importance, and are intended to aid physicians with clinical decision-making. These NCCN Guidelines Insights focus on recent select updates to the NCCN Guidelines, including familial genetic alterations in AML, postinduction or postremission treatment strategies in low-risk acute promyelocytic leukemia or favorable-risk AML, principles surrounding the use of venetoclax-based therapies, and considerations for patients who prefer not to receive blood transfusions during treatment.
Mandy R. Sakamoto, Megan Eguchi, Christine M. Azelby, Jennifer R. Diamond, Christine M. Fisher, Virginia F. Borges, Cathy J. Bradley and Peter Kabos
Background: Opioid and benzodiazepine use and abuse is a national healthcare crisis to which patients with cancer are particularly vulnerable. Long-term use and risk factors for opioid and benzodiazepine use in patients with breast cancer is poorly characterized. Methods: We conducted a retrospective population-based study of patients with breast cancer diagnosed between 2008 and 2015 undergoing curative-intent treatment identified through the SEER-Medicare linked database. Primary outcomes were new persistent opioid use and new persistent benzodiazepine use. Factors associated with new opioid and benzodiazepine use were investigated by univariate and multivariable logistic regression. Results: Among opioid-naïve patients, new opioid use was observed in 22,418 (67.4%). Of this group, 611 (2.7%) developed persistent opioid use at 3 months and 157 (0.7%) at 6 months after treatment. Risk factors for persistent use at 3 and 6 months included stage III disease (odds ratio [OR], 2.16; 95% CI, 1.49–3.12, and OR, 3.48; 95% CI, 1.58–7.67), surgery plus chemotherapy (OR, 1.44; 95% CI, 1.10–1.88, and OR, 2.28; 95% CI, 1.40–3.71), surgery plus chemoradiation therapy (OR, 1.47; 95% CI, 1.10–1.96, and OR, 2.34; 95% CI, 1.38–3.96), and initial tramadol use (OR, 2.66; 95% CI, 2.05–3.46, and OR, 3.12; 95% CI, 1.93–5.04). Among benzodiazepine-naïve patients, new benzodiazepine use was observed in 955 (10.3%), and 111 (11.6%) developed new persistent use at 3 months. Tamoxifen use was statistically significantly associated with new persistent benzodiazepine use at 3 months. Conclusions: A large percentage of patients receiving curative-intent treatment of breast cancer were prescribed new opioids; however, only a small number developed new persistent opioid use. In contrast, a smaller proportion of patients received a new benzodiazepine prescription; however, new persistent use after completion of treatment was more likely and particularly related to concurrent treatment with tamoxifen.
Juan P. Cata and Daniel D. Kim
Background: The aim of this study was to assess the patterns and trends of colorectal, breast, and cervical cancer screening within a contemporary cohort of Canadian adults. Methods: Canadian Community Health Survey datasets (2007–2016) were accessed and 3 cohorts were defined: (1) a colorectal cancer (CRC) screening cohort, defined as men and women aged 50 to 74 years with complete information about CRC screening tests and their timing; (2) a breast cancer screening cohort, defined as women aged 40 to 74 years with complete information about mammography and its timing; and (3) a cervical cancer screening cohort, defined as women aged 25 to 69 years with complete information about the Papanicolaou (Pap) test and its timing. Multivariable logistic regression analysis was then performed to evaluate factors associated with not having timely screening tests at the time of survey completion. Results: A total of 99,820 participants were considered eligible for the CRC screening cohort, 59,724 for the breast cancer screening cohort, and 46,767 for the cervical cancer screening cohort. Among eligible participants, 43% did not have timely recommended screening tests for CRC, 35% did not have timely mammography (this number decreased to 26% when limiting the eligible group to ages 50–74 years), and 25% did not have a timely Pap test. Lower income was associated with not having a timely recommended screening tests for all 3 cohorts (odds ratios [95% CI]: 1.86 [1.76–1.97], 1.89 [1.76–2.04], and 1.96 [1.79–2.14], respectively). Likewise, persons self-identifying as a visible minority were less likely to have timely recommended screening tests in all 3 cohorts (odds ratios for White race vs visible minority [95% CI]: 0.87 [0.83–0.92], 0.85 [0.80–0.91], and 0.66 [0.61–0.70], respectively). Conclusions: More than one-third of eligible individuals are missing timely screening tests for CRC. Moreover, at least one-quarter of eligible women are missing their recommended breast and cervical cancer screening tests. More efforts from federal and provincial health authorities are needed to deal with socioeconomic disparities in access to cancer screening.
Medhavi Gupta, Christopher Sherrow, Maghan E. Krone, Edik M. Blais, Michael J. Pishvaian, Emanuel F. Petricoin III, Lynn M. Matrisian, Patricia DeArbeloa, Gary Gregory, Alyson Brown, Olivia Zalewski, Gillian Prinzing, Charles Roche, Kazunori Kanehira, Sarbajit Mukherjee, Renuka Iyer and Christos Fountzilas
Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic exocrine malignancy. Compared with the more common pancreatic ductal adenocarcinoma (PDAC), PACC is more common in younger White men, has earlier stages and a lower mean age (56 vs 70 years) at the time of presentation, and has a better prognosis. In addition to differences in demographic, histologic, and clinical characteristics, PACC has a genomic profile distinct from PDAC, with only rare mutations in TP53, KRAS, and p16 that are commonly found in PDAC. This case report presents a man aged 81 years who presented with a pancreatic body mass with peripancreatic lymph node enlargement. Biopsy of the mass showed acinar cell carcinoma. The patient underwent upfront surgical resection, followed by one cycle of adjuvant gemcitabine, with stoppage of therapy due to poor tolerance. Lower-dose gemcitabine was reintroduced after disease progression 6 months later. Nab-paclitaxel was added to gemcitabine after 6 cycles because of a continued increase in the size of peripancreatic lymph nodes. Combination chemotherapy was stopped after 4 cycles because of further disease progression with new liver metastasis. Molecular testing showed the presence of an SEL1L-NTRK1 fusion. Targeted therapy was started with the oral neurotrophic tropomyosin receptor kinase (NTRK) inhibitor larotrectinib at a dosage of 100 mg twice daily. At the time of writing, the patient has been on therapy for 13 months with an exceptional radiographic response and has not experienced any grade 3 adverse effects. To our knowledge, this is the first clinical report of an NTRK gene fusion in a patient with PACC. This case study highlights the significance of tumor molecular profiling in patients with pancreatic tumors, especially rare histologies.