Citations

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

AbstractBackgroundContemporary guidelines for managing PTC advise an approach wherein primary tumor and regional metastases (RM) are completely resected at first surgery and radioiodine remnant ablation (RRA) is restricted to high‐risk patients, policies our group has long endorsed. To assess our therapeutic efficacy, we studied 190 children and 4242 adults consecutively treated during 1936–2015. Subjects and methodsMean follow‐up durations for children and adults were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed in 86% of children and 88% of adults, followed by RRA in 30% of children and 29% of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor recurrence (TR) and cause‐specific mortality (CSM) details were taken from a computerized database.ResultsChildren, when compared to adults, had larger primary tumors which more often were grossly invasive and incompletely resected. At presentation, children, as compared to adults, had more RM and distant metastases (DM). Thirty‐year TR rates were no different in children than adults at any site. Thirty‐year CSM rates were lower in children than adults (1.1 vs. 4.9%; p = 0.01). Comparing 1936–1975 (THEN) with 1976–2015 (NOW), 30‐year CSM rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08). However, MACIS <6 children and adults in 1976–2015 had significantly higher recurrence at local and regional, but not at distant, sites. MACIS 6+ adults, NOW, compared to THEN, had lower 30‐year CSM rates (30 vs. 47%; p < 0.001), unassociated with decreased TR at any site.ConclusionsChildren, despite presenting with more extensive PTC when compared to adults, have postoperative recurrences at similar frequency, typically coexist with DM and die of PTC less often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30‐year CSM rate of 30%.

Background Thyroid cancer ranges from well-differentiated lesions with an excellent prognosis to anaplastic carcinoma, which is almost uniformly fatal. Thus, methods to assess the behavior of thyroid malignancies are necessary to arrive at appropriate treatment decisions. Methods We discuss the factors that affect the prognosis of patients with well-differentiated thyroid malignancies, including papillary, follicular, Hürthle cell, and medullary thyroid carcinomas. We also review the presentation, therapy, and outcome of patients seen at our center over a span of 50 years. These data have identified those prognostic factors that are predictive of survival and recurrence in differentiated thyroid cancer. Results Several classifications with different variables have been developed to define risk-group categories. Three widely used systems, in addition to the TNM staging system, include AGES, AMES, and MACIS. Conclusions A better understanding of independently important prognostic variables will result in improved patient care and treatment.

Key Points SCHOLAR-1 is the first patient-level analysis of outcomes of refractory DLBCL from 2 large randomized trials and 2 academic databases. SCHOLAR-1 demonstrated poor outcomes in patients with refractory DLBCL, supporting a need for more effective therapies for these patients.