Laparoscopic surgery for adrenocortical carcinoma: Estimating the risk of margin-positive resection.

BACKGROUND: Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection. METHODS: Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multivariable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set. RESULTS: Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification. CONCLUSIONS: An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.

Insurance Coverage of Prophylactic Mastectomies: A National Review of the United States.

BACKGROUND: Breast cancer is associated with a multitude of risk factors, such as genetic predisposition and mutations, family history, personal medical history, or previous radiotherapy. A prophylactic mastectomy (PM) may be considered a suitable risk-reducing procedure in some cases. However, there are significant discrepancies between national society recommendations and insurance company requirements for PM. MATERIALS AND METHODS: The authors conducted a cross-sectional analysis of insurance policies for a PM. One-hundred companies were selected based on the greatest state enrolment and market share. Their policies were identified through a Web-based search and telephone interviews, and their medical necessity criteria were extracted. RESULTS: Preauthorized coverage of PMs was provided by 39% of insurance policies (n = 39) and 5 indications were identified. There was consensus amongst these policies to cover a PM for BRCA1/2 mutations (n = 39, 100%), but was more variable for other genetic mutations (15%-90%). Coverage of PM for the remaining indications varied among insurers: previous radiotherapy (92%), pathological changes in the breast (3%-92%), personal history of cancer (64%) and family history risk factors (39%-51%). CONCLUSION: There is a marked level of variability in both the indications and medical necessity criteria for PM insurance policies. The decision to undergo a PM must be carefully considered with a patient's care team and should not be affected by insurance coverage status.

Treat Now or Treat Later: Comparative Effectiveness of Adjuvant Therapy in Resected Stage IIIA Melanoma.

BACKGROUND: Adjuvant therapy for most sentinel-node-positive (stage IIIA) melanoma may have limited clinical benefit for older patients given the competing risk of non-cancer death. The objective of this study is to model the clinical effect and cost of adjuvant therapy in stage IIIA melanoma across age groups. STUDY DESIGN: A Markov decision analysis model simulated the overall survival of patients with resected stage IIIA melanoma treated with adjuvant therapy vs observation. In the adjuvant approach, patients are modeled to receive adjuvant pembrolizumab (BRAF wild type) or dabrafenib/trametinib (BRAF mutant). In the observation approach, treatment is deferred until recurrence. Transition variables were derived from landmark randomized trials in adjuvant and salvage therapy. The model was analyzed for age groups spanning 40 to 89 years. The primary outcome was the number needed to treat (NNT) to prevent one melanoma-related death at 10 years. Cost per mortality avoided was estimated using Medicare reimbursement rates. RESULTS: Projections for NNT among BRAF wild type patients increased by age from 14.71 (age 40 to 44) to 142.86 (age 85 to 89), with patients in cohorts over the age of 75 having an NNT over 25. The cost per mortality avoided ranged from $2.75 million (M) (age 40 to 44) to $27.57M (age 85 to 89). Corresponding values for BRAF mutant patients were as follows: NNT 18.18 to 333.33; cost per mortality avoided ranged from $2.75M to $54.70M. CONCLUSION: Universal adjuvant therapy for stage IIIA melanoma is costly and provides limited clinical benefit in patients older than 75 years.

Contralateral prophylactic mastectomy in the setting of breast cancer diagnosis and their insurance coverage in the United States.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) is more common in the United States than the rest of the world. However, the benefit of this procedure is still under question in many breast cancer scenarios. CPM utilization in the United States is in part dependent on a patient's health insurance coverage of breast oncology surgery and any desired reconstruction. However, there are great discrepancies in the coverage provided by insurers. METHODS: The authors conducted a cross-sectional analysis of insurance policies for a CPM in the setting of diagnosed breast cancer. One hundred companies were selected based on their state enrollment and market share. Their policies were identified through a Web-based search and telephone interviews, and their medical necessity criteria were extracted. RESULTS: Of the 100 companies assessed, 36 (36%) had a policy for CPM. Within those, significantly more provided coverage than denied the procedure (72% vs. 25%, p < 0.0001), with the remainder providing case-by-case coverage. Eleven criteria were identified from preauthorized policies, the most common prerequisite was breast cancer diagnosis under 45 years old (n = 9, 35%). Most policies did not differentiate between gender in their policies (n = 25, 69%), but of those that did, 100% (n = 11) provided coverage for men and women, with 82% (n = 9) requiring further criteria from the female patients. CONCLUSION: The coverage of CPM in the United States varies from complete denial to unrestricted approval. This may be due to conflicting reports in the literature as to the utility of the procedure. The decision to undergo this procedure must be taken with thoughtful consideration and the support of a multidisciplinary approach.

Optimizing dendritic cell-based approaches for cancer immunotherapy.

Dendritic cells (DC) are professional antigen-presenting cells uniquely suited for cancer immunotherapy. They induce primary immune responses, potentiate the effector functions of previously primed T-lymphocytes, and orchestrate communication between innate and adaptive immunity. The remarkable diversity of cytokine activation regimens, DC maturation states, and antigen-loading strategies employed in current DC-based vaccine design reflect an evolving, but incomplete, understanding of optimal DC immunobiology. In the clinical realm, existing DC-based cancer immunotherapy efforts have yielded encouraging but inconsistent results. Despite recent U.S. Federal and Drug Administration (FDA) approval of DC-based sipuleucel-T for metastatic castration-resistant prostate cancer, clinically effective DC immunotherapy as monotherapy for a majority of tumors remains a distant goal. Recent work has identified strategies that may allow for more potent "next-generation" DC vaccines. Additionally, multimodality approaches incorporating DC-based immunotherapy may improve clinical outcomes.