Recent Publications by CFE Educators

Importance

Controversy exists around the American Joint Committee on Cancer (AJCC) TNM staging system for medullary thyroid cancer (MTC). Because of the rarity of the disease and limited available data, the staging system for MTC has been largely extrapolated from staging for differentiated thyroid cancer.

Objectives

To evaluate how well the current (seventh and eighth editions) AJCC TNM staging system correlates with survival for patients with MTC and to suggest a possible revision.

Design, Setting, and Participants

This population-based retrospective cohort analysis used the National Cancer Database to select patients aged 18 years or older diagnosed with MTC in the United States between 1998 and 2012. Patient demographic and tumor characteristics were assessed, and pathologic tumor stages were provided as T, N, and M categories. Recursive partitioning with bootstrapping was used to divide patients by TNM stages into groups with similar survival. The newly identified groupings were validated in a Surveillance, Epidemiology, and End Results (SEER) cohort. Data analysis was conducted between July 17, 2016, and November 11, 2016.

Main Outcomes and Measures

Overall survival and disease-specific survival.

Results

Of the 3315 patients with MTC included in the analysis, 1941 (58.6%) were women. The median (interquartile range) age was 54 (42-65) years, and 2839 (85.6%) self-reported their race/ethnicity as white. The current AJCC TNM staging system classified 941 of these patients (28.4%) as stage I, 907 (27.4%) as stage II, 424 (12.9%) as stage III, and 1043 (31.5%) as stage IV. Recursive partitioning analysis yielded 4 TNM groups: stage I (T1N0-1aM0, T2N0M0), stage II (T1N1bM0, T2N1a-bM0, and T3N0M0), stage III (T3N1a-bM0, T4N0-1bM0), and stage IV (T1-4N0-1bM1). Based on these proposed TNM groupings, 1797 of the 3315 patients (54.2%) were classified as stage I, 684 (20.6%) as stage II, 669 (20.2%) as stage III, and 165 (5.0%) as stage IV. Under the proposed TNM groupings, survival differences across TNM groups were more distinct than under the current AJCC TNM staging system. With stage I as the reference, the hazard ratios of the proposed TNM groupings and the current AJCC TNM staging system were 2.19 (95% CI, 1.37-3.12) vs 1.45 (95% CI, 1.09-1.92) for stage II, 4.20 (95% CI, 2.75-5.75) vs 2.17 (95% CI, 1.59-2.89) for stage III, and 10.97 (95% CI, 5.52-18.57) vs 5.33 (95% CI, 4.13-6.86) for stage IV. In a SEER cohort, the proposed TNM groupings were better at discriminating survival than was the current AJCC TNM staging system.

Conclusions and Relevance

The current AJCC TNM staging system for MTC appears to be less than optimal in distinguishing risk of mortality among stage groups, upstaging a significant number of patients to stage IV. The current AJCC TNM staging system could be improved with the new TNM groupings proposed here for more accurate risk stratification and potential treatment selection.

BACKGROUND

The use of non-vitamin K oral anticoagulants (NOACs) has increased steadily following marketing approval; however, their relative safety in nonvalvular atrial fibrillation (NVAF) patients in real-world clinical practice remains unclear.

OBJECTIVE

To compare the risk of major bleeding during anticoagulation therapy between warfarin and NOACs.

METHODS

This retrospective cohort study analyzed administrative claims data on new NVAF users of warfarin, dabigatran, apixaban, or rivaroxaban in routine clinical care from November 2010 to February 2015 in a commercially insured population in the United States. The primary outcome was time to first major bleeding event requiring hospitalization. Patients were followed until discontinuation or switch of anticoagulants, health plan disenrollment, death, or end of study. All patient characteristics were balanced after propensity score inverse probability of treatment (IPT) weighting. Event rates by type of anticoagulant exposure were compared using IPT-weighted Cox proportional hazards models.

RESULTS

The study cohort comprised 44,057 patients who used warfarin (n = 23,431), dabigatran (n = 8,539), apixaban (n = 3,689), and rivaroxaban (n = 8,398). Overall mean (SD) age was 70 (12) years, and 41% of the patients were women. A total of 2,337 major bleeding events occurred during 36,636.2 person-years of follow-up. The unadjusted rate of major bleeding with warfarin was 6.0 per 100 person-years versus 2.8 with dabigatran, 3.3 with apixban, and 5.0 with rivaroxaban. Relative to warfarin, major bleeding risk was lower with dabigatran (HR = 0.67, 95% CI = 0.60-0.76) and apixaban (HR = 0.52, 95% CI = 0.41-0.67). Compared with rivaroxaban, major bleeding risk was also lower with dabigatran (HR = 0.67, 95% CI = 0.58-0.78) and apixaban (HR = 0.52, 95% CI = 0.40-0.68). Major bleeding risk was similar for rivaroxaban and warfarin. Relative to apixaban, dabigatran was associated with a significantly higher risk of major gastrointestinal bleeding (HR = 1.43, 95% CI = 1.09-1.88).

CONCLUSIONS

Study results were consistent with safety findings from pivotal clinical trials comparing NOACs with warfarin and added the perspective of a large real-world observational study that compared bleeding risks associated with NOACs during anticoagulation therapy. Apixaban and dabigatran were associated with lower major bleeding risk compared with warfarin or rivaroxaban; however, apixaban had a lower risk of major gastrointestinal bleeding than dabigatran. These findings can help inform the choice of an optimal agent, which must balance effectiveness and bleeding risk in complex patients.

DISCLOSURES

This study was funded by Anthem. Adeboyeje, Sylwestrzak, and Barron are employees of HealthCore, a wholly owned and independently operated subsidiary of Anthem. White, Rosenberg, Abarca, and Crawford are employees of Anthem. Study concept and design were primarily contributed by Adeboyeje and Sylwestrzak, along with the other authors. Adeboyeje took the lead in data collection, along with Sylwestrzak and Barron. Data interpretation was performed primarily by Rosenberg, Crawford, and Redberg, with assistance from the other authors. The manuscript was written by all the authors and revised primarily by White, Abarca, and Redberg, along with the other authors.

OBJECTIVES

Statins are recommended to reduce serum cholesterol in patients at risk for atherosclerotic cardiovascular disease. Despite the prevalence of statin use, little is known about the indications for new prescriptions. We assessed the concordance of new statin prescriptions in the Veterans Health Administration (VHA) compared with the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) guidelines (the guidelines in force in 2012) and the American College of Cardiology (ACC)-American Heart Association (AHA) 2013 guidelines.

STUDY DESIGN

Cross-sectional study.

METHODS

We identified every patient who received a new prescription (no statin use in the prior year) in the VHA in 2012. Patients were excluded if they had incomplete data, triglycerides greater than 400 mg/dL, or fewer than 2 primary care visits to ensure adequate baseline data to calculate Framingham and ACC-AHA 2013 risk scores.

RESULTS

We identified 250,243 new statin prescriptions in 2012 in the VHA, with 121,081 meeting inclusion criteria. Among new prescriptions, 68% were prescribed for primary prevention and 32% were prescribed for secondary prevention. Among patients receiving new statins for primary prevention, 48% did not have an indication supported by the ATP III guideline and 20% did not have an indication supported by the ACC/AHA guideline. Overall, approximately 19% of patients may have received a statin for an indication not supported by either guideline.

CONCLUSIONS

Veterans are commonly prescribed statins for indications not supported by professional society guidelines. The finding of common use of statins outside established guidelines represents an opportunity to improve the quality and value of the healthcare delivery.

Neuromyelitis optica (NMO), formerly known as Devic disease, is an autoimmune astrocytopathic disease characterized by transverse myelitis and optic neuritis. Most patients demonstrate a relapsing course with incomplete recovery between attacks, resulting in progressive disability. The pathogenesis involves production of aquaporin-4 antibodies (AQP4-IgG) by plasmablasts in peripheral circulation, disruption of the blood-brain barrier, complement-mediated astrocyte injury, and secondary demyelination. The diagnosis relies on characteristic clinical manifestations in the presence of serum AQP4-IgG positivity or specific neuroimaging findings, and exclusion of alternative etiologies. Current treatment involves aggressive immunosuppression with pulse-dose steroids during acute attacks and long-term immunosuppression for attack prevention.