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Purpose Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and Methods Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. Results The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. Conclusion In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.

A majority of cancer diagnoses and deaths occur in patients age ≥ 65 years. With the aging of the US population, the number of older adults with cancer will grow. Although the coming wave of older patients with cancer was anticipated in the early 1980s, when the need for more research on the cancer-aging interface was recognized, many knowledge gaps remain when it comes to treating older and/or frailer patients with cancer. Relatively little is known about the best way to balance the risks and benefits of existing cancer therapies in older patients; however, these patients continue to be underrepresented in clinical trials. Furthermore, the available clinical trials often do not include end points pertinent to the older adult population, such as preservation of function, cognition, and independence. As part of its ongoing effort to advance research in the field of geriatric oncology, the Cancer and Aging Research Group held a conference in November 2012 in collaboration with the National Cancer Institute, the National Institute on Aging, and the Alliance for Clinical Trials in Oncology. The goal was to develop recommendations and establish research guidelines for the design and implementation of therapeutic clinical trials for older and/or frail adults. The conference sought to identify knowledge gaps in cancer clinical trials for older adults and propose clinical trial designs to fill these gaps. The ultimate goal of this conference series is to develop research that will lead to evidence-based care for older and/or frail adults with cancer.

RVOT Atypical VariantsBackgroundRight ventricular outflow tract (RVOT) arrhythmias are a common form of ventricular tachycardia (VT) in patients with structurally normal heart. The underlying mechanism is due to triggered activity. Mapping and ablation is relatively straightforward targeting the earliest point of activation. Previously reported causes of difficult ablation in the RVOT region include under recognized right ventricular cardiomyopathy/sarcoidosis, presence of endocavitary structures, close proximity to the coronary vasculature, and origin from non‐RVOT structures.Methods and ResultsWe identified all patients undergoing PVCs/sustained RVOT VT ablation from January 2013 to December 2013. This included 33 patients. Of these, we identified procedures that were considered difficult despite a single morphology arrhythmia being targeted and no underlying cardiomyopathy present. Difficulty was specifically considered when ablation at the earliest site of activation was not successful and eventual successful ablation was at a distance of greater than 15 mm from the early activation site. We identified 3 patients (n = 3, 100% male) with evidence of reentrant arrhythmia based on slow conduction zones necessary for the tachycardia/arrhythmia, mid diastolic signals during VT or preceding bigeminal PVCs, pace mapping from the site abnormal signals reproducing the arrhythmia morphology but with prominent conduction delay, the entire cycle length of the tachycardia or coupling interval for the PVCs being mapping, or based on reset characteristics.ConclusionIn patients with atypical forms of RVOT VT, careful mapping and ablation of the myocardial sleeves near the pulmonic valve can eliminate the arrhythmia.

Epicardial Access and ObesityIntroductionPercutaneous epicardial access for ablative therapies is an increasingly common technique utilized for refractory ventricular arrhythmias. There are, however few known data on obesity and complication rates associated with this procedure.Methods and ResultsWe retrospectively reviewed the charts of subjects undergoing epicardial access at Mayo Clinic between January 2004 and June 2013. Baseline clinical and echocardiographic data were collected for each subject, who was then classified into body mass index (BMI) categories as underweight, normal weight, overweight, and obese based on a BMI of <18.5, 18.5–24.99, 25–29.99, and ≥30, respectively. Events and complications were recorded, and procedural and clinical success rates were determined.There was no statistically significant difference in access approach, procedural or clinical outcomes, or complications among the BMI categories. Note that 95.1%, 91.7%, and 93.1% derived procedural success among the normal weight, overweight, and obese categories, respectively (P value = 0.81). Similarly, there was no difference in clinical outcomes with success rates of 68.3%, 66.7%, and 75.9% between the respective groups (P value = 0.54). At 5 years, there was a trend toward increased mortality among obese individuals (28.8%) compared to normal weight (8.8%) and overweight (9.8%) patients (P value = 0.139).ConclusionPercutaneous epicardial access, mapping, and ablation can be performed in obese individuals with similar outcomes to those of lower weight category. Obesity should not preclude the use of percutaneous epicardial access when clinically indicated.

ScopeWe reevaluated previously reported associations between variants in pathways of one‐carbon (1‐C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.Methods and resultsOdds ratios (OR) for 446 genetic variants were estimated among 13 410 OC cases and 22 635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10−5) and rs828054 (OR = 1.06; p = 1 × 10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1‐C transfer, previously reported with OC, suggested lower risk at higher folate (pinteraction = 0.03–0.006).ConclusionVariation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP‐by‐folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.