Citations

Background. We sought to study the association between RPS case volume and outcomes. Although a relationship has been demonstrated between case volume and patient outcomes in some cancers, such a relationship has not been established for retroperitoneal sarcomas (RPSs). Study Design. The National Cancer Database (NCDB) was queried for patients undergoing treatment for primary RPS diagnosed between 2004 and 2013. Mean annual patient volume for RPS resection was calculated for all hospitals and divided into low volume (<5 cases/year), medium volume (5–10 cases/year), and high volume (>10 cases/year). Risk-adjusted regression analyses were performed to identify predictors of 30-day surgical mortality, R0 margin status, and overall survival (OS). Results. Our study population consisted of 5,407 patients with a median age of 61 years, of whom 47% were male and 3,803 (70%) underwent surgical resection. Absolute 30-day surgical mortality and R0 margin rate following surgery for low-, medium-, and high-volume institutions were 2.4%, 1.3%, and 0.5% (p=0.027) and 68%, 65%, and 82%, (p<0.001), respectively. Five-year overall survival rates for low, medium, and high-volume institutions were 56%, 57%, and 66%, respectively (p<0.001). Patients treated at low-volume institutions had a significantly higher risk of 30-day mortality (adjusted OR = 4.66, 95% CI 2.26–9.63) and long-term mortality (adjusted HR = 1.56, 95% CI 1.16–2.11) compared to high-volume institutions. Conclusion. We demonstrate the existence of a hospital sarcoma service line volume-oncologic outcome relationship for RPS at the national level and provide benchmark data for cancer care delivery systems and policy makers.

Introduction. Optimization of outcomes of extra-abdominal STS is not clearly understood. We sought to determine whether hospital surgical volume and adherence to NCCN guidelines, or both, are associated with outcomes in the treatment of extra-abdominal soft tissue sarcoma (STS).Methods. The National Cancer Database (NCDB) was queried for patients undergoing surgery for extra-abdominal STS diagnosed from 2003 to 2007. Mean annual hospital volume for STS surgery was divided into volume terciles (1T ≤3, 2T 4–10, and 3T ≥11 cases/year). Adherence to NCCN guidelines was determined. Primary outcome was overall survival.Results. Our study population consisted of 13,684 patients with a median age of 56 years. 3T hospitals were more likely to adhere to NCCN guidelines for stage III patients (63% versus 47%;p≤0.001) than 1T hospitals. On multivariable analysis, adherence to NCCN guidelines was associated with improved survival (HR = 0.79, CI 0.73–0.87;p<0.001), but hospital volume was not (3T versus 1T: HR = 0.92, CI 0.82–1.02;p=0.12). Five-year overall survival was comparable for compliant groups at 1T, 2T, and 3T hospitals (72%, 72.4%, and 72.6%, resp.). 3T hospitals were not associated with a lower risk of 30-day mortality (OR 0.70, 95% CI 0.44–1.11) compared to 1T hospitals but did have a higher R0 resection rate (OR 1.43, 95% CI 1.32–1.54).Conclusions. Adherence to NCCN guidelines, irrespective of hospital volume, is associated with improved overall survival for patients with extra-abdominal STS. High-volume hospitals more often adhere to guidelines, but low-volume hospitals that follow national guidelines may achieve comparable outcomes.

AbstractEpidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.

Background: Although the hallmark of long-QT syndrome (LQTS) is abnormal cardiac repolarization, there are varying degrees of phenotypic expression and arrhythmic risk. Our aim was to evaluate the performance of a morphological T-wave analysis program in defining breakthrough LQTS arrhythmic risk beyond the QTc value. Methods and Results: We analyzed 407 genetically confirmed patients with LQT1 (n=246; 43% men) and LQT2 (n=161; 41% men) over the mean follow-up period of 6.4±3.9 years. ECG analysis was conducted using a novel, proprietary T-wave analysis program. Time to a LQTS-associated cardiac event was analyzed using Cox proportional hazards regression methods. Twenty-three patients experienced ≥1 defined breakthrough cardiac arrhythmic events with 5- and 10-year event rates of 4% and 7%. Two independent predictors of future LQTS-associated cardiac events from the surface ECG were identified: left slope of T wave in lead V6 (hazard ratio=0.40 [0.24–0.69]; P <0.001) and T-wave center of gravity x axis (last 25% of wave) in lead I (hazard ratio=1.90 [1.21–2.99]; P =0.005), C statistic of 0.77 (0.65–0.89). When added to the QTc (C statistic 0.68 for QTc alone), discrimination improved to 0.78. Genotype analysis showed weaker association between these T-wave variables and LQT1-triggered events while these features were stronger in patients with LQT2 and significantly outperformed the QTc (C statistic, 0.82 [0.71–0.93]). Conclusion: Detailed morphological analysis of the T wave provides novel insights into risk of breakthrough arrhythmic events in LQTS, particularly LQT2. This observation has the potential to guide clinical decision making and further refine risk stratification.