Comparing Multivisceral Resection with Tumor-only Resection of Liposarcoma Using the Win Ratio.

BACKGROUND: Multivisceral resection of retroperitoneal liposarcoma (LPS) is associated with increased morbidity and may not confer a survival benefit compared with tumor-only (TO) resection. We compared both approaches using a novel statistical method called the "win ratio" (WR). METHODS: Patients who underwent resection of LPS from 2004 to 2015 were identified from the National Cancer Database. Multivisceral resection was defined as removal of the primary site in addition to other organs. The WR was calculated based on a hierarchy of postoperative outcomes: 30-day and 90-day mortality, long-term survival, and severe complication. RESULTS: Among 958 patients (multivisceral 634, TO 324) who underwent resection, the median age was 63 years (interquartile range [IQR] 54-71) with a median follow-up of 51 months (IQR 30-86). There was no difference in the WR among patients who underwent TO versus multivisceral resection in the matched cohort (WR 0.82, 95% confidence interval [CI] 0.61-1.10). In patients aged 72-90 years, those who underwent multivisceral resection had 36% lower odds of winning compared with patients undergoing TO resection (WR 0.64, 95% CI 0.40-0.98). A subgroup analysis of patients classified as not having adjacent tumor involvement at the time of surgery revealed that those patients who underwent multivisceral resection had 33% lower odds of winning compared to TO resection (WR 0.67, 95% CI 0.45-0.99). CONCLUSIONS: Based on win-ratio assessments of a hierarchical composite endpoint, multivisceral resection in patients without adjacent tumor involvement may not confer improved outcomes. This method supports the rationale for less invasive resection of LPS in select patients, especially older patients.

Disparities in Survival and NCCN Guideline-Concordant Care in Patients With Extremity Soft Tissue Sarcoma.

BACKGROUND: Based on the NCCN Guidelines for Soft Tissue Sarcoma (STS), treatment of extremity STS (ESTS) includes radiation therapy (RT) and surgical resection for tumors that are high-grade and >5 cm. ​​The aim of this study was to describe the association between neighborhood socioeconomic status (nSES), concordance with NCCN Guidelines recommendations, and outcomes in patients with ESTS. METHODS: Patients with ESTS diagnosed from 2006 through 2018 were identified in SEER registries. The analytic cohort was restricted to patients with high-grade tumors >5 cm without nodal or distant metastases who received limb-sparing surgery. Patient demographics and tumor characteristics associated with receipt of RT were analyzed using adjusted regression analyses. Kaplan-Meier curves and adjusted accelerated failure time models were used to examine disparities in cancer-specific survival. RESULTS: Of 2,249 patients, 29.0% (n=648) received neoadjuvant RT, 49.7% (n=1,111) received adjuvant or intraoperative RT, and 21.3% (n=476) did not receive RT. In adjusted analyses, lower nSES was associated with lower likelihood of receiving RT (odds ratio, 0.70 [95% CI, 0.57-0.87]; P<.001). Low nSES was associated with worse cancer-specific survival (hazard ratio, 1.19 [95% CI, 1.01-1.40]; P=.04). Race and ethnicity were not significant predictors of receipt of RT or cancer-specific survival in the fully adjusted models. CONCLUSIONS: Patients from lower nSES areas were less likely to receive NCCN Guideline-recommended RT for their ESTS and had worse cancer-specific survival. Efforts to better define and resolve disparities in the treatment and survival of patients with ESTS are warranted.

Use of neoadjuvant paclitaxel in breast angiosarcoma-Impact on surgical resection and response rates.

OBJECTIVE: Breast angiosarcoma is a tumor that can arise as a primary breast tumor or in association with prior radiation therapy. Angiosarcomas are uniquely sensitive to paclitaxel. This study evaluated the impact neoadjuvant paclitaxel (NAC) therapy has on surgical outcomes, tumor recurrence, and survival in breast angiosarcomas. METHODS: Patients with angiosarcoma of the breast, either primary or radiation-associated, were identified from a prospective institutional database. Patients receiving NAC were compared to those treated with upfront surgery. Clinical and pathological variables were compared using Student's t-test or Fisher's exact test, differences in survival were calculated using Kaplan-Meier methods. RESULTS: Twenty-four patients with angiosarcoma of the breast were identified, 10 with primary angiosarcoma and 14 with radiation-associated angiosarcoma. Twelve patients received NAC, 6 of each with primary angiosarcoma or radiation-associated angiosarcoma. Of these 12 patients, 11 had a margin negative resection (91%) of which, nine had a complete pathological response on surgical pathology. Of the 12 surgery-first patients, four (n = 4/12, 33%) had positive surgical margins, two of the four underwent reoperation. With a median follow-up of 16 months, four NAC patients had recurrence (33%) compared to six patients in the surgery-first group (58%) (p = 0.41). While not statistically significant, NAC patients had a 33% less risk of recurring compared to surgery-first patients ([hazard ratio =0.67 (95% confidence interval 0.16-2.72; p = 0.6]). CONCLUSION: NAC for breast angiosarcoma may be associated with high rates of complete pathological response and margin-negative resection. However, this did not impact overall survival. Future prospective control studies and longer follow-up periods are warranted to understand the impact on recurrence and survival.

tRFUniverse: A comprehensive resource for the interactive analyses of tRNA-derived ncRNAs in human cancer.

tRNA-derived ncRNAs are a heterogeneous class of non-coding RNAs recently proposed to be active regulators of gene expression and be involved in many diseases, including cancer. Consequently, several online resources on tRNA-derived ncRNAs have been released. Although interesting, such resources present only basic features and do not adequately exploit the wealth of knowledge available about tRNA-derived ncRNAs. Therefore, we introduce tRFUniverse, a novel online resource for the analysis of tRNA-derived ncRNAs in human cancer. tRFUniverse presents an extensive collection of classes of tRNA-derived ncRNAs analyzed across all the TCGA and TARGET tumor cohorts, NCI-60 cell lines, and biological fluids. Moreover, public AGO CLASH/CLIP-Seq data were analyzed to identify the molecular interactions between tRNA-derived ncRNAs and other transcripts. Importantly, tRFUniverse combines in a single resource a comprehensive set of features that we believe may be helpful to investigate the involvement of tRNA-derived ncRNAs in cancer biology.

Radiation therapy for retroperitoneal sarcoma: practice patterns in North America.

BACKGROUND: The addition of radiation therapy (RT) to surgery in retroperitoneal sarcoma (RPS) remains controversial. We examined practice patterns in the use of RT for patients with RPS over time in a large, national cohort. METHODS: Patients in the National Cancer Database (2004-2017) who underwent resection of RPS were included. Trends over time for proportions were calculated using contingency tables with Cochran-Armitage Trend test. RESULTS: Of 7,485 patients who underwent resection, 1,821 (24.3%) received RT (adjuvant: 59.9%, neoadjuvant: 40.1%). The use of RT decreased annually by < 1% (p = 0.0178). There was an average annual increase of neoadjuvant RT by 13% compared to an average annual decrease of adjuvant RT by 6% (p < 0.0001). Treatment at high-volume centers (OR 14.795, p < 0.0001) and tumor > 10 cm (OR 2.009, p = 0.001) were associated with neoadjuvant RT. In contrast liposarcomas (OR 0.574, p = 0.001) were associated with adjuvant RT. There was no statistically significant difference in overall survival between patients treated with surgery alone versus surgery and RT (p = 0.07). CONCLUSION: In the United States, the use of RT for RPS has decreased over time, with a shift towards neoadjuvant RT. However, a large percentage of patients are still receiving adjuvant RT and this mostly occurs at low-volume hospitals.

Allostatic load as a predictor of postoperative complications in patients with breast cancer.

Allostatic load (AL) is a biological measure of cumulative exposure to socioenvironmental stressors (e.g., poverty). This study aims to examine the association between allostatic load (AL) and postoperative complications (POC) among patients with breast cancer. Females ages 18+ with stage I-III breast cancer who received surgical management between 01/01/2012-12/31/2020 were identified in the Ohio State Cancer registry. The composite AL measure included biomarkers from the cardiovascular, metabolic, immune, and renal systems. High AL was defined as composite scores greater than the cohort's median (2.0). POC within 30 days of surgery were examined. Univariable and multivariable regression analysis examined the association between AL and POC. Among 4459 patients, 8.2% had POC. A higher percentage of patients with POC were unpartnered (POC 44.7% vs no POC 35.5%), government-insured (POC 48.2% vs no POC 38.3%) and had multiple comorbidities (POC 32% vs no POC 20%). Patients who developed POC were more likely to have undergone sentinel lymph node biopsy followed by axillary lymph node dissection (POC 51.2% vs no POC 44.6%). High AL was associated with 29% higher odds of POC (aOR 1.29, 95% CI 1.01-1.63). A one-point increase in AL was associated with 8% higher odds of POC (aOR 1.08, 95% CI 1.02-1.16) and a quartile increase in AL was associated with 13% increased odds of POC (aOR 1.13, 95% CI 1.01-1.26). Among patients undergoing breast cancer surgery, increased exposure to adverse socioenvironmental stressors, operationalized as AL, was associated with higher odds of postoperative complications.

Impact of Neoadjuvant Therapy for Pancreatic Cancer: Transatlantic Trend and Postoperative Outcomes Analysis.

BACKGROUND: The introduction of modern chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). A recent North American study demonstrated increased use of NAT and improved operative outcomes in patients with PDAC. The aims of this study were to compare the use of NAT and short-term outcomes in patients with PDAC undergoing pancreatoduodenectomy (PD) among registries from the US and Canada, Germany, the Netherlands, and Sweden. STUDY DESIGN: Databases from 2 multicenter (voluntary) and 2 nationwide (mandatory) registries were queried from 2018 to 2020. Patients undergoing PD for PDAC were compared based on the use of upfront surgery vs NAT. Adoption of NAT was measured in each country over time. Thirty-day outcomes, including the composite measure (ideal outcomes), were compared by multivariable analyses. Sensitivity analyses of patients undergoing vascular resection were performed. RESULTS: Overall, 11,402 patients underwent PD for PDAC with 33.7% of patients receiving NAT. The use of NAT increased steadily from 28.3% in 2018 to 38.5% in 2020 (p < 0.0001). However, use of NAT varied widely by country: the US (46.8%), the Netherlands (44.9%), Sweden (11.0%), and Germany (7.8%). On multivariable analysis, NAT was significantly (p < 0.01) associated with reduced rates of serious morbidity, clinically relevant pancreatic fistulae, reoperations, and increased ideal outcomes. These associations remained on sensitivity analysis of patients undergoing vascular resection. CONCLUSIONS: NAT before PD for pancreatic cancer varied widely among 4 Western audits yet increased by 26% during 3 years. NAT was associated with improved short-term outcomes.

International differences in the selection and outcome of minimally invasive and open distal pancreatectomy: A transatlantic analysis.

BACKGROUND: The efficacy and safety of minimally invasive distal pancreatectomy have been confirmed by randomized trials, but current patient selection and outcome of minimally invasive distal pancreatectomy in large international cohorts is unknown. This study aimed to compare the use and outcome of minimally invasive distal pancreatectomy in North America, the Netherlands, Germany, and Sweden. METHODS: All patients in the 4 Global Audits on Pancreatic Surgery Group (GAPASURG) registries who underwent minimally invasive distal pancreatectomy or open distal pancreatectomy during 2014-2020 were included. RESULTS: Overall, 20,158 distal pancreatectomies were included, of which 7,316 (36%) were minimally invasive distal pancreatectomies. Use of minimally invasive distal pancreatectomy varied from 29% to 54% among registries, of which 13% to 35% were performed robotically. Both the use of minimally invasive distal pancreatectomy and robotic surgery were the highest in the Netherlands. Patients undergoing minimally invasive distal pancreatectomy tended to have a younger age (Germany and Sweden), female sex (North America, Germany), higher body mass index (North America, the Netherlands, Germany), lower comorbidity classification (North America, Germany, Sweden), lower performance status (Germany), and lower rate of pancreatic adenocarcinoma (all). The minimally invasive distal pancreatectomy group had fewer vascular resections (all) and lower rates of severe complications and mortality (North America, Germany). In the multivariable regression analysis, country was associated with severe complications but not with 30-day mortality. Minimally invasive distal pancreatectomy was associated with a lower risk of 30-day mortality compared with open distal pancreatectomy (odds ratio 1.633, 95% CI 1.159-2.300, P = .005). CONCLUSIONS: Considerable disparities were seen in the use of minimally invasive distal pancreatectomy among 4 transatlantic registries of pancreatic surgery. Overall, minimally invasive distal pancreatectomy was associated with decreased mortality as compared with open distal pancreatectomy. Differences in patient selection among countries could imply that countries are in different stages of the learning curve.