bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new clinically based staging system for gallbladder cancer.
Authors: Yadav Siddhartha , Prasai Kritika , Mady Mohamed , Hassan Mohamed Abdelrahim Muddathir , Roberts Lewis R. , Mahipal Amit 
Published: January 2019

433 Background: Current staging systems for gallbladder cancer (GBC) are inadequate, as they are based on surgical pathology, and therefore are not relevant for unresectable patients and patients undergoing neoadjuvant chemotherapy. Methods: Patients with a confirmed diagnosis of GBC who were seen at Mayo Clinic between the years 2000 and 2016 were included in this analysis. Data on demographic and tumor characteristics and outcomes were collected by retrospective review of electronic medical records. A model predictive of overall survival was developed using Cox proportional hazard regression analysis. Harrel’s C-statistic was calculated to evaluate the predictive accuracy of the model and compared with the TNM staging system. Results: A total of 523 patients were included in the final analysis, with a median age of diagnosis of 68 years. The median duration of follow up of the entire cohort was 12 months. In multivariate analysis, factors predictive of poorer overall survival were: ages 65-74 years (HR : 1.80, 95% CI: 1.33–2.43) and ages 75+ years (HR: 2.93, 95% CI: 2.12–4.06) compared to age <55 years; tumor size ≥ 5 cm by imaging (HR: 1.24, 95% CI: 1.01–1.55); nodal involvement by imaging (HR:1.61, 95% CI: 1.23–2.10); involvement of distant organs by imaging (HR: 2.85, 95% CI: 2.16–3.75); ECOG performance score of 2 or higher (HR: 1.78, 95% CI: 1.36–2.32) compared to ECOG 0-1; albumin level <3.5 g/dL (HR: 1.40, 95% CI: 1.08–1.81); and alkaline Phosphatase level ≥ 200 IU/L (HR: 1.49, 95% CI: 1.21–1.84). Using these seven predictive factors of survival we created a four-tier staging system. The median survivals of Stages I, II, III and IV created in our novel system were 64, 34, 20 and 7 months with corresponding hazard ratios of 1, 1.5, 2.5 and 8.5 respectively. The C-statistic for this novel staging system was 0.68 compared to C-statistic of 0.69 for the TNM staging system, indicating similar performance in predicting survival. Conclusions: We have created a novel clinically-based staging system for patients with GBC based on nonoperative information at the time of diagnosis which performs on par with the current surgical pathology based TNM staging system.
Comparison of neoadjuvant and adjuvant therapy for resectable pancreatic cancer using Markov decision modeling.
Authors: Choi Minsig , Ishizawa Sayaka , Liang Yan , Rashidian Sina , Sasson Aaron R. , Feinberg Eugene 
Published: January 2019

448 Background: Meta-analysis of smaller studies have shown that neoadjuvant chemotherapy is more beneficial for patients with resectable pancreatic cancer than upfront surgery by comparing life expectancy (LE) and quality-adjusted life expectancy (QALE) computed from Markov models. The study results utilized literature data using several small clinical trials but no individual patient data was used and only gemzar based therapy was studied. Methods: Markov model was used to calculate the LE and QALE for adjuvant and neoadjuvant chemotherapy and individual patient parameters was used in the model to refine certain clinical outcome datapoints. We used 278 patients pancreatic cancer data from 2008 to 2017 from Stony Brook University and used the literature data from randomized clinical trials studying gemzar (GEM), gemzar and capecitabine (GEM+CAP) and modified FOLFIRINOX (mFOL). The median OS for each model was obtained by computer simulation. Results: Intensive adjuvant chemotherapy using mFOL had best simulation outcome with median OS (52.5 months), LE (81.5 months), and QALE (65.0 quality-adjusted life months) compared to using GEM (40.5, 66.5, and 52.9 months for median OS, LE, and QALE), GEM+CAP (16.5, 28.0, and 21.9 months for median OS, LE, and QALE), and 5-FU (16.5, 26.9, and 21.1 months for median OS, LE, and QALE). The neoadjuvant chemotherapy approach improved LE and QALE but not in median OS when compared to adjuvant therapy. Conclusions: Mathematical modeling confirms the improved clinical outcome for modified FOLFIRINOX in resectable pancreatic cancer. The benefit of neoadjuvant chemotherapy approach suggest further clinical trials are needed to determine the better treatment strategy for pancreatic cancer patients.
Neoadjuvant therapy for body and tail pancreatic adenocarcinoma: Propensity score matched analysis using the National Cancer Database.
Authors: Ivanics Tommy , Leonard-Murali Shravan , Han Xiaoxia , Steffes Christopher P. , Kwon David S. , Shah Rupen A. 
Published: January 2019

450 Background: The role of neoadjuvant systemic therapy in the management of body and tail pancreatic ductal adenocarcinoma (PDAC) is unknown. The aim of our study was to investigate the outcomes associated with neoadjuvant therapy for early stage body and tail PDAC. Methods: The National Cancer Database (NCDB) was queried for stage I and II body and tail PDAC between 2006-2014. Groups were defined according to treatment sequencing strategies into an upfront resection group (UR), resection followed by adjuvant therapy (R+AT), neoadjuvant therapy followed by resection (NAT+R), and neoadjuvant therapy followed by resection and adjuvant therapy (NAT+R+AT). Patients who underwent neoadjuvant therapy followed by resection were matched by propensity score with patients who underwent upfront resection. Overall survival was compared using Kaplan-Meier method and Cox proportional hazards regression model. Results: 441 patients received NAT+R with or without AT compared to 1323 patient who underwent UR with or without AT. NAT+R had lower pathologic stage, lymph node positivity and a higher rate of margin negative resections compared to the matched UR cohort. In the propensity matched cohort, the median survival (MS) was higher in the neoadjuvant (NAT+R/NAT+R+AT) group compared to the upfront resection (UR/R+AT) group (28.6 vs. 22.9 mo; p<0.001). When further stratified by treatment sequencing the MS was longer in a NAT+R+AT cohort compared to the R+AT group (36.0 vs. 25.3 mo; p<0.05) (Table). However, there was no difference in MS between R+AT and NAT+R cohorts. On multivariable analysis, receipt of NAT represented an independent factor for survival (NAT+R+AT HR 0.41, 95% CI 0.32-0.54; NAT+R HR, 0.53, 95% CI 0.44-0.64; R+AT HR 0.61, 95% CI 0.53-0.70). Conclusions: There appears to be a survival benefit with neoadjuvant systemic therapy in patients with early stage body and tail PDAC. A systemic perioperative treatment sequencing approach (NAT+R+AT) appears to have the greatest survival benefit. [Table: see text]
Impact of neoadjuvant radiation on survival in patients with pancreatic cancer undergoing neoadjuvant chemotherapy followed by pancreatectomy.
Authors: Macedo Francis Igor , Azab Basem , Picado Omar , Yakoub Danny , Livingstone Alan S , Franceschi Dido , Dudeja Vikas , Merchant Nipun B. 
Published: January 2019

453 Background: Pancreatic adenocarcinoma (PDAC) carries a dismal prognosis. Neoadjuvant chemoradiation therapy (NACR) has been introduced to enhance the outcomes of patients with borderline resectable and locally advanced PDAC, however the role of radiation therapy remains largely unknown. Methods: The National Cancer Database (NCDB) was queried for patients with stage I-III PDAC who underwent surgical resection from 2004 to 2014. Patients undergoing NACR were compared to those undergoing neoadjuvant chemotherapy (NAC) alone. The association between clinical characteristics and overall survival (OS) was assessed using the Kaplan-Meier method and multivariable Cox regression model. Results: Of 3,133 patients, 2,351 (75%) patients underwent NACR and 782 (25%), NAC alone. Most patients were Caucasians (84%), treated at academic institutions (67%) and underwent pancreaticoduodenectomy (74%). Median follow-up time was 32 months (IQR, 22-50 months). Median number of lymph nodes examined (LNE) and number of positive nodes (NPN) were significantly decreased in NACR (13 vs. 16, p < 0.001 and 0 vs. 1, p < 0.001, respectively). Rates of margin positivity, median OS and 5-year OS were similar between 2 groups (NACR vs. NAC: 15% vs. 17%, p = 0.545; 25.7 months (95% CI 24.4–26.7) vs. 25.1 months (95% CI: 23.9–27.5), and 20% vs. 22%, p = 0.616, respectively, Figure 1). Subgroup analysis of high-risk features (R1/R2 and N1) also showed no difference in survival outcomes. Neoadjuvant radiation was not an independent predictor associated with OS, whereas advanced age, R1/R2, T3/T4, N1, and poorly differentiated histology were independent negative prognostic factors. Conclusions: NACR is associated with lower rates of lymph node positivity, however this did not translate in survival or margin positivity benefit compared to NAC alone. The role of radiotherapy in PDAC continues to evolve, however no convincing data is currently available to advocate the widespread use of radiotherapy in the neoadjuvant setting. Further evidence with prospective clinical trials is still warranted to confirm these findings.
Resection margin distance in extrahepatic cholangiocarcinoma: How much is enough?
Authors: Rahnemai-Azar Amir A. , Ronnekleiv-Kelly Sean , Abbott Daniel , Ethun Cecilia Grace , Poultsides George A. , Tran Thuy , Fields Ryan , Krasnick Bradley Aaron , Martin Robert C. G. , Scoggins Charles Raben , Idrees Kamran , Isom Chelsea A , Hatzaras Ioannis , Shenoy Rivfka , Shen Perry , Perkins James D. , Pawlik Timothy M. , Maithel Shishir K. , Weber Sharon M. 
Published: January 2019

455 Background: Surgical resection is required for curative treatment of patients with extra-hepatic cholangiocarcinoma (EH-CCA). The objective of this study was to determine if the distance of surgical margin was associated with outcome. Methods: Patients who underwent curative-intent resection for EH-CCA between 2000 and 2015 at 10 hepatobiliary centers across the U.S. were evaluated using prospectively collected data. Cox proportional hazard model was utilized to evaluate the influence of the extent of the margin on outcome. Results: 538 patients with EH-CCA who underwent curative-intent resection were included: 383 (71%) undergoing R0 resection, 153 (28%) undergoing R1 resection, and 2 with R2 resection. A negative surgical margin (R0) was associated with improved recurrence-free (RFS) and overall survival (OS) (RFS: 10.5% vs. 3.6% (R1) and OS: 25.8% vs. 9.3% (R1). Subsequently, further analysis on 161 patients with complete data on distance of resection margin, all undergoing R0 resection, was performed to assess the impact of extent of margin on outcome. On multi-variable analysis, the resection margin distance, analyzed as a continuous variable, was not associated with either improved RFS (RR 1.00, 95% CI 0.96-1.05; p 0.71) or OS (RR 0.99, 95% CI 0.96-1.01; p 0.49). Increasing age, increased tumor size, and LN metastasis were identified as independent predictors of OS; while RFS were mainly dependent on tumor size and LN metastasis (Table). Conclusions: Achieving R0 resection is acceptable for EH-CCA tumors, and obtaining additional margin does not confer a benefit on overall survival. Increasing age, tumor size, and LN metastasis are independent predictors of RFS and OS, but increased margin width is not associated with improvement in either. Multivariable analysis of factors affecting OS of patients with extra-hepatic CCA who underwent surgical resection, with significant factors noted in bold. [Table: see text]
Racial/ethnic disparities in the use of high-volume centers for hepatobiliary and pancreatic cancer surgery.
Authors: de Geus Susanna W , Sachs Teviah E. , Ng Sing Chau W , McAneny David B. , Tseng Jennifer F. 
Published: January 2019

457 Background: The impact of hospital volume on the outcomes of cancer surgery has been well established. The present studies investigates how race/ethnicity influences the utilization of high-volume centers for hepatobiliary and pancreatic surgery. Methods: Patients that underwent surgery for hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), ampullary adenocarcinoma (AC), or pancreatic ductal adenocarcinoma (PDAC) between 2006 and 2015 were identified from the National Cancer Data Base. Hospitals were divided into low- and high-volume centers based on the medium number of cancer surgeries per year. Multivariable logistic regression analyses predicting receipt of care at a low-volume center based on age, sex, race/ethnicity, comorbidities, insurance, income, travel distance, geographic location, urban/metro location, and tumor stage were performed. All analyses were performed separately by tumor type. Results: 8,962 patients with HCC, 2,119 with ICC, 3,973 with ECC, 5,125 with AC, and 25,231 with PDAC were identified. Non-Hispanic black patients were more likely to undergo resection for AC (vs. non-Hispanic white: AOR, 1.326; p = 0.0125) or PDAC (vs. non-Hispanic white: AOR, 1.187; p = 0.0002) at a low volume centers. Hispanic patients more often underwent surgery for ECC (vs. non-Hispanic white: AOR, 1.731; p < 0.0001) or PDAC (vs. non-Hispanic white: 2.030; p < 0.0001) cancer at a low-volume center. Patients of Asian descent were significantly less often treated for HCC at a low volume center (vs. non-Hispanic white: AOR, 0.644; p < 0.0001) compared to non-Hispanic whites. Non-Hispanic black, Hispanic, or Asian race/ethnicity did not impact the likelihood of receiving care at a low volume center for any other tumor types. Conclusions: The results of this study suggest that race/ethnicity influences the likelihood of receiving care at a high-volume cancer center, even after controlling for other barriers to access to care, including insurance status, income and travel distance.
Does a longer waiting period after neoadjuvant radiochemotherapy improve the oncological prognosis of rectal cancer?: Three-year follow-up results of the GRECCAR-6 randomized multicenter trial.
Authors: Lefevre Jeremie H. , Mineur Laurent , Cachanado Marine , Rullier Eric , Rouanet Philippe , De Chaisemartin Cecile , Meunier Bernard , Mehrdad Jafari , Cotte Eddy , Desrame Jérôme , Karoui Mehdi , Benoist Stephane , Kirzin Sylvain , Berger Anne , Panis Yves , Piessen Guillaume , Saudemont Alain , Prudhomme Michel , Simon Tabassome , Parc Yann ,   The French Research Group of Rectal Cancer Surgery (GRECCAR)
Published: January 2019

483 Background: There are controversial data on the impact of a long waiting period between radiochemotherapy (RCT) and resection for rectal cancer on the rate of complete pathological response (pCR = ypT0N0). The impact on the oncological prognosis is also unknown. We present the 3 years survival results of the GRECCAR6 trial. Methods: The GRECCAR6 trial was a phase III, multicentre, randomized, open-label, parallel-group, controlled trial. Patients with cT3/T4 or TxN+ tumours assessed by radiological examination (MRI and/or endo-ultrasound) of the mid or lower rectum who had received RCT (45-50 Gy with intravenous 5-FU or capecitabine) were included and randomized between 7 weeks or 11 weeks of waiting period. Primary endpoint was the pCR rate. Secondary endpoints were overall, disease-free survival and rate of recurrences. Results: A total of 265 patients from 24 participating centres were enrolled between October 2012 and February 2015. Among them, 253 patients underwent surgery with mesorectal excision. The rate of pCR was 17% (43/253). Mean follow-up from surgical resection was 32±8 months. 25 deaths occurred with a 89% OS at 3 years. DFS was 67.7% at 3 years due to 77 deaths or recurrences. 3-years local and distant recurrences rates were 9.2% and 24.9%, respectively. The group of randomization had no impact on the OS (p = 0.9486) and the DFS (p = 0.8672). Distant (p = 0.8589) and local (p = 0.5780) recurrences were also not influenced by the waiting period. Patients with a pCR had an excellent prognosis with an overall survival of 94.5% versus 87.9% for the remaining patients at 3 years (p = 0.232) and a DFS of 89.6% versus 63.4% (p = 0.0025). On multivariate analysis, DFS was influenced by low rectal tumors (OR=1.74; [1.03; 2.94], p = 0.037), R1 resection (OR = 2.03; [1.18; 3.50], p = 0.011), ypT3-T4 (OR = 2.4; [1.12; 5.19], p = 0.0245) and N+ (OR = 2.85; [1.76; 4.61], p < 0.001). Conclusions: Waiting 4 weeks longer after radiochemotherapy has no influence on the oncological outcomes of T3/T4 rectal cancers. Clinical trial information: NCT01648894.
Total neoadjuvant therapy with short course radiation compared to concurrent chemoradiation in rectal cancer.
Authors: Chapman William , Kim Hyun , Bauer Philip , Makhdoom Bilal , Trikalinos Nikolaos , Pedersen Katrina , Glasgow Sean , Roy Amit , Roach Michael Charles , Mutch Matthew G , Parikh Parag , Hunt Steven 
Published: January 2019

486 Background: Total Neoadjuvant Therapy (TNT), or delivery of all radiation and chemotherapy prior to surgery, has improved complete response and downstaging rates compared to adjuvant therapy in patients with rectal cancer. Data regarding the use of short course radiation in the setting of TNT (SC-TNT) are limited. This study compares the pathologic complete response rate (pCR), Neoadjuvant Rectal (NAR) Score – a validated predictor of outcome based on tumor downstaging, and recurrence rates for patients receiving SC-TNT versus chemoradiation (CRT). Methods: Patients who underwent neoadjuvant therapy followed by total mesorectal excision for Stage II or III rectal cancer from 2009 to 2018 were included in this retrospective cohort study. CRT recipients (50-55Gy/25-28 fx with concurrent 5-FU or capecitabine) comprised one cohort; the other included SC-TNT recipients (25-35Gy/5 fx followed by CAPOX or FOLFOX chemotherapy). The primary outcome of pCR rate was assessed in univariate analysis; the secondary outcome of NAR score was calculated and categorized as “Low” ( < 8), “Intermediate” (8–16), and “High” ( > 16). Finally, recurrence rates were measured and classified as local, distant, or both. Results: Of 388 eligible patients, 236 (60.8%) were treated with CRT and 152 (39.2%) underwent SC-TNT. On univariate analysis, the SC-TNT cohort had more advanced disease (77% Stage III disease vs. 67%, p = 0.04) and longer elapsed time between radiation completion and surgery (Median 131 vs. 63 days; p < 0.01). SC-TNT achieved a numerically higher pCR rate compared to CRT (25.0% vs. 19.1%, p = 0.16). Odds of achieving a “low” NAR Score trended higher among the SC-TNT cohort (OR 1.49, 95% CI 0.96 – 2.31). Recurrence rates were also similar (14.3% vs. 14.9%, p = 0.87) over comparable follow-up (CRT = 30.5 months [IQR 11.1 – 49.0]; SC-TNT = 22.3 months [IQR 10.8 – 61.0]; p = 0.82). Conclusions: SC-TNT yielded a pCR rate of 25% and overall recurrence rate of 14.9% among patients with locally advanced rectal cancer. Short course radiation with neoadjuvant multiagent chemotherapy is at least as effective as long-course CRT. [Table: see text]
Metastatic patterns and prognostic significance of signet ring cell carcinoma of the colon: Retrospective analysis of SEER database.
Authors: Khoury John , Chacko Rebecca , Macari David , Gbadamosi Bolanle , Ezekwudo Daniel , Blankenship Leann , Anderson Joseph M , Jaiyesimi Ishmael A. 
Published: January 2019

488 Background: Signet ring cell carcinoma of the colon (SRCC) represents less than 1% of all colon carcinomas. We retrospectively examined the metastatic patterns and prognosis of SRCC in comparison to adenocarcinoma (AC) of the colon. Methods: A total of 763 patients diagnosed with SRCC and 42,875 patients with AC of the colon from 2010 to 2012 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Age, race, gender, primary site, grade, stage, metastatic site and survival data were collected. Results: Out of 43,638 patients, 78.7% were white, 12.5% black and 8.8% other races. Median age of diagnosis was 67.5 years for SRCC as compared to 69.1 years for AC . SRCC was more likely to be grade III or IV (92% vs 21.6%; p < 0.001), to be found in the right colon (63.7% vs 49.4%; p < 0.001) and to present as advanced stage (40.2% vs 29.4% for stage III and 37.1% vs 22.3% for stage IV; p < 0.001). SRCC was more likely to present with metastases to the brain (11.0% vs 1.3%; p < 0.001) and bone (6.4% vs 4.1%; p < 0.001), while AC subjects were more likely to present with metastases to the liver (77.0% vs 22.1%; p < 0.001) and lung (21.2% vs 5.8%; p < 0.001). The 5 year overall survival rate (5-YSR) was 28.2% (CI, 24.5% to 32.4%) for SRCC compared to 50.8% (CI, 50.1% to 51.6%) for AC (Hazard ratio for death, 1.38; CI, 1.26 to 1.52; P < 0.001). The differences in stage specific 5-year survival rates for SRCC and AC were not statistically significant for stage I and stage II. However, SRCC had a lower 5-YSR for stage III (34.5% vs 55.4%) and stage IV (3.3% vs 10.8%). Conclusions: SRCC of the colon has worse survival rates for advanced stages when compared to AC. SRCC presents at earlier age, with advanced tumor grade and stage at diagnosis. The metastatic behavior of SRCC is different than AC with a higher incidence of brain and bone metastases at diagnosis.
Impact of cardiac comorbidity on use and outcomes of adjuvant chemotherapy (ADJ) for colorectal cancer (CRC): A real-world population-based study.
Authors: Liu Shiru Lucy , Gill Sharlene , Cheung Winson Y. 
Published: January 2019

491 Background: Cardiac comorbidities such as myocardial infarction (MI) and congestive heart failure (CHF) may pose challenges in the treatment of CRC. As the population ages, cancer patients (pts) will be increasingly affected by cardiac comorbidities. We performed a population-based analysis of CRC to evaluate the prevalence of MI and CHF, use of ADJ, and survival outcomes. Methods: We evaluated 8601 pts diagnosed with resected stage 2 or 3 CRC from 2004 to 2015 in Alberta, Canada. Baseline patient, tumor, and treatment characteristics were compared between those with and without MI or CHF. Survival analysis was conducted using Kaplan-Meier methods and Cox regression models. Results: In total, 506 (5.9%) patients (pts) had MI and 440 (5.1%) had CHF. CRC patients with prior MI or CHF were older (median 76 and 79 years, respectively) and had worse Charlson Comorbidity Index (median CCI 2 for both) than those without cardiac comorbidities (median age 67 and CCI 0) (p < 0.001). Only 24% and 15% of pts with a MI or CHF history, respectively, received ADJ when compared to their counterparts (52% and 53%, respectively, p < 0.001). Among those who received ADJ (N = 3409), an oxaliplatin-based regimen was used in 26% of MI pts versus 42% of those without MI (p = 0.002), and in 31% of CHF pts versus 42% of those without CHF. Kaplan-Meier analysis revealed significantly worse overall survival (OS) in pts with prior MI (9.1 vs 4.3 years, p < 0.001) or CHF (9.2 vs. 2.7 years, p < 0.001) when compared to those without. However, cancer-specific survival (CSS) was not statistically different with or without MI (p = 0.348) and with or without CHF (p = 0.611). In Cox regression that adjusted for use of ADJ, MI was no longer a significant predictor of OS (HR = 1.01, 95% confidence interval (CI) 0.88-1.15), but CHF remained significant (HR 0.65, 95% CI 0.57-0.74). Neither MI nor CHF were predictors of CSS (HR 1.09, 95% CI 0.98-1.33, and HR 0.94, 95% CI 0.77-1.15). Conclusions: CRC pts with MI or CHF experienced lower use of ADJ and worse OS, but no difference in CSS was observed. ADJ-treated pts with prior MI appeared to benefit while worse outcomes in pts with prior CHF appear to be driven by non-cancer related causes.