bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant therapy duration and outcome of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC).
Authors: Shahda Safi , Perkins Susan , Cramer Harvey M , House Michael Garrett , Nakeeb Attila , Zyromski Nicholas J , Ceppa Eugene P , Sehdev Amikar , Akisik Fatih , Lin Jingmei , Schmidt Christian , Ellsworth Susannah G. , O'Neil Nina , Link Kristen , O'Neil Bert 
Published: January 2019

436 Background: Neoadjuvant chemotherapy (NA CT) may improve surgical selection for resectable (R) PDAC, and margin negative resection in borderline resectable (BR) PDAC. Optimal duration of NA CT is unknown, as is the role of XRT with modern chemotherapy. We compared survival outcomes by duration of NA CT and NA CT + XRT. Methods: Patients with R or BR PDAC who underwent NA CT with or without XRT and followed by curative resection were included in this analysis. Data was extracted from an IRB approved pancreatic cancer database at Indiana University. Disease Free (DFS) and Overall (OS) survival were calculated from the surgery date and compared between: 1) < 3 v ≥ 3 months NA CT and 2) NA CT with/without XRT. Results: Between Summer 2008 and Summer 2018, 116 patients received NA CT with or without XRT and completed surgical resection. Median (range) age was 63 years (36, 84), stages were R=47%, BR=53%. Most patients received modified FOLFIRINOX or FOLFIRINOX (59 %), or gemcitabine/nab-paclitaxel (13%) and 24% received XRT. There were four (3 %) pathologic complete responders, all in the ≥ 3 mo NA CT + XRT group. Percent node positive was lower in NA CT + XRT versus NA CT only (median 0% vs 7.4%, p < 001), but did not differ by duration of NA CT. With a median (range) follow-up time of 13.7 mo (0.7, 83.0), median OS was 22.5 mo (19.5, 29.8) with < 3 mo NA CT versus 16.3 (12.2, 18.9) with ≥ 3 mo NA CT (p = 0.02) and was 22.6 mo (17.0, 82.9) with NA CT + XRT versus 19.5 (13.1, 22.5) in NA CT only (p = 0.03). There was no difference in DFS by duration of NA CT or XRT. Conclusions: In this study, patients who received a shorter course of chemotherapy and radiation had improved mOS when calculated from the surgery date. While this unexpected results could reflect selection bias of therapy, further analysis will account for tumor stage at diagnosis, perioperative complications and use propensity score adjustment to examine/adjust for possible treatment selection bias.
MSI-low is an intermediate type between MSI-high and MSS in esophagogastric junction adenocarcinoma.
Authors: Imamura Yu , Toihata Tasuku , Takamatsu Manabu , Tanaka Norio , Mine Shinji , Mori Seiichi , Oki Eiji , Morita Masaru , Baba Hideo , Sano Takeshi , Watanabe Masayuki 
Published: January 2019

44 Background: High level of microsatellite instability (MSI-high) is an actionable molecular status in oncology, informing tumor response to immune checkpoint inhibitor. However, little is known about MSI-low. The aim of this study is to unveil the characteristics of MSI-low tumor in esophagogastric junction (EGJ) adenocarcinoma. Methods: Using 372 cases with chemo-naive EGJ adenocarcinoma tissue, MSI testing and Epstein Barr Virus (EBV)-DNA detection were performed by DNA fragment analysis (BAT25, BAT26, BAT40, D2S123, D5S346, and D17S250) and real-time PCR, respectively. MSI-high was defined as having two or more unstable markers, MSI-low as one, and microsatellite stable (MSS) as none. MSI status was compared with clinicopathological and molecular status including epigenetic alteration in MLH-1, LINE-1, and CpG methylator phenotype (CIMP), TP53 status (sequencing and immunohistological expression), Ki-67 index, intra-/peri-tumoral lymphocyte counts (CD8+ or FOXP3+), combined positive score (CPS) of PD-L1 expression. Results: MSI-low was detected in 29, MSI-high in 28, and EBV (+) in 9 cases. Three cases with MSI-low showed EBV (+), but MSI-high and EBV (+) were mutually exclusive. In 363 EBV (-) cases, MSI-low was associated with younger age (MSI-high 71.7 ± 11.3, MSI-low 61.3 ± 12.5, and MSS, 65.0 ± 12.3 years old, P = 0.003). Notably, MSI-low exhibited an intermediate type between MSI-high and MSS, in terms of no. of lymph node metastasis, and tumor immune microenvironment [no. of intra-/peri-tumoral CD8+ cells, no. of intra-/peri-tumoral FOXP3+ cells, and CPS of PD-L1 (all P among the 3 groups < 0.05)]. In contrast to MSI-high tumors, MSI-low tumor was not associated with epigenetic alteration in any of MLH-1, LINE-1, or CIMP status. In survival analysis, 3-year disease-specific survival rate of MSI-low was better than that of MSS tumors, and similar to MSI-high (92.2% for MSI-low, 92.2% for MSI-high, and 69.6% for MSI-low). This trend was also observed in time to recurrence (P = 0.01). Conclusions: MSI-low cases exhibited an intermediate immune microenvironment between MSI-high and MSS, and favorable outcome. Our results may implicate MSI-low as a predictive biomarker for immune checkpoint inhibitor.
Comparison of radiation treatment volumes for borderline resectable pancreatic cancer.
Authors: Bluemel Trevor Scott , Kharofa Jordan 
Published: January 2019

440 Background: Optimal radiation target volumes for downstaging and local control in patients with borderline resectable pancreatic cancer (BRPCa) are undefined. Most local recurrences are near the celiac axis (CA) and superior mesenteric artery (SMA), as demonstrated by pattern of failure mapping (Dholakia et al IJROBP 2013). Methods for generating target volumes include symmetric margins around the tumor or a customized approach. We investigated three current prospective trials’ coverage of vascular regions at risk of recurrence. Methods: CT simulation scans of 14 patients with BRPCa from an institutional prospective trial were used to create treatment volumes for comparison. Treatment volumes from three current prospective trials (PREOPANC, Alliance A021101, and Alliance A021501) were generated for each patient based upon their respective protocols. The trials’ volumes were compared to two reference volumes created for coverage evaluation. A customized vasculature (CustVasc) CTV was based on the CA, SMA, and vessels abutting the tumor. The Hopkins PTV reference volume was based upon the proximal 1 cm of the CA and 3 cm of the SMA, and expanded according to the study’s protocol. Boolean operators located regions the three prospective trials would not provide treatment when compared to reference volumes. Results: Table outlines the target volumes and the proportion of the CustVascPTV and Hopkins PTV covered by each trial definition. Conclusions: Symmetric expansion from the primary tumor to generate target volumes may not adequately cover the mesenteric vasculature which is at high risk of local recurrence and varies based on patient/tumor anatomy. An approach utilizing a customized target volume that specifically includes the SMA and CA will improve coverage to this region at high risk of local recurrence.[Table: see text]
Neutrophil-to-lymphocyte ratio as a prognostic marker in patients with metastatic gallbladder cancer.
Authors: Mady Mohamed , Prasai Kritika , Yadav Siddhartha , Hassan Mohamed Abdelrahim Muddathir , Roberts Lewis R. , Borad Mitesh J. , Mahipal Amit 
Published: January 2019

442 Background: Neutrophil to lymphocyte ratio (NLR) has been used as an inflammation-based prognostic marker for various malignancies. The aim of our study was to determine whether NLR can independently predict the overall survival in patients with metastatic gallbladder cancer (GBC). Methods: We identified patients diagnosed with GBC who were treated at Mayo Clinic between the years 2000 and 2016. Patients who had nonmetastatic GBC were excluded along with the patients who did not have data for neutrophils and lymphocytes. Optimal cutoff point for NLR was identified by plotting martingale residuals against NLR and patients were divided into two groups, ≥ 5 or < 5. Demographic, follow-up data and outcomes were collected by retrospective review of electronic medical records. Fisher’s exact test was used to compare categorical variables, while The Mann- Whitney U test was used to compare continuous variables. Kaplan-Meier curves were plotted for NLR ≥ 5 and NLR < 5 and overall survival (OS) between the two groups were compared using log rank test. Multivariate survival analysis was performed using Cox-proportional hazard regression. Results: A total of 231 patients met our inclusion criteria, of which, 138 (60%) had NLR < 5 and 93 (40%) had NLR ≥ 5. Patients with NLR ≥ 5 were more likely to be older and have poor performance score, lower albumin level, higher alkaline phosphatase level, and higher platelet count. There were no significant differences noted in gender, race and administration of chemotherapy between the two groups. In univariate analysis, patients with NLR ≥ 5 at presentation had a significantly worse OS compared to those with NLR < 5 (Median survival: 3.6 vs. 8.8 months, p < 0.001). In multivariate analysis, adjusting for age, ECOG status, albumin, ALP, AST, ALT, bilirubin, platelet count and administration of chemotherapy, NLR of ≥ 5 was associated with a worse OS compared to NLR < 5 (HR: 1.70, 95% CI:1.20 – 2.39. p < 0.05). Conclusions: Our study demonstrates that NLR ≥ 5 is an independent predictor of poor prognosis in patients with metastatic gallbladder cancer.
Combination therapy with TACE + ablation versus TACE + SBRT for hepatocellular carcinoma (HCC): Comparative analysis with propensity score-weighted cohorts.
Authors: Nabavizadeh Nima , Jahangiri Younes , Rahmani Ramtin , Degnin Catherine , Chen Yiyi , Geeratikun Yindee , Hung Arthur , Thomas Charles R. , Kolbeck Kenneth , Schenning Ryan , Kaufman John , Farsad Khashayar 
Published: January 2019

443 Background: To assess the relative efficacy and toxicity associated with TACE+Ablation (Ablation) or TACE+SBRT (SBRT) in a large cohort of patients with unresectable HCC. Methods: Patients with HCC undergoing Ablation or SBRT from 2006-2016 with available follow up were included. Treatment groups were different at baseline regarding tumor stage (BCLC A, B and C: 96%, 4%, 0% (Ablation) vs. 73%, 14% and 13% (SBRT), P < 0.001) and severity of liver disease (CTP A, B, and C: 55%, 45% and 0% (Ablation) vs. 50%, 41%, and 9% (SBRT), P = 0.007). Propensity scores were calculated with age, sex, BCLC stage, CTP class, etiology of liver disease, tumor number, and diameter to balance the cohorts. Average treatment effects on survival with multivariable propensity score-weighted competing risk Cox regression models were evaluated, with BCLC stage, number of treated tumors and liver transplant as additionally controlled variables. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), local tumor control and hepatotoxicity. Treatment-related hepatotoxicity was defined as a two point change in CTP within six months after treatment. Results: 192 subjects were included (101 Ablation, 91 SBRT; median age=60 years, 75% men). Liver disease included HCV (78%), alcohol (35%) and NASH (8%). Liver transplant-adjusted 1- and 2-year OS rates were significantly greater for Ablation vs SBRT (88% vs. 75% and 77% vs. 50%, P<0.001). 1-and 2-year PFS rates were significantly greater for Ablation vs. SBRT (84% vs. 65% and 75% vs. 51%, P < 0.001). 1- and 2- year local tumor control rates were similar with both strategies (99% vs. 91% and 94% vs. 87%, P=0.298). Propensity score-weighted multivariable analysis showed significantly higher OS (sHR: 2.31, P = 0.006) and PFS rates (sHR:1.75, P = 0.008) with Ablation compared to SBRT. Ablation was also associated with lower post-treatment hepatotoxicity compared with SBRT (5% vs. 12%, P = 0.001). Conclusions: TACE+Ablation demonstrated higher OS/PFS and lower post-treatment hepatotoxicity compared with TACE+SBRT. Local disease control up to two years was equivocal, potentially suggesting equipoise for bridge to transplant.
Impact of an inter-professional clinic on pancreatic cancer outcomes: The Princess Margaret Cancer Centre (PM) experience.
Authors: Albaba Hamzeh , Dodd Anna , Prince Rebecca M. , Aung Kyaw Lwin , Hedley David W. , Gallinger Steven , Kim John , Brierley James D. , Moura Shari , Moignard Stephanie , Fraser Adriana , Hutchinson Shawn , Espin-Garcia Osvaldo , Moulton Carolanne , Wei Alice Chia-chi , Greig Paul David , McGilvray Ian M , Dhani Neesha C. , Elimova Elena , Knox Jennifer J. 
Published: January 2019

444 Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have limited treatment options. Management of complex symptoms and psychosocial implications requires an interprofessional approach as prognosis is often measured in months. A multidisciplinary approach has been associated with improvement in clinical outcomes including survival. We aimed to evaluate the impact of an inter-professional approach for PDAC patients at the Wallace McCain Centre for Pancreatic Cancer (WMCPC) at PM on their management and clinical outcomes. Methods: We undertook retrospective review of all patients with PDAC seen at PM two years before (July ‘12 – June ‘14) and two years after (July ‘14 – June ‘16) establishment of the WMCPC. Standard therapies (surgical approach, chemotherapy, radiation therapy) were the same during both time periods. Comparison of overall survival (OS), stage at diagnosis, surgical outcomes, waiting times, and proportion seen by social worker, dietician and clinical nurse specialist (CNS) was explored with descriptive statistic and survival analysis. Results: A total of 993 patients were reviewed; 482 patients pre- and 511 patients post-WMCPC. Age (median 67 yrs), sex (54% men) and stage III/IV (52%) were similar in both groups. There was a trend to improved OS in the post-WMCPC group (9.6 vs. 10.9 m; p = 0.055); multivariable analysis found a significant improvement in OS after adjustment for performance status and stage (p = 0.023; HR 0.84, 95% CI 0.72-0.98). Rate of R0 versus R1/R2 resection for curative surgery (n = 264, 28%) was similar in both groups. Time from referral to first clinic visit significantly decreased from 13.4 to 8.8 days in the post-WMCPC group (p < 0.001) as did time from first clinic appointment to diagnostic biopsy (25.9 vs. 16.9 days, p = 0.022). Patients in the post-WMCPC were more frequently seen by a social worker, dietician or CNS (8% vs. 38%, 9% vs. 35% and 31% vs. 50% respectively, p < 0.001). Conclusions: Establishment of an interprofessional clinic for the treatment of PDAC patients at PM has streamlined diagnosis, aided symptom management and improved overall survival. This has implications for planning care delivery models and proves the value of this intervention.
Rare subtypes of pancreatic cancer: Clinical outcomes and implications for clinical trial enrollment.
Authors: David John , Tuli Richard , Nissen Nicholas , Gong Jun , Gangi Alexandra , Placencio-Hickok Veronica , Gresham Gillian , Hendifar Andrew Eugene 
Published: January 2019

445 Background: Pancreatic cancer subtypes such as adenosquamous (AS) and squamous cell carcinoma (SCC) are rare and poorly understood. Treatment recommendations are extrapolated from pancreatic adenocarcinoma (AC) and these patients are often included in AC clinical trials. Herein, we describe clinical outcomes and inclusion of these subtypes in AC clinical trials. Methods: The National Cancer Database (NCDB) was queried to identify patients with AC, AS, and SCC between 2004 and 2014. Overall survival was evaluated using Kaplan-Meier methodology and multivariable (MVA) cox regression models were fit to identify differences in survival outcomes between subtypes adjusted by baseline demographic and clinical variables. ClinicalTrials.gov was interrogated to identify inclusion of AS and/or SCC in contemporary PA clinical trials. Results: We identified 115,061 patients with pancreatic cancer. Median age was 69 (range 18 – 90) and median follow up was 54 months (95% CI 53 – 55). Age, sex, median income, education, comorbidities, race, and stage were significantly associated with overall survival (OS). OS by subtype compared to AC: AS HR of 0.98 (p = 0.59) and SCC HR 1.29 (p < 0.001). OS by subtype and stage compared to AC: stage I/II, AS HR of 0.98 (p = 0.59), SCC HR 1.44 (p = 0.001); stage III, AS HR of 1.32 (p = 0.02) and SCC HR 1.48 (p = 0.01); stage IV, AS HR of 1.1 (p = 0.06), SCC HR 1.2 (p = 0.06). Data from 283 phase II or III interventional trials completed between 2008-2018 were exported from clinicaltrials.gov. The majority of trials listed did not specify inclusion or exclusion of AS or SCC subtypes. Conclusions: This is the largest report of clinical outcomes in rare subtypes of pancreatic cancer. SCC and to a lesser extent, AS, have worse OS compared to AC. It is unclear how rare pancreatic cancer subtypes are handled in the inclusion and analysis of clinical trial data and how this may impact enrollment and survival outcomes.[Table: see text]
Small bowel adenocarcinoma: A single center experience.
Authors: Hannan Lindsay Marie , Harris William Proctor , Shankaran Veena , Coveler Andrew L. , Pritchard Colin , Zhen David Bing , Cohen Stacey , Konnick Eric Quentin , Chiorean E. Gabriela , Wong Kit Man 
Published: January 2019

449 Background: Small bowel adenocarcinoma (SBA) represents only 2% of GI malignancies. There is limited data to guide clinical decisions, largely extrapolated from colorectal cancers (CRC). We evaluated treatment strategies and outcomes in patients (pts) with early and advanced SBA. Methods: We identified 56 pts with SBA diagnosed between 1/2005 - 1/2018 and treated at our institution. Demographics, pathological features, treatments, and molecular data were abstracted via medical record review. Data was analyzed with SAS statistical software. Results: Median age was 61, 54% male, site: duodenum (D 37.5%), duodenal ampula (A 17.9%), jejunum (J 19.6%), ileum (I 12.5 %), unknown (12.5%). Predisposing conditions were: IBD (6), Lynch (2), and Peutz-Jeghers syndromes (1). Stage (stg) at diagnosis was I (5%), II (20%), III (34%) and IV (41%). Primary tumor resection occurred in 33 pts: 21 received adjuvant chemotherapy, mostly FOLFOX; 17 developed metastatic disease. Treatment for metastatic SBA (n = 40) included 5FU-based chemotherapy without or with anti-VEGF (n = 18), or anti-EGFR therapies (n = 9). Median lines of therapy was 2 (range 1-7). For pts with stg I-III SBA, median DFS/OS was 21/38 mos. For stg IV pts, OS was 19.8 mos; 18/35/8/14 mos for D, A, J and I, respectively. Molecular biomarkers with targeted (28) or next generation sequencing (10) were available for 28 metastatic SBA pts: KRAS MUT (8), TP53 MUT (5), ERBB2 MUT (2), MSI-H (2), ERBB2, CCNE1 amplification (1 each), and NRAS, BRAF, CDKN2A, ERBB3, ATM, PIK3CA MUT (1 each). OS was 20 vs 19 mos for pts with KRAS WT vs MUT stg IV SBA, respectively. Among 16 pts with KRAS WT SBA, OS for those treated (9) or not (7) with anti-EGFR antibodies was 25 mos vs 21 mos. One pt with KRAS WT, ERBB2 amplification/ERBB2 V777L activating mutation is alive 5yrs+ from stg IV diagnosis on anti-EGFR plus chemotherapy (best response was 4 mos SD with trastuzumab/pertuzumab). Conclusions: This retrospective study demonstrates heterogeneity among SBA, overall inferior outcomes compared to CRC pts, and emphasizes genomic alterations which could be exploited therapeutically. Randomized studies for KRAS WT SBA pts should test the benefit from anti-EGFR targeted therapies in this rare tumor type.
Genomic profile of gastric cancer in the United States versus East Asia.
Authors: Gilmore Gregory A. , Barakat Mohamad , Chaudhary Uzair Bashir , Gregg Jeffrey P. , Fathi Amir 
Published: January 2019

45 Background: Gastric cancer is the fourth most common cancer type and is the third leading cause of cancer deaths worldwide. Much heterogenicity exists in gastric cancer including geographic variation, with significantly higher incidence in Eastern Asia and a well-known but poorly understood relationship with Asian ethnicity. It has thus been hypothesized that differences in incidence and survival between United States and Asia may be related to a difference in the underlying tumor biology. Methods: We sought to compare the mutational frequencies by comparison of proportions of the 25 most frequent mutations between a US and Chinese population. The US population was derived from The Cancer Genome Atlas (TCGA) PanCancer Atlas comprising 440 patients and the Chinese from a University of Hong Kong Study comprising 100 patients. Results: We found there was a statistically significant difference (P ≤ 0.05) in the frequency of recurrent mutations between US and China population in 14 of the 25 most common genes mutations (table). Conclusions: This data suggests an underlying difference in the mutational profile of gastric cancers in the US as compared with Asia. These findings thus may help to describe the differences in incidence, histology, and outcomes that has been well described in the literature between these two regions of the world. [Table: see text]
Association between sarcopenia and gastric carcinogenesis: A health check-up cohort study.
Authors: Kim Young Min , Kim Jie-Hyun , Baik Su Jung , Jung Da Hyun , Park Jae Jun , Youn Young Hoon , Park Hyojin 
Published: January 2019

46 Background: Insulin resistance which is a mechanism of metabolic syndrome has been known to promote carcinogenesis of various malignancies. In addition, metabolic syndrome is associated with sarcopenia. Thus, the aim was to investigate the association between sarcopenia and gastric carcinogenesis including precancerous conditions: atrophic gastritis (AG), intestinal metaplasia (IM), and gastric adenoma. Methods: The study subjects were an adult population who underwent gastroduodenoscopy at Gangnam Severance Check-up Center. AG and IM were evaluated by endoscopic findings. Sarcopenia based on muscle mass was defined as appendicular skeletal muscle (ASM) as a percentage of body weight that was less than 1 standard deviation below the sex-specific mean for healthy adults aged 20 to 39 years (cutoff point: 29.3% in male and 26.7% in female). Obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to the Asia-Pacific criteria. Sarcopenic obesity was a condition of combined sarcopenia and obesity. The association between sarcopenia and gastric lesions was evaluated. Results: 8,356 patients were enrolled this study. Among them, 12 (0.14%) and 3,552 (42.5%) patients were diagnosed as gastric cancer and precancerous conditions, respectively. 5 (41.7%) of 12 gastric cancer patients and 594 (16.9%) of 3.552 patients with gastric precancerous conditions were diagnosed with sarcopenia. Both diabetes mellitus (DM) (OR = 5.152, P = 0.005) and sarcopenic obesity (OR = 4.139, P = 0.016) were independent predictive factors for gastric cancer. And smoking, alcohol, DM, hypertension, dyslipidemia, Helicobacter pylori, and sarcopenia were significantly associated with gastric precancerous conditions. Conclusions: Sarcopenia and sarcopenic obesity were significantly associated with gastric carcinogenesis. Thus, sarcopenia may be one of the risk factors for gastric carcinogenesis.