bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine and S-1 as first-line chemotherapy in patients with metastatic or advanced pancreatic cancer.
Authors: Fang Weijia , Zhao Peng , Zheng Yi , Jiang Weiqin 
Published: March 2017

492 Background: Gemcitabine and S-1 are both effective antitumor chemotherapeutic agents for pancreatic cancer. We evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer. Methods: Patients with previously untreated metastatic or advanced pancreatic cancer who had measurable lesion(s) were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m (2) during 30 min on days 1 and 8 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-14 followed by a drug-free interval of 1 week every 21-day cycle. Results: Twenty-five patients were enrolled between 2012 and 2014. The assessed overall response rate was 24 % partial response in 6 patients, 56 % stable disease in 14 patients, and 20 % progressive disease in 5 patients. Sixteen patients (64 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.6 months (95 % CI 4.1-6.7 months) and 10.2 months (95 % CI 6.5-14.2 months). The major hematological toxicities were included grade 3/4 leucocytopenia in 8 patients (32 %), grade 3/4 neutropenia in 13 patients (52 %), and one patients (4 %) suffered grade 1 febrile neutropenia. The common grade 3/4 non-hematological toxicity was Anorexia, rash and fatigue, held the proportion of 12%, 16% and 12%, respectively. Conclusions: Gemcitabine and S-1 (GS) combination therapy showed promising activity with acceptable toxicities as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer.
The Charlson age comorbidity index to predict prognosis in patients with resected pancreatic cancer.
Authors: Asano Tomonari , Fujii Tsutomu , Yamada Suguru , Yabusaki Norimitsu , Ninomiya Go , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: March 2017

495 Background: The Charlson age comorbidity index (CACI) is a useful measure of comorbidity to standardize the evaluation of surgical patients and has been reported to predict postoperative mortality in various cancers. Methods: A total of 379 patients who underwent R0/R1 resection for pancreatic cancer between 2003 and 2014 were enrolled in this study. According to the CACI, the age-adjusted comorbidity index was calculated by weighting individual comorbidities; CACI < 4 was considered the low-CACI group, whereas CACI ≥ 4 was considered the high-CACI group. The correlations between the CACI and clinicopathologic features and survival outcomes were statistically analyzed. Results: The patients with a high CACI were more likely to be old and had higher CA19-9 levels and lower incidences of portal vein resection and blood transfusion. The rate of patients who received chemotherapy was significantly higher in the low-CACI group than in the high-CACI group (87% vs. 69%, P< 0.0001). There was no difference in relapse-free survival (RFS) between the low- and high-CACI groups; however, the overall survival (OS) rate was significantly higher in the low-CACI group than in the high-CACI group ( P= 0.047). Multivariable analysis showed that a high CACI was a predictor of poor survival. In the high-CACI group, patients with high relative dose intensity (RDI) for postoperative adjuvant chemotherapy had significantly better RFS and OS than those with low RDI (both P< 0.0001). Conclusions: The CACI was a significant independent predictor of prognosis and compliance for postoperative adjuvant chemotherapy and could be clinically useful for decision-making in the treatment strategy for pancreatic cancer.
Gemcitabine plus nab-paclitaxel use in metastatic pancreatic cancer: A study of 40 patients.
Authors: Barrera Ivan , Filimon Sabin Dragos , Meng Jassy , Kavan Tomas , Rho Young soo , Batist Gerald , Kavan Petr 
Published: March 2017

498 Background: Metastatic pancreatic adenocarcinoma (mPDAC) carries a dismal prognosis, with often a poor response to treatment (Tx). Although gemcitabine with nab-paclitaxel (GnP) is now a standard 1st-line (1L) Tx in mPDAC, provincial policies limit its use. To understand the implications of the restriction, this real-life study was conducted. Methods: A historical prospective data was compiled using the local electronic medical record (Endovault Oncology v3.0, NY) at the Jewish General Hospital-McGill. All patients (pts) diagnosed with mPDAC that received GnP from 2013-2016 were identified. Demographics and Tx data was obtained. Primary objective was to evaluate tolerability in all lines of Tx [grade >2 CTCAE v4.03, mean Tx delay (mTxd)]. Secondary objectives were Tx attrition and outcomes [RECIST 1.1, complete response (CR), stable disease (SD) and progression disease (PD)]. Results: Of the 40 pts (female 60%, median age 64.3), 25 (62.5%) had primary at the head of the pancreas and 30 (75%) liver metastasis. 1L Tx: GnP 24 (60%), FOLFIRINOX 10 (FFX, 25%), Gemcitabine 5 (Gc, 12.5%) and FOLFOX 1 (2.5%). 70% of both FFX and Gc pts had grade 2 peripheral neuropathy (PN), neutropenia (NEUT) and fatigue. Half GnP pts had grade 2 NEUT and fatigue. mTxd in GnP, FFX and Gc were 7, 14 and 7 days. All FFX and Gc pts had PD. GnP cohort had 1 CR and 7 SD. 2L Tx was in 22 (55%): GnP 13 (59.5%), FFX 3 (13.5%), Capecitabine 2 (9%), FOLFOX 2 (9%) and Gc (9%). FFX pts 66.6% had grade 3 fatigue. GnP pts had grade 2 NEUT, PN and fatigue in 53.8%, 15.3% and 46.2%. mTxd were GnP 14 days and FFX 14 days. Except 1 SD, all FFX pts had PD. GnP pts had 1 CR, 6 SD, and 6 PD. All pts on Capecitabine, FOLFOX and Gc had PD. 3L Tx was in 6 (15%): 3 GnP (50%) and 3 on clinical trials (50%). All pts had PD and < 3 cycles. In 1L FFX pts, 7/10 and 3/6 went on to receive GnP in 2L and 3L. All 1L Gc pts had 2L GnP. Only 3 pts and 1 pt from 1L GnP pts went on to receive 2L and 3L Tx. Conclusions: Due to access limitations to GnP, its use was likely reserved for poor performance status pts. Instead, 1L FFX was used when possible. 1L FFX pts received more Tx lines due to initial pt selection. Further studies are needed in broader populations to evaluate optimal 1L Tx selection accounting for expected attrition and overall survival.
Analysis of PDL1 expression and T cells infiltration in 1014 gastric cancer patients.
Authors: Xing Xiaofang , Li Ziyu , Wang Jiping , Ji Jiafu 
Published: March 2017

50 Background: Although immune checkpoint inhibitors have demonstrated promising results in melanoma and lung cancer, their effects on gastrointestinal cancer are still under investigation. Understand the prognostic effect of PDL1 expression, infiltration by CD8+ and CD3+ T cells in gastric cancer (GC) might help the identification of candidate patient who might benefit from immunotherapy. Methods: Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens with PD-L1 antibodies. Immune cell markers CD3 and CD8 were also stained and the quantitative differences were calculated using automated image analysis. Results: 37.8% of the cases showed a membranous PD-L1 expression in tumor cells and 74.9% in tumor infiltrating immune cells. GC patients with high level PDL1 expression in tumor cells or in immune cells were both associated with better survival compared with those with negative expression (5-year OS, 61% vs. 48%, P = 0.000, and 55% vs. 45%, P < 0.0001, respectively). As continuous variables, higher CD3+ and CD8+ cell density were associated with patients’ overall survival and the associations remained as the significant prognostic factors that predict favorable outcomes even after adjusting other unknown confounding factors.(HR: 0.974, 95%CI: 0.963-0.985, P = 0.000; and HR: 0.973, 95%CI: 0.960-0.986, P = 0.000 for CD3 and CD8 respectively). We also observed the close relationship between CD3+, CD8+ cell density and PDL1 expression both in tumor cells and in infiltrating immune cells. Conclusions: This study indicates that PDL1 expression, and TILs in particular, are important prognostic biomarkers. Patients with higher CD8 and CD3 T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. The counterintuitive observation that higher PD-L1 expression associating with better patients’ outcome highlights the need to assess both PDL1 expression in all tumor compartments and the characterization of the GC immune microenvironment.
Association of specific gene expression profiles with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma.
Authors: McLaren Patrick James , Barnes Anthony P , Terrell Willy Z , Vaccaro Gina M. , Wiedrick Jack , Hunter John G. , Dolan James P. 
Published: March 2017

51 Background: Predicting prognosis in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to therapeutic response. In this study, we analyzed specific predictor genes expressed in tumor specimens from our institutional repository. Our aim was to determine if specific gene expression profiles are associated with pathologic complete response (pCR) after neoadjuvant chemo-radiotherapy (CRT). Methods: We investigated eleven genes identified from prior studies (CCL28, SPARC, S100A2, SPRR3, SIRT2, NOV, PERP, PAPSS2, DCK, DKK3, ALDH1) that have significant association with esophageal cancer progression. Patients with esophageal adenocarcinoma treated with neoadjuvant CRT followed by esophagectomy at our institution between January 2011 and July 2015 were included. Quantitative real-time polymerase chain reaction was conducted on pre-treatment biopsy specimens to determine gene expression. Patients were classified into two groups: 1) pCR and, 2) no or poor response (NR) after CRT based on final pathology report. An omnibus test using Mahalanobis distance was applied to evaluate overall genetic expression differences between groups. Log-rank tests compared the differential expression of individual genes. Results: 29 patients (11 pCR and 18 NR) were analyzed. Overall, gene expression profiles were significantly different between pCR and NR patients (p < 0.01). In particular, CCL28 was over-expressed in pCR (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3-was under-expressed in pCR patients (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031). Conclusions: Esophageal adenocarcinoma patients with a pCR after neoadjuvant therapy have genetic profiles that are significantly different from typical NR profiles. In our population, the genes CCL28 and DKK3 are potential predictors of treatment response.
Comparing mortality of colorectal cancer and gastrointestinal bleeding among patients with long-term use of low dose aspirin: A population-based study of 689,209 patients.
Authors: Sung Joseph , Tsoi Kelvin Kf 
Published: March 2017

527 Background: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well-known to protect against colorectal cancer (CRC) development but increase risk of gastrointestinal bleeding (GIB). Few large-scale studies have compared the benefit and risk of long-term aspirin usage. This cohort study aims to evaluate the use of low-dose aspirin to prevent CRC and the risk of GIB associated with the aspirin use. Methods: A population-based clinical dataset was used to compare incidence and mortality of CRC and GIB patients receiving low-dose aspirin with sex-and-age matched controls (in 1:2 ratio). Patients with aspirin≤6 months were excluded. Clinical data of 206,243 aspirin users (mean dose 80 mg/day, mean duration 7.7 years) and 482,966 non-users were included. All patients must have at least 10-year follow up on clinical outcome. Results: Among aspirin users 5,776 (2.80%) were diagnosed with CRC; 2,097 (1.02%) died of the malignancy. 16,483 (3.41%) non-users were diagnosed with CRC; 7,963 (1.65%) died of CRC. Using the cox-proportional hazard regression, aspirin usage showed a modest but significant reduction in CRC mortality (HR = 0.65; 95% CI = 0.62 to 0.69). On the other hand, 11,187 (5.42%) aspirin users developed GIB, and 841 (0.41%) died. 15,186 (3.14%) non-users developed GIB, and 1,682 patients (0.35%) died. Aspirin users showed modest but significant increased risk of GIB-related mortality (HR = 1.24; 95% CI = 1.14 to 1.35). Conclusions: The long-term use of low dose aspirin shows preventive effect on CRC, but also increases the associated GIB risk. Considerations of prophylactic use of aspirin should balance the benefit and the risk of this treatment to the target population. [Table: see text]
Impact of adjuvant chemotherapy on recurrence risk in stage II colon cancer.
Authors: Adesoye Taiwo , Hu Chung-Yuan , Cuddy Amanda , Francescatti Amanda B. , Schumacher Jessica R. , You Y. Nancy , Van Loon Katherine , Schrag Deborah , McKellar Daniel P. , Winchester David Porter , Chang George J. 
Published: March 2017

533 Background: Although clinical guidelines recommend consideration of adjuvant chemotherapy in high-risk stage II colon cancer, the impact on recurrence risk and cancer related survival is unclear. Furthermore, among Medicare patients, adjuvant chemotherapy was not associated with improved survival. We examine the effect of adjuvant chemotherapy on recurrence risk and overall survival in a diverse cohort. Methods: 6,095 patients who underwent surgery for stage II-III colon cancer (2006-2007) were randomly selected from facilities reporting to the National Cancer Data Base for additional abstraction of tumor information, 5 year recurrence and survival. Death or second cancer within 6 months were excluded. Patients were classified as high or low risk using standard pathologic factors. Multivariate Cox regression with propensity score weighting was performed to compare recurrence risk and overall survival. Results: Of 3,423 patients with stage II colon cancer, 26.9% (n = 883) received chemotherapy compared to 76.2% (n = 1,839) of stage III patients. Among stage II patients, 47.8% (n = 1,636) had at least one high risk feature and 30.8% (n = 481) of these received chemotherapy. Five year recurrence rate in stage II patients was 13% (n = 392), greater in high risk compared to non-high risk patients (13.3% vs 9.3% p < 0.0001) and 24.4% (n = 874) in stage III patients. Chemotherapy did not improve recurrence risk in stage II patients regardless of risk status (High risk: hazard ratio [HR] 1.37; 95% CI 0.96 - 1.97; Non-high risk: HR 1.39; 95% CI 0.91 - 2.11). Chemotherapy was associated with a significant improvement in recurrence risk in stage III patients (HR 0.79; 95% CI 0.63 - 0.96). However, chemotherapy was associated with improved overall survival in both high (HR 0.69; 95% CI 0.51 - 0.92) and non-high risk stage II patients (HR 0.76; 95% CI 0.55 - 1.04), and also in stage III patients (HR 0.47; 95% CI 0.41 - 0.54). Conclusions: Adjuvant chemotherapy was not associated with a lower recurrence rate among stage II colon cancer patients. The observed survival benefit associated with chemotherapy is likely attributable to non-oncologic factors such as patient selection. Decision-making regarding chemotherapy use in this cohort should be carefully approached.
The association between insurance status and survival in patients with stage III colon cancer.
Authors: Ahmed Aabra , Walters Ryan W , Tahseen Ahmed Ibrahim , Silberstein Peter T. 
Published: March 2017

535 Background: Colon cancer is the third most frequent cancer diagnosis, and primary payer status has been shown to be associated with treatment modalities and survival in cancer patients. The goal of our study was to determine between-insurance differences in survival in patients with pathologic stage III colon cancer using data from the National Cancer Data Base (NCDB). Methods: We identified 130,998 patients with pathologic stage III colon cancer in the NCDB diagnosed between 2004 and 2012. Kaplan-Meier curves and multivariable Cox regression models were estimated to determine the association between insurance status and survival. Results: Private insurance patients were 41% less likely than Medicaid patients to die, 28% less likely to die than uninsured patients, and 14% less likely to die than those with Medicare (p<0.01). Medicare patients were 18% were less likely to die compared to uninsured patients (p<0.01) and 19% less likely to die compared to Medicaid patients (p<0.01). Medicaid and noninsured patients had comparable likelihoods of dying (p=0.76). Those with no comorbidities were 36% less likely to die than those with 2+ comorbidities (p<0.01). Each additional year in age added a 3% likelihood of dying (p<0.01). Patients with chemotherapy were 57% less likely to die compared to patients not receiving chemotherapy (p<0.01). Private insurance had the greatest percentage of patients receiving chemotherapy at 82%. Conclusions: Of all variables examined, chemotherapy provided the greatest increased chance of survival. Comorbidities were also a significant contributor to survival. Private and Medicare patients were likely to survive longer than uninsured and Medicaid patients. Furthermore, having Medicaid did not provide an advantage in survival over having no insurance. [Table: see text]
Molecular characterization of squamous cell carcinoma of the anal canal (SCCA).
Authors: Weinberg Benjamin Adam , Lenz Heinz-Josef , Arguello David , El-Deiry Wafik S. , Xiu Joanne , Gatalica Zoran , Liu Zhuqing , Chen Sting , El Ghazaly Hesham , Hwang Jimmy J. , Philip Philip Agop , Shields Anthony Frank , Marshall John , Salem Mohamed E. 
Published: March 2017

538 Background: Nivolumab has shown promising results in SCCA patients. The majority of SCCA cases have been linked to prior human papillomavirus (HPV) infection. However, HPV negative tumors are frequently TP53 mutated and often resistant to therapy. Molecular characteristics of SCCA are largely undefined. Here we explored the underlying biology of SCCA and the differences between TP53-wild type ( TP53-WT) and TP53-mutated ( TP53-MT) tumors. Methods: SCCA specimens underwent multiplatform testing with protein expression (IHC), gene amplification (ISH), and sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses. Results: In total, 253 tumors were studied. The most frequently mutated genes included PIK3CA (24%), BRCA2 (14%), FBXW7 (12.4%), TP53 (9.7%), and PTEN (8.9%). In a subset of 23 tumors subjected to Illumina NextSeq (592 gene) testing, the most common mutations were NOTCH2 (30%), NOTCH1 (27.3%), POLE (21.7%) , TSC2 (17.4%), PTEN (14.3%), BRAF (13.6%), BRCA2 (13.0%), PIK3CA (13.0%), and FBXW7 (9.5%). Tumors frequently expressed MRP1 (97.6%), EGFR (92.7%), TOP2A (88.5%), TOPO1 (69.5%), MGMT (67.8%), and RRM1 (59.9%). Expression of PD-1 was seen in 55.8% (24/43) of tumors, and PD-L1 in 15.4% (9/34). HER2 was amplified in 2% (3/147) of samples, which has not been previously described in SCCA. When compared with TP53-WT (n = 93) tumors, T P53-MT (n = 10) had higher rates of BRAF (22% vs. 1%, p < 0.001) and RB1 mutations (44% vs. 0%, p < 0.001), whereas TP53-WT had higher expression of TOPO1 (76% vs. 40%, p = 0.01) and TUBB3 (19% vs. 50%, p = 0.02). There were no differences between the two groups in the frequency of PD-1 or PD-L1 expression. Mean TMB was 8.6 mutations/megabase and, using a TMB cut-off > 17 mutations/megabase to define high vs. low TMB, 6.7% of tumors were TMB-High. High TMB did not correlate with PD-1 (p = 0.50) or PD-L1 status (p = 0.52). Conclusions: Molecular profiling differences between TP53-MT and TP53-WT SCCA indicate different carcinogenic pathways and biology, which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.
Direct access screening colonoscopy as a safe and effective approach to increasing colorectal cancer screening.
Authors: Estrada Joaquin J , Bedon Ana M , Kaminski Jan P , Rodriguez Gabriel , Ali Mahmoud , Albert Andrew 
Published: March 2017

540 Background: This year 135,000 patients will be diagnosed with colorectal cancer (CRC) and it is the second leading cause of cancer deaths in the US. CRC is largely preventable when screening is conducted. Nearly 60% of patients over 50 report never receiving any form of CRC screening. Colonoscopy remains the gold standard for CRC screening. Unfortunately, several barriers exist to obtaining this life-saving screening option (i.e. access to gastroenterologists, patient anxiety and lack of knowledge about the procedure). Our Direct Access Screening Colonoscopy program (DASC) has provided a successful solution to address many of these deterrents. Methods: In July 2015, the DASC program was launched at Advocate Illinois Masonic Medical Center. A nurse navigator telephonically completes health questionnaires and if patients were determined to be without significant comorbidities, they would be enrolled in the program. Prior to the procedure, the nurse would address all questions, instructions and bowel preparations. Patients that were not eligible for the program were navigated to a gastroenterologist for a formal evaluation. A retrospective review of all patients that underwent screening colonoscopy from July 2015 to July 2016 was conducted. Data collected included patient demographics, quality of preparation, Adenoma Detection Rate (ADR), patient satisfaction, and complications. Results: A total of 644 patients were referred for DASC. 373 patients (58%) were eligible for inclusion within the program. At the time of submission, 289 completed their colonoscopy. 201 patients (70%) had a normal colonoscopy. 88 patients were found to have at least one adenoma (ADR- 30%). No patients experienced any complications following DASC. Patient satisfaction scores were significantly higher for those who underwent DASC. The overall screening rate nearly doubled after implementation of the DASC program (30% vs 59%). Conclusions: Direct Access Screening Colonoscopy is a novel method to that increased the overall screening rate for CRC by almost 100%. It is a safe and effective alternative to the conventional process of obtaining a colonoscopy and can positively impact patient satisfaction and outcomes.