bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of resected duodenal and ampullary adenocarcinoma.
Authors: Crown Angelena , Edwards Alicia M , Rocha Flavio G. , Picozzi Vincent J. , Helton Scott , Biehl Thomas R , Alseidi Adnan , Lin Bruce S. 
Published: February 2017

362 Background: Duodenal and ampullary adenocarcinomas are rare gastrointestinal cancers that share similar anatomic location and treatment strategy. We report a single-institution experience regarding the association between clinicopathologic features, treatment, and survival outcomes. Methods: A retrospective review of all patients resected with curative intent for duodenal adenocarcinoma (DUO) between 2005-2015 and ampullary adenocarcinoma (AMP) between 2011-2015 at VMMC was performed. For AMP, histologic subtyping into intestinal (IT) and pancreatobiliary (PB) phenotypes was determined. Demographic and clinicopathologic parameters were compared between DUO and AMP patients using Chi-square test. Overall survival was calculated using Kaplan-Meier analysis and prognostic factors were identified by univariate Cox regression. Results: Patients with DUO (n = 44) presented at higher T-stage (p = 0.002) and with larger tumors (4.35cm vs 2.33cm, p < 0.001) than AMP patients (n = 46). DUO patients had a higher rate of surgical complications (68% vs 41%, p = 0.01) with a trend for more pancreatic fistulas (36% vs 20%, p = 0.08). There was no difference in median overall survival between groups. Factors positively influencing survival included Caucasian race (p = 0.02) and normal CA19-9 level at diagnosis (p = 0.01). Tumor factors negatively influencing survival included positive lymph nodes (p = 0.04), lymphovascular invasion (p = 0.001), and perineural invasion (p = 0.02). Within AMP, the PB subtype presented at higher T-stage (p = 0.01) and with more positive lymph nodes (p = 0.03) than IT. There was no difference in survival between subtypes. Majority received adjuvant chemotherapy (88.8% in AMP, 76.3% in DUO), fewer received adjuvant radiotherapy (23.3% in AMP, 30% in DUO), but no survival difference was seen. Conclusions: DUO presents with larger tumors and higher T-stage than AMP and is associated with more surgical complications. The PB phenotype has more advanced pathologic features than IT. No survival difference was seen between anatomic locations or subtypes. Better surgical and chemotherapeutic strategies may be needed to overcome high risk features. Longer follow-up with more patients is needed to confirm these findings.
Survival impact of neoadjuvant therapy in resected pancreatic cancer.
Authors: Mirkin Katelin Anne , Hollenbeak Christopher S , Wong Joyce 
Published: February 2017

367 Background: Pancreatic cancer carries a dismal prognosis, with surgical resection and adjuvant therapy offering the only hope for long-term survival. In recent years, neoadjuvant therapy (NAT) has been employed to optimize outcomes. This study evaluates the impact of NAT on survival in patients with resected stage I-III pancreatic cancer. Methods: The National Cancer Data Base (2003-2011) was analyzed for patients with clinical stage I-III resected carcinoma of the pancreas who underwent NAT or surgery first +/- adjuvant therapy. Univariate statistics were used to compare characteristics between groups. Analysis of variance and Kaplan Meier analyses were used to compare median survival for each clinical stage of disease. Multivariate analyses were performed using a Cox proportional hazards model. Results: 16,122 patients who underwent NAT and 16,869 patients who underwent surgery-first were included. Patients who underwent NAT tended to be younger, covered by private insurance, have a higher median income, greater comorbidities, higher clinical stage disease, and undergo a whipple. Additionally, NAT patients had a greater number of positive regional lymph nodes (9 vs. 6, respectively), although a similar number of nodes retrieved, and higher pathological stage disease. In patients with clinical stage I disease, adjuvant therapy was associated with improved median survival than NAT and surgery-alone (24.8, 18.5, 17.9 months, p < 0.0001, respectively). However, in stage II, adjuvant and NAT offered similar median survival, which was improved over surgery-alone (20.5, 20.1, and 12.4 months, p < 0.0001, respectively). In stage III, NAT had improved median survival than the other groups (19.6, 14.2, 8.6 months, p < 0.0001, respectively). In the multivariate survival analysis, patients who received NAT had a 22% lower hazard of mortality up to 5 years as compared to adjuvant therapy (p < 0.0001). Conclusions: Neoadjuvant therapy in advanced stage pancreatic cancer confers a survival benefit and may allow more patients to undergo surgery; NAT appears to offer similar survival as adjuvant therapy in early stage pancreatic cancer.
Systemic therapy in elderly patients with advanced biliary tract cancer: Sub-analysis of ABC-02 and 10 other prospective studies.
Authors: McNamara Mairead G , Bridgewater John A. , Lopes Andre , Wasan Harpreet , Malka David , Jensen Henrik R , Okusaka Takuji , Knox Jennifer J. , Wagner Anna Dorothea , Cunningham David , Shannon Jenny , Goldstein David , Moehler Markus H. , Bekaii-Saab Tanios S. , Valle Juan W. 
Published: February 2017

382 Background: Outcomes in elderly patients (pts), with advanced biliary tract cancer (ABTC) receiving palliative chemotherapy are unclear. The aim of this study was to assess the outcome of monotherapy vs combination therapy in elderly pts with ABTC in ABC-02, and 10 other prospective studies of systemic therapy. Methods: Multivariable analysis was employed to explore impact of therapy on progression-free (PFS) and overall survival (OS) in 2 age cohorts; non-elderly ( < 70 yrs) vs elderly ( ≥ 70 yrs). Results: Overall, 1163 pts were recruited from Jan 97-Dec 13. Median age of entire cohort was 63 yrs (range 23-85); 260 (22%) were ≥ 70 yrs, 18 (2%) were ≥ 80 yrs. In pts ≥ 70 yrs; 208 had ECOG PS 0-1, 129; male and 174; metastatic disease. Combination therapy was platinum-based in 9 studies. Among the 260 pts ≥ 70 yrs, 182 (70%) received combination therapy. Baseline characteristics/therapy received was balanced in both age cohorts. Median follow-up time for all pts was 42 months (95% CI 37-51). Median PFS for those < 70 yrs and ≥ 70 yrs was 6.0 (95% CI 5.5-6.4) and 5.0 months (95% CI 4.2-6.4) respectively. Median OS for pts < 70 yrs and ≥ 70 yrs was 10.2 (95% CI 9.6-11.1) and 8.8 months (95% CI 7.9-9.6) respectively. For the entire cohort, the PFS and OS were significantly better in those pts receiving combination therapy: HR 0.66, 95% CI 0.58-0.76, P < 0.0001 and HR 0.72, 95% CI 0.63-0.82, P < 0.0001 respectively, and in group ≥ 70 yrs: HR 0.54 (95% CI 0.38-0.77, P = 0.001) and HR 0.6 (95% CI 0.43-0.85, P = 0.004) respectively. In pts < 70 yrs, stage (locally advanced vs metastatic) and ECOG PS were prognostic for PFS (P < 0.001 and P = 0.04 respectively) and OS (P < 0.001 and P = 0.001 respectively) and in pts ≥ 70 yrs, they were prognostic for OS (P = 0.03 and P = 0.02 respectively). There was no evidence of interaction between age ( < 70 yrs and ≥ 70 yrs) and treatment (monotherapy and combination therapy) for PFS (P = 0.66) or OS (P = 0.75). Conclusions: In ABTC, PFS and OS in elderly pts receiving palliative chemotherapy (monotherapy or combination therapy) are comparable with that of non-elderly pts, therefore age in isolation should not influence treatment decisions. Clinical trial participation among elderly pts with ABTC is appropriate.
FOLFIRINOX and gemcitabine/nab-paclitaxel efficacy in the treatment of locally advanced unresectable pancreatic adenocarcinoma.
Authors: Bednar Filip , Ocuin Lee Mayer , Steve Jennifer , Zenati Mazen S , Winters Sharon , Hogg Melissa Ellen , Bahary Nathan , Zeh Herbert J. , Zureikat Amer H. 
Published: February 2017

399 Background: Locally advanced (LA) unresectable pancreatic adenocarcinoma (PDA) historically portends a poor prognosis with a median OS of 9-11 months. Recently, two multi-drug regimens – FOLFIRINOX and gemcitabine/nab-paclitaxel – have proven effective in the metastatic setting. We hypothesized that use of these regimens in the LA setting may improve survival. Methods: A retrospective review of a single institution’s cancer registry of all consecutive LA (unresectable) PDA patients between 2010 and 2014 was performed. LA status was verified by review of the triphasic, pancreas protocol CT scan at diagnosis using the 2015 NCCN criteria for resectability. Patients were divided into 4 groups: Group 1 = no therapy, Group 2 = “old” gemcitabine or 5-FU-based chemotherapy (CTX), Group 3 = “new” CTX (FOLFIRINOX and/or Gem/nab-paclitaxel), and Group 4 = resection after downstaging. Demographic, tumor related variables, and treatment outcomes were analyzed. Results: LA disease was verified in 107 consecutive patients. Median age was 69 years (range 36-92) and 50.5% were male. Median follow-up was 13.2 months (range 0.6-60.4). Median OS for Groups 1 (n=15), 2 (n=24), 3 (n=49), 4 (n=19) was 1.4, 11, 17.3, and 32 months respectively (p<0.001). On Cox multivariate regression (adjusted for age, sex, anatomic variables, and CA19-9 level at diagnosis), radiation (HR 0.44, p=0.003), older CTX (HR 0.16, p=0.007), newer CTX (HR 0.10, p=0.001), use of 2 or more lines of CTX (HR 0.16, p=0.022), CA19-9 decrease by >50% with any line of therapy (HR 0.31, p<0.001), and surgery (HR 0.28, p=0.002) were all significant predictors of OS in this cohort. On multivariate analysis between groups 2 and 3, newer CTX compared to older CTX (HR 0.490, p=0.02) and radiation (HR 0.510, p=0.015) provided an OS benefit. Conclusions: Compared to older CTX regimens, FOLFIRINOX and Gemcitabine/nab-paclitaxel improve survival in verified LA PDA patients. For the subset that ultimately undergoes resection, survival outcomes rival those of historically published resectable cohorts.
Multicenter double-blind randomized phase II: FOLFOX + ziv-aflibercept/placebo for patients (pts) with chemo-naive metastatic esophagogastric adenocarcinoma (MEGA).
Authors: Enzinger Peter C. , McCleary Nadine Jackson , Zheng Hui , Abrams Thomas Adam , Yurgelun Matthew B. , Azzoli Christopher G. , Cleary James M. , Rubinson Douglas Adam , Brooks Gabriel , Chan Jennifer A. , Goyal Lipika , Meyerhardt Jeffrey A. , Ng Kimmie , Schrag Deborah , Savarese Diane M. F. , Graham Christopher , Carey Margaret M. , Fuchs Charles S. 
Published: February 2017

4 Background: FOLFOX has RR 53% and PFS 6.8 months in MEGA (CALGB 80403). VEGF inhibition has improved survival in some but not all randomized trials in MEGA. Ziv-aflibercept binds VEGF-A, B and PlGF and has improved survival in refractory metastatic colorectal cancer. Methods: All pts received mFOLFOX6 q14d. Pts were randomized 2:1 to A) ziv-aflibercept 4mg/kg/d1 or B) placebo. Pts were restaged every 8wks. Primary endpoint: 6mos PFS. Results: 64 pts enrolled (Jan 2013-Apr 2015): sex: 55M/9F; age (median): 32-83 (62); ECOG PS 0/1/2: 33/28/3; primary tumor: esophagus 26/GEJ 18/gastric 20; measurable/evaluable: 52/12; metastases: LN 48/liver 25/lung 15, other 12/adrenal 4/bone 3. Of 64 pts: 34 POD, 9 off for tox, 4 died on tx, 3 withdrew, 4 other, 10 on tx (see Table). Conclusion: Ziv-aflibercept did not significantly improve the efficacy of FOLFOX. HTN was predictive of response to ziv-aflibercept. Except for HTN, there was no significant difference in toxicity between tx arms. Clinical trial information: NCT01747551. [Table: see text]
Neoadjuvant chemotherapy for gall bladder cancer: Does it increase resectability?
Authors: Raj Dheeraj , Singh Shivendera , Gupta Nikhil , Rathi Sudheer 
Published: February 2017

406 Background: Surgery is the treatment of choice for patients with carcinoma gall bladder patients (GBC). However, most of the patients are metastatic at the time of diagnosis with only a fraction of patients deemed non metastatic. Many are locally advanced either infilterating liver, orinvolving adjacent other organs. Studies with gemcitabine for metastatic biliary tract cancers have shown promising results. Extrapolating these results to locally advanced GBC might improve the outcomes in these otherwise poor risk patients. Methods: Patients with locally advanced GBC from January 2013 to June 2014 who were considered borderline resectable on cross sectional imaging were planned for preoperative gemcitabine based chemotherapy to downsize the tumor and make them resectable. Gemcitabine and cisplatin based chemotherapy was given to all these patients and evaluated after 3 cycles. Those who became resectable were taken up for surgery and rest were given additional three cycles of chemotherapy. Results: 840 patients of GBC were seen in the out patient department since January 2013. Of these, 40 patients with locally advanced GBC were considered for neoadjuvant chemotherapy (Gemcitabine and cisplatin). However, only 22 patients actually received neoadjuvant chemotherapy. Out of these 22 patients, 4 are still receiving chemotherapy. Of 18 patients who completed there chemotherapy schedule, 2 patients lost to follow up after receiving 3 cycles of chemotherapy. 15 patients (83.3%%) had good radiological response to chemotherapy and were advised surgery. One patient had no radiological response. 3 patients refused surgery inspite of good radiological response. 13 patients (including the patient who did not have radiological response) underwent surgery. Out of 13 patients, 4 patients had metastatic disease intraoperatively. 9 out of 16 patients (56.25%) underwent R0 resection. Conclusions: Best surgical outcomes are seen with those undergoing RO resection. Neoadjuvant chemotherapy can downsize the tumor in approximately 50% of the patients leading to R0 resection. Neoadjuvant chemotherapy should be considered in locally advanced GBC with the aim of increasing the resectablility in these patients.
Prognostic effect of angiotensin-converting-enzyme inhibitors (ACEI) and diuretics in patients with pancreatic cancer.
Authors: Al-Shamsi Humaid Obaid , Shalaby Akram , Dar Aneeqa Yousaf , Hassan Manal , Wolff Robert A. , Li Donghui 
Published: February 2017

420 Background: Prior history of chronic medical conditions and medical treatment exposure has been significantly associated with the development and prognosis of different cancers. Population-based studies reported a reduced cancer-related mortality among patients with pancreatic cancer who were Statin or Metformin users as compared with non-users. We aimed to study the effect of antihypertensive medications on the survival outcome of pancreatic cancer. Methods: Under institutional ethical approval, medical records were reviewed and clinical characteristics at baseline (time of diagnosis) were retrieved. Blood pressure and antihypertensive medications use were documented including Angiotensin Converting Enzyme Inhibitor (ACEI), diuretics, Angiotensin Receptor Blockers (ARBs) and Beta-Blockers (BB). Hazard ratios (HRs) and 95% CIs were calculated by using Cox proportional hazard models with a backward stepwise selection procedure to identify independent prognostic factors for overall survival. Results: A total of 1,204 patients with adenocarcinoma of the pancreas were diagnosed at MD Anderson Cancer center between 1999 and 2009 were identified. The mean age value (± SD) is 61.9± 10 where 58.6% (N=705) were men and 87.5% (N=1,054) were white. The majority of patients were Caucasian (87%). 41.9% had metastatic disease. A total of 639 (53%) patients had chemotherapy with or without radiation. ACEI and diuretics use independently reduced all-cause mortality, ACEI by 24% with HR 0.76 (CI 0.63-0.91), and diuretics by 26% with HR 0.73 (CI 0.60- 0.89). Neither ARBs nor beta blockers use was statistically significant in reducing all-cause mortality (HR.80, CI 0.63 -1.0), BB HR 0.85 (CI 0.7-1.0). Conclusions: Our findings indicate a significant impact of anti-hypertensive medications including ACEI and diuretics on pancreatic cancer outcomes with improved survival in users versus non-users, this effect was independent of the cancer treatment received, tumour histology and site of metastasis. The potential antitumor activities of these agents in pancreatic cancer should be studied further.
Association of the immune checkpoint molecule expression with neutrophil-lymphocyte ratio in patients with gastric cancer: A retrospective study.
Authors: Tanaka Hiroaki , Tamura Tatsuro , Kimura Kenjiro , Sakurai Katsunobu , Toyokawa Takahiro , Amano Ryosuke , Kubo Naoshi , Muguruma Kazuya , Ohira Masaichi , Hirakawa Kosei 
Published: February 2017

48 Background: Programmed cell death (PD) -1, one of immune checkpoint molecules, expresses on T cells and induces immune tolerances in tumor microenvironment by binding to the ligand PDL-1 on the cancer cells. The clinical effect of immune checkpoint inhibitors such as anti-PD-1/PDL-1 antibody was demonstrated in various cancer including malignant melanoma, lung cancer and gastric cancer. The development of biomarkers for case selection that these inhibitors are effective will be in urgent need. We previously showed that neutrophil-lymphocyte ratio (NLR), a marker for general immune response, was related with postoperative recurrence and advanced stage of gastric cancer. In this study, we report the association of pretreatment NLR with PD-1/PDL-1 expression in the primary tumor of gastric cancer. Methods: Using immunohistochemistry, we retrospectively examined the expression of PDL-1 and infiltration of PD-1+ cells in primary tumor from 180 patients who had undergone surgery for gastric cancer between 2007 and 2010 at the Department of Surgical Oncology of Osaka City University. Results: Positive expression of PDL-1 was observed in 78 (43%) patients. PDL-1 expression was correlated with tumor infiltrated PD-1+ cells and related poor prognosis of the patients with Stage II/III. NLR was correlated with pathological stage and lymph node metastasis. In the positive PDL-1 group, NLR was significantly increased compared with negative group. However, the number of infiltrated PD-1+ cells was not correlated with NLR. Conclusions: PDL-1 expression in gastric cancer tissues was associated with pretreatment NLR, indicating that local immune suppression could be reflected in the systemic immune responses. Our data also suggested that NLR might be one of surrogate marker for PD-1/PDL-1 blockade therapy for gastric cancer.
Neoadjuvant chemoradiation for fixed cT3 or cT4 rectal cancer: Results of a Polish II multicentre phase III study.
Authors: Bujko Krzysztof ,   on behalf of the Polish Colorectal Study Group
Published: February 2017

489 Background: The study tested whether preoperative 5x5 Gy and consolidation chemotherapy is more locally efficacious than standard preoperative chemoradiation in “unresectable” cancer (ClinicalTrials.gov NCT00833131). Methods: Patients with fixed cT3 or cT4 rectal cancer without distant metastases were randomized either to 5x5 Gy and 3 courses of FOLFOX4 after one week rest (experimental group) or to 50.4 Gy delivered in 28 fractions given simultaneously with a 5-Fu bolus, leucovorin and oxaliplatin (control group). For the second study part, oxaliplatin was delivered to the two groups at the discretion of the participating centre. Both groups underwent surgery about 12 weeks after starting radiation and about 6 weeks after neoadjuvant treatment. Results: 515 patients were eligible for analysis; 261 in the experimental group and 254 in the control group. Acute toxicity of neoadjuvant treatment was recorded in 74% of patients in the experimental group and in 83% in the control group, p = 0.007; the rate of patients with grade 3+ toxicity was identical in the two groups - 24%. R0 resection rates (primary endpoint) and pathological complete response rates were respectively in the experimental group and in the control group 77% vs. 71% (p = 0.081) and 16% vs. 11.5% (p = 0.19). Median follow-up was 35 months. At 3 years, rates of overall survival, disease-free survival and cumulative incidence of local failure were respectively in the experimental group and in the control 73% vs. 64.5%, p = 0.055; 53% vs. 52%, p = 0.74 and 22% vs. 21%, p = 0.82. Conclusions: The trial showed no difference in local efficacy between preoperative 5x5 Gy with consolidation chemotherapy and standard preoperative chemoradiation. The trend towards improved overall survival, lower toxicity, lower cost and convenience favors 5x5 Gy with consolidation chemotherapy. Clinical trial information: NCT00833131.
Overall response rate (ORR) in STEAM, a randomized, open-label, phase 2 trial of sequential and concurrent FOLFOXIRI-bevacizumab (BEV) vs FOLFOX-BEV for the first-line (1L) treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Bendell Johanna C. , Tan Benjamin R. , Reeves James Andrew , Xiong Henry , Somer Bradley G. , Lenz Heinz-Josef , Hochster Howard S. , Scappaticci Frank , Sommer Nicolas , Day Bann-mo , Hurwitz Herbert 
Published: February 2017

492 Background: 3-drug chemotherapy (CT) + BEV (cFOLFOXIRI-BEV) significantly improved efficacy vs FOLFIRI-BEV for 1L mCRC tx, but safety and the impact of subsequent fluoropyrimidine-BEV maintenance tx require further definition. The phase 2 STEAM (NCT01765582) trial assessed efficacy of 1L cFOLFOXIRI-BEV vs FOLFOX-BEV and safety of alternating 2-drug CT (FOLFOX and FOLFIRI) + BEV tx monthly in a sequential sFOLFOXIRI-BEV regimen. Methods: Pts with unresectable, previously untreated mCRC were randomized 1:1:1 to BEV-containing (5 mg/kg) arms (cFOLFOXIRI, sFOLFOXIRI [alternating FOLFOX and FOLFIRI every 4 weeks {q4w}], or FOLFOX q3w) in a 4–6 month induction phase, followed by BEV-containing maintenance tx. Stratification factors included extent of metastatic disease and tumor location. Primary objectives: 1L ORR, 1L progression-free survival (PFS), safety. Secondary objectives: resection and conversion to resectable disease rates, time to 2L PFS, overall survival. ORR was tested with a 1-sided alpha of 5%; tx arms were compared with a stratified 1-sided Cochran-Mantel-Haenszel test. PFS was analyzed descriptively. Results:Among 280 enrolled pts (median age, 57.5 yrs), 186 remainined in the study on July 1, 2015. Efficacy and safety are shown (see Table). Conclusion: While not statistically significant, there was a trend of increased ORR with cFOLFOXIRI-BEV vs FOLFOX-BEV in 1L mCRC tx. Analysis of PFS is ongoing. All 3 regimens were well tolerated. Clinical trial information: NCT01765582. [Table: see text]