bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot trial of CRLX101 in patients (pts) with advanced, chemotherapy-refractory gastroesophageal cancer (GEC).
Authors: Chao Joseph , Lin James , Frankel Paul Henry , Clark Andrew J. , Wiley Devin T. , Garmey Edward Graeme , Fakih Marwan , Lim Dean , Chung Vincent M. , Luevanos Eloise , Eliasof Scott , Davis Mark E. , Yen Yun 
Published: February 2017

44 Background: Camptothecin (CPT) derivatives such as irinotecan have activity in 2nd-line therapy in advanced GEC with reported response rates of 0-15%. CRLX101 is an investigational nanoparticle-drug conjugate (NDC) with a CPT payload. Preclinical evidence indicates preferential uptake in tumors, and animal GEC xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in patients with chemotherapy-refractory GEC. Data demonstrating preferential tumor uptake of CRLX101 has been presented separately and here we report on the clinical outcomes of patients enrolled. Methods: All pts initiated CRLX101 dosed intravenously at RP2D (15 mg/m2) on days 1 and 15 of a 28-day cycle until disease progression or intolerant toxicity. While detection of preferential CRLX101 tumor uptake was the primary endpoint, with 10 pts enrolled a secondary analysis could be performed with the study having 90% power to detect ≥ 1 responder if the true response rate is ≥ 21%. Responses were assessed using RECIST 1.1. Results: Between Dec. 2012 and Dec. 2014, 10 patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) GEC and adenocarcinoma histology were enrolled and evaluable for response and toxicity. The median time-to-progression was 1.9 mo (range 0.6-8.7 mo). Best response was seen in 1 pt with stable disease (SD) for 8 cycles. Only ≥ grade 3 toxicities related to CRLX101 occurred in a single patient with grade 3 anemia and chest pain who was able to resume therapy without any further toxicity after CRLX101 was reduced to 12 mg/m2. Conclusions: CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in advanced GEC should focus on combination strategies. Its favorable toxicity profile and evidence of preferential tumor uptake support further clinical research of combining CRLX101 with other targeted therapies such as anti-angiogenesis (ramucirumab) and/or immune checkpoint inhibitors. Clinical trial information: NCT01612546 Clinical trial information: NCT01612546.
Variations in the perioperative management of pancreatoduodenectomy between academic and community institutions: An IHPBA/AHPBA web-based survey.
Authors: Anantha Sandeep , Macedo Fransisco Igor , Race Alice J , Singh Awinderpreet , Mittal Vijay K , Parikh Janak A , Jacobs Michael J 
Published: February 2017

448 Background: Pancreatoduodenectomy is the surgical treatment for pancreatic head and periampullary malignancy and is performed by surgeons practicing in all kinds of hospital settings, academic, community and hybrid. The perioperative management is varied amongst surgeons owing to diverse training experience. We aim to evaluate these variations by comparing the hospital settings. Methods: A pilot 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members between May and August 2015 regarding practice patterns and perioperative care of pancreatoduodenectomy. Results: We received 285 responses with participants from academic (56.1%), community (12.6%) or hybrid institutions (31.2%). Most participants performed 10-25 cases annually in each group (46.9%, 50%, 51.7%, respectively). Surgeons from academic institutions routinely culture bile intraoperatively more often than in community institutions (46.3% vs. 22.2%, p<0.01). However, surgeons from community programs tend to continue prophylactic antibiotics beyond 24 hours (30.6% vs. 44.4%, p<0.01) and are more likely to use antibiotic abdominal irrigation (2.5% vs. 11.1%, p<0.01) as compared to those from academic institution. Routine postoperative culture and measurement of amylase rich drain fluid, types of drains (self-suction or gravity), length of postoperative antibiotic regimen, type of skin closure and wound care were statistically similar Conclusions: Our survey included a wide range of members from academic, community and hybrid centers. Practice patterns vary significantly among surgeons practicing in academic, community or hybrid institutions and are not standardized. Further studies are warranted to elucidate the impact of these variations on surgical outcomes of patients undergoing pancreatoduodenectomy.
Characterizing tumor responses from RAINBOW, a randomized phase III trial of ramucirumab (RAM) plus paclitaxel (PAC) vs placebo (PBO) plus PAC in patients (pts) with previously treated advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Bodoky Gyorgy , Gil-Delgado Marian , Cascinu Stefano , Lipatov Oleg N. , Cunningham David , Van Cutsem Eric , Muro Kei , Chandrawansa Kumari , Liepa Astra M. , Carlesi Roberto , Ohtsu Atsushi , Wilke Hansjochen 
Published: February 2017

45 Background: In RAINBOW, OS and PFS were improved for pts with previously treated gastric/GEJ adenocarcinoma in the RAM + PAC arm. Objective response rate was also significantly improved: 28% (92/330) RAM + PAC vs 16% (54/335) PBO + PAC (P =.0001). Timing and duration of responses and quality of life (QoL) are described. Methods: Patients were randomized 1:1 to RAM 8 mg/kg or PBO on days 1 and 15 + PAC 80 mg/m2 on days 1, 8, and 15 (28-day cycle). Radiographic assessment of disease per RECIST v1.1 and assessment of QoL with the EORTC QLQ-C30 were done at baseline and 6-wk intervals following the first dose of study therapy. Time to response (TTR) was the time from randomization to first tumor response (complete or partial). Duration of response (DoR) was the time from first tumor response to disease progression. A swimmer plot of DoR, survival, and status at study end was developed. Time-to-event curves were generated using the Kaplan-Meier method. Hazard ratio (HR) for DoR was generated from a stratified Cox model. QoL scores were classified as improved or worsened if change from baseline was ≥ 10 points (100-point scale), otherwise considered stable. Results: Median TTR was 6.7 wks (range 4.3-33.3) for RAM + PAC pts and 6.6 wks (5.1-37.1) for PBO + PAC pts. A detailed swimmer plot confirms a majority of RAM + PAC pts (58% [53/92]) and PBO + PAC pts (61% [33/54]) responded by the first 6-wk assessment. Of these responders, 11% (6/53) and 6% (2/33) were still responding at 12 mos. Median DoR was 4.4 mos (95% CI 4.1, 5.5) in the RAM + PAC arm and 2.8 mos (95% CI 2.1, 4.2) in the PBO + PAC arm (HR = 0.66, 95% CI 0.45, 0.97; P =.0332). At 6 wks, rates of improved/stable QoL scores among responders were similar between treatment arms and higher among the responders (73% RAM + PAC vs 74% PBO + PAC) than in the intent-to-treat population (53% vs 50%). Conclusions: Patients with advanced gastric/GEJ cancer not only showed an improved response rate with RAM + PAC, but responses were also more durable. For the majority of pts, response occurred within the first 6 wks of therapy and was associated with QoL benefit. Clinical trial information: NCT01170663.
Predictors and survival for pathologic tumor response grade (TRG) in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy (SBRT).
Authors: Mellon Eric Albert , Hoffe Sarah E. , Frakes Jessica M. , Strom Tobin Joel Crill , Springett Gregory M. , Shridhar Ravi , Centeno Barbara , Malafa Mokenge Peter , Hodul Pamela Joy 
Published: February 2017

453 Background: Neoadjuvant therapy response correlates with survival in several gastrointestinal malignancies. Thus, we intensified our neoadjuvant approach to pancreas adenocarcinoma in part to induce greater response. Here we analyzed whether pre- and post- therapy CA19-9 or SUVmax correlated with College of American Pathology TRG at pancreatectomy and whether TRG associated with survival. Methods: After IRB approval, we identified BRPC and LAPC patients treated in our standardized pathway who underwent surgical resection with reported TRG (n = 81, median follow-up 30.8 months). Patients had baseline CA19-9, CT, endoscopic ultrasound, and FDG PET/CT then underwent multi-agent chemotherapy (79% with planned 3 cycles of GTX) followed by 5 fraction SBRT. They then underwent restaging CT, PET/CT, and CA19-9 prior to resection. Overall (OS) and progression free survival (PFS) were estimated and compared by Kaplan-Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, re-staging, and change in CA19-9 (16% with missing values or CA19-9 < 5 excluded) and SUVmax (14% with missing values or no hypermetabolism excluded). Results: Decrease in CA19-9 before and after neoadjuvant therapy correlated with improved TRG (p = 0.02) as did re-staging SUVmax (p < 0.01), though not decrease in SUVmax (p = 0.08). The TRG groupings had similar OS and PFS except the TRG 0 (complete response) group. Compared to TRG 1-3 patients (median OS 38.4 months, median PFS 17.8 months), the 6 patients with TRG 0 had no deaths (p = 0.05) and only 1 failure (p = 0.03). A group of 10 TRG 1 patients with only isolated tumor cells remaining had similar outcomes to the other TRG 1-3 patients. Conclusions: Pre-operative PET-CT and CA19-9 response correlate with neoadjuvant therapy response by TRG. Patients with complete pathologic response have superior outcomes. This provides rationale for further intensification of neoadjuvant therapy in BRPC and LAPC. Further work seeks to identify techniques to better select which BRPC and LAPC patients should undergo tumor resection.
Conditional probability of survival in gallbladder carcinoma as a prognostic tool for long term survivors.
Authors: Rajeev Rahul , Berger Nicholas Gerard , Hammad Abdulrahman Y , Miura John Thomas , Johnston Fabian McCartney , Gamblin T. Clark , Turaga Kiran 
Published: February 2017

455 Background: Gallbladder carcinoma (GBC) often presents in an advanced stage and despite radical resection and nodal harvest, prognosis remains poor. Conventional survival statistics do not account for time elapsed from diagnosis and may not carry relevant prognostic information for long term survivors. This study sought to estimate the conditional probability of survival (CS) in patients of GBC. Methods: Patients with GBC were identified from the Surveillance, Epidemiology and End Results (SEER) database (1988-2012). Overall probability of survival (OS) was estimated using Kaplan-Meier method. Cumulative incidence method was employed to calculate CS. Results: Of 15,046 GBC patients identified, Stage IV disease was the most common presentation (n = 5625). Surgical intervention was reported in 9,720(65%) patients with cholecystectomies (n = 8254) outnumbering radical resections (n = 1116). 3-year OS for all stages was 18% and conditional probability of surviving additional 3 years (CS3) at 1, 2 and 3 years from diagnosis was 42%, 57% and 66% respectively. Stage III and IV disease had 3-year OS rates of 19% and 3% respectively while CS3 increased progressively with each year survived(33% and 17% at 1 year, 51% and 34% at 2 years, 60% and 56% at 3 years). Conclusions: Conditional probability of survival is favorable in patients surviving one year from diagnosis and shows an increasing trend with time. Improvements in survival are more substantial in patients with adverse initial prognosis. Conditional survival provides valuable information on prognosis to patients after curative surgery and can be the basis of follow-up guidelines.
Effect of transarterial chemoembolization prior to selective internal radiation therapy on yttrium-90 microsphere delivery in hepatocellular carcinoma patients.
Authors: Lin Mu-Han , Saboury Babak , Mohammadi Homan , Moeslein Fred M , Chuong Michael David 
Published: February 2017

458 Background: Transarterial chemoembolization (TACE) and selective internal radiation therapy (SIRT) are commonly used for treatment of liver tumors. The use of TACE, which is macroembolic, prior to SIRT may cause hemodynamic changes in tumor vasculature that impair yttrium-90 (90Y) microsphere delivery to the targeted lesions. This work aims to quantify dosimetric tumor coverage using positron emission tomography (PET) dosimetry after SIRT alone compared to TACE followed by SIRT. Methods: A total of 40 consecutive hepatocellular carcinoma (HCC) SIRT patients who had a post-SIRT PET scan were evaluated. Yttrium-90 PET scan was performed within 2 hours after completion of SIRT. 3D dose distribution of each patient was then reconstructed from the PET images. To quantify the quality of SIRT microsphere delivery, we evaluated the selectivity index (SI) defined as the ratio of the average dose inside the treated lesion(s) and the average dose of the normal liver. The SI values of patients were compared based on whether TACE was previously used. Results: Thirty patients had complete data for analysis. The average dose for a total of 125 targeted lesions was 106 Gy (range 0 Gy – 495 Gy). The average SI of the entire patient group was 3.0, indicating that the targeted lesion dose was three times higher than normal liver dose. The average SI was 1.7 for the 13 patients who had prior TACE and 3.8 for the 17 patients who did not have prior TACE (p = 0.01). Nearly 80% of the patients with prior TACE demonstrated poor 90Ymicrosphere delivery (SI < 2) while none demonstrated excellent microsphere delivery (SI > 4). On the other hand, the incidence of SI < 2 and SI > 4 among patients with no prior TACE was 24% and 40%, respectively. Conclusions: 3D dose evaluation using post-SIRT PET suggests that 90Y microsphere delivery to liver tumors is impaired among patients who received prior TACE compared to those who receive SIRT alone. These data warrant evaluation of clinical outcomes in SIRT patients based on prior use of TACE and may provide a rationale for the use of SIRT prior to TACE.
Phase Ib trial of gemcitabine with yttrium-90 in patients with hepatic tumors of pancreatobiliary origin.
Authors: Kim Hyun S , Camacho Juan C. , El-Rayes Bassel F. 
Published: February 2017

460 Background: The rationale for combining Gemcitabine (G) with Yttrium-90 (Y90) is based on G being a potent radio sensitizer and activity of Y90 against liver tumors of pancreatobiliary histology. Therefore, a safety and efficacy trial of adding G to Y90 is required. Methods: Eligibility: Chemo-naïve patients with histologic diagnosis of unresectable PC or CC with liver predominant disease. Design: Open label phase I design with 3+3 G dose escalation. Induction G on Day 1 followed by Y90 on Day 2 and subsequent pre-assigned dose levels of G until week 12. Primary objective: To determine the maximal tolerated dose of G that can be used in combination with Y90. Secondary objectives: To characterize the toxicity, evaluate hepatic progression free survival (HPFS); determine tumor response rate using RECIST and PERCIST criteria; determine the progression free survival (PFS) and overall survival (OS). Correlative Imaging: 18-FDG PET/CT with contrast at baseline and 12 weeks. Results: 14 patients were recruited and 8 met the inclusion criteria. Seven out of eight patients tolerated the dose escalation regime of G (dose level 1-400 and dose level 2-600mg/m2). All the patients developed grade 1 toxicities (Hepatobiliary 25%, Bone marrow 25%, Fatigue 100%). Three patients (37.5 %) had grade 2 hepatobiliary toxicity and one patient (12.5 %) had grade 3 hepatobiliary toxicity, which required short-term hospitalization. No radiation pneumonitis, gastrointestinal ulceration, or procedure-related mortality occurred. Six patients (75%) developed grade 1 toxicity (fatigue). All of the patients had SD in the liver by RECIST; the objective response rate was 62.5% by PERCIST (CR12.5%, PR50%, SD25% PD12.5%). Overall objective response rate was 0% by RECIST (SD62.5%, PD37.5%); and 50% for PERCIST (CR12.5%, PR37.5%, SD12.5%, PD37.5%). The median OS from diagnosis was 13.8 months (95% CI, 9.65 to 26.29 months) and from Y90 therapy 10.9 months (95% CI, 6.47 to 22.39 months). PFS was 6.92 months (95%CI, 4.37-16.5 months) and HPFS of 8.72 months (95%CI, 4.48-19.36 months). Conclusions: In patients with hepatic tumors of pancreatobiliary origin, Gemcitabine at 600mg/m2 with Y90 therapy appears to be a viable and safe therapy. Clinical trial information: NCT01434459.
Peripheral trafficking of bone marrow-derived stem cells in patients with different types of gastric neoplasms: Significance of complement and interleukins.
Authors: Blogowski Wojciech , Zuba-Surma Ewa , Budkowska Marta , Salata Daria , Tarnowski Maciej , Dolegowska Barbara , Starzynska Teresa 
Published: February 2017

49 Background: Increasing evidence suggests that gastric malignancy may be a stem cell disorder. Methods: Using FACS analysis supported by ImageStream technique verification, various populations of bone marrow-derived stem cells (BMSCs), such as Lin-CD45-CD133+CXCR4+ very small embryonic/epiblast-like stem cells (VSELs), CD45-STRO-1+CD105+ mesenchymal stem cells (MSCs), Lin-CD45+CD133+ hematopoietic stem/progenitor cells (HSPCs), and CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were enumerated and sorted from peripheral blood samples of patients with gastric cancer (n = 23) and other gastric tumors (GISTs, NENs, lymphomas; n = 15) and control patients (n = 15). RT-qPCR analysis for the expression of cancerous, embryonic, and tissue trans-differentiation markers (Oct-4, Nanog, TFF-1, TFF-2, Lgr-5, BMI-1) in circulating VSELs was employed. The plasma levels of stromal-derived factor-1 (SDF-1), complement-derived anaphylatoxins/molecules (C3a, C5a, C5b-9/MAC), and interleukins (IL-6, IL-8, IL-17 and IL-23) were measured. Results: Significantly lower numbers of circulating HSPCs, and intensified peripheral trafficking of both VSELs and MSCs was observed in patients with gastric cancer, but not in those with other types of gastric tumors. In gastric cancer patients, the circulating VSELs presented higher gene expression of Oct-4, Nanog, Lgr-5, BMI-1, and TFF-1/2. The abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was not associated with the clinical stage of the disease or with the systemic levels of stromal-derived factor-1 (SDF-1), but correlated with the levels of C5b-9/MAC, IL-6, IL-8 and IL-23. Conclusions: Abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Selected interleukins and complement cascade-derived molecules, but not SDF-1, seem to be significant players associated with this phenomenon (POIG.01.01.02-00-109/09 and IP2014003273).
ACCORD12/0405-Prodige 2 phase III trial neoadjuvant treatment in rectal cancer: Results after 5 years of follow-up.
Authors: Francois Eric , Gourgou-Bourgade Sophie , Azria David , Conroy Thierry , Bouche Olivier , Doyen Jerome , Seitz Jean-François , Mineur Laurent , Etienne Pierre-Luc , Gerard Jean-Pierre 
Published: February 2017

490 Background: The ACCORD 12 randomized trial was aiming at improving ypCR by increasing the radiation dose and adding oxaliplatin (OX) to a standard RT 45 Gy with concurrent capecitabine. On short term benefit of OX was not demonstrated (Gérard JP et al. J Clin Oncol. 2010;28:1638-44) at 3 years no significant difference in clinical outcome was achieved (Gérard JP et al. J Clin Oncol. 2012;30:4558-65. François E et al. Radiother Oncol. 2014;110:144-9). This is an update of results at 5 years. Methods: Between 11/2005 and 07/2008, 598 patients were randomized. Inclusion criteria: adenocarcinoma of rectum accessible to digital examination, T3 Nx M0 (or T2 distal anterior rectum). Randomization was between two neoadjuvant treatments chemo radiotherapy: Cap45 (45 Gy + capecitabine) and Capox50 (50 Gy + cape. and oxaliplatin). Main end point was sterilization of the operative specimen. Bowel function for patients treated with anterior resection was analyzed with a global score (1 very poor to 7 excellent). A total of 253 patients received adjuvant chemotherapy usually with FOLFOX: 133 in Cap45, 120 in Capox50. Results: In the ITT population, with a median follow-up of 60 months, updated carcinologic results were calculated using the Kaplan-Meier method. Out of 299 pts randomized in CAP45 and 299 pts in CAPOX50 results were respectively the following 1) 5y-cumulative incidence of Loc. Recurrence : 8.8% vs 7.8% (p = 0.78 HR = 0.92 [0.51-1.66]) 2) 5y-cumulative incidence of dist metastasis : 29.3% vs 27.1% (p = 0.48 HR = 0.89 [0.62-1.54]) 3) 5y-disease free survival rate : 60.4% vs 64.7% (p = 0.25 HR = 0.86 [0.66-1.11]) 4) 5y-overall survival rate : 76.4% vs 81.9% (p = 0.06 HR = 0.71 [0.50-1.01]) 5) bowel function median score : 5.2 [1-7] vs 4.9 [1-7]. Conclusions: At 5 years there was no significant difference in terms of local recurrence or distant metastases rates between both regimens. The new finding is a trend for improved overall survival in the Capox 50 groups may be related to subsequent salvage secondary treatments. At time of meeting the prognostic factors will be available in details and these results put in perspective with other phase III trial testing the role of oxaliplatin in Europe and the US. Clinical trial information: NCT00227747.
A novel 2-gene blood test for colorectal cancer recurrence.
Authors: Pedersen Susanne Kartin , Symonds Erin L , Mansfield Scott , Byrne Susan , Bambacas Libby , Hollington Paul , Murray David , Baker Rohan , LaPointe Lawrence Charles , Young Graeme P 
Published: February 2017

495 Background: Annual computed tomography (CT) scans and periodic carcinoembryonic antigen (CEA) testing are monitoring methods for colorectal cancer (CRC) recurrence. We have previously described a 2-gene blood test for CRC (methylated BCAT1 and IKZF1) that may indicate tumour DNA shedding into the blood. The aim was to compare the 2-gene and CEA blood tests at detecting recurrence in CRC surveillance patients. Methods: Methylated BCAT1/IKZF1and CEA (positive ≥5ng/mL) were measured in patients previously diagnosed with CRC (excluding those undergoing active treatment). McNemar’s test was used for statistical analyses, using clinical findings including CT to diagnose recurrence. Results: At study midpoint, 340 patients were enrolled (64% men, average 64yr at diagnosis), including 59 patients with blood testing done pre- and post-resection, and 105 with CT surveillance scans (median 18 months after primary diagnosis). Following resection (median 2.3 months), 91% of patients who were 2-gene positive prior to treatment showed either no detectable methylated BCAT1/IKZF1(26/35) or significantly reduced levels in blood (6/35). Residual disease was found in two patients (2/3) who remained gene positive post treatment. Recurrence was identified in 30/105 (29%) patients with surveillance CT scans. Of these, 67% and 27% were 2-gene and CEA positive, respectively, with 8 (27%) cases positive by both tests (Table 1, p<0.001). In 13 cases with local recurrence, 54% were 2-gene positive, with only 1 (8%) positive by both tests (p=0.03). In 17 cases with distant recurrence, respective 76% and 41% were 2-gene and CEA positive (p=0.03). In patients with no evident disease, 20% were positive for one test but not the other (2-gene test, 16%; CEA, 4%; p = 0.04). Conclusions: Following resection, most patients had either reduced or no methylated BCAT1/IKZF1 in blood, indicating a correlation with the presence of cancer. Two-gene positivity correlated with local (54%) and distant (76%) recurrence with 2.5-fold more recurrence cases detected than with CEA. The 2-gene test may be better than CEA for recurrence monitoring. [Table: see text]