bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of robotic-assisted approach on lymphadenectomy for colorectal cancer.
Authors: Gamagami Reza , Kozak Paul , Kakarla Venkata R. 
Published: March 2017

787 Background: In most recent years, robotic assisted laparoscopic surgery (RALS) has proven to be a viable alternative to laparoscopic and traditional open surgery for colorectal cancer. Obtaining the adequate number of lymph nodes is not only essential for accurate staging, but also impacts both prognosis and the need for adjuvant chemotherapy. To date, the efficacy of lymph node harvest for RALS is not well studied or established. The aim of our study is to analyze the impact of RALS on lymphadenectomy for colorectal cancer. Methods: We performed a retrospective review of patients who underwent curative resections for colorectal cancer over a five-year period at a single institution by a single surgeon. Resections were classified as right-sided, sigmoid, or rectal, and subdivided into robotic and non-robotic surgery groups. The demographic data and histopathology were obtained, with an emphasis on the number lymph nodes harvested (LNH) during resections. Emergencies and non-curative resections were excluded. Results: Between January 2010 and December 2015, 136 patients with colorectal cancer underwent curative resections. Sixty-four underwent right-sided resections (28 laparoscopic, 36 robotic). Twenty-five underwent sigmoid resections (11 laparoscopic, 14 robotic), and 47 underwent rectal resections (15 open, 32 robotic). There was no significant difference in age, sex, BMI and ASA scores between the cohorts examined. The mean number of LNH with RALS was significantly higher in all three groups (right-sided—24 vs. 15 ( p= .0001), sigmoid—16 vs. 12 ( p= .046), rectal—19 vs. 4 ( p= .0016)). There was no difference in the rate of adequate lymph node extraction for staging purpose, i.e., 12 lymph nodes in all three groups. Conclusions: Robotic-assisted laparoscopic surgery is associated with a statistically significant increase in lymph node harvest for right-sided, sigmoid and rectal resections for malignancy. Future studies with larger sample sizes are necessary to validate these findings.
Comorbidities limiting recruitment of colorectal cancer (CRC) patients in early-phase trials.
Authors: Duma Narjust , Wang Yucai , Gonzalez Velez Miguel , Kothadia Sejal , Mariotti Veronica , Parrondo Ricardo Daniel , Hubbard Joleen Marie , Adjei Alex A. , Halfdanarson Thorvardur Ragnar 
Published: March 2017

791 Background: With the surge of drug development in the past decade, early phase clinical trials (EPCT) have gained value evaluating the potential benefits of new therapies. The inclusion/exclusion criteria in EPCT are usually rigorous and may exclude many patients (pts) commonly seen in clinical practice. Our objective was to identify the most common comorbidities excluded in EPCT for CRC. Methods: ClinicalTrials.gov was queried on December 1stof 2015. We reviewed the characteristics and eligibility criteria of 369 phase I/II interventional drug trials including: experimental arm therapy, location, and exclusion/inclusion criteria. Logistic regressions were completed and exclusion was studied as a binary variable. Results: Of the 369 trials, 68% were phase II and 32% phase I. 46% were conducted in the United States, 30% in Europe, 15% in Asia and 9% in other locations. 74 (20%) trials excluded pts > 70 years of age. 142 (39%) trials required creatinine levels < 1.5 mg/dl, liver enzymes (AST/ALT) < 2.5 and bilirubin < 1.5 of the upper limit of normal. Cytopenia was a significant exclusion factor: 147 (47%) trials required Hgb > 9 g/dl and 218 (59%) excluded pts with platelets < 100,000/dl. In terms of comorbidities, 98 (27%) trials excluded pts with heart failure (NYHA class 3/4), 74 (20%) with atrial fibrillation, 112 (31%) with any anticoagulation therapy and 155 (42%) with positive HIV. Trials located in the US were more likely to exclude pts with Hgb < 9g/dl (OR: 1.5, 95%CI: 1.1-2.3, p < 0.05), immunotherapy trials were more likely to exclude pts on any anticoagulation (OR:1.8, 95%CI: 1.2-2.8, p < 0.007) and targeted therapy trials were more likely to exclude pts with history of DVT/PE or cardiovascular diseases (OR: 3.4, 95%CI: 1.9-5.8, p < 0.0001; OR: 2.3, 95%CI: 1.3-3.8, p < 0.002, respectively). Conclusions: 20% of EPCTs on CRC excluded pts with advanced age, organ dysfunction and common comorbidities. Many of the EPCT reviewed were not inclusive of our aging oncology population who are more likely to have multiple comorbidities. Investigators should review whether sufficient justification exists for every exclusion criterion before their incorporation in future trial protocols.
Pembroliuzmab in gastrointestinal (GI) malignancies with defective DNA mismatch repair (dMMR): A single institution experience.
Authors: Cavalieri Courtney C , Swanson Eric , Whisenant Jonathan R. , Weis John R. , Gilcrease Glynn Weldon , Stenehjem David D. , Sharma Sunil , Garrido-Laguna Ignacio 
Published: March 2017

792 Background: Defective DNA mismatch repair is associated with increased mutation load and expression of neoantigens. Increased activity of PD-1 inhibitor is reported in patients with GI cancers with dMMR. Here, we describe our experience at Huntsman Cancer Institute with PD-1 inhibition in subjects with GI malignancies with dMMR. Methods: Retrospective chart review of patients with metastatic GI malignancies with dMMR, treated with pembrolizumab at Huntsman Cancer Institute between July 15, 2015 and September 26, 2016. Results: A total of 9 patients were identified that received at least 1 dose of pembrolizumab (colorectal n=5; cholangiocarcinoma n=2; pancreatic n=2). Of the 9 patients, 5 received concurrent cytoxic chemotherapy. Median number of doses given was 3 (range 1 to 17). Three patients received pembrolizumab on clinical trial with concomitant mFOLFOX6. Five patients have restaging scans at the time of abstract submission. The first patient has cholangiocarcinoma and experienced a -73% response per RECIST criteria from baseline (time to progression +8 months). The second patient has pancreatic adenocarcinoma and showed a total -56.7% response per RECIST criteria from baseline (time to progression +5 months). The third patient has colorectal carcinoma and had stable disease by RECIST at restaging after 2 months (biochemical response with a 50% decrease in CEA). The fourth patient has cholangiocarcinoma and had a biochemical response with a 50% decrease in CA 19-9 and a mixed response on first restaging scan (time to progression +3.5 months). All 4 of these patients continue to have response to therapy at the time of abstract submission. The fifth patient who had colorectal cancer and died from upper GI bleeding. Restaging CT scans showed response to therapy after 6 weeks of treatment. Four additional patients initiated treatment recently and have yet to undergo restaging scans. Conclusions: Single-institution data seem to confirm activity of PD-1 inhibitor in GI malignancies that harbor dMMR. All 5 restaged patients demonstrated response to PD-1 inhibition by RECIST criteria or decreased tumor marker. Updated responses for all patients will be presented during the meeting.
Protective effect of ursodeoxycholic acid against chemotherapy-induced mucositis.
Authors: Kim Seung Han , Chun Hoon Jai , Lee Jung Min , Lee Sang Yup , Choi Byeong Kwang , Yoo In Kyung , Lee Jae Min , Choi Hyuk Soon , Kim Eun Sun , Keum Bora , Jeen Yoon Tae , Lee Hong Sik , Kim Chang Duck 
Published: March 2017

796 Background: Gastrointestinal mucositis is a serious side effect of chemotherapy. It increases the frequency of infection, risk of bleeding, and duration of hospitalization, consequently reducing subsequent chemotherapy doses. Ursodeoxycholic acid (UDCA), which is currently used in various liver diseases, exerts direct cytoprotective effects by stabilizing membranes, inhibiting apoptosis, and acting as an antioxidant. The protective effect of UDCA against chemotherapy-induced mucositis was assessed using an in vivo animal model. Methods: Sprague-Dawley rats were randomly assigned to the following 5 groups: non-chemotherapy and vehicle; 5-fluorouracil (5-FU) and vehicle; 5-FU and 10 mg/kg/day UDCA; 5-FU and 100 mg/kg/day UDCA; and 5-FU and 500 mg/kg/day UDCA. 5-FU (400 mg/kg) or physiological saline (control) was administered by intraperitoneal injection. UDCA was orally administered 1 day before 5-FU injection for 6 days. One day after the final UDCA dose, rats were sacrificed, and the intestines were dissected for tissue sampling and laboratory analysis. Results: UDCA promoted a higher body weight recovery, decreased villus destruction, and reduced inflammatory cytokines levels, at doses of 10 and 100 mg/kg/day. Villous fusion and destruction were pronounced in the 5-FU group compared with those observed in the UDCA-treated group or controls. The jejunal villous lengths were as follows: 212.8±58.0 µm, 331.3±18.0 µm, and 310.0±112.6 µm, in the 5-FU and vehicle, 5-FU and 10 mg/kg UDCA (p = 0.006), and 5-FU and 100 mg/kg UDCA groups (p = 0.046), respectively. Real-time polymerase chain reaction (RT-PCR) showed that IL-6 and TNF-α levels decreased in the 10 mg/kg and 100 mg/kg UDCA co-administration groups. Further, myeloperoxidase activity decreased in the UDCA co-administration group. Conclusions: UDCA significantly attenuated the reduction of the height of small intestinal villi and reduced inflammatory cytokine levels, thus highlighting the potential of UDCA as a preventive agent against chemotherapy-induced gastrointestinal mucositis. The specific protective mechanisms of UDCA on the gastrointestinal tract should be determined.
Retrospective review of outcomes in patients (pts) with synchronous metastatic rectal cancer (mRC) receiving initial non-surgical management.
Authors: Torti Ella , Park James O , Chiorean E. Gabriela , Kim Edward Y. , Cohen Stacey , Coveler Andrew L. 
Published: March 2017

797 Background: Management of mRC trends toward initial non-surgical management of the primary tumor based on studies demonstrating low complications rates from un-resected primary colonic tumors. The fixed location of the rectum may increase local complications. This study characterizes complications of pts with synchronous mRC with an intact primary tumor. Methods: A retrospective review of records from 2001 to 2013 identified pts with mRC by ICD-9/10 codes. Pts with treatment-naïve mRC without significant local symptomatology were evaluated. Time to complications and death were calculated. Pathology, stage, baseline CEA, RAS, BRAF and initial treatment were evaluated for prognostic significance. Results: Forty-four pts were identified with mRC; eight were excluded for initial resection for a symptomatic primary. Among the 36 evaluable pts treated with initial chemotherapy, 14 (39%) developed complications related to the primary tumor, of whom 5 (14%) developed two or more complications. Six (17%) required operative intervention due to primary tumor complications (two died prior to planned procedure). Complications were: perforations/abscesses/fistulae (6), bowel obstruction (5), severe bleeding (5), urinary obstruction/infection (3) and, pain requiring palliative treatment (1). Interventions included blood transfusions (5), stents (3), radiotherapy (3), I&D/drains (3) and, nephrostomy (2). Of 22 pts who did not develop any complications, 15 underwent curative resection of all sites of disease. Six remain disease free and nine relapsed, all distantly. None of the 14 who developed complications underwent curative operation. The median time to complication was 2.5 months. Median overall survival was 37 and 52 months for those with and without complications, respectively. Median time from complication to death was 21 months. Pts aged > 50 vs < 50 were more likely to have complications of the primary tumor (57% vs 21%). Conclusions: mRC pts with intact primary tumors may develop complications at a higher rate (39%) than those with colon cancer (11%). These findings will need to be confirmed with larger datasets and examine for specific treatment effects.
Comprehensive genomic profiling (CGP) of esophageal and tubular GI tumors to identify frequencies of ErbB family member amplification with therapeutic implications.
Authors: Bailey Mark , Ali Siraj Mahamed , Schrock Alexa Betzig , Klempner Samuel Jacob , George Ben , Lipson Doron , He Jie , Miller Vincent A. , Stephens Phil , Ross Jeffrey S. 
Published: March 2017

8 Background: As described in the MyPathway study, amplification and other mutations in ErbB-family proteins are actionable events across solid tumors. Targeting ERBB2 amplifications (amp) in tubular GI cancers (TGC) improves patient outcomes. ErbB family comparisons across anatomic sites is lacking and here we describe the largest known series in TGC. Methods: DNA was extracted from 12,685 FFPE clinical TGC specimens, including 1,720 esophageal CA*. CGP was performed on hybrid-capture, adaptor ligation based libraries to a mean coverage depth of 720X for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. Results: Across all TGC cases, amp was the most frequent genomic alteration among ErbB members at 8.7%. ERBB2 amp was 2.3x as common as EGFR amp across TGC. Across TGC sites, EGFR amp was most frequent in esophageal SCC (13.7%) and ERBB2 amp was most common in gastroesophageal junction adenoCA (21%) compared with overall frequencies of 2.7% and 5.5% respectively. ERBB3 and ERBB4 amp were rare, and most common in gastroesophageal adenoCA relative to other TGC. Clinical support with outcomes for patients treated with anti-ErbB targeted therapy across TGC will be presented, including profiling from cases of acquired resistance to anti-ErbB targeted therapy. Conclusions: Among TGC, esophageal CA harbored the most ErbB family member amp with variation by histology. Profiling across ErbB proteins in TGC suggests biologic differences and may affect response to treatment. CGP can expand the population who may benefit from anti-ErbB directed therapies and refine treatment choices. Further research is warranted. [Table: see text]
The utilization of multidiciplinary tumor boards (MDT) in clinical routine: Results of a health care research study focusing on patients with metastatic colorectal cancer.
Authors: Homayounfar Kia , Lowes Markus , Kleiss Mathias , Lueck Rainer , Detken Sven , Nietert Manuel , Beissbarth Tim , Stanek Kathrin , Langer Claus , Ghadimi Michael , Conradi Lena-Christin 
Published: March 2017

805 Background: Multidisciplinary Tumor Boards (MDT) have been advocated as standard of care in modern oncology. German cancer guidelines for metastasized colorectal cancer (mCRC) recommend discussing every patient (pt) with colon cancer (CC) after primary surgery and every pt with clinical stage IV CC as well as every rectal cancer (RC) pt prior to any therapy in a MDT. In this study we evaluated how extensive this approach has been implemented in clinical routine and how MDT discussion influences treatment decisions within a representative region with established access to MDTs for all actors. Methods: All major institutions treating oncological pts in southern Lower Saxony and Northern Hesse (N = 11) were invited to participate in the study. Pts with mCRC and diagnosis of the first metastasis between 01/2011 and 12/2013 were eligible. A standardized pt report form was developed and data were collected in a GCP-conform EDC-system named secuTrial. Results: A university medical center, 4 teaching hospitals, 1 communal hospital and 3 oncological focus practices participated in the study. In total, 470 pts (CC n = 278, RC n = 192) with a median age of 70 (range 22-92) years were enrolled. 286 (60.9%) pts had synchronous and 184 (39.1%) pts had metachronous metastases. Discussion within an MDT was performed in 141 (62.9%) of 224 CC pts after primary surgery and in 70 (38.3%) of 183 pts with clinical stage IV CC prior to any therapy. In RC pts, MDT discussion prior to any therapy happened in 91 (47.4%) pts. Curative resection of metastases was performed in 193 (41.1%) cases. Pts > 70 years (n = 250) received significantly more often chemotherapy ± surgery when presented in an MDT (85.8% versus 64.4%, p = 0.0002). In pts with single organ metastases the resection rate was not significantly different (48.4% versus 56.9%, p = 0.1574) but preoperative chemotherapy was more often indicated (56.7% versus 33.3%, p = 0.0056) when pts were discussed in a MDT. Conclusions: In clinical routine MDT discussion is not as established as advocated by national guidelines. Treatment decisions differ depending on MDT discussion especially in older pts and those with single organ metastases.
Maintenance treatment with capecitabine plus cetuximab after first-line standard fluorouracil-based chemotherapy plus cetuximab for patients with RAS wild-type advanced colorectal cancer.
Authors: Yuan Xianglin , Zhao Ben , Qiu Hong , Zhang Mingsheng , Zou Yanmei 
Published: March 2017

806 Background: The optimum duration of first-line treatment with chemotherapy in combination with cetuximab (CET) in patients with RAS wild-type (wt) advanced colorectal cancer (ACRC) is unknown. The current study was designed to evaluate the efficacy and safety of maintenance treatment (MT) with capecitabine (CAP) plus CET in ACRC. Methods: The trial was conducted at Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, China. We included patients with previously untreated RAS wt ACRC, with stable disease or better after induction treatment with 4-6 months of standard fluorouracil-based chemotherapy plus CET, WHO performance status of 0 or 1. The selected patients were assigned to MT-CAP (1250mg/m2 orally twice daily on day 1-14 every 3 weeks), and CET (400 mg/m2 on day 1 of the first week, then 250 mg/m2 on day 1 every week). We assessed disease status every 6 weeks. The primary endpoint of the study was disease progression or unacceptable toxicity, defined as progression-free survival (PFS). All endpoints were calculated from the time of inclusion. Analyses were done by intention to treat. Results: From Jan. 1, 2014 to May 1, 2016, we assigned 13 patients to MT-CAP plus CET. Median follow-up time was 22 months. Median PFS was 16.7 months, and the PFS of MT was 12.1 months. MT was well tolerated, and none of the 13 patients discontinued treatment due to toxic effects. The general quality of life did not deteriorate during MT. Conclusions: MT-CAP plus CET after 4-6 months of standard chemotherapy and CET in ACRC patients was effective and did not compromise life quality. Based on these results, we launched a single arm, open-label, multi-center, Phase 2 clinical trial to investigate the efficacy and safety of MT-CAP plus CET after first-line standard fluorouracil-based chemotherapy plus CET for patients with RAS wt ACRC. The trial was registered with ClinicalTrials.gov, number NCT02717923, and approved by the Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Clinical trial information: NCT02717923.
Clinical significance of intratumoral HER2 heterogeneity (IHH) using endoscopic biopsy specimens in patients with HER2-positive gastric cancer (GC) who received T-mab-based chemotherapy.
Authors: Yagi Shusuke , Wakatsuki Takeru , Yamamoto Noriko , Chin Keisho , Takahari Daisuke , Ogura Mariko , Ichimura Takashi , Nakayama Izuma , Matsushima Tomohiro , Osumi Hiroki , Suenaga Mitsukuni , Ozaka Masato , Shinozaki Eiji , Ishikawa Yuichi , Yamaguchi Kensei 
Published: March 2017

81 Background: We recently reported the clinical significance of IHH in trastuzumab (T-mab) based chemotherapy using surgical specimens; namely homogeneously HER2 positive GC was associated with longer survivals compared with heterogeneously HER2 positive GC (ASCO-GI 2015). However, three quarters of patients were diagnosed as having GC by endoscopic biopsy and no data are available as to whether IHH using endoscopic biopsy specimens predict T-mab efficacy. In this study, we addressed clinical usefulness of IHH using endoscopic biopsy specimens. Methods: Patients who received T-mab based chemotherapy and had endoscopic biopsy specimens available for IHC test were retrospectively examined. When all biopsy specimens which contained cancer cells were diagnosed HER2 IHC3+, it was defined as “Inter-specimens homogeneously HER2 positive (Inter-homo)”, and the others were defined “Inter-hetero”. When all tumor cells showed HER2 overexpressed within a specimen, it was defined “Intra-specimen homogeneously HER2 positive (Intra-homo), and the others were defined “Intra-hetero”. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods and compared using the log-rank test. Results: 57 patients were enrolled in this study. The median age was 67 years old and 70% were male. PS 0, GEJ cancer, intestinal type histology, and visceral metastasis (lung or liver) were found in 74% , 25% , 60% , and 53% , respectively. After the median follow-up period of 12.1 months, the median PFS and OS were 7.6 and 16.9 months, respectively. Significant survival differences were shown only in the comparison between inter-homo and inter-hetero; inter-homo group (n = 34) showed significantly longer PFS (8.5 vs. 5.1 months, HR 0.52 95%CI 0.27-0.98, p = 0.038) and OS (27.6 vs. 12.1 months, HR 0.27 95%CI 0.12-0.61, p = 0.001), respectively. Conclusions: Our data suggest that, in contrast to surgical specimens, the assessment of HER2 heterogeneity using endoscopic biopsy specimens may be useful for negative selection of patients who are unlikely to benefit from T-mab based chemotherapy.
A pilot study of apatinib reversing paclitaxel resistance in heavily pretreated advanced gastric cancer (AGC).
Authors: Lin Rongbo , Zhao Shen , Li Hui , Liu Jie , Fan Nanfeng 
Published: March 2017

89 Background: In vitro or vivo, apatinib can reverse ABC-mediated multidrug resistance not only by inhibiting their transport function, but also by downregulating ABC expression. Methods: The patients with advanced gastric adenocarcinoma were resistant to paclitaxel-containing regimen (disease progression during or within 3 months after chemotherapy) and had measurable lesions received apatinib 850 mg, po, qd combined with paclitaxel alone (80 mg/m2 d1, d8, and d15, repeated 4-weekly) or POF (reported in 2007, 2008, 2009, 2010 ASCO, paclitaxel 135 mg/m2, oxaliplatin 85 mg/m2, and leucovorin 400 mg/m2, d1; 5-FU 2400 mg/m2 for 46h, repeat 2-weekly). The choice of regimen was left to clinician discretion in term of performance status and whether the agent that will be given has been resistant. Results: From 14th August 2015 to 1st March 2016, seven patients were eligible. The median age was 49 years (range, 43 to 67 years), 5 were males and 2 were females. The prior chemotherapeutic agents were summarized in table. Four patients had disease progression during apatinib. Two PRs, four SDs (unconfirmed), and one early death were observed. At a median follow-up of 238 days, the median progression-free survival was 124 days, the median survival was 194 days (range, 33 to 398+ days). Grade 3 to 4 neutropenia, anaemia, hypertension, fatigue, stomatitis was one patient respectively. No treatment-related death occurred. Conclusions: This study showed promising result that apatinib reverses paclitaxel resistance in heavily pretreated AGC. Clinical trial information: NCT02697838. [Table: see text]