bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim follow up results from a phase II study of neoadjuvant chemoembolization of resectable colorectal liver metastases (CRLM) with transcatheter hepatic therapy with irinotecan-eluting beads.
Authors: Jones Robert Peter , Malik Hassan Zakria , Fenwick Stephen W , Terlizzo Monica , O'Grady Elizabeth , Stremitzer Stefan , Gruenberger Thomas , Poston Graeme John 
Published: February 2017

519 Background: 65% of patients undergoing liver resection for CRLM experience disease recurrence within 3 years. Perioperative chemotherapy improves 3-year progression free survival, and good pathologic response is associated with improved overall survival. However, systemic neoadjuvant chemotherapy increases operative morbidity. DEBIRI gives sustained delivery of drug directly to tumor, maximising response and reducing systemic exposure. This study examined the feasibility, safety and long-term outcome of patients treated with neoadjuvant DEBIRI before resection. Methods: Patients with resectable CRLM received single targeted DEBIRI (up to 200mg) 1 month pre-hepatectomy. Primary end-point: tumor resectability, secondary end-points: safety, pathologic response, disease-free (DFS) and overall survival (OS). Results: DEBIRI performed in 40 patients. Post-TACE complications: 1 acute pancreatitis (3%); 4 post-embolization syndromes (10%). 38 patients underwent hepatectomy (2 peritoneal disease, resectability rate 95%). 30-day operative mortality 5% (n=2), neither death TACE related (1 intraoperative pneumomediastinum, 1 aspiration pneumonia). Both operative deaths excluded from follow up analysis. 63 lesions (median 2 per patient) targeted with DEBIRI. Histology: no residual disease 17%; 1-49% residual disease 59%; >50% residual disease 22%; no response 2%. Median follow up 293 days. Fourteen patients (36%) had disease recurrence, median DFS 387 days (95% CI 276-498). Eight (57%) had hepatic recurrence, 2 (14%) had pulmonary recurrence and 4 (29%) had both pulmonary and hepatic recurrence. One patient died of hepatic and pulmonary recurrence after 565 days. Conclusions: Resection after neoadjuvant DEBIRI for CRLM demonstrated a good safety profile in this study population. Single DEBIRI treatment resulted in impressive pathologic response, with patterns of recurrence comparable to reported series of resection alone. Further trials assessing combination DEBIRI and systemic chemotherapy are necessary. Clinical trial information: NCT00844233.
Expression of growth and cell proliferation factors in gastric carcinomas: The association with poor overall survival on patients with intestinal type.
Authors: Begnami Maria D. , Neves Jose Ivanildo , Chaves Marcos , De Barros E Silva Milton Jose , Costa Wilson Luiz , Coimbra Felipe José Fernandez , Diniz Alessandro Landskron , Ribeiro Heber Salvador de Castro , Pinto Clovis 
Published: February 2017

52 Background: Gastric carcinomas (GC) express a variety of growth factors and cell proliferation acting in the mechanisms of tumor invasion and spread. The expression of angiogenic factors such as vascular endothelial growth factor (VEGF) has been demonstrated in diffuse type GC, whereas expression of growth factors is associated with intestinal-type carcinomas. Objective: To study the immunohistochemical expression of proteins associated with growth factors and cell proliferation in GC. Methods: We studied 400 GC, arranged in duplicates in 2 blocks of tissue microarray (TMA). Immunohistochemistry was performed using antibodies: c-MET (Novocastra), TGFbetaI (Santa Cruz), TGFbetaII (Santa Cruz), c-erbB-2 (Dako) and VEGF (Santa Cruz). Cases were considered positive for TGFbetaI, TGFbetaII and VEGF when cytoplasmic staining was observed in more than 10% of tumor cells. Positive cases for c-met and c-erbB-2 were detected when strong staining on the membrane cells was observed in more than 10% of neoplastic cells. Results: Expression of TGFbetaI, TGFbetaII and VEGF were detected in 314/385 (81%), 370/382 (96%) and 333/366 (90%) of GC. 333/376 (88%) cases were positive for c-met and 54/385 (14%) for c-erbB-2. Intestinal type carcinomas were more often positive for TGFbetaII (p = 0.01), VEGF (p = 0.001), c-met (p = 0.01), and c-erbB-2 (p = 0.001). According to univariate statistical analyzes expressions of TGFbeta II, c-met and c-erbB-2 were independent factors associated with overall survival of patients with GC. Conclusions: The proteins associated with growth factors and cell proliferations are differentially expressed in intestinal type of GC. Our findings pointed them out as biological factors associated with worse prognosis and important therapeutic targets.
First-line clinical trials and metastatic colorectal cancer: How selected are clinical trial participants?
Authors: Field Kathryn M , McKendrick Joseph James , Shapiro Jeremy David , Tie Jeanne , Bae Susie , Burge Matthew E. , Yip Desmond , Nott Louise M. , Gibbs Peter 
Published: February 2017

524 Background: Guidelines recommend that oncology patients have the opportunity to participate in a clinical trial wherever possible. It is purported that as trial participants are often younger and fitter, data extrapolation from trial outcomes to patients seen in routine care may be difficult. We compared characteristics of patients with metastatic colorectal cancer (mCRC) participating in a first-line clinical trial with those treated in routine care. Methods: The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed mCRC comprehensive database, was used to identify patients treated on a first-line trial compared with those receiving combination chemotherapy; single-agent therapy; or no chemotherapy. Data collection began in June 2009 and is ongoing at 15 Australian centres to date. Results: Of 671 patients, 49 (7.3%) participated in a first-line clinical trial. Patients on trial were significantly younger, with 49% (n=24) trial participants being under 60 years, compared with 33% (n=128) receiving combination chemotherapy off study (p=0.047), 13% (n=13) single-agent therapy (p<0.0001) and 10% (n=15) no treatment (p<0.0001). All trial participants were ECOG performance status 0-1, compared with 87% (n=335) of non-trial patients receiving combination chemotherapy (p<0.0001), 80% (n=82) receiving single-agent therapy (p<0.0001) and 52% (n=76) no treatment (p<0.0001). Similarly, Charlson comorbidity score was significantly lower in trial participants, with 88% (n=43) having a score 0-3 (less comorbidity) versus 71% (n=272) receiving combination chemotherapy, 39% (n=40) receiving single-agent therapy and 25% (n=36) no treatment. Preliminary analysis suggests significant overall survival benefit for the clinical trial cohort. Conclusions: Consistent with available literature, trial participants with mCRC are significantly younger, fitter and of better performance status than those who receive similar chemotherapy off-trial or no treatment. The impact of trial participation on survival may be thus subject to multiple factors biasing for a better outcome, including the contributing benefit of younger age and less comorbidity.
Effect of trastuzumab on telomere-related proteins and the relationship to the sensitivity of HER2-amplified human gastric cancer cells to oxaliplatin and cisplatin.
Authors: Liu Yongping , Ling Yang , Qi Qiu feng , Pan Yaodong 
Published: February 2017

53 Background: HER2 amplification occurs in about 20% of gastric cancers, and trastuzumab in combination with cisplatin based chemotherapy has been reported to improve oncological outcomes in gastric and gastro-oesophageal junction cancer with HER2 gene amplification. The aim of this study was to evaluate the potentially useful combined antitumor efficacy of trastuzumab and platinum agents in gastric cancer cells and to elucidate further the mechanisms possibly involved in the interaction between the trastuzumab and platinum agents. Methods: Gene expression was determined by using real-time quantitative PCR in gastric cancer cell lines. The chemosensitivity of gastric cancer cells to platinum agents and the apoptotic effect of drugs in vitro were evaluated using cellTiter 96 Aqueous One Solution Cell Proliferation Assay kit and double staining with both Annexin-V-FITC and PI, respectively. Results: Treatment with 1.0μg/ml trastuzumab for 48h could significantly increase sensitivity of oxaliplatin or cisplatin in HER2 amplified gastric cancer cells, and the IC50 of oxaliplatin and cisplatin were reduced to about 3.29 times and 6.91 times, respectively. Apoptosis analysis also indicated that trastuzumab significantly increased both oxaliplatin and cisplatin-induced apoptosis in NCI-N87 cells. Analysis of telomere-related genes revealed that trastuzumab singly and pretreatment with trastuzumab for 48h followed by oxaliplatin or cisplatin for another 48h could significantly downregulate the mRNA expression of TPP1, TRF1, TRF2, TRF2IP, POT1 and TIN2 genes. Conclusions: Our results describe the potential role of low dose trastuzumab to increase sensitivity of oxaliplatin and cisplatin in HER2 amplified gastric cancer cells, which may be partially through downregulating the expression levels of telomere-related genes.
Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?
Authors: Wong Hui-li , Field Kathryn M , Tie Jeanne , Kosmider Suzanne , Shapiro Jeremy David , McKendrick Joseph J , Parente Phillip , Lipton Lara Rachel , Yip Desmond , Parakh Sagun , Nott Louise M. , Gibbs Peter 
Published: February 2017

534 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centres. Results: Of the 679 patients entered, 129 (19.0%) had an ECOG PS ≥ 2. In total, 77 (11.3%) were PS 2, 41 (6.0%) PS 3 and 11 (1.6%) PS 4. Chemotherapy was administered to 55 (71.4%) PS 2 and 15 (36.6%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (55.0% versus 86.8%, p<0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (38.0% vs 71.6%, p<0.0001) or bevacizumab (15.5% vs 46.9%, p<0.0001). Overall survival (OS) was reduced with declining PS, with medians of 31.2, 9.0, 3.0 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p<0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.8 vs 4.1 months for untreated patients, p<0.0001). At one and two years, 22 (31.4%) and 8 (11.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.
Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer (mCRC): Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial—Comparison of the efficacy of KRAS status.
Authors: Nakamura Michio , Yuki Satoshi , Dazai Masayoshi , Kobayashi Yoshimitsu , Kato Takashi , Naruse Hirohito , Kudo Mineo , Akakura Nobuaki , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

536 Background: Mutations of the KRAS gene were identified as a predictive marker in mCRC for anti-EGFR antibody. Previously reported data suggest that the longer overall survival (OS) observed with bevacizumab (BV) treatment in mCRC is independent of alterations in the KRAS status. We analized efficacy of BV combined irinotecan and S-1 (IRIS/Bev) in mCRC relative to KRAS status. Methods: In the retrospective analysis (n=53) of patients who participated in the Phase II trial of IRIS/Bev, additional statistical analyses were done with data from KRAS mutational analyses. In this trial, eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, and no history of prior chemotherapy. S-1 40-60 mg twice daily p.o. was given on days 1-14 and irinotecan 100 mg/m2 and bevacizumab 5 mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine Progression-free survival (PFS) and OS. Log-rank test was used to compare with mutant or wild-type KRASin terms of PFS and OS. All statistical tests were performed using SPSS. Results: The target number of 53 patients was enrolled as of March 2009. KRAS status was assessed in 43 patients (wild = 27, mutant = 16). Response rate was 63.0% with wild-type and 68.8% with mutant-type KRAS, that was not significant (p=0.752). The median Progression-free survival was 17.1 months with wild-type and 22.7 months with mutant-type KRAS, that was not significant (p=0.531). And median OS was 49.0 months with wild-type and 38.0 months with mutant-type KRAS, that was not significant(p=0.906) as well. Conclusions: IRIS/Bev provides clinical benefit in patients with mCRC expressing either mutant or wild-type KRAS. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab: TRICOLORE study) is already started. Comparison of the efficacy of KRAS status is also planned in this study. Clinical trial information: NCT00569790.
Correlation of psychosocial factors (PSF) before and throughout treatment with response to chemotherapy (CTx) in patients (pts) with advanced gastrointestinal (GI) cancers: Does psychosocial status predict tumor remission?
Authors: Offergeld Anna Maria , Drabik Anna , Oechsle Karin , Mehnert Anja , Atanackovic Djordje , Arnold Dirk , Stein Alexander 
Published: February 2017

542 Background: CTx has shown to have a positive impact on improving or maintaining quality of life (QoL) in patients with advanced GI cancers. The role of PSF in relation to objective tumor response (OTR) to CTx is not well described yet. We thus evaluated the predictive value of pretreatment PSF on OTR as well as the continuous evaluation of PSF in regard to OTR throughout treatment. Methods: Eligible pts had metastatic or recurrent GI cancer and were about to receive first- and second-line palliative CTx. QoL, physical symptoms and PSF were assessed by the EORTC QLQ C30, the MSKCC-Symptom Assessment Scale (MSAS), and a modified Brief-COPE before treatment start and after discussing the results of the first follow up OTR assessment. OTR was either classified according to RECIST or using a remission based approach (RA), classifying response as any decrease in size, and no change or progression as non-response. Results: 50 pts (median age 61.8 years, ECOG 0/1/2 12%/62%/26%, 21 female, 40% colorectal, 28% biliopancreatic, 24% esophagogastric, 78% 1st line CTx) were enrolled. OTR was 32% partial response, 50% stable disease and 18% progressive disease according to RECIST, and 60% response vs. 40% non-response according to RA. Interestingly, patients responding (RECIST and RA) to CTx had better role/emotional/cognitive functioning, mental state, global distress index, active coping, positive reframing, and belief in control over their lives, and less acceptance of their disease before treatment. PSF significantly predicted response (RA) to CTx, even if adjusted for age, cancer type, and line of treatment (p<0.05). During course of treatment, PSF remained largely unchanged in responders, whereas non-responders loose belief and confidence in control, safety and equity and tend to increased denial (RECIST and RA). Those findings were more pronounced using the RA classification than RECIST. Conclusions: Pretreatment PSF seem to have predictive value for response to CTx in GI cancer patients. PSF changes in non-responding patients may be an early indicator for the need for psychological support in this patient group.
Risk of arterial (ATE) and venous thromboembolism (VTE) in a population-based cohort of bevacizumab-treated metastatic colorectal cancer (mCRC) patients.
Authors: Yu Irene S. , Cheung Winson Y. 
Published: February 2017

545 Background: Bevacizumab is associated with both arterial (ATE) and venous thromboembolic (VTE) events, estimated to be </=15% from clinical trials. Our objectives were to 1) characterize the incidence of ATE or VTE among mCRC patients receiving bevacizumab in a non-clinical trial setting; 2) determine patient and treatment-related factors that predispose to an increased risk of ATE or VTE; and 3) explore how thromboembolism is managed and whether bevacizumab is discontinued and/or resumed after an event. Methods: A random sample of mCRC patients diagnosed between 2008 and 2009, referred to 1 of 5 regional cancer centers in British Columbia, and who were offered bevacizumab was reviewed. Summary statistics were used to describe and compare clinical factors between those who experienced an ATE or VTE and those who did not. Results: Of the 200 mCRC patients offered bevacizumab, 10 never received the drug and 12 were lost to follow up. Among the 178 remaining patients, median age was 61 years, 103 (58%) were male, and 121 (85%) had ECOG 0 to 1. A total of 39 patients (28%) experienced at least 1 documented thromboembolic event. Compared to patients who developed a clot, those who did not had similar median age (62 vs 61), gender distribution (23% men and 20% women), ECOG 0 to 1 (84% vs 85%) and body mass index (26.4 vs 25.3). However, the mean number of bevacizumab doses was higher in the group with thromboembolism (12.6 vs 9.0), suggesting a potential dose-related effect. There were a total of 43 VTE and 5 ATE events documented, with 7 of the 39 patients (18%) experiencing more than 1 event. Bevacizumab was held or discontinued in 60% of cases, but it was continued in 25% of the cases; 4% of the events were fatal, and 10% of the VTE/ATE occurred after bevacizumab was stopped. Conclusions: The incidence of ATE and VTE in a non-study setting appears to be higher than that reported in clinical trials. There may be a dose-related effect. Bevacizumab was not consistently held or discontinued in the setting of a VTE or ATE. Development of guidelines for the management of thromboembolism with bevacizumab may be warranted.
Retrospective study to evaluate interstitial lung disease secondary to oxaliplatin-containing chemotherapy at an NCI-designated comprehensive cancer center.
Authors: Sahai Vaibhav , Nimeiri Halla Sayed , Vergo Maxwell Thomas 
Published: February 2017

547 Background: Oxaliplatin-induced interstitial lung disease (ILD) in gastric and colorectal cancer (CRC) patients is rarely reported and its clinical features remain to be clarified. Methods: Using a computerized database, we retrospectively identified 621 patients with gastric or CRC treated with oxaliplatin-containing regimen from February 2003 to September 2011 at an NCCN institution. Out of 621 patients, chart review was done for 135 patients who developed lung toxicity during or post-chemotherapy. For purpose of data collection, lung toxicity was defined as pulmonary fibrosis, pneumonitis, ARDS, pneumonia-organism unspecified and acute respiratory failure. Imaging data was reviewed for all patients until death or at least 1 year after diagnosis. Results: Of 621 patients, 4 patients developed ILD (0.64%) and of those 2 died due to the toxicity (0.32%). Of the 4 patients, three were symptomatic, three had high Brinkman Index (BI) (≥600) and two showed pulmonary opacities other than lung metastases before chemotherapy. All developed ILD during or within 30 days of oxaliplatin-containing chemotherapy. Extensive work-up in 3 of 4 patients was negative for infection. Chemotherapy regimens included 5-fluorouracil/oxaliplatin (n=2; 85 mg/m2), epirubicin/5-fluorouracil/oxaliplatin (n=1; 130 mg/m2) and capecitabine/oxaliplatin (n=1; 130 mg/m2) with a median of 4.5 cycles (range 2–17 cycles) and a median dose of administered oxaliplatin of 473 mg/m2 (range 260–1445 mg/m2). Conclusions: This is the first retrospective review of patients who received oxaliplatin-containing chemotherapy to determine the incidence and significance of lung toxicity in U.S. and the first to include gastric cancer patients. ILD following oxaliplatin-containing regimen is an uncommon but life-threatening complication. The incident population is too small to infer correlation with BI but it does not seem to correlate with dose or intensity of oxaliplatin. Oncologists should consider chemotherapy-induced hypersensitivity pneumonitis in their differential diagnosis when assessing patients with new onset shortness of breath during or shortly after chemotherapy.
Reasons for delay in time to initiation of adjuvant chemotherapy (AC) for colon cancer (CC).
Authors: Wasserman David Warren , Booth Christopher M. , Hopman Wilma , Al Sharm Abdullah , Biagi James Joseph 
Published: February 2017

548 Background: AC improves survival among patients with colon cancer. Two meta-analyses have demonstrated a decrease in survival with increasing time to AC (TTAC). In this study, we examined individual patient charts to determine reasons for delay in AC. Methods: Medical records of patients with CC who initiated AC Aug 2005-Nov 2010 at the Cancer Centre of Southeastern Ontario were reviewed to capture patient, disease, and treatment characteristics including: medical comorbidities, post-operative complications, whether AC was or was not ordered after initial consultation, and the reasons behind the decision. Dates of surgery, referral, consult, central venous catheter (CVC) insertion, and first cycle of AC were recorded. Patients were then categorized into Group 1-medical/surgical reason for delay (MSRD), defined as presence of post-operative complications or intercurrent medical illness, and Group 2–no MSRD. In Group 2, patients were further categorized as having a non-MSRD, defined as patients in whom AC was deferred at time of consultation due to patient preference and/or further investigations required, vs none. A multivariate logistic regression model was used to determine factors associated with TTAC > 8 weeks (w). Results: For 171 patients: Mean age - 67; 52% male; 79% stage 3; IV AC – 80%, Oral AC – 20%. TTAC for all cases was 8.3 ± 2.3w. Mean intervals ± SD between surgery and TTAC in weeks were: surgery to referral 3.1 ± 2.0; referral to consult 2.5 ± 2.3; consult to oral AC 2.0 ± 2.1; for IV AC, consult to CVC 2.2 ± 1.3, and CVC to AC 0.7 ± 0.8. TTAC did not differ between patients with comorbidities (N= 89) and those without (N=82), p= 0.64, but was greater for patients in Group 1 (N=41 with MSRD) vs Group 2 (N = 130), p= 0.002. In Group 2, 43.8% (N=57) had TTAC > 8w while only 20% of cases (n=26) had a non-MSRD. Factors associated with TTAC>8w were MSRD [OR=5.6 (2.3-13.7), p = <0.001] and non-MSRD [OR=6.7 (2.3-19.5), p = <0.001]. Conclusions: Although medical/surgical complications are a strong predictor of delayed TTAC, this only applies to a small proportion of cases. Accordingly, in most patients TTAC>8w is unrelated to their post-operative medical condition and likely reflects health system and logistical issues.