bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-institution experience using transarterial chemoembolization (TACE) with carboplatinum (carbo) and doxorubicin in patients (pts) with hepatocellular carcimona (HCC) awaiting liver transplantation (LTx).
Authors: Switzer B. A. , Harvey K. , Grossman S. R. , Phillips D. A. , Shah S. A. , Bozorgzadeh A. , Piperdi B. 
Published: February 2017

336 Background: LTx is the best treatment option for multinodular HCC and those with advanced liver dysfunction. Tumor progression occurs in 20-50% of pts on liver transplant list. TACE is increasingly used as locoregional therapy and as a bridge to LTx. We report here our single institutional experience with TACE using carbo and doxorubicin in pts with HCC awaiting LTx. Methods: Retrospective chart review was performed in all pts who had TACE between 2008 and June 2010. Our institutional protocol uses a fixed dose of carbo 300mg, doxorubicin 50mg, in 10ml of lipoidol solution. We analyzed pt demographics, etiologies of liver disease, Child-Pugh status, CLIP scores, size of tumor, alpha-fetoprotein (AFP), toxicity, length of stay, and transplantation statistics. Results: 32 pts (28 men) were treated with 39 TACE procedures. The median age was 57 (32-83). 28 of 32 had cirrhosis with Child's A/B/C 36/51/18% respectively. The major etiologies of cirrhosis were hepatitis C (HCV) 8, alcohol and HCV 19, alcohol 7; portal vein thrombosis in 8 pts. The median tumor size was 6.2 cm (range 2-12 cm) and 81% were multifocal CLIP score 0,1/2,>3 were 5/62/38%. There were no mortality within 30 days of TACE procedure. The majority of the pts were discharged after 24 hr observation; 6 pts require readmissions within 30days. There was no systemic hematologic toxicity. 11 pts had elevated AFP at baseline and 6/11 (54%) had >50 % reduction in AFP value. 11pts (34%) received Ltx; 3 pts came off the LTx list due to disease progression, 2 pts are still on transplant list, and 16pts not able to be listed. 42% of pts received sorafenib in addition to TACE. The median time from last TACE to LTx was 55 days and 4 pts received transplantation within 30days. Very good pathological treatment effect was observed in 8/11 explanted liver. Conclusions: Our regimen of TACE with carbo/doxorubicin appears to be a safe and tolerable approach for localized treatment as a bridge to liver transplantation. It has acceptable toxicity and is associated with good AFP and pathological responses. We plan to evaluate different baseline parameters for better pt selection. No significant financial relationships to disclose.
Evaluation of obstructive jaundice as a poor prognostic factor after curative resection of advanced gallbladder cancer.
Authors: Nasu Y. , Kondo S. , Hirano S. , Tanaka E. , Tsuchikawa T. , Matsumoto J. , Kato K. 
Published: February 2017

340 Background: Gallbladder cancer (GBC) is one of the most common malignancies of the biliary tract. Because of the lack of specific presentations, this condition is frequently diagnosed only at an advanced stage. Obstructive jaundice is generally regarded as an indicator of far advanced disease, unresectability, and poor prognosis. The aim of this study was to evaluate clinicopathological factors, especially jaundice, influencing outcome after radical resection of gallbladder cancer, in order to identify the patients benefiting from radical surgery. Methods: Seventy-five patients with GBC underwent surgical resection between 1998 and 2008. A retrospective analysis was conducted on sixty-four patients with UICC T2 or more tumors. Clinicopathologic features, extents of resection, and survival rates were investigated retrospectively. Obstructive jaundice was defined that serum T-bil level was more than 2.0 mg/ml. Patients with jaundice underwent ENBD or PTBD and curative resection was performed when serum T-Bil level decreased below 2.0 mg/ml. Right after laparotomy, para-aortic lymphadenectomy and frozen section pathology were performed to convert a radical resection to a palliative procedure when a para-aortic lymph node was positive. Results: The three and five-year disease-specific survival rates were 47% and 41%, respectively. Nine patients survived for more than five years.Univariate analysis showed that blood loss during operation, hepatic invasion, portal vein invasion, N category, M category after postoperative pathological examination and residual tumor were significant prognostic factors (p<0.05), but multivariate analysis showed that M category only was independent prognostic factor (p<0.05). Five-year disease-specific survival rates for patients with (n=37) and without (n=27) obstructive jaundice were 47% and 35%, respectively (p=0.69). Conclusions: Obstructive jaundice had no impact on postoperative survival as long as metastatic disease was exclueded and adequate resection of the hepatic hilum was performed. Aggressive surgery might bring long-term survival in selected patients even with obstructive jaundice by advanced gallbladder cancer. No significant financial relationships to disclose.
Hypofractionated radiotherapy for patients with locally advanced pancreatic cancer using tomotherapy Hi-Art and CyberKnife: A study of the treatment outcome and failure patterns.
Authors: Jang H. 
Published: February 2017

342 Background: To evaluate the treatment outcome and pattern of failure in the patients with locally advanced pancreatic cancer, who were treated with hypofractionated radiotherapy (RT) using TomoTherapy Hi-Art and Cyberknife. Methods: From April 2004 to May 2010, Twenty four patients with locally advanced pancreatic cancer received hypofractionated RT using TomoTherapy Hi-Art and Cyberknife at Seoul St. Mary's Hospital, the Catholic University of Korea. Eleven patients (45.8%) were treated using TomoTherapy Hi-Art and 13 patients (54.2%) using Cyberknife. The total dose delivered were 45∼55 Gy (median: 50 Gy) in 15∼22 fractions with TomoTherapy Hi-Art and 24∼40 Gy (median 30 Gy) in 3∼5 fractions with Cyberknife. The RECIST version 1.1 was used for the response evaluation. The follow-up duration was 3.0∼77.1 months (median: 34 months). Results: In the initial response evaluation, the rates of partial response, stable disease and progressive disease were 45.8%, 54.2% and 0%, respectively. Median survival duration was 11.1 months. One year and two year survival rates were 39.4% and 21.1%, respectively. Two patients (8.3%) had local failures and 11 patients (45.8%) had distant failures. Distant failures were main cause of failures. Median time to distant failures was 7.8 months and one year distant progression-free survival rate was 35.1%. The difference of the treatment outcome between TomoTherapy Hi-Art and Cyberknife was not statistically significant. Most patients experienced abdominal discomfort and pain after RT. However, no severe gastrointestinal complication such as ulcer, bleeding, perforation and fistula were noted. Conclusions: Hypofractionated RT for the patients with locally advanced pancreatic cancer showed excellent local control. However, overall survival still remains poor because of distant failures. Therefore, effective systemic chemotherapy should be considered with RT, either concurrently or sequentially. No significant financial relationships to disclose.
Safety of liver resection for HCC in patients previously treated with sorafenib.
Authors: Belghiti J. , Saget A. , Fuks D. , Dokmak S. , Faivre S. J. , Ronot M. , Paradis V. 
Published: February 2017

345 Background: The efficiency of sorafenib in HCC has led to its utilization in the neo-adjuvant setting in selected cases. We assessed the safety of liver surgery in patients previously treated with sorafenib. Methods: From January 2009 to April 2010, 8 patients were resected following treatment with sorafenib. The median length of treatment was 1.5 months (range: 0.23-15). Mean size of tumors was 6.4cm (2-10). Alphafoetoprotein (AFP) was elevated in 5 patients, ranging from 45 to 100,000. Six patients had chronic liver disease. The cohort of 8 patients was cross-matched with 17 comparable patients who underwent primary resection without sorafenib during the same period. Results: After sorafenib therapy there was a decrease of HCC size (n=4, median size decrease of 55%) and AFP level (n=4). AFP returned to normal in 3 patients. Peri-operative data showed that previous treatment with sorafenib was not associated with increased length of surgical procedure (265 vs. 293 min), blood loss (400 vs. 530cc) or blood transfusion (0 vs. 5 Units). No mortality was reported, while overall morbidity (50 vs. 61%), length of stay (10 vs. 12 days) and intensive care requirement (43 vs. 44%) were similar in both groups. Recovery of postoperative liver biochemical tests did not show significant differences between the groups. Specimen analysis showed a higher rate of tumor necrosis in the sorafenib group (100% vs 46%) while no hepatotoxicity induced by chemotherapy was found. Conclusions: The administration of preoperative sorafenib therapy, which can improve disease control of HCC, does not increase operative risk. No significant financial relationships to disclose.
Hepatic artery infusion for recurrent or chemoresistant hepatic malignancy.
Authors: Wanebo H. J. , Reddy Sanikommu S. , Padmaja V. , Taneja C. , Cummings F. J. , Begossi G. , Belliveau J. 
Published: February 2017

351 Background: Previously treated hepatic colorectal metastases (CRC) and advanced hepatocellular cancer (HCC) are tumor challenges frequently unresponsive to systemic chemotherapy (CT). We reviewed survival outcome in chemoresistant/high-risk patients following hepatic artery infusion (HAI) in 21 CRC pts, 10 HCC pts, and 6 miscellaneous metastatic cancers. Methods: Patient groups: 21 CRC pts (16 M, 5 F), mean age 63, 16 had metachronous (DFI-17 mos), and 5 synchronous CA; liver extent: 76% multiple (>5) mets or extensive bilateral, CEA (ng/m), >100, 8 pts > 50 (3 pts) < 5 (3 pts) and NA = 7 pts. Previous CT:FU/LV (11pts), oxaliplatin (OX) or irinotecan (IR) (10 pts). Liver surgery: partial resection/RFA = 9 pts. HCC = 9 pts, cholangio CA (1), M/F 5/5; av. age 63. Previous RX hepatic lobectomy 4 pts, RFA/TACE = 3 patients. Miscellaneous GP (therapy): hepatic lobectomy + HAI were done in metastatic lung (1), breast (1), advanced gall bladder cancer (GBCA) (T 3-4) (2 pts); HAI alone was done in Br. CA (1) carcinoid (1) treatment protocols: CRC protocol: HAI-FUDR 12-15 mg/kg/d, dexamethasone 2mg.kg/d, leucovorin 20 mg/m2 /d (14 d) plus bolus infusion (d1), oxaliplatin (OX) 130 mg/m2 (or cisplatin (CIS) 100 mg/m2 d1); systemic RX: d20-30. OX I.V. 130 mg/m2, capecitabine 750-1,000 mg/m2/d x 10 days (also used in Miscel. Grp.) HCC Protocol: HAI-14 d as in CRC Protocol. Bolus infusion d1-doxorubicin 75 mg/m2 or OX or CIS as in CRC schema. Results: CRC:OS-CRC post start HAI = med/16mos., 2yr/5yr = 27%/6%. HCC OS = 9 mos. Median (3-12 mos in 9 evaluable pts.; 1 HCC pt, with recurrence 2 yr. post central hepatectomy was treated over 3.5 yrs. with HAI + RFA/TACE – (OS-67mo). Miscellaneous group included lung (11 mos) Br CA (23, 9 mos) adv. Carcinoid (3 mos), GBCA (2 pts > 60 mos). Major complications: pump malfunction (4 pts), misperfusion (2) pts, infected pocket (2) pts, duodenal fistula (1) pt. Conclusions: Hepatic artery infusion alternating with systemic chemo therapy has apparent survival benefit in selected patients with persistent or progressive chemo resistant malignancy from metastatic CRC, HCC, or selected miscellaneous cancers (breast, lung, liver, gall bladder cancer) and warrants further study. No significant financial relationships to disclose.
Gallbladder cancer: The forgotten medical oncologist.
Authors: Teo M. , O'Keeffe M. , Moylan E. , O'Reilly S. , Bird B. R. , Power D. G. 
Published: February 2017

354 Background: Gallbladder cancer (GBC) is rare, is often diagnosed at an advanced stage, and survival >1 yr is uncommon. Recent randomized trials have demonstrated improved survival with well-tolerated chemotherapies. In this light, we retrospectively reviewed referral patterns to medical oncology services in our region. Methods: Prospectively maintained departmental databases from three hospitals serving 480,000 people were reviewed. Patient demographics, disease and treatment details, and outcomes were analyzed. Regional figures were obtained from National Cancer Registry data. Results: Between March 2003 and September 2010, 17 GBCs were referred to medical oncology, representing 25.5% of total GBC diagnosed in the region (Table). Median age at diagnosis was 63.6 years (range 47.0–72.5) and 65% (n=11) were female. The majority (n=13) initially presented with metastatic or locally advanced disease and 6 of these patients underwent cholecystectomy. Of those with early-stage disease, 2 patients were referred with relapsed disease and 2 were referred for adjuvant treatment. Sites of involvement were liver (10), lymph nodes (3), peritoneum (3), duodenum (2), gallbladder bed (1), and pancreas (1). No extra-abdominal metastases were noted. All patients were scheduled for chemotherapy, but 3 were not treated due to worsening performance score. Of the 14 patients who received chemotherapy, 7 received gemcitabine, 5 received 5FU and 2 received cisplatin/gemcitabine. Median duration of chemotherapy was 3.8 months (range 0.7–8.1) and 3 patients (21%) received second-line chemotherapy. 13 patients (76.5%) had died at the time of analysis. Median follow-up was 6.7 months (range 1.7-73.9) and median overall survival was 6 months. Conclusions: A minority of patients with GBC were referred to medical oncology. Given the emergence of level 1 evidence reporting a survival benefit with well-tolerated combination chemotherapy and the potential for adjuvant treatment, higher referral rates may lead to improved outcome. [Table: see text] No significant financial relationships to disclose.
Prospective study of genetic mutations in matched tumor and plasma specimens in colorectal cancer patients.
Authors: Perkins G. , Dukes J. , Yap T. A. , Riisnaes R. , Pope L. , Cassidy A. , Denholm K. A. , Gonzalez de Castro D. , Chau I. , De Bono J. S. 
Published: February 2017

356 Background: Circulating free DNA (cfDNA) represents a minimally-invasive resource for detecting mutations in advanced cancer patients. The primary objective of this study was to determine if cfDNA is representative of tumor tissue for multiplex mutation detection utilizing Sequenom MassARRAY. Methods: Samples were spiked with dilutions (10ng/μl to 0.01ng/μl) of HCT116 DNA containing KRAS G13D mutations to determine assay sensitivity and specificity. Metastatic colorectal cancer patients referred to the Drug Development Unit at the Royal Marsden Hospital between 9/09-8/10 gave their consent to provide DNA from matched archival formalin fixed paraffin-embedded (FFPE) tumor and plasma. Samples had ∼200 described gene mutations genotyped using Sequenom MassARRAY (OncoCarta Panel). Results: Serial dilution spiking experiments revealed that the KRAS G13D mutation was reproducibly detectable to 40ng/mL of HCT116 DNA; 26 patient samples were then analyzed. KRAS, BRAF and PIK3CA mutations were detected in 8 (31%), 3 (12%) and 3 (12%) tumor specimens respectively; 100% concordance for KRAS status was observed between multiple FFPE biopsies from the same patient and analysis by Amplification Refractory Mutation System (ARMS)-Scorpion PCR. The median quantity of cfDNA was 353ng/ml (range 106-4603). Concordance between matched FFPE and cfDNA was 88% for KRAS and 100% for BRAF mutations. No patients with wildtype KRAS or BRAF tumor genotypes had mutations in their respective cfDNA confirming the high specificity of cfDNA analysis. Three patients had detectable PIK3CA mutations; 1 patient had a E346K mutation detected in both FFPE tissue and plasma; 1 patient had E545K detected only in FFPE and the other had E542K detected in a liver metastasis but not in the colorectal primary or plasma. The recently reported oncogenic AKT1 E17K mutation was detected in 1 patient in tissue and plasma. No mutations in any of the other tested oncogenes studied were detected. Conclusions: A high concordance in detected mutations was observed between FFPE tumor and matched cfDNA. cfDNA is representative of tumor DNA and may be used for the prospective selection of cancer patients for treatment with targeted therapeutics. No significant financial relationships to disclose.
Compliance, capacity, and quality in colonoscopy screening for CRC: A novel solution.
Authors: Lloyd S. C. 
Published: February 2017

357 Background: CRC is predominately preventable with high quality colonoscopy screenings. Unfortunately, less than half of Americans are “up-to-date.” When referred by primary care providers, less than half complete the process. We proposed to include the primary care provider (PCP) in a novel training program to extend skills from sigmoidoscopy to full colonoscopy in a “mentored and monitored” model. We know that quality in colonoscopy can vary widely (ten fold within a single 12-man group). The protective benefits of colonoscopy reflect the thoroughness of the removal of polyps. Unfortunately, the ACS projections for 2010 predict an increase of 4,400 deaths from CRC over 2009, an 8% rise! Furthermore the death rate for African American men has RISEN 28% since 1960. We are loosing a battle for which we posses the tools to win. To achieve victory we must successfully address all three factors: compliance, capacity and quality. Methods: Thirty primary care physicians in two states (SC, FL) were recruited. We measured compliance rates within the practice before and after enrollment. We further evaluated quality of the colonoscopies as reflected in completion, yield and complications. Results: Compliance more than doubled (38% to 84%). As a compliance enhancement tool, the results were outstanding. The evaluation of quality then became of paramount importance. The gross completion rate was 98.3%, the adenoma detection rate (reflecting polyp yield) was 38%. In over 20,000 cases there were only 5 perforations, substantially below published rates. The quality was consistently at the level of experienced conscientious gastroenterologists. The details of the training program and the use of the “two-man” colonoscopy technique have been reviewed elsewhere (MEDICAL CARE, Aug 2010). Conclusions: If replicated nationally, this model has the potential for saving 25,000 lives annually. The participation of the patient's PCP is a powerful influence for improved compliance. The availability of an “expert” for mentoring and monitoring results in outstanding and consistent quality. The model has the potential to dramatically enhance compliance simultaneously increasing capacity while maintaining outstanding quality. No significant financial relationships to disclose.
Evaluation of response after chemoradiation for rectal cancer as a predictive factor for the benefit of adjuvant chemotherapy: A pooled analysis of 2,724 individual patients.
Authors: Beets G. L. , Maas M. , Nelemans P. J. , Valentini V. , Crane C. H. , Capirci C. , Roedel C. , Kuo L. , Garcia-Aguilar J. , Glynne-Jones R. 
Published: February 2017

361 Background: Neoadjuvant chemoradiation (CRT) for rectal cancer increasingly results in pathologic response. It has been suggested that patients with different degrees of response might not have the same benefit of adjuvant chemotherapy. The aim was to determine whether patients with a pathologic complete response (pCR), ypT1-2 or ypT3-4 tumor after CRT for rectal cancer have different benefits of adjuvant chemotherapy for disease-free survival. Methods: Authors from studies evaluating different degrees of response to CRT were contacted to share individual patient data. The collected individual patient data were pooled into one dataset. To evaluate the effect of adjuvant chemotherapy on disease-free survival multivariate analyses according to the Cox proportional hazards model were performed. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for 3 subgroups: patients with pCR(ypT0N0), ypT1-2 tumor and ypT3-4 tumor after CRT. To determine benefit of adjuvant chemo for different pathologic N-stages we performed subgroup analyses. Results: 2,724 patients were included. 811 had pCR (28%), 863 had ypT1-2 (30%) and 1050 had ypT3-4 (37%). Median follow-up was 50 months (range 0-277). 41% underwent adjuvant chemotherapy, which consisted mostly of 5-FU based chemotherapy. The HR with 95%CI for disease-free survival for adjuvant chemotherapy was 0.94 (0.50-1.78) for patients with pCR, 0.61 (0.40-0.92) for patients with ypT1-2 tumors and 0.97 (0.75-1.25) for patients with ypT3-4 tumors. ypT1-2N0 patients benefited most from adjuvant chemo: HR 0.45 (0.27-0.75) vs. 0.79 (0.31-1.95) for patients with ypT1-2N+. For ypT3-4 patients pN-stage did not alter benefit of adjuvant chemo. Conclusions: Patients with pCR or ypT3-4 residual tumor after CRT do not seem to benefit from adjuvant chemo. This might be due to the already good prognosis of patients with pCR and less responsiveness to 5-FU based chemotherapy in the poor responders (the ypT3-4 tumors). Possibly adjuvant chemotherapy can be omitted or adapted for these patients. Patients with ypT1-2N0 benefit most from adjuvant chemo. No significant financial relationships to disclose.
AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer.
Authors: De Gramont A. , Van Cutsem E. , Tabernero J. , Moore M. J. , Cunningham D. , Rivera F. , Im S. , Makrutzki M. , Shang A. , Hoff P. M. 
Published: February 2017

362 Background: Bevacizumab (BEV), a humanized anti-VEGF monoclonal antibody, has demonstrated clinical efficacy in combination with 5-FU-based regimens in patients with metastatic colorectal cancer. The therapeutic impact of concurrent BEV with either FOLFOX4 or XELOX chemotherapy in the adjuvant setting was evaluated in this international, controlled phase III trial. Methods: Eligible patients had high-risk stage II or stage III colon cancer and had undergone surgical resection. Patients were randomly assigned to one of three treatment groups and stratified by geographic region and tumor stage: Arm A: FOLFOX4 on weeks 1–24; Arm B: FOLFOX4 + BEV on weeks 1–24, then BEV alone on weeks 25–48; Arm C: XELOX + BEV on weeks 1–24, then BEV alone on weeks 25–48. The primary endpoint was disease-free survival (DFS) for patients with stage III colon cancer; secondary endpoints included overall survival (OS), and safety. DFS/OS follow-up assessments were performed every 6 months after randomization for 4 years, then annually until recurrence or death. Results: 3,451 (2,867 stage III) patients were enrolled between December 2004 and June 2007; median age was 58–59 years. Median duration of follow-up was 48 months (range 0–66 months). BEV did not prolong DFS or OS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer based on the final efficacy analysis conducted in September 2010. Efficacy results favored the chemotherapy-alone control arm. Numerically more relapses and deaths occurred in both the BEV arms compared to control. The observed adverse events were consistent with those previously reported in pivotal trials of BEV across tumor types for approved indications. Conclusions: The primary endpoint of the AVANT study was not met. BEV does not prolong DFS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer. The safety profile of BEV was consistent with prior study results. [Table: see text]