bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant therapy in resected pancreatic cancer: A systematic review of literature with meta-analysis of randomized clinical trials.
Authors: Drudi Fabrizio , Tassinari Davide , Ridolfi Claudio , Affatato Alessandra , Tamburini Emiliano , Santelmo Carlotta , Carloni Federica , Gianni Lorenzo , Veneroni Luigi , Donati Gabriele , Ravaioli Alberto 
Published: February 2017

342 Background: To assess the role of adjuvant treatments (AT), adjuvant chemotherapy (AC) and adjuvant chemo-radiotherapy (ACR) in resected pancreatic adenocarcinoma. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 1966 to 2011 was independently performed by two authors (FD and DT). All the randomized phase III trials investigating the role of AT in radically resected pancreatic cancer were considered eligible and included into the pooled analysis. 5-year-survival rate in patients treated with AT was the primary end point of the trial, 5-year-survival rate of patients treated with AC and ACR, and the 5-year-survival number needed to treat (NNT) of AT, AC and ACR were the secondary ones. Results: The outcomes of 1402 patients enrolled in 8 trials were compared in the pooled analysis. 816 patients were treated with AT (540 with AC and 276 with ACR), and 586 were enrolled in the control arm (no adjuvant treatment). Significant improve in 5-year-survival rate was observed for AT and AC (odds ratio of 0.636, p<0.05 and 0.422, p<0.01 respectively), but not for ACR (odds ratio=1.139, p=0.489), with a 5-year survival NNT of 20, 10 and 38 respectively for AT, AC and ACR. Low to moderate heterogeneity between the trials was documented both for AT (I2=58%) and AC (I2=31.63%), but not for ACR (I2=0%,). Conclusions: Our data confirm that adjuvant chemotherapy improves the 5-year survival rate in radically resected cancer patients and gemctabine based regimens seem to be better than FU based regimens.
Developments of treatment of advanced intrahepatic cholangiocarcinoma: An analysis of systemic and local therapy modes in 57 patients.
Authors: Stuebs Patrick , Habermann Peter , Garlipp Benjamin , Schuette Kerstin , Zierau Kathrin , Lippert Hans , Fahlke Joerg 
Published: February 2017

346 Background: Treatment of advanced CCC remains difficult. Sophisticated therapy of individual locations is essential due to differing biological characteristics. Apart from recent systemic therapeutic approaches, combined treatments using, among others, locally ablative procedures offer chances of extended life expectancy. Methods: This analysis is based on a phase II study on treatment of advanced BTC (biliary tract cancer) with gemcitabine/docetaxel(G/D) in 79 patients (pts).Observing purely intrahepatic CCC, omitting Klatskin tumors, modes of therapy were advanced further. In addition to local ablation by TACE (TA) systemic therapy was modified using Gemcitabine/Oxaliplatin(G/O). TACE could only be employed initially in purely intrahepatic inoperable findings. Treatment was later adjusted using local brachytherapy followed by intraarterial chemotherapy with 5-FU (AL + i.a.). A retrospect data analysis of 57 pts diagnosed with advanced intrahepatic CCC was deployed after collecting cases prospectively. A matched pair analysis in relation to data from systemic treatment was performed. Ultimately, 5 groups were formed: 1- 12 pts being treated with TACE only (TA); 2- 15 pts receiving TACE initially followed by systemic therapy of progressive disease (TA+G/D); 3- 11 pts receiving G/D; 4- 14 pts receiving G/O; 5- 5 pts receiving AL+i.a. Treatment continued until either disease progressed or inacceptable side effects occurred. Results: Median time of survival in the TA group was 4.2 months, TA+G/D 20.1 months, G/D 8.5 months and G/O 15.0 months. Currently no conclusive data has been obtained in the AL+i.a. group, yet. Median time to tumour progress was 2.1 months in TA, 5.1 months in TA+G/D, 3.5 months in G/D and 7.7 months in G/O. In the G/O group a case of secondary respectability occurred. Results were achieved with an acceptable toxicity profile and satisfactory quality of life. Conclusions: When the advanced intrahepatic CCC, voiding Klatskin tumours, are limited to the liver and do not offer the possibility of surgical intervention, a combination of treatments should be commenced. Improved systemic protocols can additionally achieve extended time of survival.
Experience with sorafenib treatment of hepatocellular carcinoma (HCC) in patients in a Brazilian center.
Authors: Alves Daniele Evaristo , Alves Rogério , Poletti Paula , Gampel Otavio 
Published: February 2017

350 Background: HCC is the most important cause of death in patients with liver cirrhosis. Sorafenib is established as treatment for patients with compensated liver disease, but there are few studies for patients with more advanced cirrhosis. Methods: From May 2008, 75 patients intermediate - advanced (according to BCLC) HCC patient initiated sorafenib at 800 mg daily doses, 71 were treated or had been treated for more than 1 month and were recruited to data analysis on August 2011, regarding sex, age, association with diabetes, etiology of cirrhosis, treatment intervals, dose reductions, adverse events, response rates, Child-Pugh’s classification, global survival and survival according Child-Pugh status Results: The median age of study population of 75 patients (60 men and 15 women) was 63,78 years. The cirrhosis etiology was 46% VHC, 13% N.AS.H, 10,71% cryptogenic cirrhosis and 6.15% with VHB. 40% of the patients were Child A, 41.5% B and 10.8% C . 34% were diabetic, the median treatment interval of sorafenib was 223 days (7-1080 days); Overall response rate was 66%: 37.5 % had stable disease and 25% had partial response with tumor shrinkage by Recist criteria. Adverse events were related in 53.84 % of the patients and 60 % of them needed to have dose modifications. The common adverse events were diarrhea: 48.5%, nausea and vomiting: 31.4 %, abdominal pain: 45.7%, hand-foot syndrome 25.7%, arterial hypertension 8.5% and 8.5 % bleeding. The incidence of adverse events didn’t differ considering each Child-Pugh’s subgroup. The median survival time was 12.1 months. The one and two year survival preliminary rate were 75 % and 68% in Child-Pugh A patients and 40 and 10 % in Child-Pugh B patients (p=0.002) respectively. Conclusions: Our results contributed to emphasize treatment safety of sorafenibe within Hcc patients with more advanced liver disease. In this study population, 52.7% of the patients had liver disease Child B/C and sorafenib was well tolerated (53 % had adverse events) in all subgroups with acceptable response and treatment intervals despite of advanced liver disease, but the survival rates trends to be statistically higher in patients with Child A than Child B.
The efficacy of capecitabine and temozolomide for the treatment of metastatic neuroendocrine tumors: Memorial Sloan-Kettering Cancer Center experience.
Authors: Ganetsky Alex , Adel Nelly G. , Do Kinh Gian , Reidy Diane Lauren 
Published: February 2017

363 Background: Emerging literature has suggested the benefit of capecitabine/temozolomide (C/T) therapy in metastatic pancreatic NETs (pNETs) as first line therapy. We conducted a retrospective analysis of the efficacy of (C/T) therapy in all patients with metastatic NETs treated at MSKCC. Methods: Using the electronic pharmacy database, we included all patients’ ≥ 18 years of age who received C/T combination therapy for pNETs between 1/2003-10/2010. Primary endpoint was the overall response rate (ORR). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Response rates were evaluated by a radiologist using CT scans and per RECIST 1.1. MGMT tumor expression was conducted to correlate with response. Results: Twenty patients (mean age 64, 35% female) were identified. There were 16 (80%) pNETs (1 functional, 15 nonfunctional), 2 (10%) carcinoid, 1 high grade biliary (5%) and 1 (5%) gastric neuroendocrine carcinoma. Eight tumors were low grade (1 carcinoid, 7 pNET), 8 intermediate grade (7 pNET, 1 carcinoid), and 4 high grade (2 pNET, 1 stomach, 1 biliary). Twelve (60%) received C/T in the first-line setting and 8 in the relapsed setting. Six (30%) had a partial response and 7 (35%) had stable disease. There were no complete responses ( Table 1 ). With a median follow-up of approximately 3 years, the PFS was 16.4 months. Four pNET patients had unresectable disease at presentation and 2/4 were resected and rendered free of disease after C/T therapy. There were no high grade responders. Liver tumor burden (0%, <10%, 10-50%, >50%), number of prior treatments, and tumor grade did not predict response. Grade 3-4 events potentially related to C/T included neutropenia (1/20, 5%), nausea (3/20 15%), diarrhea (1/20, 5%), and fatigue (3/20, 15%). Conclusions: Combination C/T for the treatment of pNETs is an effective regimen for well differentiated NETs irrespective of tumor burden and prior treatment. No responses were seen in our carcinoid patients. MGMT expression will be presented at the meeting. [Table: see text]
Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory K-RAS wild-type (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO.20 trial.
Authors: Siu Lillian L. , Shapiro Jeremy D. , Jonker Derek J. , Karapetis Christos Stelios , Zalcberg John Raymond , Simes John , Couture Felix , Moore Malcolm J. , Price Timothy Jay , Siddiqui Jehan , Nott Louise M. , Charpentier Danielle , Liauw Winston S. , Sawyer Michael B. , Jefford Michael , Magoski Nadine M , Haydon Andrew Mark , Walters Ian B. , Tu Dongsheng , O'Callaghan Christopher J. ,   NCIC Clinical Trials Group and AGITG
Published: February 2017

386 Background: The anti-EGFR monoclonal antibody CET has improved survival in pts with MET, chemotherapy refractory, K-RAS wild type (WT) CRC. The addition of BRIV, a tyrosine kinase inhibitor targeting vascular endothelial and fibroblast growth factor receptors (VEGFR/FGFR), to CET has shown encouraging activity in an early phase clinical trial. Methods: Pts with MET CRC previously treated with combination chemotherapy were randomized 1:1 to receive CET 400 mg/m2 IV loading dose followed by weekly maintenance of 250 mg/m2 plus either BRIV 800 mg PO daily (Arm A) or placebo (Arm B). Pts may have had 1 prior anti-VEGF, but no prior anti-EGFR therapy. The trial was amended shortly after opening to enrol K-RAS WT pts. Primary endpoint was overall survival (OS). Results: From 02/2008 to 02/2011, 750 pts were randomized (376 in Arm A and 374 in Arm B). Demographics: median age=64 (range 27-88); male=64%; ECOG 0:1:2 (%)=32:58:10; >3 prior chemotherapy regimens=92%; prior anti-VEGF therapy=41%; K-RAS WT=97%. Median OS in the intent-to-treat population was 8.8 months in Arm A and 8.1 months in Arm B, hazard ratio (HR)=0.88; 95% CI=0.74 to 1.03; p=0.12. Median progression-free survival (PFS) was 5.0 months in Arm A and 3.4 months in Arm B, HR=0.72; 95% CI=0.62 to 0.84; p<0.0001. Both partial responses (13.6% vs 7.2%, p=0.004) and stable disease (50% vs 44%) were higher in Arm A. Incidence of any ≥grade 3 adverse event (AE) was 78% in Arm A and 53% in Arm B. Most frequent ≥grade 3 AEs were fatigue (25%), hypertension (11%) and rash (10%) in Arm A, vs fatigue (11%), rash (5%) and dyspnea (5%) in Arm B. Time to deterioration of physical function was shorter and global quality of life scores were lower in Arm A vs Arm B. Pts received ≥90% dose intensity of CET=57% in Arm A vs 83% in Arm B; of BRIV/placebo=48% in Arm A vs 87% in Arm B. Conclusions: Despite positive effects on PFS and objective response, the combination of CET+BRIV did not significantly improve OS in pts with MET, chemotherapy refractory, K-RAS WT CRC. AEs were consistent with those reported for each drug given as monotherapy.
Second primary malignancy in patients with long survival after esophagectomy for squamous cell carcinoma of the esophagus.
Authors: Hiraiwa Kunihiko , Koyanagi Kazuo , Kawakubo Hirofumi , Omori Tai , Kakefuda Toshihiro 
Published: February 2017

42 Background: Patients after esophagectomy for esophageal squamous cell carcinoma (ESCC) were reported to have a remarkably high risk of subsequent cancer of head and neck cancer (Matsubara, et al. J Clin Oncol 2003). The outcome was reported to be signiﬁcantly less favorable as a result of difﬁculty in early detection. However, magnifying endoscopy combined with narrow band imaging (NBI) system recently allowed early detection of head and neck cancer. This study was to assess the risk of subsequent malignancies after esophagectomy for ESCC for the establishment of an adequate follow-up program. Methods: Eighty patients with ESCC who had undergone radical esophagectomy at the Kawasaki Municipal Hospital from 2000 to 2006 were eligible for this study. Among the eighty patients, we analyzed 41 cases who survived more than 5 years after esophagectomy. Results: Median survival of the 41 patients was 7.1 years. Two patients who developed squamous cell carcinoma in the lung within 5 years after esophagectomy were not included in the group of subsequent second malignancies, because it was difficult to distinguish primary tumors from metastatic tumors. Second malignancies were found in 7 (17.1%) of 41 patients subjected to curative esophagectomy. Subsequent malignancies were most frequently found in the head and neck region (n = 4; 57.1%), followed by the residual esophagus (n = 1; 14.3%), colon (n = 1; 14.3%), and breast (n = 1; 14.3%). The subsequent cancers in head and neck, and residual esophagus were detected from 1 to 9 years after esophagectomy in an early stage with magnifying endoscopy combined with NBI system. They were curatively resected by endoscopic laryngo-pharyngeal surgery (ELPS) and endoscopic submucosal dissection (ESD). The subsequent cancers in colon and breast were also curatively resected by operation. Conclusions: Patients after esophagectomy for ESCC had a high risk of subsequent cancer of head and neck cancer. Minute postoperative surveillance with magnifying endoscopy combined with NBI system is strongly recommended even more than 5 years after esophagectomy. Early detection of second malignancies allowed less invasive treatment such as ELPS and ESD with favorable outcome.
Disease-related knowledge and attitudes among familial adenomatous polyposis kindreds.
Authors: James Aimee S. , Chisholm Phillip , Baxter Melanie , Davidson Nicholas 
Published: February 2017

423 Background: Familial Adenomatous Polyposis (FAP) is a highly penetrant autosomal dominant disorder, for which patients and their first degree relatives (FDRs) should receive genetic counseling in addition to regular endoscopic and clinical screening. Previous studies indicate under-use of screening and preventive care among FAP families but the reasons are not well understood. Our objective was to identify potential areas of need for information and support among FAP kindreds from a single center registry. Methods: FAP patients and FDRs were solicited to participate in a survey on health and information needs. Multiple attempts were made to reach potential respondents. Sixty-one patients were solicited and 40 surveys were collected (Response Rate = 61%). Survey respondents also recruited 10 additional FDRs. Participants (N=50) could choose to complete their survey online, by telephone, or on paper. Descriptive analyses were conducted using SPSS. Results: The average age of respondents was 50.2 years, 62% (n=31) were female; and 70% (n=35) had FAP. Among the responses to knowledge questions, half of respondents (n=25) stated that children who do not inherit FAP from their parents can still pass on the disease to their own children. In addition, only 62% (n=31) answered correctly that children of an affected FAP parent have a 50% risk of the disease ; nearly a quarter (n=12; 24%) said they did not know. Respondents also reported FAP-specific needs, including worries and concerns about children developing FAP (19% rated this as moderate or high), fears about developing cancer (33%), uncertainty about the impact of FAP (38%), dealing with the impact of FAP on the family (34%), obtaining medical information about FAP (37%), and understanding information relevant to FAP (31%). Conclusions: The data in this single center survey suggest that substantial knowledge gaps exist within FAP kindreds, both in affecteds and also FDRs. In particular, there was incomplete understanding regarding the heritable risks and also disease specific risks for children. These data indicate that members of FAP kindreds have unmet needs regarding their disease and risk, and want information that can help them manage their disease.
Early thermal quantitative sensory testing to measure acute oxaliplatin neurotoxicity and predict chronic neuropathy in gastrointestinal malignancies.
Authors: Reddy Sangeetha , Kwon Nancy , Nimeiri Halla Sayed , Mulcahy Mary Frances , Harden Robert Norm , Benson Al Bowen , Paice Judith A. , Vergo Maxwell Thomas 
Published: February 2017

425 Background: Acute oxaliplatin neurotoxicity has been shown to be predictive of chronic oxaliplatin neuropathy. A recent study by Attal et al showed that tQST (thermal quantitative sensory testing) at cycle 4 provides a noninvasive method for predicting chronic neuropathy. A high risk population defined as those experiencing pain with a ≥ 20 degree cold stimulus had an OR of 39 for developing a severe chronic neuropathy at 1 year. Our study was designed to test the utility of tQST at earlier time points for predicting chronic neuropathy. Methods: Gastrointestinal cancer patients receiving FOLFOX were evaluated over a 1 year period for the development of acute and chronic oxaliplatin neurotoxicity: before starting FOLFOX, 1 hour into oxaliplatin infusion, before cycles 2, 4 and 12, and 1 year after start of treatment. Patients underwent a series of QSTs to measure thermal and mechanical sensitivities, fine motor skills, vibration detection, validated questionnaires, and presence of hyperalgesia. Results: Preliminary analysis of 13 patients using cycle 4 data as a surrogate for chronic neuropathy shows that cold pain (the temperature at which subjects report pain) prior to starting FOLFOX and at cycle 2 is predictive of cold pain at cycle 4, rs = 0.67 (p=.01) and 0.49 (p=0.09), respectively. There is a significant difference in cold pain across all time points between high and low risk populations(p=0.02 at baseline, p=0.04 during cycle 1, p=0.08 at cycle 2, and p=0.03 at cycle 4). Correlation between cycles 1 and 4 is seen for changes in cold sensitivity from baseline, rs = 0.52 (p=0.07). Conclusions: Baseline tQST correlates to cycle 4 measurements and may be an early predictor of patients at the highest risk for chronic neuropathy. These preliminary data indicate an inherent, pre-existing sensitivity to oxaliplatin induced chronic neuropathy for high risk patients which can be detected with tQST. Early identification of these patients can allow for preventive measures to decrease the incidence of this debilitating chronic adverse effect of oxaliplatin. A larger biomarker validation study is planned using tQST to stratify patients into high and low risk.
Prognostic effects of circulating markers of epithelial mesenchymal transition (EMT) in metastatic colorectal cancer patients.
Authors: Shah Neeraj Nailesh , Lieu Christopher Hanyoung , Ivan Cristina , Overman Michael J. , Shimizu Masayoshi , Morris Jeffrey , Tran Hai T. , Heymach John , Calin George , Kopetz Scott 
Published: February 2017

456 Background: EMT is a phenotypic description of cancer cells that include loss of cell adhesion, increased motility, invasion, and chemoresistance. EMT gene signature is a poor prognostic feature in colon cancer. Circulating markers to decipher the EMT signature in colorectal cancer patients (CRC pts) would therefore be of clinical relevance. Studies have shown that miR-21, IL-6 and IL-8 have been associated with EMT in cancer cells in vitro and their expression has been shown to be highly correlated in primary colon cancer tissue Methods: Plasma samples were obtained from two mCRC cohorts: 120 pts with unresectable metastases, and 91 pts who subsequently underwent partial hepatectomy with curative intent. Circulating levels of IL-6, IL-8 and miR-21 (normalized by miR-16) were measured, and dichotomized using previously published cutoffs. Pts with high levels of ≥2 of 3 EMT markers were categorized as having an EMT phenotype. Survival analysis was by log-rank and proportional hazard. Results: As previously seen in colon tissue, miR-21, IL-6 and IL-8 expression were correlated in plasma samples (P<0.001) and individually associated with shorter overall survival (P<0.05). The EMT phenotype, present in 44% of both cohorts, was a strong predictor of poor overall survival in the unresectable cohort (HR 2.6, 95% CI 1.6 to 4.1, median OS 15.5 mo v 27.1 mo, P<0.001) as well as in the validation resectable cohort(HR 3.8, 95% CI 1.9 to 7.7, median OS 41.5 mo vs 81.9 mo, P<0.001). This effect was sustained in a multivariate analysis after adjustment for tumor volume and clinical characteristics (HR 1.92, P=0.009 in unresectable cohort and HR 3.53, p=0.002 in hepatectomy cohort). The EMT phenotype was also predictive of shorter progression-free survival (HR 2.2, 15.8 mo vs 7.8 mo, P=0.02) and relapse-free survival (HR 2.1, 18.4 mo vs 31.4 mo, P=0.01) in the two respective cohorts, consistent with prior preclinical data correlating EMT with chemoresistance Conclusions: As surrogates of EMT, circulating levels of miR-21, IL-6 and IL-8 are co-expressed in plasma of mCRC pts and can be used to predict overall survival and benefit from chemotherapy. This finding highlights the clinical relevance of EMT in colon cancer biology
Relationship of incomplete inhibition of PI3K pathway signaling and efficacy of cetuximab in KRAS wild-type colorectal cancers.
Authors: Corcoran Ryan Bruce , Ebi Hiromichi , Ryan David P. , Meyerhardt Jeffrey A. , Engelman Jeffrey A. 
Published: February 2017

462 Background: Therapies targeting receptor tyrosine kinases (RTKs) are typically effective only when they lead to simultaneous downregulation of PI3K-AKT and MEK-ERK signaling. Cetuximab is a monoclonal antibody directed against EGFR that has been approved for the treatment of metastatic colorectal cancer, and several studies have suggested that its benefit is restricted to patients with KRAS wildtype cancers. However, even in KRAS wildtype colorectal cancers, the response rate to single-agent cetuximab is low, and the mechanistic basis for this is not well-understood. Methods: The ability of cetuximab to downregulate PI3K-AKT and MEK-ERK signaling in a panel of KRAS wildtype colorectal cancer cell lines was assessed by immunoblotting. We preformed immunoprecipitations of the regulatory subunit of PI3K on lysates derived from cell lines and primary colorectal tumor specimens to identify the RTKs involved in PI3K activation. Cetuximab-based therapeutic combinations were evaluated in KRAS wildtype cell lines and tumor xenograft models. Results: Cetuximab led to effective inhibition of MEK-ERK signaling (>75% reduction in phospho-ERK), but led to incomplete inhibition of PI3K-AKT signaling (0-50% reduction in phospho-AKT) in all KRAS wildtype colorectal cell lines tested. PI3K regulatory subunit immunoprecipitations revealed multiple RTK inputs to PI3K in cell lines and primary tumors, most notably from IGFIR. Combined treatment with cetuximab and an IGFIR inhibitor or a PI3K inhibitor led to improved efficacy in vitro and in tumor xenograft models. Conclusions: Cetuximab fails to completely downregulate PI3K-AKT signaling in KRAS wildtype colorectal cancer cell lines. Biochemical analysis of cell lines and primary colorectal tumors reveals that additional RTKs other than EGFR play a role in PI3K activation in these cancers. Therefore, combining cetuximab with targeted therapies directed against the PI3K pathway may lead to improved efficacy in KRAS wildtype colorectal cancers.