bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (MCRC): Results of the phase III randomized TRIBE trial.
Authors: Loupakis Fotios , Cremolini Chiara , Masi Gianluca , Lonardi Sara , Zagonel Vittorina , Trenta Patrizia , Tomasello Gianluca , Ronzoni Monica , Ciuffreda Libero , Zaniboni Alberto , Tonini Giuseppe , Buonadonna Angela , Valsuani Chiara , Chiara Silvana , Carlomagno Chiara , Boni Corrado , Marcucci Lorenzo , Boni Luca , Falcone Alfredo 
Published: February 2017

336 Background: First-line FOLFOXIRI demonstrated superior activity and efficacy compared to FOLFIRI. Moreover, the outcome is improved by the addition of bev to first-line doublets. A phase II study of FOLFOXIRI/bev showed promising activity and manageable toxicities. The present trial compared FOLFOXIRI/bev to FOLFIRI/bev as first-line treatment in unresectable mCRC. Methods: Eligibility criteria included: measurable and unresectable mCRC, age 18-75 years, no prior chemotherapy for advanced disease. Patients (pts) were randomized to either FOLFIRI/bev (bev 5 mg/kg, irinotecan 180 mg/sqm, l-LV 200 mg/sqm, 5FU bolus 400 mg/sqm, 5FU infusion 2400 mg/sqm over 48h q2w, arm A) or FOLFOXIRI/bev (bev 5 mg/kg, irinotecan 165 mg/sqm, oxaliplatin 85 mg/sqm, l-LV 200 mg/sqm, 5FU infusion 3200 mg/sqm over 48h q2w, arm B). Treatment was planned for a maximum of 12 cycles followed by maintenance with bev and 5FU until progression. Primary endpoint was progression-free survival (PFS). Results: Between July 2008 and May 2011, 508 pts were randomized among 35 italian centers. Pts characteristics were (arm A/arm B): median age 60/61 yrs, ECOG PS 1-2 11%/10%, synchronous metastases 81%/79% multiple sites of disease 74%/70%. At a median follow-up of 20.9 months 391 pts have progressed. The study met its primary endpoint: FOLFOXIRI/bev significantly increased PFS (median 9.5 vs 11.9 months, HR 0.72 [95%CI:0.59-0.87], p=0.001). Response rate was also significantly increased (53% vs 64%, p=0.015). Main per patient toxicities were (arm A/arm B): grade 3-4 diarrhea 10%/18%, grade 3-4 vomiting 3%/4%, grade 3-4 stomatitis 4%/8%, grade 3-4 peripheral neurotoxicity 0%/5%, grade 3-4 neutropenia 20%/49%, febrile neutropenia 6%/8%, hypertension 2%/4%, thromboembolic events 7%/7%, bleeding 1%/1%. Deaths within 60 days were 3% and 4%. Conclusions: FOLFOXIRI/bev significantly increases PFS and response rate compared to FOLFIRI/bev. Chemotherapy- and bev-related toxicities occur with the expected incidence. Clinical trial information: NCT00719797.
Use of adjuvant chemotherapy (AC) and outcomes in stage II colon cancer (CC) with versus without poor prognostic features.
Authors: Kumar Aalok , Kennecke Hagen F. , Lim Howard John , Renouf Daniel John , Woods Ryan , Speers Caroline , Cheung Winson Y. 
Published: February 2017

338 Background: AC is frequently considered in patients (pts) with "high risk" stage II CC, defined by the presence of >/=1 poor prognostic features such as obstruction or perforation, T4 stage, <12 lymph nodes removed, positive resection margins, and lymphovascular or perineural invasion. Survival benefits associated with AC use in high risk pts remain largely unproven. Our aims were to examine patterns of AC use in stage II CC and to explore the impact of AC on survival in high vs. low risk pts. Methods: All pts with stage II CC in British Columbia from 1999 to 2008 and evaluated at 1 of 5 regional cancer centers were reviewed. Kaplan-Meier and Cox regression methods were used to correlate high vs. low risk status and receipt of AC with relapse-free (RFS), disease-specific (DSS), and overall survival (OS). Results: We identified 1,697 pts: 1,236 (73%) high risk and 461 (27%) low risk among whom 363 (29%) and 61 (13%) received AC, respectively. Individuals with high risk disease who received AC were younger (median 62 vs. 72 yrs, p<0.01) and had better performance status (ECOG 0/1 47% vs. 34%, p=0.02). For high risk pts, AC was associated with improved 5-year OS (Table). Adjusting for confounders, an OS advantage from AC persisted for high risk pts (HR 0.67, 95CI 0.52-0.86, p=0.002), with no significant RFS or DSS benefits. Subgroup analyses revealed individuals with T4 lesions had significantly improved RFS (HR 0.63, 95CI 0.42-0.95, p=0.03), DSS (HR 0.59, 95CI 0.37-0.93, p=0.03), and OS (HR 0.50, 95CI 0.33-0.77, p=0.002). For low risk pts, AC was associated with worse RFS (HR 2.27, 95CI 1.03-4.97, p=0.04) and DSS (HR 2.97, 95CI 1.10-8.02, p=0.03). Conclusions: In this population-based cohort study, AC was associated with an OS advantage in high risk pts, likely due to pt selection. RFS and DSS benefits were mainly seen in T4 lesions, suggesting a limited role for AC in pts deemed high risk. A possible trend towards harm was seen in the low risk group receiving AC. Better risk stratification schemes including those that incorporate molecular testing are warranted. [Table: see text]
Founder mutation versus full sequencing of MYH for increasing clinical sensitivity.
Authors: Ceulemans Sophia , Arnell Christopher , Burbidge Lynn Anne , Abbott Brian , Kaldate Rajesh R. , Landon Michelle 
Published: February 2017

343 Background: MYH-associated polyposis is an autosomal recessive syndrome caused by biallelic mutations in the base excision repair gene MYH. Initial reports indicated that a majority of European biallelic individuals carried two founder mutations, Y165C and G382D. A common MYH analysis strategy involves evaluation of the two founder mutations (FMs) with subsequent full sequencing only if one of the FMs is identified. This study aimed to determine the sensitivity of full MYH sequencing over the strategy described above in a cohort of individuals that has undergone genetic testing by a commercial laboratory. Methods: A retrospective analysis was performed on 1,522 individuals who had clinical MYH testing ordered either independently or in conjunction with APC gene analysis. All patients underwent MYH analysis for Y165C and G382D. Subsequent full gene sequencing was performed for all patients, except for those biallellic for the two FMs. Demographic, personal, and family cancer histories were collected on the test request form. Results: 86 biallelic individuals were identified, with 47 carrying two FMs, 18 carrying one FM and one mutation identified on sequencing, and 21 carrying biallelic mutations identified only on full sequencing. 21/86 (24.4%) biallelic MYH mutation carriers would have been missed by FM analysis only. The mutation spectrum is distributed among different ethnicities (Table). The majority of individuals met clinical criteria for a polyposis syndrome, with 21 individuals reporting more than 99 adenomas (24.4%) and 50 individuals reporting 20-99 adenomas (58.1%). Conclusions: Analysis of only the two MYH FMs would miss 24% of biallelic individuals in our cohort. Due to the ethnicity distribution of mutations, it is difficult to predict who would be missed by this strategy. Consideration of MYH full sequencing is warranted to achieve highest clinical sensitivity. [Table: see text]
Predicting risk of chemotherapy-induced side effects in patients with colon cancer with single-nucleotide polymorphism (SNP) Bayesian networks (BNs).
Authors: Sonis Stephen T. , Schwartzberg Lee Steven , Walker Mark S. , Weidner Susan M , Alterovitz Gil 
Published: February 2017

344 Background: Patients receiving standard chemotherapy for colon cancer are at significant, but unequal, risk for development of treatment-induced side effects. Currently, there is no accurate way to identify these risks for individual patients. This study adopted a novel approach to creating a risk prediction model for chemotherapy-induced side effects through the development of clusters of SNPs defined by BNs. It was designed to assess the feasibility of identifying SNP-BNs that could accurately predict the risk for 6 common, and often debilitating, side effects: chemotherapy-induced nausea/vomiting (CINV), diarrhea, oral mucositis (OM), cognitive dysfunction (CD), peripheral neuropathy (PN), and fatigue. Methods: Patients (n=57) with colon cancer who received at least 3 cycles of FOLFOX6 +/- bevacizumab (along with standard supportive care strategies) were enrolled. Saliva samples were collected, DNA was isolated, and SNPs were analyzed on Illumina Omni microarrays (2.5 x 106 SNPs). Side effects under consideration were observed using Patient Care Monitor, a validated patient-reported symptom assessment instrument. BNs were developed for each of the 6 side effects and cross-validated using robust statistical analyses. Results: The percentage of patients who experienced moderate-to-severe side effects was notable despite supportive care measures. These included the following: CINV (32%), diarrhea (16%), OM (26%), CD (21%), PN (26%), and fatigue (56%). SNP-BNs were defined for each of the 6 side effects and were found to predict risk with a high degree of accuracy (>90%) and receiver operating characteristic (ROC) curves (>0.920). Conclusions: This study calls attention to the fact that treatment-related side effects persist in patients receiving FOLFOX6 +/- bevacizumab for colon cancer. SNP-BNs were identified that could accurately predict 6 of the most common treatment-related side effects. This genomic-based tool has the potential to offer clinicians accurate and actionable information for individualizing a patient’s cancer care plan.
Marker detection in rectal cancer chemoradiation response using an exhaustive combinatorics approach.
Authors: Smith David D. , Avila Karin , Chen Zhenbin , Li Wenyan , Garcia-Aguilar Julio 
Published: February 2017

347 Background: Our objective was to detect a set of markers that predicted tumor response to chemoradiationtherapy (CRT) in a prospective phase II protocol. Our hypothesis was that certain combinations of markers had a synergistic effect on those patients with a complete response (pCR) versus other responses. Methods: 132 rectal cancer patients’ tumors were evaluated for mutations and polymorphisms in 23 genes. The factors were selected prospectively as having the potential to influence CRT outcome. Our selected risk factors were transformed to yes/no values from predetermined cutoffs. We performed a massive computational combinatorics search for those combinations of factors associated with tumor response (3 million possible combinations). Our best sets of candidates were those with the largest association with tumor response to CRT (CR vs other) by Fisher’s Exacttests after adjusting for False Discovery Rate. Results: 33 of 132 (25%) patients achieved a pCR and 99 (75%) patients had non-pCR. Our results showed that sets of markers may work alone or synergistically. For example, some markers may not be associated with CRT response by themselves, but are highly correlated to outcome in the presence of other markers. Interactions such as we modeled here are often not considered by informatics software due to computational complexity. Conclusions: A combinatorics approach is computationally expensive but is able to detect marker combinations that are more complex (i.e., nonlinear) than those commonly used in popular informatics software. Our methods are readily extensible to any marker detection scenario, given sufficient computational resources. [Table: see text]
Phosphorylated AMP-activated protein kinase and MAPK3/1 expression associated with prognosis for patients with gastric cancer.
Authors: Kim Jong Gwang , Chae Yee Soo , Kang Byung Woog , Lee Yoo Jin , Kim Min Chan , Kim Ki Han , KIm Su-Jin 
Published: February 2017

36 Background: Phosphorylated AMP-activated protein kinase (pAMPK) has central roles in cellular metabolic sensing and energy balance homeostasis, and interact with various pathways [e.g., TP53, MTOR, NUAK2 (sucrose nonfermenting-lkie kinase), MAPK3/1(ERK), and PDK (pyruvate dehydrogenase kinase)]. The present study analyzed the expression of pAMPK, NUAK2, MAPK3/1, and PDK-1 and their impact on the survival of patients with resected gastric cancer. Methods: Six hundred and twenty-one patients with surgically resected gastric adenocarcinoma with curative intent were enrolled in the present study. Immunohistochemical staining for pAMPK, NUAK2, MAPK3/1, and PDK-1 was performed using tissue microarrays of operative specimens of gastric cancer. The expressions were divided into two or three groups according to the intensity score [pAMPK: negative (0), weak to intermediate positive (2), strong positive (3); NUAK2: negative (0), positive (2); MAPK3/1: negative (0), focal positive (2), diffuse positive (3); PDK-1: negative (0), positive (2)]. Results: Positive pAMPK, NUAK2, MAPK3/1, and PDK-1 expression was observed in 379 (61.0%), 257 (41.4%), 327 (52.7%), and 67 (10.8%) cases, respectively. Multivariate survival analysis showed that the survival for the patients with negative expression of pAMPK was worse than for the patients with the weak to strong positive expression [disease free survival (DFS): hazard ratio (HR)=1.361, P=0.029), and the negative expression of MAPK3/1 was also associated with a worse survival compared to the positive expression (DFS: HR=1.401, p=0.029). Conclusions: pAMPK and MAPK3/1 expressions were found to be an independent prognostic marker for patients with gastric cancer. Accordingly, the analysis of pAMPK and MAPK3/1 expression can help identify patient subgroups at high risk of a poor disease outcome.
Colorectal cancer inherited susceptibility: The first replication study in the Brazilian population.
Authors: Gomy Israel , Santos Erika Maria Monteiro , Spilborghs Graziela Machado Gruner Turco , Viola Sandra Regina de Araujo da Silva , Aguiar Samuel , Carraro Dirce Maria , Rogatto Silvia Regina , Carvajal-Carmona Luis , Rossi Benedito Mauro 
Published: February 2017

361 Background: Inherited susceptibility to colorectal cancer (CRC) is known since twin studies have revealed 35% of heritability. Genome-wide association studies (GWAS) have uncovered less than a half of this proportion through genotyping tagSNPs of individuals with European ancestry. To date only 20 common SNPs have achieved genome-wide significance and replication studies from non-European populations are scarce. Here we show preliminary data of the first study of CRC inherited susceptibility in the Brazilian population and aimed to replicate European studies. Methods: We genotyped 1,395 individuals (675 cases and 720 controls) for 10 tagSNPs (rs6983267, rs4939827, rs4779584, rs16892766, rs10795668, rs4444235, rs9929218, rs10411210, rs961253, rs3802842) using TaqMan SNP Genotyping Assays and SDS2.3 software (Applied Biosystems). We exclude from the analysis SNPs with significant deviation from Hardy-Weinberg equilibrium. Results: Significant association was found between six out of ten SNPs and CRC risk for most genetic models. One SNP (rs10411210) was associated with a low risk of CRC. Conclusions: Despite we did not analyze population stratification, this study partially replicate European GWAS in an admixed population. Therefore, it is worth to explore other ethnic backgrounds that would ultimately help to uncover the missing heritability of CRC and narrow the boundaries of the genetic architecture of CRC susceptibility. [Table: see text]
Presenting characteristics of insured and uninsured patients with anorectal malignancy referred for radiotherapy at an urban safety net hospital.
Authors: Nichols Romaine Charles , Morris Christopher G. , Zaiden Robert Anthony , Awad Ziad , Colaco Rovel , Hoppe Bradford S. , Mendenhall William M. , Mendenhall Nancy Price 
Published: February 2017

363 Background: This retrospective study compares: presenting characteristics; time intervals between symptom emergence, tissue diagnosis and initiation of therapy; and survival, for insured (IP) and uninsured patients (UP) with anal (22) or rectal (39) malignancy referred for radiotherapy at University of Florida Shands Hospital in Jacksonville. Methods: From 5/2002 to 8/2012, 63 newly diagnosed patients were evaluated. 2 patients were excluded due to mental illness. Records were reviewed to capture: 1.) Patient demographics; 2.) Stage at diagnosis; 3.) Weight loss at diagnosis; 4.) Patient reported date of symptom onset; 5.) Date of tissue confirmation of malignancy; 6.) Date of first therapeutic intervention (i.e. surgery, chemotherapy or radiotherapy); 7.) Insurance status at each of the above time points; and 8.) Survival data. Results: At the time of symptom emergence, 32 patients were uninsured and 29 were insured. Median age of UP was 52 years vs. 64 years for IP (P=0.0005). UP experienced median intervals of 258.5 days between symptom emergence and tissue confirmation of malignancy vs. 58 days for IP (P=0.0013). UP experienced median intervals of 314.5 days between symptom emergence and treatment initiation vs. 120 days for IP (P=0.0024). UP presented with T4 primary tumors in 41% of cases vs. 7% for IP (P=0.0027). UP presented with a median weight loss of 10 lbs vs. 0 lbs for IP (P=0.0158). UP presented with lymph node metastasis in 66% of cases vs. 45% for IP (P=0.1264). With a median follow up of 22 months for UP and 32 months for IP, 2 year actuarial overall survival was 87% for UP and 74% for IP (P=0.5503). Conclusions: UP presented at a younger age than IP (P=0.0005) and demonstrated:1.) Longer intervals between symptom emergence and tissue confirmation of malignancy (P=0.0013); 2.) Longer intervals between symptom emergence and treatment initiation (P=0.0024); 3.) Greater likelihood of presenting with a T4 tumor (P=0.0027); 4.) Greater weight loss at presentation (P=0.0158); 5.) A trend toward a greater likelihood of presenting with lymph node metastasis (P=0.1264); 6.) No difference in actuarial 2 year survival from date of diagnosis compared to IP. (P=0.54).
Population-based trends in positron emission tomography (PET) utilization after resection for colon cancer.
Authors: Bailey Christina Edwards , Hu Chung-Yuan , You Y. Nancy , Rodriguez-Bigas Miguel A. , Kaur Harmeet , Ernst Randy , Skibber John Michael , Chang George J. 
Published: February 2017

365 Background: While most colon cancer staging and treatment guidelines do not routinely include PET imaging, its use has been increasing. The primary aim of this study is to evaluate the trends in PET utilization during the first 2 years after diagnosis of colon cancer. Methods: A retrospective cohort study of patients ≥ 65 years old with colon cancer who underwent surgical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (2001-2007, Medicare Part A/B only) and had at least 2 years of follow-up was performed. PET utilization was assessed using the test for trends and multivariate logistic regression for patient, tumor and treatment response characteristics. Results: Of 28,762 patients who underwent primary resection of colon cancer, 3,897 (13.6%) had at least one PET scan within 2 years after surgery. The utilization rate steadily increased from 7.5% in 2001 to 18.7% in 2007 (p = 0.01). A total of 7,175 PET scans were performed on 3,897 patients, among which 2,348 (60.2%) had 1 PET scan, 834 (21.4%) had 2 PET scans and 715 (18.4%) had >2 PET scans. The majority of PET scans were performed within 2 months after surgery (n=1314) and a 2ndpeak was observed at 9 months. Additional factors significantly associated with increased PET scan use included SEER region, stage, and grade (Table). Conclusions: The utilization of PET scans after colon cancer resection has steadily increased since 2001 with the majority of PET scans being performed within 2 months after surgery and its use was subject to geographic variation. Further study is needed to examine the impact of this pattern on long-term oncologic outcomes. [Table: see text]
Association of radiologically defined hepatosteatosis and colorectal cancer liver metastases.
Authors: Parasca Adrian D. , O'Brien Timothy E. 
Published: February 2017

367 Background: Non alcoholic fatty liver disease (NAFLD) is common, with a prevalence estimated at 15-35%. NAFLD was found to be an independent risk factor for colorectal cancer (CRC). The relationship between CRC and metastasis to a fatty liver has not been well established. We performed a retrospective chart review to address the association of radiologic hepatosteatosis and liver metastases in patients with CRC. Methods: Medical records of 291 patients diagnosed with colorectal adenocarcinoma between 2006-2010 at MetroHealth Medical Center were reviewed. Patients with CRC and no abdominal imaging within 3 months of diagnosis were excluded. Demographic and tumor related data were collected. Presence of hepatic steatosis was defined by radiographic reports (CT, MRI, or US). Results: 6/38 (18.8%) patients with hepatosteatosis had liver metastases, compared to 60/253 (23.7%) with no steatosis. The difference did not reach statistical difference (p=0.40). Hepatosteatosis was noted in 27/280 (9.6%) contrasted CTs, 4/42 (9.5%) MRIs and 12/54 (22.2%) U/S. 66 (22.7%) patients had liver metastases. Patients with ≤3 metastases were less frequent in the non-fatty 22/59 (37.3%) vs fatty liver group 3/6 (50%), but this was not statistically significant (p=0.67). Fatty liver patients were more likely to have a stage ≤ II compared to non-fatty liver patients (OR 2.40, p=0.018). Patients with hepatosteatosis had a higher mean BMI (32.8 vs 27.6, p<0.001). BMI was an independent predictor of steatosis. Alcohol consumption was not associated with BMI or steatosis. There was no statistically significant difference between racial groups and gender with respect to steatosis and liver metastases. Conclusions: This retrospective study suggests that liver metastases in CRC patients are less common in those with fatty livers compared to those with non-fatty livers. CRC patients with hepatosteatosis were also more likely to have earlier stage disease. Larger studies are needed to confirm these findings.