bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse clinical outcome and predictors for clinical outcome in patients with HCC treated with TACE.
Authors: Bhardwaj Prarthna , Prins Petra , Kim Alexander Y. , Jha Rheena , Wang Hongkun , Sullivan David , Taher Salha , Zhang Tiger , Zhu J , Marshall John , He Aiwu Ruth 
Published: February 2017

442 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the second leading cause of cancer-related death, worldwide. This reflects the challenges facing HCC treatment. Methods: Patients (pts) with HCC receiving TACE treatment (n = 96) were examined retrospectively for clinical outcome and its possible predictors. The number of TACE treatments and the time elapsed between each treatment were assessed and correlated with overall survival (OS) using the log rank test of Kaplan Meier curves. T-stage, level of differentiation, vascular invasion, and Child Pugh score at the time of HCC diagnosis were compared among pts who received different numbers of TACE treatments (Kaplan-Meier survival analysis, ANOVA and student T test). Results: TACE treated pts had a median OS of 46 month (mo) and progression free survival of 12 mo (difference in time between the date of first progression and the date of diagnosis). Pts received 1-2 (n = 52), 3-4 (n = 28), or 5-6 (n = 16) TACE treatments. We found that pts who had only 1-2 TACE treatments had significantly shorter median OS (38 mo) than those who received 3-4 or 5-6 treatments (48 and 83 mo; p < 0.05). Of the 96 pts studied 22, 33, 37, and 3 pts had T1, T2- T3 and T4-stage HCC, respectively. Only 39 pt tumors underwent pathological analysis, and 13 were well-differentiated (WD), while 24 were moderately- or poorly- differentiated (MPD) (p > 0.05). Tumor T-stage and differentiation were correlated with the number of TACE treatments received. Thus, 30% of pts (n = 10) with T2-stage disease compared with 10% (n = 4) with T3-stage disease received 5-6 TACE treatments (p < 0.001). Similarly, 30% of WD cases (n = 4) compared with only 8% of MPD cases (n = 2) received 5-6 TACE treatments (p < 0.001). The duration between the second and third TACE treatments ( < 4 mo, 5-8 mo or > 8 mo) seemed to correlate with outcome (p < 0.05). Conclusions: Pt survival time following TACE treatment is diverse and correlates with the number of TACE treatments. Pts with T3-stage, or MPD HCC tended to receive fewer TACE treatments than those with T2-stage or WD HCC, and have worse outcomes. Other therapies should certainly be considered for pts with T3-stage and/or MPD tumors.
Two-arc volumetric modulated arc therapy to provide dosimetric advantages for pancreas stereotactic body radiotherapy.
Authors: Molitoris Jason K , Brown Christopher , Chen Shifeng , Marter Kimberly , Spaeth Kristin , Regine William , Chuong Michael David 
Published: February 2017

445 Background: Stereotactic body radiation therapy(SBRT) is increasingly used in locally advanced pancreatic cancer (LAPC). SBRT can be delivered using 3D conformal, static intensity modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT) techniques. Prior data suggest advantages of using VMAT over IMRT for single-fraction pancreas SBRT. We performed the first dosimetric comparison of IMRT with one and two arc VMAT for 5-fraction pancreas SBRT, a more commonly used regimen. Methods: We generated 5-fraction SBRT plans for 12 LAPC patients who were previously treated at our institution with standard fractionation. The prescription dose was 33 Gy delivered in 6.6 Gy fractions. Assuming breath hold, 3 plans were generated for each patient: 9-beam static IMRT, 1-arc VMAT (VMAT1), and 2-arc VMAT (VMAT2) targeting the primary tumor. Target coverage and normal tissue doses were compared between the delivery techniques. Results: Each plan met target coverage planning goals. More VMAT2 plans (100%) were able to meet all normal tissue constraints than VMAT1 (83.3%) or IMRT (75%). Duodenal dose was most lowest for VMAT2 compared to VMAT1 and IMRT for mean dose (8.66 vs. 9.00 vs. 8.99 Gy); D4% (25.9 vs. 26.6 vs. 26.3 Gy); V10Gy (38.02 vs. 39.33 vs. 40.11%), V15Gy (23.98 vs. 25.88 vs. 25.97%), V20Gy (12.73 vs. 13.84 vs. 14.95%), and V25Gy (5.96 vs. 6.85 vs. 6.78%)(all p < 0.05). The tumors closest to the duodenum had statistically significantly improved V30Gy for VMAT2 compared to VMAT1 and IMRT (both p < 0.001). VMAT1 and VMAT2 reduced dose to the stomach, spinal cord, and liver compared to IMRT; kidney dose, however, was lowest using IMRT. VMAT2 plans had the highest conformity, but required the most monitor units to deliver. Delivery time was significantly longer with IMRT, compared to VMAT1 and VMAT2 (8.25 vs. 2.16 vs. 3.33 mins). Conclusions: These data suggest that VMAT2 should be strongly considered for 5-fraction pancreas SBRT because of superior normal tissue sparing, more conformal target volume coverage, and faster treatment delivery time (compared to IMRT). Further evaluation is needed to clarify whether the dosimetric advantages of VMAT2 are clinically significant.
A prospective study evaluating stereotactic body radiation therapy in unresectable, recurrent, or residual pancreatic adenocarcinoma.
Authors: Rosati Lauren M. , Moningi Shalini , Hacker-Prietz Amy , Laheru Dan , Zheng Lei , De Jesus-Acosta Ana , Le Dung T , Moore Joseph A. , Fishman Elliot K. , Raman Siva P. , McNutt Todd R. , Pawlik Timothy M. , Eckhauser Fred E , Weiss Matthew J. , Herman Joseph M. 
Published: February 2017

454 Background: The purpose of this prospective, non-randomized phase II single-institution study was to evaluate if local control can be achieved with reasonable acute and late GI toxicity using fractionated SBRT in patients with unresectable, recurrent, or residual locally advanced pancreatic cancer (LAPC). Methods: A total of 24 patients with LAPC were enrolled from June 2013 to August 2014. Eligibility required stability after induction chemotherapy or residual disease or local failure after surgery. Induction chemotherapy regimens consisted of: (1) gemcitabine alone (8%); (2) gemcitabine-based regimens (17%); (3) FOLFIRINOX-based regimens (63%); or (4) combination regimens (13%). Chemotherapy was discontinued one week prior to SBRT. Patients received a median cumulative dose of 33 Gy in 5 fractions (5-6.6 Gy/fraction). Patients were permitted to resume chemotherapy one week post-SBRT. Toxicity was assessed using the NCI CTCAE version 4.0. Results: Of the 24 patients, 58% were male and 50% had tumors in the head of the pancreas. Median age at diagnosis was 66.8 years, and median follow-up from the date of diagnosis was 11.9 months (range, 7.4-29.7 months). There have not been any acute or late grade ≥ 2 gastritis, enteritis, fistula, or ulcer toxicities (primary endpoint). Median OS has not yet been reached, median LPFS was 19.3 months (95% CI, 12.3-14.8), median DMFS was 13.6 months (95% CI, 9.2-17.9) and median PFS was 13.6 months (95% CI, 13.5-25.2). Plasma CA 19-9 level was non-significantly reduced after SBRT, displaying a -9.15 average percent change from baseline (median time after SBRT, 1.2 months). FFLP at 1 year was 83.9%. Eight (33%) patients underwent successful surgery following SBRT, with rates of both margin- and node-negative resection being 75%. Conclusions: Chemotherapy followed by fractionated SBRT results in favorable local control and survival with minimal acute and late GI toxicity. A notable proportion of patients initially deemed unresectable underwent successful resection. This study suggests that SBRT can be safely given following more aggressive multiagent chemotherapy in patients with LAPC. Clinical trial information: NCT01781728.
Palliative treatment in extrahepatic biliary malignancies: A multi-institutional cohort.
Authors: Wilson Ana , Ethun Cecilia Grace , Poultsides George A. , Tran Thuy , Idrees Kamran , Isom Chelsea A , Fields Ryan C. , Krasnick Bradley , Weber Sharon M. , Salem Ahmed I. , Martin Robert C. G. , Scoggins Charles Raben , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Beal Eliza W , Hatzaras Ioannis , Shenoy Rivfka , Maithel Shishir Kumar , Pawlik Timothy M. 
Published: February 2017

456 Background: Extrahepatic biliary malignancies (EBM) are often first diagnosed at advanced stages when the disease is no longer surgically resectable. While palliative resection may provide a more definitive solution for patients with jaundice, it also carries a higher risk of complications than endoscopic or percutaneous drainage. Herein, we analysed patients undergoing both methods of palliation to better delineate these risks. Methods: 172 patients who underwent palliative treatment for EBM between 2000 and 2014 were identified from 10 major hepato-biliary centers participating in the EBM Consortium. Clinicopathologic, operative and outcome data were collected and analyzed. We used propensity score matching to correct for confounding by indication. Results: 113 patients underwent surgery with palliative resection of their tumor (65.7%), while 59 underwent diagnostic surgery, but were treated with percutaneous or endoscopic biliary drainage instead of resection (34.3%). Patients who were not resected were more frequently jaundiced preoperatively (p = 0.001), and were more likely to undergo repeat drainage procedures (p < 0.001). After matching for functional status, age, and clinical jaundice, patients who underwent resection had significantly more complications (55.6% vs. 34.0%; p = 0.035), a higher median number of complications (1 vs. 0; p = 0.0149), a higher Clavien Dindo Grade (IIIa vs. II; p = 0.0261), a longer hospital stay (8 vs. 4 days; p < 0.001), and a notable trend towards higher perioperative mortality (10.9% vs. 1.96%; p = 0.069). Meanwhile the postoperative bilirubin level was equal among the resected (1.80 mg/dL (IQR, 0.60-8.90)) and drainage groups (2.45 (IQR 0.60-10.5))(p = 0.477), and both groups had a statistically significant drop after treatment (resection 8.30 mg/dL to 1.80 mg/dL, p < 0.001; drainage 8.4 to 2.45, p < 0.001). Conclusions: Both palliative resection and biliary drainage successfully treated EBM patients’ hyperbilirubinemia. However, in a propensity score matched group, palliative resection patients had more complications and a trend towards more perioperative mortality, urging caution in the selection of patients for these procedures.
Early detection of colorectal neoplasia: Combination of eight cancer-associated blood-based protein biomarkers.
Authors: Christensen Ib J. , Wilhelmsen Michael , Gawel Susan , Yang Xiaoqing , Brunner Nils , Martens Frans , Heijboer Annike , Davis Gerard , Nielsen Hans J. 
Published: February 2017

488 Background: Assessment of 8 blood based protein markers for identifying colorectal neoplasia. Methods: 4,698 subjects scheduled for first time ever colonoscopy with symptoms potentially attributable to colorectal neoplasia were accrued. Plasma levels of AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3, and TIMP-1 were determined by using the Abbott ARCHITECT i2000 automated immunoassay platform. Three clinical endpoints were chosen for this presentation: 1. CRC, 2. CRC and high risk adenoma, 3. CRC and other cancers. Logistic regression was used for statistical analysis of each endpoint. A final reduced model was selected choosing the best combination of 4 markers with the highest likelihood score statistic. Results: 512 CRC’s were identified, 323 CC and 189 RC. Malignancies other than CRC were detected in 177 subjects, 699 adenomas were identified including 298 with high risk, 1342 subjects had non-invasive bowell disease, and 1978 had a “clean” colon. Univariate analysis of each endpoint demonstrated that all markers were statistically significant. Multivariable logistic regression showed that the blood based markers in combination significantly predicted the 3 endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the 3 endpoints. The area under the receiver operating characteristic curves were 0.83, 0.74 and 0.82 respectively. The postive predictive value (PPV) at 90% sensitivity was 18% for endpoint 1 and the negative predictive value (NPV) was 97%. For endpoints 2 and 3, the PPV’s were 25% and 20% and the NPV’s were 93% and 96%. Conclusions: A subset of 4 biomarker in combination identify subjects with a high risk of CRC.
Changes in apparent diffusion coefficient evaluated with diffusion-weighted MRI to predict complete pathologic response after neoadjuvant therapy for rectal cancer: Literature review and meta-analysis.
Authors: Desiato Vincenzo , Rosman Alan S , Newman Elliot , Berman Russell S. , Pachter H. Leon , Melis Marcovalerio 
Published: February 2017

503 Background: A complete pathological response (pCR) is observed in 9-38% of all patients undergoing neo-adjuvant chemo-radiation therapy (CRT) for locally advanced rectal cancer (ARC). Imaging techniques that can reliably assess CRT results may enhance identification of those pCR patients for which surgery may potentially be avoided. Recently, several studies have suggested that diffusion-weighted magnetic resonance imaging (DW-MRI) may predict pathologic response by measuring tumor apparent diffusion coefficient (ADC). ADC can be measured before (pre-ADC) and/or after CRT (post-ADC). Both pre- and post-ADC, as well as the variation between pre- and post-ADC (Δ-ADC) can be used to assess pCR. We aimed to assess the reliability of ADC at predicting pCR in ARC patients treated with CRT. To determine the most effective ADC timing to evaluate pCR. Methods: A systematic review of available literature was conducted to compare all the studies of DW-MRI for identification of pCR after CRT for ARC. For each parameter (pre-ADC, post-ADC and D-ADC) we pooled sensitivity and specificity and calculated the area (AUC) under the summary receiver operating characteristics (sROC) curve. Results: We found 10 prospective and 8 retrospective studies examining correlation of ADC and CRT results. Overall, pCR rate was 25%. Pooled sensitivity, specificity, and AUC were: 0.743, 0.755, and 0.841 for pre-ADC; 0.745, 0.706, and 0.782 for post-ADC; and 0.832, 0.806, and 0.895 for D-ADC. Conclusions: Our meta-analysis confirms that at least 25% of patients with ARC experiences pCR after CRT. DW-MRI is a promising technique for assessment of CRT results and D-ADC appears to be the most effective parameter for prediction of pCR.
Molecular characterization of colorectal tumors in young patients compared with older patients and impact on outcome.
Authors: Heeke Arielle Celeste , Xiu Joanne , Reddy Sandeep K. , Jiang Jiji , Wang Hongkun , Marshall John , Salem Mohamed E. 
Published: February 2017

505 Background: The incidence of colorectal cancer (CRC) among young individuals is rising. The effect of an individual’s age on their tumor molecular profile is unknown. Methods: Molecular profiles of 4,821 tumors obtained from younger and older CRC patients (pts) were reviewed and correlated with pt outcome. Protein expression (IHC), gene amplification (ISH), sequencing (NGS and Sanger), and fragment analysis were performed. T and Fisher’s exact tests determined differences between age groups; Kaplan-Meier methodology estimated survival. Results: Tumors from 1,277 younger (median age 40; range 15-45 yr) and 3,544 older (72; 65-98) pts were studied. Most frequently mutated genes included TP53, APC, KRAS, PIK3CA, SMAD4, and BRCA1/2. Mutation rates for BRAF (14.4% vs. 4.8%, p < 0.001), APC (62% vs. 54%, p = 0.0034), FBXW7 (9.6% vs. 5.5%, p = 0.01), and KRAS (45% vs. 41%, p = 0.02) were higher in older pts; NRAS mutation rates (4.5% vs. 3.9%) were similar in both groups. Younger pts had higher overexpression rates of HER-2/neu (3.2% vs. 1.8%, p = 0.017) and MGMT (64% vs. 58%, p = 0.001). Microsatellite instability (MSI), determined by IHC (MLH1, MSH2, MLH6 and PMS2) and fragment analysis, was similar between cohorts (10.3% vs. 8.1%), but somatic MSI high (determined by concurrent BRAF mutation) was higher in older pts (6% vs. 0%, p < 0.0001). There was no difference in TS (37% vs. 34%), ERCC1 (25% vs. 26%) or TOPO1 (49% vs. 46%) expression between age groups. Older pts showed a trend toward higher PD-L1 expression (2.9% vs. 0.7%, p = 0.0512) but there was no difference in the frequency of PD-1 expression on tumor-infiltrating lymphocytes (39% vs. 43%). Outcome was evaluable for 82 pts (younger, 47; older, 35). Most pts received FOLFOX + Bev as first line Rx. Median OS was worse in younger pts (p = 0.03). Low ERCC1 expression was associated with prolonged survival in older (p < 0.01) but not in younger (p = 0.3) pts. There was no association between TOPO1 expression and OS (p = 0.8). Pts with low TS expression showed a trend toward longer OS (p = 0.08). Conclusions: Young pts with CRC may carry genetic alterations that are distinct from older pts. A better understanding of disease biology may help to identify therapeutic targets for younger pts.
Small RNA sequencing of colorectal cancer to reveal differences in microRNA expression between normal and tumor tissue.
Authors: Mjelle Robin , Sjursen Wenche , Thommesen Liv , Hofsli Eva 
Published: February 2017

506 Background: MicroRNAs (miRNAs) are promising biomarkers and therapeutic agents for colorectal cancer (CRC). However, much remains to be known about the biology of miRNAs and miRNA variants in tumor tissue and why the expression differs from normal tissue. Methods: RNA from 48 normal and 48 cancer tissue samples were sequenced using the Illumina small RNA sequencing protocol. Samples were taken from both male and female patients with tumor stage 1-4. Results: We show that almost 50% of microRNAs (miRNAs) are differentially expressed between normal and cancer tissue. When analyzing pre-miRNAs that map to genomic clusters, so-called clustered miRNAs, we show that miRNAs in the same cluster often have similar expression profiles. This shows that common changes in co-expressed miRNAs seem to explain some of the miRNA expression changes between normal and tumor samples and indicates that altered pri-miRNA transcription is the mechanism for at least some of the miRNA changes. Analyses of miRNA variants, so-called isomiRs, revealed large variations between tumor and normal samples, similar to those observed for the canonical miRNAs. Different isomiR types show different expression profiles in tumor vs normal samples, indicating that miRNA processing is altered in tumor cells. Finally, we show that several canonical miRNAs and isomiRs correlate with genetic signatures in the tumor samples, including KRAS and BRAF mutation, Microsatellite instability and MLH1 methylation, indicating that tumor subtypes have different miRNA expression. Conclusions: Our results show that miRNA expression predicts tumor subtypes with different genetic signatures. We show that some of the changes in miRNA expression are due to different transcription programs in cancer vs normal tissue.
Verification of T-plus staging system for colorectal cancer based on nomogram analysis of single center’s 25-year follow-up.
Authors: Ding Ke-Feng , Li Jun , Kong Xiang-Xing , Tang Ke-Jun , Bei Di-Kai , Yuan Ying , Zhang Su-Zhan , Zheng Shu 
Published: February 2017

516 Background: We proposed T-plus staging system which abandon the criterion to discriminate stage II/III by lymph node status and strengthens weighting of the T stage according to cluster analysis of the summary survival data of SEER. In this study, this principle of the T-plus staging system was verified with single center data by nomogram analysis. Methods: The 1,099 patients with colorectal cancer diagnosed before 2005 were analyzed to build a novel staging system based on nomogram (nomo-staging system). The remaining 981 patients diagnosed after 2005 were used to test the performance of nomo-staging system, T-plus staging system and the 7th edition TNM staging system by Akaike information criteria (AIC), Harrell’s c-index and the area under the curve (AUC) of Receiver Operating Characteristic to predict 5-year overall survival. A smaller AIC, higher c-index and higher AUC indicated a better staging system. Results: The nomo-staging system and T-plus staging system were listed in Table 1. The validation found that the 7th edition TNM staging system showed the weakest performance. For AIC, both nomo-staging system and T-plus staging system showed smaller value than the 7th edition TNM staging system (3214.912 vs. 3224.643 vs. 3229.810). For Harrell’s c-index, both the T-plus staging system and nomo-staging system showed higher value than the 7th edition TNM staging system (0.6814 vs. 0.6787 vs. 0.6778). For AUC to predict 5-year OS, the T-plus staging system and nomo-staging system showed slightly higher value than the 7th edition TNM staging system (0.6944 vs. 0.6924 vs. 0.6913). Conclusions: We propose replacement of lymph node status as the criterion to discriminate colorectal cancer stage II/III with greater weighting of the T stage. [Table: see text]
Racial and sex disparities in changing trends of squamous cell cancer of the anus (SSCA).
Authors: Gupta Arjun , Zhu Hong , Christie Alana , Meyer Jeffrey John , Khan Saad A. , Beg Muhammad Shaalan 
Published: February 2017

520 Background: Squamous cell carcinoma of the anus (SSCA) is one of only few cancers with rising incidence in the United States (US). This is believed to represent changing epidemiology of human papillomavirus (HPV) and Human Immunodeficiency Virus (HIV). We explored the racial and sex disparities in the rising incidence of SSC. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify subjects with SCCA from 2000-2012. Age-standardized incidence rates (IR) per 100,000 for 2000-2012 time period were generated in Rate Session in SEER for white males (WM), white females (WF), black males (BM) and black females (BF). The 2000 US standard population was used for age standardization. The trend of change of IR between groups was compared by testing the interaction between time and group in the linear regression model. SAS 9.4 was used for analysis Results: Among 11,739 new cases of SSCA racial and sex distribution of cases was WM:32%, WF:54%, BM:5.4%, BF:5.4%. Median overall survival (OS) was WM:101 months (m), WF:139 m, BM: 71 m, BF 103 m (p < 0.005). The IR had the highest rate of increase for WF and BM (0.06/100,000 cases annually) while rates for BF and WM increased by 0.04 and 0.02/100,000 cases annually respectively. The overall test for difference in trend among WF, WM, BF and BM groups had a p-value of 0.0099. Conclusions: The rate of increase of SSCA IR is highest for WF and BM. Additionally WF have the highest age standardized incidence of SCCA as well as the highest OS compared to other groups. These data support disparities in epidemiology and survival of anal cancer.