bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palliative chemotherapy and travel distance impacts hospice referral in patients with stage IV pancreatic cancer.
Authors: Duff Jennifer Michelle , Thomas Ryan M. 
Published: March 2017

490 Background: Despite advances in chemotherapy (CTx), the prognosis for metastatic pancreatic ductal adenocarcinoma (mPDAC) is poor and while hospice is known to improve end-of-life care, referrals are often placed close to death. This may be due to accessibility issues or misconceptions that referral implies abandonment. We hypothesized that utilization of palliative CTx and travel distance to the treatment center impacts hospice referral patterns. Methods: Patients with histologically confirmed or radiographically presumed mPDAC as their initial diagnosis were retrospectively identified in a Veterans Administration Medical Center (VAMC) from 2005-2014. Demographic and clinical data were collected according to timing of hospice referral. Results: Fifty-eight mPDAC patients were identified with a median age of 63yr of which 57 (98.3%) were male. Palliative CTx was used in 26 (44.8%) patients with 32 (55.2%) not treated due to poor performance status (n = 18; 56.3%) or patient refusal (n = 14; 43.8%). Of the 52 (89.7%) patients referred to hospice, the median time from diagnosis to referral and referral to death was 2.4wk (Interquartile Range [IQR] 14.9) and 3.1wk (IQR 6.5), respectively. The median time to hospice referral was 18.7wk for patients treated with CTx vs 1.4wk for those who did not undergo therapy (p < 0.001). The median distance from residence to the VAMC was 58.5mi (IQR 77). Subset analysis for those living > 60mi vs < 60mi to the VAMC, the median time to hospice referral was 1.7wk vs 4.7wk, respectively (p = 0.1). With no significant differences between groups in age, sex, race, or disease burden, univariate analysis demonstrated that those referred to hospice > 2.4wk from diagnosis more often received CTx (p < 0.001) and lived > 60mi from the treatment center (p = 0.05). Conclusions: The majority of patients with mPDAC were enrolled in hospice and while travel distance trended to shorter time to referral, this was not significant. However, receipt of palliative chemotherapy did delay referral and those with this delay lived farther from the hospital. These data suggest that physicians delay hospice care in patients who are able to tolerate treatment and travel long distance to receive it.
Sorafenib treatment for advanced hepatocellular carcinoma: Effectiveness, safety, and controversial points.
Authors: Oikawa Takayoshi , Sawara Kei , Kuroda Hidekatsu , Takikawa Yasuhiro 
Published: March 2017

496 Background: Sorafenib is only molecular target drug for hepatocellular carcinoma (HCC) in worldwide, however the effect and toxicity are different from cytotoxic anticancer agent. We evaluated that the efficacy and safety of sorafenib for unresectable HCC. Methods: This study population included fifty-eight patients that we can follow-up in 80 patients treated by sorafenib between May 2009 and May 2015 in our hospital. We evaluated the profile of sorafenib treatment (cause, initial dose, rate of changing dose), clinical response by mRECIST, adverse events by CTCAE v.4.0, Overall survival (OS) (total OS, median OS), conversion therapy and tumor response after progressive disease (PD). Results: HBV/HCV/alcohol/NBNC: 17/19/15/5, Child Pugh grade A/B: 54/4, cStage Ⅱ/Ⅲ/ⅣA/ⅣB: 1/17/15/23, extrahepatic spread(EHS) (lung /bone /adrenal gland /others): 9/5/2/7, prior treatment : 42/58 (72.4%). Cause of sorafenib treatment : TACE refractory (28%), vascular invasion or EHS (48%), initial dose 400mg (90%), changing dose :escalation (400→800); 15.5% reduction;10.3%. tumor response: objective response; 11.4%, disease control rate (DCR); 60.5%, OS: median OS 8.6 months, 3 year survival rate; 8.1%. There was significant difference in OS between Child Pugh score(CPS) (CPS:5, mOS 17.8 months, p < 0.01). Adverse events: skin disorders (17.2%), gastrointestinal disorders (17.2%), hepatobilliary disorders (17.2%), respectively. In clinical course of after PD response, 10 patients (17.2%) received hepatic arterial infusion chemotherapy for conversion therapy from sorafenib, and had 40% of DCR. Conclusions: Sorafenib is good therapeutic drug for advanced HCC and TACE refractory patients. Taking 400mg dosage of sorafenib is good response which depends on liver function. After PD response by sofafenib, conversion therapy from sorafenib has possibilities of good response.
Primary results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001).
Authors: Terashima Masanori , Doki Yuichiro , Kurokawa Yukinori , Mizusawa Junki , Katai Hitoshi , Yoshikawa Takaki , Kimura Yutaka , Takiguchi Shuji , Nishida Yasunori , Iwasaki Yoshiaki , Fukushima Norimasa , Kaji Masahide , Hirao Motohiro , Kurita Akira , Ito Seiji , Yabusaki Hiroshi , Sano Takeshi , Katayama Hiroshi , Nakamura Kenichi , Sasako Mitsuru ,   Stomach Cancer Study Group, Japan Clinical Oncology Group
Published: March 2017

5 Background: The role of bursectomy dissecting the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon for preventing peritoneal metastasis had long been controversial. We conducted a phase III trial evaluating the role of bursectomy in patients with subserosal (SS) / serosal (SE) gastric cancer. Patient accrual had been completed on Mar. 2015. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; cT3(SS) or cT4a(SE). Patients were intraoperatively randomized to non-bursectomy arm or bursectomy arm. Primary endpoint was overall survival. A total of 1,200 patients were required to detect a hazard ratio of 0.77 with a one-sided alpha of 5% and 80% power. Results: Between Jun 2010 and Mar 2015, 1,204 patients were accrued from 57 institutions (non-bursectomy 602, bursectomy 602). Patients’ background and operative procedures were well balanced between the arms. After completion of patient enrollment, the second interim analysis was performed on Sep 2016, with 54% (196/363) of the expected events observed. The 3y-survival were 86.0% (95%CI, 82.7 to 88.7) in non-bursectomy arm and 83.3% (95%CI, 79.6 to 86.3) in bursectomy arm. Hazard ratio for bursectomy was 1.075 (98.5%CI: 0.760 to 1.520) with predictive probability in favor of bursectomy at the final analysis of 12.7%. These results led to early study termination based on the recommendation of the Data and Safety Monitoring Committee. Operation time was longer (median 222 min vs 254 min) and blood loss was larger (230 ml vs 330 ml) in bursectomy arm; however, the incidence of patients received blood transfusion was not different between the arms (4.8% vs 4.5%). Although the incidence of pancreatic fistula was a bit higher in bursectomy arm (2.5% vs 4.8%), the incidence of Grade 3 or higher complications was not different between the arms (11.6% vs 13.3%). Five patients in non-bursectomy arm and one patient in bursectomy showed in-hospital death. Conclusions: Although bursectomy can be safely performed without increasing morbidity and mortality, bursectomy was not recommended as a standard treatment for cT3 or cT4 gastric cancer. Clinical trial information: UMIN000003688.
Molecular variances between rectal and left-sided colon cancers.
Authors: Marshall John , Lenz Heinz-Josef , Xiu Joanne , El-Deiry Wafik S. , Swensen Jeffrey , El Ghazaly Hesham , Gatalica Zoran , Hwang Jimmy J. , Philip Philip Agop , Shields Anthony Frank , Salem Mohamed E. 
Published: March 2017

522 Background: Recent analysis of CALGB 80405 showed that left sided colon tumors (LT) respond differently to biologics compared with right-sided tumors, likely due to molecular differences. Molecular variations between LT and rectal tumors remain undefined. Herein, we report our exploration of these variations. Methods: Tumors with origins clearly defined as splenic flexure to descending colon (SFT), sigmoid colon (SgT), or rectum (RT) were included. Protein expression, gene amplification and NextGen sequencing was tested. Microsatellite instability (MSI) was measured by PCR. Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses. Results: In total, 1,457 primary tumors (SFT 125; SgT 460, and RT 872) were examined. When compared with SFT, RT had a higher frequency of TP53 (71% vs. 57%, p = 0.03) and APC (66% vs. 49%, p = 0.01); a lower frequency of PIK3CA (11% vs. 22%, p = 0.02), BRAF (3% vs. 15% p = 0.0001), GNAS (0.9% vs. 4%, p = 0.04), HNF1A (0.7% vs. 5%, p = 0.01), and CTNNB1(0.3% vs. 4%, p = 0.003); and a higher expression of TOPO1 (52% vs. 31%, p = 0.0001), ERCC1 (29% vs. 15%, p = 0.03), and MGMT (64% vs. 53%, p = 0.048). When compared with SgT, RT had higher expression of TLE3 (33% vs. 23%, p = 0.007), TOPO1 (52% vs. 35%, p < 0.001), TUBB3 (41% vs. 28%, p = 0.003), and MGMT (64% vs. 54%, p = 0.003). There were no differences between SFT, SgT, and RT in the frequency of PD-L1 expression (5%, 2%, and 2%) on tumor cells, PD-1 expression on tumor-infiltrating lymphocytes (54%, 42%, and 42%), or Her-2 expression (1%, 2%, and 3%) and amplification (3%, 3%, and 5%). MSI was seen in 7% of SFT, 4% of SgT, and 0.7% of RT (total LT vs. RT, p = 0.01). Mean TML was 23, 6.5, and 7 mutations (mut)/MB (332 tumors), and the portion of tumors carrying a TML of > 17mut/MB was 9%, 1.6%, and 4% for SFT, SgT, and RT, respectively. In all 3 cohorts, a TML > 17 mut/MB was highly concordant with MSI. There was a correlation between PD-1 and TML in RT (p = 0.04) but not in SFT or SgT. There were no correlations between PD-L1 and TML. Conclusions: Tumors arising in the rectum may carry genetic alterations that are distinct from LT. A better understanding of disease biology may help to identify therapeutic targets and advance precision medicine
Cost-effectiveness of surveillance after curative resection (CR) of metastatic colorectal cancer (CRC).
Authors: Lee-Ying Richard M. , Kennecke Hagen F. , Nguyen Liem , Cheung Winson Y. 
Published: March 2017

526 Background: Surveillance after CR of stage I-III CRC is recommended by most major oncology organizations to detect asymptomatic recurrences. Such recurrences are more likely to benefit from early interventions such as CR of metastases. Only the NCCN recommends a surveillance schedule after CR of metastases that includes CEA testing, imaging and clinical evaluation every 3-6 months for 2 years, and then every 6-12 months in years 3 to 5. Periodic endoscopy is also recommended. It is unclear if there is cost-effective surveillance strategy for metastatic CRC after CR. Methods: A Monte Carlo micro-simulation model was constructed using a 1-month cycle length and 10 year time horizon. Surveillance strategies were compared based on NCCN guidelines, with testing every 3 months (3M) or 6 months (6M), as well as two alternate strategies of testing every 12 months (12M) or no surveillance (None) for 5 years. Recurrence, repeat CR rates, and survival outcomes were modeled from population-based outcomes of 257 patients who had CR of mCRC in British Columbia, Canada. Asymptomatic recurrences were more likely to undergo CR, compared to symptomatic ones. Additional costs, utilities, and probabilities were derived from the literature. Costs are in 2015 CAD and utilities in Quality-adjusted life years (QALY), and both discounted at 3% and half-cycle corrected. Analyses were performed using TreeAge Pro with 1000 trials and 1000 distribution samplings. Results: The incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) are listed in the Table. Increasing the frequency of surveillance tests does lead to modest gains in QALY, however, the cost of surveillance and subsequent treatment is high. Using a willingness to pay threshold of 150 000 CAD, the 6M strategy would be favored. Conclusions: In the Canadian context, the optimal surveillance strategy after CR of mCRC matches with the 6M strategy recommended by the NCCN. An additional Canadian data set will be used to externally validate the model outcomes. [Table: see text]
Importance of genetic testing for patients with multiple colorectal cancer primaries.
Authors: Elsas Caroline , LaDuca Holly , Profato Jessica , Mak Bryan 
Published: March 2017

528 Background: Individuals with hereditary colorectal cancer (CRC) may be at increased risk for a second primary CRC. Therefore, a personal history of multiple CRCs may be considered an indication for genetic testing. Methods: Multi-gene panel test (MGPT) results and age at CRC diagnoses were reviewed for 7046 CRC patients who underwent testing from March 2012 to June 2016. Depending on the panel ordered, analysis of up to 49 genes associated with CRC and/or other cancers was performed. The diagnostic yield and age at CRC diagnoses were compared between patients with a history of one CRC (n=6739) and those with two or more CRCs (n=307). Results: Individuals with a history of multiple CRCs had an overall positive rate of 23.8% (n=73), as compared to 12.4% (n=836) in those with a history of one CRC (OR=2.2; p=1.1E-7; 95%CI [1.653,2.907]). In the multiple CRCs group, 77 mutations were identified as follows: MLH1 (n=29), MSH2 (n=18), MSH6 (n=5), PMS2 (n=5), biallelic MUTYH (n=5), CHEK2 (n=5), APC (n=2), BRCA2 (n=3), RAD50 (n=1), BRIP1 (n=1), BRCA1 (n=1), ATM (n=1), and PTEN(n=1). Four patients carried mutations in two different genes. Of the mutation-positive patients with multiple CRCs, 72.6% were diagnosed with their first CRC before age 50, as compared to 59.3% of mutation-positive patients with one CRC. Consequently, the mutation-positive rate increased to 36.3% in patients with multiple CRCs whose first CRC was diagnosed before age 50; whereas it was 12.4% for patients diagnosed with both CRCs at age 50 or above. Conclusions: Overall, individuals with multiple CRCs were approximately twice as likely to be mutation-positive than those with a history of one CRC. This data highlights the importance of genetic testing for those with multiple CRCs, particularly in cases where the first CRC is diagnosed before age 50. Additionally, genetic testing of patients with early onset CRC at the time of diagnosis has the potential to capture patients who may benefit from consideration of additional options to reduce their risk of developing a secondary CRC. Furthermore, mutations were identified in various genes associated with extra-colonic cancers, presenting additional opportunities for cancer risk reduction in patients and their relatives.
Characterization of tumor mutation burden (TMB) in gastrointestinal (GI) cancers.
Authors: Salem Mohamed E. , Xiu Joanne , Weinberg Benjamin Adam , El-Deiry Wafik S. , Weiner Louis M. , Gatalica Zoran , Liu Zhuqing , El Ghazaly Hesham , Xiao Nianqing , Hwang Jimmy J. , Philip Philip Agop , Shields Anthony Frank , Lenz Heinz-Josef , Marshall John 
Published: March 2017

530 Background: GI cancers are generally insensitive to immune checkpoint inhibitors (ICIs). Response to ICIs has been shown to correlate with TMB. Herein, we attempt to quantify TMB in GI cancers and its correlation with PD-1/PDL-1 expression. Methods: Tumor from various GI sites: right-sided and left-sided colon cancers (RT and LT), rectal cancer (RC), small bowel adenocarcinoma (SBA), gastric adenocarcinoma (GA), anal cancer (SCCA), hepatocellular carcinoma (HCC), esophageal adenocarcinoma and squamous cell carcinoma (EA and E-SCC), biliary cancer (BC), pancreatic adenocarcinoma (PA), and pancreatic neuroendocrine tumors (PNET), were analyzed by NextGen sequencing. TMB was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. MSI was assessed by fragment analysis. Correlation of PD-1/PD-L1 expression with TMB was calculated by student’s t test. Results: In total, 1375 tumors were examined. Among the different GI cancer types, RT and LT had the highest TMB (mean: 11.6 and 9.9 mutations [mut]/megabase [MB]), whereas BC and PA had the lowest levels (mean: 5.7 and 4.9 mut/MB) (Table). Overall primary tumors had higher TMB than metastases (mean: 8.3 vs. 6.5 mut/MB, p = 0.037). Using a cut-off of 17 mut/MB to define high vs. low TMB, high TMB was seen in all 24 MSI-H and 2 MSS colon tumors with POLE mutations, but not in other MSS colon tumors (n = 325, p < 0.0001). Similarly, among 6 GA tumors tested for MSI, high TMB was seen in 2 MSI-H while low TMB was seen in the 4 MSS tumors. Overall high TMB was seen most frequently in RT (12%), GA (11%), and SCCA (8%), and least frequently in PA (1.3%) and E-SCC (0%). PD-1 correlated with TMB in some tumor types (RT and RC), as did PD-L1 (RT and HCC). Conclusions: TMB varies among GI cancers. Forthcoming prognostic analysis to assess the correlation between TMB and response to ICIs in GI cancers is underway. [Table: see text]
Awareness and misconceptions of colorectal cancer risk factors among laypersons and physicians.
Authors: Viguier Jerome , Eisinger François , Couraud Sebastien , Guibaudet Lysel , Blay Jean-Yves , Greillier Laurent , Lhomel Christine , Cortot Alexis B. , Morere Jean F. , Pivot Xavier B. 
Published: March 2017

536 Background: The aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. The colorectal cancer (CRC) screening program is in place and targets the 50-74-yr age group. CRC prevention also relies on increased awareness of known risk factors (behavioral [BRF] or non-behavioral [NBRF]). This analysis focuses on awareness of CRC risk factors among the lay population and physicians. Methods: The 4th nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1463 individuals with no history of cancer (age, 40-75 yrs) was interviewed between June 12 and July 10, 2014. A mirror survey on a representative sample of 301 physicians was conducted between July 9 and August 8, 2014. Interviewees were asked to cite the five main RF for CRC. Results: Heredity/family history of CRC was widely cited by physicians but far less by laypersons (LP) (95.3% vs. 26.1%, P < 0.01). Digestive disorders, age, polyps and Crohn’s disease were also cited as NBRF by 38.2%, 22.9%, 15.3% and 12.3% of physicians, respectively. In comparison, these RF were very rarely cited by LP (5.4%, 1.5%, 1.7% and 0.1%, respectively, P < 0.01). Unhealthy-lifestyle RF were cited by 86.4% and 52.7% of physicians and LP, respectively (P < 0.01): poor eating habits, ranked first for both physicians and LP (80.1 vs 46.8%, P < 0.01), including unbalanced or excessively rich diet (52.8% vs. 41.2%, P < 0.01) and excessive quantities of red meat (12.6% vs. 2.2%, P < 0.01). Among unhealthy-lifestyle RF, after poor eating habits, physicians cited first tobacco (24.3%), then alcohol (19.9%), and lack of exercise (14.6%) as other BRF. These were cited by 12.2% (P < 0.01), 16.0% (NS) and 4.7% (P < 0.01) of LP, respectively. Overweight/obesity was cited by 19.6% of physicians but by only 1.8% of LP. Conclusions: Overall, there is a lower level of awareness of CRC risk factors in lay persons than in physicians. Physicians are generally aware that heredity/family history and unhealthy lifestyle are the major RF for CRC, in line with the widely recognized RF. In contrast, lay persons rank BRF highest, and notably those related to poor eating habits.
Performance of 18FDG-PET in the management of non-metastatic HIV+ anal squamous cell carcinoma (ASCC).
Authors: Baba Hamed Nabil , Deplanque Gael , Kassis Raid , Gatineau Michel , Staudacher Lionel , Chaiba Imene , Savinelli Francesco , Sverdlin Robert , Maiga Oumou , Marin Jean Luc , de Parades Vincent , Lemarchand Nicolas , Marty Olivier , Levoir Damien , Loriau Jerome , Zerbib Eric , Zins Marc , Boulay Isabelle , Raymond Eric 
Published: March 2017

541 Background: ASCC remains rare, but the incidence has been increasing over the last decade, especially in patients with HIV infection (HIV+). A recent meta-analysis demonstrated the usefulness of 18FDG-PET in initial staging and response assessment in ASCC. HIV+ patients may develop opportunistic infections which can cause false positives lymph nodes on PET scanning and, therefore, our objective was to evaluate performance of 18FDG-PET in HIV+ patients. Methods: Retrospective analysis of consecutive patients with non-metastatic ASCC, treated in our institution during six years. HIV+ patients were analyzed separately in two groups according to their lymph nodes status, group 1 (Gr 1): N0, group 2 (Gr 2): N1, N2, N3. Results: A total of 87 patients with ASCC were analyzed, including 24 HIV+ patients (21 males, median age was 53 for male and 50 for women). There were 15 patients in Gr 1 and 9 in Gr 2. All patients performed conventional imaging (MRI and CT-scan). In Gr 1, 12/15 patients had 18FDG-PET, it resulted in upstaging nodal disease in 2 patients. In Gr 2, 6/9 patients had 18FDG-PET, it resulted in upstaging nodal disease in 1 patient and downstaging nodal disease in 2 patients. Both of sensibility and specificity of FDG-PET were 83% in our HIV+ population. All patients underwent Mitomycine C and 5FU based chemoradiation or exclusive radiation therapy. Mean radiation dose received was 63.3Gy in G1 and 63.9Gy in G2. 18FDG-PET drives a modification in treatment strategy in only 1 patient in both of groups. Post-treatment 18FDG-PET was performed 4 months after treatment completion. Among patients who had post-treatment 18FDG-PET, a metabolic complete response was observed in 6/11 patients in Gr 1 and 3/5 patients in Gr 2. Survival at 5 years was 89% and 75% in Gr 1 and Gr 2, respectively. Conclusions: Based on our experience, 18FDG-PET drives substantial changes neither in staging nor in therapeutic strategy for ASCC HIV+ patients, however, it may be useful for radiation therapy planning.
Incidence of colorectal carcinoma following liver transplantation: A retrospective analysis using the United Network for Organ Sharing (UNOS) database.
Authors: Krishnan Mridula , Gharzai Laila , Qurie Ahmad , Diab Osama , Narayanan Mahesh Anantha , Vivekanandan Renuga , Walters Ryan W 
Published: March 2017

542 Background: Since 1988, approximately 145,000 liver transplants (LT) have been performed in the United States, with 7,127 in 2015 alone. Several malignancies occur more frequently in solid organ transplant recipients. Studies have shown increased risk of Colorectal cancer (CRC) post LT in adults with primary sclerosing cholangitis, whether the risk of de novo CRC is increased or not remains controversial. Methods: A retrospective analysis was conducted using the UNOS database. Between-group differences in CRC rates were compared using Fisher’s exact test whereas, the differences in observed years between liver transplant and CRC were compared using negative binomial regression models. Results: We retrospectively analyzed 12,337 recipients of LT within the UNOS database. The overall incidence of CRC post LT was estimated to be at 3.8 percent. Interestingly, the incidence was higher in women and non-obese recipients. All immunosuppressive agents within the limits of the database were analysed for maintenance and anti-rejection. The two agents with some increase in incidence were cyclosporine and cellcept but this was statistically insignificant.(Table 1) Women and elderly ( > 65 years) were likely to develop CRC approximately 25 percent earlier than men and younger patients (p = 0.003 and p = 0.001, respectively). Conclusions: Studies have shown a trend toward increased incidence of CRC post LT. These studies were limited by the sample size and were single-center trials. To date there are no elaborate guidelines on surveillance of CRC in LT recipients. In our study there was a shorter interval to development of CRC in older patients and women, suggesting that this population may benefit from early initiation of screening. [Table: see text]