bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin analogues to stimulate cell growth in human cancer initiating cells (CICs).
Authors: Holgado Esther , Cortes Semperes Maria , Pernia Olga , Arrizabalaga Olatz , Ibañez de Cáceres Inmaculada , Hitt Ricardo , De Castro Javier , Ayuso Sacido Angel , Perona Rosario , Belda-Iniesta Cristobal 
Published: March 2020

1575 Background: Conflicting epidemiologic studies have suggested insulin and their analogues currently used in the management of type 2 diabetes to be involved in tumor progression and development. Surprisingly, time of exposure to insulin analogs reported in those retrospective studies is too short for be a carcinogen. We hypothesized that differential affinity that insulin analogs display for insulin receptor and IGF-1R at CICs may account for this possibility. [AspB10]insulin (X10) is a long-acting insulin analog that displays greater affinity for IGF1R than either the long-acting insulin analog GLA or human insulin (HI) in vitro. X10 is tumorigenic in animal models whereas GLA is not. GLA is rapidly metabolized to the metabolites, M1 and M2 that exhibit metabolic and mitogenic profiles similar to that of HI in vitro. CICs are cancer cells with self-renewing, stem cell-like properties with the ability to proliferate and differentiate into specific cells found in tumor types and thus they are able to maintain tumor bulk. Many cancers are thought to be initiated by CICs, and there is evidence that they cause cancer recurrence, metastatic progression and resistance to therapies. Our aim was to compare the mitogenic activity of HI, GLA, X10, M1 and M2 on human CICs in vitro. Methods: CICs derived from 10 human cell lines including glioma, lung, breast, colon, and prostatic cancers were isolated and grown in defined growth medium (no serum) with either HI, GLA, X10, M1 or M2. Growth was estimated using the MTS colorimetric assay. Results: HI, GLA and X10 stimulated CIC growth to a similar extend, whereas M1 and M2 had growth promoting activity similar to medium without HI. Similar results were obtained when measuring diametric sphere growth. Additionally, AKT phosphorylation levels were increased 2-fold after stimulation with HI, GLA or X10, whereas stimulation with M1 or M2 did not produce a significant increase. Conclusions: This is the first study that has explored the biology of CICs treated with insulin analogs. The data show that GLA displays a mitogenic profile comparable to that of human insulin for all CIC lines tested, whereas M1, has even less growth promoting activity.
Survival rates in patients with primary metastatic breast cancer over a 10-year period: A retrospective analysis based on individual patient data from a multicenter data bank.
Authors: Barinoff Jana , Harter Philipp , Heitz Florian , Dittmer Christine , Kuemmel Sherko , Hils Rita , Lorenz-Salehi Fatemeh , Traut Alexander , du Bois Andreas 
Published: March 2020

1577 Background: Approximately 6% of patients with breast cancer have distant metastases at the time of the initial diagnosis. The aim of this analysis was to examine the overall survival rate over time and to investigate the effect of new therapy options. Methods: This retrospective analysis was performed based on the data bank of the Clinic for Gynaecological Oncology/ Dr. Horst Schmidt Klinik, Wiesbaden and the Clinic for Gynaecological Oncology and Senology/ Kliniken Essen Mitte, Essen. The patients with primary metastatic breast cancer (pmBC) who were diagnosed and treated at the accredited breast cancer centres of these clinics were enrolled between 1998 and 2007. The date of diagnosis was used to define 2 specifically chosen 5-year periods: 1998–2002 and 2003–2007. The follow-up time was on average 76 months. The Breslow Test was used to evaluate changes in the median survival time and to detect factors associated with the increase in survival rates. Results: Two hundred sixteen patients with complete baselines were analysed. Ninety patients were diagnosed between 1998 and 2002, and 126 patients received their diagnosis of pmBC between 2003 and 2007. The tumour-biological factors were the same in both groups, whereas the therapeutic concepts were different—the later group (2003–2007) received more aromatase inhibitors, taxane-based chemotherapy and trastuzumab. This finding resulted in an increased median survival time from 31 months in the years 1998–2002 to 44 months in the group with the first diagnosis between 2003 and 2007. Conclusions: Primary metastatic breast cancer occurred at constant rates over last 10 years. The tumour findings did not change in the time between the two examined groups; however, the treatment options in the 2003–2007 group included newly approved therapies. The time period of the first diagnosis was detected as a risk factor for overall survival. Those patients diagnosed in the more recent time frame had a significantly improved survival rate. The establishment of new therapy options may explain this finding.
Survival outcomes for patients with equivocal 18FDG-PET CT scan for extrahepatic disease prior to liver resection for metastatic colorectal cancer.
Authors: Kumar Rajiv , Beeke Carol , Ullah Shahid , Price Timothy Jay , Padbury Rob , Roder David , Karapetis Christos Stelios 
Published: March 2020

1581 Background: Patients considered for liver resection (LR) for hepatic metastases from metastatic colorectal cancer (mCRC) have an 18FDG-PET CT scan (PET) to exclude extrahepatic disease (EHD). The prognostic significance of an equivocal PET on overall survival (OS) for patients who proceed to LR is not entirely clear. The aim of the study is to compare OS for patients with equivocal PET prior to LR to those with a PET negative for EHD. Methods: The South Australian Metastatic Colorectal Cancer Registry collects data for mCRC patients diagnosed after February 1, 2006. Patients were included if they had LR and a PET prior to LR. PETs were coded as no EHD and possible EHD. The Cox proportional hazard model was applied to analyse the outcome of patients with an equivocal PET for EHD on OS, adjusting for possible confounders. Results: Of the 2,480 patients on the registry, 273 had had LR. Of these, 183 (67.0%) had a PET prior to LR, with 137 having no EHD and 46 having possible EHD. The no EHD and possible EHD groups were well balanced for patient, tumour and treatment characteristics – mean age: 66.7 yrs-vs-68.4 yrs, male gender: 61.3%-vs-63.0%, KRAS wildtype: 11.0%-vs-16.3%, stage IV disease at initial diagnosis: 49.6%-vs-54.3%, colonic primary: 74.4%-vs-65.2%, one LR: 82.5%-vs-89.1%, one line of chemotherapy: 52.4%-vs-48.6% and well-moderate tumour differentiation: 85.7%-vs-86.4%. The median follow-up was 32.9 months for no EHD and 33.6 months for possible EHD (P-value = 0.84). The OS for no EHD compared with possible EHD at 1-year was 98.5%-vs-93.5%, at 2-years was 87.6%-vs-88.0%, and at 5-years was 61.5%-vs-59.4%. The unadjusted hazard ratio for OS was 1.22 (95% CI 0.64–2.34, P-value = 0.54) for possible EHD. On adjustment for age, gender, stage at diagnosis, primary site, number of LRs, lines of chemotherapy and tumour differentiation, the hazard ratio remained non-significant; however lower (HR=0.76 (95% CI 0.37–1.59, P-value = 0.47)), for possible EHD. Conclusions: A PET was only performed in 67.0% of patients who had LR for mCRC. There was no difference in OS between patients with no EHD and possible EHD on PET who proceed to LR.
Influence of physical activity on recurrence and survival of colorectal cancer patients: A meta-analysis.
Authors: Des Guetz Gaetan , Bouillet Thierry , Uzzan Bernard , Chouahnia Kader , Nicolas Patrick , Zelek Laurent H. , Morere Jean F. 
Published: March 2020

1583 Background: Colorectal cancer (CRC) predominates in developed countries among sedentary populations. A meta-analysis (MA) showed that physical activity (PA) decreased the incidence of new cases of CRC. The impact of PA on recurrence and mortality of non-metastatic CRC patients is still controversial. Methods: We performed a literature-based meta-analysis of all published observational studies, using the following keywords (colorectal cancer, physical activity, survival) in PubMed and EMBASE. We searched for a dedicated MA in the Cochrane Library (none found). We cross-checked all references. Pre- and post-diagnostic PA levels were assessed with MET (Metabolic Equivalent Task). Usually, high PA levels corresponded to > 17 MET hours/week. Overall survival (OS) and cancer-specific survival (CSS) were assessed by means of Hazard Ratios (HRs) with their 95 % Confidence Interval (CI). We pooled adjusted HRs since the variables of adjustment were almost identical between studies (age, sex, BMI, tobacco use, alcohol and red meat consumptions ). By convention, when higher PA levels were associated to an improved survival compared with lower PA levels, HRs for detrimental events were < 1. We used EasyMA software. We used fixed effect model whenever possible and random effect model only in case of between-study heterogeneity. Results: Eight studies (11298 participants) published from 2006 to 2013 met the inclusion criteria, representing 3110 males and 3710 females, 3072 colon and 1318 rectum cancers. Mean age was 67 years (range 21-82 years). HR CSS for post-diagnostic PA (higher PA level vs. lower) was 0.61 (CI: 0.44-0.86; random effect model). The corresponding HR for OS was 0.62 (CI: 0.54-0.71). HR CSS for pre-diagnostic PA was 0.80 (CI: 0.69-0.92). The corresponding HR for OS was 0.74 (CI: 0.63-0.86). Conclusions: This MA is the first to show that higher PA levels are associated with a better CSS, suggesting that sustained PA should be advised for non-metastatic CRC patients. OS also significantly improved, not surprisingly since PA should reduce risk of cardio-vascular events. These findings should be tempered by the rather small number of studies included.
Breast cancer subtype variation by ethnicity in a population-based cohort in British Columbia.
Authors: Wan Dante , Villa Diego , Woods Ryan , Yerushalmi Rinat , Gelmon Karen A. 
Published: March 2020

1585 Background: Reports suggest breast cancer subtypes (BCS) are different in developing countries, often attributed to ethnicity. We assessed BCS in our multiethnic population with access to screening mammography and universal health care. Methods: The Breast Cancer Outcomes Unit database was used to identify women diagnosed with invasive breast cancer in 2006 and referred to the BCCA. Ethnicity was abstracted by chart review from a patient questionnaire completed by all new referrals. Ethnicities were grouped into: Caucasian (CA), East Asian (EA), Aboriginal (A), South Asian (SA), South-East Asian (SEA) and Other (O). BCS were grouped as: ER/PR+ HER2-, ER/PR+ HER2+, ER/PR- HER2+, ER/PR- HER2-. Rates of ER and HER2 positivity and BCS were compared by ethnicity using the Chi-square test; age at diagnosis was compared by ethnicity using the Kruskal-Wallis test. Results: 2,222 women were eligible with 2072 having completed questionnaires. Median age was 59 years. The distribution of ethnicities: 73% CA, 8% EA, 4% A, 3% SA, 3% SEA and 9% O. T stage was T1 57%, T2 34%, T3 8% and Tx 1%. N stage was N0 55%, N1 25%, N2 9%, N3 3% and NX 9%. 4.5% were Stage IV at diagnosis. HER2 positivity was significant by ethnicity; 14% CA, 18% EA, 25% A, 29% SA, 26 % SEA, 17% O (p = 0.0008). Age varied significantly (p<0.0001); mean age in SEA was 53 compared to 60 years in CA. Conclusions: Although the subsets are small there appear to be differences in the rates of ER and HER2 positivity by ethnicities. ER negative disease was more frequent in Aboriginal and South Asians. These groups and SE Asians had more HER2 + disease. Validation on larger populations is pending. Genomics analysis may provide epidemiologic information. Differences in BCS may impact screening and prevention strategies. [Table: see text]
Frequency of oncogenic alterations in five driver genes in Chinese female lung adenocarcinoma.
Authors: Xu Ren , Ma Jie , Xie Li-Qun , Tao Hui-Qing , Wei Bing , Guo Yong-Jun , Bao Wen-Jing , Tong Guang-Quan , Ding Lu , Zhan Min-Ning , Yong Ma Zhi 
Published: March 2020

1588 Background: Currently, 5 driver genes (EGFR, K-RAS, B-RAF, ALK, RET) have been widely explored and become new targets of NSCLC, however no report has been found in Chinese female lung adenocarcinoma, who were prone to EGFR mutations and therefore, are the targets for TKIs therapy. Methods: FFPE-tissues from 310 female lung adenocarcinoma adopted in Hunan or Henan province between 2000 and 2012 were investigated. Oncogenic alterations in newly found 5 driver genes were analyzed. ARMS was used to study EGFR, K-RAS and B-RAF mutation. The reverse transcription and real-time PCR were performed to detect either ALK and RET fusions or ALK and RET gene expression. Sequencing was further applied to confirm the subtypes of fusions. Results: Among 310 samples, 149 (48.1%) EGFR mutations, 16 (5.2%) KRAS mutations, 0 (0%) BRAF mutations, 23 (7.4%) ALK fusions and 5 (1.6%) RET fusions were detected. Only EML4-ALK fusion but no other ALK fusions were found. Further research showed that cases (22, 95.6%) with high ALK expression were often accompanied by EML4-ALK fusion and poorly differentiated adenocarcinoma. Two RET fusions, KIF5B-RET and CCDC6-RET were found, with 2 cases and 3 cases, respectively. The ratio of RET/ABL mRNA levels was significantly higher in CCDC6-RET samples with poorly differentiated adenocarcinoma. However, with KIF5B-RET fusion, relatively high RET/ABL mRNA expression was detected in one KIF5B-RET sample with moderately differentiated adenocarcinoma, while no RET expression was detected in other two KIF5B-RET samples with highly differentiated adenocarcinoma. Conclusions: This is the first research about the oncogenic alterations of 5 important driver genes in Chinese female lung adenocarcinoma, as well as the correlation between ALK fusion and ALK expression or between RET fusion and RET expression, thus laying good foundation for understanding the genetic mutation spectrum in female lung adenocarcinoma.
Rapid online feedback to improve clinical trial accrual: CODEL anaplastic glioma (AG) (NCCTG/Alliance N0577) as a model.
Authors: Massett Holly , Jaeckle Kurt A. , Dilts David M. , Denicoff Andrea , Souhan Erin , Hopkins Jenny R , Mann Bhupinder Singh 
Published: March 2020

1596 Background: Structured feedback from community oncologists regarding trial design rarely occurs. Survey templates were created to assess trial feasibility, design and scientific interest from the community, with the aim of improving accrual. We report results from a survey regarding redesign of the Phase III CODEL trial for newly diagnosed 1p/19q codeleted AG, which employed this approach. Methods: A field-tested, online survey template was tailored for CODEL and emailed to U.S. and international oncologists. The survey assessed (a) practice changes resulting from ASCO 2012 data from RTOG 9402 (abstract # 2008b) and EORTC 26951 (abstract # 2); (b) scientific interest in a redesigned trial; and (c) potential accrual issues. Respondents reviewed a brief trial concept and answered 15 questions anonymously via a web-based system. Results: 173 oncologists completed the survey over 2 weeks in Sept 2012(48% US, 52% Int’l; 35% med oncs, 31% rad oncs, 29% neuro-oncs). Results from the 2 prior studies substantially influenced clinicians’ treatment decisions for patients with newly diagnosed 1p19q codeleted AG--from only 9% recommending RT+PCV prior to the ASCO reports, to 46% after the results were presented. Previously, 25% recommended RT alone, and after ASCO, no one did. Most indicated strong interest in the revised CODEL research questions, trial design, randomization arms, and in re-opening the revised trial. The most interesting schema was a 3-arm design (selected by 45% of respondents): (RT + procarbazine, CCNU and vincristine chemotherapy [PCV]) vs. (RT + Temozolomide [TMZ]) vs. (TMZ alone), with neuro-oncs (49%) preferring it most, and rad oncs least (36%). The second most interesting choice (27%) was RT+PCV vs. RT+TMZ; the third choice (20%) was RT+TMZ vs. TMZ alone. Most (61%) felt patients would accept any arm. Respondents encountered eligible patients frequently enough to meet projected CODEL accrual goals. Conclusions: Survey findings significantly influenced decisions on how best to redesign the CODEL trial. Rapid, web-based surveys of community oncologists can provide important feedback regarding level of interest, which might facilitate timely accrual and trial completion.
Phase III randomized, double-blind, placebo-controlled trial of donepezil in irradiated brain tumor survivors.
Authors: Rapp Stephen R. , Case Doug , Peiffer Ann , Naughton Michelle Joy , Stieber Volker W. , Bayer Gerald K. , Bilodeau Paul A. , Moore Dennis Frederic , Falchuk Steven Charles , Needles Burton M. , Piephoff James , Edenfield William j , Giguere Jeffrey K. , Erickson Nicholette , Loghin Monica Elena , Shaw Edward G. 
Published: March 2020

2006 Background: This RCT assessed the effect of 24 weeks of 5-10 mg per day of donepezil, an acetyl cholinesterase inhibitor, on cognitive functioning (primary endpoint) and fatigue, mood and QOL in long-term brain tumor survivors following partial or whole-brain irradiation. Cognitive results are reported herein. Methods: From 2/08-12/11,198 adult primary and metastatic brain tumor survivors > 6 months post radiation treatment (>30 Gray) recruited at 24 sites affiliated with the Wake Forest Community Clinical Oncology Program Research Base, 3 CTSU sites and M.D. Anderson Cancer Center were randomly assigned to receive donepezil (n=99) or placebo (n=99). Cognitive function was assessed at baseline, 12 and 24 weeks with Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure, Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard. A Cognitive Composite (CC) score was the primary outcome. Results: The sample was 91% White, 54% female, and median age was 55 yrs. 66% had primary tumors, 27% brain metastases and 8% PCI. Median time since diagnosis: 38 mos. 95% had 0-1 ECOG performance status scores. 74% completed the study. CC score improved significantly by 24 weeks in both arms (p < .01); however, there was not a statistically significant difference between groups (p = .57). Donepezil group performed better than placebo on HVLT Recognition (p = .03) and Discrimination (p = .01) and GP-Dominant Hand (p = 0.02). Significant interactions were found between treatment arm and baseline cognitive scores for: CC (p = .01), HVLT Immed. Recall (p = .03), HVLT %Savings (p < .01), Digit Span Forward (p = .01), ROCF Copy (p = .03), TMT-B (p = .05) and GP-Dominant (p < .01). In all cases, the benefit of donepezil, relative to placebo, was greater for those with worse baseline scores. Conclusions: Long-term brain tumor survivors treated with brain irradiation who have cognitive impairment can benefit from 5-10mg of donepezil for 24 weeks. Improvements in verbal memory, working memory, visuo- and psychomotor performance and executive functioning were observed in this group. (Study supported by NIH/NINR grant 5R01NR009675-04, NIH/NCI grant 2 U10 CA 81851-09-13 and Eisai, Inc.) Clinical trial information: NCT00369785.
Interim analysis of a phase I/II study of panobinostat in combination with bevacizumab for recurrent glioblastoma.
Authors: Lee Eudocia Quant , Reardon David A. , Schiff David , Drappatz Jan , Muzikansky Alona , Hammond Samantha , Grimm Sean Aaron , Norden Andrew David , Beroukhim Rameen , McCluskey Christine Sceppa , Chi Andrew S. , Batchelor Tracy , Smith Katrina H. , Gaffey Sarah C. , Gerard Mary , Snodgrass Susan M. , Raizer Jeffrey J. , Wen Patrick Y. 
Published: March 2020

2013 Background: Bevacizumab is frequently used to treat recurrent GBM, but responses are generally not durable. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic effects in GBM and may work synergistically with bevacizumab. We conducted a multicenter phase I/II trial of panobinostat in combination with bevacizumab in patients with recurrent GBM. Methods: In the phase II trial, patients with recurrent GBM were treated with oral panobinostat 30 mg three times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was 6-month progression-free survival (PFS6) and the study was powered to discriminate between a 35% and 55% PFS6 rate (85% power at an alpha level of 0.07). A planned interim analysis specified suspension of accrual and careful data review if 12 or more of the first 21 patients accrued to the study progress within 6 months of initiating treatment. Patients with recurrent GBM enrolled in the phase I study at the maximum tolerated dose (which is the phase II dose) were eligible for inclusion in the interim analysis. Results: Thirteen of the first 21 patients accrued to the GBM arm of the study had progressed within 6 months of initiating study treatment. The study was closed to further accrual and a planned interim analysis was performed. Median age was 53 (range 22-66) and median KPS was 80% (60%-100%). PFS6 rate was 33.9% [95% CI 12.8, 56.5), median was PFS 5 months [95% CI 3 months, NR], and median OS was 342 days [95% CI 203 days, NR]. Five patients (23.8%) achieved partial responses. Conclusions: Although reasonably well-tolerated, this phase I/II study of panobinostat and bevacizumab in recurrent GBM did not meet criteria for continued accrual and the study was closed. Updated outcome and safety data will be presented at the meeting. Study Supported by: Novartis and Genentech Clinical trial information: NCT00859222.