bluuebunny/crossref_metadata_2025_split huggingface dataset:
The incidence, risk factors and prognostic implications of venous thromboembolism in Asian patients with non-small cell lung cancer.
Authors: Lee Yun-Gyoo , Kim Inho , Lee Eunyoung , Bang Soo-Mee , Kang Chang Hyun , Kim Young Tae , Kim Hak Jae , Wu Hong-Gyun , Kim Young Whan , Kim Tae Min , Lee Keun-Wook , Lee Se-Hoon , Kim Dong-Wan , Heo Dae Seog 
Published: March 2020

1590 Background: The goal of this study was to describe the incidence, risk factors and prognostic implications of venous thromboembolism (VTE) in Asian patients with non-small cell lung cancer (NSCLC). The association between specific gene mutations and the risk of VTE was also evaluated. Methods: A total of 1998 consecutive patients with NSCLC were enrolled and analyzed retrospectively. To minimize potential confounding, we used propensity score-matching to compare overall survival between patients with and without VTE. Results: The 6-month and 2-year cumulative incidences of VTE were 4.2% and 6.4%, respectively. The risk of VTE increased 2.45-fold with each advancing stage in NSCLC (common hazard ratio [HR] 2.45; 95% CI 1.96–3.05; P<0.001). In multivariate analyses, the effects of therapeutic variables including surgery, chemotherapy, and radiotherapy on the development of VTE were modified by NSCLC stage. Therefore, we calculated stratum-specific HRs by performing stratified analyses for each stage. The independent predictors of VTE were advanced age, pneumonectomy (vs. lobectomy) and palliative radiotherapy (vs. no radiotherapy) in localized NSCLC and no surgery (vs. lobectomy) and palliative radiotherapy (vs. no radiotherapy) in locally advanced NSCLC. Adenocarcinoma histology (vs. squamous cell carcinoma) was the only independent risk factor for increased risk of VTE in metastatic NSCLC. EGFR mutation was independently associated with a 47% lower risk of VTE in adenocarcinoma compared to wild type (HR 0.53; 95% CI 0.29–0.99; P=0.045). Among both the entire and propensity score-matched cohorts, a significant survival difference was observed between patients with and without VTE in localized NSCLC, but not in locally advanced or metastatic NSCLC. The strong association we observed between VTE and the increased rate of recurrence (risk ratio 2.0; 95% CI 1.28–3.12; P=0.009) can explain the significant difference in survival in localized NSCLC. Conclusions: Approximately 6.4% of Asian patients with NSCLC developed VTE during a 2-year period. The association between VTE and decreased survival was limited to localized NSCLC.
A retrospective study on the role of diabetes and metformin in colorectal cancer disease progression.
Authors: Ramjeesingh Ravi , Orr Christine , Richardson Lyndsay , Hammad Nazik 
Published: March 2020

1593 Background: Recent studies have suggested a potential epidemiological role for diabetes as an independent risk factor for the development of colorectal cancer (CRC). These studies have furthermore suggested patients with diabetes who develop colorectal cancer have an increased mortality. Methods: To identify a potential correlation between CRC and diabetes, we are performing a retrospective chart review of CRC patients treated at the Cancer Center of Southeastern Ontario diagnosed from January 2005 to December 2011. 1,300 colorectal cancer patient charts have been identified through Ontario Cancer Registry Data based on confirmed ICD-10 diagnosis codes and the variables of 200 random patients have been extracted into our database thus far. The final analysis will be completed April 2013. Results: Preliminary analysis of the database has indicated that the average age of patients with CRC was 69 years with 55% being women. The incidence of diabetes in our CRC population was 19%, double the rate of diabetes in the general population in Canada. As expected, the rate of co-morbidities excluding diabetes was higher in the diabetic group (92.9% vs 69.3%; p=0.004). When we looked at the diabetic population specifically, the rate of death was not significantly different compared to the non-diabetic population (13.2% vs 12.7%, p=0.94), however those with diabetes presented with later-stage (stage 2/3/4) disease (92.1% versus 88.6%). The average number of days from the time of diagnosis to death in the diabetic group (200 days) was half compared to the non-diabetic group (420 days, p=0.014). However, there was no statistical difference in the percentage of progression, number of different metastatic sites or the burden of metastatic disease amongst the two populations. A subgroup analysis of diabetic patients on metformin illustrated that the death rate (p=0.06), rate of progression (33% vs 20%) and those presenting with later stage disease was higher in patients not on metformin compared to those on the drug. Conclusions: Our preliminary work suggests diabetics with CRC may have a worst prognosis however taking metformin may have a positive impact on prognosis.
Survival after cancer diagnosis among patients with higher income and education in Israel, a country with highly appreciated health service.
Authors: Rottenberg Yakir , Zick Aviad , Peretz Tamar 
Published: March 2020

1598 Background: In recent years, the 5 year survival following cancer diagnosis is about two thirds. Among patients with various chronic diseases, improved survival is known to be associated with higher income and education. The aim of the current study is to assess the influence of income and education on survival following cancer diagnosis in Israel. Methods: Retrospective cohort study, using baseline measurement from the 1995 census conducted by the Central Bureau of Statistics in Israel. Cancer data were obtained from the Israel Cancer Registry. Cox proportional hazards ratios were calculated for mortality among cancer patients and adjusted for age, sex, religious, income and education years. The first model excluded cancers associated with early detection (breast, prostate, colorectal and cervix), and a second model excluded also lung cancer in order to control for smoking which is common in lower socioeconomic status. Results: A total of 3,712 cases of cancer and 1,252 deaths were reported during the study period. Higher income (HR=0.985 per 1000NIS, approximately 330$ in 1995's value, p=0.016) and education (HR=0.957 per year of education, p<0.001) were associated with decreased risk of death after cancer diagnosis. Jews had better prognosis than non-Jews following cancer diagnosis (HR=0.62, p<0.001), while males (HR=1.54, p<0.001) and age (HR=1.036 per year, p<0.001) had been associated with worse prognosis. The association between higher income and education was not changed in a model which excluded lung cancer. Conclusions: Higher income and education are associated with improved survival after cancer diagnosis. In the light of current study, further studies are needed to depict the variation in cancer incidence, stage at diagnosis and treatment disparities related to socioeconomic variables.
Effect of statin and metformin on survival in veterans (V) with B-cell lymphoproliferative disorders (BLD).
Authors: Srinivas Shanthi , Gonzalez Melanie L. , Khan Sunniya , Gandhi Arpita , Crump Barbara , McPherson Monica , Paz-Querubin Emma R , Chang Victor T , Kasimis Basil 
Published: March 2020

1602 Background: The incidence of BLD has been increasing in V. As many V are on statin and metformin for comorbid conditions, we evaluated the impact of their use on survival. Methods: In an IRB-approved protocol, we reviewed the records of 332 V diagnosed with BLD from January 1997 to Dec 2011 for demographics, height(H),weight(W), BMI,statin and metformin use, clinical and laboratory data and ECOG PS. Comorbidity was assessed using the Charlson Comorbidity Index (CCI),Kaplan-Feinstein Index (KFI) and Cumulative Illness Rating Scale (CIRS). Cox regression analysis was performed using SAS v 9.2. Results: There were 332 V with a median (M) age of 70 years (27-94). The M for H 70 inches (58-78), W 183lbs (99-356.5) and BMI 26.7 kg/m2 (15.54 -48.45). The M for hemoglobin(Hgb) 12.8 g/dl (7.3-17.4), albumin 3.9(1.2-5.4), lactate dehydrogenase( LDH) 183 IU/L (85-1905), beta 2-microglobulin 2.6 mg/dl (0.8-39) . The M for CCI was 4.7 (0.8-12), KFI 2 (0-3), CIRS15 3 (0-6), CIRS16 6(0 -14), CIRS17 1.9(0-6), CIRS18 0(0-3), CIRS19 0(0-3). M survival was 1297days(4-7468).The number of V receiving statin was 167 (51%) and metformin 46 (14%). Statin use was a predictor of survival by both univariate and multivariate analysis but metformin was a predictor only by univariate analysis. Conclusions: Statin use was an independent and significant predictor of survival in this group of V with BLD and needs to be validated in a larger group of patients. [Table: see text]
Identification of the occult tumor in cancer of unknown primary (CUP): A priority based on histology.
Authors: Kim Chong Sung , Hannouf Malek Bassam , Brackstone Muriel , Winquist Eric , Zaric Gregory S 
Published: March 2020

1605 Background: The poor prognosis of cancer of unknown primary (CUP) patients is likely to improve with knowledge of the primary site. CUP patients form a diverse clinicopathological group; however, there remains doubt as CUP may indeed represent a unique clinical classification. Methods: We used the Ontario Cancer Registry to identify all patients diagnosed with cancer from January 2000 to December 2005. We linked these patients with the Canadian Institute of Health Information Same Day Surgery and Discharge Abstract Database to identify those who were initially diagnosed with a metastatic tumour. Information on clinical and pathological characteristics including age, gender, primary tumour site, histology, and second primary were available from the Ontario Cancer Registry. We stratified results according to primary tumour site and histology. Five-year survival data were available for all patients and were obtained from the Ontario Cancer Registry. Results: Of 52,619 patients diagnosed with metastatic tumour at the time of their initial cancer diagnosis, 4,866 (9.2%) patients were diagnosed with CUP and 47,753 (90.8%) patients were diagnosed with metastasis of known primary. The 5-year Kaplan-Meier estimate of CUP overall survival (OS) differed significantly with patients diagnosed with metastasis of known primary (median OS= 1.0 versus 10.4 months, respectively, log–rank test p<0.0001). In subgroup analyses, the 5-year OS of CUP patients with adenocarcinoma (n=1,389, median OS=1.83) was significantly worse when compared to metastatic adenocarcinoma of known primary (log-rank test p<0.0001). An identical result was obtained with CUP patients of undifferentiated histology (n=3,230). The 5-year OS of CUP patients with squamous cell carcinoma (n=247, median OS=18.5) did not differ significantly with those of other squamous cell carcinoma groups of known primary (log-rank test p>0.56). Conclusions: Although CUP patients as a whole have a poor prognosis compared to other metastatic patients of known primary, distinct subsets of CUP patients have similar prognosis. These data suggest that an intensive diagnostic approach for identification of the primary is not justified for all CUP patients.
Optimizing the identification of anaplastic oligodendroglioma patients that benefit from adjuvant PCV chemotherapy using the Illumina platform: A further report from EORTC study 26951.
Authors: Van Den Bent Martin J. , Erdem Lale , Gorlia Thierry , Taphoorn Martin JB , Kros Johan M , Wesseling Pieter , Allgeier Anouk , Dubbink Hendrikus J , Idbaih Ahmed , Sanson Marc , French Pim ,   EORTC Brain Tumor Group
Published: March 2020

2011 Background: Adjuvant PCV chemotherapy improves overall survival (OS) in 1p/19q co-deleted grade 3 gliomas. Analyses of EORTC 26951 and RTOG 9402 suggest that other molecularly defined subsets of grade III tumors benefit as well. We previously identified a CpG-Island Hypermethylated Phenotype (CIMP+) as a candidate biomarker. This was further explored in a larger series using snap frozen (SF) or formalin fixed paraffin embedded (FFPE) tumor material, and compared to the value of 1p/19q, IDH1/2 and MGMT status. Methods: Methylation profiles were assessed using the Infinium HumanMethylation 27 or 450 BeadChip (Illumina). MGMT promoter methylation was re-assessed with a logistic regression model (MGMT-STP27) using probes cg1243587 and cg12981137 of the platform as described (Bady et al, Acta Neuropathol 2012;124:547-60). These probes correspond to area’s of the promoter correlated to MGMT protein expression. Previously, MGMT promoter methylation had been assessed using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA). Results: Methylation profiling was conducted in 115 patients. CIMP status correlation between FFPE and SF was excellent (R2 0.96). In multivariate analysis, 1p/19q co-deletion and CIMP status were independent prognostic factors. Although 1p/19q status and IDH mutational status identify subgroups with more benefit of PCV chemotherapy, tests for interaction remain negative (p 0.25 and 0.33 respectively); MGMTstatus (MS-MLPA) had no impact (p = 0.70). However, CIMP status was of borderline predictive significance (p= 0.07), and MGMT-STP27 was of statistical significance (p = 0.003; HR unmethylated 1.61, 95% CI [0.71, 3.66], HR methylated 0.37, 95% CI 0.23, 0.61]. Conclusions: CIMP status and MGMT promoter methylation assessed with Illumina HumanMethylation BeadChips appear the most informative tests for identifying grade III glioma patients benefitting from the addition of PCV to RT. Validation in an independent dataset is required. Clinical trial information: NCT00002840.
The Stupp regimen preceded by early post-surgery temozolomide versus the Stupp regimen alone in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM).
Authors: Zhou LF , Yao Yu , Yang Shuyuan , Yang Xuejun , Wang Xiang , Zhang Xiang , Zhang Liwei , Lu Yicheng , Chen Zhong-ping , Zhang Jianmin , Qi Songtao , Wang Renzhi , You Chao , Mao Ying , Wang Jisheng , Chen Juxiang , Yang Qun-ying , Shen Hong , Li Zhiyong , WB Ma 
Published: March 2020

2022 Background: In treatment of newly diagnosed GBM with the Stupp chemo-radiotherapy regimen, following by adjuvant chemotherapy, patients were treated with temozolomide (TMZ) & combined radiotherapy 4-5 weeks after surgery. In the interval between surgery and chemo-radiotherapy, it is not known whether additional TMZ treatment will improve efficacy or safety. This trial evaluated the safety and efficacy of the Stupp regimen + early post-surgery TMZ chemotherapy in the treatment of patients with newly diagnosed GBM. Methods: The trial was a multi-center, randomized open-label study. 99 newly diagnosed GBM patients were enrolled and randomly assigned to the Stupp regimen + early post-surgery TMZ chemotherapy arm (experimental group, n = 52) or to Stupp regimen alone (control group, n = 47). Fourteen days after surgery, the patients in experiment group recieved TMZ orally at 75mg/m2/day for 14 days. The primary endpoint of the study was the overall survival (OS). The secondary endpoints included the progression-free survival (PFS), objective tumor assessment and adverse events (AEs). Results: The median OS time was 17.58 months (95% CI: 15.18 – 23.03 months) in the experiment group and 13.17 months (95% CI: 11.14 – 18.76 months) in the control group (log-rank test, p = 0.021). There is no significantly difference in the median PFS between experiment group and control group (8.74 months, 95% CI: 6.41-14.85 months vs 10.38 months, 95% CI: 8.18-15.44 months, p = 0.695). No statistically significant difference was detected as regards to the objective tumor assessments. There is no significance in OS or PFS between MGMT positive and MGMT negative groups. TMZ treatment was well tolerated in the study. AE types and rates were generally similar between the two groups. There were 22 SAEs in this study, with only 1 SAE (lung infection) in Stupp regimen group was possibly drug-related. Conclusions: The addition of early post-surgery TMZ chemotherapy to the Stupp regimen for newly diagnosed GBM resulted in a statistically significant survival benefit with minimal additional toxicity. Clinical trial information: NCT00686725.
A phase I study of cediranib in combination with cilengitide in patients with recurrent glioblastoma.
Authors: Gerstner Elizabeth Robins , Levine Mike , Ye Xiaobu , Mikkelsen Tom , Nabors Louis B. , Olson Jeffrey J. , Kaley Thomas Joseph , Wen Patrick Y. , Batchelor Tracy , Grossman Stuart A. 
Published: March 2020

2054 Background: Despite high vascularity, duration of response of glioblastoma (GBM) to anti-angiogenic therapy is short. One proposed mechanism of resistance is via co-option of native brain blood vessels and tumor infiltration into normal appearing brain. We designed a Phase I study of cediranib, a VEGFR tyrosine kinase inhibitor, in combination with cilengitide, an integrin inhibitor, to block this infiltrative relapse. Methods: A phase I study was conducted through the Adult Brain Tumor Consortium in patients with recurrent GBM. Once the MTD was determined, 40 patients enrolled in a dose expansion cohort. Standard eligibility criteria were included and all patients needed to have at least 1 cm of residual disease to assess tumor response. In the dose expansion cohort, 20 patients had received prior anti-VEGF therapy and 20 had never received anti-VEGF therapy. The primary endpoint was the safety of cediranib with cilengitide. Secondary endpoints were overall survival, the proportion of patients alive and progression free at 6 months (APF6), radiographic response (RR), and exploratory analyses of advanced MRI (perfusion, permeability, diffusion imaging) and blood biomarkers. Results: Forty-five patients were enrolled with a median age of 54 (23-80) and a median KPS 80 (60-100). No DLTs were observed and the MTD was cediranib 30mg daily and cilengitide 2000 mg twice weekly. There were no unexpected Grade 3 or 4 toxicities. Thirty patients experienced disease progression, 8 patients went off study for toxicity, and 5 patients withdrew from the study. Thirty nine patients have died. Partial response was seen in 2 patients, stable disease in 13, progression in 21, and 7 patients were not evaluable for RR. Median OS was 6.4 months, median PFS was 2.4 months, and APF6 was 7.5%. Conclusions: Combination cediranib/cilengitide was well tolerated but the median PFS/OS, APF6, and RR were not very promising. Ongoing analysis of the correlative imaging and blood biomarkers may shed light on a subset of patients who might benefit from this regimen and if anti-VEGF therapy blocked the penetration of cilengitide into the tumor. Clinical trial information: NCT00979862.
Methotrexate, rituximab, and temozolomide in CNS lymphoma: The Mayo Clinic experience.
Authors: Gupta Vinay , Wolf Robert C. , Johnston Patrick B. 
Published: March 2020

2058 Background: We present a tertiary center experience with high-dose methotrexate, rituximab and temozolomide (MRT) chemotherapy in both primary and secondary CNS lymphoma. Methods: A retrospective analysis was performed for a total of 27 patients (20 male, 7 female) who underwent treatment at Mayo Clinic, Rochester between November 2010 and October 2012. The median age was 63 years (range 23-73). Of these, 12 patients were diagnosed with primary CNS lymphoma, while 15 patients had secondary CNS lymphoma. All patients received at least 1 cycle of MRT. The most common histological subtype was diffuse large cell lymphoma (23 of 27 patients). Other histological subtypes were high grade lymphoma (2 patients), Burkitt’s lymphoma (1 patient) and Mantle cell lymphoma (1 patient). Results: Of 26 patients, who underwent imaging studies for response assessment after MRT, 14 patients achieved complete response (CR), 4 patients achieved partial response (PR), 2 patients had stable disease, while 6 patients had evidence of disease progression. Overall, the median number of chemotherapy cycles with MRT was 3 (range 1-6). For patients, who achieved CR, the median number of MRT cycles was 4 (range 2-6). MRT was well tolerated. Of 27 patients, who underwent their entire treatment at Mayo Clinic, grade 3 or higher treatment related toxicity were noted to be as follows – neutropenia (9/27), thrombocytopenia (4/27), anemia (7/29), and transaminitis (10/27). 16 of 27 patients proceeded to high dose chemotherapy and autologous stem cell transplant. Out of 16 patients, 14 received BCNU/Thiotepa as conditioning regimen, while 2 patients underwent BEAM conditioning. All 16 patients who underwent transplantation remain in CR at this time. Of the remaining 11 patients, 4 are being planned for autologous transplantation, 2 received and responded to salvage chemotherapy, while 5 patients died of progressive disease. Conclusions: Overall, the MRT regimen was well tolerated. Overall response rate was noted to be 67% (18 of 27 patients) and achieved CR in 54% patients (14 of 26 patients). Patients who underwent autologous stem cell transplantation as consolidation therapy continue to do well at a median followup of 12.5 months (range 2-20 months).
Prophylactic anticonvulsants in patients (pts) with primary brain tumor (PBT): Have we really agreed to a consensus?
Authors: De Oliveira Julia Andrade , De Santana Iuri Amorim , Caires Inacelli Queiroz de Souza , Caires-Lima Rafael , Miranda Vanessa Costa , Protásio Bruno Mendonça , Rocha Lucila Soares Da Silva , Braga Henrique Faria , Mencarini Ana Cristina Malacarne , Teixeira Manoel Jacobsen , Martins Castro Luiz Henrique , Feher Olavo 
Published: March 2020

2060 Background: Routine prophylactic antiepileptic drugs (AED) use to prevent seizures in PBT seizure-naïve pts is not supported by current guidelines. However, the best management of prophylactic AED started in the perioperative setting is still unclear. Additionally, AED can have serious side effects, might have a negative impact on cognition and may present significant drug interactions. Little is known about actual current practice patterns regarding prophylactic AED in PBT. In this report we investigated prophylactic AED use in a tertiary care institution. Methods: We reviewed medical files of 260 consecutive patients, registered in our center between 2008 and 2012, focusing on prophylactic AED use. Collected data included: patient demographics, starting date, AED type, and indication. A descriptive analysis was performed with SPSS IBM version 20.0. Results: Median age was 44.5 years (11 - 83). Most pts had an ECOG PS ≤ 1 (76.4%). Overall, AED were used by 218 pts. Most common agents were: phenytoin (68.8%), carbamazepine (27.1%) and phenobarbital (16.1%). Among 141 seizure-naïve pts, 99 (70.2%) received AED as primary prophylaxis (PP). Only 14 pts (14.1%) had the drug eventually discontinued, in a median time of 5.9 months (1.1 – 76.8m). AED were used as PP in 60% of pts with low-grade gliomas, 73.3% with anaplastic gliomas and 93.9% with glioblastomas. Twenty-seven pts (27.3%) on PP presented seizures, generally associated with tumor progression. For most of them a new anticonvulsant was added for seizure control. Of the 42 seizure-naïve pts who did not receive prophylactic AED, only two presented seizures during or within the first week post-radiotherapy. Conclusions: In our study population, prophylactic AED use in PBT was extremely high (70.2% of seizure-naive pts). Postoperatively, AED were discontinued in a small minority of pts, and even so, only after a prolonged period of time. Very few seizures occurred in pts not receiving prophylactic AED. Our results suggest that practice patterns regarding prophylactic AED in PBT still contradict established guidelines.