tbuckley/cabot-search huggingface dataset:
Resection margins after radical cystectomy at academic versus community cancer centers.
Authors: Kyle Scarberry, Kelly Scarberry, Shree Agrawal, Simon P. Kim
Journal: Journal of Clinical Oncology (2017)

315 Background: Positive surgical margins are reported in 1-5% of specimens following radical cystectomy (RC) for urothelial carcinoma of the bladder (UC). Negative margin (R0) resection correlates with improved overall survival (OS) following RC in individual institutional analyses compared to microscopic (R1) or grossly (R2) positive margins. The present study hypothesized that RC surgical resection margins vary between treating centers. Methods: Patients with UC undergoing RC were identified from the National Cancer Database (2004-2013). Treating centers were categorized as Academic Cancer Centers (ACC) and Community Cancer Centers (CCC). Rates of R0 vs. R1/2 resection were examined and logistic regression was performed to determine predictive factors for margin status. Results: A total of 40,187 patients were identified with a median age of presentation of 68 years. RC was performed equally at ACC (52%) compared to CCC (48%). Neoadjuvant chemotherapy was utilized more often at ACC (21%) compared to CCC (14%). RC at ACC was associated with higher rates of R0 resections (90%) compared to CCC (88%) (p &lt; 0.001). On logistic regression, after adjusting for age, sex, ethnicity, comorbidities, disease stage, tumor grade, tumor size, and use of neoadjuvant chemotherapy, RC at ACC were associated with decreased risk of experiencing positive margins (OR = 0.79, 95% CI 0.74-0.85). Following multivariate regression, RC performed at ACC were associated with a significant hazard ratio (HR) for survival (HR = 0.88, 95% CI 0.85-0.91). Compared to all variables, R1/2 resection status was the next most significant predictor for poor survival in RC patients (HR = 1.83, 95% CI 1.75-1.91) after cancer stage. Conclusions: Surgical margin is an important, independent risk factor for mortality in patients undergoing RC for UC. RC at ACCs is associated with a higher rate of negative resection margins, suggesting that site of care may impact bladder cancer patient’s oncologic outcomes.
POWER: An open-label, randomized phase III trial of cisplatin and 5-FU with or without panitumumab (P) for patients (pts) with nonresectable, advanced, or metastatic esophageal squamous cell cancer (ESCC).
Authors: Markus Hermann Moehler, Ingo Ringshausen, Ralf Hofheinz, Salah-Eddin Al-Batran, Lothar Mueller, Peter C. Thuss-Patience, Kersten Borchert, Aysun Karatas, Ralph Keller, Anja Klein, Anne Kranich, Baruch Brenner, Sylvie Lorenzen, Manfred P. Lutz, Richard Greil, Josep Tabernero, Eric Van Cutsem, Ullrich Graeven
Journal: Journal of Clinical Oncology (2013)

TPS4158 Background: More than 50% of pts with esophageal cancer have locally advanced or metastatic disease at the time of initial diagnosis. For this group chemotherapy is increasingly used intending local and distant tumor control, improvement of quality of life (QoL) and longer survival. Previous data suggested that EGFR-targeting antibodies may be safely combined with cisplatin and 5-FU, and in addition may increase the efficacy of the standard cisplatin/5-FU regimen [Lorenzen et al, Ann Oncol2009; 20(10): 1667-1673]. Methods: In this open-label, randomized (1:1), multicenter, multinational phase III trial pts with nonresectable, advanced or metastatic ESCC, not eligible for definitive radiochemotherapy, are included. Pts have measurable or non-measurable disease according to RECIST 1.1 and an ECOG PS 0-1. Previous chemotherapy of ESCC in the metastatic setting, concurrent radiotherapy involving target lesions and previous exposure to EGFR-targeted therapy are excluded. Pts receive either CTX (cisplatin 100 mg/m² on day 1 and 5-FU 1000 mg/m²/d on day 1-4) or CTX + P (9 mg/kg on day 1). Cycles are repeated every 3 weeks until progression of disease. Tumor assessment is performed every 9 weeks. The primary objective is to demonstrate superiority of CTX + P over CTX alone in terms of overall survival. Secondary endpoints are progression-free survival, 1-year survival, response rate, safety and tolerability, and QoL. A translational analysis in tumor tissue and serum samples is included. 300 pts are planned to be enrolled for a power of 90% to reject the null hypothesis in which the median overall survival in the control and experimental groups are 6 and 9 months, respectively. 18 pts have been enrolled to date. A Data Monitoring Board will review safety data after 40, 100 and 200 pts. The clinical trial registry number is NCT1627379. Clinical trial information: NCT01627379.
Treatment strategy for colorectal liver metastases: Clinical impact of FOLFOXIRI regimen for unresectable cases.
Authors: Yuji Morine, Mitsuo Shimada, Satoru Imura, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saito, Daichi Ishikawa, Hiroki Teraoku, Masato Yoshikawa, Jun Higashijima
Journal: Journal of Clinical Oncology (2017)

780 Background: Recent advances in systemic chemotherapy, including molecular target agents, can introduce “Conversion surgery” and achieve R0 resection even for initially unresectable colorectal liver metastasis (CRLM). We investigated the optimal indication for initial surgical induction and treatment strategy for unresectable CRLM. Methods: Our current surgical indication for CRLM as follows: i) curative resection is achievable, ii) no limitation of tumor size and number, and iii) future remnant liver volume over 35%. Additionally, same indication is applied even after chemotherapy.Two hundreds forty-one cases from 1994 to 2015, consisted of 134 initially resectable case and 107 unresectable cases, were included. Among 107 unresectable cases, 55 cases received current chemotherapy such as FOLFOX, FOLFILI, XEROX and FOLFOXIRI. Results: 1) Optimal indication for initially resectable case:Multivariate analysis revealed MDN (Maximum Diameter × Number) index more than 30 of metastatic liver tumor (HR3.06), non-curative resection of metastatic liver tumor (HR4.082) and poor differentiation of primary tumor (HR11.14).2) Treatment strategy of unresectable case for “Conversion surgery” (FOLFOXIRI vs. other regimen): Forty-two unresectable cases with MDN &gt; 30 were included. Of those 14 cases, FOLFOXIRI regimen was applied. Regarding clinicopathological factors, the use of molecular targeted drug was introduced in all patients of FOLFOXIRI group, but 67.9% patients of other regimen group. The “Conversion” rate in FOLFIXIRI group and other regimen group were 64.3% and 39.3% (p = 0.126), and median period until “Conversion” were 6.2 courses and 11.8 courses (p = 0.038). Regarding tumor necrotic rate, FOLFOXIRI regimen induced higher necrotic rate than other regimen group (77.9% vs. 50.4%, p = 0.073). Overall survival in FOLFOXIRI group has been better than that in other regimen group and 3-years survival rates were 83.3% and 48.0% (p = 0.044). Also, relapse free survival in FOLFOXIRI group was significantly better than that in other regimen group (p = 0.002). Conclusions: MDN can predict surgical outcome for CRLM. FOLFOXIRI plus molecular target drug may be a promising option for CRLM with MDN &gt; 30.
Impact of the EndoPredict-clin score on risk stratification in ER-positive, HER2-negative breast cancer after considering clinical guidelines.
Authors: Martin Filipits, Peter Christian Dubsky, Margaretha Rudas, Jan C. Brase, Ralf Kronenwett, Karsten E. Weber, Christoph Petry, Marcus Schmidt, Irmard Luisser, Evelyn Klug, Michael Gnant
Journal: Journal of Clinical Oncology (2012)

542 Background: Many ER-positive, HER2-negative breast cancer patients are treated by adjuvant chemotherapy according to current clinical guidelines. We retrospectively assessed whether the combined gene expression/ clinicopathological EndoPredict-clin (EPclin) score improved the accuracy of risk classification in addition to considering clinical guidelines. Methods: Three clinical breast cancer guidelines (National Comprehensive Cancer Center Network (NCCN), German S3 and St. Gallen 2011), and the EPclin score - assessed by quantitative RT-PCR in formalin-fixed paraffin-embedded tissue - were used to assign risk groups in 1,702 ER-positive, HER2-negative breast cancer patients from two randomized phase III trials (Austrian Breast and Colorectal Cancer Study Group 6 and 8) treated with endocrine therapy only. Results: Although all analyzed clinical guidelines identified a low-risk group with improved metastasis-free survival, the overwhelming majority of all patients (81-94%) were classified as intermediate / high risk. In contrast to that, the EPclin classified only 37% of all patients as high risk and that stratification resulted in the best separation between low and high risk groups (p &lt; 0.001, HR = 5.11 (3.48-7.51). Consequently, the majority of all patients deemed intermediate / high risk by the clinical guidelines was re-classified as low risk by the EPclin score. Kaplan Meier analyses demonstrated that the re-classified subgroups (47 to 57% of all patients) had an excellent 10-year metastasis-free survival of 95% comparable to the clinical assigned low-risk groups although encompassing a higher proportion of the trial patients. Conclusions: The EPclin score predicted distant recurrence more accurately than all three clinical guidelines and is especially useful to reclassify patients considered as intermediate / high risk by the guidelines. The data suggests that the EPclin score provides clinically useful prognostic information beyond common clinical guidelines and can be used to accurately identify the clinically relevant group of patients who are adequately and sufficiently treated with adjuvant endocrine therapy alone.
Inherited pathologic mutations and family history in patients with prostate cancer.
Authors: Shuwen Lin, Elisa M. Ledet, Joshua Schiff, Emma M. Ernst, Cathryn E. Garvey, Brian E. Lewis, Oliver Sartor
Journal: Journal of Clinical Oncology (2017)

185 Background: In prostate cancer (PCa), germline pathogenic variants have previously been underestimated. PCa patients (pts) with DNA repair defects have a higher percentage of non-PCa family history (FH) with the most common cancers being derived from the breast, GI tract, ovary, pancreas, lymphoma/leukemia. The goal of this study was to evaluate and characterize pathogenic variants detected in PCa patients undergoing both enhanced FH screening and genetic testing. Methods: In this single-institution study, 535 PCa pts from Tulane Cancer Center over the last year underwent enhanced FH screening, and FH of PCa and other cancers were collected. 124 PCa pts including those with both localized and metastatic disease were identified to have a FH that met NCCN guidelines for genetic testing. Genetic testing was done using a commercially available panel (Invitae, San Francisco, CA) of 25-79 cancer-related genes for mutations and selected exonic deletions/duplications. Results: Of the 124 tested pts, 21 pts (16.9%) had ≥ 1 germline pathogenic variant (PV) and 47 pts (37.9%) had ≥ 1 germline variant of unknown significance (VUS). PVs included: BRCA2 (n = 4), BRCA1 (n = 3), CHEK2 (n = 3), MUTYH (n = 3), ATM (n = 2), TP53 (n = 2), MITF (n = 1), NBN (n = 1), PMS2 (n = 1), and (RAD51D (n = 1). Of the 124 tested pts, 68 pts (54.8%) had PCa FH, 68 (54.8%) had breast cancer FH, 22 (17.7%) had pancreatic cancer FH, 16 (12.9%) had ovarian cancer FH, and 37 (29.8%) had both breast and PCa FH. Between the pt groups (those with PVs, VUSs and negative results), there were no differences in FH rates of PCa, breast, pancreatic, or ovarian cancer. There was no significant difference in the age at diagnosis (dx) between the groups or between pts with PCa FH and those without. The median ages at dx were 65 for PV pts, 60 for VUS pts, and 59 for negative result pts. There were no statistically significant differences in initial Gleason score or metastatic disease status in these three groups (p = 0.35 and p = 0.66). Conclusions: In this dataset, FH cannot discriminate between those with and without inherited PV using a broad panel of genes that include those that alter DNA repair. The implications of these findings are broad. [Table: see text]
Development of algorithms for a quantitative real time-PCR assay to determine EGFRvIII status in glioblastoma patients from rindopepimut clinical trials.
Authors: Jim Yan, Donald James Witt, Don Kafader, Alan Wookey, Steve Anderson, Li Cai, Marcia Eisenberg, Abdel Halim
Journal: Journal of Clinical Oncology (2015)

e14004 Background: The Epidermal growth factor receptor variant III (EGFRvIII) is a commonly expressed biomarker in glioblastoma and a target for anti-EGFRvIII therapeutic. Determination of EGFRvIII status is important for identifying patients for the treatment, as patients with the mutation are more likely to respond to the treatment. A qRT-PCR assay was developed and validated for comparison of the expression of EGFR wildtype and vIII mutant forms. However, an algorithm is needed to determine the mutation status using the Ct and delta Ct. The goal was to develop and evaluate algorithms for determining the EGFRvIII status using this assay. Methods: Results of the qRT-PCR assays of ~4,900 clinical specimens from Rindopepimut clinical trials were used to develop the algorithms. From the test results, 1763 samples were used as training set, with a subset of samples verified by bi-directional Sanger sequencing and used as test set in predictive modeling. Nine predictive models including Support Vector Machine (SVM), Partition Tree as well as an existing cut-off were tested to evaluate the prediction performance. Results: Among the nine models, the SVM and Partition Tree algorithms, demonstrated best performance with overall accuracy of 99.7% (99.93% for the positive and 98.64% for the negative) and 99.2% (99.87% for the positive and 95.93% for the negative) respectively. The Partition Tree model produced a delta CT cut-off of 10.98 that is close to the previously established cut-off of 11, and confirmed this cut-off is sound for patient sample evaluations. In combination with this cut-off, the partition tree and the SVM algorithms allow the leverage of the Ct values in addition to the delta Ct to increase the consistence and accuracy. Conclusions: A Partition Tree algorithm and a SVM model were developed and tested. Either one of the two algorithms can be added to the existing cut-off to ensure the consistency and accurate assessment of EGFRvIII in Glioblastoma, and may aid in the development of strategies for stratifying Glioblastoma patients for EGFRvIII-directed therapies. Clinical trial information: NCT00458601, NCT01480479.
The protective effect of hormonal intake on risk of hepatocellular carcinoma in the United States.
Authors: Gehan Botrus, Ahmed S Shalaby, Ahmed Omar Kaseb, Renato Lenzi, Reham Abdel-Wahab, Robert A. Wolff, Manal Hassan
Journal: Journal of Clinical Oncology (2015)

4019 Background: In the United States, the incidence of hepatocellular carcinoma (HCC) has been tripled over the last two decades. Despite the overwhelming effect of several environmental risk factors of this cancer, the association between oral contraceptive (OC) and hormone replacement therapy with HCC has been poorly investigated. The current study aimed at addressing such association among American women. Methods: Under the IRB approval from the University of Texas MD Anderson Cancer Center, we conducted hospital-based case-control study where cases are pathological or radiological diagnosed patients with HCC. Controls are spouses of patients at MD Anderson who had cancers other than GI cancers. Between 2005 and 2014 total of 235 female cases and 257 female controls were enrolled. Cases and controls were interviewed for lifetime intake of OC, hormonal replacement, type of hormone, method of hormonal use, and duration of exposure. We performed multivariate logistic regression analyses by using all variables that were significant at P < .05 in the univariate analyses to estimate odds ratio (OR) and 95% confidence interval (CI). The estimated ORs were adjusted for age, race, diabetes, hepatitis C virus, hepatitis B virus, cigarette smoking, alcohol drinking, and family history of cancer. Results: Ever use of OC was reported by 75.1% of the controls and 61.3% of the cases (P= .001) leading to 43% reduction in HCC risk where the estimated OR (95% CI) was 0.57 (.35-.91). Ever intake of estrogen hormone during lifetime was recalled by 49.8% controls and 30.6% cases (P =.001) yielding 62% reduction in HCC risk, OR (95% CI) = .38 (.24-.59). Combined hormonal use from OC and estrogen hormonal replacement was reported by 89% of the controls and 75% of cases. The estimated OR (95% CI) was .47 (.27-.84), P= .01. A dose response relationship was observed with duration of exposure where the estimated OR (95% CI) were .53 (.28-1), .37 (.16-.83), and .35 (.19-.64) for lifetime years of exposure of < 5, 5-10, and > 10 years respectively. Conclusions: This is the largest study in USA showing protective effect of hormonal use on HCC. Experimental investigations are necessary for thorough assessment of the relationship between hormonal exposure and risk of HCC in females.
Emerging findings in the Cancer Research UK stratified medicine program.
Authors: Emily Shaw, Alice Tuff, Rowena Sharpe, Louise K. Jones, Tarita Turtiaien, Michael Griffiths, Rachel Butler, David Gonzalez de Castro, Malcolm David Mason, V. Peter Collins, Frances Rae, T.R. Jeffry Evans, Stephen R. D. Johnston, Jane Rogan, Andrew Hanby, James Peach, Peter W. M. Johnson
Journal: Journal of Clinical Oncology (2012)

TPS10633^ Background: Molecular analysis of tumours may be used to identify those predicted to benefit from novel targeted therapies. The Cancer Research UK programme is piloting plans to apply such testing broadly across the UK healthcare system, linking molecular phenotype to clinical outcomes. Methods: The Stratified Medicine Programme (SMP) aims to develop a model for high quality, large-scale molecular characterization of cancer specimens through an initiative developed in partnership with AstraZeneca, Pfizer, the UK Department of Health and academic researchers. Phase One of the SMP is a two year feasibility study. It aims to demonstrate the submission of consented blood samples and sections of surplus diagnostic formalin-fixed paraffin-embedded tumour tissue from 9,000 patients at centres across the UK to one of three ‘technology hubs’ for mutation testing of genes of potential clinical interest (KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT) in six selected tumour types. The tests are technically validated and will be completed in clinically relevant timescales. Data including pathological and treatment information and clinical outcome is also collected for the recruited patients, linked to the genetic data and stored in a central data repository hosted within the National Cancer Registration Service. The study opened in September 2011 at 7 sites across the UK and by the end of 2011, 760 patientswith breast, lung, prostate, colorectal, ovarian cancer or metastatic malignant melanoma had consented to participate. 142 sets of molecular results had been returned to clinical teams. Updated figures will be presented at the meeting, by which time the programme is projected to have accrued 4000 subjects. By 2013, we hope to have developed a scalable model for routine, high quality, prospective molecular characterisation of tumours for NHS cancer patients, with consent for the collection, storage and research use of population-scale genetic and clinical outcome data. We will report the emerging results from the Stratified Medicines Programme and early insights into implications for wider implementation across the UK healthcare system.
Clinical features of patients with Zika and dengue virus co-infection in Singapore
Authors: Po Ying Chia, Haur Sen Yew, Hanley Ho, Angela Chow, Sapna P. Sadarangani, Monica Chan, Yiu Wing Kam, Chia Yin Chong, Koh Cheng Thoon, Chee Fu Yung, Jia Hui Li, David C. Lye, Partha Pratim De, Lisa F.P. Ng, Tsin Wen Yeo, Yee Sin Leo
Journal: Journal of Infection (2017)
Serum 25-hydroxyvitamin D levels correlation with EGFR mutational status in pulmonary adenocarcinoma.
Authors: Dong-Yeop Shin, Soyeun Kim, Sunhoo Park, Jae Soo Koh, Cheol Hyeon Kim, HeeJong Baek, Sung Hyun Yang, Im Il Na
Journal: Journal of Clinical Oncology (2014)

e19100 Background: To explore the potential association between serum 25-hydroxyvitamin D [25(OH)D] levels and mutations in epidermal growth factor receptor (EGFR) in patients with pulmonary adenocarcinoma. Methods: We analyzed clinical data from 135 patients whose serum 25(OH)D levels were measured and EGFR mutational status was tested at the time of diagnosis. The relationship between 25(OH)D and clinical factors such as EGFR mutational status and sex was examined. Results: The median serum 25(OH)D level in patients with pulmonary adenocarcinoma was 16.8 ng/ml (range: 3.0 – 84.3 ng/ml). 25(OH)D level was lower in female patients than male patients (p = 0.03). Of interest, 25(OH)D level of patients with EGFR mutated tumors was low compared with those with wild type (median 18.2 ng/ml vs. 14.7 ng/ml, p = 0.011). After a dose response relationship between EGFR mutations and 25(OH)D levels (as a continuous variable) was observed (OR = 0.96, p = 0.036), we categorized 25(OH)D levels into low (≤ 16.8ng/ml) vs. high (>16.8ng/ml). Multivariate analysis revealed the association between low 25(OH)D levels and high incidence of EGFR mutations (adjusted OR = 2.42, 95% CI: 1.11-5.26, p= 0.026). Conclusions: This study suggests that low 25(OH)D levels are associated with EGFR mutations in pulmonary adenocarcinoma. EGFR mutation and its association with clinical factors including 25(OH)D level. Univariate Multivariate OR (95% CI) p value OR (95% CI) p value Sex (female) 5.25 (2.51-11.00) <0.001 2.66 (1.02-6.94) 0.046 Smoking 0.18 (0.086-0.39) <0.001 0.40 (0.15-1.05) 0.062 Stage (metastasis) 0.75 (0.38-1.49) 0.41 25(OH)D (≤16.8ng/ml) 3.16 (1.55-6.43) 0.002 2.42 (1.11-5.26) 0.026