tbuckley/cabot-search huggingface dataset:
EGFR mutation type and efficacy of afatinib in patients who previously treated with EGFR-TKI.
Authors: Kawashima Yosuke, Satoru Kitazono, Natsuki Takano, Tomoyo Oguri, Yuichi Tambo, Noriko Yanagitani, Atsushi Horiike, Fumiyoshi Ohyanagi, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2016)

e20535 Background: Recent phase III studies demonstrated that afatinib improve overall survival in NSCLC patient with common EGFR mutation as compared with 1st line chemotherapy. The different efficacy of afatinib between EGFR mutation types (E19 del and E21 L858R) were observed in the subset analysis. However, it is not unclear that the difference is consistent in patients pretreated with EGFR-TKI such as gefitinib or erlotinib Methods: Total of 59 patients were treated with afatinib after failure of gefitinib and/or erlotinib in our hospital. Efficacy of afatinib in the patients were evaluated in each EGFR mutation types. Results: Among 59 patients, 28(47.4%) were E19 del and 25 (42.4%) were E21 L858R. 41 (69.5%) patients received one prior EGFR-TKI and 18 (30.4%) patient received two or more EGFT-TKI treatment. Median Time to Treatment failure (mTTF) of afatinib was 69 days (range 2-433days) in all population. mTTF of afatinib in patients with E19 del was 54 days (95% CI 23-86). mTTF of afatinib in patients with E21 L858R was 69 days (95% CI 39-99). 31 patients were rebiopsied and samples were reanalyzed EGFR mutations before afatinib treatment. T790M mutations were detected in 13 (41.9%) patients. Median TTF of afatinib was 63 days in T790M positive group and 70 days in T790M negative group (HR = 1.05, 95%CI 0.45-2.54, p = 0.89) Conclusions: There was no significant differences in efficacy of afatinib between EGFR mutation types in patients who previously treated with EGFR-TKI.
A randomized, open label, multicenter phase 2 study to evaluate the efficacy of sorafenib in patients (pts) with advanced Renal Cell Carcinoma (RCC) after a radical resection of the metastases.
Authors: Elena Verzoni, Paolo Grassi, Rosanna Montone, Claudia Maggi, Francesco Cognetti, Michele Milella, Alessandra Bearz, Cinzia Ortega, Franco Morelli, Vincenzo Emanuele Chiuri, Andrea Necchi, Filippo G. De Braud, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2015)

TPS4581 Background: Complete response with targeted agents approved for metastatic renal cell carcinoma (mRCC) is rarely achieved. Retrospective findings seem to indicate that metastasectomy (Mtx) may improve survival in selected pts. The RESORT study was designed to evaluate whether Mtx followed by sorafenib may provide an additional clinical benefit. VEGF expression may represent a prognostic factor for survival Methods: Overall 132 mRCC pts undergoing complete Mtx will be randomized 1:1 (66 pts per arm) to receive either sorafenib or best supportive care (BSC) for 52 weeks or until disease recurrence. Prognostic factors including time from nephrectomy, site of disease and number of lesions will be used to stratify pts Key inclusion criteria: Maximum 3 metastatic lesions. Complete removal of all metastatic lesions. Microscopic examination of margins showing no tumor cells (R0 resection) No more than three months from Mtx Pts will be recruited from 16 Italian centers. The primary endpoint is recurrence-free survival (RFS), defined as the time from randomization to diagnosis of disease relapse or death. Secondary endpoints are Overall survival (OS) and safety. Circulating levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) will be evaluate from consenting pts (optional) at baseline, every 3 months, and at the end of treatment. Sorafenib will be administered at the dose of 400 mg orally once daily for 21 days and then increased to 400 mg twice daily if the patient has not experienced grade 2 skin toxicity or any other grade 3 toxicities. Imaging assessments will be performed every 12 weeks Statistical plan Kaplan-Meier methods will be used for survival analyses and the log-rank test to compare sorafenib arm and BSC arm according to the stratification factors. The hazard ratio (HR) will be determined at the 95% confidence interval (CI). The hypothesis is to increase the RFS time from 12 months (BSC arm) to 18 months (sorafenib arm), corresponding to a 50% improvement. With a study power of 80% and a 1-sided error of 0.15, the estimated number of events required is 86. Twenty-six out of 132 pts have been enrolled Clinical trial information: NCT01444807.
Lifestyle issues affecting health and well-being of BRCA mutation carriers.
Authors: Aileen Caceres, Cynthia Buffington, Olga Ivanov, Karen Wiercinski, Nicole Centers
Journal: Journal of Clinical Oncology (2016)

e21574 Background: The BRCA protein helps to prevent cancer by repair of damaged or mutated cells and by enhancing apoptosis. Obesity, sedentary activity, a poor diet, life stressors and sleep loss cause metabolic and hormonal changes that increase the risk for mutagenesis, tumor growth and progression. Therefore, a healthy lifestyle is likely to be particularly important for reduction of cancer occurrence among BRCA mutation carriers. The purpose of this study was to study the lifestyles of BRCA mutation carriers and identify conditions that could increase their risk for primary or secondary cancer. Methods: The study population included 38 BRCA mutation cancer survivors, 44 BRCA mutation previvors, and 24 controls. Diet was analyzed by 3-day food records; physical activity, anxiety, quality of life were assessed by standardized questionnaires; and body size and composition were determined by 4-lead bioelectric impedance. Results: No significant differences between BRCA previvors, survivors or the non-BRCA mutation controls were found as regards diet (calories, macronutrients, micronutrients), blood pressure, heart rate, body mass index, education, use of coffee, cigarettes or alcohol. Body weight and BMI also did not differ between groups, although the BRCA survivors, as compared to previvors and controls, had a greater % of body fat and lower lean tissue mass in association with reduced physical activity and function. BRCA carriers (previvors, survivors) exhibited significantly (p < 0.05) greater psycholological distress (high anxiety, reduced emotional quality of life) than non-BRCA controls and in association with poor sleep quality and reduced sexual activity and libido. Conclusions: BRCA mutation carriers display several lifestyle conditions that could adversely affect health and quality of life including psychological distress, reduced sexual activity and libido, poor sleep quality, and adverse body composition relative to low physical activity and function.
Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease
Authors: Joshua D. Chandler, Camilla Margaroli, Hamed Horati, Matthew B. Kilgore, Mieke Veltman, H. Ken Liu, Alexander J. Taurone, Limin Peng, Lokesh Guglani, Karan Uppal, Young-Mi Go, Harm A.W.M. Tiddens, Bob J. Scholte, Rabindra Tirouvanziam, Dean P. Jones, Hettie M. Janssens
Journal: European Respiratory Journal (2018)

Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression. CF patients aged 12–38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the Perth–Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis (PRAGMA-%Bx). Small molecules in bronchoalveolar lavage fluid (BALF) were measured with high-resolution accurate-mass metabolomics. Myeloperoxidase (MPO) was quantified by ELISA and activity assays. Increased PRAGMA-%Dis was driven by bronchiectasis and correlated with airway neutrophils. PRAGMA-%Dis correlated with 104 metabolomic features (p&lt;0.05, q&lt;0.25). The most significant annotated feature was methionine sulfoxide (MetO), a product of methionine oxidation by MPO-derived oxidants. We confirmed the identity of MetO in BALF and used reference calibration to confirm correlation with PRAGMA-%Dis (Spearman's ρ=0.582, p=0.0029), extending to bronchiectasis (PRAGMA-%Bx; ρ=0.698, p=1.5×10 −4 ), airway neutrophils (ρ=0.569, p=0.0046) and BALF MPO (ρ=0.803, p=3.9×10 −6 ). BALF MetO associates with structural lung damage, airway neutrophils and MPO in early CF. Further studies are needed to establish whether methionine oxidation directly contributes to early CF lung disease and explore potential therapeutic targets indicated by these findings.
Effect of a genomic classifier on adjuvant treatment decision-making among patients with high-risk pathology at radical prostatectomy: Results from the multicenter prospective PRO-IMPACT study.
Authors: John L. Gore, Marguerite Du Plessis, Maria Santiago-Jimenez, Kasra Yousefi, Darby J. S. Thompson, David Y. T. Chen, William R. Clark, Michael E. Franks, Lawrence Ivan Karsh, Adam S. Kibel, Hyung Lae Kim, Brian R. Lane, Yair Lotan, William Thomas Lowrance, Paul Maroni, Scott David Perrapato, Edouard John Trabulsi, Robert J. Waterhouse, Elai Davicioni, Daniel W. Lin
Journal: Journal of Clinical Oncology (2016)

5053 Background: The decision to provide adjuvant therapy to men with high risk pathology after radical prostatectomy (RP) is confounded by tremendous uncertainty. We prospectively evaluated the impact of a previously validated genomic classifier (the Decipher test, henceforth referred to as GC) which predicts metastasis risk after RP, on urologists’ decision-making for adjuvant treatment. Methods: 150 adjuvant patients were enrolled into the study by 43 urologists; 19 community and academic practices. Patients with pathologic T3 staging (pT3) or positive surgical margin (SM+) after RP were included. Physicians provided a management recommendation prior to obtaining GC and again upon receiving results. Patients completed validated surveys on decision quality and PCa-related anxiety. Results: Results were available for 141 patients. Median patient age at RP was 64 years; 66% and 51% had pT3 and SM+ pathology, respectively. The median 5-year predicted probability of metastasis by GC was 5.0% (interquartile range [IQR] 2.2%-10.7%). GC classified 48%, 20% and 32% of men as low-, intermediate- and high-risk, respectively. Pre-GC, observation was recommended for 88%; 12% received a recommendation for adjuvant radiation therapy (ART). Post-GC, 18% (95% CI 12-26%) of treatment recommendations changed, including 9% of low-risk and 31% of high-risk patients. Decisional Conflict Scale (DCS) scores decreased (indicating higher decision quality) after exposure to GC results (median DCS pre-GC 25 [IQR 10-44], median DCS post-GC 20 [IQR ], p < 0.001). GC results were associated with the decision to pursue ART in multivariable logistic regression (OR 1.47; 95% CI 1.18-1.83). Conclusions: Observation is the predominantly prescribed management strategy among PCa patients with high risk features at RP. Knowledge of GC results was associated with treatment decision-making among these patients: patients at low risk for metastasis had higher rates of observation recommendations and patients at high risk had higher rates of ART recommendations. Decision quality was improved for patients exposed to GC results. Clinical trial information: NCT02080689.
TCT-258 Comparing Outcomes of Local and General Anesthesia in TranscathEter Aortic Valve Replacement (COLGATE-AVR): the Cleveland Clinic Foundation Experience
Authors: Jimmy Kerrigan, Krystof Andress, Neha Gupta, Kinjal Banerjee, Jayendrakumar Patel, Matthew Summers, Terence Hill, Zoran Popovic, L. Leonardo Rodriguez, William Stewart, Stephanie Mick, Amar Krishnaswamy, E. Murat Tuzcu, Andrej Alfirevic, Lars Svensson, Shiva Sale, Anand Mehta, Samir Kapadia
Journal: Journal of the American College of Cardiology (2018)
TCT-230 FFR-Guided Angioplasty Using Paclitaxel-Coated Balloons Without Stents vs. Bioresorbable Scaffolds: a Randomized Clinical Trial in Stable Coronary Artery Disease
Authors: Sylvia Otto, Kerstin Heitkamp, Marcus Franz, P. Christian Schulze, Tudor Poerner
Journal: Journal of the American College of Cardiology (2018)
Cancer patients with undiagnosed and poorly managed diabetes mellitus.
Authors: Sooha Kim, Anukul Garg, Fharat Raja
Journal: Journal of Clinical Oncology (2017)

e18232 Background: Cancer patients are at increased risk of developing diabetes mellitus (DM) or having worsening control of their pre-existent DM. The causes of this are multifactorial but the use of steroids, either in the palliative setting or short-term whilst on chemotherapy, is a significant contributor. An audit carried out at a district general hospital demonstrated that 5% of all oncology admissions were secondary to DM complications. A study was conducted to evaluate the prevalence of impaired blood glucose (BG) control and to assess the value of routine HbA1c testing in this population. Methods: Patients having routine chemotherapy blood tests were also tested for HbA1c over a 10 day period in December 2016. HbA1c diagnostic criteria was used as per NICE guidelines. Information on previous diabetic status, primary tumour type, chemotherapy status (number of cycles and treatment intent) was recorded. Results: 134 patients were tested for HbA1c; 28 (21%) had a HbA1c diagnostic of DM and 32 (24%) were at high risk of DM. The mean HbA1c of those in the DM group was 67.3 mmol/mol (range 48-120). Of the 28 with a HbA1C diagnostic of DM, 13 (46%) were already known to have DM with 15 (54%) being newly diagnosed from this study. 11 (73%) of those with a new diagnosis of DM were receiving a short course of steroids with chemotherapy. 12 patients in the DM group were having chemotherapy with curative intent; 6 of whom were newly diagnosed. Conclusions: 11% of the study cohort met criteria for a new diagnosis of DM with 73% of this group receiving steroids. NICE advises on monitoring of BG for all diabetics receiving steroids. Monitoring of BG and using anti-diabetic medications could prevent DM related complications. This highlights the need to involve local diabetic services and primary care providers for diabetic management. 43% of patients in DM group were receiving chemotherapy with curative intent. This has large implications on cancer survivorship and it is vital that these patients receive appropriate DM treatment. This will not only improve quality of care and patient satisfaction but also lead to significant cost savings from reduced admissions and length of stay in hospital. We therefore recommend a routine HbA1c test for all cancer patients having chemotherapy.
The impact of published guidelines on chemotherapy dosing in overweight and obese patients in the adjuvant setting: A single institution experience.
Authors: Hassan Issa, Suman Paul, Brian Fink
Journal: Journal of Clinical Oncology (2016)

e18201 Background: In April 2012, the American Society of Clinical Oncology (ASCO) published the first guidelines for dosing chemotherapy in obese patients. The guidelines recommend full weight-based cytotoxic chemotherapy doses to be used most of the time to treat overweight and obese patients, particularly when the goal of treatment is cure. These guidelines were discussed during a journal club meeting as part of the educational activities of the University of Toledo medical oncology fellowship at the time of its publication, therefore as part of a quality improvement initiative, we compared our practice before and after the publication of these guidelines. Methods: We retrospectively reviewed our practice in administering chemotherapy in the adjuvant setting in patients with body mass index (BMI) 25-35 at the University of Toledo Cancer Center between December 2009, and December 2014. We included patients with the following cancers: colorectal, lung, breast, and ovarian. We excluded patients who were older than 70 years, had poor performance status with the Eastern Cooperative Oncology Group (ECOG) score > 2, or had renal failure or liver dysfunction that would limit the clinician’s ability to give full dose chemotherapy. Results: The total number of patients included in the study was 89, of which 46 finished their treatment before the publication of the guidelines, and 43 after. Chemotherapy was dosed based on actual body weight at a significantly higher rate after the publication of the guidelines in the overweight: BMI 25-30 (72.50% vs 93.75% p 0.021) and obese patients: BMI > = 30 (34.62% vs 75% p 0.01). There was no significant compromise in the ability to complete the planned number of chemotherapy cycles in patients whose chemotherapy was given based on their actual body weight. Conclusions: ASCO evidence-based guidelines have had a positive impact on our practice in dosing chemotherapy in overweight and obese patients. This study illustrates a successful example of using guidelines as an educational tool in an attempt to alter physician’s behavior within the environment of a medical oncology fellowship program.
SHIVA: Randomized phase II trial comparing molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer—Overall survival (OS) analysis.
Authors: Sylvain Dureau, Francesco Ricci, Marie Alt, Delphine Loirat, Marie-Paule Sablin, Maud Kamal, Ivan Bieche, Sebastien Armanet, Jean-Pierre Delord, Anthony Goncalves, Celine Gavoille, Coraline Dubot, Nicolas Isambert, Mario Campone, Olivier Tredan, Miguelle Marous, Aurelien Latouche, Lisa Belin, Christophe Le Tourneau
Journal: Journal of Clinical Oncology (2017)

11515 Background: The SHIVA trial is a multicentric randomized phase II trial comparing molecularly targeted therapy among 11 drugs based on tumor molecular profiling versus conventional therapy in patients with any type of cancer that is refractory to standard of care (NCT01771458). Only patients who had a druggable molecular alteration (DMA) identified on a mandatory tumor sample from a metastatic site using targeted sequencing, CGH and IHC were randomized. Cross-over was allowed at disease progression. The trial did not show any difference for its primary endpoint (PFS) [Le Tourneau et al., Lancet Oncol 2015]. We report here the OS of randomized and non-randomized patients. Methods: OS was estimated in the 4 following groups: 1) randomized patients, 2) patients for whom a DMA was identified but who were not subsequently randomized because they did not meet the randomization criteria (PS of 0 or 1, adequate organ function), 3) non-randomized patients because of the absence of DMA, and 4) non-randomized patients because no genomic analyses were performed. Since 70% of patients randomized into the standard arm eventually crossed over to the targeted therapy arm, all randomized patients were analyzed in group 1. The groups were compared in terms of patient characteristics using student and χ2 tests. OS was estimated using the Kaplan Meier method. Results: Among 741 patients included in SHIVA, 8 patients were included twice. Follow-up data were available for 680 out of the 733 patients. 197, 78, 222 and 183 patients belonged to groups 1 to 4, respectively. Median OS of the whole cohort was 7.9 months [95% CI: 7.0–9.1].As compared to non-randomized patients due to the absence of identified DMA, non-randomized patients with a DMA had a significantly worse prognosis: HR = 2.3 [95% CI: 1.7–3.0] (p &gt; 0.0001) whereas randomized patients had a non-significant trend toward a better prognosis: HR = 0.85 [95% CI: 0.7–1.1] (p = 0.18). Conclusions: A statistically significant difference in OS was only observed in patients with a DMA who were not randomized. However, our analysis does not allow showing an intrinsic prognostic value of the DMA on OS.
Tumor associated macrophages to predict the efficacy of bevacizumab plus chemotherapy in patients with advanced colorectal cancer.
Authors: Hakan Akbulut, Fatma Sena Dost Gunay, Bilge Ayca Kirmizi, Elif Berna Koksoy, Arzu Ensari, Fikri Icli
Journal: Journal of Clinical Oncology (2017)

e15103 Background: The tumor-associated macrophage (TAM) is one of the major components of tumor microenvironment. Neuroendocrine differentiation (NED) of the tumor has been linked to poor prognosis. We aimed to investigate the role of TAM infiltration and NED in tumor tissue on the efficacy of bevacizumab plus chemotherapy in patients with advanced colorectal cancer. Methods: A total of 123 consecutive patients with advanced colorectal cancer treated with bevacizumab plus either irinotecan or oxaliplatin-based combination chemotherapy were included in the study. Along with clinicopathological parameters including age, tumor location (right versus left colon), pretreatment CEA level, KRAS mutation status, tumor grade, histologic subtype (mucinous vs non-mucinous), the presence of NED and the level of TAM infiltration were studied as covariates for survival analysis. The patients with at least 2% or more staining with either synaptophysin or chromogranin A were regarded as NED positive. The +2 or less staining with anti-CD68 was regarded as low for TAM infiltration and +3 or +4 staining as high. The overall (OS) and progression-free survival (PFS) times were calculated from the start of bevacizumab. Results: Thirty-five percent of the patients were given bevacizumab in the first line setting, the others mainly at the second line. The chemo backbone was FOLFIRI in 75% of the patients. The median OS was 15,1 and PFS 7,1 months. The ratio of NED negative and TAM infiltration low patients were 73,9% and 13,8 %, respectively. The univariate analysis yielded only the NED and higher TAM infiltration as the significant factors for PFS. However, only NED was significant for PFS in the multivariate analysis (HR:0.542). The left-sided tumors and the low levels of TAM infiltration were the favorable factors for OS in the univariate analysis. However, the TAM level was the only independent factor predicting the OS (26,7±8,8 vs 14,1±1,7 months, respectively; HR: 0,301). Conclusions: Our results suggest that the TAM infiltration in the tumor tissue could be used as a predictive marker of efficacy of bevacizumab plus combination chemotherapy in patients with advanced colorectal cancer.