tbuckley/cabot-search huggingface dataset:
Real-life 2-year therapeutic strategies in the management of 525 small-cell lung cancers (SCLCs) in French general hospitals.
Authors: Didier Debieuvre, Francois Goupil, Philippe Brun, Adrien Diximier, Geoffroy De Faverges, Cecilia Nocent-Ejnaini, Jacky Crequit, Vuillermoz Blas Sylvie, Christophe Perrin, Olivier Leleu, Michel Carbonnelle, Bernard Asselain, Francois Blanchon, Francis Martin, Michel Grivaux
Journal: Journal of Clinical Oncology (2015)

e18552 Background: In the last few years, new drugs and strategies have emerged in the management of lung cancer (LC). ESCAP-2011-CPHG, promoted by the French College of General Hospital Respiratory Physicians, described therapeutic strategies in LC in the first 2-year after diagnosis. ESCAP-2011-CPHG is an ancillary study of KBP-2010-CPHG, a prospective multicenter epidemiological study aiming to describe the characteristics and survival of patients with LC diagnosed in 2010 and managed in French general hospital chest departments. Methods: For each patient, a standardized form was completed following each change in treatment strategy up to 2 years after diagnosis. Results: 53 of the 104 centers (7051 patients) participating in KBP-2010-CPHG agreed to participate in ESCAP-2011-CPHG, which corresponded to 3943 patients, including 525 patients with SCLC. In SCLC patients, mean follow-up was 10.5 months (SD: 8.8) and median number of strategies, 2 (IQR: 1-3). Strategy 1 (chemotherapy, 75%; radiochemotherapy, 15%; radiotherapy, 10%; exclusive support care, 8%; curative surgery, 2%) lasted 5.4 months (SD: 4.5). 195 (37%) patients died during strategy 1, and 309 (59%) had a 2nd strategy. Strategy 2 (chemotherapy, 55%; radiotherapy, 47%; exclusive support care, 14%; curative surgery, 6%), lasted 3.6 months (SD: 3.5). 134 (43%) patients died during strategy 2, and 153 (50%) had a 3rd strategy. Strategy 3 (chemotherapy, 61%; exclusive support care, 27%; radiotherapy, 17%) lasted 2.7 months (SD: 2.4). 90 (59%) patients died during strategy 3, and 54 (35%) had a 4thstrategy. For strategy 1, cisplatin (46%) and carboplatin (42%) were the most frequent drugs associated with etoposide. For strategy 2, the most frequently prescribed drugs were topotecan (22%), etoposide (21%), or carboplatin (20%). Few patients received targeted therapy ( < 1% in strategies 1 and 2). Conclusions: These findings are preliminary and need to be further analyzed per type of patient, cancer stage, or therapeutic strategy. Analyses of combinations of strategies or chemotherapies are also planned.
Upper genitourinary tract transitional cell carcinoma (TCC): Long-term outcome data from a large single institutional series
Authors: R. Roy, N. Radhakrishnan, M. Kaufman, A. Thomas, G. Weiss, U. Iqbal, B. Mehrotra
Journal: Journal of Clinical Oncology (2007)

15582 Background: TCC of the upper urinary tract (renal pelvis and ureters) is a relatively rare entity and carries a poor prognosis. Literature regarding long term outcomes are lacking. We embarked on a review of pt records to evaluate patterns of practice: ie adjuvant therapies and survival outcomes of pts treated at our tertiary care institution. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry data were analysed for all adult pts with TCC of the renal pelvis and ureter diagnosed from 1995 to 2005. Only patients with locoregionally confined disease were included in this study. Pt characteristics recorded: age, sex, site of disease, stage, grade, treatment modalities and survival outcome. Results: 175 patients were identified. Med. age: 75 yrs (range 40–90). Gender: M:F:107:68; Sites: Renal Pelvis: n=128; Ureters: n=47; Stages: Stg 0: n=46 (26.28%), Stg I: n=68 (38.85%), Stg II: n=19 (10.85%), Stg III: n=29 (16.57%), Stg IV (excl. M1):n=13 (7.4%). Gr 1: n=13 (7%), Gr 2: n=49 (28%), Gr 3: n=78 (45%), Gr 4: n=20 (11%); Unknown n=14 (8%). Gr 3/4 distribution for Stages 0, I, II, III, and IV were 17 (37%), 32 (47%), 15 (72%), 23 (79%) and 11 (84%) respectively. Treatment Modalities: All pts were treated with surgical resection; adjuvant chemotherapy was utilized in Stg I: 5/68; Stg II: 3/19; Stg III: 5/29; Stg IV: 1/13 pts. Adjuvant RT was administered in Stg III: 1/29; Stg IV: 3/13 pts. Med. survival and OS at 1, 2, 5 and 10 yrs are shown in Table 1 for all pts treated with surgical resection alone as standard therapy. Med. Survival of all patients who received any adjuvant therapy was 24 mos. Conclusions: Increasing frequency of higher grade disease was present in higher stage patients. Long term survival of early stage disease despite surgical resection is poor with 5 year OS of 45–62% in Stages 0-II and worse with higher stages III and IV with 5 yr OS of 17- 21%. Clearly, better adjuvant or neo-adjuvant strategies are needed to improve this dismal prognosis. [Table: see text] No significant financial relationships to disclose.
LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes
Authors: Qianxia Zhang, Maria Chikina, Andrea L. Szymczak-Workman, William Horne, Jay K. Kolls, Kate M. Vignali, Daniel Normolle, Maria Bettini, Creg J. Workman, Dario A. A. Vignali
Journal: Science Immunology (2017)

Regulatory T cell–specific deletion of LAG3 in nonobese diabetic mice reduces the incidence of autoimmune diabetes.
BRCA1 like copy number profiles to predict benefit of intensified alkylating chemotherapy in breast cancer.
Authors: Philip C. Schouten, Sabine C. Linn, Sebastian Aulmann, Hans-Peter Sinn, Andreas Schneeweiss, Frederik Marme
Journal: Journal of Clinical Oncology (2013)

11023 Background: DNA copy number profiles can identify patients with a defect in BRCA1. We previously showed that patients with a BRCA1-like profile benefit from intensified alkylating chemotherapy (IA, 4 cycles 5-fluorouracyl, epirubicin, cyclophosphamide + 1 cycle carboplatin, thiotepa and cyclophosphamide with autologous stem cell transplantation (ASCT)). Presumably, this is because of the defect in error free homologous recombination DNA repair. Here we present an independent study of BRCA1-like profiles to predict benefit of IA chemotherapy (2 cycles induction chemotherapy consisting of 2500 mg/m2 ifosfamide and 40 mg/m2 epirubicin, followed by 12 g/m2 ifosfamide, 900 mg/m2 carboplatin, 180 mg/m2 epirubicin with ASCT) versus adriamycin-cyclophosphamide or cyclophosphamide-methotrexate-5-fluorouracyl regimens in high risk breast cancer. Methods: We isolated tumor DNA from 117 patients of a case-control study of high risk breast cancer patients to apply a marker by treatment interaction study design to assess overall survival. We generated copy number profiles and classified them to be BRCA1-like or non-BRCA1 like. We used Fisher Exact tests to calculate correlations and performed Kaplan-Meier and Cox regression analyses to investigate whether patients with a BRCA1-like tumor benefit from IA chemotherapy compared to an AC/CMF regimen. Results: 16 of 117 (14%) patients had a BRCA1-like profile. BRCA1-like status was associated with high tumor grade (p=0.03), triple negative status (p=0.0005) and high N stage (p=0.03). When corrected for hormone receptor and HER2 status, size, positive lymph nodes, and grade we found that BRCA1 like patients had a 6-fold decreased chance of death (HR: 0.15, 95% confidence interval: 0.03-0.80, p: 0.03) compared to non-BRCA1 like patients (HR: 0.94, 95% confidence interval: 0.53-1.67, p: 0.84). The interaction test between IA chemotherapy and marker status was significant (p: 0.04). Conclusions: We provide independent validation of the previous finding that breast cancer patients with a BRCA1 like copy number profile benefit highly from intensified alkylating chemotherapy.
Patient-reported outcomes in metastatic breast cancer: QoL, needs, and expectations of survivors.
Authors: Maira Caleffi, Norah Ana Burchardt, Helio Pasqualotto Scapin, Isabel Crivelatti, Carlos Spode Gomes, Ana Lucia Gomes, Paula Raffin Pohlmann
Journal: Journal of Clinical Oncology (2017)

228 Background: Breast cancer is still a leading cause of death and suffering worldwide. To date, metastatic breast cancer (MBC) is a treatable but incurable disease. Molecular subtypes influence outcomes, with recent increase in median overall survival to 56 months in HER2+ disease (Swain et al NEJM 2015). The success of MBC treatment underscores the increasing importance of discussing quality of life (QoL) and patients’ needs. A survey evaluating patient-reported outcomes was carried out in a Brazilian center with the aim of evaluating patient’s QoL, needs and expectations. Methods: In this IRB approved study, MBC patients were selected from clinical database for phone interviews. During the call, verbal consent was obtained and recorded. Patients answered a standardized questionnaire containing 28 questions about their experience with MBC. RedCap database was created with data from interviews for further analysis. Results: A total of 94 patients with MBC were initially screened. From these, 50 were interviewed (24 deceased, 6 declined and 14 had technical problems). Patient’s age ranged from 31-87y. In 44% family income decreased after MBC diagnosis. Median time from diagnosis of MBC to interview was 62 months (range 1-274 months). Most patients (86%) kept themselves informed about MBC; main sources being doctors (100%), internet (76%), media (71%), other patients (54%), and family (48%). Only 6% didn’t know what MBC meant. Majority were on therapy: chemotherapy/injectables (54%), oral medication (36%), and radiation (2%). Most (86%) preferred follow up by a multidisciplinary team, and 18% would prefer exclusive MBC clinics. Only 6% accepted the label “metastatic”. Less popular labels were “advanced disease” (6%), “recurred” (4%), “palliative” (4%), or “disseminated” (0%). They preferred this disease phase be called “controlled disease” (50%) or “chronic disease” (28%). Conclusions: The main sources of information about MBC for patients are the internet and their providers. In this center, communication between providers, policy makers and MBC patients could potentially be improved with terminology changes, since patients would prefer the metastatic phase of their disease be called “Controlled Disease”.
Omentin as a potential biomarker related to exercise and cancer risk.
Authors: Michaela Onstad, Karen Basen-Engquist, Rosemarie Schmandt, Samuel C Mok, Chi Lam Au Yeung, Stacie Scruggs, Karen H. Lu
Journal: Journal of Clinical Oncology (2015)

1571 Background: Omentin is a protective adipokine whose circulating levels are inversely related to BMI, waist circumference, and insulin resistance. Serum levels are lower in women with endometrial and ovarian cancers compared to healthy controls. Our in vitro studies demonstrate that exogenous omentin suppresses ovarian cancer cell motility and invasion potential and inhibits tumor growth indirectly. Given its inverse relationship with obesity and insulin resistance, we hypothesized that serum omentin can be increased with exercise. Methods: We conducted a pilot study of healthy individuals participating in a 10 week community exercise program aimed at training beginning runners for a 5K race. At the start of the program, anthropometric measures were taken, serum collected, and a whole body dual-energy X-ray absorptiometry (DXA) was done to measure percent body fat (%BF) and percent lean body mass (%LBM). These were repeated at completion of the program. Spearman’s rank correlation was used to analyze the association between omentin, anthropometric measures and body composition. Paired t-tests and Wilcoxon signed-rank test were used to analyze changes in omentin. Results: 40 participants were enrolled and 28 completed all follow-up studies. Baseline omentin was negatively associated with waist circumference (p = 0.03) and %BF (p = 0.01), and positively associated with %LBM (p = 0.009). 11 participants decreased their %BF at completion of the program, whereas 17 had no improvement or increased their %BF. Those who decreased %BF had in increase in serum omentin (median = + 89.23ng/mL), whereas those who had no improvement or increased their %BF showed a decrease in omentin (median = - 69.98ng/mL). The change in omentin was different between these groups, approaching statistical significance (p = 0.06). Conclusions: Omentin is negatively associated with waist circumference and %BF, and positively associated with %LBM. Changes in serum omentin due to exercise may be reflective of changes in body composition. As the correlation between omentin and cancer risk is further established, it may serve as a useful biomarker for patients to receive specific interventions. Omentin warrants inclusion in future research involving energy balance and cancer.
Fourth-line targeted therapy in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).
Authors: Igor Stukalin, Connor Wells, Anna Paola Fraccon, Felice Pasini, Camillo Porta, Raphael Brandao Moreira, Sandy Srinivas, I. Alex Bowman, James Brugarolas, Jae-Lyun Lee, Frede Donskov, Benoit Beuselinck, Aristotelis Bamias, Brian I. Rini, Hao-Wen Sim, Neeraj Agarwal, Sun Young Rha, Ravindran Kanesvaran, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2017)

498 Background: Fourthline targeted therapy efficacy in mRCC is not well characterized and is not reimbursed in many jurisdictions worldwide. Methods: The IMDC consists of consecutive patient series from 35 international cancer centers. It was queried for mRCC patients who received fourth line targeted therapy. Kaplan Meier estimates were used for time to treatment failure (TTF) and overall survival (OS). Results: 594 out of 7498 (8%) mRCC patients initially treated with first line targeted therapy eventually received fourth line therapy from a class of approved agents. Baseline characteristics are displayed in Table 1. The most common fourth line therapies were everolimus 17%, sorafenib 15%, axitinib 13%, pazopanib 13%, sunitinib 13%, nivolumab 7%. IMDC prognostic group distributions (Heng et al JCO 2009) and their associated survivals (both determined from fourth line therapy initiation) were 5% favorable risk (OS 23.1 (14.7-not reached)), 66% intermediate risk (OS 13.8 (11.4-17.5)), and 29% poor risk (OS 7.8 (4.93-12.2)) (OS p&lt;0.0001). Overall response rate for fourth-line therapy was 12.5% and 41.5% had stable disease in those patients that were evaluable (n=407). Median TTF on fourth line therapy was 4.40 months (95% CI 3.98-5.06) and median OS from fourth line therapy initiation was 12.8 months (95% CI 11.4-14.4). Conclusions: Fourth line targeted therapy has demonstrated activity, is uncommon, and should be offered to clinically eligible patients. Further studies are required to determine appropriate sequencing. IMDC criteria appear to stratify favorable/intermediate/poor risk patients well in the fourth line setting. [Table: see text]
Overall response rate as a surrogate of progression-free survival with molecular targeted agents: A meta-analysis of phase III trials in advanced non-small cell lung cancer.
Authors: Hiroaki Akamatsu, Keita Mori, Takashi Kikuchi, Hiroki Ueda, Keiichiro Akamatsu, Masanori Nakanishi, Yasuhiro Koh, Kazuto Matsunaga, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2015)

e19142 Background: Development of molecular targeted agents (MTAs) is active in advanced non-small cell lung cancer (NSCLC). Some of them demonstrated high overall response rate (ORR), and durable progression-free survival (PFS). To screen MTAs effectively in early clinical trials, ORR is a candidate surrogate marker. Methods: We extracted phase III trials which were for advanced NSCLC using MTA as monotherapy, published between 2000 to 2014. The trials were categorized into 3 groups (genetically enriched, clinically enriched, and non-enriched). ORR and median PFS were analyzed using Spearman’s rank order correlation. Results: Twenty-five trials (27 arms) using 6 MTAs (afatinib, crizotinib, erlotinib, gefitinib, icotinib, and vandetanib) were identified. Total number of the patients was 7050, and median number of the patients per arm was 196 (range, 68-695). About half of the trials were for the first-line treatment. Ninety percent of participants had good performance status. Of 25 trials, 8 were genetically enriched, 4 were clinically enriched, and others were non-enriched trials. ORR was strongly correlated with median PFS (ρ = 0.88, p < 0.0001). ORR of genetically enriched trials was the highest (55-80%), and that of non-enriched trials was the worst (3-28%). Conclusions: With MTAs, ORR is highly correlated with median PFS in advanced NSCLC. Almost all trials with high ORR ( > 50%) were genetically enriched.
A panel of biomarkers to improve specificity in presurgical assessment of adnexal masses for risk of ovarian malignancy.
Authors: Zhen Zhang, Danni Li, Lori J. Sokoll, Xiaer Sun, Robert Bristow, Daniel W Chan
Journal: Journal of Clinical Oncology (2013)

5573 Background: OVA1 is a panel of biomarkers cleared by FDA currently in clinical use for pre-surgical assessment of adnexal masses for risk of ovarian malignancy. To further improve the specificity of OVA1, we evaluated biomarkers using a designed set of clinical samples enriched with OVA1 false positive benign patients and selected insulin-like growth factor binding protein 2 (IGFBP2), interleukin 6 (IL6), and follicle-stimulating hormone (FSH) to be further evaluated along with the original five biomarkers of OVA1 on a prospectively collected clinical sample set. The inclusion of FSH was to eliminate the need for menopause-specific cutoffs. Methods: Consecutive patients with a documented pelvic mass planned for surgical intervention were prospectively enrolled at 27 sites. Exclusion criteria included a diagnosis of malignancy in the previous 5 years or initial enrollment by a gynecologic oncologist. At the time of analysis, 384 subjects had all biomarker values. Among them 69 were ovarian cancer cases (13 LMPs, 27 stages 1/2, 19 serous, 11 endometrioid , 5 mucinous, and 4 clear cell). Biomarkers were tested by ELISA and reported as continuous values. Using a subset of the samples, the biomarkers were first selected for inclusion in a final panel based on contributions in multivariate models estimated by bootstrap. The selected biomarkers were further assessed for ability to improve specificity of risk stratification at a fixed sensitivity over that of OVA1 using the full data set. This was done by cross-validation of multivariate models with 50/50 split between training and testing. Results: The final panel of biomarkers consisted of CA125II, prealbumin, IGFBP2, IL6, and FSH. At a fixed sensitivity of 90%, the mean and median specificity of models using the new panel in testing were 78.2% (95% CI: 76.7 – 79.8%), and 80.6%, respectively. The mean and median absolute improvements over that of OVA1 were 18.6% (95% CI: 16.4% – 20.9%) and 20.3%, respectively. Conclusions: The new panel demonstrated the potential to significantly improve specificity over that of the first-generation OVA1 algorithm, while maintaining a high sensitivity in pre-surgical assessment of adnexal masses for risk of malignancy.
Deciding on the Duration of Dual Antiplatelet Therapy—When the Choice Between 2 Evils Is Still Evil
Authors: Marco Valgimigli, Giuseppe Gargiulo
Journal: JAMA Cardiology (2017)

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Characterization of maize chitinase‐A, a tough allergenic molecule
Authors: M. Volpicella, C. Leoni, I. Fanizza, M. Distaso, G. Leoni, L. Farioli, T. Naumann, E. Pastorello, L. R. Ceci
Journal: Allergy (2017)

Food allergies are recognized as an increasing health concern. Proteins commonly identified as food allergens tend to have one of about 30 different biochemical activities. This leads to the assumption that food allergens must have specific structural features which causes their allergenicity. But these structural features are not completely understood. Uncovering the structural basis of allergenicity would allow improved diagnosis and therapy of allergies and would provide insights for safer food production. The availability of recombinant food allergens can accelerate their structural analysis and benefit specific studies in allergology. Plant chitinases are an example of food allergenic proteins for which structural analysis of allergenicity has only partially been reported. The recombinant maize chitinase, rChiA, was purified from Pichia pastoris extracellular medium by differential precipitation and cation exchange chromatography. Enzyme activity was evaluated by halo-assays and microcalorimetric procedures. rChiA modeling was performed by a two-step procedure, using the Swiss-Model server and Modeller software. Allergenicity of rChiA was verified by immunoblot assays with sera from allergic subjects. rChiA is active in the hydrolysis of glycol chitin and tetra-N-acetylchitotetraose and maintains its activity at high temperatures (70°C) and low pH (pH 3). The molecule is also reactive with IgE from sera of maize-allergic subjects. rChiA is a valuable molecule for further studies on structure-allergenicity relationships and as a tool for diagnosing allergies.