tbuckley/cabot-search huggingface dataset:
Observational retrospective study to describe the management of advanced epidermal growth factor receptor (EGFR) mutated (M+) non-small cell lung cancer (NSCLC) patients (pts) in Spain (NCT01795352).
Authors: Edurne Arriola, Ramon Garcia Gomez, Pilar Diz, Margarita Majem, Maite Martinez Aguillo, Javier Valdivia, Alfredo Paredes, Jose Miguel Sanchez Torres, Sergi Peralta, Isidoro C. Barneto, Maria Carmen Gonzalez-Arenas
Journal: Journal of Clinical Oncology (2014)

e19133 Background: Activating mutations (mut) in EGFR gene confer sensitivity to the EGFR tyrosine kinase inhibitors (TKIs) in pts with advanced NSCLC improving progression free survival (PFS) rates. This study has been performed to describe the management patterns of advanced EGFR mutated NSCLC pts in Spain Methods: The study population comprised pts with advanced EGFR M+ NSCLC diagnosed from April 2010 to December 2011 in 18 Spanish centers. Retrospective data collection took place between March and November 2013 and was based on available information reported on the medical records Results: A total of 181 evaluable pts were enrolled in the study. Median age was 71.6 (IQR 16.8) years. The majority of pts were Caucasian (98.3%), female (61.9%), never-smokers (54.9%), PS 0-1(80.1%) and had non-squamous histology (93.9%). Mutation testing was performed preferentially in biopsy material (68.7%) in external laboratories in 68.0% with RT-PCR-based tests 87.9% (Therascreen EGFR PCR Kit 51.5%). Median turnaround time was 9 days. We observed 9.4% any exon 18 mut, 53.3% exon 19 deletion, 21.1% L858R mut, 3.9% any exon 20 mut, 3.9% L861Q mut and 8.3% other exon 21 mut. The vast majority of pts (92.8%) received first line (1L) treatment being EGFR TKIs in 81.5% (82.6% gefitinib and 17.4% erlotinib), chemotherapy (CT) in 13.7%, and CT follow by TKI in 4.8 %. Only 47.0% of pts received second-line (2L) treatment. Pts who progressed on TKI, in 2L, were treated with CT (33.9%), TKI+CT (8.9%), or different TKIs (9.8%). At the time of analysis, the median follow-up time was 13.3 months (range 0.4-38 months). Efficacy results by line and treatment for pts evaluable for response (150) are shown in the Table. Conclusions: EGFR TKIs are the standard treatment for EGFR M+ pts in Spain. Efficacy results provided by this study based on a daily practice setting resemble those from the phase III trials in this selected population. Treatment (n) ORR (%) DCR (%) mPFS (m) First line TKI (124) 46.8 87.9 9.9 Gefitinib (100) 50 86 9.9 Erlotinib (24) 36.4 95.5 9.9 CT (18) 22.2 77.8 5.2 CT à TKI (8) 25.0 100.0 7.6 Second line TKI (18) 22.2 55.6 4.9 CT (36) 13.9 69.4 4.8 TKI+CT (8) 25 87.5 5.1
Abstract 19386: Effects of Early Administration of Unfractionated Heparin During Prolonged Cardiac Arrest in a Porcine Model of Extracorporeal Cardiopulmonary Resuscitation
Authors: Nicole L Werner, Joseph P Phillips, Jacob R Hirschl, Madison S Bachman, Brendan M McCracken, Caitlin P Worthey, Xiaodan Ren, Joshua M Mergos, Cindy H Hsu, William C Stacey, Robert H Bartlett, Alvaro Rojas Pena, Robert W Neumar
Journal: Circulation (2017)

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is a feasible and effective resuscitation strategy for refractory cardiac arrest, but often fails to restore heart and brain functi...
Cell-Free Mitochondrial DNA Is Elevated in Sickle Cell Disease Patients, and Serve As a Potential Proinflammatory DAMP
Authors: Laxminath Tumburu, Shohini Ghosh-Choudhary, Emilia Alina Barbu, Simon Yang, Lauren D Harrison Ware, Ilker Tunc, Fayaz Tasaduck Seifuddin, Mehdi Pirooznia, Jun Zhu, Swee Lay Thein
Journal: Blood (2018)
Clinical and pathologic characteristics of ovarian cancer patients with BRCA1 and BRCA2 mutations in Turkish population.
Authors: Pinar Saip, Demet Akdeniz, Bugra Tuncer, Seda Kilic, Ozge Sukruoglu, Kevser Altundag, Leyla Kilic, Rumeysa Ciftci, Hulya Yazici
Journal: Journal of Clinical Oncology (2014)

e16526 Background: Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing ovarian cancer. We determined the regional distributions of ovarian cancer and BRCA1/2 gene mutations frequency in general Turkish Populations including Balkan Turks and also demographical, clinical and pathological characteristics according to BRCA mutation status. Methods: Demographical and clinical/pathological features were examined in total 179 ovarian cancer patients who tested for BRCA1/2mutations between 1994-2013 at Division of Cancer Genetics in Oncology Institute at The University of Istanbul. Results: Of the 179 women included in this study, 144 women (80,4%) tested negative for mutations in the BRCA1 or BRCA2 genes, 20 women (11.2%) had a BRCA1 mutation, 15 women (8,4%) had a BRCA2 mutation. A total of 35 mutations (20 BRCA1 and 15 BRCA2) were identified in the 179 ovarian cancer samples studied. The clinical stage, pathological stage and histological grade at diagnosis of BRCA-positive cancers were similar to those of BRCA-negative cancers (p>0,05). The type of histology of mutation carriers and noncarriers were statistically significant. BRCA1 mutation carriers had higher serous type histology than BRCA-negative cases or BRCA2 mutation carriers (P=0,002). Alcohol intake of ovarian cancer patients were found statsisticaly significant between the three groups (p=0,05). We found 19,5% (35/179) BRCA1/2 mutations in Turkish patients including Balkan Turks with a family history of breast and ovarian cancer. BRCA1/2mutation rates were higher at cases with two or more breast or ovarian cancer family histories and were found a significant statistically (p<0.001). There is no statistical significance between three groups for the aoveral survival (p>0.05). Conclusions: In this study, our results demonstrate clearly that the pathologic stage of BRCA-related ovarian cancer was similar to that of BRCA-negative ovarian cancers and also serous tumor histology is higher in BRCA1 mutation carriers than BRCA-negative patients and BRCA2 mutation carriers. The alcohol intake is a risk factor for ovarian cancer cases with BRCA1 carriers.
Volume of metastases and survival in patients with synchronous metastatic renal cell carcinoma (mRCC) of intermediate Memorial Sloan Kettering Cancer Center (MSKCC) prognosis.
Authors: Axel Bex, Roderick de Bruijn, Jasper Nijkamp, Allard Noe, Simon Horenblas, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2014)

e15605 Background: Patients with synchronous mRCC respond heterogeneously to targeted therapy, even when MSKCC or Heng prognostic risk is comparable. The objective was to analyse if prediction of survival for patients with synchronous mRCC and an identical MSKCC risk profile could be further refined by the volume of the primary tumour, the metastases, or both. Methods: The predictive value of the different volumes on survival of > 2 years (>2y) was analyzed retrospectively in patients with synchronous mRCC and intermediate MSKCC prognosis. Volumes of primary tumour and all metastases on pre-treatment CT were segmented in 3D using in-house developed software. A multivariate analysis was performed including the variables age; gender; Karnofsky performance status; Heng risk profile; primary, metastatic and total tumour volume; number of metastatic sites and nephrectomy status. Results: From 146 patients with synchronous mRCC treated at a single institution with targeted therapy since 2006, 71 patients were identified with intermediate MSKCC prognosis and complete pre-therapeutic CT of the abdomen and chest. Nineteen patients had a survival of >2y. At multivariate analysis only metastasis volume (MV) (p=0.012) and cytoreductive nephrectomy (CN) status (p=0.006) was significantly associated with >2y-survival. Of the patients who did not undergo CN (n=30), only 3 (10%) survived >2y. By contrast, of the patients who underwent CN (n=41), 16 (39%) survived >2y. In the CN group patients surviving >2y had a mean MV of 43 cc versus 87 cc for those surviving <2y. Prediction of survival using only MV with ROC analysis resulted in an area under the curve of 0.723, which was significant (p=0.004). For example, among patients with > 85 cc of metastasis (n=25) only 2 (8%) survive >2y. Conclusions: In patients with synchronous mRCC and MSKCC intermediate risk the likelihood to survive >2y was 27%. Only MV and CN were associated with survival. Where MV is an independent variable, performing CN is not, due to selection bias. These results suggest that MV can be used to select patients with a low chance of long term survival, which may aid in selecting treatment options.
Outcomes in Children with Severe Vasculopathy from Sickle Cell Anemia after Treatment with Chronic Transfusion, Surgical Revascularization and/or Allogenic Hematopoetic Stem Cell Transplantation
Authors: Courtney W. Johnson, Suvankar Majumdar, Andrew D. Campbell, Suresh Magge, Deepika S. Darbari, Jennifer Webb, Yaser A. Diab, Robert Sheppard Nickel, Barbara Speller-Brown, Jessica Carpenter, Allistair Abraham
Journal: Blood (2018)
Expression of interleukin-1α (IL1-α) and risk of distant metastases (DM) in head and neck squamous cell carcinoma (HNSCC).
Authors: Antonio Lopez-Pousa, Xavier Leon, Mercedes Camacho, Luis Vila, IVANA GABRIELA SULLIVAN, Montserrat Lopez, Jacinto Garcia, Georgia Anguera, Cristina Arqueros, Dhiossett Condori, Josep M. De Vega, Nuria Farre, Oscar Gallego Rubio, Jordi Craven, Miquel Quer, Agust Barnadas
Journal: Journal of Clinical Oncology (2014)

6078 Background: There is a lack of biologic predictive factors in HNSCC patients. Interleukin-1α is a cytokine that participates in the mechanisms of carcinogenesis in patients with HNSCC, through the induction of the expression of genes involved in angiogenesis process and metastases. The aim of our study was to evaluate the relationship between the levels of expression of IL-1α and clinical behaviour in patients with HNSCC Methods: In this retrospective study, we have included 157 consecutive HNSCC patients with complete remission after multimodal treatment, with a minimum 2-years follow-up. mRNA expression of IL-1α and β-actin was quantified by RT-PCR in tissue samples. Relative expression was expressed as IL-1α/β-actin ratios. Multivariate analysis and a recursive partitioning analysis were performed. Results: During the follow-up period 46 p (29%) had a local failure, 23 (14.6%) regional failure and 18 (11.5%) DM. Frequency of DM in patients with low levels of IL-1α expression ( n = 103, 65.6%) was 5.1 %, and in patients with high levels (n = 54, 34.4%) was 23.5 . %. The 5-y DM free-survival was 93% vs 68.6% (low vs high expression). These differences are maintained regardless local and regional control. The only variables significantly associated with the risk of DM in the multivariate analysis were the presence of lymph node involvement at diagnosis (HR 3.1, 95% CI : 0.9- 9.6, p= 0.050), and elevated expression of IL-1α (HR 6.1 , 95% CI : 2.0-18.4, p=0.001). Conclusions: High levels of IL-1α expression is an independent factor associated with the risk of DM and survival. Although it should be validated prospectively, is a factor to be considered both clinically and in clinical trials.
Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts
Authors: Zachary S Wallace, Yuqing Zhang, Cory A Perugino, Ray Naden, Hyon K Choi, John H Stone
Journal: Annals of the Rheumatic Diseases (2019)

IgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes.We used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis.In the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1-3 (316, 178 and 445 mg/dL, respectively, p<0.001).We identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.
Randomized phase II trial of NGR-hTNF with an anthracycline in platinum-refractory or -resistant ovarian cancer (OC).
Authors: Domenica Lorusso, Giovanni Scambia, Nicoletta Colombo, Nicholas Reed, Carmen Pisano, Rosemary Lord, Giorgia Mangili, Annamaria Mosconi, Francesco Raspagliesi, Antonella Palazzo, Antonino Ditto, Vanda Salutari, Carmine Conte, Giulia Amadio, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2014)

5523 Background: Low-dose NGR-hTNF induces in preclinical models an early tumor blood vessel stabilization that enhances T-lymphocyte infiltration and survival, an effect that is mediated by CD8+ effector cells Methods: OC patients with disease progression while receiving or within 6 months after completion of ≤ 2 platinum/taxane lines were stratified by platinum resistance (refractory or resistant), PS (0 or 1/2) and anthracycline (doxorubicin, D or pegylated liposomal doxorubicin, PLD) and randomly assigned to receive D (60 mg/m2 q3w) or PLD (50 mg/m2 q4w) with (arm A) or without (arm B) NGR-hTNF (0.8 µg/m2 q3w). Progression free survival (PFS) was primary endpoint (β=20%; α=20%, hazard ratio, HR=0.62; n=100). Main secondary aims were overall survival (OS), response rate (RR, complete plus partial response) and adverse events (AE) Results: Baseline characteristics in arm A (n=58) vs B (n=51): median age, 60 vs 60 years; resistant, 71% vs 75%; PS of 0, 79% vs 82%; serous, 67% vs 71%; two prior lines, 48% vs 35%; D, 81% vs 84%; median baseline peripheral blood lymphocyte count (PBLC), 1.4/mL vs 1.6/mL. In all, 262 cycles were given in arm A (mean 4.5; range 1-20) and 227 in B (4.4; 1-8). Grade 3/4 AEs (arm A vs B): neutropenia, 29% vs 22%; anemia, 4% vs 6%. With median follow-up time of 16.1 months, there was no significant difference between the two arms in PFS (stratified HR=1.08; 95% CI, 0.70-1.65), RR (odds ratio=1.34; 0.21-8.33) and OS (HR=0.70; 0.42-1.17). Median and 18-month OS rates were 12.1 months (6.9-17.2) and 44% (±7) vs 9.4 months (8.4-10.4) and 22% (±7) for arm A vs B, respectively. In resistant disease (n=79), median OS was 14.2 months for arm A and 9.5 months for arm B (HR=0.66; 0.36-1.21). In patients with baseline PBLC above the median value (n=56), median OS was not reached yet for arm A compared with 9.5 months for arm B (HR=0.45; 0.22-0.91; p=0.02). Follow-up assessment for a next patient cohort (n=24) receiving a weekly schedule of NGR-hTNF is ongoing Conclusions: NGR-hTNF plus D/PLD was safely given, without increase in PFS over D/PLD in unselected population. Consistently with previous findings, significantly improved OS rates for the combination were noted in patients with high baseline lymphocyte counts Clinical trial information: NCT01358071.
Validation of the Mexican-Spanish version of the EORTC QLQ-INFO25 instrument in patients with gastrointestinal cancers.
Authors: Maricela Salas-Becerril, Silvia R Allende-Perez, Alejandra Monroy, Vincenzo Aiello-Crocifoglio, Luis F. Onate-Ocana
Journal: Journal of Clinical Oncology (2018)

818 Background: Information received by the cancer patient is a main component of an evaluation of quality of care. The most frequently used instrument to do so is the EORTC QLQ-INFO25, and our aim is to validate its Mexican-Spanish version in patients with gastrointestinal cancer. Methods: This is a prospective study including patients who responded the QLQ-INFO25 instrument at a cancer referral center. Reliability and validity tests were performed, and the association of scale scores with clinical variables is shown. Results: One hundred thirty six patients were included, 70 female and 66 males. Mean age was 56.2 years; 111 corresponded to colorectal and 25 to gastroesophageal cancer. Questionnaire compliance rates were high and both instruments were well accepted; no missing values were found. Convergent item correlation in the QLQ-C30 ranged from 0.223 to 0.822 and in the QLQ-INFO25 from 0.008 to 0.768, respectively. Divergent item correlation ranged from 0.011 to 0.674 and from 0.014 to 0.662, respectively. Cronbach’s α coefficients of eight of nine multi-item scales of the QLQ-C30 and all four multi-item scales of the QLQ-INFO25 instruments were &gt; 0.7 (range, 0.655–0.905). Selected scales of both instruments distinguished among esophagogastric or colorectal cancer. Conclusions: The Mexican-Spanish version of the QLQ-INFO25 questionnaire provides domains not covered by the generic instrument, it is reliable and valid to be used in clinical trials assessing patients’ appraisal on the received information by the health personnel.
Next-generation sequencing (NGS) as part of pathologic diagnostic armamentarium.
Authors: Lorna Rodriguez-Rodriguez, Kim M. Hirshfield, Shridar Ganesan
Journal: Journal of Clinical Oncology (2014)

11076 Background: Because genomic alterations inform tumor biology, treatment decisions, and new research opportunities, we established a Molecular Tumor Board. Cases with NGS results from a CLIA certified assay are presented and therapeutic strategies are suggested when appropriate. Cases called for re-consideration of final pathologic diagnosis are presented as example of the utility of NGS in aiding final diagnosis and recommending treatment of unusual cases. Methods: NGS on formalin-fixed, paraffin embedded tumors (N=101 patients) was done using hybridization-captured, adaptor ligation–based libraries to high, uniform coverage for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Data curation was performed by Precision Medicine physicians at Rutgers Cancer Institute of New Jersey. Cases were presented formally at the Molecular Tumor Board where systems biologists, oncologists, pathologists, and scientists discussed de-identified data. Results: Five cases had ambiguous diagnoses: three gynecologic malignancies, a brain tumor of unknown origin (presented in detail elsewhere), and a presumed lung carcinoma with concomitant pancreatic cancer. One case had two tumor foci sharing almost all of the genomic alterations and were more similar to those found in sarcoma than in GIST, the final diagnosis was metastatic ovarian carcinosarcoma. In another, a presumed recurrence of ovarian cancer had alterations that were more consistent with pancreatic primary. By tumor board recommendations, the patient underwent endoscopic biopsy of the pancreas that uncovered a primary pancreatic cancer. In two cases, mutational analysis revealing shared mutations between two tumor foci overcame diagnostic dilemma of new primary versus metastasis. Conclusions: NGS assays are useful to identify actionable genomic changes and challenge pathologic diagnosis, translating into patient benefit. Genomic alteration signatures should be validated for tumors that are rare, difficult to diagnose or unusually recalcitrant to treatment. NGS should become part of the pathologic armamentarium for tumor diagnosis.
Computed tomographic window setting for predicting invasive adenocarcinomas in pulmonary nonsolid tumors.
Authors: Takashi Eguchi, Akihiko Yoshizawa, Satoshi Kawakami, Tetsuya Umesaki, Hirotaka Kumeda, Hiroyuki Agatsuma, Takao Sakaizawa, Yoshiaki Tominaga, Masayuki Toishi, Masahiro Hashizume, Takayuki Shiina, Kazuo Yoshida, Tomonobu Koizumi
Journal: Journal of Clinical Oncology (2014)

7556 Background: Nonsolid pulmonary tumors are occasionally diagnosed as invasive adenocarcinomas. Preoperatively distinguishing adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma is essential for treatment decision making. However, this distinction is potentially difficult to make using the conventional computed tomographic (CT) settings, that is, the lung and mediastinal windows. This study aimed to evaluate novel CT window settings for preoperative detection of invasive adenocarcinomas. Methods: We retrospectively evaluated 101 nonsolid tumors resected between July 2006 and November 2013. In the preoperative CT procedures performed, the predictive invasion diameter was determined as the maximum diameter of the residual tumors under the window level/window width settings as follows: −600/0, −550/0, −500/0, −450/0, −400/0, −350/0, and −300/0. Correlation analyses were used to verify whether each viewing condition could be useful for predicting pathological invasion. Then, a receiver operating characteristic (ROC) curve analysis was performed to evaluate the usefulness of the predictive invasion diameter for predicting pathological invasive adenocarcinomas that have a maximum invasion diameter of more than 5 mm. Results: Thepathological classification of the lesions was AIS for 47 lesions, MIA for 30 lesions, and invasive adenocarcinoma for 24 lesions (lepidic, 10 lesions; papillary, 8 lesions; and acinar, 6 lesions). The mean pathological invasion diameter was 2.9 ± 3.7 mm. The correlation coefficients between the pathological and predictive invasion diameters under the −600/0, −550/0, −500/0, −450/0, −400/0, −350/0, and −300/0 settings were 0.60, 0.61, 0.64, 0.66, 0.57, 0.47, and 0.41, respectively. In the ROC analysis, the sensitivity and specificity for predicting invasive adenocarcinomas in the window setting of −450/0 was 91.7% and 81.5%, respectively. For this, the cutoff predictive invasion diameter was set at 5.3 mm, and the area under the curve was 0.91. Conclusions: The window level/window width setting of −450/0 might be useful for predicting invasive adenocarcinomas in pulmonary nonsolid tumors.