tbuckley/cabot-search huggingface dataset:
Prognostic value of PD-L1 expression in colorectal cancer.
Authors: Albert Y. Lin, Natalia B. Kouzminova, Thomas Chou
Journal: Journal of Clinical Oncology (2017)

610 Background: Growing evidence have shown promise for targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling in several tumors. However, the role of PD-L1 expression in colorectal cancer (CRC) tumor cells and its interaction with other clinicopathologic factors remain elusive. Methods: We constructed a tissue microarray with paraffin-embedded primary colon cancer tissue (n=103; stage I, 22; II: 44; III: 37). Expression levels of biomarkers (PD-L1, EGFR, p53, Ki67, LEF1, VEGF, COX2, MMR – by IHC, and MiR-34a - by in situ hybridization), clinicopathologic variables and clinical outcomes were investigated. H-score evaluation of PD-L1 was performed. Tumors with an H score &gt;55, derived using Cutoff Finder, were considered PD-L1 positive for use in Kaplan-Meier survival analysis with log-rank test and in Cox regression models for recurrence-free survival (RFS) and overall survival (OS). Results: Median follow-up time for the entire cohort was 4.7 years (range 0.1-20.8). Positive PLD1 was identified in 89% of cases. As a group, cases with positive PD-L1 expression had better OS than those with negative expressions (12.2 vs 3.3 years) (p = 0.043), especially in cases with mismatch repair proficiency (MMR-P, 12.1 vs 1.0 years) (p &lt;0.001). Negative PD-L1 expression in cases who had no chemotherapy was associated with worse outcome for OS (p=0.001) and RFS (p=0.008). There was no significant association between PD-L1 expression and gender, age, tumor size, pathologic stage or tumor grade. However, PD-L1 expression was significantly associated with MiR-34a (p&lt;0.001) and p53 overexpression (p=0.008) with a trend toward association in cases with mismatch repair proficiency (MMR-P, p=0.053). Conclusions: Our results suggest that negative PD-L1 expression appears to have negative prognostic value with worse RFS and OS in stage I - III CRC patients, especially those who had not received any chemotherapy. Given a recent study suggesting p53/miR-34a/PD-L1 axis as a novel mechanism of immune evasion, and strong correlation in the PD-L1/p53 and PD-L1/miR-334a expressions in our cohort, further investigation of their interactions is warranted that may lead to identifying their predictive value for immuno/chemotherapy.
Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial
Authors: Sandrine Andrieu, Sophie Guyonnet, Nicola Coley, Christelle Cantet, Marc Bonnefoy, Serge Bordes, Lawrence Bories, Marie-Noëlle Cufi, Thierry Dantoine, Jean-François Dartigues, Françoise Desclaux, Audrey Gabelle, Yannick Gasnier, Alain Pesce, Kristel Sudres, Jacques Touchon, Philippe Robert, Olivier Rouaud, Philippe Legrand, Pierre Payoux, Jean-Paul Caubere, Michael Weiner, Isabelle Carrié, Pierre-Jean Ousset, Bruno Vellas, Bruno Vellas, Sophie Guyonnet, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Sandrine Andrieu, Christelle Cantet, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre-Jean Ousset, Bertrand Fougère, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Marie Noëlle-Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li, Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristel Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule, Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Sophie Peiffer, Anne Hitzel, Michèle Allard, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Christian Vincent, Bertrand Perret, Claire Vinel, Pascale Olivier-Abbal
Journal: The Lancet Neurology (2017)
Improved imaging-pathology correlation with MR imaging-derived, 3D-printed, patient-specific whole-mount molds of the prostate.
Authors: Daniel N. Costa, Yonatan Chatzinoff, Niccolo M. Passoni, Payal Kapur, Claus G Roehrborn, Yin Xi, Neil Rofsky, Jose Torrealba, Franto Francis, Cecil Futch, Phyllis Hagens, Hollis Notgrass, Susana Otero-Muinelo, Rajiv Chopra, Ivan Pedrosa
Journal: Journal of Clinical Oncology (2017)

44 Background: A critical requirement for imaging-pathology correlation is adequate image registration. Since the prostate is deformable, sectioning the gland in a plane similar to imaging is challenging. To improve the in vivo imaging and ex vivo histology image registration, 3D-printed, patient-specific, MRI-derived molds (PSMs) for whole-mount processing have been proposed. This study compared the anatomical registration of preoperative MRI and prostate whole-mounts obtained with PSMs versus conventional whole-mount sectioning (WMS). Methods: Based on an a priori power analysis, 50 men who underwent 3T prostate MRI followed by radical prostatectomy were included. Two blinded and independent readers (R1, R2) outlined the contours of the gland and of the tumor in the MRI using regions of interest (ROIs). These were compared with the ROIs from the whole-mount histology, the reference standard, using PSMs in the study group (n=25) or conventional WMS in the control group (n=25). The spatial overlap across the MRI and histology data sets was calculated using the Dice similarity coefficient (DSC) for the prostate overall and tumor. Results were compared using Wilcoxon rank sum test. Results: The MRI-histopathology anatomical registration for the prostate gland overall and the tumor were significantly superior with the use of PSMs than with the use of WMS for both readers (Table). Conclusions: The use of PSMs for prostate specimen whole-mount sectioning provides significantly superior anatomical registration of in vivo multiparametric MRI and ex vivo prostate whole-mounts than conventional WMS. The use of PSMs should facilitate the exchange of information across imaging and pathology required for research and patient care. [Table: see text]
Impact of comprehensive tumor profiling using a targeted next-generation sequencing panel in Brazil.
Authors: Raphael Brandao Moreira, Marcelo Rocha S Cruz, Jessica Ribeiro Gomes, Tercia Tarciane Soares de Sousa, Marcus Paulo Fernandes Amarante, Fabio Schutz, Marcos André Costa, Carolina Kawamura Haddad, Rafael Schmerling, Fernando C. Maluf, Antonio C. Buzaid, Renata D'Alpino D'Alpino
Journal: Journal of Clinical Oncology (2015)

e22175 Background: Several patients with advanced cancer maintain good performance status even after disease progression following all standard therapies. Next-generation sequencing (NGS) is a powe...
Quality of life of elderly patients undergoing concomitant chemoradiation therapy for head and neck cancers, including assessment of geriatric parameters.
Authors: Martine Extermann, William J Fulp, Ji-Hyun Lee, Julie Ann Kish, Marina Sehovic, Donald Poon, Clement Gwede
Journal: Journal of Clinical Oncology (2012)

6100 Background: Data on the quality of life of older patients undergoing concomitant chemoradiation therapy (CCRT) for head and neck (H&amp;N) cancer are very scarce and no study has focused specifically on them. Furthermore, no study has assessed the contribution of geriatric symptoms to their quality of life. Methods: We prospectively assessed patients aged 65 and older undergoing curative intent CCRT for H&amp;N cancers, either alone or adjuvantly after surgery. We used the Quality of life-Radiation Therapy Instrument (QOL-RTI), with its H&amp;N module (Trotti et al., 1998). In addition we created a 12-items senior adult questionnaire (SAQ). Patients were assessed at baseline, at 4 weeks, at the end of treatment (EOT), and 2 months after EOT (recovery). Results: Fifty patients were enrolled. Median age was 69 years (range 65-87). Eighty-two percent of patients had locally advanced stage IV disease. Twenty-eight percent had prior surgery. All patients were treated with IMRT, 92% at 70 Gy. The most frequent chemotherapy regimen was cisplatin q3wks (58%), followed by weekly carboplatin (24%). Patients had on average 4 comorbidities (CIRS-G), 54% of them a grade 3 or 4 disease. Forty-four percent were independent in IADL, and 98% were ECOG PS 0 or 1. The baseline scores were QOL-RTI: 7.72 (SD 1.36), H&amp;N module 7.7 (SD 2.16), SAQ 8.21 (SD 1.54). At EOT, the scores were 6.22 (1.26), 4.59 (1.82), 7.38 (1.38) respectively, and at recovery 7.17 (1.25), 6.06 (1.66), 7.96 (1.16). The scores paralleled functional evolution, as 24% of patients had an ECOG PS 2 and 76% were IADL dependent at EOT; 16% ECOG 2-3 and 55% IADL dependent at recovery. Cronbach alphas for the 3 QOL measures were 0.88, 0.89, and 0.81, suggesting adequate internal consistency reliability. The SAQ was low-to-moderately correlated with the other two QOL measures (r=0.22 to 0.59) at different points of assessment. Conclusions: Older H&amp;N cancer patients experience significant impact of CCRT on their function, and on their quality of life on all three measures. Most recover after two months, although some may take longer. A geriatric module adds significant information to the general QOL-RTI and H&amp;N questionnaires.
Early-phase (EP) clinical trials (CTs) in the community: Results from the National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) Early-Phase Working Group (EPWG) Baseline Assessment Study (BAS).
Authors: Ronald S. Go, Howard Zaren, Suresh G Nair, Keith S. Lanier, Michael A. Thompson, Rebecca A. Enos, Jinxiu Zhao, Deborah L. Fleming, John Charles Leighton, Thomas Edward Gribbin, Donna M. Bryant, Angela Carrigan, Jennifer C. Corpening, Kimberly A. Csapo, Eileen P. Dimond, Christie Ellison, Maria Magdalena Gonzalez, Jodi L. Harr, Kathy Wilkinson, Andrea Denicoff
Journal: Journal of Clinical Oncology (2012)

e16561 Background: The NCCCP is a network of 30 community cancer center (CCC) sites that strive to expand cancer research capacity and deliver advanced care in the community. The EPWG was formed to facilitate NCCCP site participation in EP (phase I-II) CTs, thus allowing patients (pts) to be treated within their communities. This study describes the CT infrastructure at NCCCP sites and its association with EP accrual. Methods: A BAS was conducted to obtain data on NCCCP site CT infrastructure, funding, sponsor affiliations, and barriers to EP CTs. To evaluate EP performance, EP accruals during July 2010-June 2011 were obtained. High accruing sites were those with EP accrual above the median EP accrual per 1,000 new analytical cases seen in 2009 or 2010. Results: 27 sites, caring for ~56,000 new cancer pts annually, participated in the study. Median number of accruing EP trials/site was 6 (mean 7.4). Median EP accrual/site was 14 (mean 16). Median EP accrual rate was 7/1,000. Trials with a phase I component were open at 21 sites. Most sites (24) are members of multiple CGs (median 4) and enroll pts via the CTSU (70%). The more common barriers to EP trial implementation were related to infrastructure (59%), cost (52%), and access to trials (41%). When accrual rates to NCCCP CTEP EP trials only were analyzed, we found that between high vs low accruing sites, respectively, higher accrual rates were associated with higher number of CRAs devoted to EP trials (median 3.25 vs 1; P= .05) and lower proportion of funding from industry (median 18% vs 40%; P=.02). We did not, however, find significant associations when EP trials were examined across all sponsors. Conclusions: CCCs are capable of conducting, and actively participating in, EP trials. Infrastructure and collaborations are critical components of success. Our study provides useful information for those planning to begin EP trials in the community setting. [Table: see text]
Phase I pharmacokinetic study of dasatinib (BMS-354825) in patients with advanced malignancies and varying levels of liver dysfunction: S0711, a SWOG early therapeutics committee study.
Authors: John Sarantopoulos, Antje Hoering, Timothy W. Synold, Devalingam Mahalingam, Ding Wang, Heinz-Josef Lenz, Pat O'Rourke, Rachel Sexton, Peter J. Van Veldhuizen, Monica M. Mita, Lucas Wong, Alain C. Mita, Anthony B. El-Khoueiry, Vincent M. Chung, David R. Gandara, Sheela Tejwani, Naoko Takebe, Chris H.M. Takimoto, S. Percy Ivy, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2012)

3078 Background: Dasatinib (D) is a first in class Src kinase inhibitor, and inhibits BCR-Abl, c-Kit, PDGFR-beta, EPHA2 and Src family kinases including Src, Lck, Yes, Fyn at nanomolar concentrations. Initially FDA approved for use in imatinib resistant CML. It is a small molecule targeted therapy hepatically metabolized primarily by CYP3A4. We conducted a phase I study to determine maximum tolerated dose (MTD) and pharmacokinetics (PK) of D in patients (pts) with liver dysfunction (LD). Methods: Pts with advanced solid tumors or lymphoma, Zubrod ≤2, no baseline ascites or pleural effusions, adequate renal and bone marrow function, received PO D daily. Cycles q28 days. Pts stratified into 4 LD groups: normal, mild, moderate, severe, using Child-Pugh classification (CPC). Data also collected for NCI ODWG Organ Dysfunction Working GroupCriteria. D dose was escalated in sequential cohorts of pts within each LD category. Blood analysis for D concentrations were determined during cycle 1 using a validated LC-MC/MS assay. Study objectives included characterizing safety, tolerability, PK, identifying the MTD and obtaining preliminary evidence of efficacy. Results: 54 registered pts, 51 pts received 51 cycles of D at doses starting at 100 mg in mild LD (50-140 mg). Median age 60, male 55%, Zubrod 1 70%. CRC 27%. Groups: normal-17, mild-20, moderate-13, severe-1 pt(s). Related AEs include fatigue 35%, diarrhea 27%, anemia 27%, nausea 25%, vomiting 21%, lymphopenia 13%, rash 13%, pleural effusion 8%. 1 DLT of increased CK in a pt in moderate LD with past history of similar episode with previous sorafenib. Previous linear PK disposition, and no accumulation. No apparent PK differences between normal and mild groups. Cycle 1 Day 1 D 140 mg Normal Group: C max 129 ng/mL. Mild Group 140mg: C max 157 ng/mL. Prolonged disease stabilization (≥4 cycles) in 6 pts, 3 CRC (4,5,8); 1 Pancreas, HCC, Bladder (4,5,6). Conclusions: Recommended dose for Dasatinib given PO QD for pts with mild, moderate, or severe LD using clinical criteria with CPC and no baseline ascites, are 140 mg, 70 mg, insufficient pts, respectively. Dose adjustment not necessary in pts with mild LD.
Outcomes of adjuvant chemotherapy after neoadjuvant chemoradiotherapy for esophageal cancer.
Authors: Ravi Shridhar, Jamie Huston, Kenneth L Meredith
Journal: Journal of Clinical Oncology (2017)

92 Background: The use of adjuvant chemotherapy (AC) after neoadjuvant Chemoradiotherapy (NCR) and surgery for esophageal cancer is controversial. The purpose of this study is determine if AC is associated with an overall survival (OS) benefit after NCR. Methods: The National Cancer Database was queried to identify esophageal cancer patients who underwent NCR and surgery between 2006 and 2013 and stratified by treatment with AC. Propensity score matching was utilized against age, pathologic tumor and nodal stage, histology, and margin status. Kaplan-Meier and log-rank analysis was used to determine OS benefit. Univariate (UVA) and multivariate (MVA) was performed with Cox proportional hazard ratio analysis. Results: We identified 1816 patients. AC was associated with improved OS. The median and 3-year OS for AC versus none was 36.4 months and 50% versus 30.9 months and 45%, respectively, (p = 0.02), however, the benefit was restricted to node positive (N+) patients. The median and 3-year OS for AC versus none in N+ patients was 31 months and 44% versus 26 months and 36%, respectively, (p = 0.03). UVA revealed that AC only benefitted patients with N+, R0 resection, and adenocarcinoma. UVA revealed that age, pathologic T3-4, N+, high grade, and R1 resection were associated with increased mortality, while removal of &gt; 10 nodes and AC was associated with decreased mortality. MVA revealed that age, pathologic T3-4, N+, high grade, and R1 resection were associated with increased mortality, while removal of &gt; 10 nodes was associated with decreased mortality. MVA revealed that AC was not prognostic for OS in all patients nor in N+ patients. Conclusions: This is the largest analysis on the use of AC after NCR and surgery for esophageal cancer. While there is an OS benefit favoring AC, the benefit is restricted to N+ patients. However, no benefit to AC was seen on MVA. Clinical trials are needed to address the role of AC after NCR in esophageal cancer.
Laparoscopic function-preserving gastrectomy based on sentinel node concept for early gastric cancer patients.
Authors: Hiroya Takeuchi, Osamu Goto, Ayako Shimada, Kazumasa Fukuda, Rieko Nakamura, Koichi Suda, Norihito Wada, Hirofumi Kawakubo, Naohisa Yahagi, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2017)

26 Background: Recent meta-analyses have shown acceptable SN detection rates and accuracy of determination of lymph node status. SN mapping may play a key role to obtain individual metastatic information and allows modification of the surgical procedures such as function-preserving gastrectomy for early gastric cancer. Methods: A dual-tracer method that employs radioactive colloids and blue dyes is currently considered the most reliable method for the stable detection of SNs in patients with early gastric cancer. The new technologies such as indocyanine green infrared or fluorescence imaging are also useful for accurate SN mapping in gastric cancer. Results: SN mapping has been performed for 489 patients with clinically T1N0M0 gastric cancer in our institute since 1999. Sensitivity to predict the lymph node metastasis was 90%, and overall accuracy of nodal status based on SN concept was 99 % (484 of 489). Sentinel lymphatic basin dissection is strongly recommended to cover the false-negative results of SN mapping in clinical practices. Based on these results, laparoscopic minimized gastrectomy such as partial resection, proximal gastrectomy, segmental gastrectomy and pylorus-preserving gastrectomy with individualized selective and modified lymphadenectomy for early gastric cancer with negative SN has been performed in our institution. The recent appearance of a new technique, referred to as non-exposed endoscopic wall-inversion surgery (NEWS) is a technique of full thickness resection using endoscopy and laparoscopic surgery without transluminal access mainly designed to treat gastric cancer with partial resection. The combination of NEWS with SN biopsy is expected to become a promising, ideal minimally invasive, function-preserving surgery for cN0 early gastric cancer. We initiated a new multicenter prospective trial to evaluate function-preserving gastrectomy with SN mapping in terms of long-term survival and patients’ QOL. Conclusions: Our results suggested that SN concept for cN0 early gastric cancer could be validated, and function-preserving surgery based on the SN concept which might retain the patients’ quality of life should be established as the next surgical challenge.
Phase I study of doxorubicin (D) plus anti-insulin-like growth factor 1 receptor (IGF-1R) antibody cixutumumab (IMC-A12) in advanced soft tissue sarcoma (STS).
Authors: Rashmi Chugh, Kent A. Griffith, Bruce Brockstein, Samir D. Undevia, Walter Michael Stadler, Scott Schuetze
Journal: Journal of Clinical Oncology (2012)

10028 Background: IGF1R is overexpressed in many STS, but its exact role in the biology of the disease is unclear. Anti-IGF1R antibody cixutumumab (C) has shown acceptable toxicity in a single-agent phase 2 study of STS. Here we performed a dose escalation study of C with D in STS. Methods: Eligible pts had advanced STS, ECOG ≤2, age&gt;16, ≤1 prior chemotherapy, fasting glucose&lt;120 mg/dL and acceptable organ function. C was administered IV over 60 min on D1,8,15 at one of three dose levels and D as a 48 hr infusion on D1 of a 21-day cycle. After 6 cycles of combination rx, pts with SD or better continued on single agent C. The Time-to-Event Continual Reassessment Method (TITE-CRM) was used to estimate the probability of DLT at each dose level and to assign patients to the dose with the estimated probability of DLT closest to but not exceeding 30%. Results: 30 pts with STS were enrolled between 9/08-1/12. Median age was 64 (range 29-80); 17M/13 F, 7 pts received prior chemo. One pt withdrew prior to rx; 5 pts are on active rx. Reasons for discontinuation were: progression (18), toxicity (3), death (1), pt decision (2). DLTs observed were hyperglycemia and mucositis. Grade 3 decrease in cardiac left ventricular ejection fraction was observed in 2 pts at dose level 2 after 4 or more cycles. Common G1/2 nonhematologic AEs: nausea (73%), fatigue (68%), pain (59%), diarrhea (41%), constipation (36%), hyperglycemia (32%), mucositis (32%), nail changes (27%), weight loss (27%). Gr3/4 toxicities in &gt;10%: hyperglycemia (18%), lymphopenia (18%), anemia (14%), neutropenia (14%), thrombocytopenia (14%). Median PFS was 5.3 months, 95% CI 2.7 -7.9 months. Four of 22 pts (18%) evaluable for response achieved a PR. Conclusions: C and D is tolerable and the recommended phase II dosing is dose level 3. The potential of cardiotoxicity should be monitored and assessed further in ongoing studies of this regimen. [Table: see text]