tbuckley/cabot-search huggingface dataset:
Germline genetic testing in unselected pancreatic ductal adenocarcinoma (PDAC) patients.
Authors: Mary Linton Bounetheau Peters, Randall Brand, Erkut Hasan Borazanci, Lindsey Stobie, Beth Dudley, Eve Karloski, A James Moser, Arlene Colvin, Cynthia Lim, Nathan Bahary, Weijing Sun, John C. Rhee, Barry C. Lembersky, Ronald G. Stoller, Holly LaDuca, Jill S Dolinsky, Emily Dalton, Virginia Speare, Mary Helen Black, Nadine M. Tung
Journal: Journal of Clinical Oncology (2017)

1501 Background: The aim of this study is to assess the prevalence of known heritable germline mutations in unselected PDAC patients and to determine how well current guidelines for genetic testing identify mutation carriers. Methods: Consecutive, unselected patients with recently diagnosed PDAC from three centers were enrolled from May to December 2016 in an ongoing prospective study. A three-generation pedigree was obtained. Germline mutations in 12 genes associated with PDAC risk ( APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, PALB2, PMS2, STK11, TP53) and in 19 genes related to other cancer risks were screened for by NGS. American College of Gastroenterology and NCCN criteria for genetic testing for BRCA1/2, Lynch syndrome, and Familial Pancreatic Cancer (FPC) were assessed. Results: Among 183 patients, 46% are female, 79% are Caucasian and 10% are Ashkenazi Jewish, with median (IQR) age 68 (62,75) years at diagnosis. 41% of patients met ³1 criteria for genetic testing (35.5% BRCA1/2, 2.7% Lynch, 9.3% FPC). Twenty patients (11%) were found to have a total of 21 pathogenic mutations (table). Mutation status was not associated with age at diagnosis, sex, or personal history of cancer (all p &gt; 0.05). Six mutation carriers (30% of positives) did not meet current criteria for genetic testing. Conclusions: Preliminary results show that 6.6% of unselected PDAC patients carry a germline mutation in a gene known to increase PDAC risk and 4.3% have a mutation in genes not previously linked to PDAC. Existing testing criteria did not identify 30% of carriers. Continued refinement of guidelines is necessary to align genetic testing with inherited PDAC risk. Clinical trial information: NCT02790944. [Table: see text]
A 7-Gene Signature as a Potential Clinical Molecular Assay to Predict Recurrence of Dukes’ B Colon Cancer
Authors: John Jiang, Conor Delaney, Ian Lavery, Yi Zhang, Tom Briggs, Michelle McGreevy, Dmitri Talantov, Dondapati Chowdary, Marek Skacel, Elena Manilich, Abhijit Mazumder, David Atkins, Graham Casey, Yixin Wang
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5668 

Colorectal cancer is one of the most common malignancies and the second cause of death from cancer in the US. The 5-year survival rate for patients with Dukes’ B colon cancer is approximately 75%. Currently, there is no clinical test available to determine the 25% of the patients with high-risk of recurrence. We have previously identified a 23-gene signature that predicts individual risk for recurrence. However, this discovery result was from a case-control study and has not been tested in a representative patient group of Dukes’ B colon cancer. The present study tests this gene signature in an independent group of Dukes’ B patients. We analyzed the total RNA of frozen tumor samples from 123 Dukes’ B patients of two independent sources and applied the 23-gene signature to the patient group in order to determine the risk of recurrence for each individual patient. In the independent set of 123 patients, the 23-gene signature proved to be highly informative in identifying patients with distant recurrence in both univariate (hazard ratio, HR 2.56; 95% confidence interval CI, 1.01 - 6.48) and multivariate analyses (HR, 2.73; 95% CI, 0.97 - 7.73). Furthermore, we have simplified the 23-gene signature to a 7-gene signature due to the composition of this representative patient group, and developed a real time quantitative (RTQ)-PCR assay for this gene signature using archived standard clinical FPE samples of 110 Dukes’ B colon tumor patients. The 7-gene signature was a strong prognostic factor in both univariate (HR, 6.55; 95% CI, 2.89 - 14.8) and multivariate analyses (HR, 13.9; 95% CI, 5.22 - 37.2).

Our results clearly demonstrate the prognostic value of the pre-defined gene signature for Dukes’ B colon cancer patients and show the feasibility of performing the test in clinic. The ability to identify colon cancer patients with an unfavorable outcome may help physicians and patients to seek more aggressive therapies.
Safety and efficacy of single bolus dose of recombinant factor VIIA in patients undergoing orthotopic liver transplantation
Authors: RM Planinsic, G Testa, S Emre, L Grande, A Candela, J van der Meer, Robert Porte, RM Ghobrial, H Isoniemi, P Schelde, E Erhardsen, G Klintmalm
Journal: Hepatology (2002)
Extraosseous Extension of Aggressive Vertebral Hemangioma as a Potential Pitfall on 68Ga-PSMA PET/CT
Authors: Stephan Probst, Franck Bladou, Gad Abikhzer
Journal: Clinical Nuclear Medicine (2017)

A 74-year-old man with newly diagnosed prostate cancer underwent Ga-PSMA PET/CT, which demonstrated intense uptake in and adjacent the L2 vertebral body. Subsequent MRI of the lumbar spine showed an aggressive L2 hemangioma with adjacent soft tissue extension. There was congruence of the intraosseous and extraosseous components of the hemangioma and the PSMA PET uptake. This is a rare but important potential pitfall in Ga-PSMA PET/CT-a soft tissue lesion with intense tracer uptake related not to a nodal metastasis of prostate cancer but to extraosseous extension of an aggressive vertebral body hemangioma.
Evaluation of breast cancer patients' and oncologists' expectations for integrative oncology in an ethnically diverse population.
Authors: Catherine Lee, Monica Lieberman, Farooq Faheem, Jeremy Ramdial, Eugene Ahn, Jorge Antunez de Mayolo, Rakesh Singal, Damien Mikael Hansra
Journal: Journal of Clinical Oncology (2016)

e12028 Background: We aim to compare how NCCN guideline recommended integrative services are valued between oncologists (MD) & breast cancer patients (pts). Methods: IRB approval obtained. Breast cancer Pts & MDs at an academic tertiary care medical center were enrolled to complete a survey. Demographics include: age, gender, race, & ethnicity. Clinical info include: cancer subtype & treating MD. Survey consisted of 7 questions assessing opinions on integrative care asking: “In addition to standard care, it is important to incorporate/provide” nutrition services, exercise therapy, spiritual/religious counseling, supplement/herbal advice, support groups, music therapy, or other complimentary medicine services (acupuncture, massage, relaxation therapy). Answers recorded on a 5 point scale (1 = highly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = highly agree) & converted into 2 categories (1,2,3 = neutral/disagree vs. 4,5 = agree). Fisher’s exact test with 2 sided p-value used to compare significance between MD & pt responses. Results: 181 pts and 55 MDs enrolled from June 2013 to October 2015. Mean age 54, median age 54, range 18-88 with 92% female and 3% male, 5% unspecified. 63% of patients were Hispanic vs. 37% not Hispanic. 11% white, 7% black/African American, 1% Asian/Pacific Islander, and 18% other/non-specified. Significance disparities were demonstrated: 88% of pts agree that nutritional advice is important vs. 69% of MDs, p = 0.0028, exercise therapy (91% vs. 71%, p = 0.0006), spiritual/religious (69% vs. 47%, p = 0.0066), supplement/herbal therapies (88% vs. 44%, p < 0.0001), music (63% vs. 29%, p < 0.0001), &“other complementary services” (82% vs. 47%, p < 0.0001). Non statistical favoring of support groups by pts observed (74% vs. 66% respectively, p = 0.2890). Conclusions: With the exception of support groups, pts value integrative modalities more than MDs. It is expected that increased availability & utilization of integrative oncology modalities could improve breast cancer patient satisfaction, quality of life, & other clinical endpoints.
NCCTG N1174: Phase I/comparative randomized phase (Ph) II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma (GBM) (Alliance).
Authors: Evanthia Galanis, S. Keith Anderson, Nicholas A. Butowski, Adilia Hormigo, David Schiff, David Dinh Tran, Antonio Marcilio Padula Omuro, Kurt A. Jaeckle, Shaji Kumar, Timothy J. Kaufmann, Jan C. Buckner, Erin Twohy, Caterina Giannini, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2017)

2023 Background: TRC105 is a humanized antibody targeting CD105 (endoglin), a member of the TGFβ receptor superfamily. CD105 is expressed in glioma stem cells and circulating endothelial cells (CECs) in GBM patients (pts), increasing following VEGF inhibition. N1174 was conducted in recurrent bevacizumab (bev) naïve GBM pts to investigate the hypothesis that CD105 blockade+bev can delay development of bev resistance. Methods: After a ph I cohort (15 pts) established the ph II dose of TRC105 as 10 mg/kg IV over 4 hours every 7 days in combination with standard dose bev, the ph II trial used 1:1 randomization with 90% power and 0.10 type I error to detect a 3 month (mo) difference in progression-free survival (PFS) between the two arms. CECs including CD105 positive subsets were measured by flow cytometry at baseline and multiple time points. Results: Based on 101 evaluable ph II pts, there was no significant difference in PFS between TRC105+bev and bev only (2.9 vs 3.2 mo, respectively; HR=1.14, 95% CI 0.73-1.77, p=0.57), or overall survival (10.0 vs 7.4 mo; HR 1.02 95% CI 0.63-1.65, p=0.93). Response rate (complete or partial) was 12.2% (6/49) for TRC105+bev and 11.6% (5/43) for bev only. Overall incidence of grade (gr) 3+ toxicity was higher for TRC105+bev (67.3% vs 32.7%, p&lt;0.001) mainly due to 14 pts with gr 3 anemia in the TRC105+bev arm vs 0 in the bev only pts. Gr 3+ non-heme toxicities were higher in pts receiving TRC105+bev vs bev only (50% vs 30.6%, p=0.07), mainly due to headache (6 vs 1 pts) and hyperglycemia (3 vs 0 pts). CECs remained stable in combination treated pts, suggesting a possible impact of the anti-CD105 blockade, but increased at progression in the bev only arm. There was no association between PFS and initial changes in CEC values, independent of treatment received. Conclusions: TRC105 plus bev did not prolong median PFS vs single agent bev in recurrent GBM pts, although it was associated with a non-significant prolongation of OS. These data and associated correlative analysis of CECs from study pts point against endoglin being a clinically significant factor for the development of bev resistance. Support: U10CA180821, U10CA180882. Clinical trial information: NCT01648348.
Evaluation of MET and HER2 expression in primary and metastatic tumor in Chinese advanced gastric cancer patients.
Authors: Miaozhen Qiu, Ruihua Xu, Yi-xin Zhou, Jacqueline Huang, En-Tzu Tang, Zhiqiang Du, Fanny Zhang
Journal: Journal of Clinical Oncology (2016)

e15538 Background: Gastric cancer is a heterogeneous disease. Whether the expression and amplification of c-Met/HER2 differ between the primary and metastatic lesion and their impacts on prognosis remain controversial. Methods: Paired (primary and metastatic) baseline tumor biopsy samples (formalin fixed, paraffin embedded) from patients with unresectable gastric cancer archived at Sun Yat-Sen University Cancer Center were assessed for c-MET and HER2 by IHC and FISH, respectively. MET-IHC-positive: membrane protein staining in ≥25% or ≥50% of tumor cells. Fisher exact and McNemar test was used to evaluate the association and difference between primary and metastasis lesion. Log-rank test was used for median overall survival (mOS) comparison. Results: 65 patients had evaluable IHC samples for both primary and metastatic lesions. MET positive rates were 27.7% and 32.3% for primary and metastatic sites, based on 25% cutoff, P =0.648, 18.5% and 23.1% for primary and metastatic sites, based on 50% cutoff, P=0.549. Of 55 patients with evaluable FISH samples, 6 (10.9%) metastatic sites and 3 (5.5%) primary sites had MET gene amplification, P=0.625. The concordance rate between primary and metastasis lesion was 70.8% by 25% IHC cutoff, 83.1% by 50% IHC cutoff and 94.5% by FISH. HER2 positive rate was 20.5% and 15.9% for primary and metastatic sites, respectively, P=0.188. Concordance rate of HER2 between primary and metastasis sites was 91.0%. OS by different status of MET and HER2 is shown in the Table. For MET primary+ patients, those with metastasis- had better OS than metastasis+ patients (mOS: 16.0m vs. 7.5m, P=0.005, 25% cutoff). Conclusions: No difference was found for MET or HER2 expression in primary and metastatic sites. Cutoff 50% was more powerful to detect the survival difference between MET positive and negative patients. MET positive in the metastasis lesion predicted a poorer prognosis. Primary lesion Metastatic lesion Positive (n) Negative (n) Pvalue Positive (n) Negative (n) Pvalue HER2 IHC and FISH mOS, month 14.7 (9) 14.1 (35) 0.700 14.7 (7) 14.1 (37) 0.912 MET IHC 25% cutoff mOS, month 11.2 (18) 15.0 (47) 0.170 11.2 (21) 14.7 (44) 0.446 50% cutoff mOS, month 8.1 (12) 15.0 (53) 0.032 5.5 (15) 15.0 (50) 0.003
Prognostic impact of pre- and postoperative chemotherapy in various breast cancer subtypes considering nodal status.
Authors: Naoki Hayashi, Madoka Iwase, Atsushi Yoshida, Yuko Takahashi, Junko Takei, Koyu Suzuki, Seigo Nakamura, Hideko Yamauchi
Journal: Journal of Clinical Oncology (2016)

e12577 Background: It is obvious that pre- and postoperative chemotherapy have same prognostic impact in overall breast cancer patients. However, the prognostic impact in each breast cancer subtypes considering nodal status is uncertain. Our aim was to assess whether prognostic impact of pre- and postoperative chemotherapy was different in each breast cancer subtypes considering nodal status. Methods: A total of 1327 patients who underwent breast surgery from 2004 to 2009, including 869 patients (65.5%) received preoperative chemotherapy and 458 patients (34.5%) received postoperative chemotherapy, were retrospectively analyzed. Breast cancers were classified into 4 subtypes based on ER and HER2 status. Results: In triple negative (TN) breast cancer patients with clinically node-negative (cN0), postoperative chemotherapy (n = 116) significantly improved disease-free survival (DFS) compared to preoperative chemotherapy (n = 63) (p = 0.001). In terms of overall survival (OS), there was a similar trend (p = 0.081). For the TN patients with large tumor > cT2, postoperative chemotherapy improved DFS compared to preoperative chemotherapy (p = 0.004). In TN patients with clinically node-positive (cN+), there was no difference of DFS and OS between patients received pre- and postoperative chemotherapy (p = 0.465 and 0.527, respectively). In ER-positive/HER2-negative patients with cN0, postoperative chemotherapy (n = 193) significantly improved DFS period compared to preoperative chemotherapy (n = 160) (p = 0.01) while there was no difference in terms of OS. In 135 ER-positive/HER2-positive patients and 176 ER-negative/HER2-positive patients, there was no difference of prognostic impact between pre- and postoperative chemotherapy regardless of nodal status. Conclusions: For TN patients with cN0 but a large tumor, which may have a rapid progression and develop metastasis, postoperative chemotherapy may be superior to preoperative chemotherapy. For ER-positive/HER2-negative patients with cN0 even having a large tumor, preoperative chemotherapy is not effective to improve prognosis. Therefore, primary surgery may be preferred rather than preoperative chemotherapy for these patients.
Traitement des troubles moteurs œsophagiens non achalasiques par dilatations pneumatiques
Authors: D Benajah, V Thetiot, F Richy, L Message, H Lamouliatte, F Zerbib
Journal: Endoscopy (2005)

Le but de cette étude était d'évaluer les résultats des dilatations pneumatiques (DP) dans la prise en charge de ces troubles moteurs en comparaison de ceux obtenus dans l'achalasie.
Emergent or Urgent Appendectomy?—A Changing Perspective
Authors: Rachel M. Landisch, Marjorie J. Arca, Keith T. Oldham
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Efficacy analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec (T-VEC) and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma.
Authors: Georgina V. Long, Reinhard Dummer, Antoni Ribas, Igor Puzanov, Ari VanderWalde, Robert Hans Ingemar Andtbacka, Olivier Michielin, Anthony J. Olszanski, Josep Malvehy, Jonathan S. Cebon, Eugenio Fernandez, John M. Kirkwood, Thomas Gajewski, Christine K. Gause, Lisa Chen, Kevin Gorski, Abraham Anderson, David Ross Kaufman, Jeffrey Chou, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2016)

9568 Background: T-VEC is a herpes simplex virus (HSV)-1 -based oncolytic immunotherapy designed to selectively replicate in tumors, produce GM-CSF and stimulate antitumor immune responses in melanoma. T-VEC significantly improved durable response rate vs GM-CSF in stage IIIB-IV melanoma patients (pts) with injectable tumors. Pembro inhibits programmed cell death protein 1 and improves survival in advanced melanoma. The combination may further improve clinical benefit. Here we report phase 1b efficacy, safety and biomarker data from a phase 1b/3 study of T-VEC+pembro in unresectable stage IIIB-IV melanoma (NCT02263508) with all pts having started on T-VEC+pembro ≥ 6 mo prior. Methods: Key inclusion criteria: unresectable stage IIIB-IV melanoma, injectable lesions; no prior systemic tx; and ECOG PS 0-1. T-VEC: ≤ 4 mL in (sub)cutaneous/nodal lesions, 106 PFU/mL d1, 108PFU/mL d22 then Q2W; pembro: IV, 200 mg d36 then Q2W. Tx until first occurrence of: complete response (CR); no injectable tumors (for T-VEC); confirmed PD per modified immune-related response criteria (irRC); tx intolerance; 24 mo of pembro. T cell subsets were evaluated by flow cytometry at baseline, during T-VEC alone, and during combination. Results: Of the 21 pts enrolled from Dec 2014 – Mar 2015, 48% had IIIB-IVM1a, 52% IVM1b/c, 76% HSV-1+, and 19% BRAFmut+. Median follow-up at data cut was 33 w. All pts received at least one dose of T-VEC+pembro. Tx-related AEs occurred in all pts: 33% G3/4, and no G5. Most common AEs were fatigue (62%), pyrexia (52%), and chills (48%). Per irRC, in 21 pts, confirmed/not yet confirmed objective response rate (ORR) was 48%/57%; CR rate was 14%/24%. Median time to response was 17 wks. Circulating CD8+ T cells including those expressing defined immune modulatory receptors (eg Tim3, BTLA) became elevated during tx with T-VEC initially but decreased after pembro began on d 36. Conclusions: The combination of T-VEC+pembro was associated with clinical benefit in advanced melanoma, as assessed by ORR and CR rate. A randomized, double-blind phase 3 trial of T-VEC+pembro vs T-VEC placebo+pembro is under way. Updated clinical and biomarker data will be presented at the meeting. Clinical trial information: NCT02263508.
Opposite Effects of Bruton Tyrosine Kinase (BTK) Inhibitor Therapy with Ibrutinib and FCR Chemo-Immunotherapy on the Normal B Lymphocyte Repertoire in Patients with Chronic Lymphocytic Leukemia
Authors: Simon Schliffke, Mariela Sivina, Ekaterina Kim, Benjamin Thiele, Nuray Akyüz, Clemens Falker-Gieske, Toni Thenhausen, Artus Krohn-Grimberghe, Carsten Bokemeyer, Nitin Jain, Zeev Estrov, Alessandra Ferrajoli, William G. Wierda, Michael J. Keating, Jan A. Burger, Mascha Binder
Journal: Blood (2016)
Key Roles of the Raf-1 and Akt in Drug Resistance, Cell Cycle Progression and the Prevention of Apoptosis in Hematopoietic Cells.
Authors: Steven L. Abrams, Linda S. Steelman, John G. Shelton, William H. Chappell, Ellis W.T. Wong, Fred E. Bertrand, James A. McCubrey
Journal: Blood (2005)
Reply: What Should Be the Cutoff Value of Blood Eosinophilia as a Predictor of Inhaled Corticosteroid Responsiveness in Patients with Chronic Obstructive Pulmonary Disease?
Authors: Nicolas Roche, Kenneth R. Chapman, Claus F. Vogelmeier, Felix J. F. Herth, Chau Thach, Robert Fogel, Petter Olsson, Francesco Patalano, Donald Banerji, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Management of lobular carcinoma in situ: A decision analysis.
Authors: Stephanie M Wong, Natasha K. Stout, Rinaa S. Punglia, Mehra Golshan
Journal: Journal of Clinical Oncology (2016)

1048 Background: Women diagnosed with lobular carcinoma in situ (LCIS) have a three to ten-fold increased risk of developing invasive breast cancer, and controversy remains regarding the best strategy for management of this diagnosis. We sought to evaluate the life expectancy and survival differences offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy (BPM). Methods: We constructed a Markov simulation model to determine life expectancy (LE) gains and survival for hypothetical cohorts of women diagnosed with LCIS at age of 40, 50 and 60 under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, effectiveness of preventive strategies and complication rates were derived from published studies and the Surveillance, Epidemiology and End Results database. Sensitivity analyses were performed to evaluate the stability of results to changes in model parameters. Results: Assuming a breast cancer incidence of 1-2% per year under active surveillance, a 50-year-old woman diagnosed with LCIS would have a total LE of 31.6-32.3 years, and would gain 0.32-0.64 years in LE by adding chemoprevention and 0.70-1.28 years by BPM. In our model, the largest gains were seen in young women aged 40-years at diagnosis, while increasing age at diagnosis attenuated gains associated with active prevention strategies. Ten-year overall survival (OS) with active surveillance ranged from 96.1-97% if diagnosed at 40-years, 93.6-94.5% at 50-years, and 88.5-89.3% at 60-years. Absolute percent differences in overall survival ranged from 0.5-1.1% with chemoprevention and 0.7-1.7% with BPM. Conclusions: Among women with a diagnosis of LCIS, LE gains were seen for risk-reducing strategies such as chemoprevention and BPM, particularly in younger women. Coupled with information about the potential side effects associated with each management strategy, these results may be useful to help guide women and their physicians in the decision making process.