tbuckley/cabot-search huggingface dataset:
Impact of crizotinib on survival in patients with advanced, ALK-positive NSCLC compared with historical controls.
Authors: A. T. Shaw, B. Y. Yeap, B. J. Solomon, G. J. Riely, A. J. Iafrate, G. Shapiro, D. B. Costa, M. Butaney, S. I. Ou, R. G. Maki, Y. Bang, M. Varella-Garcia, R. Salgia, K. D. Wilner, K. Kulig, P. Selaru, Y. Tang, E. L. Kwak, J. W. Clark, D. R. Camidge
Journal: Journal of Clinical Oncology (2011)

7507 Background: ALK represents one of the newest tyrosine kinase targets in lung cancer. In a seminal phase I trial, the ALK tyrosine kinase inhibitor crizotinib showed marked antitumor activity in patients with advanced, ALK+ NSCLC. However, in the absence of randomized data, the impact of crizotinib on overall survival (OS) of these patients is not known. Methods: We examined survival of 82 ALK+ patients who enrolled in the expansion cohort of the phase I trial of crizotinib (Kwak et al., NEJM, 2010). For comparators, we identified 37 ALK+ patients from phase I sites who were not treated with crizotinib (ALK+ controls), as well as 253 ALK-/EGFR- patients from one site (ALK- controls). All ALK+ and ALK- controls had advanced NSCLC. Results: In 82 ALK+ patients treated with crizotinib, 1-yr OS was 77% and 2-yr OS was 64%; median (med) OS has not been reached (NR). OS did not differ based on sex (p=0.35), ethnicity (Asian vs non-Asian, p=0.46), smoking history (never vs any smoking, p=0.82) or age (< or > 60 yrs, p=0.93). Among the 37 ALK+ controls, 1- and 2-yr OS was 73% and 33%, respectively, and med OS was 20 mos. As ALK+ controls were identified at sites outside of Korea, we compared controls with the non-Korean cohort of crizotinib-treated patients (n=56). Both groups were similar in age (median 51 vs 51, p=0.97), sex (57% vs 46% F, p=0.40), smoking history (68% vs 79% neversmokers, p=0.33), presence of brain mets at any time (49% vs 48%, p=1.00), number of prior therapies (mean 2.05 vs 2.09, p=0.17), and types of prior chemotherapy. We examined subsets of ALK+ patients by line of therapy. Survival of 32 patients treated with 2nd /3rd line crizotinib was significantly longer than that of 24 ALK+ controls (p=0.004): 1-yr OS was 71% vs 46%, 2-yr OS was 61% vs 9%, and med OS was NR vs 11 mos for the subset of crizotinib-treated patients vs the subset of ALK+ controls, respectively. For 123 ALK- controls in the 2nd line setting, the 1- and 2-yr OS was 49% and 33%, respectively, and the med OS was 11 mos. Conclusions: In patients with ALK+ NSCLC, crizotinib therapy is associated with a higher OS than that of historical, crizotinib-naïve controls. We propose that crizotinib represents a new standard of care for patients with ALK+ NSCLC.
Abstract 12724: Smoking is Associated with Presence of Vulnerable Plaques: A Three Vessel Optical Coherence Tomography Study
Authors: Farhad Abtahian, Taishi Yonetsu, Koji Kato, Haibo Jia, Rocco Vergallo, Jinwei Tian, Sining Hu, Iris McNulty, Hang Lee, Christopher Raffel, So-Yeon Choi, Catalin Toma, Ik-Kyung Jang
Journal: Circulation (2013)

Background: Smoking is associated with high incidence of cardiovascular events including acute coronary syndrome (ACS). We sought to characterize coronary plaques in patients with ongoing smoking u...
FDG Uptake in Non–Small Cell Lung Cancer Is Not an Independent Predictor of EGFR or KRAS Mutation Status
Authors: Seok Mo Lee, Sang Kyun Bae, Soo Jin Jung, Chun K. Kim
Journal: Clinical Nuclear Medicine (2015)

Purpose Data in the literature regarding the use of 18F-FDG avidity of non–small cell lung cancer (NSCLC) as an imaging biomarker to predict the status of epidermal growth factor receptor (EGFR) mutation are conflicting. Association between KRAS mutation and FDG avidity of NSCLC on PET/CT is not well known. We assessed whether the EGFR or KRAS mutation status in NSCLC can be predicted by FDG avidity by performing several different subgroup analyses to better compare with various published results. Patients and Methods After obtaining institutional review board approval, we enrolled patients (1) who had FDG PET/CT performed for staging of NSCLC, (2) with EGFR and KRAS mutational status of tumor identified, and (3) without uncontrolled diabetes. Univariate and multivariate regression analyses were performed to assess the relationship between the independent clinical variables (sex, age, smoking history, tumor histology, tumor size, stage, and SUV-derived variables) and the EGFR and KRAS mutation status. Separate analyses were performed for patients with adenocarcinomas. Results There were 206 patients (age, 33–88 years; 148 male/58 female; 71 ever-smokers/135 never-smokers; 135 adenocarcinoma/71 squamous cell carcinoma; 22 stage I-II/184 stage III-IV; tumor size, 1.2–15.0 cm; SUVmax, 2.9–36.4; EGFR mutations present in 47; KRAS mutations present in 20). In multivariate analysis, sex, smoking history, histology, and tumor size were significantly associated with EGFR mutation but none of the SUV-derived variables was. Likewise, no correlation was found between the SUV-derived variables and KRAS mutation. Conclusions Our results suggest that FDG avidity of NSCLC has no significant clinical value in predicting the EGFR or KRAS mutation status.
Multiple GSTM gene family members are recurrence risk markers in breast cancer
Authors: Michael Kiefer, Kenneth Hoyt, James Hackett, Michael Walker, Joffre Baker
Journal: Cancer Research (2006)

3604   The human GSTM (GSTμ) gene family consists of five different closely related isotypes, GSTM1-GSTM5. GSTM proteins conjugate glutathione to various electrophilic small molecules, facilitating clearance of the electrophiles from cells. Evidence exists that several metabolites of estrogen, including estrogen semi-quinones and estrogen quinones (catechol estrogens), are toxic and mutagenic (Cavalieri  et al.,Proc Natl Acad Sci  94:10937-42,1997). The activity of one or more GSTM enzymes may limit mutational damage caused by these estrogen metabolites. Accordingly, cancer cells expressing elevated levels of GSTM enzymes might be expected to exhibit better differentiation and reduced heterogeneity. We have reported five independent clinical studies in which GSTM gene expression was examined by quantitative RT-PCR in formalin-fixed, paraffin embedded primary breast cancer tissues. GSTM expression correlated strongly with favorable clinical outcome in each of these studies (Esteban  et al .,  Prog Proc Am Soc Clin Oncol  22:850 abstract, 2003; Cobleigh  et al., Clin Cancer Res (in press) ; Paik  et al .,  Breast Cancer Res Treat  82:A16 abstract, 2003; Habel  et al ,  Breast Cancer Res Treat  88:3019 abstract, 2004: Paik  et al, N Engl J Med  351:2817-26, 2004). In these studies the probe used could not discriminate between GSTM1 and several other GSTM family members as a result of the strong sequence similarity of the GSTM genes, amplicon size limitations and the stringent sequence criteria for probe-primer design, leaving the possibility that several of the GSTM genes may be favorable markers. To address this, we have designed gene-specific probe/primer sets for GSTM1-5 by utilizing noncoding sequences as the source of probe/primer sets. We have now examined the levels of these GSTM RNA transcripts in 125 breast cancer tumor specimens that have linked clinical records. Statistical analysis reveals a modest range of correlated expression between the gene family members (Pearson R ranging between 0.15-0.47) in breast tumor tissue. Importantly, in this study, increased expression of all five GSTM genes correlated with increased disease-free survival when analyzed in a univariate Cox Proportional Hazards (PH) Model (HR and p values ranging between 0.57-0.79 and 0.0003-0.0493, respectively). Furthermore, a multivariate stepwise Cox PH analysis indicated that GSTM2 and GSTM3 contribute independent recurrence risk information. In summary, we have used noncoding gene sequence to design RT-PCR assays that discriminate between the closely related members of the GSTM gene family, and have studied the relationship between expression of these genes and breast cancer recurrence risk. The results indicate that all five GSTM genes are correlated with the likelihood of breast cancer recurrence and suggest that certain GSTM family members contribute independent prognostic information.
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack
Authors: Walter N. Kernan, Catherine M. Viscoli, Karen L. Furie, Lawrence H. Young, Silvio E. Inzucchi, Mark Gorman, Peter D. Guarino, Anne M. Lovejoy, Peter N. Peduzzi, Robin Conwit, Lawrence M. Brass, Gregory G. Schwartz, Harold P. Adams, Leo Berger, Antonio Carolei, Wayne Clark, Bruce Coull, Gary A. Ford, Dawn Kleindorfer, John R. O’Leary, Mark W. Parsons, Peter Ringleb, Souvik Sen, J. David Spence, David Tanne, David Wang, Toni R. Winder
Journal: New England Journal of Medicine (2016)

Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.
Simple Limbal Epithelial Transplantation
Authors: Sayan Basu, Shraddha P. Sureka, Swapna S. Shanbhag, Abhinav R. Kethiri, Vivek Singh, Virender S. Sangwan
Journal: Ophthalmology (2016)

This study describes the long-term clinical outcomes of autologous simple limbal epithelial transplantation (SLET), a relatively new technique of limbal stem cell transplantation.This was a single-center prospective interventional cases series.This study included 125 patients, 65 adults and 60 children who developed unilateral limbal stem cell deficiency (LSCD) after suffering with ocular surface burns and underwent SLET between 2010 and 2014.A 1-clock hour limbal biopsy sample was obtained from the unaffected eye. At the same sitting, the recipient eye was surgically prepared and the donor tissue was divided into small pieces and transplanted using an amniotic membrane scaffold with fibrin glue.The diagnosis and outcome in every case was validated by 5 independent masked assessors. The primary outcome measure was restoration of a completely epithelized, stable, and avascular corneal surface. The secondary outcome measure was improvement in visual acuity. Complications, risk factors for failure, and immunohistochemistry analysis of corneas that underwent SLET also were described.At a median postoperative follow-up of 1.5 years (range, 1-4 years), 95 of 125 eyes (76%; 95% confidence interval, 68.5%-83.5%) maintained a successful outcome. Kaplan-Meier analysis revealed a comparable survival probability at 1 year of 80% in adults and 72% in children (P = 0.304). Two-line improvement in visual acuity was seen in 75.2%, and 67% of successful cases attained 20/60 or better vision (P < 0.0001). Progressive conjunctivalization occurred in 18.4% of eyes. The clinical factors associated with failure were identified as acid injury, severe symblepharon, SLET combined with keratoplasty, and postoperative loss of transplants (P ≤ 0.0075). Success rates were comparable among faculty and trainees (P = 0.71). Immunohistochemistry revealed successful regeneration of normal corneal epithelium (CK3(+)/12(+)) without admixture of conjunctiva cells (Muc5AC(-)/CK19(-)) and replenishment of limbal stem cell (ΔNp63α(+)/ABCG2(+)) reserve.Autologous SLET is an effective, reliable and replicable technique for long-lasting corneal regeneration and vision restoration in unilateral chronic ocular surface burns. Simple limbal epithelial transplantation is probably preferable to other techniques of limbal stem cell transplantation, particularly where cell cultivation facilities are unavailable.
Clinical Sequencing Contributes to a<i>BRCA</i>-Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course
Authors: Jocelyn S Chapman, Saurabh Asthana, Lindsay Cade, Matthew T Chang, Zhen Wang, Charles J Zaloudek, Stefanie Ueda, Eric A Collisson, Barry S Taylor
Journal: Journal of the National Comprehensive Cancer Network (2015)

Cancer is currently classified and treated using an approach based on tissue of origin. Ambiguous or incorrect diagnoses, however, are common and often go unnoticed. Clinical cancer sequencing can provide diagnostic precision, therapeutic direction, and hereditary cancer risk assessment. This report presents a patient with an initial diagnosis of metastatic pancreatic adenocarcinoma (PDA), a disease with a dismal prognosis. Tumor sequencing revealed genomic abnormalities inconsistent with PDA, instead suggesting serous ovarian cancer. This molecular rediagnosis was further refined by the identification of a BRCA2 truncating mutation in the tumor, subsequently confirmed to be a germline event. These findings prompted the initiation of platinum-based chemotherapy, which produced a life-altering response, and referral to genetic counseling for her offspring. These results suggest that clinical tumor sequencing can simultaneously clarify diagnoses, guide therapy, and inform familial risk, even in patients with end-stage metastatic disease, making the case for the development of specific strategies to deploy sequencing coupled with big data in oncology to improve clinical cancer management.
Sustainable Development Goals Launched
Authors: M. J. Friedrich
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 19994: Outcomes Following Thoracic Endovascular Aortic Repair in Patients With Bovine Aortic Arch Anatomical Variants: A 14-year Single Centre Experience
Authors: Prakash Saha, Ashish S Patel, Adnan Bajwa, Hany Zayed, Tom Carrell, Rachel Bell, Bijan Modarai
Journal: Circulation (2014)

Introduction: Bovine aortic arch (BA) anatomical variants have been associated with an increased incidence of thoracic aortic disease but whether this anatomical variant affects outcomes after inte...
Large Bowel Cancer in Women in Relation to Reproductive and Hormonal Factors: A Case-Control Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J D Potter, A J McMichael
Journal: JNCI Journal of the National Cancer Institute (1983)

A community-based case-control study of the effect of reproductive factors on risk of large bowel cancer in Australia is described. The study involved 155 cases (99 colon cancer, 56 rectal cancer) and 311 controls who were interviewed with regard to pregnancies and their outcomes, lactation, menstrual history, and oral contraceptive (OC) use. Increasing parity was associated with a decreasing risk of colon cancer; para 0, relative risk (RR)=1; para 1-2, RR=0.9, 95% confidence interval (CI)=0.4-1.8; para greater than or equal to 3, RR=0.4, 95% CI=0.2-0.8; later age at first live birth (AFLB) was associated with increasing risk (AFLB less than or equal to 21 yr, RR=1; 22-25 yr, RR=2.3, 95% CI=1.0-5.5; greater than or equal to 26 yr, RR=2.7, 95% CI=1.2-6.2). These effects were independent of each other. Parity appeared to exert its predominant effect on risk of cancer of the right colon. OC use was more common among controls than cases (RR=0.5; 95% CI=0.3-1.2 for ever vs. never users) and showed a dose-response effect in multiple logistic analysis. The pattern of point-estimate RR for rectal cancer was largely congruent with those for colon cancer but was not significantly different from 1.0.
Prognostic factors for the recurrence of renal cell carcinoma after radical nephrectomy
Authors: C. H. Ohlmann, T. Schneider, S. Wille, U. Engelmann, A. Heidenreich
Journal: Journal of Clinical Oncology (2006)

14629 Background: Recurrence of renal cell carcinoma depends mainly on tumor stage at the time of radical nephrectomy and increases with increasing T-stage. Up to 30% of patients with T1–2 tumors will experience local or distant recurrence. Recommendations for the follow-up include chest x-ray every 6 months for stages T1–4 and abdominal CT-scan for pT3–4 for the first 3 years. The aim of our study was to identify prognostic factors predicting recurrence of RCC in order to individualize follow up strategies. Methods: We retrospectively analyzed the charts of 177 patients with RCC who underwent radical nephrectomy. In 163/177 (92%) of the patients the histology revealed renal cell carcinoma. The median-follow up was 4.5 (1–6) years. The prognostic significance of histology, gender, age, c-reactive protein, hemoglobin, hematuria, gross hematuria, weight loss, flank pain and metastases at the time of surgery for risk of recurrence was calculated by uni- and multivariate analysis. Cancer specific survival (CSS) was analyzed by the Kaplan-Meir method. Results: Logistic regression analysis identified presence of metastases at time of surgery (p ≤ 0.0005), hematuria (p ≤ 0.0005) and flank pain (p = 0.011) as independent prognostic factors for the recurrence of RCC. The risk of recurrent disease is 33.5% with one, 70 to 83% with two and 95.6% with the presence of all 3 markers. 3-year CSS is 69% vs. 82% in symptomatic vs. asymptomatic patients (p = 0.1352), 45% vs. 90% in M1/N1 vs. M0/N0 (p = 0.0001) and 78% vs. 88% in pT3b vs. &lt;pT3b (p = 0.0102). Conclusions: In our study we were able to identify prognostic factors for the recurrence of renal cell carcinoma. Based on this model the follow-up of patients can be individualized according to the risk for recurrence after radical nephrectomy. No significant financial relationships to disclose.
A3 adenosine receptor is highly expressed in hepatocellular carcinoma: A new therapeutic target
Authors: S. Bar Yehuda, S. Stemmer, D. Castel, A. Ohaion, S. Cohn, F. Barer, A. Zabuti, P. Fishman
Journal: Journal of Clinical Oncology (2006)

13164 Background: The A 3 adenosine receptor (A 3 AR) belongs to the family of the Gi-protein associated receptors and is highly expressed in various solid tumor tissues. The high receptor expression is reflected also in the peripheral blood mononuclear cells (PBMNC) of the cancer patients. Synthetic agonists to A 3 AR such as IB-MECA and Cl-IB-MECA (CF101 and CF102, respectively) suppress the development of melanoma, colon and prostate carcinoma in vitro and in vivo. The molecular mechanism involves de-regulation of the Wnt and the NF-kB signal transduction pathways. In this study we looked at A 3 AR expression in tumor and PBMNC of hepatocellular carcinoma (HCC) patients. In addition, receptor status model and the effect of CF102 on tumor development were examined in an HCC rat. Methods: A 3 AR mRNA expression level was examined in paraffin embedded slides derived from human HCC samples. A 3 AR protein expression was evaluated in human PBMNC by Western blot (WB) analysis. Rat HCC was established by inoculating N1S1 cells to the liver. Oral treatment with CF102, administered BID, was initiated 24h after tumor inoculation. A 3 AR and key growth regulatory proteins expression level in tumor lesions and PBMNC was tested by WB analysis. Results: A 3 AR was found to be highly expressed in the human HCC tumor tissue and the PBMNC compared to normal adjacent and PBMNC from healthy subjects, respectively. Similar data were found in tumor and PBMNC derived from N1S1 hepatoma bearing rats. In tumor lesions from CF102 treated animals, down-regulation of PKB/Akt, IKK, NF-κB and TNF-α, members of the NF-kB pathway was noted. In addition de-regulation of the Wnt pathway was observed by up-regulation of GSK-3β and down-regulation of β-catenin, Lef/Tcf and c-Myc, resulting in tumor growth inhibition. Conclusion: CF102, a small orally bioavailable molecule, binds to the A 3 AR which is highly expressed on tumor cells and via the de-regulation of the NF-kB and Wnt pathway induces inhibition of HCC growth. No significant financial relationships to disclose.
<i>DPYD</i>Genotyping to Predict Adverse Events Following Treatment With Fluorouracil-Based Adjuvant Chemotherapy in Patients With Stage III Colon Cancer
Authors: Valérie Boige, Marc Vincent, Philippe Alexandre, Sabine Tejpar, Stefania Landolfi, Karine Le Malicot, Richard Greil, Pieter Jan Cuyle, Mette Yilmaz, Roger Faroux, Axel Matzdorff, Ramon Salazar, Côme Lepage, Julien Taieb, Pierre Laurent-Puig
Journal: JAMA Oncology (2016)

Previous pharmacogenetic studies have shown the prognostic impact of several rare dihydropyrimidine dehydrogenase gene (DPYD) variants on fluorouracil-related adverse events (fluorouracil AEs). However, conflicting results highlight the need for prospective validation in large, homogeneous patient populations uniformly treated with current standard combination therapies used in colon cancer (CC).To determine the impact of DPYD variants on fluorouracil AEs in patients with stage III CC treated with a fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) regimen.Pharmacogenetic substudy of 1545 patients who participated from December 2005 to November 2009 in the European Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 randomized phase 3 clinical trial.Patients with resected stage III CC were randomized to receive standard adjuvant FOLFOX4 alone or FOLFOX4 combined with cetuximab for 6 months.Patients were genotyped on 25 DPYD variants. We tested the individual associations between each DPYD variant and grade 3 or greater fluorouracil AEs.A total of 1545 patients (57.6% male; median [range] age, 60 [19-75] years) were included in the analysis. The incidence of grade 3 or greater fluorouracil AEs in D949V and V732I (DPYD*6) carriers was 18 in 21 (85.7%) and 121 in 199 (60.8%), respectively. After adjusting for multiple variables, statistically significant associations were identified between grade 3 or greater fluorouracil AEs and both D949V (odds ratio [OR], 6.3 [95% CI, 2.0-27.0]; P < .001) and V732I variants (OR, 1.7 [95% CI, 1.3-2.4]; P < .001). Grade 3 or greater overall hematologic adverse events were associated with V732I (OR, 1.9 [95% CI, 1.4-2.6]) and D949V (OR, 5.2 [95% CI, 2.0-16.0]), and V732I was associated with grade 3 or greater neutropenia (OR, 1.8 [95% CI, 1.3-2.4]). The association of V732I with the occurrence of grade 3 or greater fluorouracil AEs and overall hematologic adverse events was validated in an independent cohort of 339 patients with metastatic colorectal cancer receiving FOLFOX4 in the Fédération Francophone de Cancérologie Digestive 2000-05 phase 3 trial.In this large phase 3 study, statistically significant associations were found between DPYD variants (D949V and V732I) and increased incidence of grade 3 or greater fluorouracil AEs in patients treated with adjuvant fluorouracil-based combination chemotherapy. Further studies are warranted to confirm and quantitate these associations.eudract Identifier 2005-003463-23.