tbuckley/cabot-search huggingface dataset:
Benefits of a free lunch: Final results of a randomized controlled trial evaluating a free lunch-continuous quality improvement intervention for colorectal cancer (CRC) screening in the Veterans Administration (VA) health care system
Authors: E. F. Powell, M. R. Ferreira, N. C. Dolan, M. L. Fitzgibbon, T. C. Davis, D. Liu, A. W. Rademaker, M. S. Wolf, C. L. Bennett
Journal: Journal of Clinical Oncology (2005)

3622 Background: CRC is the third most common cancer in the US and the second most common in the VA. Although CRC screening is recommended for persons ≥ 50 years, screening rates are low -accounting for the lowest of 17 routinely evaluated VA performance measures. A health care provider-directed intervention for CRC screening conducted during a free lunch period at a VA Medical Center was evaluated. Methods: Veterans > 49 years who attended general medicine clinics, at average risk for CRC and noncompliant with CRC screening were included in an intervention (firm A) versus control (firm B) randomized study. The Rapid Estimate of Adult Literacy in Medicine (REALM) was administered to a subset of patients. Providers in firm A attended lunchtime quarterly feedback sessions that provided information on provider and firm specific CRC rates for screening recommendation and performance. CRC recommendation and screening rates were compared for firms A and B. Results: Veterans (1015 in firm A and 963 in firm B) and providers (60 in firm A and 53 in firm B) participated in the study. CRC screening recommendation and performance rates were higher for patients in firm A compared to firm B (76% vs 69%, p=.02 and 41% vs 32%, p=.003, respectively). Among providers in firm A, those who attended feedback lunch sessions recommended CRC screening more often than providers in firm A who attended no sessions (64% vs 54% of patient visits, p<.01) and their patients were more likely to undergo CRC screening (42% vs 29%, p< .05). Among 392 Veterans whose literacy skills were evaluated, 36% had skills <9th grade. Veterans with lower literacy skills in firm A were more likely than Veterans with lower literacy skills in firm B to undergo CRC screening (56% vs 30%, p=.002). Conclusions: CRC screening is an underutilized cancer prevention tool in the VA health care system. A provider-directed intervention conducted in conjunction with a free lunch and which includes feedback about CRC screening rates among Veterans, especially those with limited literacy skills, may result in improved CRC screening rates in the VA health care system. No significant financial relationships to disclose.
The association between body mass index and baseline clinical stage of esophageal carcinoma.
Authors: Y. Hayashi, A. M. Correa, W. L. Hofstetter, A. A. Vaporciyan, D. C. Rice, G. L. Walsh, R. J. Mehran, A. Suzuki, J. H. Lee, M. S. Bhutani, S. H. Lin, J. Welsh, D. Maru, S. Swisher, J. A. Ajani
Journal: Journal of Clinical Oncology (2011)

4090 Background: High body mass index (H-BMI; ≥25 kg/m2) is common in US adults. We previously reported that H-BMI and low clinical stage were associated in a small cohort of esophageal carcinoma patients treated with surgery only. We present data in a larger cohort of esophageal carcinoma patients to validate this relationship and study surgical complications. Methods: From a prospectively maintained database, we analyzed 925 esophageal carcinoma patients who had surgery with or without adjunctive therapy. Results: Among 925 patients, 69% had H-BMI and 31% had normal BMI (<25 kg/m2; N-BMI). Median overall survival (MS) of all patients was 45.20 months. MS of N-BMI patients was 36.66 months compared to 53.20 months for H-BMI patients (p=0.005). H-BMI was associated with male gender (p≤0.001), lower esophageal location (p≤0.001), adenocarcinoma (p≤0.001), lower baseline T-stage (p=0.002), lower clinical stage (p=0.003), coronary artery disease (p=0.036), diabetes (p≤0.001), and postoperative wound infection (p=0.025). N-BMI was associated with weight loss (p≤0.001), smoking history (p=0.014), and baseline nodal positivity (p=0.019). In multivariate analysis, older age (p≤0.001), squamous histology (p=0.002), smoking history (p=0.040), weight loss (p=0.002), higher clinical stage (p≤0.001), number of positive post-operative nodes (p=0.005), higher pathological stage (p≤0.001), and American Society of Anesthesia scores 3/4 (p≤0.001) were independent prognosticators for poor overall survival. Conclusions: Our data shows an association between H-BMI and early baseline clinical stage of esophageal carcinoma. The better MS in patients with H-BMI is likely attributable to this association.
Prognostic significance of HER2 expression and associated clinical characteristics in esophageal adenocarcinoma.
Authors: Ellie Chan, Ahmad Alkhasawneh, Lizette Vila Duckworth, Tania Zuluaga Toro, Wei Hou, Hui Yan, Steven J. Hughes, Thomas J. George
Journal: Journal of Clinical Oncology (2013)

114 Background: The incidence of adenocarcinoma of the esophagus (EA) and gastroesophageal junction (GEJ) is on the rise. Her2Neu (HER2) is overexpressed in 20-25% of gastric cancers and is associated with poor prognosis. However, the prognostic significance of HER2 in EA/GEJ is less clear. Methods: This retrospective analysis included all sequential patients (pts) with EA or GEJ who underwent primary resection at the University of Florida from 2001 to 2011without neoadjuvant therapy or HER2 inhibition. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on paraffin embedded tumor specimens with HER2 expression scored as negative (-) (0 or 1+), indeterminate (2+) or positive (+) (3+). Results: 56 pts were eligible for analysis (45 M/11 F) with median age 67 years (37-83). Mean BMI was 29.6±6.6 and 43 pts (92%) had underlying Barrett’s esophagus. Most tumors (60%) were stage I (T1N0). Overall testing revealed tumors to be HER2 + (38%), indeterminate (21%) or - (41%). 50% of Stage I, 18% of stage IIA, 33% of stage IIB, and 14% of stage III tumors were HER2 + (p=0.035 for stage I compared to other stages). Underlying Barrett’s esophagus was associated with HER2 + (60 vs. 0%; p=0.045). The median follow up of the entire cohort was 2.9 years. Overall survival (OS) at 3 years was 80% for stage I, 50% for stage IA, 40% for stage IIB and 50% for stage III (p= 0.153). 3 year OS for HER2+ pts was 64% vs. 70% for HER2- (p=0.63). Univariate analysis did not show significant correlation among tobacco use, BMI, disease progression, survival and HER2 expression. Conclusions: This data suggests that HER2 overexpression is more frequent in early stage disease with underlying Barrett’s esophagus. Our data do not support HER2 as a prognostic factor in EA/GEJ. The relationship of HER2 overexpression in the development of early stage GEJ, particularly in the setting of Barrett’s, is of clinical interest. Further investigation is warranted.
Impact of DNA mismatch repair deficiency on relapse rate in early-stage, sporadic colorectal cancer.
Authors: Veronika Buxhofer-Ausch, Heike Bauer, Marina Mollik, Angelika Reiner-Concin, Guenther Nirnberger, Christian Sebesta, Stephan Kriwanek, Robert Zeillinger, Christoph A. Ausch
Journal: Journal of Clinical Oncology (2013)

415 Background: 15-20% of sporadic colorectal cancers (CRC) are characterized by DNA mismatch repair (MMR) deficiency resulting in the phenomenon of microsatellite instability (MSI). There is evidence that CRC with MSI have a significant better prognosis compared to those with intact MMR. We investigated MMR gene expression in patients (pat.) with CRC and correlated it with early relapse rate. Methods: The study relates to 146 pat. with primary CRC UICC stage 0-II who underwent surgical resection at the Donauspital in Vienna and had a complete follow up of at least 60 months. Expression of the MMR genes MLH1, PMS2, MSH2, MSH6 was detected by immunohistochemical staining. Expression of MMR genes was correlated with pat. and disease characteristics as well as relapse frequency within the first 5 years after diagnosis. Chi-squared test was used to compare the distribution of the given variables between MMR gene proficient and deficient pat. Results: Mean age of the total group was 66.14 years, 45.2% were females and 54.8 males. Localization of the tumor was the colon in 69.2% and the rectum in 30.8% of pat., respectively. 33.6% of diseases were classified as UICC stage 0-I, and 66.4% as UICC stage II. 37/ 146 pat. experienced relapse, mean duration to relapse was 2.17 years. 13.7% of all pat. displayed a MMR deficient state. All MMR deficiencies occurred in the colon, none in rectum tumors. MLH1 was always associated with PMS2 deficiency and occurred in 9.6% of pat. There was a significant difference in sex distribution between the proficient and deficient group with 71.4% females with MLH1/PMS2 deficiency (p= 0.038). MSH2 deficiency was detected in 1 pat. only. MSH6 deficiency occurred in 5.5% of pat., none of the variables was significantly different distributed between the proficient and deficient group. None of the MMR deficiencies correlated with relapse rate. Conclusions: Our data suggest that the supposed better prognosis of MMR deficient compared to proficient pat. might not be explained by a different relapse rate within 5 years from diagnosis. Larger and prospective trials are warranted to elucidate plausible explanations for the proposed survival benefit of a MMR deficient state.
HMGB1-driven Feedforward Hepatocyte Necroptosis Circuit in Lethal Acetaminophen-induced liver injury
Authors: Charlotte Minsart, Claire Liefferinckx, Sandrine Rorive, Arnaud Lemmers, Eric Quertinmont, Eric Trepo, Isabelle Salmon, Jacques Devière, Christophe Moreno, Isabelle I.A. Leclercq, Richard Moreau, Thierry Gustot
Journal: Hepatology (2015)
EGFR tyrosine kinase inhibitor in advanced non-small cell lung cancer with wild-type EGFR.
Authors: Z. Wang, Y. L. Wu, J. Yang, B. Wang, Y. Huang, Q. Zhou, C. Xu
Journal: Journal of Clinical Oncology (2011)

e18072 Background: EGFR mutation is a predictor for response to EGFR-TKI in non-small cell lung cancer (NSCLC). In second-line setting, EGFR mutation is not the determinant for the selection of TKI. Now we discuss the efficacy of TKI in NSCLC with wild-type EGFR. Methods: All lung cancer patients treated in our cancer center between April 2005 and February 2009 were screened. Eligiblity criteria included advanced stage (stage IIIB or stage IV) or recurrent NSCLC, wild-typed EGFR and KRAS and administering gefitinib or erlotinib. Cutoff date of follow-up was the end of October 2009. Results: Fifty-one NSCLC patients (median age 61 years, range 32-85 years) in stage IV were enrolled, including male, 38; female, 13; adenocarcinoma, 36; squamous cell carcinoma, 8; large cell carcinoma, 4; adnosquamous cell carcinoma, 2; carcinoid carcinoma, 1; taking gefitinib, 17; taking erlotinib, 34. And response was PR, 2,3.9% (95%CI 0 - 9.3%); SD, 30, 58.8% (95%CI 45.3%-72.3%); PD, 19, 37.3%(95%CI 24.0%- 50.5%). Disease control rate (PR+SD) was 62.8% (95%CI 49.5%-76.0%). Overall survival was 13.4 weeks (95%CI 4.1%-22.8%). The patients were categorized based on variables of gender, performance status (PS), smoking status, prior chemotherapy, brain metastasis, pathology, rash, response and different TKI. Patients with poor PS, brain metastasis prior to TKI and mild skin rashes tended to have lower disease control rate. Univariate analysis was used to compare overall survival within each group. Three variables, i.e. PS, response and different TKI had significant influence on the overall survival. Multivariate regression analysis of overall survival confirmed that, at alpha=0.05 level, three variables, which were PS (0-1 vs 3-4, HR, 2.51, 95%CI 1.11-5.68), response (PR+SD vs PD, HR, 4.61, 95%CI 1.97-10.77) and different TKI (gefitinib vs erlotinib, HR, 2.87, 95%CI 1.31-6.29), significantly impacted the overall survival. Conclusions: For advanced NSCLC with wild-typed EGFR, the response to TKI might was influenced by PS, brain metastasis and different selection of TKI. And the above three variables probably have impact on the overall survival. However, because the research is retrospective, the selection bias may exists.
Local control of lung tumors by percutaneous fluoroscopic computer tomography guided cryoablation
Authors: M. Kawamura, Y. Izumi, N. Tsukada, H. Yashiro, S. Nakatsuka, K. Nakano, S. Kuribayashi, K. Kobayashi
Journal: Journal of Clinical Oncology (2005)

7186 Background: Cryoablation is reestablishing itself as a potential tool in multi-modality treatment against cancer in organs such as liver, kidney, prostate, and uterus. We found only one clinical report of cryoablation against lung tumors, performed through a thoracotomy (Xiang J et al, 1995). Percutaneous cryoablation of lung tumors with the help of recent high resolution fluoroscopic computed tomography (FCT), offers potential local tumor control in patients with prohibitive surgical risks. In the present study, we evaluated local control using FCT guided cryoablation in lung tumors less than 3 cm in diameter. Methods: Primary or metastatic lung tumors less than 3 cm in diameter which were not candidates for surgical resection were included in this study. These tumors were treated locally with curative intent by cryoablation, and followed up for 6 months or more. To evaluate local control, dynamic CT scan was taken every 3 months after cryoablation. A single cryoprobe was inserted into the center of the tumor percutaneously with FCT guidance under local anesthesia. Freeze-thaw cycles were repeated 3 times. This study was approved by the School of Medicine Keio University institutional review board. Written consent was obtained from all patients. Results: 61 tumors were cryoablated in 32 cases. Age 36–79 (58), 1 was primary lung cancer, and 31 were lung metastases. Up to 5 tumors were treated in one session. Local recurrence was experienced in 5 tumors(8.2%). Additional cryoablation was performed against 4 of these tumors successfully, and follow up is being continued. Further treatment was not possible in 1 tumor due to psychosis. Pneumothorax requiring chest tube drainage occurred in 3 procedures. Phrenic nerve paralysis occurred in 1, and segmental atelectasis occurred in 1 procedure with a centrally located tumor. Conclusions: The present study suggests that percutaneous FCT guided cryoablation against lung tumors is feasible. Local control for lung tumors within 3cm in diameter was 92% in this set of patients. Locally recurrent tumors could be treated by additional cryoablation. In order to further improve local control, we are currently inserting multiple probes adjacent to the tumor, so as to encase the tumor. No significant financial relationships to disclose.
Effect of the ultraconserved noncoding RNA uc.338 on cellular growth of hepatocarcinoma.
Authors: C. Braconi, T. Kogure, N. Valeri, P. Gasparini, N. Huang, G. Nuovo, L. Terracciano, C. M. Croce, T. Patel
Journal: Journal of Clinical Oncology (2011)

202 Background: The role of non-protein coding (nc)RNAs in cancer is unknown but emerging evidence suggests that deregulated expression of ncRNA may contribute to cancer pathogenesis. We sought to examine the role of ultraconserved ncRNA (ucRNA) that are 100% conserved across the human, rat and mouse genomes in hepatocellular cancers (HCC). Methods: Whole genome ucRNA expression profiling was performed using a custom microarray, and verified by real time PCR in cell lines and by in situ hybridization in a tissue microarray comprising of 221 human HCC, 72 non cirrhotic (NC) and 97 cirrhotic (C) liver tissues. ucRNA expression was manipulated with siRNA or plasmid-over-expressing ucRNA, and the effects on anchorage-dependent and independent growth, and cell cycle assessed using cell viability, soft agar assays and flow cytometry. Gene ontology analysis was performed by evaluating uc338-dependent changes on mRNA expression using Affymetrix chips. Results: 56 ucRNAs were aberrantly expressed with 33 increased and 23 decreased in HepG2 cells compared to non-malignant hepatocytes. The greatest change was observed with uc.338 (6.9-fold increase). uc.338 expression was significantly increased in several HCC cell lines. uc.338 expression was detected in 170 cases (77%) of HCC, with 62% of these showing a moderate to strong expression. Compared to non- malignant adjacent tissue, uc.338 expression was increased in 97/156 of HCC. The mean % of cells expressing uc.338 was 4% in NC liver, 15% in C and 24% in HCC. Inhibition of uc.338 reduced anchorage dependent and independent growth, and cell cycle progression in both human and murine malignant hepatocytes. Gene annotation enrichment analysis of mRNAs that were altered by inhibition of uc.338 expression identified the top over-represented GenMAPP pathways as: cell cycle, mRNA processing, RNA transcription, G1 to S cell cycle. Moreover, enforced expression of uc.338 increased cell growth in nonmalignant hepatocytes. Conclusions: These data showing that uc.338 is selectively overexpressed in HCC and promotes cell growth provides new insights into the role of RNA genes in HCC. No significant financial relationships to disclose.
Axitinib second-line therapy for metastatic renal cell carcinoma (mRCC): Five-year (yr) overall survival (OS) data from a phase II trial.
Authors: R. J. Motzer, T. de La Motte Rouge, A. L. Harzstark, M. D. Michaelson, G. Liu, V. Gruenwald, A. Ingrosso, M. A. Tortorici, P. W. Bycott, S. Kim, B. I. Rini
Journal: Journal of Clinical Oncology (2011)

4547 Background: Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1–3. Axitinib in patients (pts) with cytokine-refractory mRCC (Rixe et al, Lancet Oncol 2007:975) showed an objective response rate (ORR) of 44%, median progression-free survival of 13.7 months, and median overall survival (OS) of 29.9 months (N=52). Updated 5-yr OS data is presented. Methods: Between 10/2003 and 4/2004, 52 pts were enrolled. Pts had histologically confirmed mRCC, measurable disease, Eastern Cooperative Oncology Group performance status (PS) of 0/1, and had failed a prior IL-2/interferon regimen. Starting axitinib doses were 5 mg twice daily; samples were obtained for peak/trough axitinib plasma levels. In 2/2007, 24 of 52 enrolled pts were alive (censored), and 11 pts continued to receive long-term axitinib in a second study. The updated OS data were collected through a third study to estimate the 5-yr survival rate of the originally enrolled 52 pts. Death dates or recent known-alive dates were available for 50 pts. Results: Of the 52 pts, 35 died of progressive disease, 5 died of “unknown causes,” 10 were alive, and 2 were lost to follow-up. Median follow-up for OS was 5.9 yrs. The 5-yr survival rate was 20.6% (95% CI, 10.9–32.4%). Treatment-emergent, all-causality grade ≥3 adverse events for the 52 pts included diarrhea (19%), fatigue (19%), hypertension (17%), weight loss (8%), and dehydration, myocardial infarction, and stomatitis (6% each). Hypothyroidism (all grades) was observed in 23%. Comparing the characteristics of the 5-yr survivors (n = 10) vs <5-yr survivors (n = 40), the former had higher ORR (100% vs 30%), longer axitinib therapy duration (median 5.8 yr vs 0.67 yr), and better baseline PS (80% vs 53% with PS 0) but were of similar median age (57 vs 60), gender (80% vs 75% males), and risk factors (50% vs 40% with zero MSKCC factors). The cycle 1 day 1 peak concentrations for the 5-year survivors appeared to have a narrower distribution (range, 23–69 ng/mL) compared with the <5-yr survivors (range, 7–147 ng/mL). Conclusions: Axitinib can produce greater than 5-yr OS in selected pts with mRCC. No new toxicities emerged with long-term axitinib therapy.
E2809: Androgen receptor (AR) modulation by bicalutamide (Bic) and MK-2206 (MK) in men with rising PSA at high-risk of progression after local prostate cancer (PC) treatment.
Authors: Anna C. Ferrari, Yu-Hui Chen, Gary R. Hudes, Michael Anthony Carducci, Emmanuel S. Antonarakis, Noah M. Hahn, Yu-Ning Wong, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2016)

9 Background: Men with PSA recurrence and fast PSA doubling time (PSADT) are at high risk of progression. While castration effectively decreases PSA and delays metastases, it compromises heath and quality of life without clear survival benefit. E2809 tested whether blocking Akt with MK alone or together with the AR using Bic, would be more effective than Bic alone to suppress AR activity without castration. Methods: 108 PSA-recurrent N0 M0, non-castrate PC patients (pts) with PSADT&lt;12 months (mo) and PSA&gt;2ng/mL; were randomized 1:1 to 11, 4-week (wk) treatment (tx) cycles (cy), up to18cy: arms (A) cy1-3, observation, cy 4-11, Bic 50 mg daily; (B) cy1-3 MK 200 mg once wk orally, cy 4-11 MK+Bic. Endpoints: Primary: proportion of pts with PSA &lt;0.2 by cy11 (90% power to detect 45% vs. 20% using 0.1 level one-sided Fisher’s exact test); Secondary, PSA decline: ≥85%; nadir levels before and after Bic. Toxicity (Tox). Results: 54 pts/arm. Baseline characteristics (median (m) or %, A/B): age, 66/67 years; Gl&gt;7 81/81%; &gt;T2b 98/86%; prostatectomy, 81/75%; radiation, 30/31%; previous castration, 43/46%; testosterone, 302/333 ng/dL; PS 0, 94/93%; mPSA 5.1/6.1ng/dL; PSADT&lt;9 mo, 87/81%, &lt;3 mo 24/37%; Tox. Grade(G)/n: G4: A, 0; B, 2 (embolism, hyperglycemia). G3: A, 1(LFTs); B, 32, 60% (rash 20, hyperglycemia 5, low lymphs, 5; hypertension, 4). At 23.9 mo follow-up, 1 death B. Tx . A: 4 no tx; 14 (26%) started Bic early; 9 (16.7%) stopped &lt;11cy without SAE’s; 41 (76%) completed 11cy, 23 (43%) 18cy. B: 7 (13%) started Bic early; 21 (39%) stopped &lt;11cy due to AE’s in 14 (66%) cases; 32 (59%) completed 11cy, 14 (26%) 18cy. PSA&lt;0.2 at 44wks (cy11): A, 6 (11.1%); B, 8 (14.8%), p=0.39. Among evaluable pts, PSA ≤0.2 occurred only after Bic: A: 10/49 pts (20.4%); B: 16/45 pts (35.6%), p=0.08. Conclusions: Overall, by intent to treat analysis at 44 wks, MK alone had no effect on PSA, nor did it increase response to Bic by any set criteria. High MK discontinuation due to rash before cy11 may have blunted the significance of a higher proportion of evaluable pts on MK+Bic achieving PSA ≤0.2ng/ml compared to Bic alone. Clinical trial information: 01251861.