tbuckley/cabot-search huggingface dataset:
The association of HGF/Cmet overexpression with clinicopathologic factors in hepatocellular carcinoma.
Authors: Laura Williams Goff, Fyza Y Shaikh, Liping Du, Mary Kay Washington, Safia N Salaria
Journal: Journal of Clinical Oncology (2015)

297 Background: The Cmet receptor tyrosine kinase is overexpressed in 20-50% of hepatocellular cancers (HCC) and has been associated with aggressive features. Little is known about the clinical characteristics of patients whose tumors overexpress Cmet. We examined Cmet expression levels on a series of 80 HCC samples to evaluate for an association between overexpression and clinicopathologic features. Methods: Samples from 80 patients with HCC were assessed with immunohistochemistry (IHC) analysis for hepatocyte growth factor (HGF) and Cmet. Positive staining was correlated with age, sex, race, HCC risk factors, tumor grade, stage, metastatic sites and survival. Results: Hepatitis B virus (HBV) patients were more likely to have Cmet positive tumors than those with other risk factors for HCC such as hepatitis C or alcohol. Higher tumor grade was associated with Cmet positivity. No evidence of association between Cmet positivity and survival was seen although HGF positivity tended to associate with a trend toward decreased survival. Conclusions: Cmet pathway overexpression in HCC is associated with distinct clinical and pathologic features. [Table: see text]
Clinical application of electrogastrography (EGG) in stomach cancer patients with distal gastrectomy.
Authors: Yong Ho Kim, Sung Il Choi, Jae Wook Song
Journal: Journal of Clinical Oncology (2013)

59 Background: Electrogastrography (EGG) is a method of measuring action potentials of the stomach. The purposes of this study were to investigate postoperative changes in the EGG and then evaluated gastric motility and to determine the correlation between EGG and quality of life (QOL) of stomach cancer patients with distal gastrectomy. Methods: This study analyzed 20 cases of stomach cancer patients between May 2010 and Dec. 2010. All patients were measured EGG and QOL at 1, 12, and 24 weeks after the operation. The EORTC quality of life questionnaire QOL-C30 version 3.0 and QOL-STO22 were used in this study to assess QOL of gastric cancer patients. Results: Fasting and postprandial mean dominant frequency at 1 week after the operation were 2.7 and 2.6 cycles per minute (cpm), and 2.9 and 2.7 cpm at 12 weeks. Fasting and postprandial dominant power at 1 week were 36.5 and 36.4 dB, and 36.3 and 40.1 dB at 12 weeks. After postoperative week 12, the mean percentage of normal rhythm in both recordings was not changed, whereas the mean percentage of bradygastria was decreased and tachygastria was increased. Regarding QOL, global health, physical, emotional and social status were improved, but pain, insomnia, diarrhea, and financial status was worsened at 12 weeks. On the STO22, the correlation between the QOL and EGG parameters was not significant (p&gt;0.05). Conclusions: These suggest that EGG is a simple and noninvasive method and may be applicated for evaluating motility and autonomic functions of the remnant stomach after distal gastrectomy.
Phase II study of weekly irinotecan (CPT-11) associated to protracted oral tegafur (TGF) in previously untreated, advanced colorectal cancer (ACRC)
Authors: E. Saigi, E. Batiste-Alentorn, N. Diaz, A. Galan, A. Salud, J. M. Campos, F. Losa, M. Gallen, B. Massuti, D. Asensio
Journal: Journal of Clinical Oncology (2005)

3725 Background: CPT-11 and 5-fluorouracil (5-FU) are active agents in ACRC. Its combination provides an objective response rate approaching 50%. Oral TGF is a 5-FU prodrug which presents a good safety profile. Methods: Patients with previously untreated, histologically confirmed, unresectable ACRC are included if they have measurable disease; adequate bone marrow, liver, and renal functions; PS (ECOG) 0–2; life expectancy >3 months, and written informed consent. Treatment consists of 90-min continuous infusion CPT-11 (80 mg/m2) on days 1, 8, 15 and 22; oral TGF (800 mg/day) and oral Folinic acid (45 mg/day) on days 2–28, in a 36 days cycle. A maximum of 6 cycles are planned. Response evaluation is done every 2 cycles. Results: Until November 2004, 41 patients have been included: 61% males, 39% females. Mean age: 67 years (range 36–76). PS: 0 (50%), 1 (46%), 2 (4%). Tumor location: colon (54%), rectum (19%) and rectum-sigma (27%). 266 infusions have been administered (mean 9.5, range 2–24). 13 patients are assessable for response: 1 (7.7%) complete response, 6 (46.1%) partial responses, 2 (15.4%) stable disease and 4 (30.8%) disease progression. 26 patients are assessable for toxicity. Grade 3–4 adverse events: diarrhea 9 (35%), nausea/vomiting 6 (23%), asthenia 5 (19%), neutropenia 4 (15%), anorexia 2 (8%), infection 2 (8%) and transaminase increase 2 (8%). Conclusions: Our results seem to confirm that this schedule is active in untreated ACRC patients, with predictable and manageable toxicity. Severe toxicity has been seen in a few cases, being diarrhea the most frequent. This schedule seems an option in the clinical setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Prasfarma/Almirall Prasfarma/Almirall
Prospective Phase II Pilot Study of Rabbit Antithymocyte Globulin (ATG, Thymoglobuline) with Ciclosporin for Patients with Acquired Aplastic Anemia and Matched Pair Analysis with Patients Treated with Horse ATG (Lymphoglobuline) and Ciclosporin: A Study From the EBMT Severe Aplastic Anemia Working Party (RATGAA07)
Authors: Judith C Marsh, Gérard Socié, Hubert Schrezenmeier, Andre Tichelli, Antonio M. Risitano, Jakob R. Passweg, Carlo Dufour, Mahmoud Aljurf, Hazza A Al-Zahrani, Rosi Oneto, Philip Sedgwick, Barrois Alain, Shahram Kordasti, Modupe Elebute, Ghulam J. Mufti, Andrea Bacigalupo
Journal: Blood (2011)
Results of Project LEAD (Leading the Way in Exercise and Diet) - A trial testing an intervention of telephone-counseling and mailed materials in improving physical functioning among older breast and prostate cancer survivors
Authors: W. Demark-Wahnefried, M. C. Morey, E. C. Clipp, D. C. Snyder, R. Sloane, C. F. Pieper, H. J. Cohen
Journal: Journal of Clinical Oncology (2005)

8138 Background: Declines in physical function occur with cancer, and threaten ability to maintain independence. Functional decline is a serious problem among older cancer survivors, since functional status already may be compromised. Adherence to healthy lifestyle behaviors may be one way that older cancer survivors may improve physical functioning. Methods: An intervention development study of the Duke Claude D. Pepper Ctr was undertaken among breast and prostate cancer survivors (age 65+) to determine if a 6M diet-exercise intervention of tailored mailed materials and telephone counseling would significantly improve physical activity (CHAMPS) and diet quality (DQI-R), and ultimately lead to improved physical function (SF-36) when compared to an attention control intervention on general health topics with identical delivery. Durability of effects were assessed at 12M follow-up. Power calculations, based on significance for change by intervention status and wave using a conservative approach of repeated measures mixed models, indicated a need for 420 subjects. Results: Drop-out rates were were lower than estimates (8% in both arms), however due to stringent inclusion criteria on function, we only accrued 182 subjects. Preliminary analyses on baseline to 6M mean change scores for the experimental vs. control arms were as follows: physical function [+3.14 vs. -0.47; p=.19]; frequency of physical activity [+.97 vs. -1.32; p=.08]; and diet quality [+2.96 vs.-2.95; p=.02]. At 12M, the intervention arm experienced change scores (relative to those at 6M) of -3.67 for physical function (p=.89), -1.25 for physical activity (p=.47), and -2.29 for diet quality (p=.89), indicating non-significant recidivism. Conclusions: This distance medicine based intervention improved diet and physical activity behaviors among elderly cancer survivors and positively reoriented physical function, however given inadequate power, these changes were only statistically significant with respect to diet quality. These findings hold promise of potential benefit and suggest a need for further study. No significant financial relationships to disclose.
Clinical and molecular characterization of refractory <i>BRAF</i> mutant metastatic colorectal carcinoma (mCRC): Vall d’Hebron Institute of Oncology phase I program cohort.
Authors: Enrique Sanz-Garcia, Elena Elez, Guillem Argiles, Javier Hernandez-Losa, Ana Vivancos, Debora Moreno, Teresa Macarulla, Jaume Capdevila, Maria Alsina, Tamara Sauri, Cinta Hierro, Analia Azaro, Cristina Cruz Zambrano, Marta Vilaro, Jose Jimenez, Stefania Landolfi, Paolo Nuciforo, Santiago Ramon y Cajal, Jordi Rodon, Josep Tabernero
Journal: Journal of Clinical Oncology (2015)

587 Background: BRAF mutation (mt) occurs in 5-8% of mCRC and its role as a negative prognostic factor is well known. The up-front detection of BRAF mt is not standardized beyond the boundaries of research. However, since novel emerging specific therapies are increasingly available in clinical trials, the prior determination of this mutation is now warranted. Methods: From 07/2010 to 01/2014, 581 patients (pts) with advanced refractory mCRCunderwent genetic tumor profiling as part of the VHIO Phase I Trial Molecular Prescreening Program. BRAF mt was determined by Sanger sequencing or multiplex PCR and mass detection (MassARRAY, Sequenom) of 268 frequent hotspots in 25 oncogenes including, KRAS, NRAS, and PIK3CA. PTEN status was also assessed by immunohistochemistry. Results: 581 samples were analyzed detecting BRAF mt in 56 (9.6%). In the BRAF mt population, median age was 61 years (45-80) and 54% had right-sided CRC. Metastatic sites were found at: liver 61%; peritoneum 52%; lung 39%. Median number of standard treatment was 4 (0-8) including cetuximab and/or panitumumab in 73%. BRAF V600E mutation was detected in 53 samples whereas V600K, D594V and D594G were seen in one sample each. PTEN was analyzed in 44.6% of samples resulting in low expression (H-score &lt;50) in 56%. Other co-existing mutations were PIK3KCA H1047R, PIK3CA E545K, NRAS G12V, GNAS R201C and EGFR S768I. 22 pts were enrolled at least in one phase I trial with drugs targeting either BRAF alone (n=12) or combined with anti-EGFR (n=5), MEK (n=2), PI3K (n=1) inhibitors or double MEK/PI3K inhibition (n=2). Partial responses (PR) were seen in 3 pts (2 with BRAF inhibitor and EGFR inhibitor and 1 with BRAF inhibitor as a single agent). Conclusions: BRAF mt mCRC pts in our institution have a similar pattern to other series reported. Notably, PTEN low expression was present in almost half of the samples analyzed and other co-existent mutations in the ERK and PI3K pathways were detected. This observation, coupled with the clinical outcome observed with single agent BRAF inhibition in this population, suggests that these patients may derive greater benefit from dual BRAF and either EGFR, MEK or PI3K inhibition.
Does prostate inflammation on a negative prostate biopsy vary by race? Results from the REDUCE study.
Authors: Adriana Vidal, Lauren Howard, Daniel Moreira, Ramiro Castro, Gerald L. Andriole, Emanuela Taioli, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2016)

116 Background: Prostateinflammation is linked with prostate cancer. However, whether prostate inflammation varies by race is unclear. Methods: We analyzed baseline acute and chronic prostate inflammation by race in REDUCE. REDUCE was a 4-year, multicenter, placebo-controlled study where all men received a single, negative prostate biopsy within 6 months prior to enrollment. Among 8,046 men who met the inclusion criteria, we included those with data on baseline biopsy prostate inflammation, acute/chronic or none, determined by central pathology. Logistic regression was used to compare prostate inflammation by race, and models were adjusted for demographic and clinical features. Results: Of the 8,046 men, 7,326 were white (91.1%), 184 (2.3%) black, 132 (1.6%) Asian, 323 (4.0%) Hispanic, and 81(1%) unknown. Seventy eight percent of men had chronic and 15% had acute prostate inflammation. Men with chronic inflammation were older (p&lt;0.001), while men with acute inflammation were younger (p&lt;0.001) compared to men with none prostate inflammation. Both acute and chronic inflammation was associated with lower PSA (all p≤0.0001), smaller prostate volume (all p≤0.0001) and geographic region (all p≤0.006). On crude analysis, compared to whites, Asian men were two times more likely to have acute prostate inflammation (OR=1.92, 95%CI: 1.29-2.85, p=0.001), whereas the associations with Hispanic and black race were not significant (all p≥0.39). However, on multivariable analysis, black men were 36% less likely to have acute prostate inflammation (OR=0.64, 95%CI: 0.41-0.99, p=0.04), whereas the likelihood of having acute prostate inflammation remained high in Asians (OR=1.85, 95%CI: 1.25-2.85, p=0.004). No associations by race were found with chronic prostate inflammation. Conclusions: Given that at the population level, black race is a high risk factor for PC and Asian men have lower risk of PC, these data indicate that the presence of acute inflammation in a negative prostate biopsy could be an indication of future PC risk. Further studies to confirm these findings are needed. Clinical trial information: NCT00056407.
Can PSA density and free-to-total PSA ratio improve our ability to predict prostate cancer on biopsy? Results from a prospective, multi-institutional, and contemporary cohort.
Authors: Samarpit Rai, Nachiketh Soodana-Prakash, Nicola Pavan, Bruno Nahar, Amil Patel, Yan Dong, Ramgopal Satyanarayana, Dipen Parekh, Sanoj Punnen
Journal: Journal of Clinical Oncology (2016)

57 Background: Several studies have reported an increased value of PSA density (PSAD) and free−to−total PSA ratio (f/t PSA) over PSA alone in predicting prostate cancer (PCa). Despite this, they remain underutilized. This study analyzed a cohort of men referred for prostate biopsy (PB) to determine if PSAD and f/t PSA enhanced the prediction of any PCa and/or significant PCa (Gleason score ≥ 7) compared to PSA. Methods: 1,370 prospectively enrolled patients were referred for a PB across 26 urological centers. A phlebotomy was performed immediately prior to PB for PSA and f/t PSA measurement. PSAD was calculated using prostate volume obtained during the trans−rectal ultrasound (TRUS) guided PB. The area under the receiver operating characteristic curve (AUC) was used to assess the added discriminative value of PSAD and f/t PSA when added to a base model consisting of PSA, age, prior biopsy status, and DRE for the prediction of any and significant PCa. Results: Of the 1,290 men in the final cohort, 301 (23%) and 284 (22%) men were diagnosed with low−grade (Gleason score = 6) and significant PCa respectively. The median PSAD values in men with no PCa, low−grade PCa, and significant PCa were 0.09, 0.11, and 0.17 ng/mL/cc, respectively (P &lt; 0.0001). The median f/t PSA in men with no PCa, low−grade PCa, and significant PCa was 0.21, 0.17, and 0.12 respectively (P &lt; 0.0001). The AUC for a model incorporating PSAD showed superior predictive value compared to the base model for diagnosing any PCa (AUC 0.76 versus 0.70, P &lt; 0.0001) and significant PCa (AUC 0.82 versus 0.77, P &lt; 0.0001). Similarly, a model with f/t PSA showed superior predictive value compared to the base model for diagnosing any PCa (AUC 0.73 vs 0.70, P &lt; 0.0001) and significant PCa (AUC 0.82 versus 0.77, P &lt; 0.0001). While PSAD showed superior predictive value over f/t PSA for predicting any PCa (AUC 0.76 versus 0.73, P = 0.0062), there was no difference in their discrimination of significant PCa. Conclusions: PSAD and f/t PSA add substantial predictive power to the diagnostic armamentarium for any and significant PCa. Their calculation may reduce the number of unnecessary biopsies being performed for PCa detection.
The effect of bevacizumab on tumor response and primary resistance to systematic therapy.
Authors: V. Ranpura, X. Su, S. Wu
Journal: Journal of Clinical Oncology (2011)

399 Background: The angiogenesis inhibitor bevacizumab in combination with chemotherapeutic agents or cytokines are used extensively in the treatment of metastatic tumors including renal cell carcinoma (RCC). Risk factors for the treatment response are not clear. We performed a systemic review and meta-analysis of published randomized controlled trials (RCT) to determine the effect of bevacizumab on tumor response to systematic therapy. Methods: We searched databases from Pubmed, Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences up to May 2010 to identify relevant studies. Tumor response was defined according to RECIST criteria. Eligible studies include RCTs in which bevacizumab in combination with systematic therapy was compared with systematic therapy alone. Relative risk (RR), and 95% confidence intervals (CIs) were calculated using a random-effects or fixed-effects model based on heterogeneity of included studies. Results: A total of 8,972 patients from 16 studies were included for analysis. Overall, bevacizumab significantly increased the response rate with an RR of 1.67 (95% CI: 1.41–1.84). The effect varied significantly with tumor types (p=0.007), with the highest seen in RCC (RR 2.17, 95% CI: 1.71–2.74), and the lowest seen in mesothelioma (RR 1.14, 95% CI: 0.89–1.44). No significant difference was found between bevacizumab at 2.5 and 5 mg/kg/week. Also, bevacizumab significantly reduced the risk of primary resistance to systematic therapy (RR 0.83, 95% CI: 0.70–0.99; p=0.04). The risk reduction varied significantly with tumor types (p=0.02), with the highest reduction seen in RCC (RR 0.76, 95% CI: 0.51–1.14) and colorectal cancer (RR 0.74, 95% CI: 0.51–1.09). Notably, bevacizumab significantly increased the risk of primary resistance to chemotherapy in mesothelioma (RR 1.34, 95% CI: 1.03–1.74). No significant correlation was found between the effect on response rates and progression-free survival (p=0.62) or overall survival (p=0.63). Conclusions: Bevacizumab has a significant effect on tumor response and primary resistance to systematic therapy, particularly in RCC. [Table: see text]
Molecular and clinical characterization of 1,577 primary prostate cancer tumors to reveal novel clinical and biological insights into its subtypes.
Authors: Felix Yi-Chung Feng, Scott Tomlins, Mohammed Alshalalfa, Nicholas Erho, Kasra Yousefi, Shuang Zhao, Robert Benjamin Den, Adam Dicker, Edward M. Schaeffer, Eric A. Klein, Cristina Magi-Galluzzi, R. Jeffrey Karnes, Robert B. Jenkins, Bruce J. Trock, Angelo Demarzo, Elai Davicioni
Journal: Journal of Clinical Oncology (2015)

9 Background: Prostate cancer molecular subtypes based on ETS gene fusions and SPINK1 were originally identified through outlier gene expression profiling analysis. Such molecular subtypes may have utility in disease stratification and clonality assessment, complementing available purely prognostic tests. Hence, we determined the analytical validity of molecular subtyping in a large sample of PCa treated with radical prostatectomy. Methods: We analyzed Affymetrix Human Exon 1.0ST GeneChip expression profiles for 1,577 patients from 8 radical prostatectomy (RP) cohorts. Multi-feature random forest classifiers and outlier analysis were used to define microarray-based molecular subtypes. Results: A random forest (RF) classifier was trained and validated to predict ERG fusion status using a subset with known ERG rearrangement status defined by FISH, achieving &gt;95% sensitivity and specificity in the validation subset. Less frequent rearrangements involving other ETS genes or SPINK1 over-expression were predicted based on gene expression outlier analysis. Across cohorts, 45%, 9% 8% and 38% of PCa were classified as ERG+, ETS+, SPINK+, and Triple Negative, respectively. Global gene expression analysis shows that the four subtypes could be collapsed into three entities (ERG+, ETS+ and SPINK+/Triple Negative) based on expression patterns and clinical characteristics similarity. A series of multivariable analyses further revealed, ERG+ to be associated with lower pre PSA and Gleason scores but more likely to have EPE and occur in patients with European American ancestry compared to the ETS+, SPINK+/Triple Negative tumors (p&lt;0.001). In contrast, patients with ETS+ were more likely to have SVI compared to both ERG+ and SPINK/Triple Negative (p=0.01), while SPINK+/Triple Negative had higher Gleason scores and were more likely to occur in African Americans (p&lt;0.001). Conclusions: The Decipher platform can accurately determine ERG rearrangement status and PCa molecular subtypes. Inclusion of molecular subtyping, such as m-ERG status, may enable additional precision medicine opportunities in prognostic tests
Longitudinal Tracking of MDS Patients Using Next Generation Sequencing Provides a Predictive Measure for Azacitidine Response and AML Progression
Authors: Taehyung Kim, Joon Ho Moon, Yoo Jin Lee, Marc Tyndel, Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Seung Hyun Choi, Chul Won Jung, Jun Ho Jang, Heeje Kim, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Zhaolei Zhang, Dennis Dong Hwan Kim
Journal: Blood (2016)
Final results of a first-in-human phase I trial of PBI-05204, an inhibitor of AKT, FGF-2, NF-Kb, and p70S6K in advanced cancer patients.
Authors: H. A. Henary, R. Kurzrock, G. S. Falchook, A. Naing, S. L. Moulder, J. J. Wheler, A. M. Tsimberidou, J. Durand, P. Yang, M. J. Johansen, R. Newman, R. Khan, U. Patel, D. S. Hong
Journal: Journal of Clinical Oncology (2011)

3023 Background: PBI-05204 (Oleandrin), a cardiac glycoside, inhibits the α-3 subunit Na-K ATPase pump. Relative expression of the α-3 subunit in tumor cells correlates with proliferation. Oleandrin inhibits FGF-2 export, activation of NF-Kβ, phosphorylation of Akt, p70S6K, decreasing mTOR activity. In this first-in-human study, we sought to determine the MTD/recommended phase II dose and to define the pharmacokinetics (PK) and pharmacodynamics (PD) of PBI-05204 in advanced cancer patients (pts). Methods: Trial was a 3+3 phase I design. PBI-05240 was given for 21 of 28 days. Dose was increased by 100% if no related grade 2 adverse event (AE) emerged and increased by 50% if a grade 2 AE occurred. Blood samples were drawn for PK and drug-mediated changes in pAkt, p70S6K, and S6 (mTOR effectors) expression in peripheral blood mononuclear cells (PBMCs) for PD analysis. Results: 46 pts were dosed at 8 dose levels (DL) of PBI-05204 (0.6 to 10.2 mg/day). 2 dose-limiting toxicities occurred at DL 8 (grade 3 proteinuria,fatigue) thus the MTD was DL7. Most common AEs were fatigue (56.1%), abdominal pain (41.5%), constipation (41.5%), nausea (41.5%), and diarrhea (39.0%). Cardiac disorders were reported in 10 pts (24.4%), all grade 1, except for 1 pt with grade 2 SVT. Of the 45 evaluable pts, 7 had stable disease for > 4 months, with bladder, colorectal, fallopian tube, breast, appendecal and pancreatic carcinoma (2 pts). Dose dependent mean peak concentrations as high as 2 ng/mL were achieved. Mean AUC: 5 – 36 μg/L*hr across DLs with a half-life range of 6-14 hrs. Western blot analysis of PBMCs showed markedly reduced phosphorylation of Akt, p70S6K, and S6 in a time dependent manner in 7 pts (1 at DL 2, 3, 1 at DL 5 and 2 at DL 6). Reduction of these effectors was concomitant with higher levels of Na, K-ATPase aƒ{3 subunit expression. In these pts, results of proteomic array analysis showed other oncogenic pathways-NFkB, VEGF and STAT5 were down regulated after 21 days on study. Conclusions: PBI-05204 is well tolerated up to 10.2/mg/day with very little AEs or cardiotoxicity. Initial PD analysis suggesting target effect.