tbuckley/cabot-search huggingface dataset:
A phase I study of temsirolimus as novel therapeutic drug for patients with unresectable hepatocellular carcinoma (HCC).
Authors: Stephen Lam Chan, Frankie Mo, Edwin P. Hui, Jane Koh, CM Chu, Joyce Hui, Leung Li, Herbert H. Loong, Wing Ming Ho, Brigette Ma, Ka Fai To, Simon Yu, Anthony T. C. Chan, Winnie Yeo
Journal: Journal of Clinical Oncology (2013)

e15048 Background: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in hepatocellular carcinoma (HCC). Preliminary studies on mTOR inhibitors such as temsirolimus show promising results but there is limited data on the dose limiting toxicities (DLTs) in chronic liver disease, a co-morbidities commonly occurring in HCC pts. This phase I study aims to determine DLTs and maximum tolerated dose (MTD) of temsirolimus in advanced HCC. Methods: Patient (Pt) eligibilitie criteria include unresectable disease, ECOG &lt;= 2, adequate organ functions. Temsirolimus was given i.v. in 250ml NS over 30 min on day 1, 8, and 15 every 3 weeks; dose levels were: 20 (level I), 25 (level II) and 30 mg (level III). DLTs are defined as grade 4 hematological toxicity or grade 3/4 non-haematological toxicity during cycle 1 (according to NCI CTC v3), or treatment delay &gt;2 weeks. The MTD is defined as the dose below which &gt; 2 of 3 or &gt; 2 of 6 patients experiencing DLT. After determination of the MTD, additional pts to make up to 10 patients were treated at this dose to further define toxicity. The study has been registered in ClinicalTrials.gov (NCT00321594). Results: 19 pts were entered; level I (n=3), level II (n=10), and level III (n=6). 2 of the 6 pts in level 3 developed DLT; 1 developed grade 3 syncope and 1 had treatment delay for &gt;2 weeks due to prolonged neutropenia. In cycle 1, grade 3/4/5 toxicities included: raised ALP 2/0/0, oral mucositis 2/0/0, neutropenia 1/0/0, syncope 1/0/0, dehydration 1/0/0 and dysphagia 1/0/0. A total of 77 cycles were administered; overall grade 3/4/5 toxicities: raised ALT 2/0/0, raised ALP 2/0/0, raised bilirubin 2/0/0, cough 1/0/0, dehydration 1/0/0, dysphagia 1/0/0, dyspnea 1/0/0, abdominal distension 1/0/0, anemia 1/0/0, hemorrhoids 1/0/0, hyperglycemia 1/0/0, hypokalemia 2/0/0, hyponatremia 1/0/0, infection 5/0/0 (1 dental, 2 pulmonary, upper airway 2), oral mucositis 2/0/0, neutropenia 1/0/0, thrombocytopenia 2/0/0, pleural effusion 1/0/0, pneumonitis 1/0/0, syncope 1/0/0. Clinical benefit rate (PR, CR or SD ≥12 weeks) was 36.8% (7 of 19 pts had confirmed SD). Conclusions: At the MTD of 25 mg weekly every 3 weeks, temsirolimus is well tolerated with no DLTs. Clinical trial information: NCT00321594.
Statin use and all-cancer mortality: Prospective results from the Women’s Health Initiative.
Authors: Ange Wang, Aaron K Aragaki, Jean Y. Tang, Allison W. Kurian, JoAnn E Manson, Rowan T. Chlebowski, Michael S. Simon, Pinkal M. Desai, Sylvia Wassertheil-Smoller, Simin Liu, Stephen Kritchevsky, Heather A. Wakelee, Marcia L. Stefanick
Journal: Journal of Clinical Oncology (2015)

1506 Background: Statin medications are widely used for lipid lowering and heart disease prevention. Retrospective studies and basic scientific evidence have suggested that statins may also reduce cancer mortality. Data fromthe Women’s Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT) were used to investigate the association between statin use and all-cancer mortality in a prospective cohort of postmenopausal women. Methods: The WHI study enrolled women aged 50-79 from 1993-1998 at 40 U.S. clinical centers. Among 146,326 participants with median 14.6 follow-up years, 23,067 incident cancers and 3,152 cancer deaths were observed. Cox proportional hazards models were used to investigate the relationship between statin use (as a time-dependent exposure) and cancer mortality. Analyses were adjusted for age, race/ethnicity, education, smoking, body mass index, physical activity, family history of cancer, current health care provider, hormone use, age at menarche, solar irradiance, and history of heart disease/diabetes. Results: Compared with never users, current statin use was associated with significantly decreased cancer mortality (HR 0.78; 95% CI 0.71-0.86). Use of other lipid lowering medications was associated with a similar reduction in cancer deaths compared to monotherapy statin use (p-het = 0.57). The reduction in cancer death associated with statin use was not dependent on statin potency (p-het = 0.22), lipophilicity/hydrophilicity (p-het = 0.43), type (p-het = 0.34) or duration (p-het = 0.33). Current statin use was associated with significantly decreased mortality of multiple cancer types, including breast, colorectal, ovarian, digestive, and bone/connective tissue cancer deaths, but not lung cancer. However, past statin users were not at lower risk of cancer death compared to never users (HR 1.06; 95% CI, 0.85-1.33); additionally, statin use was not associated with a reduction in cancer incidence despite its effect on mortality (HR, 0.96; 95% CI: 0.92-1.001). Conclusions: In a cohort of postmenopausal women, regular use of statins or other lipid-lowering medications may decrease cancer mortality, regardless of the type, duration, or potency of statin medications used. Clinical trial information: NCT00000611.
Association between Mad1 G558A and ERCC1 C8092A polymorphisms and response to induction chemotherapy in advanced ovarian carcinoma
Authors: P. Figueroa, C. Castro Hernández, M. Santibáñez Andrade, M. Díaz Romero, F. Morales Vázquez, D. Gallardo Rincón, L. A. Herrera Montalvo
Journal: Journal of Clinical Oncology (2009)

5568 Background: Platinum and taxane remain active drugs in the treatment of ovarian cancer.The polymorphism C8092A of ERCC1 is involved in NER pathway of platinum induced damage DNA and Mad1 G558A with modulation of the chromosomal segregation. As primary aim we evaluated the influence of these polymorphisms in the chemotherapy response. Methods: ERCC1 C8092A and Mad1 G558A polymorphism allelic and genotypic frequency was determined on DNA isolated from blood tumor samples by PCR and specific digestion in 56 patients with cancer of advanced ovary who received induction chemotherapy with 3 courses of paclitaxel 175 mg/m 2 and AUC6 carboplatin every 3 weeks. Informed consent was obtained for all subjects and the study was approved by the hospital ethic committee. Results: Between January 2008 to June 2008, 56 women were evaluated, with age media was 53 years, majority characteristics were stages III (66.9%) 37 and IV (33.1%) 19 patients, histology serous papillary (94.6%) high-grade differenced (73.2%). Mad1 genotype were 7 G/G (12.5%), 30 were G/A (53.6%), 19 were A/A( 33.9%), and ERCC1 genotype were 20 C/C (35.7%), 30 were C/A (53.6%) and 6 were A/A (10.7%). All biochemical response by Rustin criteria was noted in 89.28%. Allele A for Mad1 is more frequently observed in patients with ovarian carcinoma versus in mexican healthy women (61% vs. 49%) and suggests the possibility that the polymorphism of Mad1 is a marker of risk for ovary cancer (RR = 1, 15, p &lt; 0, 05). According our aim we observed a higher response in allele G (91.89%) than allele A (87.75%) of Mad1 (p &lt; 0.10).Interestingly allele A of ERRC1 was not associated greater response (88.88% vs. 92%, p &gt; 0.10). Additionally we evaluated the predictive value of Ca 125 return to normal range after 3 chemotherapy courses, showed in 22 patients (39.28%) in univariate analysis we noted that allele G of Mad1 has been linked to improved response (p = 0.041). Conclusions: This is the first study in ovary cancer that evaluates predictive value of two SNP, one of them involved in the spindle checkpoint and the other in DNA repair mechanism (NER), suggesting to Mad1 G558A likely risk polymorphism for ovary cancer and response to chemotherapy based on taxanes, which may be a predictive biomarker. No significant financial relationships to disclose.
Epidermal growth factor receptor (EGFR) testing among veterans diagnosed with lung cancer in the VA.
Authors: Julie Ann Lynch, Brygida Berse, Kelly Kristin Filipski, Scott Kulich, Andrew N Freedman, Scott L. DuVall, Michael J. Kelley
Journal: Journal of Clinical Oncology (2015)

e17582 Background: Molecular profiling has resulted in new, targeted therapies that may improve survival for non-small cell lung cancer patients (NSCLC). Erlotinib is used in stage-IV patients and requires testing patients’ tumors for EGFR mutations. In 2010, guidelines recommended screening for EGFR gene mutations in non-squamous, stage IV NSCLC patients. Current guidelines recommend testing for all patients diagnosed with adenocarcinoma. Data on population-level implementation of molecular tests are sparse, yet are crucial to evaluate differences in access and outcomes. Methods: Patient-level test orders and results from January 2011 until December 2013 were provided by reference laboratories that conduct molecular testing for VA medical centers (VAMCs). The VA Central Cancer Registry (VACCR) reported clinical characteristics of lung cancer patients diagnosed in 2011 and 2012. We analyzed rate of testing, prevalence of EGFR mutations, clinicians’ perspectives regarding testing, and characteristics that predicted likelihood to undergo testing. Results: Our previous data showed that in 2010, 15 VAMCs ordered 93 assays. Lab data from 2011 to 2013 identified 986 tests ordered by 70 VAMCs, of which 352 were newly diagnosed patients included in the VACCR for 2011/2012. Patient characteristics of those tested were: 95% male, age (M=67, range 23 to 93). VACCR data (95% male, age (M=68, range 28 to 97) showed that 2,889 (19.64%) of Veterans diagnosed in 2011/2012 were eligible for EGFR testing. Clinicians reported an expected low rate of EGFR mutations among the Veteran clinical phenotype (histology, smoking status, gender). Lab and VACCR data confirmed this. Activating EGFR mutations were detected in 5.6% of cases. The 2361G>A polymorphism, missense mutations expected to be clinically insignificant, and variants of unknown significance were detected in 16.7%, 2.3% and 0.8% of patients, respectively. 70.1% of patients were negative for EGFR mutations. 4.4% of tests were not processed for technical reasons. Conclusions: Veterans have a much lower rate clinically actionable EGFR mutations than the reported average of 15%. Among Veterans diagnosed with lung cancer, 52% are current smokers, 40% are former smokers, which may explain the low rate of EGFR mutations.
Effect of thymidine kinase 1 expression on prognosis and treatment outcomes in refractory metastatic colorectal cancer: Results from two randomized studies of TAS-102 versus a placebo.
Authors: Takayuki Yoshino, Eiji Shinozaki, Kentaro Yamazaki, Yoshito Komatsu, Tomohiro Nishina, Hideo Baba, Akihito Tsuji, Yasushi Tsuji, Kensei Yamaguchi, Naotoshi Sugimoto, Tadamichi Denda, Kei Muro, Tetsuji Takayama, Taito Esaki, Yasuo Hamamoto, Toshikazu Moriwaki, Yasuhiro Shimada, Masahiro Goto, Takanori Tanase, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2017)

529 Background: TAS-102 is an oral nucleoside antitumor agent, comprising trifluridine (FTD) and tipiracil. FTD is incorporated into DNA after phosphorylation by thymidine kinase 1 (TK1). This study aimed to investigate the association between TK1 expression and TAS-102 efficacy in refractory metastatic colorectal cancer (mCRC) patients (pts). Methods: Data from two randomized phase 2 and phase 3 studies of mCRC pts refractory to standard therapies were analyzed for treatment outcomes in relation to TK1 expression. Expression was measured using immunohistochemistry, and staining was classified according to intensity and scored 0, 1+, 2+, or 3+. Occupancy rates of the areas scored 2+ and 3+ in tumor cells were calculated in 5% intervals, and divided into two groups (high or low TK1) at each cut-off point. Results: TK1 expression was evaluated in 329 pts. Baseline characteristics and treatment outcomes were comparable between the TK1-refined and intention-to-treat populations. Pts with high TK1 expression who received the placebo had a poor prognosis, while those receiving TAS-102 showed a significant improvement in overall survival (OS) at cut-off points of 5% to 15%, and 30%. Conclusions: High TK1 expression could be a poor prognostic factor and a predictive factor of TAS-102 efficacy in mCRC pts. [Table: see text]
Combination of the Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 with bendamustine (B)/rituximab (R) (BR) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Interim results of a phase Ib/II study.
Authors: Susan Mary O'Brien, Jacqueline Claudia Barrientos, Ian W. Flinn, Paul M. Barr, Jan Andreas Burger, Tasheda Navarro, Danelle Frances James, Eric Hedrick, Jonathan W. Friedberg, Jennifer R. Brown
Journal: Journal of Clinical Oncology (2012)

6515^ Background: BTK is an essential mediator of B cell receptor signaling and a critical kinase for lymphoma cell survival. PCI-32765 (P), an oral, selective, irreversible inhibitor of BTK, inhibits proliferation, migration and adhesion in CLL cells, and is highly active as a single agent for the treatment of R/R CLL pts. (O’Brien ASH 2011). BR produces an overall response rate (ORR) of 59% in R/R CLL (Fischer JCO 2011). We report interim data on P combined with BR. Methods: R/R CLL pts received P 420 mg orally daily for 28-day (D) cycles (C) until disease progression (PD). B was administered 70 mg/m 2 on D1 and D2 combined with R 375 mg/m 2 on D0 for C1 and 500 mg/m 2 on D1 for subsequent courses for a maximum of 6 cycles. Response was evaluated according to IWCLL criteria. Results: 30 pts were enrolled. Median age of pts was 62 yrs (range 41-82). 46% of pts were Rai stage III/IV and the median # of prior therapies was 2 (range 1-4). 37% and 13% were considered refractory (treatment free interval &lt;12 mo) to a purine analog containing regimen or BR, respectively. Bulky disease was present in 52%. Adverse events (AE) have been consistent with that expected with BR. Gr 3/4 neutropenia and thrombocytopenia have been noted in 47% and 10% of pts, respectively. Grade &gt;3 non-hematologic AEs potentially related to P included rash (3 pts) and fatigue and tumor lysis reported in 2 pts each. There were no Gr 3/4 infusion reactions. There have been no discontinuations (D/C) due to AE and no deaths on study. At a median follow-up of 4.9 mos (range 2.7-8.3 mo) 16 pts have completed BR and 14 pts are still receiving BR. The ORR is 90% (27/30 pts) (CR 10%, PR 80%). 2 additional pts achieved a nodal response with residual lymphocytosis. Responses appear independent of high-risk clinical or genomic features. 90% of pts remain on study; reasons for D/C include PD (n=2) and 1 pt pursuing SCT. Conclusions: PCI-32765, in combination with BR, is highly active. The high ORR, low rate of PD, and good tolerability compares very favorably with historical controls, warranting additional investigation of this combination.
Change in second-hand smoke exposure after a lung and head and neck cancer diagnosis and subsequent patient smoking cessation.
Authors: Lawson Eng, Devon Alton, Tom Yoannidis, Yuyao Song, Robin Milne, Samantha Sarabia, Zahra Merali, Steven Habbous, M Catherine Brown, Ashlee Vennettilli, Frances A. Shepherd, Natasha Leighl, Andrew J. Hope, Doris Howell, Jennifer M. Jones, Peter Selby, Wei Xu, David Paul Goldstein, Meredith Elana Giuliani, Geoffrey Liu
Journal: Journal of Clinical Oncology (2015)

9556 Background: Exposure to second-hand smoke (SHS) after a cancer diagnosis is associated with continued smoking in lung and head and neck (HN) cancer patients (PMID: 24419133, 23765604). We evaluated whether complete reduction/cessation of SHS exposure around and after a diagnosis of lung or HN cancer is associated with smoking cessation in the cancer patient. Methods: Lung and HN cancer patients from Princess Margaret Cancer Centre (2006-12) completed questionnaires at diagnosis and follow-up (median 2 years apart) that assessed smoking history and SHS exposures (cohort design). These cancers were chosen because these patients had the highest rates of smoking at the time of diagnosis. Multivariate logistic regression analysis evaluated the association of cessation of SHS exposure after a diagnosis of cancer with subsequent smoking cessation, adjusted for significant covariates. A cross-sectional study (2014) of 90 lung and HNC smoking patients assessed consistency in associations. Results: For the cohort, 261/731 lung and 145/450 HN cancer patients smoked at diagnosis; subsequent overall quit rates were 69% and 50% respectively. 91% of lung and 94% of HN cancer patients were exposed to SHS at diagnosis while only 40% (lung) and 62% (HN) were exposed at follow-up. Cessation of SHS exposure was associated with smoking cessation in lung (aOR = 4.76, 95% CI [2.56-9.09], P< 0.001), HN (aOR = 5.00 [1.61-14.29], P< 0.001), and in both cancers combined (aOR = 5.00 [3.03-8.33], P< 0.001). The cross-sectional study had a similar trend for cessation of SHS with smoking cessation, but a lower magnitude of association (OR = 2.73, P= 0.09). However, when asked directly, only 13% of patients quit smoking with another individual. Conclusions: Cessation of SHS exposure was a frequent occurrence around cancer patients. This cessation of SHS exposure is significantly associated with smoking cessation in lung and HN cancer patients. However, few patients quit smoking at the same time as their friends, family or household. Changing the environment around cancer survivors to reduce SHS exposure and encouraging households/friends to quit smoking may both improve cessation rates in cancer patients.
Nab-paclitaxel (Nab-P) and gemcitabine (G) first-line chemotherapy (CT) in patients (pts) with metastatic pancreatic cancer (mPC) who relapsed after adjuvant treatment (ADJ T): A “REAL LIFE” study.
Authors: Guido Giordano, Michele Milella, Giovanni Lo Re, Mariacristina Di Marco, Davide Melisi, Alessandro Passardi, Antonio Febbraro, Aldo Iop, Vanja Vaccaro, Luisa Foltran, Paola Bertocchi, Francesca Bergamo, Silvia Vecchiarelli, Elisa Giommoni, Vincenzo Ricci, Maria Bernardetta Aloi, Enrico Vasile, Alberto Zaniboni, Vittorina Zagonel, Ferdinando De Vita
Journal: Journal of Clinical Oncology (2017)

396 Background: Nab-P and G represents a standard of care in first line mPC treatment. Only 5% of pts in Nab-P + G arm received ADJ T in the MPACT phase III trial. Accordingly, there is a lack of information about Nab-P + G benefit in this population. Aim of this analysis was to evaluate outcomes in mPC “real life” pts receiving first-line Nab-P + G after relapsing from ADJ T. Methods: Clinical records of 330 mPC pts receiving Nab-P + G with standard schedule as first line CT were retrospectively reviewed, investigating, efficacy (Progression Free Survival, PFS and Overall Survival, OS defined as time elapsed from the start of Nab-P + G to progression or death respectively) in pts treated with prior ADJ T. Analysis was then performed in ADJ T subgroup according disease free survival (DFS) cut-off ( ≤ 6 vs 6-12 vs ≥ 12 months). OS and PFS were estimated with Kaplan-Meyer method with 95% CI. Cox-regression model was applied to the data with univariate and multivariate approach. Results: At time of data analysis in the entire cohort median (m) OS was 11.3 months (95% CI 9.157-13.443); mPFS 7 months (95% CI 5.827-8.173). 90 out of 330 pts (27.3%) had received G-based ADJ T with mDFS of 29.2 months (95% CI 25.62-32.78). In the overall population at multivariate analysis, ADJ treatment was an independent prognostic factor related to better OS (HR 0.53, 95% CI 0.40-0.66; p &lt; 0.001) and PFS (HR 0.69, 95% CI 0.49-0.89; p = 0.024). Median OS in ADJ T pts was significantly higher than pts who had not received ADJ T (15.0 vs 10.8 months respectively; p = 0.012). A similar trend in mPFS was observed in ADJ T versus non ADJ T pts (8.6 vs 6.9 months; p = 0.06). Pts with longer DFS after ADJ T showed major benefit in mOS (16.3 vs 13.1 vs 8.7 months in ≥ 12 vs 6-12 vs ≤ 6 months DFS respectively; p &lt; 0.001). No significant differences in mPFS were observed in the three subgroups (p = 0.271). Conclusions: Nab-P + G is a standard of care also in pts treated with ADJ T. ADJ treatment is an independent prognostic factor related to better survival, maybe reflecting the effect of prior radical surgery. Pts who received G-based ADJ T may benefit of Nab-P+G combination with an increased survival in pts with longer DFS.
Aspirin for the Prevention of Cardiovascular Disease: U.S. Preventive Services Task Force Recommendation Statement
Journal: Annals of Internal Medicine (2009)

Description: Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation about the use of aspirin for the prevention of coronary heart disease. Methods: Review of the literature since 2002, focusing on new evidence on the benefits and harms of aspirin for the primary prevention of cardiovascular disease, including myocardial infarction and stroke. The new evidence was reviewed and synthesized according to sex. Recommendations: Encourage men age 45 to 79 years to use aspirin when the potential benefit of a reduction in myocardial infarctions outweighs the potential harm of an increase in gastrointestinal hemorrhage. (A recommendation) Encourage women age 55 to 79 years to use aspirin when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in gastrointestinal hemorrhage. (A recommendation) Evidence is insufficient to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and women 80 years or older. (I statement) Do not encourage aspirin use for cardiovascular disease prevention in women younger than 55 years and in men younger than 45 years. (D recommendation)
Comparison of real prognosis and estimated prognosis by Adjuvant! Online in breast cancer in sites of Itajaí, Brazil.
Authors: Giuliano Santos Borges, Evandro De Azambuja, Rodrigo Rovere, Paulo Henrique Colchon, Marcos Cesar Staak Junior
Journal: Journal of Clinical Oncology (2012)

e12035 Background: Internet-available programme Adjuvant! Online is widely regarded as one of the best tools to estimate prognosis as well as benefit of adjuvant therapy in breast cancer. Methods: It is a retrospective cohort study, with a post hoc analysis with 214 patients of three different Brazilian services in which were measured the year overall and disease free survivals in a follow up of three years, and the same endpoints were estimated on a 10 year basis by the Adjuvant! Online programme. Results: See table. Conclusions: Our study shows interesting trends in breast cancer survival, even though the number of patients accrued may not be enough to have full external validity. We conclude that the OS and DFS rates in our sample compared to the one calculated by the Adjuvant! Online programme display agreement, following the same pattern, considering different periods of follow up (much longer in the internet tool). The only group which had poor concordance was the group of younger patients (i.e., under 40), even though it was the least represented group in our sample. Nevertheless, it can be suggested that the programme underestimates the usually bad prognosis in these cases, as broadly documented in medical literature. Our study shows interesting trends in breast cancer survival, even though the number of patients accrued may not be enough to have full external validity. [Table: see text]