tbuckley/cabot-search huggingface dataset:
Breast cancer in Angola, molecular subtypes: The first preliminary study.
Authors: Lúcio Lara Santos, Fernando Miguel, Lygia Vieira Lopes, Julio Oliveira, Eduardo Ferreira, Carlos Lopes
Journal: Journal of Clinical Oncology (2017)

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.
Double blind phase III trial of effects of low dose 13-cisretinoic acid on prevention of second primaries in stages I-II head and neck cancer: A trial of the ECOG-ACRIN Cancer Research Group (C0590).
Authors: Aarti K. Bhatia, Ju-Whei Lee, Harlan Pinto, Charlotte D. Jacobs, Paul J. Limburg, Robert Arusell, Eamonn Patrick Dunphy, Janardan D. Khandekar, Seth Reiner, Luis Baez-Diaz, Paul Celano, Shuli Li, Yi Li, Barbara Burtness, Kishan J. Pandya
Journal: Journal of Clinical Oncology (2016)

1507 Background: 13-Cisretinoic acid (13-CRA) is a synthetic derivative of Vitamin A. Trials of high-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHN) showed encouraging results. We report the results of a long-term Phase III randomized trial that compared low-dose 13-CRA versus placebo, among patients with early-stage SCCHN in development of second primary tumors (SPTs) and overall survival (OS). Methods: 176 patients treated for Stage I/II SCCHN were randomized to low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for two years, with additional 5 years of follow-up. The Kaplan-Meier method was used to estimate the survival distribution of time to SPTs and time to all-cause death (OS). Results: 13-CRA did not significantly reduce the number of SPTs (22/91 in the 13-CRA vs 23/85 in the placebo arm, p = 0.73). The most common sites of SPTs were head and neck (11) and lung (10). No significant differences in second primary-free survival between the arms were noted (Hazard ratio (HR) 0.79, 95% confidence interval (CI) = 0.44 to 1.42, p= 0.42). Despite limited power, there was a trend to improved OS for the 13-CRA arm (HR 0.75, 95% CI 0.51 to 1.10, p = 0.14) particularly among female patients (N=39, HR 0.44, 95% CI 0.18 to 1.05, p = 0.065) and never/former smokers (N=129, HR 0.61, 95% CI 0.37 to 1.01, p = 0.055), at 15 years. HRs for death comparing never-smokers vs current and former smokers vs current smokers were 0.05 and 0.26, respectively (p=0.003 and p<0.0001, respectively). 77% patients received at least 1 year of treatment and 52% completed 2 years. Main 13-CRA related toxicites were fatigue, dry skin, cheilitis, nausea and elevated triglycerides and were mostly low-grade. Conclusions: Low-dose 13-CRA for 2 years did not demonstrate a significant benefit in decreasing the incidence of SPTs or prolonging OS, despite some potential survival advantages observed among female patients and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials.
Prevalence of low vitamin D in patients with breast cancer in a predominantly Hispanic population at the American Mexican border.
Authors: Safa Farrag, Alok kumar Dwivedi, Salman Otoukesh, Nabeel Badri, Luis Sanchez, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2016)

e12051 Background: Low level of Vitamin D(VD) has been linked with a higher risk of cancers in multiple epidemiological studies. Some studies have suggested that VD deficiency is associated with increased risk of certain cancers as well as worse cancer prognosis. The aim of this study was to assess the prevalence of low VD in patients with breast cancer in a predominantly Mexican Hispanic/Latino patient population, a fast growing and relatively understudied population. Methods: We sought to determine the serum VD levels in breast cancer patients diagnosed at the Texas Tech University Breast Center in El Paso, TX, between 2012-2014 via a retrospective chart review of the Electronic Medical Records. We evaluated clinical associations with low level of VD. Unpaired t-tests and Fisher’s exact tests were used. The cutoffs to define VD deficiency and insufficiency were based on the Endocrine Society Guidelines, which defined VD deficiency as serum level of 25(OH)D below 20 nanogram(ng)/millileter(ml), and VD insufficiency as serum level of 25(OH)D between 21–29 ng/ml. Results: We included a total of 83 patients. VD insufficiency was seen in 86% of patients (95% CI: 0.76-0.92) and deficiency in 39% (95% CI: 0.28-0.50). Mean age 57 years, 94% were Hispanics. Tumor characteristics were as follows: 75 % Estrogen receptor (ER) positive; 63% Progesterone receptor (PR) positive 63%; 20% Her2 neu positive; and 16% were “triple negative”. 10% had Stage 0, 38% stage 1, 28% stage 2, 20% stage 3, and 4% stage 4. No significant associations were observed between VD deficiency and age, stage or tumor characteristics. Conclusions: VD deficiency is widely prevalent in Hispanic/Latino patients with breast cancer in El Paso, TX. This is quite alarming in view of possible increased risk of cancer with low VD and potentially worse cancer outcomes. Efforts should be made to screen for, diagnose and treat VD deficiency in this patient population. Further pharmacogenomics studies are warranted to explore the underlying etiology of VD deficiency in this paradoxically sunny region.
Imagerie des carcinoses péritonéales: Comparaison du scanner et du pet-scan
Authors: C Dromain, S Leboulleux, M Pocard, A Auperin, D Malka, D Elias
Journal: Endoscopy (2006)

Evaluer et comparer la performance du scanner et du PET-scan au 18F-FDG pour le bilan diagnostic et d'extension des carcinose péritonéale.
The opportunity cost (OC) of low adherence with screening (scr) recommendations for colorectal cancer (CRC).
Authors: Afsaneh Barzi, David I. Quinn, Gregory Idos, Heinz-Josef Lenz, Sarmad Sadeghi
Journal: Journal of Clinical Oncology (2016)

1553 Background: Scr rates are <60% below the Healthy People 2020 target of 70.5%, leaving 20 million people unscreened. Prior cost effectiveness analyses (CEAs) have shown that although Scr is more costly compared to No Scr, the incremental cost effectiveness ratios (ICERs) for Scr are favorable. However, these CEAs did not include the costs of drugs such as oxaliplatin and bevacizumab. More effective treatments and longer overall survival with advanced CRC result in higher average societal costs of care. Methods: A Markov model was built to represent the CRC incidence and its natural history in the US general population. Individual level simulation was used to compare the benefits of CRC Scr from a societal perspective. Costs and effects were discounted (Dis) at 3%. 12 Scr strategies (ST) were compared to No Scr. Dis Life Years (LY), incidence reduction (IR), CRC mortality reduction (CMR), and Dis costs were measured. ICERs were calculated. Results: Among the STs studied, only stool DNA Scr cost more than No Scr. CS is the most effective Scr ST and the least expensive. This represents an OC of $554 per eligible individual for non-compliance with Scr and is the result of increasing costs of CRC care. With 20 mil individuals at risk for preventable CRC, the OC is staggering. Conclusions: With improved survival, increasingly costly treatment regimens, and additional lines of treatment, the OC for not Scr will increase. Efforts to improve Scr adherence can result in significant societal savings by preventing the losses from OC. Strategy Comparative Effectiveness Costs Cost Effectiveness Dis LY IR CMR Cancer Care OC ($) ICER Status (Rank) No Scr 15.205 0 0 3415 554 - D ST 1: FOBT 15.215 12 17 3164 303 - D ST 2: FIT 15.211 6 12 3303 442 - D ST 3: FOBT + FS 15.217 14 19 3170 309 - D ST 4: FIT + FS 15.214 8 14 3338 477 - D ST 5: CS 15.227 23 34 2861 0 0 U (1) ST 6: FS 15.221 11 21 3145 284 - D ST 7: FOBT 2 15.218 12 20 3054 193 - D ST 8: FIT 2 15.215 5 14 3186 325 - D ST 9: FOBT 2 + FS 15.219 13 21 3128 267 - D ST 10: FIT 2 + FS 15.217 7 17 3256 395 - D ST 11: DNA 15.216 14 18 4296 1435 - D ST 12: DNA 3 15.219 14 21 4161 1300 - D FOBT: Fecal Occult Blood Test, FIT: Fecal Immunochemical Test, DNA: Stool DNA Test. Stool tests are done annually or at the interval listed. D: Dominated. U: Undominated.
TG6002: A novel oncolytic and vectorized gene pro-drug therapy approach to treat glioblastoma.
Authors: Ahmed Idbaih, Philippe Erbs, Johann Foloppe, Hervé Chneiweiss, Juliette Kempf, Michel Homerin, Charlotte Schmitt, Ludovic Nguyen Them, Jean-Yves Delattre
Journal: Journal of Clinical Oncology (2017)

e13510 Background: Glioblastoma (GBM) is an incurable disease challenging innovations for significant therapeutic progress. TG6002 is a vaccinia virus that replicates mainly in tumor cells after deletion of genes coding for thymidine kinase and ribonucleotide reductase. TG6002 alsoexpresses the yeast-originated gene FCU1 encoding cytosine deaminase and uracilphosphoribosyltransferase that transforms the pro-drug flucytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluoro-uridilyl monophosphate (5-FUMP), respectively. The proof of this ‘suicide gene’ concept has been demonstrated in man, using a non-replicative vaccinia virus hosting the FCU1gene (Husseini F et al, ASCO 2012). TG6002 mechanism of action then associates oncolysis of tumor cells, immune reaction against released tumor antigens and local chemotherapy. Methods: Prior to initiating clinical development, the anti-tumor activity of the TG6002/5-FC combination was investigated, using U-87MG human GBM cell line and patient-derived cell lines (PDCL). Results: The growth of U-87MG subcutaneous tumors implanted in nude mice was inhibited by systemic administration of TG6002 with or without 5-FC. Mice treated with TG6002 only survived significantly longer than controls; this survival benefit was not modified by addition of 5-FC to TG6002. In contrast, in an orthotopic brain tumor model, mice survived significantly longer when treated intravenously by TG6002 alone, and oral 5-FC added a significant survival benefit. In this model, TG6002 was found in the brain of xenografted mice but not in that of control mice without tumor, indicating a tumor-specific replication of TG6002. PDCL were also exposed in vitro to TG6002. Evidences of virus replication and tumor cells death were detected. In addition, TG6002 exhibited a synergistic cytotoxic effect when combined with temozolomide in this model, suggesting a potential interest for clinical development of this combination. Conclusions: Taken together, our results support initiation, in recurrent GBM patients, of a phase 1 clinical trial testing TG6002 safety in combination with 5-FC, as a first step toward investigation of clinical efficacy of this therapeutic combination in GBM.
A preoperative window study of metformin for the treatment of endometrial cancer.
Authors: Kevin M. Schuler, Brooke S. Rambally, Megan J. DiFurio, Paola A. Gehrig, Victoria Lin Bae-Jump
Journal: Journal of Clinical Oncology (2013)

5519 Background: Obesity and diabetes have been linked to poorer survival and increased recurrence rates in endometrial cancer. The anti-diabetic medication, metformin, has been shown to have anti-tumorigenic effects in vitro and in vivo, via AMPK activation and inhibition of the mTOR pathway. We conducted a pre-operative window clinical trial of metformin in obese endometrial cancer patients to evaluate short-term in vivo molecular changes. Methods: Women with endometrioid endometrial cancer who were obese (BMI&gt;30) were recruited from a gynecologic oncology clinic. Once enrolled, patients had a repeat pre-treatment endometrial biopsy and then began metformin at a dose of 850 mg PO once daily for 1-4 weeks prior to hysterectomy/surgical staging. A tissue microarray, using triplicate cores from each specimen, was constructed from paired formalin-fixed, paraffin-embedded endometrial biopsy (pre-treatment) and hysterectomy (post-treatment) specimens. The expression of Ki-67, a marker of cell proliferation, was measured by immunohistochemistry. Individual slides were digitized using the Aperio ScanScope (Aperio Technologies, Vista, CA), and digital images were analyzed using Aperio ImageScope software. The Signed Rank Test was used for statistical analysis. Results: Sixteen patients have completed the protocol. The mean duration of treatment was 14.5 days. Percent Ki-67 staining decreased significantly with metformin treatment (mean of 19.5% decrease, p = 0.026). Two patients experienced grade 1 toxicities, including mild abdominal pain and loose stools. Ten of the 16 patients responded to metformin based on decreased proliferation from their pre- to post-treatment specimens. There were no differences in median age, BMI, HgbA1c, or number of doses taken between responders and non-responders to treatment. Pre-treatment Ki-67 levels were statistically higher in the women that responded to metformin treatment (52% versus 27.5%, p = 0.0067). Conclusions: Metformin significantly reduced proliferation in a pre-operative window study in obese endometrial cancer patients, providing further support for therapeutic clinical trials of metformin in this obesity-driven disease.
Abstract 13127: Prognostic Value of Hemodynamic Profiles in Children With Dilated Cardiomyopathy Listed for Heart Transplantation
Authors: Tajinder P Singh, Peta Alexander, Elizabeth D Blume, Kimberlee Gauvreau
Journal: Circulation (2013)

Congestion is the primary hemodynamic abnormality in most adults in chronic heart failure. Hemodynamic abnormalities have not been systematically evaluated in pediatric heart failure. We sought (1)...
Abstract 13727: A Protective Role of Fibroblast Growth Factor 23 Against Vascular Calcification
Authors: Takehiro Nakahara, Keiko Kawai-Kowase, Hiroki Matsui, Tatsuya Iso, Toshihiro Utsugi, Shoichi Tomono, Masashi Arai, Masahiko Kurabayashi
Journal: Circulation (2013)

Introduction: Fibroblast growth factor 23 (FGF23) has been postulated to be involved in vascular calcification. However, both clinical and basic research demonstrated conflicting evidence indicatin...
Outcomes of chemotherapy/trastuzumab treated locally advanced HER2+ breast cancer in British Columbia between 2005 and 2010.
Authors: Wendie-Lou D. Den Brok, Caroline Speers, Scott Tyldesley, Lovedeep Gondara, Alan Nichol, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2016)

e12079 Background: Adding trastuzumab (T) to chemotherapy (CT) improves HER2+ breast cancer (BC) outcomes. With the exception of the NOAH study, neoadjuvant (neo) and adjuvant (adj) trials enrolled few patients (pts) with locally advanced (LA) disease. We performed a retrospective analysis in LA HER2+ BC to better understand prognosis in this disease. Methods: Using the BC Outcomes Unit database, we identified all pts referred to the British Columbia Cancer Agency with clinically (c) LA HER2+ BC between 05/2005 and 12/2010, who received standard neo or adj CT/T. LA was defined as T4Nany, T3N1-3, TanyN2-3. Adj cases with c but not pathological (p) LA stage were excluded. Five-year (5 y) relapse free survival (RFS) and BC specific survival (BCSS) were estimated for the overall cohort, by hormone receptor (HR) status, for neo and adj CT/T, and by pathologic complete response (pCR) in neoadj cases. Results: We identified 380 cases. Median follow up was 6.4 y. Adj (258) and neo (122) cases differed in HR- status (35% vs 43%), inflammatory presentation (1% vs 37%), and disease burden (c T4N1-3 2% vs 35%; cT4N0 1% vs 21%; cT3N1-3 3% vs 33%). Among neo cases, pCR rate was 48% (52% in HR-, 43% in HR+). For adj cases, p stage was T4N1-3 in 3%; T3N1-3 in 20%, and T0-2N2-3 in 77%. The table belowshows 5 y RFS and BCSS estimates. Conclusions: HR- BC had 15% lower 5 y RFS than HR+ disease. Neo cases had higher disease burden, explaining thier worse RFS and BCSS. Higher pCR rate in HR- disease, and better RFS and BCSS for pCR vs non-pCR is consistent with neo trials. Allowing for differences in follow up, stage, and HR status, our results for neo CT/T are similar to those in the NOAH study. They confirm the need to improve therapy in LA HER2+ BC, especially HR- and non-pCR cases. Neo pertuzumab and post-neo TDM-1 may in part address this need. 5-year RFS, BCSS. n (%) 5y RFS %, (95% CI) p-value 5y BCSS%, (95% CI) p-value All 380 75 (71, 80) - 81 (76, 84) - HR+ 230 (61) 82 (76, 86) - 88 (83, 92) - HR- 143 (38) 67 (58, 74) - 70 (61, 76) - Adj 258 (68) 80 (74, 84) 0.002 85 (80, 89) 0.004 Neo 122 (32) 66 (57, 74) 71 (62, 79) pCR yes (26 HR+, 32 HR-, 1 unk) 59 (48) 81 (68, 89) 0.002 85 (72, 92) 0.001 pCR no (34 HR+, 29 HR-) 63 (52) 53 (39, 64) 59 (45, 70)
Detection and prognostication of hepatocellular carcinoma by quantitative analysis of aberrantly methylated DNA in serum using a non-bisulfite-based method
Authors: KC Allen Chan, Paul Lai, Tony Mok, Henry Chan, Chunming Ding, SW Yeung, YM Dennis Lo
Journal: Clinical Cancer Research (2007)

PR-1  Background: Hypermethylation of the RASSF1A gene is frequently observed in hepatocellular carcinoma (HCC). In this study, we have investigated the use of quantitative analysis of circulating hypermethylated RASSF1A sequences for detecting and prognosticating HCC.  Methods: In module 1, 63 pairs of HCC patients and age- and sex-matched chronic hepatitis B virus (HBV) carriers, and 30 healthy volunteers were studied. In module 2, 22 HCC patients with cancer detected through a surveillance program for HBV carriers were studied. The concentrations of circulating hypermethylated RASSF1A sequences were determined by real-time PCR after methylation-sensitive restriction enzyme digestion. As this method did not require bisulfite conversion, its sensitivity was higher than that reported for bisulfite-based methylation-specific PCR assays for the detection of tumor-derived DNA in plasma.  Results: Hypermethylated RASSF1A sequences were detected in the serum of 93% HCC patients, 58% HBV carriers and none of the healthy subjects. The median RASSF1A levels for the HCC patients and the HBV carriers were 770 copies/mL and 118 copies/mL, respectively (P
Outcomes in patients with relapsed/refractory Hodgkin lymphoma (RR-HL) with progression after autologous stem cell transplantation in the current era of novel therapeutics.
Authors: Steven Michael Bair, Lauren E. Strelec, Sunita Nasta, Anthony R. Mato, Daniel Jeffrey Landsburg, Edward Allen Stadtmauer, Alison W. Loren, Stephen J. Schuster, Jakub Svoboda
Journal: Journal of Clinical Oncology (2016)

2543 Background: Patients (pts) with RR-HL who progress or relapse following autologous stem cell transplantation (ASCT) have a poor prognosis, with a historical median overall survival (OS) of 27 months (Crump, Blood 2008). More recently, these pts have been treated with novel therapies, particularly brentuximab vedotin (BV). We hypothesized that these agents have contributed to greater OS in this population. Methods: We conducted a retrospective study of all pts with RR-HL who underwent ASCT at the Univ. of Pennsylvania between 2004 and 2014. Therapy was given at discretion of the treating physician and reported data were collected through 10/2015. The primary endpoint was median OS from post-ASCT relapse. Results: Of 136 pts, 69 (50.7%) relapsed or progressed after ASCT. Median age was 37.5 years. Of pts who relapsed post-ASCT, 27 (40%) were exposed to at least one or more novel agents after relapse including 23 (34%) pts who received BV, 6 (9%) nivolumab, 5 (7%) lenalidomide, and 4 (6%) panobinostat. Median OS and follow-up were 34 and 72 months, respectively. Pts treated with novel agents had significantly prolonged OS compared to pts treated with conventional chemotherapy only (86 vs 22 months; p = 0.007). Other factors associated with improved OS in univariate analysis included age at relapse, response to ASCT, and radiation treatment (XRT) after post-ASCT relapse. Conclusions: Pts with RR-HL post-ASCT who are treated with novel agents may achieve prolonged OS when compared to chemotherapy alone. These results suggest improved outcomes when matched to historical controls and are likely a more accurate estimate of OS in the current era of expanded therapeutic options. # of pts Median OS, mos (95% CI) P-value Overall 69 34.1 (24.5 - 69.4) Age <60 at relapse 60 46.1 (26.0 - 85.6) 0.0395 Age ≥60 at relapse 9 19.0 (0.5 - n/a) Response to ASCT: CR/PR/SD 33 84.3 (33.8 - n/a) 0.0024 Response to ASCT: PD 31 22.4 (12.8 - 34.1) Novel agent: Yes 27 85.6 (46.1 - n/a) 0.0068 Novel agent: No 41 25.6 (12.8 - 33.8) Post-transplant XRT: Yes 46 51.8 (26.0 - n/a) 0.013 Post-transplant XRT: No 21 24.5 (10.7 - 59.3)
Combined BTK and PI3Kδ Inhibition with Acalabrutinib and ACP-319 Improves Survival and Tumor Control in CLL Mouse Model
Authors: Carsten U. Niemann, Helena I. Mora-Jensen, Eman L. Dadashian, Fanny Krantz, Todd Covey, Shih-Shih Chen, Nicholas Chiorazzi, Raquel Izumi, Roger Ulrich, Brian J. Lannutti, Adrian Wiestner, Sarah E.M. Herman
Journal: Clinical Cancer Research (2017)

Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of Bruton tyrosine kinase (BTK) and PI3Kδ is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon, and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3Kδ and BTK inhibitors.Experimental Design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3Kδ inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL.Results: We found significantly larger reductions in tumor burden in the peripheral blood and spleen of combination-treated mice. Although single-agent therapy improved survival compared with control mice by a few days, combination therapy extended survival by over 2 weeks compared with either single agent. The combination reduced tumor proliferation, NF-κB signaling, and expression of BCL-xL and MCL-1 more potently than single-agent therapy.Conclusions: The combination of acalabrutinib and ACP-319 was superior to single-agent treatment in a murine CLL model, warranting further investigation of this combination in clinical studies. Clin Cancer Res; 23(19); 5814-23. ©2017 AACR.
Abstract 19162: Impaired Segmental Coronary Artery Distensibility is Associated with Vulnerable Plaque Composition Measured by Virtual Histology Intravascular Ultrasound
Authors: Naser Ahmadi, Eric Yang, Fereshteh Hajsadeghi, Hormoz B Mirshkarlo, Matthew Budoff, David Shavelle, Ramin Ebrahimi
Journal: Circulation (2010)