tbuckley/cabot-search huggingface dataset:
Prognosis by breast cancer subtypes in patients treated with adjuvant chemotherapy in a clinical trial.
Authors: A. M. G. Ali, E. Provenzano, J. Abraham, J. M. Bartlett, C. J. Poole, L. Hiller, J. Dunn, C. Twelves, H. M. Earl, C. Caldas, P. Pharoah
Journal: Journal of Clinical Oncology (2011)

12 Background: Breast cancer can be classified into molecular subtypes that have distinct survival patterns. The purpose of this study was i) to evaluate the prognostic significance of breast cancer subtypes in a cohort of women taking part in the NEAT and BR9601 clinical trials comparing CMF with ECMF, and ii) to evaluate whether the subtypes were predictive of the added benefit of epirubicin in these trials. Methods: Tumor tissue microarrays were stained and scored for ER, PR, HER2, EGFR and CK5/6. These were used to classify the tumors into six intrinsic subtypes (1). We used Cox regression to compare overall survival (OS), breast cancer specific survival (BSS) and relapse free survival (RFS) in the different subgroups. We also compared the effect of ECMF with CMF by subgroup. Results: IHC data were available for 1725 cases of whom 805 were Luminal 1-basal negative, 153 were Luminal 1-basal positive, 174 were Luminal 2, 192 were HER2-like, 230 were core basal phenotype and 171 were 5-negative phenotype. Median follow-up time was 7 years. The prognostic effects of the subtypes were similar to those reported for unselected breast cancer cases irrespective of adjuvant therapy (Blows FM, et al. PLoS Med 2010;75:e1000279.). In particular, the luminal 1-basal negative tumors were associated with the best prognosis in five years after surgery and the HER2-like tumors were associated with the poorest prognosis. ECMF has previously shown to be associated with a 33% relative risk reduction for OS compared to CMF (Poole CJ et al. N Engl J Med 2006;35518:1851-62.). There was little evidence for significant heterogeneity of effect by tumor subtype for any end point (OS P= 0.40, BSS P=0.53 RFS P=0.50). However, there was an observed trend towards the largest additional benefit from ECMF being in women with tumors of the 5-negative phenotype (OS HR=0.39 95% CI 0.21-0.73) and the smallest being in Luminal 1-basal negative tumors (OS HR=0.86 95% CI 0.64-1.16). Conclusions: In a clinical trial in which all patients received chemotherapy, we confirmed that breast cancer subtypes show distinct behaviour with differences in short and long term survival. The benefit of ECMF over CMF was statistically similar in all disease subtypes.
Is it possible to get adequate dose coverage of a clinical target volume (CTV) to account for the possible extra capsular extension in early-stage prostate cancer by low dose rate (LDR) brachytherapy?
Authors: E. P. Saibishkumar, D. Iupati, J. Borg, K. Fernandes
Journal: Journal of Clinical Oncology (2011)

98 Background: There is no consensus for the definition and evaluation of CTV in post-implant setting for LDR prostate brachytherapy to account for extra capsular extension in clinically localized prostate cancer. In this study, we defined a CTV and evaluated its dosimetry in the post implant CT/MR scans done at 1 month after the LDR brachytherapy procedure. Methods: The initial consecutive 71 patients who underwent LDR brachytherapy under a single physician at Princess Margaret Hospital from June 2009 to July 2010 were included in this retrospective study. On the post implant MRI, the CTV was created by adding 3mm uniform margins around the prostate but respecting the anatomical boundaries like bone, bladder and rectum. Post implant dosimetry was based on CT/MR fusion using the dosimetric parameters V80, V90, V100, V150, V200, D80, D90 and D100. Implants were qualified as optimal if their V100 was &gt;85% and D90 was &gt;90% for both prostate and CTV. Univariate analysis was performed to evaluate associations of factors with V100 and D90 for the CTV using Wilcoxon rank sum test and Fisher's exact test. Results: The mean (SD) prostate V100 and D90 were 95.5% (4.2) and 117% (10) respectively with only 1 patient having sub optimal implant (V100 &lt;85% and D90 &lt;90%). The mean (SD) V100 and D90 for the CTV were also acceptable at 90.6% (4.9) and 103% (9), respectively. Six patients had V100 &lt;85% and 7 patients had D90 &lt;90% for the CTV. On univariate analysis, edema and seed implantation technique correlated with sub-optimal implant for the CTV. The mean (SD) edema for patients with V100 &lt;85% was 18% (10) and with D90 &lt;90% was 15% (12). The corresponding values for the optimal implants both in terms of V100 and D90 were 3% (13). Patients implanted with exclusively loose seeds (15 patients only) had higher incidence of sub-optimal implants (26%) compared to patients who had strands on the antero-lateral margins (56 patients; 3.5%). Conclusions: In this study, adequate dose coverage of CTV was achieved in most patients with current technique but implants with optimal dosimetry to prostate still may have sub-optimal D90 and V100 for the CTV. No significant financial relationships to disclose.
Efficacy and rectal toxicity of hypofractionated radiation therapy with daily image guidance.
Authors: A. M. McDonald, M. C. Dobelbower, R. Y. Kim, R. Jacob, J. Bishop, J. B. Fiveash
Journal: Journal of Clinical Oncology (2011)

85 Background: To assess the biochemical control rates and long-term rectal side effect profile of hypofractionated image guided radiation therapy for prostate cancer. We hypothesize that daily CT-based image guidance will allow a higher dose per fraction to be safely administered, shortening the overall treatment time from 8 weeks to 4-5.5 weeks. Methods: 160 patients were treated with image guided radiation therapy with or without adjuvant hormonal ablation between 2005 and 2009 for patients &lt;= T3a N0 M0. Patients were classified into risk groups with 51 patients defined as low risk, 67 as intermediate risk, and 43 as high risk. Mean age was 70.2 years. All patients were treated with 60/67.6/70/70.2 Gy to the prostate divided into 20/26/28/27 fractions. 57% of patients received hormone therapy. Daily CT or fiducial-based image guidance was performed prior to each fraction. The median follow up was 34 months. Biochemical control was defined by the Phoenix definition. Rectal toxicity was graded by the CTCAE 4.0 scale. In general patients with rectal bleeding more than once per week were started on rectal steroids. Results: 12/160 (7.5%) of patients had late grade 2 or worse rectal toxicity after radiation treatment. The Kaplan-Meier estimate for grade 2 rectal toxicity at 2 years was 6.9%. The crude rate of biochemical no evidence of disease was 96.3%. Kaplan Meier estimates for biochemical no evidence of disease at 3 and 5 years are 0.98/0.84, 0.97/0.97, and 1.0/0.67 for low, medium, and high-risk patients respectively. Log-rank analysis showed no statistically significant difference among the dosing regimens for toxicity-free survival (p=0.24). Conclusions: With daily image guidance hypofractionated radiation therapy is clinically safe with moderate late rectal toxicity. Early follow-up suggests high efficacy. Ongoing and future randomized trials such as RTOG 0415 will be required to confirm these findings. No significant financial relationships to disclose.
Risk of breast cancer among Japanese women with a positive family history.
Authors: J. Suzuki, T. Hojo, K. Jimbo, S. Asaga, T. Kinoshita
Journal: Journal of Clinical Oncology (2011)

191 Background: Most breast cancer cases are sporadic, rather than associated with inherited gene mutations, such as BRCA1 and BRCA2. However, women with a family history of breast cancer are at increased risk of developing breast cancer compared to those women without any family history, even if they lack these gene mutations. Methods: We analyzed 10892 patients including bilateral breast cancer cases (total of 11398 breast cancers) who underwent surgery at our hospital between 1962 and 2009. We excluded 295 cases whose family history data were not available. Clinical and pathological differences between following patient groups were tested; 9528 patients or 9955 cancers (88%) with negative family history (FH-), 896 patients or 951 cancers (8%) who had at least one first-degree relative with breast cancer (1FH+), 468 patients or 492 cancers (4%) who had second-degree relative with breast cancer (2FH+), and 1364 patients or 1443 cancers (12%) with family history regardless of first- or second-degree relative (FH+). Significance was established at a p-value of &lt; 0.05. Results: Among the family members, sisters were more likely to have treated for breast cancer (38% in FH+ group), followed by mothers (27%), aunts (26%), grandmothers (7%), and daughters (2%). The incidence of developing contralateral breast cancer was significantly higher in 1FH+ group, compared to patients in FH- and 2FH+ groups. No other factors showed any significant difference, including the incidence of cancer in other organs, pathological characteristics, and age of onset, although BRCA1 and BRCA2 mutation may be associated with increased risk of developing breast cancer at younger age. Outcome studies with available data did not show any significant difference in overall survival between FH+ and FH- patients. Conclusions: A Japanese woman with a positive family history has a higher risk of developing breast cancer than women without any close relatives with breast cancer, similar to the results reported in Western countries where prevalence of breast cancer is higher. Regular checkup of contralateral breast is important for those patients whose first-degree relatives have also been diagnosed with breast cancer.
High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice
Authors: Francine Z. Marques, Erin Nelson, Po-Yin Chu, Duncan Horlock, April Fiedler, Mark Ziemann, Jian K. Tan, Sanjaya Kuruppu, Niwanthi W. Rajapakse, Assam El-Osta, Charles R. Mackay, David M. Kaye
Journal: Circulation (2016)

Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease.Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess-treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets.We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens. Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal Egr1, a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart.A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function.
Late Responders to Imatinib: Is Timing of Achievement of Complete Cytogenetic and Molecular Responses the Same in Previously Treated as Compared to the Newly Diagnosed CML Patients?
Authors: Vanesa Scholl, Roberta Bitencourt, Arthur Moellmann, Rocio Hassan, Moises Rocha, Jane Dobbin, Ilana Zalcberg
Journal: Blood (2008)
Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study
Authors: Delphine Rea, Franck E. Nicolini, Michel Tulliez, François Guilhot, Joelle Guilhot, Agnès Guerci-Bresler, Martine Gardembas, Valérie Coiteux, Gaelle Guillerm, Laurence Legros, Gabriel Etienne, Jean-Michel Pignon, Bruno Villemagne, Martine Escoffre-Barbe, Jean-Christophe Ianotto, Aude Charbonnier, Hyacinthe Johnson-Ansah, Marie-Pierre Noel, Philippe Rousselot, François-Xavier Mahon
Journal: Blood (2016)
ABO blood group and survival in pancreatic cancer.
Authors: Christina Wai, Karthik Devarajan, John Parker Hoffman
Journal: Journal of Clinical Oncology (2012)

380 Background: ABO blood group has been shown to be a risk factor in many gastrointestinal cancers. Recent studies have shown that patients with non-O blood groups have a higher risk of pancreatic adenocarcinoma compared to those with blood group O. Based on this finding, we were interested in seeing if a particular ABO blood group would have an impact on survival outcomes in pancreatic cancer. Methods: A retrospective chart review of 236 pancreatic patients who underwent surgical resection at a major cancer center from January 1998 to July 2011 was performed. Data were collected for demographics, ABO blood group, Rh factor, CA 19-9 level, use of neoadjuvant therapy, pathological stage, surgical margins and peritoneal washings. Overall survival (OS) was compared amongst the different blood groups. Results: There were 118 male and 118 female patients. The median age at diagnosis was 68. Of the 236 patients, 80 (33.9%) were blood group O, 108 (45.8%) were blood group A, 32 (13.6%) were blood group B and 16 (6.8%) were blood group AB. For all patients, there was no statistically significant association between ABO blood group and OS (log rank test p = 0.7). Furthermore, no survival difference was seen between O and non-O blood groups when the data was stratified by stage and neoadjuvant therapy. Conclusions: Like other GI malignancies, ABO groups have been shown to be linked to the risk of pancreatic cancer. The mechanism by which this occurs is not completely clear. In our analysis of ABO blood groups, they were not shown to be prognostic indicators. There does not appear to be a difference in overall survival between patients with O blood group and those with non-O blood groups.
Risk of breast cancer (BC) relapse after 5 years of adjuvant tamoxifen (AT) in estrogen/progestrone-positive (ERP) patients (pts).
Authors: A. Barzi, B. A. Sisk, C. Yu, G. T. Budd, M. W. Kattan
Journal: Journal of Clinical Oncology (2011)

253 Background: Current standard of care for pts with ERP BC is 5 years of AT or aromatase inhibitors (AIs). Based on MA17 data, practitioners offer extended adjuvant therapy with AIs to post menopausal women. Extended therapy is costly and has side effects. Identifying pts with higher risk of relapse will allow practitioners to offer extended therapy to selected pts. Methods: Among 334 pts from the Cleveland Clinic BC surgery dataset, 38 had relapsed (local and systemic) and 39 had died of other causes. The 5 year absolute risk of late recurrence was calculated by cumulative incidence. We used a multivariable competing risks regression (CRR) analysis to determine the association of clinical parameters with late recurrence and treat death from other causes as competing risk. The predictor variables we tried to include are age at surgery, stage, pathology, progesterone receptor status and Charlson Comorbidity Index (CCI). Due to the limited number of recurrences, a parsimonious model with 3 predictors was desired. The model with the highest discrimination accuracy (quantified by Concordance index (CI)) selected as the basis of the final nomogram (ng). The ng was internally validated using ten fold cross-validation. The calibration of the ng prediction was checked visually by plotting the ng predicted risk of 5 year recurrence against the observed cumulative incidence from the data. Results: The 5-year risk of late recurrence or death from other causes were 0.066 (0.039 – 0.093) or 0.050 (0.026 – 0.073) respectively. The model that included age (&lt;=60 vs &gt; 60), stage (I vs others) and CCI had the highest discrimination (CI = 0.551), on which a final ng was constructed for predicting the 5-year probabilities of late recurrence. In our previous work we showed that CI in Adjuvnat Online (AO) is 0.569. Our calibration curve after ten-fold cross-validation looks comparable to AO model. Conclusions: We built and internally validated a ng for predicting the absolute probability of late recurrence for pts who completed five-year AT. Given the small size of our data set and the low number of recurrences our ng has fair discrimination and good calibration; however we were unable to outperform AO.
Microglia-Like Monocytic Cells Derived From Bone Marrow Cells Phagocytose Amyloid-β and Facilitate Phagocytosis Of Amyloid-β By Resident Microglia
Authors: Kazuyuki Takata, Yumiko Toji, Shohei Kawanishi, Tetsuya Takada, Kitamura Yoshihisa, Eishi Ashihara
Journal: Blood (2013)
Mammography screening and surgical breast cancer treatment in Norway.
Authors: P. Suhrke, J. Mæhlen, E. Schlichting, P. H. Zahl
Journal: Journal of Clinical Oncology (2011)

177 Background: We have investigated whether the introduction of organized mammography screening in Norway led to less aggressive breast cancer surgery in the invited age group. Methods: We obtained aggregate incidence and surgical treatment data for women treated for ductal carcinoma in situ or invasive breast cancer from the Norwegian Cancer Registry. Rates of breast operations (mastectomy plus breast conserving therapy) and rates of mastectomy only for three age groups; women aged 40-49, 50-69 and 70-79 years were calculated. Changes in rates from a pre-screening period (1993-95) to a screening introduction phase (1996-2004) and then to a screening period (2005-08) are presented as hazard ratios comparing invited and non-invited women. Results: From the pre-screening period (1993-95) to the screening period (2005-08) the annual breast operation rate increased by 70% (HR=1.70 95% CI 1.62 to 1.78), from 180 to 305 per 100 000 women in the invited age group (50-69 years). In contrast, the increase was only 8% (HR=1.08 95% CI 1.00 to 1.16), from 133 to 144 per 100 000 women per year in the younger, non-invited age group (40-49 years) while an 8% decline (HR=0.92 95% CI 0.86 to 1.00), from 227 to 214 per 100 000 women per year occurred in the older, non-invited age group (70-79 years). In the screening period (2005-08) mastectomy rates fell similarly in invited and non-invited women. However, during the screening introduction phase (1996-2004) the mastectomy rate was 31% (HR=1.31 95% CI 1.20 to 1.43) higher in screened compared to non-screened younger age group. Annual mastectomy rates increased in invited from the pre-screening period to the screening introduction period from 156 to 167 per 100,000 women compared to a decline from 109 to 91 per 100,000 women in younger non-invited. Conclusions: Mammography service screening is associated with a marked increase in breast operation rates in the invited age group and also an increase in mastectomy rates. While overdiagnosis likely caused the initial increase in mastectomy rates and the overall increase in use of surgery in the age group subjected to screening, the more recent decline in mastectomy rates has affected all age groups and is likely to have been caused by changes in surgical policy.
An AGITG trial –A randomised phase II study of pre-operative cisplatin, fluorouracil and DOCetaxel +/-radioTherapy based on poOR early response to cisplatin and fluorouracil for resectable esophageal adenocarcinoma
Authors: A. Barbour, E. Walpole, G.T. Mai, H. Chan, E. Barnes, D. Watson, S. Ackland, V. Wills, J. Martin, M. Burge, C. Karapetis, J. Shannon, L. Nott, V. Gebski, K. Wilson, J. Thomas, G. Lampe, J. Zalcberg, J. Simes, M. Smithers
Journal: Annals of Oncology (2016)
Pharmacokinetic Behavior of IB1001, An Investigational Recombinant Factor IX, in Patients with Hemophilia B: Repeat Pharmacokinetic Study and Subgroup Analysis
Authors: Uri Martinowitz, Amy D. Shapiro, Doris V. Quon, Miguel Antonio Escobar, Christine L Kempton, Peter Collins, Pratima Chowdary, Michael Makris, Pier Mannuccio Mannucci, Massimo Morfini, Leonard A. Valentino, Edward D. Gomperts, Martin Lee
Journal: Blood (2011)
Retroviral Gene Transfer with Triple Genetic Reporter Genes into Human Cord Blood CD133+ Cells.
Authors: Ting Niu, Amer M. Najjar, Simon N. Robinson, Hong Yang, William K. Decker, John D. McMannis, Jingjing Ng, Michael W. Thomas, Richard E. Champlin, Juri G. Gelovani, Elizabeth J. Shpall
Journal: Blood (2004)
Prognostic importance of cell-cycle activity and genotype in gastrointestinal stromal tumors.
Authors: T. Nishida, T. Omori, S. Nakayama, M. Shibayama, T. Matsushima, H. Ishihara, T. Takahashi, M. Tsujimoto
Journal: Journal of Clinical Oncology (2011)

e20501 Background: Size, mitosis and locus are important for risk stratification of gastrointestinal stromal tumors (GIST). Genotype and cell cycle are suggested related to aggressiveness and progression, and considered to have prognostic impact, although most reports have analyzed expression of proteins or mRNAs. In this study, we examined the biological and prognostic values of CDK activities in primary GIST with R0 surgery. Methods: Histologic Dx was done with HE and IH. Using lysate of frozen materials from 76 pts with GIST (n=70), leiomyoma (2), schwannoma (3) and abdominal sarcoma (1), CDK-specific activities were measured by the C2P system (activities of CDK1 & CDK2). The median age was 64 yrs and 33 (45%) pts were male. The median follow-up was 37 months. Results: KIT and PDGFRA mutations were found in 57 and 7 GIST pts, respectively, and deletion of codon 557-558 in 16 pts. Two pediatric GISTs and one with NF-1 had no mutation in both genes. CDK activities were measurable in 63 (86%) pts, and median activities of CDK1 and CDK2 of GIST (19 U and 81) were not different from those of other tumors (18 and 47). In GIST, 20 recurrences and 6 deaths were observed. Size (p=0.0001), location (p=0.0007), mitosis (p=0.0044), rupture (p=0.0105), deletion of 557-558 (p=0.0037), CDK2 (p=0.0005) and CDK ratio (CDK2/CDK1) (p=0.0004) were significantly related to recurrence. In Cox regression analysis, only mitosis (p=0.0189) and CDK2 (p=0.0070) were significantly related with recurrence. In univariant analysis, CDK2 was correlated with size, mitosis, Ki-67, location, deletion of 557-558 and rupture, and, in multiple regression analysis, CDK2 was significantly related with mitosis (p=0.0384), and marginally with location (p=0.0806). Size, location, mitosis, rupture, deletion mutations, and activities of CDK1 and CDK2 were significant prognostic factors for cause-specific survival. Conclusions: Size, mitosis, location, deletion mutation of codon 557-558 and CDK2 activity are predictive for recurrence after R0 surgery of GIST. Genotyping and cell cycle analysis may be important in GIST risk stratification.