tbuckley/cabot-search huggingface dataset:
Combretastatin A-4 phosphate (CA4P) carboplatin and paclitaxel in patients with platinum-resistant ovarian cancer: Final phase II trial results
Authors: M. Zweifel, G. Jayson, N. Reed, R. Osborne, B. Hassan, G. Shreeves, L. Poupard, P. A. Walicke, J. Balkissoon, D. Chaplin, G. Rustin
Journal: Journal of Clinical Oncology (2009)

5502 Background: CA4P is a vascular disrupting agent that in pre-clinical models can increase the efficacy of a variety of therapies. A dose escalation trial of CA4P given prior to carboplatin, paclitaxel or both showed the combination was well tolerated and responses were seen in several tumor types including 6/17 with relapsed ovarian cancer. The trial was therefore extended into a phase II trial in patients with platinum resistant ovarian cancer. Methods: Patients with ovarian cancer that had relapsed and could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63mg/m 2 18–20 hours prior to paclitaxel 175mg/m 2 and carboplatin AUC 5 repeated 3 weekly. If &gt; 2 responses were seen in first 18 patients 43 patients were to be treated to confirm response rate&gt;19%. Results: Five of the first 18 patients responded so the study was extended and closed after 44 patients were recruited, with full data available to date on 34. Weekly blood counts have demonstrated grade 3/4 neutropenia in 11 and thrombocytopenia in only 1 patient. Other grade &gt; 2 toxicity seen in &gt; 1 patient was fatigue, nausea / vomiting, pain, alopecia, rapidly reversible ataxia, diarrhoea, neuropathy and was little different to what would be expected with paclitaxel and carboplatin. Hypertension is the commonest CA4P related toxicity and was easily controlled by GTN, then prophylactic amlodipine. Responses according to GCIG criteria, have been seen in 11/34 (32%) patients with an additional unconfirmed PR. Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will hopefully confirm this. [Table: see text]
Biweekly docetaxel (Doc) followed by gemcitabine (Gem) and cisplatin (Cis) in patients (pts) with advanced non-small cell lung cancer (NSCLC): A clinical proteomic study
Authors: J. De Castro, C. Belda- Iniesta, E. Casado Saenz, J. Feliu Batlle, M. Sereno Moyano, C. Gomez Raposo, A. Pinto Marin, J. Alvar, M. González-Barón
Journal: Journal of Clinical Oncology (2007)

18096 Background: This phase II trial was carried out to test the feasibility and efficacy of sequential chemotherapy. The scheme was based on the concept of taxane sequencing in cisplatin-based doublet. Finally, we evaluated the predictive value of proteomic profile determined by SELDI-TOF for Doc responses. Methods: Eligible chemonaive stage IV and selected stage IIIB (pleural effusion) NSCLC pts received Doc 50 mg/m 2 IV day 1, every 14 days for 4 cycles followed by Gem 1,000 mg/m 2 on days 1, 8 and Cis 75 mg/m 2 on day 1, every 21 days for 4 cycles. Primary endpoints were response rate and progression-free survival. Overall survival, toxicity and predictive value of the proteomic profile were secondary endpoints. Plasma for proteomic biomarker analysis (SELDI-TOF) was taken at screening and after Doc treatment. Results: From February-05 to December-05, 39 pts were enrolled with 37 being evaluable for efficacy. Pts characteristics: Median Age: 60 years(44–82); Sex: M/F:76%/24%; Stage:IIIB/IV:32%/68%; Performance status 0/1/2:24%/65%/11%; Pathological subtypes: squamous (38%), adenocarcinoma (30%) and large cell carcinoma(32%). 15 pts showed partial response and 1 pt a complete response (objective response rate of 43%) and 14 pts had stable disease (37%). The median survival time (intent-to-treat) was 13 months with an estimated 1-year survival rate of 53%. The median time to progression was 10 months in the evaluable population. Most common grade 3–4 toxicities: After Doc treatment: anemia G3 (2 pts) and asthenia G3 (1 pt); After Gem-Cis: anemia G3 (4 pts), nausea/vomiting G3 (4 pt), neutropenia G3 (4 pts) and asthenia G3 (2 pts). There were no treatment-related deaths. Conclusions: Doc followed by Gem-Cis in sequential setting is an active, feasible and well tolerated regimen. Proteomic profile for Doc responders and no responders will be presented at the time of the meeting. No significant financial relationships to disclose.
Estrogen receptor, progesterone receptor and Her-2/neu status do not affect survival after hepatic resection of breast cancer metastases
Authors: S. R. Martinez, L. J. Foshag, D. L. Morton
Journal: Journal of Clinical Oncology (2004)

873 Background: Estrogen (ER) and progesterone receptor (PR) status and HER-2/neu protein expression are important prognostic factors for the response to various adjuvant and neoadjuvant treatments for breast carcinoma. Hepatic metastases from breast cancer are associated with a dismal prognosis, with a median survival of less than six months. We report on the utility of primary and metastatic breast cancer ER, PR and Her-2/neu expression in predicting survival after resection of breast cancer metastatic to the liver. Methods: Seventeen breast cancer patients with liver metastases underwent hepatic resection, biopsy or ablation between 1998 and 2003. Retrospective review was undertaken with respect to the following: patient age at diagnosis of hepatic metastasis; size, histology, ER status, PR status, and Her-2/neu expression of the primary tumor; axillary nodal status; and ER status, PR status, and Her-2/neu expression of liver metastases. Endpoints were overall survival from the time of primary and metastatic tumor diagnoses. Results: At a mean follow-up of 18 months after hepatic resection, the mean survival was 25 months. The average age of patients was 54.4 years. Most (90.9%) primary tumors were of ductal origin. No difference in survival from the time of primary tumor diagnosis was noted with respect to axillary nodal status (p=0.95), ER expression (p=0.96); PR expression (p= 0.07) or Her-2/neu expression (p=0.24). Similarly, no difference in survival from the time hepatic metastases were diagnosed was noted with respect to the ER, PR (p=0.38) or Her-2/neu (p=0.50) expression of the hepatic metastases. No difference in survival was noted after resection or ablation versus more limited resections or biopsy (p=0.90). Conclusions: Hepatic resection may benefit certain patients with metastatic breast cancer, but these patients cannot be identified by ER status, PR status and Her-2/neu expression. No significant financial relationships to disclose.
Ethnic variation of prognostic factors among breast cancer patients in Hawaii
Authors: J. D. Acoba, M. P. Palalay, J. Cho, D. Chow
Journal: Journal of Clinical Oncology (2004)

9512 Background: Filipino and Hawaiian women with breast cancer experience higher mortality rates than Whites and other Asian American or Pacific Island women. This discrepancy in prognosis persists after adjustment for stage and socioeconomic status, and may be due to aggressiveness of the tumors. To assess breast tumor characteristics among various ethnicities, the following analysis was performed. Methods: Data from 1195 consecutive women diagnosed between 1998–2002 were abstracted from hospital tumor registries. Data including age at diagnosis, estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status, DNA content, mitotic rate, grade, tumor size, lymph node involvement, and stage were recorded. Significant differences among ethnic groups were identified using X2 and multivariate statistical methods. Results: Filipino and Hawaiian breast cancer patients were significantly younger than White, Chinese, and Japanese patients. Filipinos and Hawaiians also presented with larger tumors, frequent lymph node involvement, and more advanced stage cancers. These two groups demonstrated higher rates of poorly differentiated tumors and HER2/neu overexpression. However Filipinos and Hawaiians differed in proportion of ER positive tumors (79% vs. 95% respectively, p<0.001). There was no significant ethnic difference regarding PR, DNA content, or mitotic rate. Conclusions: Filipinos and Hawaiians present with significantly worse prognostic tumor characteristics, and this probably contributes to their worse survival. Because they present at younger ages with more aggressive tumors, earlier screening may be warranted in these populations. No significant financial relationships to disclose.
Abstract 312: STIM1 And The Development Of Pressure-overload Induced Cardiac Hypertrophy In Rodents
Authors: Ludovic O Bénard, Daniel S Matasic, Mathilde Keck, Anne-Marie Lompré, Roger J Hajjar, Jean-Sébastien Hulot
Journal: Circulation Research (2013)

STromal Interaction Molecule 1 (STIM1), a membrane protein of the sarcoplasmic reticulum, has recently been proposed as a positive regulator of cardiomyocyte growth by promoting Ca2+ entry through the plasma membrane and the activation of Ca2+-mediated signaling pathways. We studied the role of STIM1 in a pressure-overload induced cardiac hypertrophy model in mice. We observed that STIM1 cardiac expression is increased during left ventricular hypertrophy (LVH) induced by Transverse Aortic Constriction (TAC). We then used recombinant Associated Adenovirus 9 (AAV9) to perform cardiac-targeted gene silencing in vivo. C57Bl/6 mice were injected with saline (noAAV) or with AAV9 expressing shRNA against STIM1 (shSTIM1) at the dose of 1e+11 viral genome which resulted in 70% decrease of STIM1 cardiac expression compared to control mice. Three weeks later, TAC was performed and mice were studied three other weeks later. We found that TAC-shSTIM1 treated mice did not develop LVH compared to noAAV despite the same increase in aortic pressure. Echocardiographic and hemodynamic measurements (see table) showed that TAC-shSTIM1-treated mice had LV dilation and a decreased left ventricular contractile function in line with the absence of compensatory LVH in these mice. Immunohistochemistry demonstrated that LVH prevention was observed at the cellular level with cardiac myocytes cross-section area comparable to sham littermates however with a trend towards more interstitial fibrosis. This study reveals the essential role of STIM1 in the development of compensatory LVH in mice.
Thiouracil in Toxic Goitre
Authors: D. Douglas, A. T. Kennie
Journal: BMJ (1952)

Css Valgus RigidusA. Free of pain and disablement 28 (58%,) ) 25 3 in hallux and foot(1 1 bilateral) B. Free of pain in hallux, but >89% some occasional or persis- 15 (31%) 14 1 tent pain elsewhere in foot (5 bilateral)J or disablement C. Notfreeofpainordisablement 5 (11%) 2 3(1 bilateral)
Are Guidelines Criteria for Aortic Regurgiation still Appropriate ? Results of a Natural History Study
Authors: Christophe de Meester de Ravenstein, Julie Melchior, Frederic Maes, Bernhard Gerber, David Vancraeynest, Anne-Catherine Pouleur, Philippe Noirhomme, Agnes Pasquet, Gebrine El Khoury, Jean-Louis Vanoverschelde
Journal: Circulation (2012)

Background. Indications for surgery in patients with severe AR are based on the results of a few natural history studies that were conducted before modern heart failure treatments and imaging modalities were widely available. Accordingly, the aim of the present work was to test if the criteria used to propose surgery by the guidelines are still appropriate in present times. Methods and Results. 489 patients with severe AR by Doppler echocardiography were recruited between january 1995 and december 2010. Patients were censored at the time of aortic valve surgery. Overall survival of the whole population was found to be less than that of the age- and gender matched Belgian population (83% vs 93%, log rank p  50% and those with LV end-systolic dimensions (ESD)   25 mm/m² (p<0.001, p=0.002, p=0.008 respectively). Age adjustments yielded similar results. Among the 175 initially asymptomatic patients who were followed up conservatively, the annualized risk of developing asymptomatic LV dysfunction was 0.5%/year, that of symptomatic deterioration was 2%/year and the need for surgery was 5%/year. These figures are quite similar to those reported in the literature. Conclusion. Despite significant improvements in heart failure treatments and imaging modalities, the spontaneous outcome of patients with severe AR, in the absence of surgical correction, still depends on their symptomatic status, their initial LV function and and their initial LV end-systolic dimensions, with similar cutoffs values as those reported in the guidelines. This suggests that current indications for surgery, as outlined in the guidelines are still aprropriate.
Cardiac status predicts quality of life in Hodgkin’s disease survivors
Authors: M. J. Adams, A. K. Ng, P. M. Mauch, S. E. Lipshultz
Journal: Journal of Clinical Oncology (2006)

9029 Background: Long-term survivors of Hodgkin’s disease (HD) treated with mediastinal radiotherapy suffer from a variety of subclinical cardiac abnormalities including valvar defects and findings suggestive of restrictive cardiomyopathy. Their clinical importance has not been definitively demonstrated in longitudinal studies, but they may be related to the reduced quality of life reported by many HD survivors. Methods: The overlapping participants in two independent studies of HD survivors were identified in order to form a longitudinally studied cohort. In the first study, 48 survivors of childhood and young adulthood HD were evaluated by multiple cardiac testing modalities and quality-of-life assessment including the SF-36, a mean of 16 years after diagnosis. In the second performed about 5 years later, 511 survivors took part in a survey study, which also included the SF-36 instrument. A total of 23 patients participated in both studies and formed the current study population. Correlations were performed between key cardiac abnormalities uncovered during the first study and the physical component score (PCS) of the SF-36 measured in the second study, and the changes in PCS during the time between the 2 studies. Results: Average PCS was 44.05 at time of the second study, about 6.0 points lower than at time of cardiac testing. Maximum oxygen consumption correlated with PCS at time 2 (r=0.50, p=0.029). Univariate regression suggested that for every unit decrease in maximum oxygen consumption, the PCS decreased by 0.45 units. The higher the baseline PCS, the greater the negative change in PCS. Left ventricular fractional shortening correlated with PCS at time 2 (r=−0.579, p=0.0094) but not change in PCS. Conclusions: The study suggests that objective measures of reduced cardiac function are predictive of future quality of life in HD survivors. These results however need to be verified in a larger longitudinal study that allows for multivariate analysis. No significant financial relationships to disclose.
Selective internal radiation therapy (SIRT) for treatment of patients with breast cancer with metastatic liver disease.
Authors: M. Michl, R. T. Hoffmann, R. Laubender, A. Haug, P. Bartenstein, H. Stemmler, T. Helmberger, S. Stintzing, V. Heinemann, T. F. Jakobs
Journal: Journal of Clinical Oncology (2010)

1135 Background: Selective internal radiation therapy (SIRT) has become a treatment option as salvage therapy for liver-dominant metastasis which is also used in patients (pts) with breast cancer. It is based on hepatic arterial infusion of resin microspheres containing the pure ß-emitter Yttrium-90. The goal of this cohort analysis was evaluate the clinical efficacy of SIRT and to define biomarkers predicting response to this new option. Methods: We retrospectively analyzed data from 40 pts with breast cancer (39 female, 1 male) at a median age of 60.3 yrs (31-73 yrs) who had received SIRT for metastatic liver disease from 2002-2009. We used survival analysis techniques (Kaplan-Meier estimator and Cox regression models) for this exploratory study. Results: 13 pts (33.3%) were premenopausal, 23 (59.0%) postmenopausal, and 3 (7.7%) perimenopausal; 14 pts (36.8%) overexpressed HER2/neu; 27 pts (71.1%) were hormone receptor positive; 39 pts (97.5%) had received previous chemotherapy for metastatic disease, 34 (87.2%) hormone therapy. 37 pts (94.9%) had received anthracyclines, and 34 (89.5%) taxanes before SIRT. Median time from diagnosis of breast cancer to SIRT was 6.8 yrs (1.1-27.3 yrs). In 19 pts (47.5%), metastasis was limited to the liver, 21 (52.5%) pts had liver-predominant metastasis (21 bone, 7 non-regional lymph nodes, 4 lung, 5 others). Overall response rate (ORR) in the liver was 45.5% (95% CI: 0.29-0.62). Stable disease for more than 8 weeks was achieved in 12.1% of pts. Median PFS in the liver was 3.3 mo (1.8-32.8 mo), and median TTP 3.5 mo (1.8-32.8 mo). Median overall survival (OS) was 8.2 mo. Bivariate Cox regression models (using the Wald test) for baseline biomarkers before SIRT revealed a significant correlation of CEA (p=0.022), CA 15-3 (p=0.006), and LDH (p=0.012) with OS. No correlation was observed for C-reactive protein levels (p=0.74). Conclusions: This analysis of SIRT applied in breast cancer pts with metastatic liver disease indicates substantial clinical activity of this treatment option in highly pretreated breast cancer pts. CEA, CA 15-3, and LDH baseline levels in serum before SIRT appear to be predictors for OS. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration SIRTEX
The impact of guidelines on the treatment of endometrial cancer in Germany: A nationwide analysis of the AGO in 2006 and 2009.
Authors: M. J. Battista, M. Schmidt, N. Zabel, D. Boehm, M. Mahlke, E. Steiner, H. Koelbl
Journal: Journal of Clinical Oncology (2010)

e15533 Background: The AGO established and updated guidelines on the assessment and treatment of endometrial cancer (EC) in 2006 and 2009. This prospective study tries to elucidate how patients with endometrial cancer are cared for in daily routine in Germany and to find out to which extent modification of a guideline actually changes treatment behavior on a nationwide basis. Methods: A questionnaire has been established and sent to gynecological departments in Germany. It comprises documentation of the use of peritoneal washing cytology (PWC), lymphadenectomy (LNE), adjuvant chemotherapy (CT) and adjuvant endocrine treatment (ET). The guidelines recommend performance of PWC and pelvic/paraaortic LNE. Only in very early EC disease LNE can be omitted. CT is recommended for extra-uterine disease of type I EC and for all type II EC. The guideline updated in 2009 extended the recommendation of CT by some high-risk cases of uterine disease. ET is not recommended. Results: 178/500 (35.6%) questionnaires in 2006 and 258/775 (33.3%) in 2009 were returned to our unit. A PWC was obtained in 86.9% and 94.6% in 2006 and 2009, respectively (p = 0.008). LNE in early stage type I EC was performed more frequently in 2006 as compared to 2009 (e.g., pT1a G2: 38.6% vs. 22.9%, p = 0.001; pT1b G1 47.6% vs. 39.6%, p = 0.019). In type I EC with extra-uterine disease LNE was often not advised (pelvic LNE in 2009 and 2006: pT3 76.2% vs. 80.1% and 41.5% vs. 38.0%, respectively). In 2006 and 2009 all the other stages received pelvic LNE in about 90% (e.g., pT1b G3: 96.3% vs. 95.3%; pT2a 97.6% vs. 97.6%). In 2006 paraaortic LNE was carried out less frequently compared to 2009 (e.g., pT1b G3: 70.2% vs. 90.2%, p < 0.001; pT2a: 86.3% vs. 95.7%, p < 0.001). 48.8% in 2006 vs. 63.7% in 2009 received CT (p = 0.003). 25.7% and 15.4% underwent ET in 2006 and 2009, respectively (p = 0.012). Conclusions: Common clinical-therapeutic approaches were recommended more often according to guidelines in 2009 as compared to 2006. However, there were still important aspects in the management of EC, which did not meet the recommendations of the guideline. These findings show that a better adherence to therapeutic guidelines is still warranted. No significant financial relationships to disclose.
Population based study of islet cell carcinoma
Authors: J. Mares, M. P. Eisner, C. Dagohoy, A. Phan, A. Rashid, D. B. Evans, J. C. Yao
Journal: Journal of Clinical Oncology (2007)

15103 Background: Little is known about the epidemiology and natural history of islet cell carcinoma. In this study, we examine the epidemiology, natural history, and prognostic factors impacting survival duration for islet cell carcinoma using population based registries. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program database (1973 - 2003 release April 2006) was used to identify cases of islet cell carcinoma using histology codes and tumor site. Results: 1,310 (619 women and 691 men) cases were identified. Median age at diagnosis was 59 years. The annual age-adjusted incidence in the periods covered by SEER 9 (1973–1991), SEER 13 (1992–1999), and SEER 17 (2000–2003) were 0.16, 0.14, and 0.12 per 100,000 respectively. The estimated 28-year limited duration prevalence on January 1, 2003 in the United States was 2,705 cases. Insulinomas (57%), glucagonomas (53%), and VIPomas (64%) were more likely to be located in the tail of the pancreas while gastrinomas were more likely to be located in the head of the pancreas (63%). Classified by SEER stage, localized, regional, and distant stages corresponded to 14%, 23% and 54% of cases. The median survival was 38 months. By stage, median survival for patients with localized, regional, and distant disease were 124 (95% CI, 80–168) months, 70 (95% CI, 54 - 86) months, and 23 (95% CI, 20 - 26) months respectively. By multivariate Cox proportional modeling, stage (P &lt; 0.001), primary tumor location (P = .04), and age at diagnosis (P &lt; 0.001) were found to be significant predictors of survival. Conclusion: Islet cell carcinomas account for approximately 1.3% of cancers arising in the pancreas. Most patients have advanced disease at the time of diagnosis. Despite its reputation of being indolent, survival of patients with advanced disease remains in the range of 2 years. Development of novel therapeutic approaches is needed. No significant financial relationships to disclose.
One day surgery in breast cancer patients: Safe and feasible procedure
Authors: F. Giovanardi, F. Gibertoni, L. Scaltriti, K. Cagossi, G. Di Carlo, F. Artioli, L. Cavanna, G. Giovanardi
Journal: Journal of Clinical Oncology (2008)

11589 Background: To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness. Moreover the study aimed to evaluate the management of post operative symptoms and postoperative care. Methods: From January 2006 to October 2007, all breast cancer patients undergoing conservative breast cancer surgery or total mastectomy were offered surgery as an outpatient at One Day Surgery Unit. Results: Two hundred sixty-three patients underwent outpatient surgery for a total of two hundred eighty-three surgical procedures. The age of 263 patients varied from 14 years old to 94 years old, 54 of 263 (20,5%) patients remained in the hospital for one night after surgical procedure regarding total axillary resection. In our series, no hospital readmission was recorded during the first night and the first week and no death occurred. Conclusions: Ambulatory surgery for breast cancer patients is safe and feasible. We haven’t an increased rates of physical or psychological illness from early discharge after surgery for breast cancer. This policy can be recommended for patients with support at home. No significant financial relationships to disclose.