tbuckley/cabot-search huggingface dataset:
Prevalence and characteristics of patients with metastatic prostate cancer who receive no anticancer therapy.
Authors: Alexander C. Small, Che-Kai Tsao, Erin Moshier, James Godbold, Guru Sonpavde, William K. Oh, Matt D. Galsky
Journal: Journal of Clinical Oncology (2012)

101 Background: Clinical experience reveals that a subset of patients presenting with advanced solid tumors, including prostate cancer, never receive anticancer therapy due to a variety of factors including poor functional status, comorbidities, and patient preference. We sought to determine the prevalence, and characteristics, of this patient population. Methods: The National Cancer Database (NCDB) was queried to identify patients diagnosed with stage IV prostate cancer between 2000 and 2008. Patients who received no anticancer therapy (including chemotherapy, hormonal therapy, radiation, and surgery) were identified and were further categorized by age, race, insurance status, and income. For these subcategories, prevalence ratios were generated using the proportion of untreated metastatic prostate cancer (uMPC) to metastatic prostate cancer (MPC). Results: Of the 1,201,732 patients with prostate cancer diagnosed between 2000-2008, 59,074 (4.9%) had MPC. Of those patients presenting with MPC, 6582 (11.1%) received no anticancer therapy. With every 10-year increase in age, the prevalence of uMPC increased 43% (PR=1.43; p&lt;0.0001). Blacks (PR=1.32, p&lt;0.0001) and Hispanics (PR=1.41, p&lt;0.0001) were more likely than Caucasians to have uMPC. With every $10,000 increase in income the prevalence of uMPC decreased by 7% (PR=0.93; p&lt;0.0001). Patients with Medicaid were 57% more likely to be untreated, patients with Medicare were 82% more likely to be untreated, and uninsured patients were 96% more likely to be untreated than those patients with private insurance (p&lt;0.0001). Conclusions: A large subset of patients presenting with MPC never receive anticancer therapy. While tumor biology likely plays a role with regard to rapid disease onset and progression, these data suggest that age, racial and socioeconomic disparities exist in the treatment of MPC.
Abstract 12198: Left Ventricular Filling Pressure Assessed by E/e' of Women is Higher than Men in Patients with a First ST Elevation Acute Myocardial Infarction
Authors: Noriaki Iwahashi, Kazuo Kimura, Masaomi Gohbara, Mistauaki Endo, Nobihiko Maejima, Kengo Tsukahara, Yoshio Tahara, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Shinichi Sumita, Toshiyuki Ishikawa, Kazuaki Uchino, Satoshi Umemura
Journal: Circulation (2012)

Many studies of sex-related differences in the short and long term outcomes of acute myocardial infarction (AMI) have concluded that mortality is higher among women than men. However, ...
Comparison of four strategies of follow-up in thyroid cancer patients: A cost-utility analysis
Authors: G. de Pouvourville, I. Borget, M. Allyn, M. Schlumberger
Journal: Journal of Clinical Oncology (2007)

6606 Background: In thyroid cancer patients, follow-up is designed to detect recurrent disease and consists of neck- ultrasonography (US), thyroglobulin measurement (Tg) and radioiodine whole body scan (WBS). Recent guidelines have restricted the use of WBS to suspicious cases. To insure diagnostic accuracy, follow-up control requires TSH stimulation, either with thyroid hormone withdrawal (THW) or rhTSH, which have demonstrated similar diagnostic accuracy. THW induces significant morbidity associated with hypothyroidism, leading to a decrease in patient quality of life and ability to work, whereas rhTSH is an innovative costly drug that avoids such patient burden. A societal cost-utility analysis was conducted to compare 4 follow-up strategies, combining a method of stimulation (rhTSH or THW) and a testing protocol (US+Tg+WBS or US+Tg alone). Methods: A Markov model was built to describe the follow-up of thyroid cancer patients first treated by thyroidectomy and radioiodine ablation, over 5 years. Estimates for diagnostic accuracy values and recurrence rate were extracted from a French multicenter randomized trial. Costs were computed from the perspective of the society, including medical resources consumed (hospitalisation, rhTSH, tests, treatment of recurrence). The model also incorporated the benefits of rhTSH in terms of quality of life (utility scores derived from SF36) and the reduction in duration and overall cost of sick leave. Results: Among the 753 patients included, 13 patients presented recurrence. rhTSH stimulation resulted in a higher utility score (0.802 vs. 0.637) over the period of stimulation and a reduction of 1083 € of absenteeism costs in active patients. As compared to the THW+Tg+US+WBS strategy, the incremental cost-utility ratios (ICER) showed economic dominance for the rhTSH strategies with ratios of −16,876 and −19,297 €/QALY with and without WBS respectively. The ICER for the strategy THW+US+Tg reached 29,333 €/QALY, as compared to THW+Tg+US+WBS strategy. Conclusions: the recommended strategy combining Tg determination and US after rhTSH stimulation appears the most cost-effective in the follow-up of thyroid cancer patients, as it is the strategy the less costly and associated with improved patient quality of life. No significant financial relationships to disclose.
P0081 : Reduced calcineurin inhibitor exposure early after liver transplantation protects against renal dysfunction independently of the use of basiliximab induction therapy
Authors: S. Onali, A. Mansell, S. Aspite, L De Luca, E. Tsochatzis, J. O’Beirne, D. Patch, D. Thorburn, M. Pinzani, P. Manousou
Journal: Journal of Hepatology (2015)
Chemoembolization with epirubicin drug-eluting beads (DEB-TACE) to treat early and intermediate hepatocellular carcinoma.
Authors: A. Nicolini, A. Sangiovanni, M. Iavarone, L. Martinetti, M. A. Manini, S. Crespi, C. Della Corte, S. Vavassori, M. Colombo
Journal: Journal of Clinical Oncology (2010)

4141 Background: The transarterial DEB-TACE) is a new treatment modality for hepatocellular carcinoma (HCC), whose effectiveness is poorly known. Aim: We prospectively studied the response rates to treatment and survival of patients with either Barcelona Clinic Liver Cancer (BCLC) A listed for liver transplantation (LT) or not suitable for radical therapy, and those with intermediate stage (BCLC B). Methods: 56 patients, mean age 64 yr, 36 Child-Pugh A, 24 Child-Pugh B, 32 BCLC A, 24 BCLC B, HCV related cirrhosis in 36 (64%), HBV in 1 (2%), ethanol in 7 (12%), mixed etiology in 10 (18%), cryptogenetic in 2 (4%). Serum alfafetoprotein (AFP) > 100 ng/mL in 17 (31%). Excluded were 2 patients with hypovascular tumors. DEB-TACE was repeated every other month with epirubicin (Pharmorubicin, Pfizer, Italy) loaded 100-300 μ m DC Bead (Biocompatibles, UK), until disappearance of tumor vascularization or disease progression by contrast CT scan, performed one month apart each treatment. Treatment response was evaluated by EASL modified criteria. Treatment other than DEB-TACE was allowed in patients lacking access to tumor feeding artery only. Results: After 2.2 (1-7) cycles, there were 10 (18%) complete response (CR), 16 (29%) partial response, 4 (7%) stable disease, 23 (41%) disease progression and 3 (5%) not evaluable. Neither major side-effects nor liver deterioration followed DEB-TACE. Eighteen patients (32%) required treatments other than DEB-TACE; OLT was performed in 9 (16%). Yearly mortality rate was 24%, with a median survival of 32 months (21 % and 33 months for BCLC A and 27% and 26 months for BCLC B). Child-Pugh (p = 0.043), AFP > 100 ng/mL (p = 0.01), albumin < 3.8 g/dL (p = 0.01) and ascites (p = 0.045) were significantly correlated to survival. By multivariate analysis AFP > 100 ng/mL was the only predictor of survival (p = 0.039). Conclusions: DEB-TACE is an effective and well tolerated treatment for early/intermediate HCC in patients with < 100 ng/mL AFP values. No significant financial relationships to disclose.
The role of BRCA1 in DNA repair and chemosensitivity
Authors: V. B. Sharma, A. W. Kurian, A. Feldman, J. M. Ford
Journal: Journal of Clinical Oncology (2007)

10606 Introduction: The BRCA1 tumor suppressor protein has been implicated in many cellular processes, including several different DNA repair pathways. Inherited mutations in the BRCA1 gene result in an increased risk for developing breast and ovarian cancer. BRCA1 associated tumors are frequently estrogen receptor negative thus rendering them ineffective targets of hormonal manipulations. Therefore chemotherapy is the only treatment option available to patients with metastatic disease. Methods: Global genomic repair activity was detected by an immunoslotblot assay. UV-C and chemosensitivity was determined by the MTT assay. The comet assay was used to measure oxidative DNA damage (ODD). Results: Brca1 deficient cells demonstrate decreased global genomic repair independent of p53 expression. These cells are 3-fold more sensitive to UV-C radiation, 5-fold more sensitive to cisplatin, and 25-fold more sensitive to gemcitabine than Brca1 positive cells. The combination of cisplatin and gemcitabine is synergistic. This synergy is independent of Brca1 protein expression. In addition, the cholesterol lowering drug lovastatin is able mitigate the ODD caused by hydrogen peroxide. Reduced ODD is also observed in breast epithelial cells from high risk patients after 6 months of oral lovastatin use. Discussion: These results confirm our earlier findings that BRCA1 is involved in the nucleotide excision repair pathway. In addition, we demonstrate that this effect is independent of p53 expression. We also find that Brca1 deficient MMECs are more sensitive to UV-C, and the cytotoxic drugs cisplatin and gemcitabine. Cisplatin is known to cause DNA intra- and inter-strand crosslinks whereas gemcitabine is a nucleoside analog. The increased sensitivity of Brca1 deficient MMEC's to these agents supports the role of Brca1 in the different molecular pathways involved in their repair. In addition, we demonstrate that lovastatin can overcome ODD in vitro and in vivo and may be an effective agent to modify breast cancer risk for individuals at increased risk. No significant financial relationships to disclose.
Final results of a phase I trial with the novel anthracycline derivative RTA 744 in patients with primary brain tumors
Authors: C. A. Conrad, E. Maher, T. Cloughesy, M. Groves, M. Gilbert, T. Madden, V. Levin, W. Priebe, C. Meyer, W. Yung
Journal: Journal of Clinical Oncology (2007)

2062 Background: RTA 744 is an anthracycline derivative that was shown preclinically to cross the blood-brain barrier, not be a substrate for P-gp or MRP, and improve survival in an orthotopic murine model of glioblastoma. A trial of RTA 744 was conducted in patients with progressive high-grade gliomas. Methods: RTA 744 was administered as a 2-hour intravenous infusion on each of the first 3 days of a 21-day cycle. Five dose levels were tested until an MTD was reached. Pharmacokinetic samples were taken at multiple time points on days 1–5 of cycle 1. Tumor activity was assessed according to the MacDonald criteria. Results: As of December 2006, RTA 744 has been administered to 20 patients at doses ranging from 1.2 to 9.6 mg/m 2 /day. The MTD was determined as 7.5 mg/m 2 /day, and the DLTs were neutropenia and thrombocytopenia. No neurotoxicity, cardiotoxicity, alopecia, or drug-related nausea and vomiting were reported. The pharmacokinetic profile indicates dose proportionality, with a mean plasma half-life of 35 hours. Clear evidence of anti-tumor activity has been reported in 7 of 20 patients. A Complete Response was observed in a patient with GBM after seven cycles at 2.4 mg/m 2 /day, the patient continues greater than 5 months post-RTA744 treatment. Additionally, a Partial Response (81% tumor reduction) has been observed in a patient with AO after two cycles at 7.5 mg/m 2 /day who continues on treatment at this time. A Minor Response was observed at 2.4 mg/m 2 /day, and several patients have experienced Stable Disease of several months duration. Two patients with stable disease have shown radiographic evidence of necrosis. Median time to tumor progression was 6 weeks (range 2 to &gt;50). Median number of cycles was 2 (range 1 to 7). The study is now enrolling additional patients at the MTD to further profile the drug’s safety and activity. Additionally, a once-weekly dosing schedule is being tested in a satellite cohort. Conclusions: RTA 744 is well tolerated when administered at doses up to and including 7.5 mg/m 2 /day for the first three days of a 21-day cycle. Based on clear evidence of drug activity, pivotal trials of RTA 744 in high-grade gliomas are planned as well as trials in patients with brain metastases. [Table: see text]
Variations in the clinical or histologic presentation of lymphoid pathologies over the course of time.
Authors: P. Sabin Dominguez, J. Gómez-Codina, M. Llanos, A. Rueda, J. Guma, A. Blasco, J. R. Delgado, D. Aguiar, F. J. Perez, M. Provencio
Journal: Journal of Clinical Oncology (2011)

e18539 Background: Little data is available concerning variations in the clinical characteristics of lymphoid pathologies at presentation. We decided to investigate whether any variations in these aspects had occurred in our environment during the last few years. Methods: The GOTEL group database is an archive of all new lymphoma cases, regardless of their histological subtype, diagnosed in the hospitals within the group. An analysis was made of all the records between 1st January 1999 and 1st January 2010. The number of hospitals submitting data has changed over the course of time, however data has been provided by 26 hospitals from 16 Spanish provinces. Results: A total of 3,651 cases of lymphoma were recorded within this period. Grouped by clinical features, 42.8% (1,561 patients) presented low-grade lymphomas, 30.4% (1,110 patients) intermediate-grade lymphomas, 15.2% (556 patients) Hodgkin’s lymphomas, there were 208 patients with T lymphoma (5.7%), 111 patients with high-grade lymphomas (3%), and 105 patients (2.9%) with lymphomas that were difficult to classify. A total of 6.3% of the diagnoses (231 patients) were performed prior to 1999, 29.5% between 2000 and 2001, 25.7% between 2002 and 2003, 19.7% between 2004 and 2005, 11.2 % between 2006 and 2007, and 200 entries from 2008 to the close of the study period, corresponding to 1.5% of the complete database. The median age at diagnosis was 60 years (range 7-105 years), by percentiles: 25 correspond to 44 years, 50 to 60 years and 75 to 71 years. The distribution by gender was 53.1% male, and 46.9% female. An analysis was made of all the clinical variables collected, comparing their behaviour during the different diagnostic periods. Neither the periods, gender, ECOG, stage, LDH, β2 microglobulin, Hodgkin’s or non Hodgkin’s type neoplasia, B Lymphoma versus Hodgkin’s, NK or T, nodal or extra-nodal origin, median age at diagnosis nor histological type by region of origin, showed any statistically significant differences in their distribution over the course of time. Conclusions: In our experience, there are no significant variations in the clinical presentation or histological type in lymphomas diagnosed over the course of time in Spain.
Detection and characterization of liver lesions in patients with colorectal cancer with diffusion weighted MR imaging
Authors: E. J. Rummeny, M. Bruegel, K. Holzapfel, C. Ganter, C. Mayer zum Bãschenfelde, J. Gaa
Journal: Journal of Clinical Oncology (2008)

4071 Background: In patients with colorectal cancer detection and differentiation of liver metastases is important for further treatment decissions. Recently diffusion weighted MR imaging (DWI) was introduced as an new technique for liver tumor detection and characterzation. DWI is sensitive to molecular diffusion which is the random thermal motion of molecules (Brownian motion). MR imaging is the only method by which molecular diffusion processes can be evaluated in vivo. New techniques, such as breath-hold imaging or respiratory triggered single shot echo-planar-imaging (EPI) allow to extent DWI to abdominal organs, especially the liver. First results show that DWI can be used for the reliable detection of small subcentimeter liver lesions. We evaluated this new imaging method with regard to liver lesion detection and lesion characterization in patients with colorectal cancer. Methods: 115 consecutive patients with colorectal cancer and suspected liver metastases were evaluated with multi slice-CT and MRI at 1.5 Tesla using T1- and T2-weighted pulse sequences as well as DWI with respiratory triggered single shot echo-planar-imaging (EPI). Images were analyzed by two experienced radiologist blinded to the clinical results. Results for lesion detection for CT and DWI-MRI were compared using ROC analysis. Furthermore, in a subset of 60 patients diffusion coefficients (ADCs) were calculated for the differentiation of liver lesions (benign vs malignant). Results: For lesion detection ROC analysis showed superiority (p< 0.05) of DWI as compared to MS-CT. Especially metastases with diameters of smaller 1 cm were better detected with DWI-MRI as compared to MS-CT (p < 0.02). Results for differentiation show mean ADC-values of 1.24 for normal liver while malignant tumors have ADCs of 1.04–1.22 and benign lesions such as hemangiomas or cysts of 1.9 to 3.0, respectively. Furthermore, therapeutic changes were made in 20 % of patients based on DWI. Conclusions: MR imaging using DWI is more sensitive than multi- detector row CT in the detection and characterization of liver metatstases from colorectal cancer. Thus, it can be used as a new method for liver lesion detection and characterization as well as for optimal treatment planning. No significant financial relationships to disclose.
A Killed Vaccine Derived From the Oncogenic Herpesvirus ateles2
Authors: Rainer Laufs, Hans Steinke
Journal: JNCI Journal of the National Cancer Institute (1975)

A killed herpesvirus vaccine was prepared by inactivation of the oncogenic Herpesvirus ateles (HVA) with heat and formaldehyde. The vaccine proved safe in 9 marmosets (Saguinus oedipus) during a period of 461 days. The vaccinated marmosets developed high titers of serum antibodies against HVA and were resistant to 316 lethal dose 50 (LD50) cell-free HVA; the nonvaccinated control monkeys died of malignant lymphoma. The 5 challenged monkeys are clinically well and have now been under observation for 362 days.
Changes in sexual function over time in women receiving adjuvant therapy for early stage breast cancer
Authors: J. E. Mortimer, B. Burke, S. Fisher, Y. Podbilewicz-Schuller
Journal: Journal of Clinical Oncology (2004)

622 Background: The impact of cancer therapy on sexual functioning has not been systematically studied over time in women undergoing adjuvant therapy for breast cancer. Patients were enrolled in a trial addressing the impact of surgery, chemotherapy (CT), and tamoxifen (TAM)on sexual function. Methods: Within 30 days of initiating adjuvant therapy, and 2, 6, and 12 mos. afterwards, women completed the Sexual History Form (Nowinki & Lopiccolo; Schover & Jensen). Results:75 women were enrolled with a mean age 53.7 yrs; (range 28–82 yrs); 50 (67%) were Caucasian, 22 (29%) African-American, 1 Asian, and 1 unknown. 44 (59%) underwent lumpectomy and radiation (XRT) and 31 (41%) mastectomy. CT alone was administered in 32 (43%), CT and TAM in 14 (19%), and TAM alone 20 (27%). Baseline scores were identical for women undergoing mastectomy vs. lumpectomy/XRT (p=1.0), CT vs. no CT(p=0.13), and any TAM vs. no TAM (p=0.63). After initiation of adjuvant therapy, sexual function worsens initially and improves by 12 mos. Differences between lumpectomy/XRT and mastectomy patients were not significant. Scores are expected to increase (worsen) by 3.7 points for lumpectomy/ XRT patients vs.1.8 points for mastectomy patients over the first 6 mos.of therapy, yet by 12 mos. lumpectomy/XRT patients are expected to improve by 5.1 points beyond their initial scores in contrast to mastectomy patients whose scores increase further by 1.4 points. Women receiving TAM had lower sores at 2, 6 and 12 mos. than those not receiving TAM. Women on chemotherapy exhibited the overall pattern of initial decline in sexual function with a rebound to initial level by 12 mos. In contrast, the scores of those not receiving chemotherapy steadily improved over time, an expected improvement of 11.2 points over initial levels by 12 mos. (p=0.11). Conclusions: Surgery and adjuvant therapy may adversely impact patients sexual functioning. Women treated with mastectomy and those receiving CT experienced worsening of sexual functioning, but did return to baseline levels by 12 mos. Supported by NIH CA72554-O2. No significant financial relationships to disclose.
Clinical and translational results of CALGB 40601: A neoadjuvant phase III trial of weekly paclitaxel and trastuzumab with or without lapatinib for HER2-positive breast cancer.
Authors: Lisa A. Carey, Donald A. Berry, David Ollila, Lyndsay Harris, Ian E. Krop, Douglas Weckstein, Norah Lynn Henry, Carey K. Anders, Constance Cirrincione, Eric P. Winer, Charles M. Perou, Clifford Hudis
Journal: Journal of Clinical Oncology (2013)

500 Background: Recent trials in HER2-positive (HER2+) breast cancer (BrCa) demonstrate increased pathological complete response (pCR) using dual HER2-targeting in the neoadjuvant setting and increased progression-free survival in metastatic disease. CALGB 40601 aimed to further quantify the pCR rates of weekly paclitaxel (T) and trastuzumab (H) alone or combined HER2-blockade of H with the small molecule lapatinib (L), and to identify biomarkers of sensitivity to these HER2-targeted agents. Methods: Eligible patients had newly diagnosed, noninflammatory stage II-III HER2+ BrCa and were randomized to receive T (80mg/m2/week IV) + H (4mg/kg then 2mg/kg/week IV) alone (TH) or with the addition of L (750 mg/d PO) (THL) for 16 weeks preoperatively. A third arm, T + L (1500 mg/d) (TL), was closed early when negative efficacy and toxicity data emerged from preliminary analysis of ALTTO. After surgery, 4 cycles of adjuvant dose-dense AC and 1 year H was recommended. Tumors were biopsied for research before therapy; post-Rx samples of residual disease were requested. The primary endpoint was in-breast pCR rate; the study had 85% power to detect an increase from 30% (TH) to 50% (THL). Results: 305 patients were randomized (118 THL, 120 TH, 67 TL); 68% were clinical stage II and 59% hormone receptor-positive. Grade 3+ toxicity was higher among L-containing arms, including neutropenia (12% TL, 7% THL, 2% TH), rash (15% TL, 14% THL, 2% TH), and diarrhea (20% TL, 20% THL, 2% TH). Breast pCR rates with 95% confidence limits were: 51% (42-60%) THL, 40% (32-49%) TH, 32% (22-44%) TL. pCR rate in the TH arm was higher than previous studies, and was not significantly different from THL (p=0.11). We will present molecular subtype, sequence and gene copy number abnormalities in primary tumors and residual disease. Conclusions: pCR rate was higher with combined THL compared with standard TH but did not reach statistical significance. These results are qualitatively similar to other neoadjuvant studies in HER2+ BrCa, and contribute to estimates of pCR rates after these agents. Tissue-based studies may illuminate which patients benefit from HER2-targeting using these agents. Clinical trial information: NCT00770809.