tbuckley/cabot-search huggingface dataset:
Brain metastasis-free survival in patients with HER2-positive metastatic breast cancer.
Authors: A. Berghoff, Z. Bago-Horvath, P. C. Dubsky, M. Rudas, U. Pluschnig, A. Rottenfusser, M. Gnant, G. G. Steger, C. Zielinski, R. Bartsch
Journal: Journal of Clinical Oncology (2011)

41 Background: Brain metastases (BM) are diagnosed in up to 40% of patients with HER2-positive metastatic breast cancer (MBC). Since the introduction of trastuzumab in 1999, a rising incidence of BM was reported. We aimed to identify factors that prolong BM free survival (BMFS) in all HER2-positive patients (pts) treated for MBC at the Medical University of Vienna from 1999-2009. Methods: BMFS was defined as primary study endpoint and measured as the interval from diagnosis of metastatic disease until diagnosis of brain metastases. 201 pts with HER2-positive MBC were identified from a breast cancer database. 82 pts (40.8%) were diagnosed with BM; 13 pts were excluded from this analysis as brain was the first site of disease progression. Complete data sets of 69 pts with pathologically verified HER2-positive MBC were available. HER2 status was analyzed by immunohistochemistry and reanalyzed by FISH if a score of 2= was gained. BMFS was estimated by using the Kaplan-Meier product-limit method; factors significantly associated with BMFS in the univariate analysis were included into a Cox proportional hazard model. Results: Median BMFS was 25 months (m; 95%CI 13.37-36.63 m). Trastuzumab-based treatment significantly prolonged median BMFS (29 vs. 11 m; p&lt;0.01); BMFS was further improved by trastuzumab treatment in multiple lines (30 vs. 17 m; p=0.045). Co-positivity for estrogen receptor (ER) and HER2 predicted for longer BMFS (30 vs. 15 m; p&lt;0.05). Further variables such as prior exposure to capecitabine, presence of visceral metastasis, presence of lung metastasis, stage IV disease at primary diagnosis, as well as disease free interval from adjuvant therapy were not significantly associated with BMFS. In the Cox regression model, positive ER status (HR 2.03; 95%CI 1.22-3.36; p&lt;0.05) and trastuzumab-based treatment (HR 2.72; 95%CI 1.20-6.17; p=0.017) remained independent predictors for longer BMFS. Conclusions: Trastuzumab-based therapy significantly prolongs BMFS in HER2-positive pts with MBC, probably due to improved systemic disease control. In line with known better survival outcome, ER/HER2 co-positive disease appears to be a less aggressive subtype of HER2-positive breast cancer associated with longer BMFS.
Irinotecan-induced neutropenia and UGT1A1*28: Does dose matter?
Authors: J. M. Hoskins, R. M. Goldberg, H. L. McLeod
Journal: Journal of Clinical Oncology (2007)

4023 Background: On July 7 2005, the Food and Drug Administration (FDA) of the U.S.A. and Pfizer Pharmaceuticals changed the package insert information for irinotecan to include a patient’s UGT1A1*28 genotype as a risk factor for severe neutropenia. This change resulted from the findings of four pharmacogenetic studies that identified a 2.5 to 17-fold risk of toxicity in homozygous UGT1A1*28 patients receiving irinotecan. Notably, a total number of 34 patients in the four studies were homozygous for the UGT1A1*28 allele. Subsequent studies on larger patient cohorts treated with other dosage regimens have failed to consistently replicate the UGT1A1*28 genotype-toxicity associations, thus confounding the development of dosing recommendations. This has contributed to confusion on how best to select a safe dose of irinotecan for a patient who is homozygous for UGT1A1*28. Methods: We reviewed the data presented in ten irinotecan pharmacogenetic studies (825 patients) and assessed the correlations between the incidence of irinotecan-induced hematological toxicities (grade III/IV) in UGT1A1*28/*28 patients, irinotecan dose, and overall toxicity. Results: We found that the incidence of grade III/IV hematological toxicities in UGT1A1*28/*28 patients was positively related to both irinotecan dose (Spearman Rank correlation r S =0.68; P=0.04; N=10 studies) and the overall incidence of toxicity of a regimen (r S =0.88; P=0.002; N=10 studies). The incidence of severe hematological toxicity amongst all patients was not related to irinotecan dose (r S =0.44; P=0.20, N=10 studies). Conclusions: Our results suggest that the risk of experiencing irinotecan-induced hematological toxicity for UGT1A1*28/*28 patients is a function of the dose of irinotecan administered. In the spirit of maximizing patient safety, we support the use of genotype-based dosing of irinotecan for high doses of irinotecan, but believe it may not be as useful for lower doses and suggest strategies for dosing patients with irinotecan. [Table: see text] No significant financial relationships to disclose.
Long-term effects following 4 years of randomized treatment with atorvastatin in patients with type 2 diabetes mellitus on hemodialysis
Authors: Vera Krane, Kay-Renke Schmidt, Lena J. Gutjahr-Lengsfeld, Johannes F.E. Mann, Winfried März, Florian Swoboda, Christoph Wanner
Journal: Kidney International (2016)
Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7
Authors: H Hasle, M Aricò, G Basso, A Biondi, A Cantù Rajnoldi, U Creutzig, S Fenu, C Fonatsch, OA Haas, J Harbott, G Kardos, G Kerndrup, G Mann, CM Niemeyer, H Ptoszkova, J Ritter, R Slater, J Starý, B Stollmann-Gibbels, AM Testi, ER van Wering, M Zimmermann
Journal: Leukemia (1999)
Clinical variables are associated with treatment satisfaction in patients with breast, lung, and colorectal cancer
Authors: P. C. Trask, C. Tellefsen, D. Espindle, C. Getter, K. Yost, M. Hsu
Journal: Journal of Clinical Oncology (2007)

6608 Background: The association between clinical variables (e.g. disease stage/type, side effects, ECOG performance status (PS)) and patient-reported treatment satisfaction has received little attention, despite the potential implications for treatment adherence and decision-making. We examined the relation between clinical variables and treatment satisfaction in a U.S. sample of patients with breast (BC), lung (LC), or colorectal (CRC) cancer using the Cancer Treatment Satisfaction Questionnaire (CTSQ), a recently validated 16-item measure designed to assess expectations of therapy (ET), feelings about side effects (FSE), and satisfaction with therapy (SWT). Methods: Cancer stage, line of therapy, physician-reported ECOG PS, presence vs. absence of medication side effects, and perceived change in cancer over the last two weeks were obtained on patients. These clinical variables were examined in relation to the ET, FSE, and SWT scales of the CTSQ. Higher scale scores indicated better outcomes (e.g., better satisfaction). Group means were compared using one-way ANOVAs; trends of scale scores across clinical variables were also examined. Results: Participants were 349 patients with early and late stage BC (n=137), CRC (n=121), or LC (n=91) who had ≥ 1 cycles of chemo-, bio-, or hormonal therapy in the last 6 months. In all cancer types, FSE differed by presence of side effects (BC&lt;.03; CRC&lt;.01; LC&lt;.02). In BC patients, FSE differed by stage, and ET differed significantly depending on ECOG PS (p&lt;.006) and perceived change (p&lt;.05). For CRC patients, ET significantly differed by stage (p&lt;.05) and perceived change (p&lt;.02); and SWT by presence of side effects (p&lt;.01). SWT also differed by perceived change (p&lt;.01) for LC patients. Most trends were in the expected direction. Conclusions: These results indicate that patient-reported satisfaction with therapy is correlated with clinical variables. On average, patients who perceive less improvement in their cancer, have side effects, and poorer ECOG PS are less satisfied with their current cancer therapy. Unknown is the impact of this relation on adherence and decision-making. Recent changes in healthcare suggests that treatment satisfaction may become an increasingly important measure of clinical outcome. No significant financial relationships to disclose.
Human Gastric Choriocarcinoma Serially Transplanted in Nude Mice2
Authors: Toru Kameya, Yukio Shimosato, Masaru Tumuraya, Nakaaki Ohsawa, Tatsuji Nomura
Journal: JNCI Journal of the National Cancer Institute (1976)

A gastric choriocarcinoma cell line capable of producing human chorionic gonadotropin (HCG) was studied by sc transplantation and serial passages into nude mice fed under specific pathogen-free (SPF) conditions. The tumor-take rate at the serial heterotransplantation in SPF mice was high (greater than 95%), in contrast with a low rate in coventional animals (35%). The restoration of morphology and function of the original neoplasm were exclusively verified in SPF mice. Multiple lung metastases were found in 2 animals. The production, storage, and excretion of HCG by tumor cells were confirmed by its high content in serum and cystic fluid in tumors and by its intracellular localization. The tumor cells also contained a specific placental alkaline phosphatase in their membranes. The cells were various trophoblastic types ranging from primitive cytotrophoblasts to typical syncytial cells. The hormone effects of the tumor on sex organs of tumor-bearing animals were evident.
Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non–Small Cell Lung Cancer Whose Tumors Harbor Uncommon EGFR Mutations
Authors: Barbara Klughammer, Wolfram Brugger, Federico Cappuzzo, Tudor Ciuleanu, Tony Mok, Martin Reck, Eng Huat Tan, Paul Delmar, Gaëlle Klingelschmitt, Anny-Yue Yin, Olivia Spleiss, Lin Wu, David S. Shames
Journal: Journal of Thoracic Oncology (2016)

IntroductionExon 19 deletions and the exon 21 L858R mutation of the epidermal growth factor receptor gene (EGFR) predict activity of EGFR tyrosine kinase inhibitors, including erlotinib; however, the ability of less common EGFR mutations to predict efficacy of erlotinib is unclear.MethodsThe efficacy of erlotinib in individual patients with rare EGFR mutations from the MERIT, SATURN, TITAN, TRUST, ATLAS, BeTa, and FASTACT-2 trials was analyzed and compared with data from the literature.ResultsIn the patients tested for biomarkers, the frequency of rare mutations identified here ranged from 1.7% (eight of 467) in the SATURN study to 7.4% (27 of 364) in ATLAS. Some rare mutations were associated with greater clinical benefit from EGFR tyrosine kinase inhibitor therapy or improved prognosis independent of treatment, whereas others appeared to have a poorer prognosis. In particular, exon 18 G719 mutations, exon 19 K757R and E746G mutations, the exon 20 S768I mutation, and the exon 21 G836S mutation appeared to confer a good outcome with erlotinib treatment, whereas exon 18 S720I showed a particularly poor outcome. Owing to the small number of patients with each mutation, however, it is difficult to confirm whether these rare mutations do indeed confer sensitivity or resistance to erlotinib.ConclusionsErlotinib can have different efficacy depending on the specific EGFR mutation. More research is needed to create a central database such as the My Cancer Genome database of rare mutations to definitively confirm whether these mutations are activating, resistant, or neutral.
Presentation characteristics, risk profiles and long-term outcomes in a public health system, minority patient population with diffuse large B-cell lymphoma
Authors: S. Sreenivasappa, S. Nathan, L. Fochesatto, T. Braik, N. Ignatius, D. Griza, M. Telfer, R. Catchatourian
Journal: Journal of Clinical Oncology (2008)

8590 Background: Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive form of non-Hodgkin lymphoma. We sought to characterize DLBCL in the minority patient (pt) population. Methods: 133 DLBCL pts treated at Cook County Hospital, Chicago, IL were studied as a retrospective cohort for clinical presentation, prognostic characteristics and long-term survival. Clinical and survival data were analyzed using ANOVA, Chi-square test and Kaplan Meier life-table analyses. Results: 133 pts [age at diagnosis 52.2 ± 14.2 yrs, 68 (51.1%) males, 53 (29.8%) African American (AA), 48 (36.1%) Hispanic (H), 32 (24.1%) Others (O) [Caucasian, Middle Eastern, Asian] were identified. 22 (16.5%) pts were Limited Stage [Stage 1,2 without B symptoms (BS) or bulky disease (BD)] and 111(83.5%) pts, Advanced Stage (Stage 3,4 or with BS or BD). 72 pts (54.1%) had extranodal involvement. 17 pts (12.8%) had very good risk (IPI 0), 70 (52.6%) good risk (IPI 1,2) and 46 (34.6%) poor risk (IPI 3,4,5). Treatment included regimens with and without Rituxan and radiation therapy. Complete response (CR) was seen in 88 (66.1%) and partial response (PR) in 31 (23.3%) pts with relapsed disease after CR in 11 pts (8.3%). Of the 3 ethnic groups, H pts were younger [(48.2 ± 16.1 yrs vs. AA: 54.8 ± 13.5 yrs vs. O: 53.8 ± 12.6 yrs, p=0.05). Both advanced stage at presentation (H: 79.2% vs. AA: 86.8% vs. O: 84.4%, p=NS) and poor risk IPI (H: 33.3% vs AA: 32.1% and O: 40.6%, p=NS) were comparably distributed. Survival at 29.0 ± 27.3 mos follow-up, was similar (H: 87.5% vs. AA: 88.7% vs. O: 87.5%, p=0.97). Conclusions: This minority-based DLBCL pt cohort was younger with more advanced disease at diagnosis than historical controls. Hispanic patients while generally younger, had comparable disease stage and risk profiles at presentation as the other subgroups with no differential survival noted between groups. Further investigations of disease and healthcare disparities in the underserved minority population, are warranted. No significant financial relationships to disclose.
Abstract 15491: Mitochondria Calcium Flux Plays an Important Role in Triggered Activity in Cardiomyocytes With Reduced Sarcoplasmic Reticulum Calcium Release
Authors: An Xie, Hong liu, Qiongyin Wang, Lianzhi Gu, Man Liu, Cody Rutledge, Jing Li, Terry L Vanden Hoek, Kenneth R Boheler, Samuel C Dudley
Journal: Circulation (2013)

Introduction: Decreased ryanodine receptor 2 (RYR2) levels and reduced RYR2 activity has been detected in several heart failure (HF) models. Up to 50% of HF associated sudden cardiac deaths are cau...
Allergenicity of mare’s milk in children with cow’s milk allergy
Authors: Luisa Businco, Paolo Gianni Giampietro, Patrizia Lucenti, Flavia Lucaroni, Carlo Pini, Gabriella Di Felice, Patrizia Iacovacci, Claudia Curadi, Mario Orlandi
Journal: Journal of Allergy and Clinical Immunology (2000)
Steady-state levels and bone marrow toxicity of etoposide in children and infants: does etoposide require age-dependent dose calculation?
Authors: J Boos, S Krümpelmann, P Schulze-Westhoff, T Euting, F Berthold, H Jürgens
Journal: Journal of Clinical Oncology (1995)

PURPOSE Most pediatric treatment protocols specify dose calculations for cytostatic drugs based on body-surface area (BSA). However, for children less than 1 year of age, calculation guidelines vary. Normally, reduced dosages are recommended with calculations based on body weight (BW). However, the optimal dose for infants should take age-dependent and drug-specific pharmacokinetic parameters into account. PATIENTS AND METHODS The current investigation focused on the effects of different dose-reduction rules on the steady-state levels (Css) of etoposide and related bone marrow toxicity. One hundred seventy three treatment courses in 78 children on a 96-hour continuous infusion schedule were monitored for Css (determined by high-performance liquid chromatography [HPLC]), and 100 courses were documented in detail with regard to dose calculation (125 mg/m2, 4.17/kg, or 2/3 x 4.17/kg) and toxicity. RESULTS Dose calculation on the basis of BSA led to Css of 4.9 +/- 1.2 micrograms/mL, which on the basis of BW was 3.5 +/- 1.1 micrograms/mL and 1.95 +/- 0.6 micrograms/mL (2/3.kg-dose), respectively. However, conversion of the latter levels to those expected with the regular square-meter-dose, resulted in values of 4.7 +/- 1.4 micrograms/mL and 4.2 +/- 1.2 micrograms/mL (/125 mg/m2). Lower etoposide Css levels resulted in less pronounced thrombocyte and WBC nadirs in the respective groups. The dose-calculation rules for infants, therefore, decreased both dose-intensity and related toxicity. Etoposide clearance rates related to BW (0.8 +/- 0.3 mL/min/kg) or BW (19 +/- 6 mL/min/m2) did not show any differences between children and infants, even in the age range of 3 to 12 months. CONCLUSION In the case of etoposide, special dose-calculation guidelines for infants are not substantiated by age-dependent pharmacokinetics or tolerance.
Delayed antiemetic treatment for weekly chemotherapy: Overview of 275 patients enrolled in 6 phase II trials of vhemotherapy in metastatic breast vancer
Authors: E. Terzoli, A. Fabi, E. Bria, D. Giannarelli, F. Cuppone, P. Vici, N. Salesi, P. Astorre, F. Cognetti, C. Nisticò
Journal: Journal of Clinical Oncology (2005)

8057 Background: Although weekly administration is a frequent way to administer chemotherapy, current guidelines for the prevention and control of both acute and delayed emesis do not consider such schedule. In this analysis, we retrospectly review the delayed nausea and vomiting pattern of 6 different weekly schedules in 1st line-2nd line chemotherapy for MBC patients (pts). Patients: We gathered 6 databases from 1990 to 2003, comprising of 275 patients participating in phase II trials in MBC pts using weekly chemotherapy. The trials evaluated activity and tolerability of weekly epirubicin (25 mg/m2/wk) with either lonidamine (450 mg/d) (EL, 51 pts), vinorelbine (25 mg/m2/wk) (EN, 52 pts) and paclitaxel (80 mg/m2/wk) (ET, 53 pts), in 1st line, and weekly vinorelbine (N, 25 mg/m2/wk, 40 pts), weekly docetaxel (D, 35 mg/m2/wk, 28 pts), and weekly paclitaxel (80 mg/m2/wk) plus 5-fluorouracil (300 mg/m2/wk) (TF, 51 pts) in 2d line, for 24 weeks. We considered epirubicin-based as moderately emetogenic chemotherapy (MEC), and non- epirubicin-based therapy as low emetogenic chemotherapy (LEC). For acute emesis, pts received dexamethasone 8 mg plus anti-5HT3 day 1 i.v. No antiemetic prophylaxis was given for delayed emesis. Nausea/vomiting grade 1–4 were compared (MEC vs LEC; polychemotherapy vs monochemotherapy). Results: In overall 275 pts, only 1 patient (0.4%) showed delayed G3 nausea/vomiting. No grade 4 was observed. Grade 1 and 2 were observed in 27.2% and 14.2% of the pts. MEC (156 pts) was administered as 1st line treatment, while LEC (119 pts) as 2nd line. Conclusions: In our series of pts, moderate delayed emesis (Grade 2) is not significantly different when comparing weekly MEC versus LEC. Acute antiemetic medication covers delayed emesis well for weekly MEC and LEC. Our results suggest that no prophylactic corticosteroids are needed for delayed emesis, when weekly MEC or LEC are administered. No significant financial relationships to disclose.
Fine-needle aspiration of a retropharyngeal lymph node guided by endoscopic ultrasonography
Authors: Jian-Jun Li, Long-Jun He, Guang-Yu Luo, Li-Zhi Liu, Xin-Xin Huang, Ke Pan, Guo-Liang Xu
Journal: Endoscopy (2015)

Recently, we developed a novel, minimally invasive technique – endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) via the nasopharynx – to obtain tissue samples from a retropharyngeal lymph node (RPLN) in a patient with suspected recurrent nasopharyngeal carcinoma [1]. A schematic diagram of EUS-FNA of an RPLN is shown in [Fig. 1 a].
BET Bromodomain Inhibition as a Therapeutic Strategy in Ovarian Cancer by Downregulating FoxM1
Authors: Zhenfeng Zhang, Pengfei Ma, Ying Jing, Ying Yan, Mei-Chun Cai, Meiying Zhang, Shengzhe Zhang, Huixin Peng, Zhi-Liang Ji, Wen Di, Zhenyu Gu, Wei-Qiang Gao, Guanglei Zhuang
Journal: Theranostics (2015)

Ovarian cancer is responsible for the highest mortality among all gynecologic malignancies, and novel therapies are urgently needed to improve patient outcome.Here we performed an integrative genomic analysis and identified the bromodomain and extraterminal domain (BET) protein BRD4 as a potential therapeutic target in ovarian cancer.Suppression of BRD4 using small-molecule BET inhibitors JQ1 and I-BET151, or dual kinase-bromodomain inhibitor volasertib, led to robust and broad antitumor effects across all subclasses of ovarian cancer.In contrast to many other cancers which are susceptible to BET inhibition due to downregulation of super-enhancer-dependent MYC transcript, we discovered that JQ1-sensitive ovarian cancer cells exhibited marked disruption of Forkhead box protein M1 (FoxM1) pathway, a key driver of ovarian carcinoma.These in vitro findings were further supported by in vivo efficacies of JQ1 targeting both cell line-based and patient-derived xenograft models.Our data establish a new treatment strategy against ovarian cancer by employing epigenetic vulnerabilities, and provide a mechanistic rationale for the clinical investigation of BET bromodomain inhibitors in this deadly disease.
Long-term follow-up of women enrolled in a randomized trial of adjuvant chemotherapy for early stage ovarian cancer (ICON1)
Authors: A. C. Swart
Journal: Journal of Clinical Oncology (2007)

5509 Background: ICON1 and a meta-analysis of all relevant trials demonstrated an improvement in 5 year recurrence-free and overall survival (RFS and OS) for women with early-stage epithelial ovarian cancer (ES EOC) treated with adjuvant chemotherapy compared to no adjuvant chemotherapy. We aimed to determine if this initial benefit is maintained long-term and whether benefit is different with different risk groups of patients defined by stage, grade and histology. Method: 477 women with ES EOC were recruited from centres in Italy (271 women) UK (195) Switzerland (11) between August 1991 and January 2000. 5-year results were presented at ASCO 2001. Systematic long-term follow up was planned and completed in May 2006. Results: With a median follow-up of 9.2 years, 168 women have developed recurrent disease or died and 144 women have died. The Hazard Ratio (HR) for RFS of 0.70 in favour of adjuvant chemotherapy (95% CI 0.52–0.95 p= 0.023) translated into an improvement of 10-year absolute RFS of 10% from 57 to 67%. For OS, HR was 0.74 (95% CI 0.53–1.02 p= 0.066), a corresponding improvement in 10-year absolute OS of 8% from 64% to 72%. 26% of patients died from causes other than ovarian cancer. Stage I patients were grouped as low (Ia, grade 1), medium (Ia grade 2, Ib or Ic grade 1) and high risk (Ia, grade 3, Ib or IC grade 2 or 3, any clear cell). The test of interaction between risk groups and adjuvant treatment for RFS and OS was 0.055 and 0.13, respectively. The HR, 95%CI and p value are summarised in the table . Conclusions The long-term benefit of adjuvant treatment on RFS is confirmed. There is clear evidence that adjuvant chemotherapy reduces the risk of recurrence/death or death alone in high-risk patients but not in the low-risk group. [Table: see text] [Table: see text]