tbuckley/cabot-search huggingface dataset:
Trial of chemotherapy (CHT) plus hormonal therapy an initial treatment for prostate cancer (PC)
Authors: T. Shu, J. Hernandez, M. Karediy, M. Khan, R. J. Amato
Journal: Journal of Clinical Oncology (2006)

14637 Background: The delivery of CHT in a setting of androgen-independent (AI) PC has demonstrated: survival benefit associated with a PSA decline and tolerable toxicity, thus strongly suggesting that disease modifying potential exists. Preclinical data supports the benefit of simultaneous CHT and androgen deprivation (AD). The stage is set for CHT to be given earlier in men with PC. Data suggests a transformation from an androgen-dependent to an AI phenotype is mediated by the expansion of an AI clone already present at the time of AD. If this model is correct, it would be feasible to bring CHT up front when the corresponding tumor burden is minimal. Methods: A course of CHT is defined as 8 weeks (6 on/2 off). The therapy consists of weeks 1, 3, and 5 with adriamycin 20 mg/m 2 as a 24 hour intravenous infusion on the first day of every week in combination with ketoconazole 400 mg orally 3 times a day, daily for 7 days. Weeks 2, 4, and 6 treatment consisted of docetaxel 35 mg/m 2 intravenously over 1 hour on the first day of every week in combination with estramustine 280 mg orally 3 times a day, daily for 7 days. Hormone therapy, GnRH antagonist, is initiated within the first 6 months of starting CHT. Following the completion of 3 courses of CHT, the addition of casodex occurs. Hormone management then continues for a total of 24 months, and then is discontinued. Patients (pts) are followed every 12 weeks with a PSA, testosterone and routine laboratory evaluation. For those men who have had a PSA recurrence, hormone therapy will be reinitiated. Results: 34 men have been enrolled to date. 47% of the men had no prior local therapy, while the other 35% had surgery, 15% had radiation therapy or 3% had both. 3% had a gleason 6, 41%/7, 26%/8, 27%/9 and 3%/10. 64% of the men presented with bone and/or nodal metastasis. Baseline median PSA was 11.2 (1.0–1065.5). The median PSA reduction to date has been 96% with associated nodal and bone scan improvement. Conclusion: Information regarding PSA response, radiographic outcome, toxicity and results of men who are discontinuing hormones will be presented. [Table: see text]
Docetaxel-gemcitabine in patients with HER2-negative metastatic breast cancer pretreated with anthracyclines.
Authors: Y. L. Bautista Aragon, M. A. Pluma Jimenez, A. J. Silva, M. Perez, J. A. Gutierrez, R. Villalobos, S. Rivera
Journal: Journal of Clinical Oncology (2010)

e11516 Background: Advanced breast cancer represents 15% in our institution. HER2-negative patients pretreated with anthracyclines reached their maximum efficacy with combination antimetabolites and taxanes, however optimal dose and schedule with less adverse effects is unknown. Methods: Seventeen women received gemcitabine 800 mg/m2 on days 1 and 8, and docetaxel 75 mg/m2 on day 1, with cycles repeated every 3 weeks. Results: The median age was 47 years old (39 to 61 years), objective responses were observed in 7 out of 17 evaluable patients (41%). Complete and partial response was 11% and 29%. Median time to progression 5.3 months. Treatment was usually well tolerated, with neutropenic fever in 11% of patients, grade 3 trombocytopenia in 5%, and grade 3-4 diarrea in 11% of patients. Conclusions: Gemcitabine-docetaxel combination with this dose is effective and well tolerated as first-line treatment in advanced breast cancer previously treated with anthracyclines. No significant financial relationships to disclose.
Trastuzumab plus capecitabine with or without pertuzumab in patients with HER2-positive MBC whose disease has progressed during or following trastuzumab-based therapy for first-line metastatic disease: A multicenter, randomized, two-arm, phase II study (PHEREXA).
Authors: M. Munoz-Mateu, A. Urruticoechea, R. Separovic, J. Erfán, T. D. Bachelot, J. Canon, N. Kovalenko, E. Staroslawska, B. Pikó, C. Veyret, O. Pribylova, D. L. Ciule, J. Ratnayake, S. Das, K. Mayne, G. Ross
Journal: Journal of Clinical Oncology (2011)

TPS118 Background: Pertuzumab (P) is a promising new anti-HER2 antibody which has shown both activity and good tolerability when combined with trastuzumab (H) in patients with HER2-positive breast cancer. Capecitabine (X) in combination with H has been shown to be more efficacious than X alone as second-line treatment of patients with HER2-positive metastatic breast cancer (MBC). The PHEREXA study is designed to investigate the potential benefit of administering P and H combined with X in patients with HER2-positive MBC whose disease has progressed during or following H-based therapy for first-line MBC. Methods: In this multicenter, open-label, Phase II trial (NCT01026142), patients are randomized 1:1 to Arm A (H: 8 mg/kg loading dose followed by a 6 mg/kg maintenance dose; X: 1250 mg/m2 twice daily for 14d q3w) or Arm B (H: 8 mg/kg loading dose followed by a 6 mg/kg maintenance dose; X: 1000 mg/m2 twice daily for 14d; P: 840 mg loading dose and 420 mg thereafter q3w). Enrolment began in January 2010 and 450 patients are to be recruited from ~130 sites in 19 countries. Eligible patients must have HER2-positive MBC (fluorescence or chromogenic in situ hybridization-positive and/or immunohistochemistry 3+), which has progressed during or following H-based therapy for first-line MBC, prior taxane, and left ventricular ejection fraction (LVEF) ≥50% at baseline. Exclusion criteria include prior treatment with X or P, concurrent immunotherapy or hormonal anticancer therapy, and history of LVEF decline to <50% during prior H-based therapy. The primary endpoint is progression-free survival (PFS; independent assessment). Secondary endpoints include overall survival, PFS (investigator assessment), safety/tolerability. It is planned that a panel of biomarkers including HER 1, 2 and 3 receptor status and downstream markers will be analysed. No untoward safety signals have yet been identified. There are currently 58 patients randomized in the study (as of 13 January 2011).
Prediction of distant relapse risk in stage I-II non-small cell lung cancer (NSCLC) by gene expression profiling
Authors: J. Jassem, M. Jarzab, J. Niklinski, W. Rzyman, M. Kowalska, M. Oczko-Wojciechowska, G. Kobierska-Gulida, L. Chyczewski, B. Szostakiewicz, B. Jarzab
Journal: Journal of Clinical Oncology (2007)

7657 Background: Our aim was to determine the genes predictive for relapse-free and overall survival in stage I-II NSCLC. Methods: We analyzed the gene expression profiles in lung cancer specimens collected from 70 NSCLC patients (pts) who underwent curative pulmonary resection between 1999 and 2004 in two Polish centers (Gdansk, Bialystok). There were 54 men and 16 women aged 37–77 yrs (median 62.5 yrs), 45 with squamous cell ca, 22 with adenoca and 3 with large cell ca. Eight pts were staged pT1, 59 pT2 and 3 pT3; there were 49 and 21 pN0 and pN1 pts, respectively. 30 pts had a relapse and 32 pts died (median follow-up 36 months). Samples of tumor tissue were collected intraoperatively and snap-frozen, total RNA was isolated and gene expression profiling was carried out by Affymetrix HG-U133 2.0 Plus oligonucleotide microarray. Samples were pre-processed with RMA algorithm, gene selection was carried out by Support Vector Machines and Bayesian Compound Covariate Classifier, using own procedures and BRB-Array software developed by Simon and Peng Lam. Survival time prediction was carried out by method developed by Bair and Tibshirani (PLoS Biology 2004). Results: Based on the microarray gene expression profiling, the relapse could be predicted with 75.0% specificity and 53.3% sensitivity (positive predictive value [PPV] 61.5%, negative predictive value [NPV] 68.2%). The classifier, obtained by cross-validation of 70-sample dataset, consisted of 170 transcripts. Further gene selection was based on the prediction of the relapse-free survival: 1,919 genes, selected by fitting Cox proportional hazard model (p&lt;0.05) and further used to predict survival by 4 principal components, distinguished between pts with high and low risk of relapse (p&lt;0.05, log-rank test). The prediction of death was possible with 66.7% specificity and 57.1% sensitivity (PPV 53.3%, NPV 70%), but the distinction between high- and low-risk pts was significantly weaker than based on lymph node involvement (N0 vs. N1). Thus, for the final selection of genes this clinical variable was incorporated into the model as a covariate. Conclusions: Prediction of the risk of relapse in stage I-II NSCLC based on the gene expression profile is feasible, with NPV of 68.2%. No significant financial relationships to disclose.
A phase II trial of topotecan and ifosfamide in patients with previously treated, advanced non small cell lung carcinoma (NSCLC)
Authors: V. Gebbia, M. Spada, G. Cassano, C. Brunetti, D. Germano, G. Nettis, A. Misino, D. Sambiasi, D. Galetta, V. Lorusso
Journal: Journal of Clinical Oncology (2004)

7314 Background: A number of second line treatments have been proposed in patients (pts) with advanced pretreated NSCLC. However, either single agents or two or three drug combinations achieved very poor results with no superiority of any combination over single agents. Methods: In this study we have treated 42 pts affected by advanced NSCLC previously submitted to chemotherapy (CT) with topotecan (1.2 mg/m2 ) plus ifosfamide (1,200 mg/m2) for 3 consecutive days every 3 weeks. The median age was 63 yrs with a range between 43 and 76; male/female ratio was 30/12; 14 pts had squamous carcinoma, 7 adenocarcinoma, 3 large cell, 2 broncho-alveolar carcinoma and 16 NSCLC not otherwise specified. All but one pts had previously received one CT regimen: 36 pts a cisplatinum based, 2 pts a carboplatin regimen and one pt an oxaliplatin based regimen. Moreover, one pt had previously received gemcitabine plus vinorelbine and one docetaxel alone as first line chemotherapy. The only naïve patient was included in the trial because of poor PS due to presence of brain metastases. The ECOG PS was 0 in 8 pts (19%), 1 in 11 pts (26%) and 2 in 23 pts (55%). The median number of courses administered was 3,3 (range 1–8). Results: Partial response (PR) was observed in 5/41 pretreated pts (12,2%) and in the naïve patient. In addition, one (2,4%) minimal (<50%) response (MR) plus 14 (34%) stable disease (SD) and 21(51%) progressive disease (PD) were observed. Grade 3–4 neutropenia was the dose limiting toxicity, observed in 36% of pts. Moreoveer, grade 3–4 anemia was observed in 17% and grade 3–4 thrombocytopenia in 12% of pts, respectively. One PS 2 patient died for grade 4 hematological toxicity after the first cycle. Median survival for the entire group was 26 weeks (range 1–91+) with 14% of pts alive at one yr. Conclusions: In conclusion, the combination of topotecan and ifosfamide demonstrated antitumor activity with modest side effect profile in patients with previously treated NCSLC, with an overall disease control (PR+MR+SD) of 48.8%. Nevertheless, the still low response rate and the shortness of median survival claim for more effective second line treatments in this disease. No significant financial relationships to disclose.
Abstract 9779: Nitric Oxide Generated Through Ascorbic Acid Reduction of Nitrogen Dioxide Reduces Pulmonary Vascular Resistance in Hypoxemic Swine with Minimal Inhaled and Exhaled Nitrogen Dioxide
Authors: Mark A Lovich, Natalie K Bruno, Abraham E Wei, Mikhail Y Maslov, Ryan J Denton, Lucas G Gamero, Gregory B Vasquez, Richard J Gilbert
Journal: Circulation (2011)

Background: Inhaled nitric oxide (NO) has the capacity to selectively dilate pulmonary blood vessels and improve oxygenation in patients with pulmonary diseases. NO in the presence of oxygen spontaneously converts to nitrogen dioxisw (NO 2 ), a toxic byproduct with multiple adverse pulmonary effects. The potential for co-inhalation of NO 2 drives delivery system complexity, gas monitoring and cost. We demonstrate a new method for generating inhaled NO based on reducing NO 2 just prior to inhalation, using ascorbic acid/silica gel reactor cartridges (GeNO, LLC). Ascorbic acid protonates NO 2 , yielding NO, water and dehydroascorbic acid. This reaction occurs within the ventilator hoses, leaving little time for NO 2 reformation. Methods: In vivo efficacy was assessed through the inhalation of NO (1, 5, 20, and 80 PPM) in hypoxemic swine (FiO 2 15%). NO 2 in N 2 was mixed with O 2 prior to entry into the hoses of a portable ventilator upstream of two ascorbic acid cartridges in series. Inhaled and exhaled NO and NO 2 were sampled using in-line electrochemical detectors (step response time &lt; 0.8 s, GeNO, LLC). Results: Inspired and expired NO 2 was always under 0.3 PPM in 50% and 0.9 PPM in 100% O 2 (Fig. 1). Inhaled NO significantly reduced the hypoxemia elevated mean pulmonary artery pressure and pulmonary vascular resistance at all doses (Fig. 2). Conclusion: Inspired and even expired NO 2 levels were low using ultra-fast electrochemical methods. NO supplied by this novel system was capable of reversing hypoxemia induced pulmonary hypertension. The lack of co-delivered toxic NO 2 may allow for a substantial reconsideration of the therapeutic role of inhaled NO in a wide range of respiratory diseases.
Escalating dose of continuous infusion combination chemotherapy for refractory neuroblastoma.
Authors: L A Campbell, R C Seeger, R E Harris, J G Villablanca, K K Matthay
Journal: Journal of Clinical Oncology (1993)

PURPOSE This trial was undertaken to determine if a continuous infusion format with increased dose-intensity had antitumor activity with tolerable toxicity in patients with advanced neuroblastoma. PATIENTS AND METHODS Forty heavily pretreated patients with refractory or progressive neuroblastoma received continuous infusion doxorubicin, cisplatin, and etoposide along with bolus ifosfamide in a dose-escalation format. A total of 79 courses of chemotherapy were administered at five different dose levels. RESULTS Fifteen of 35 assessable patients (43%) achieved either a partial response (PR) or complete response (CR), including five patients with a CR, three with a very good PR (VGPR), and seven with a PR. Hematologic toxicity was severe, but reversible, and other toxicities, although significant, were tolerable and much less than that accepted in a bone marrow transplantation (BMT) setting. CONCLUSION This investigation illustrates that response is possible even in an extremely poor-prognosis group of patients, and it suggests that such a regimen may be effective if given before disease progression occurs.
Abstract 15919: Cardiac Sympathetic Blockade Increases Hyperemic Myocardial Blood Flow Assessed by Contrast-Enhanced Ultrasound
Authors: Carolien S Bulte, Stephan A Loer, Otto Kamp, Christa Boer, R. A Bouwman
Journal: Circulation (2012)

Introduction Perfusion of the myocardium is primarily regulated by local metabolic and endothelial factors. Cardiac sympathetic fibers play an additional modulatory role. With this study, using hig...
Significance Of Minimal Residual Disease Detected By Multi-Color Flow Cytometry In Childhood Acute Myeloid Leukemia With The Intermideate-Risk Cytogenetics and Negative FMS-Like Tyrosine Kinase 3 Internal Tandem Duplication: A Report Of The Tokyo Children's Cancer Study Group
Authors: Dai Keino, Akitoshi Kinoshita, Daisuke Tomizawa, Hiroyuki Takahashi, Kohmei Ida, Hidemitsu Kurosawa, Kazutoshi Koike, Setsuo Ota, Noriyuki Iwasaki, Junya Fujimura, Yuki Yuza, Chikako Kiyotani, Shohei Yamamoto, Tomoo Osumi, Takahiro Ueda, Shinji Mochizuki, Keiichi Isoyama, Ryoji Hanada, Akio Tawa, Akira Kikuchi, Atsushi Manabe, Akira Ohara
Journal: Blood (2013)
Abstract 18234: Body Mass Index and Body Mass Index Z Score Trajectories from Birth to Adolescence
Authors: Masao Yoshinaga, Yumiko Ninomiya, Yuji Tanaka, Kazuyuki Tanoue, Norihito Nuruki, Masahiro Sonoda, Hideto Takahashi, Masaki shinomiya, Ayumi Miyazaki
Journal: Circulation (2012)

Background: There are 3 critical periods for developing obesity during childhood: the fetal period; a period of adiposity rebound between 4-6 years; and during adolescence. The approach of latent class growth ascertains the most interpretable set of classes. The resulting categorical latent variable represents the groups of homogenous individuals within the class to which they belong. Aim: We hypothesized that the early infantile period is another critical period at risk for developing obesity in adolescents using latent class growth models based on longitudinal height and weight data. Methods: The study cohort included 913 healthy adolescent volunteers (396 males and 517 females) aged 15-18 years in Japan. Complete data sets for height and weight at birth, 1.5, 3, 6, 9 and 12 years of age, as well as at present, were obtained. Body mass index (BMI) and age- and sex-specific BMI Z scores were used as measures of obesity. Adiposity rebound was defined as the point of minimal BMI during infancy. Three-group latent class growth models were used in the present study. Results: The BMI trajectories showed that individuals who consistently increased in BMI during infancy, i.e., they showed no adiposity rebound, were at the highest risk for adolescent obesity in both sexes. The Z score trajectories revealed that male subjects who were born with high Z scores and whose scores remained at high levels, as well as those who were born with low Z scores and whose scores had a sharp increase from birth to 1.5 years, were at risk for developing obesity. Female subjects who were born with relatively high Z scores and whose scores had a sharp increase from birth to 1.5 years were at risk. A representative figure is shown as Fig 1. Conclusion: These data suggest that the early infantile period is important for preventing further development of obesity. Further more detailed studies are required to identify individuals and the exact timing of the critical periods during early infancy to prevent later obesity.
Pulmonary lymphangitis and cancer: Prospective series of 37 patients in palliative care
Authors: A. A. Dettino, E. M. Negri, T. Pagano
Journal: Journal of Clinical Oncology (2006)

18600 Background: Lymphangitis of the lungs is an uncommon type of metastasis, mainly in breast, lung and gastric cancers, and has major impact in quality of life and an unfavorable prognosis. Survival is very poor: 50% in 3 and 15% in 6 months. Our objective was to evaluate prospectively quality of life in cancer patients with pulmonary lymphangitis, under palliative care. Methods: Patients with pulmonary lymphangitis, diagnosed either by lung biopsy (major criteria) or 3 minor criteria (cyto or histotologically proven cancer, clinical picture and image exam) were followed in 3 tertiary services, in a cohort series study. Primary end point was quality of life (QoL), measured with questionnaires in the beginning of the study and monthly afterwards (Saint George Respiratory Questionnaire -SGRQ- and Medical Outcomes Study 36-Item Short-Form Health Survey -SF36). Clinical and complementary aspects were also followed, in addition to treatment and outcome. Results: Thirty-seven patients were included from Aug/2004 to Jan/2006 - 23 female and 14 male; age from 41 to 84 (mean: 62) years. Primary tumors were: lung (20), breast (11), esophagus (2), pancreas, rectum and bone. Of those patients, 33 were able to respond QoL questionnaires in the beginning of follow-up and monthly thereafter. Median follow-up was of one month (range: 0–13); at the moment, 9 patients are still alive. Median survival was 2.5 months (range: 0,1–33), with 38% with a survival of at least 6 months. In general, QoL was poor, but improved after palliative care. Notice that values get higher as QoL improves in SF-36; however, they get lower as QoL improves in SGRQ - values were 61.5, 50.5, 61.7, and 47.5% for SGRQ and 38.1, 32.1, 32.8, 61.6 for SF36 in 0, 1, 3 and 6 months, respectively. Palliative care included: corticosteroids (65%), oxygen (51%), opioids (51%), diuretics (47%), inhalations with beta2-agonists and/or ipatropium (57%), chemo and/or hormonotherapy (51%), physical therapy (43%), antidepressants and benzodiazepines (37% each), thoracocentesis (35%), and blood transfusions. Conclusions: Even though QoL is poor and survival is short for patients with cancer lymphangitis in lungs, some improvement is possible with active palliative care. No significant financial relationships to disclose.
Preoperative risk assessment of pancreatic surgery for pancreatic cancer by the surgical Apgar score.
Authors: Toru Aoyama, Yusuke Katayama, Masaaki Murakawa, Masahiro Asari, Koichiro Yamaoku, Amane Kanazawa, Akio Higuchi, Manabu Shiozawa, Makoto Ueno, Manabu Morimoto, Makoto Akaike, Naoto Yamamoto, Takashi Oshima, Yasushi Rino, Munetaka Masuda, Soichiro Morinaga
Journal: Journal of Clinical Oncology (2015)

419 Background: Postoperative morbidity is high after pancreatic surgery. Numerous studies have evaluated factors to predict the patients at risk. Recently, a simple and easy-to-use surgical complication prediction system, the surgical Apgar score (SAS) calculated using three intraoperative parameters (estimated blood loss, lowest mean arterial pressure and lowest heart rate) has been proposed for general surgery. In this study, we evaluated the predictability of the SAS for severe complications after pancreatic surgery for pancreatic cancer. Methods: We investigated 189 patients who underwent pancreatic surgery at Kanagawa Cancer Center between 2005 and 2014. Clinicopathological data, including the intraoperative parameters, were collected retrospectively. In this study, the patients with postoperative morbidities classified as Clavien-Dindo grade II or more were classified as having severe complications. Uni- and multivariate logistic regression analyses were performed to identify the risk factors for morbidity. Results: Postoperative complications were identified in 73 patients, and the overall morbidity rate was 38.6%. The results of both univariate and multivariate analyses of various factors for overall operative morbidity showed that a SAS of 0-4 points and a body mass index &gt; 25 kg/m 2 were significant independent risk factors for overall morbidity (P=0.024 and P=0.014, respectively). The rate of abdominal abscess formation was significantly higher in the patients with a SAS of 0-4 points, while the occurrence of a pancreatic fistula was significantly higher in the patients with a body mass index &gt; 25 kg/m 2 . Conclusions: The SAS was a significant risk factor for surgical complications after pancreatic surgery for pancreatic cancer. Careful attention is required for these patients in order to help prevent complications and treat them as soon as they develop.