tbuckley/cabot-search huggingface dataset:
Treatment of advanced non-small cell lung cancer in the elderly: Spanish Lung Cancer Group (SLCG) experience
Authors: M. Provencio, C. Camps, V. Alberola, M. Dómine, D. Isla, R. De las Peñas, O. Etxaniz, M. Cobo, I. Millán, B. Massuti
Journal: Journal of Clinical Oncology (2007)

18012 Background: The number of elderly patients (p) with cancer continues to increase. Approximately two-thirds of p diagnosed with non-small cel lung cancer are &gt; 65 years (y), and nearly 50% are &gt; 70 y. The aim of our study was to discern whether clinical characteristics, toxicity, response rate, treatment and survival are different in p &lt; 70 y vs p = 70 y. Methods: We reviewed the database of 6 SLCG clinical trials with different doublet combinations from 2000 to 2005 Results: Of 1653 p included, only 280 p (17% ) were = 70 y. No significant differences were found between the two groups with respect to gender, stage, response rate or histology. However, a higher frequency of squamous cell carcinoma was found in p = 70y. No differences were found in median number of cycles administered. The only significant difference was found in the higher frequency of grade 3–4 neutropenia among p = 70 y. (Table) Conclusions: p = 70 y were a small percentage of all p included in these clinical trials. However, outcome and toxicities were similar in p = 70y vs &lt;70 y, and “fit” elderly p can be treated with standard doublets. Further research is warranted on genetic differences for customizing treatment in this population. [Table: see text] No significant financial relationships to disclose.
George Kenneth Mackenzie
Authors: J. I. (Mackenzie)
Journal: BMJ (2011)

George Kenneth Mackenzie (“Mac”) was born in 1911 and graduated MB ChB from Edinburgh University in 1936.

He served as lieutenant surgeon in the Royal Navy in destroyers during the second world war in the North Atlantic, Normandy, the Far East, and West Africa, where he met his English wife, Marjorie.

He gained his MD in 1951 and settled in family practice in West Linton, Peeblesshire.

A much loved singlehanded general practitioner of the old school, he was …
A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.
Authors: Yoshikazu Kotani, Miyako Satouchi, Masahiko Ando, Kazuhiko Nakagawa, Nobuyuki Yamamoto, Yukito Ichinose, Yuichiro Ohe, Makoto Nishio, Toyoaki Hida, Koji Takeda, Tatsuo Kimura, Koichi Minato, Akira Yokoyama, Shinji Atagi, Taro Shibata, Haruhiko Fukuda, Tomohide Tamura, Nagahiro Saijo
Journal: Journal of Clinical Oncology (2012)

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m 2 ) iv on days 1, 8, and 15, and P (60 mg/m 2 ) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m 2 ) iv on day 1-3, and P (60 mg/m 2 ) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m 2 to 35 mg/m 2 . At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.
Abstract 18511: Appropriateness of Coronary Interventions for Chronic Total Occlusion in Japan based on the U.S. Appropriateness Use Criteria
Authors: Taku Inohara, Shun Kohsaka, Hiroaki Miyata, Ikuko Ueda, Kentaro Hayashida, Yuichiro Maekawa, Akio Kawamura, Keiichi Fukuda
Journal: Circulation (2014)

Introduction: Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is widely performed in Japan, despite its technical difficulty, perceived risk of complications, and, most of all, insufficient evidence-based validation. We sought to assess its appropriateness on the basis of the appropriateness use criteria (AUC) developed by multiple American professional organizations in 2012.

Methods: Japanese Cardiovascular Database (JCD-KICS) is a large-scale multicenter PCI registry in Japan established in 2009, and is structured in collaboration with the NCDR®. We assigned an appropriateness rating to 4950 consecutive PCIs for non-acute indications registered in JCD-KICS according to the AUC. The current appropriateness criteria contain 5 CTO related scenarios (#24-29). The ratings were compared between the PCIs for lesions with and without CTO.

Results: Mapping failures were identified in 2521 procedures, and were mainly due to the PCIs without performing the prior stress test (n=934) and staged PCIs (n=750). Among 2429 successfully mapped PCIs, a total of 213 (8.8%) PCIs for CTO were identified. CTO cases had higher rates of multi-vessel diseases (16.4% vs. 10.9%, p=0.039), and were more frequently evaluated with coronary computed tomography angiography (42.7% vs. 31.5%, p=0.001). Only 16.9% of CTO cases were successfully assigned to CTO related scenarios, and other cases were mapped to non-CTO related scenarios. Overall, the rate of inappropriate indications was lower in PCIs for lesion with CTO than those without (22.5% vs 31.5%, p=0.006).

Conclusions: In contemporary multicenter Japanese PCI registry, as much as one-tenth of non-acute PCIs were attempted on CTO lesion. Despite the common belief that CTO related PCIs are performed under insufficient evidence, most of these procedures were performed under appropriate indications. However, further revision of AUC with additional CTO related scenarios are necessary for its rigorous evaluation.
Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes–Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies
Authors: Andreas M. Neophytou, Marquitta J. White, Sam S. Oh, Neeta Thakur, Joshua M. Galanter, Katherine K. Nishimura, Maria Pino-Yanes, Dara G. Torgerson, Christopher R. Gignoux, Celeste Eng, Elizabeth A. Nguyen, Donglei Hu, Angel C. Mak, Rajesh Kumar, Max A. Seibold, Adam Davis, Harold J. Farber, Kelley Meade, Pedro C. Avila, Denise Serebrisky, Michael A. Lenoir, Emerita Brigino-Buenaventura, William Rodriguez-Cintron, Kirsten Bibbins-Domingo, Shannon M. Thyne, L. Keoki Williams, Saunak Sen, Frank D. Gilliland, W. James Gauderman, Jose R. Rodriguez-Santana, Fred Lurmann, John R. Balmes, Ellen A. Eisen, Esteban G. Burchard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking.To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry.The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry.A 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function.Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.
Identification of biomarkers for overall survival of patients with metastatic renal cell carcinoma treated with MGN1601.
Authors: Viktor Grünwald, Steffen Weikert, Ingo G.H. Schmidt-Wolf, Stefan Hauser, Ekaterina Weith, Matthias Schroff, Manuel Schmidt, Marina Tschaika, Burghardt Wittig
Journal: Journal of Clinical Oncology (2013)

468 Background: The cell-based therapeutic cancer vaccine MGN1601 consists of two active pharmaceutical ingredients in fixed combination. Fourfold gene-modified, allogeneic tumor cells expressing IL-7, GM-CSF, CD80, and CD154 through MIDGE gene expression vectors are combined with the DNA-based immunomodulator dSLIMas a TLR-9 agonist. In the phase I-II clinical trial (ASET trial) heavily pre-treated patients with metastatic renal cell carcinoma (mRCC) were enrolled. Methods: TheASET study has been conducted as a multicenter, open, single-arm phase I-II study. The treatment phase (TP) consisted of 8 intradermal vaccinations, administered within 12 weeks. We analysed known mRCC prognostic factors for their predictive value, i.e. safety laboratory and immunological parameters, quality of life, local reactions and other patients’ characteristics. Results: 19 patients from the ASET study, who received at least one vaccination (ITT population), were included in the biomarker evaluation. The median overall survival (mOS) in the ITT population is currently 25 weeks. mOS of patients who discontinued TP prematurely was only 10 weeks. However, mOS of those patients who completed at least TP is not yet mature for statistical calculation (NR), but is currently estimated as 69 weeks, resulting in a highly significant difference (10 weeks vs. NR, p &lt; 0.001). Patients with an absolute lymphocyte counts (ALC) at baseline of ≥1,000/μL had increased overall survival (mOS NR vs. 16 weeks, p = 0.013), if compared to those with an ALC &lt;1,000/μL. Neutrophil lymphocyte ratios (NLR) at baseline of &gt;3, bone and liver metastasis, high MSKCC score were identified as risk factors associated with lower overall survival. ALC ≥1,000/μL after three MGN1601 vaccinations (week 5) was even more significantly associated with increased overall survival (mOS NR vs. 17 weeks, p = 0.007). The NLR and quality of life improvement at week 5 as well as local reactions at injection sites seem to correlate with OS. Conclusions: MGN1601 shows promising efficacy in late stage mRCC patients. The identified parameters should be further investigated as potential biomarkers for efficacy. Clinical trial information: NCT01265368.
Treatment of Pancreatic Cancer With Docetaxel and Granulocyte Colony-Stimulating Factor: A Multicenter Phase II Study
Authors: Nikos Androulakis, Charalambos Kourousis, Meletios A. Dimopoulos, George Samelis, Stelios Kakolyris, Nikos Tsavaris, Kostas Genatas, Gerasimos Aravantinos, Christos Papadimitriou, Spyros Karabekios, George P. Stathopoulos, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the efficacy and tolerance of single-agent docetaxel and granulocyte colony-stimulating factor in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Thirty-three chemotherapy-naive patients (median age, 65 years) with histologically confirmed pancreatic cancer were treated, after appropriate premedication, with docetaxel (100 mg/m 2 ) and granulocyte colony-stimulating factor (150 μg/m 2 /d subcutaneously days 2 through 10) every 3 weeks. World Health Organization performance status was 0 to 1 in 28 patients (85%) and 2 in 5 patients (15%). Twenty-nine patients had stage III and IV disease. RESULTS: One complete response (3%) and one partial response (3%) were observed for an overall response rate of 6% (95% confidence interval, 2.1% to 14.2%). Nineteen patients (58%) had stable disease and 12 (36%) had progressive disease. The duration of the two objective responses was 10 and 28 weeks, and the median time to tumor progression was 20 weeks. The median overall survival was 36 weeks. The actuarial 1-year survival was 36.4%. The performance status improved in seven of 21 assessable patients (24%) and pain improved in 14 of 21 (67%) assessable patients; five patients (29%) experienced weight gain during treatment. Disease-related asthenia, anorexia, vomiting, and diarrhea improved in 29%, 15%, 67%, and 47% of the assessable patients, respectively. Serum concentrations of CA 19-9 were decreased by more than 50% in seven patients (35%). Grade 3 and 4 neutropenia occurred in four patients (12%) and eight patients (24%), respectively, with two episodes of febrile neutropenia. There were no treatment-related deaths. Grade 3/4 asthenia occurred in three patients. CONCLUSION: Although docetaxel has a marginal objective activity in pancreatic cancer, it seems to have an important effect on tumor growth control, conferring a clinical benefit.
Abstract 15267: A Novel Surface ECG Based Marker of Ventricular Arrhythmia in Patients with Ischaemic Cardiomyopathy
Authors: Will B Nicolson, Matthew I Smith, Peter P Brown, Alastair J Sandilands, Peter J Stafford, Fernando S Schlindwein, Nilesh J Samani, Gerry P McCann, G. Andre Ng
Journal: Circulation (2012)

Introduction Better sudden cardiac death (SCD) risk markers are needed. Retrospective studies have shown that the Regional Restitution Instability Index (R212) is predictive of ventricular arrhythm...
Sorafenib in malignant mesothelioma (MM): A phase II trial of the Cancer and Leukemia Group B (CALGB 30307)
Authors: P. A. Janne, X. F. Wang, L. M. Krug, L. Hodgson, E. E. Vokes, H. L. Kindler
Journal: Journal of Clinical Oncology (2007)

7707 Background: Systemic chemotherapy with cisplatin/pemetrexed is the approved first line treatment regimen for patients with MM. There is no approved second line therapy. In addition, many patients, especially those &gt;70, cannot tolerate combination chemotherapy. Angiogenesis inhibitors have emerged as attractive potential therapies for MM and SU5416 and PTK787 have previously demonstrated single agent activity. We examined the efficacy of sorafenib, an inhibitor of VEGFR2 and PDGFR-b, in chemotherapy naïve and previously treated patients with MM. Methods: This was an open label single arm phase II study of sorafenib in chemotherapy naïve and previously pemetrexed treated patients with MM. Primary end point was response rate (RR). Secondary objectives were 3-month failure free and overall survival (FFS and OS). Forty-four (44) eligible patients were expected to enroll to differentiate a RR of &lt;5% versus &gt;20%, with a Type I error of 0.0675 and a power of 0.955 Results: Between 10/04 and 8/05, 51 patients were enrolled and treated with sorafenib 400 mg bid. One cycle was defined as 28 days; restaging occurred every 2 cycles. Baseline demographics: M/F (36/15); Median age (69; range 36–88; 45% &gt;70); Histology (epithelial/sarcomatoid/mixed/unknown: 37/4/8/2); pleural/peritoneal MM (46/5); ECOG PS 0/1 (11/40); chemo-naive/prior chemo (20/31). Grade 3/4 toxicities occurring in &gt;10% of patients: Fatigue (12 (25%); 11/1) and hand-foot reaction (6 (13%); 6/0). No study related deaths occurred. Estimates of RR and FFS are based on 47 patients with available follow-up data. Response: CR: 0; PR 2: 4% (95% CI; 1- 14%); SD 28 (60%); PD 11 (23%); unevaluable 6 (14%). Three month FFS was 78%; median FFS was 3.7 months and median OS was 10.7 months. The median FFS were 3.6 and 3.6 months and the median OS were 4.9 and 14.6 months in chemo naïve and previously treated patients, respectively. Conclusions: Sorafenib demonstrated modest activity in this phase II trial but did not meet its primary endpoint. The improved outcome in previously treated patients likely reflects patient selection. Ongoing correlative science studies including expression of p-ERK 1/2, baseline VEGF and PDGF levels, are being performed to help identify patient subsets who may benefit (PR or SD) from sorafenib. No significant financial relationships to disclose.
Phase II trial of anti-IGF-IR antibody cixutumumab in patients with advanced or metastatic soft-tissue sarcoma and Ewing family of tumors.
Authors: P. Schoffski, D. Adkins, J. Blay, T. Gil, A. D. Elias, P. Rutkowski, G. K. Pennock, H. Youssoufian, N. J. Zojwalla, R. Willey, D. O. Grebennik
Journal: Journal of Clinical Oncology (2011)

10004 Background: Preclinical and clinical data suggest that cixutumumab (IMC-A12), a fully human IgG1 monoclonal antibody, specifically targets the insulin growth factor-1 receptor (IGF-IR) with high affinity and antagonizes IGF-I and -II ligand binding and signaling. Cixutumumab inhibits proliferation of a variety of human tumor cell lines (Cancer Res. 2003;63:8912; Clin Cancer Res. 2005;11:3065) and may have a role in the treatment of soft tissue sarcomas and Ewing family of tumors (ES/PNET). Methods: This 5-tier, phase II study of single agent cixutumumab assessed the progressionfree survival (PFS) as a primary endpoint in patients (pts) with previously-treated, advanced or metastatic rhabdomyosarcoma (RMS), leiomyosarcoma (LMS), adipocytic sarcoma (LIP), synovial sarcoma (SYN), or ES/PNET. Patients received cixutumumab 10 mg/kg intravenously over 1 hour every other week until disease progression or discontinuation for other reasons. Simon optimal 2-stage design was applied (progression-free rate [PFR] at 12 weeks P0=20%, P1=40%, α=0.10, β=0.10); stage 1 enrolled 17 pts; stage 2 enrolled 20 pts, with at least 4 pts required in stage 1 to proceed further. Results: 113 pts were enrolled. ES/PNET, RMS, LMS, and SYN tiers were closed after the first stage due to low futility level (PFR at 12 weeks 2, 2, 3, and 3 pts, respectively). LIP tier was fully enrolled (37 pts total). Objective responses included one PR in ES and one in LIP. Stable disease as best response was seen in 21 LIP pts (57%), in 9 LMS pts (41%), in 6 SYN pts (35%), in 5 ES pts (28%), and in 4 pts (24%) with RMS. Among all enrolled pts, the most frequent treatment emergent adverse events (AEs) were hyperglycemia and asthenia. Events of ≥ Grade 3 included pain in 7 pts (6%), hyperglycemia in 6 pts (5%), thrombocytopenia in 5 pts (4%), and asthenia in 5 pts (4%). Conclusions: Cixutumumab monotherapy was well tolerated with limited Grade 3 hyperglycemia. Clinical benefit rate was highest in the LIP tier, where 22 out of 37 patients had either a PR or SD. Cixutumumab warrants further evaluation in this disease setting.
Estrogen receptor (ER) status of disseminated tumor cells in the bone marrow of breast cancer patients
Authors: F. N. Tanja, N. Krawczyk, D. Wallwiener, S. Becker, E. Solomayer
Journal: Journal of Clinical Oncology (2007)

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.