tbuckley/cabot-search huggingface dataset:
The ORCHESTRA trial: A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Authors: Elske C. Gootjes, Tineke E Buffart, M.P. Tol, J Burger, Dirk J. Grunhagen, Eric P van der Stok, Martijn R. Meijerink, Albert J. Ten Tije, Esther Van Meerten, Peter M van de Ven, Joost Nuyttens, Cornelis J Haasbeek, Cornelis Verhoef, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2016)

TPS788 Background: In the current multidisciplinary approach of mCRC, local treatment of oligometastases is common practice. Results of large case series of selected patients treated with complete surgical resection of metastatic lesions suggest that this approach substantially improves survival rates to around 30-60%. Other techniques such as radiofrequency or microwave ablation (RFA, MWA), transarterial chemoembolization (TACE) or radiotherapy can also be applied in local treatment. Curative treatment options are generally not available for patients with extensive hepatic and/or extrahepatic mCRC. These patients primarily receive palliative systemic treatment consisting of combination chemotherapy as well as targeted agents. So far, reports on the benefit of local treatment for metastases in multi-organ mCRC have major limitations, including being small, non-randomized, single-center and retrospective. The benefit from local treatment of metastases for these patients should be established to allow for interruption of the standard systemic therapy and exposure to possible adverse events from local treatment. Methods: The ‘ORCHESTRA’ trial is a randomized multicenter clinical trial for patients with multi-organ mCRC, comparing the combination of chemotherapy and maximal tumor debulking versuschemotherapy alone (NCT01792934). We will examine the interplay of both efficacy and toxicity for the combination of systemic chemotherapy and locoregional therapy. Our study design incorporates systemic as well as local therapy in the experimental arm and combines local treatment modalities to pursue maximal tumor debulking. We aim to improve overall survival of patients with multi-organ mCRC by maximal tumor debulking after induction chemotherapy with at least six months. A total of 478 patients will be included to meet the primary endpoint (power 80%, type I error rate 5%). We define local treatments feasible when they can be performed within a 3-month time period to prevent extensive delay of systemic therapy. Currently, 60 patients are included in 22 participating Dutch hospitals. Clinical trial information: NCT01792934.
The role of UGT1A1 polymorphisms (*28 and *6) in Japanese cancer patients.
Authors: S. Morimoto, M. Shimada, N. Kurita, T. Iwata, M. Nishioka, K. Yoshikawa, T. Miyatani, C. Mikami, H. Kashihara
Journal: Journal of Clinical Oncology (2011)

570 Background: Combination protocol using FU-LV with irinotecan (FOLFIRI) is currently regarded as standard first-line therapy in advanced colorectal cancer (CRC). Although irinotecan prolongs survival, it causes severe diarrhea and neutropenia. Recent pharmacogenetic studies on irinotecan have revealed significant associations of UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6, the latter being specifically detected in East Asians resulting in severe toxicity. It is necessary that the dose-finding trial that decided the optimal dose according to the gene polymorphism to draw out the maximum therapeutic effect while evading the side effect. Here we present the result of prospective trial of the safety about FOLFIRI therapy according to each gene type of UGT1A1 for Japanese patients with advanced CRC. Methods: From 2008, 250 Japanese patients in TOKUSHIMA University were enrolled in this study. Homo group (*6/*6 and *28/*28 or a both hetero types), hetero group (It was *28 and either *6 was hetero type), and wild group (*28 and *6 were wild types) were defined. On the 23 patients with advanced CRC treated with FOLFIRI after standard chemotherapy, wild and homo groups were administered 150mg/m 2 irinotecan, and homo group was 100mg/m 2 . Results: On the 23 patients, the genotypes of UGT1A1 *28 were homozygous in 1 (0.5%) and heterozygous in 5 (28%), *6 were homozygous in 0 and heterozygous in 6 (26%). In *6 heterozygous patients, severe toxicities (grade 3 or more) were found (33%), but in *28 heterozygous patients were not (0%). There was no decrease of irinotecan doses in each group. In Japanese people, UGT1A1 *6 polymorphisms were higher than *28 (*6 homo 3%, hetero 27% vs *28 homo 0.5%, hetero 13%). Conclusions: When the dosage of irinotecan is decided, it is necessary to consider the UGT1A1 *6 heterozygous in Japanese cancer patients. [Table: see text]
Nonmalignant Diagnoses in Patients
Authors: William K. Oh, Benjamin H. Lee, Nancy K. Sweitzer
Journal: Journal of Clinical Oncology (2000)

Article Tools Nonmalignant Diagnoses in Patients Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.13.2638 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10893299 Nonmalignant Diagnoses in Patients William K. OhxWilliam K. OhSearch for articles by this author , Benjamin H. LeexBenjamin H. LeeSearch for articles by this author , Nancy K. SweitzerxNancy K. SweitzerSearch for articles by this author Show More Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2000.18.13.2638 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
F<scp>ifty</scp> Y<scp>ears of</scp> R<scp>esearch in</scp> ARDS.The Epidemiology of Acute Respiratory Distress Syndrome. A 50th Birthday Review
Authors: Tài Pham, Gordon D. Rubenfeld
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Since its first description 50 years ago, no other intensive care syndrome has been as extensively studied as acute respiratory distress syndrome (ARDS). Despite this extensive body of research, many basic epidemiologic questions remain unsolved. The lack of gold standard tests jeopardizes accurate diagnosis and translational research. Wide variation in the population incidence has been reported, making even simple estimates of the burden of disease problematic. Despite these limitations, there has been an increase in the understanding of pathophysiology and important risk factors both for the development of ARDS and for important patient-centered outcomes like mortality. In this Critical Care Perspective, we discuss the historical context of ARDS description and attempts at its definition. We highlight the epidemiologic challenges of studying ARDS, as well as other intensive care syndromes, and propose solutions to address them. We update the current knowledge of ARDS trends in incidence and mortality, risk factors, and recently described endotypes.
Everolimus plus octreotide LAR versus placebo plus octreotide LAR in patients (pts) with advanced neuroendocrine tumors: Multivariate analysis of progression-free survival from the RADIANT-2 trial.
Authors: P. Ruszniewski, P. Tomassetti, S. Saletan, A. Panneerselvam, J. C. Yao
Journal: Journal of Clinical Oncology (2011)

e21084 Background: In the phase III RADIANT-2 trial, everolimus, an oral inhibitor of mTOR, plus octreotide (E+O) demonstrated a clinically meaningful increase in median progression-free survival (PFS) compared with placebo + octreotide LAR (P+O) in pts with advanced low- or intermediate-grade NET and a history of secretory symptoms associated with carcinoid syndrome (ESMO 2010 Abstract #LBA8). In order to determine the factors that significantly influence PFS, a multivariate analysis was performed. Methods: Pts with advanced NET were randomized to oral everolimus 10 mg/d + octreotide LAR 30 mg IM q 28 days (n=216) or P+O (n=213). The primary endpoint was PFS per adjudicated central review (RECIST v1.0). Multivariate analysis using a Cox-proportional hazards model was performed. Significant factors (p<0.05) were determined after a stepwise elimination of the nonsignificant factors from the model. Results: Multivariate analysis indicated that significant prognostic factors for PFS were treatment (everolimus vs placebo) (p=0.001), WHO performance status (p=0.007), lung as primary site (p=0.044), baseline CgA (p<0.001), and bone involvement (p=0.022) (Table). Conclusions: Multivariate analysis of the RADIANT-2 trial has allowed, for the first time, evaluation of the prognostic risk factors associated with PFS in a large phase III, placebo-controlled trial in pts with advanced NET. A better understanding of these risk factors can help clinicians in the treatment of their pts. Multivariate analysis of PFS. N Median PFS (95% CI) Hazard ratio (95% CI) P Treatment 0.62 (0.47, 0.82) 0.001 E+O 216 16.43 (13.67, 21.19) P+O 213 11.3 (8.44, 14.59) WHO performance status 0.69 (0.52, 0.90) 0.007 0 257 16.62 (13.63, 20.27) ≥1 170 11.10 (8.31, 14.23) Lung as primary site 1.55 (1.01, 2.36) 0.044 Yes 44 10.61 (5.55, 14.23) No 385 14.23 (11.96, 17.68) Baseline CgA 2.11 (1.53, 2.91) <0.001 Elevated 282 11.33 (9.66, 13.80) Nonelevated 138 26.84 (17.68, NA) Bone involvement 1.52 (1.06, 2.18) 0.022 Yes 59 8.31 (5.32, 13.83) No 367 15.38 (13.04, 19.19)
NGR-hTNF, a novel vascular targeting agent (VTA), as second-line therapy in malignant pleural mesothelioma (MPM): Preliminary results of multicenter phase II study
Authors: V. Gregorc, P. Zucali, G. L. Ceresoli, C. Noberasco, E. Bajetta, A. Santoro, M. G. Viganò, F. Caligaris-Cappio, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2008)

8099 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13 highly expressed on tumour blood vessels. NGR-hTNF combines direct anticancer activity and effects on tumour vascular permeability. In preclinical models, NGR-hTNF showed antitumor activity either at low doses or at high doses. Methods: Patients (pts) with advanced MPM pretreated with first-line chemotherapy received a low-dose of NGR-hTNF given at 0.8 mcg/m2 as 1-hour intravenous infusion every 3 weeks (q3w). This dose was previously selected in phase I trial based on dynamic imaging changes and preliminary clinical activity. The trial had a 2-stage design with 16 and 27 pts to be enrolled in first and second stage, respectively. Progression-free survival (PFS) was the primary end-point with reassessment performed q6w. Results: From May to December 2007, 42 pts were enrolled and 16 were included into the first-stage analysis: 75% were males; median age 64 years (range, 48–80); PS 0/1/2 7/6/3; 69% had epithelial, 12.5% sarcomatoid, 6% mixed and 12.5% unknown histology. Overall, 58 cycles (median 2, range: 1–9) were completed. Seven pts (44%; 95% CI 20- 68%) had a stable disease (SD) with a median duration of 4.4 months (range, 1.6–7.1+). The maximum changes of target lesions in SD pts ranged from 17% shrinkage to 6% growth. The estimated PFS rate at 4.5 months was 37% (95% CI 10–65%) and 3 pts (19%) are still on treatment at 6 months. To date, 26 pts are enrolled in stage 2 (5 SD, 3 PD, 18 too early) and an additional 12 pts are entering into a subsequent cohort of pts treated with a weekly schedule. Main grade 1–2 toxicities per patient were infusion-related constitutional symptoms, including chills (56%) and fatigue (31%). Neither grade 3–4 treatment-related adverse events nor toxicity-related death were observed. Conclusions: NGR-hTNF shows a favourable and manageable toxicity profile, with preliminary evidence of long-lasting disease control in chemo-pretreated MPM patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Molmed
A qualitative study of patient and clinician attitudes regarding surveillance following resection of pancreatic and periampullary cancer.
Authors: Raymond Gilbert Deobald, Eva Cheng, Yoo-Joung Ko, Frances Catriona Wright, Paul Jack Karanicolas
Journal: Journal of Clinical Oncology (2014)

339 Background: Pancreatic carcinoma is the fourth leading cause of cancer death in North America. Following surgical resection, most patients will develop recurrence within two years. Intense follow-up is often recommended; however, the impact on survival is unknown. We sought to qualitatively assess patient and clinician attitudes towards follow-up and the perceived benefits and challenges. Methods: The research team developed a semi-structured interview guide. Purposive sampling identified patients who had undergone curative attempt resection and were in active surveillance or had developed recurrence. Clinicians involved in patient care were also interviewed.Themes were derived using standard qualitative methods. Results: Fifteen patients and seven clinicians were interviewed. Patient themes included (1) Limited understanding of disease prognosis; (2) Desire for reassurance through follow-up; (3) Desire to know if and when recurrence occurred; (4) Challenging treatments; (5) Minimal difficulties with the follow-up protocol; and (6) Limited role of family doctors in pancreatic cancer follow-up. Clinician themes included (1) Expectation that patients are aware of recurrence risk; (2) Desire to provide reassurance to patients; (3) Support for intense follow-up protocol despite lack of supporting evidence; (4) Secondary goals for surveillance; (5) Perceived patient challenges in follow-up; (6) Openness to family doctors doing follow-up. Overall, the dominant theme was one of disconnect between patients and clinicians in the understanding of the disease and its prognosis. Conclusions: Patients with pancreatic or periampullary cancer have an intense need for reassurance and obtain this through the follow-up process. Consequently they express few difficulties with follow-up despite the intensity of testing. Oncologists recognize this desire for reassurance and provide it through follow-up despite the lack of evidence to show benefit. There appears to be a disconnect between patients and clinicians in the understanding of the disease and its prognosis suggesting further work is needed to improve patient-physician communication.
The effect of erlotinib on CYP3A4 activity, as quantified by the erythromycin breath test and oral midazolam kinetics in cancer patients: Preliminary results
Authors: H. Calvert, C. Twelves, M. Ranson, A. Anthoney, R. Plummer, S. Fettner, B. Dayaram, B. Lum, M. Hamilton, A. Rakhit
Journal: Journal of Clinical Oncology (2005)

3076 Background: In vitro, erlotinib (Tarceva) is both a substrate for, and an inhibitor of CYP3A4, raising the possibility of drug interactions. This was a multi-center, open label study conducted in cancer patients to evaluate the effect of erlotinib on CYP3A4 activity using two probe substrates. Erythromycin metabolism correlates well with hepatic CYP3A4 content, whereas midazolam (MDZ) reflects both intestinal and hepatic CYP3A4 activity. Methods: Erlotinib was administered as 150 mg oral tablet once daily from days 8 to 14. Erlotinib treatment was restarted on day 22 as an extension phase at the discretion of the investigator. A single oral dose of 7.5 mg MDZ oral tablet (Hoffman-La Roche, Inc., Basel, Switzerland) and 3 μCi (0.0704 mol or 0.03 mg) of [14C N-methyl] erythromycin (Metabolic Solutions, Inc. Nashua, NH) dissolved in 5% dextrose in water by intravenous injection were administered on days 1, 8, 14 and 21. Pharmacokinetics of MDZ and erythromycin breath test (ERBT) were evaluated at day 1 (pre-erlotinib), erlotinib treatment day 8 and day 14 and post-erlotinib treatment day 21. Here, we report preliminary data from sixteen completed patients (out of 28 planned). Results: Mean plasma concentration-time curve (AUC) of MDZ decreased (24% on Day 8 and 30% on Day 14) from baseline value after erlotinib treatment. Data from ERBT showed little effect of erlotinib on excretion of CO2 (6% decrease on day 8 but 7% increase on day 14). Both measures, however, were associated with wide interpatient variability. Conclusions: In conclusion, preliminary data did not demonstrate an inhibitory effect of erlotinib on clearance of MDZ (hence CYP3A4). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, OSI, Roche OSI, Roche Genentech, OSI OSI, Roche OSI, Roche
Comparison of the modality type in trials conducted by multicenter cancer cooperative groups between Japan and the United States.
Authors: F. Kunieda, K. Nakamura, T. Shibata, H. Katayama, J. Mizusawa, K. Kanato, S. Matsubara, A. Takashima, A. Kimura, I. Saito, H. Fukuda
Journal: Journal of Clinical Oncology (2011)

e16554 Background: There are several cancer cooperative groups in Japan and in the United States (US), and they are sharing roles in cancer therapeutic development. Standard treatment for many cancers is multimodality therapy including drug (Dx), surgery (Sx), and radiotherapy (Rx). There has been no study to compare the modality type in trials conducted by each cooperative group. Methods: We selected representative Japanese and US cooperative groups and examined the modalities in their trials via clinical trial registry system. The Japanese cooperative groups examined were Japan Clinical Oncology Group (JCOG), West Japan Oncology Group (WJOG), Japan Adult Leukemia Study Group (JALSG), and Japanese Gynecologic Oncology Group (JGOG). Clinical trials registered in UMIN-CTR website from June 2005 to December 2010 were examined. The US cooperative groups examined were SWOG, NCCTG, CALGB, ECOG, RTOG, and ASOCOG. Clinical trials registered in ClinicalTrials.gov website from June 2005 to December 2010 were examined. Clinical trials were categorized into 7 groups: Dx alone trials, Sx alone trials, Rx alone trials, bi-modality trials (Dx plus Sx, Dx plus Rx, and Sx plus Rx), tri-modality trials (Dx, Sx, and Rx). The distribution of Phase I, II, III in each country were also examined. Results: The distribution of modalities in Japanese and US cooperative groups was shown in the table. Dx alone trials occupied approximately 80% in SWOG, ECOG, NCCTG, and CALGB. The proportion of Rx-containing trials in RTOG was 85.7% (60/70). Sx-containing trials occupied only 8.3% (35/424) in all US trials, while it amounted to 36.6% (26/71) in JCOG trials. In other Japanese groups, most of the trials were Dx-alone trials. Phase III trials occupied 38.0% (161/424) in US, and 52.5% (63/120) in Japan. Conclusions: Sx-containing trials were dominant in JCOG. In contrast to the multimodality nature of the cancer treatment, Dx alone or Dx +Rx trials were frequent in most of the groups. US Japan Modality SWOG NCCTG CALGB ECOG RTOG ACOSOG JCOG WJOG JALSG JGOG Dx+Sx+Rx 2 2 2 3 3 2 3 1 0 0 Dx+Sx 0 2 1 2 0 2 12 0 0 0 Dx+Rx 10 11 13 8 40 0 11 3 0 0 Sx+Rx 2 1 1 1 2 0 0 0 0 0 Dx alone 78 67 64 64 9 6 29 24 13 8 Sx alone 2 0 1 0 1 3 11 0 0 0 Rx alone 0 2 0 1 15 1 5 0 0 0 Total 94 85 82 79 70 14 71 28 13 8
Neoadjuvant chemoradiation versus surgery first for resectable pancreatic head adenocarcinoma: An economic and outcome analysis.
Authors: Daniel Erik Abbott, Ching-Wei David Tzeng, Ryan P. Merkow, Scott B. Cantor, Matthew H.G. Katz, David J. Bentrem, Karl Y. Bilimoria, Christopher H. Crane, Gauri R. Varadhachary, Jason B. Fleming
Journal: Journal of Clinical Oncology (2012)

156 Background: The optimal sequence of treating pancreatic cancer (PC) with chemotherapy, radiation and surgical intervention remains elusive. Thus, cost should be considered. This study was conducted to compare the cost and outcome of a surgery first approach versus neoadjuvant chemoradiation (CRT) followed by surgery. Methods: A decision model was constructed to contrast the 2 treatment strategies. The NCDB (2003-5), ACS NSQIP (2005-9) and literature populated probabilities and outcomes in the surgery first arm, including operative outcome, complication rate, pathologic stage, adjuvant therapy and stage-specific survival based. Data from a prospectively maintained PC database (2002-8) populated the neoadjuvant arm. Costs were based on Medicare reimbursement (2011$). Survival, discounted when appropriate, was reported in quality-adjusted life months (QALM). Results: 164 pts completed neoadjuvant CRT. Of these, 36 (22%) did not proceed to surgery. Failure was due to metastases, 18(50%), prohibitive performance status (PS), 17(47%) and pt choice, 1(3%). 12 pts (7%) proceeded to laparotomy but were deemed unresectable. 116 (71%) pts underwent definitive resection. The surgery first approach cost $95,781 to yield survival of 8.7 QALM, while the neoadjuvant strategy cost $71,416 to achieve 18.8 QALM. In the neoadjuvant population, pts not undergoing surgery, those unresectable at laparotomy and those completing surgery demonstrated a cost of $12,401 to yield 7.7 QALM, $39,112 to yield 7.1 QALM and $92,887 to achieve 23.4 QALM, respectively. Conclusions: Treating pts with neoadjuvant CRT identifies those who develop early metastases or prohibitive PS and can be spared an ineffectual or prohibitively morbid operation. Our data suggest this approach is associated with improved OS at significantly lower cost. Neoadjuvant therapy for resectable PC should be employed more frequently to provide cost-effective care for this lethal disease. [Table: see text]
A phase II study of bevacizumab in combination with irinotecan plus S-1 as first-line treatment in patients with <i>KRAS </i>mutant-type metastatic colorectal cancer.
Authors: Tetsuya Eto, Toshiki Masuishi, Kohei Suzuki, Isamu Shibata, Yuichi Fukami, Toru Matsui, Takashi Ichida, Fumihiko Kusano, Junichi Tazawa, Yoshinori Sakai
Journal: Journal of Clinical Oncology (2016)

676 Background: FOLFIRI+bevacizumab (BV) is considered as a first-line treatment in patients (pts) with metastatic colorectal cancer (mCRC). The FIRIS study showed the non-inferiority of irinotecan plus S-1 (IRIS) to FOLFIRI. Therefore, we conducted a phase II study to evaluate the efficacy and safety of BV in combination with IRIS as first-line chemotherapy for KRAS mutant-type (mt) mCRC (clinical trial information: UMIN000004630). Methods: Eligibility criteria included histologically confirmed mCRC, KRAS mt, no previous chemotherapy, ECOG performance status (PS) of 0/1, and adequate organ function. S-1 was administered at 80 mg/m 2 on days 1–14 and irinotecan at 100 mg/m 2 on days 1 and 15 every 28 days. BV was administered at 5 mg/kg on days 1 and 15 every 28 days. The primary endpoint was response rate (RR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The sample size was calculated to reject a RR of 25% in favor of a target RR of 50% with a significance level of 0.05 and a statistical power of 80%. Results: Of 26 patients enrolled for the study between December 2010 and September 2015, 23 met the inclusion criteria. The patient characteristics were as follows: median age, 66 (range, 46–77) years; male/female, 15/8; PS 0/1, 9/14; number of metastatic tumors 1/ ≥ 2, 8/15; colon/rectum as the primary tumor site, 13/10; primary tumor +/−, 15/8; and unresectable/recurrent, 15/8. The RR was 60.9% (95% confidence interval (CI): 40.8%–77.8%) with complete response, 0; partial response, 14; stable disease, 8; progressive disease, 0; and not evaluable, 1. With a median follow-up period of 58.1 months, the median PFS and OS were 10.7 (95% CI: 4.7–16.8) and 28.5 (95% CI: 17.6–39.3) months, respectively. The most common grade 3 or 4 adverse events were neutropenia (35%), diarrhea (22%), leukopenia (17%), febrile neutropenia (13%), anemia (13%), and hypoalbuminemia (13%). Conclusions: BV in combination with IRIS as first-line chemotherapy showed promising anti-tumor effects and manageable toxicities for KRAS mt mCRC. Clinical trial information: UMIN000004630.