tbuckley/cabot-search huggingface dataset:
Screen failure rates in contemporary phase II/III therapeutic trials in genitourinary malignancies.
Authors: Sarah E. Wong, Scott A. North, Christopher Sweeney, Martin R. Stockler, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2016)

176 Background: Screen failures cost effort, time and resources estimated at about $2000 per patient (Bienkowski RS et al 2008). There is little published data about the frequency or causes of screen failures in genitourinary (GU) cancer clinical trials. Methods: We reviewed published articles and contacted study investigators on 42 key phase 2 and 3 trials in advanced GU cancer run from 1999 to 2015. We sought data on the numbers and causes of screen failures. Screen failures were defined as individuals who underwent screening but were not enrolled in the trial. Results: Among all 11 phase 3 trials in prostate cancer, the mean screen failure rate was 25% (17.9%-30.3%). In 4 recent trials evaluating novel androgen receptor pathway targeted agents, abiraterone and enzalutamide before or after chemotherapy for castration-resistant disease, the mean screen failure rate was 28% (range 22% to 30%). Only 2 of 3 prostate cancer chemotherapy trials completed after 2008 collected screen failure data with screen failure rates of 18 and 21%. The main reason for screen failures among all prostate cancer clinical trials was ineligibility. Among 14 phase 3 trials in kidney cancer, 5 reported rates and the mean screen failure rate was 24% (range 21%-27%). The main reasons again were ineligibility, with a very small percentage due to patient refusal. Among 17 phase 2 or 3 trials in bladder cancer, 6 reported rates and the mean screen failure rate was 13% (range 2.04% - 22.8%). The main reasons were primarily ineligibility and patient refusal to a lesser extent. Only (16/42) 38% of the trials published screen failure rates-73% of those in prostate cancer (all completed after 2008), 29% in kidney cancer, and 24% in bladder cancer. Conclusions: Contemporary trials in GU cancer that collected screen failure data had fairly consistent failure rates of 20-30% in prostate and kidney cancer. Many trials did not collect data on the numbers of and reasons for screen failures. Greater standardization of definitions, methods and reporting are needed to better understand and improve screen failure rates in GU cancer trials.
Risk-Adapted Cyclophosphamide, Thalidomide and Dexamethasone (CTD) for the Treatment of Systemic AL Amyloidosis: Long Term Outcomes among 202 Patients.
Authors: Si mon DJ Gibbs, Prayman T Sattianayagam, Helen J Lachmann, Mark Offer, Julian D Gillmore, Philip N Hawkins, Ashutosh Wechalekar
Journal: Blood (2008)
Phase I Results from a Study of Crizotinib in Combination with Erlotinib in Patients with Advanced Nonsquamous Non–Small Cell Lung Cancer
Authors: Sai-Hong Ignatius Ou, Ramaswamy Govindan, Keith D. Eaton, Gregory A. Otterson, Martin E. Gutierrez, Alain C. Mita, Athanassios Argiris, Nicoletta M. Brega, Tiziana Usari, Weiwei Tan, Steffan N. Ho, Francisco Robert
Journal: Journal of Thoracic Oncology (2016)
Development of a RNA-Seq Based Prognostic Signature in Lung Adenocarcinoma
Authors: Sudhanshu Shukla, Joseph R. Evans, Rohit Malik, Felix Y. Feng, Saravana M. Dhanasekaran, Xuhong Cao, Guoan Chen, David G. Beer, Hui Jiang, Arul M. Chinnaiyan
Journal: JNCI Journal of the National Cancer Institute (2016)

Precision therapy for lung cancer will require comprehensive genomic testing to identify actionable targets as well as ascertain disease prognosis. RNA-seq is a robust platform that meets these requirements, but microarray-derived prognostic signatures are not optimal for RNA-seq data. Thus, we undertook the first prognostic analysis of lung adenocarcinoma RNA-seq data and generated a prognostic signature. Lung adenocarcinoma RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) were divided chronologically into training (n = 255) and validation (n = 157) cohorts. In the training cohort, prognostic association was assessed by univariate Cox analysis. A prognostic signature was built with stepwise multivariable Cox analysis. Outcomes by risk group, stage, and mutation status were analyzed with Kaplan-Meier and multivariable Cox analyses. All the statistical tests were two-sided. In the training cohort, 96 genes had prognostic association with P values of less than or equal to 1.00x10-4, including five long noncoding RNAs (lncRNAs). Stepwise regression generated a four-gene signature, including one lncRNA. Signature high-risk cases had worse overall survival (OS) in the TCGA validation cohort (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 2.00 to 14.62) and a University of Michigan institutional cohort (n = 67; HR = 2.05, 95% CI = 1.18 to 4.55), and worse metastasis-free survival in the TCGA validation cohort (HR = 3.05, 95% CI = 2.31 to 13.37). The four-gene prognostic signature also statistically significantly stratified overall survival in important clinical subsets, including stage I (HR = 2.78, 95% CI = 1.91 to 11.13), EGFR wild-type (HR = 3.01, 95% CI = 1.73 to 14.98), and EGFR mutant (HR = 8.99, 95% CI = 62.23 to 141.44). The four-gene prognostic signature also stood out on top when compared with other prognostic signatures. Here, we present the first RNA-seq prognostic signature for lung adenocarcinoma that can provide a powerful prognostic tool for precision oncology as part of an integrated RNA-seq clinical sequencing program.
NETTER-1 phase III: Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate.
Authors: Jonathan R. Strosberg, Edward M. Wolin, Beth Chasen, Matthew H. Kulke, David L Bushnell, Martyn E. Caplin, Richard P. Baum, Pamela L. Kunz, Timothy J. Hobday, Andrew Eugene Hendifar, Kjell E. Oberg, Maribel Lopera Sierra, Dik J. Kwekkeboom, Philippe B. Ruszniewski, Eric Krenning
Journal: Journal of Clinical Oncology (2016)

194 Background: Currently, there are limited therapeutic options for patients with advanced midgut neuroendocrine tumors progressing on first-line somatostatin analog therapy. Methods: NETTER-1 is the first Phase III multicentric, randomized, controlled trial evaluating 177 Lu-DOTA 0 -Tyr 3 -Octreotate (Lutathera) in patients with inoperable, progressive, somatostatin receptor positive midgut NETs. 230 patients with Grade 1-2 metastatic midgut NETs were randomized to receive Lutathera 7.4 GBq every 8 weeks (x4 administrations) versus Octreotide LAR 60 mg every 4-weeks. The primary endpoint was PFS per RECIST 1.1 criteria, with objective tumor assessment performed by an independent reading center every 12 weeks. Secondary objectives included objective response rate, overall survival, toxicity, and health-related quality of life. Results: Enrolment was completed in February 2015, with a target of 230 patients randomized (1:1) in 36 European and 15 sites in the United States. At the time of statistical analysis, the number of centrally confirmed disease progressions or deaths was 23 in the Lutathera group and 67 in the Octreotide LAR 60 mg group. The median PFS was not reached for Lutathera and was 8.4 months with 60 mg Octreotide LAR [95% CI: 5.8-11.0 months], p &lt; 0.0001, with a hazard ratio of 0.21 [95% CI: 0.13-0.34]. Within the current evaluable patient dataset for tumor responses (n = 201), the number of CR+PR was 19 (18.8%) in the Lutathera group and 3 (3.0%) in the Octreotide LAR 60 mg group (p &lt; 0.0004). Although the OS data were not mature enough for a definitive analysis, the number of deaths was 13 in the Lutathera group and 22 in the Octreotide LAR 60 mg group (p &lt; 0.019 at interim analysis) which suggests an improvement in overall survival. Conclusions: The Phase III NETTER-1 trial provides evidence for a clinically meaningful and statistically significant increase in PFS and ORR, and also suggests a survival benefit in patients with advanced midgut NETs treated with Lutathera. Clinical trial information: NCT01578239.
Endothelial Microparticles (EMP) Inhibit ADAMTS13 Activity: Implications in Thrombotic Thrombocytopenic Purpura.
Authors: Joaquin J. Jimenez, Wenche Jy, Lucia M. Mauro, Ana C. Mauro, Laurence L. Horstman, Yeon S. Ahn
Journal: Blood (2005)
P0179 : The model for critically ill cirrhotics (MCIC): a novel prognostic score for predicting mortality in critically ILL cirrhotics admitted to ICU
Authors: A. Sahney, A. Choudhary, C.P. Abby, A.K. Sinha, T. Vyas, R. Maiwall, M. Sharma, L Mitra, V. Saluja, M. Premkumar, A. Bhadoria, S.K. Sarin
Journal: Journal of Hepatology (2015)
Philadelphia Chromosome Negative (Ph-) Very High Risk (VHR) Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents: The Impact of Intensified Chemotherapy on Early Event Free Survival (EFS) in Children’s Oncology Group (COG) Study AALL0031.
Authors: Kirk R. Schultz, William Paul Bowman, William Slayton, Alexander Aledo, Meenakshi Devidas, Harland Sather, Michael J. Borowitz, Stella M. Davies, Michael Trigg, Bernice Pasut, Dean Jorstad, Tammie Eslinger, Laura Burden, Chenguang Wang, Robert Rutledge, Bruce Camitta, Paul S. Gaynon, Andrew J. Carroll, Nyla A. Heerema, Naomi Winick, Stephen P. Hunger, William L. Carroll
Journal: Blood (2008)
Urinary and bowel quality of life after image-guided, intensity modulated radiation therapy to the prostate bed.
Authors: Yazan Abuodeh, Arash Naghavi, TzuHua Juan, Zhenjun Ma, Richard Wilder
Journal: Journal of Clinical Oncology (2016)

312 Background: Majority of patients with adverse pathological features on radical prostatectomy do not receive post-prostatectomy radiation due to concerns of negative impact on their quality of life (QOL). The purpose of this study is to evaluate QOL after post-prostatectomy intensity modulated radiation therapy (IMRT) in the “adjuvant”(ADJ) setting for positive surgical margins, extraprostatic extension, or seminal vesicle invasion with a PSA &lt; 0.2 ng/mL and a “salvage”(SAL) setting for a PSA ≥ 0.2 ng/mL at the start of IMRT. Methods: Between 2004 and 2013, 130 patients underwent IMRT to the prostate bed. Sexual Health Inventory for Men (SHIM), International Prostate Symptom Score (IPSS), and Expanded Prostate cancer Index Composite-26 for bowel (EPIC-26-bowel) scores were recorded before radiation and at 3-month intervals after completion of treatment to assess sexual, urinary, and rectal QOL, respectively. A mixed model for repeated measurements was used to compare QOL scores over time among various subgroups. Results: ADJ and SAL radiation were delivered to 48 (37%), 82 (63%) respectively. Total radiotherapy doses were 64.8-68.4 Gy using 1.8-Gy daily in 56 (43%) patients and 70.2-72.0 Gy in 74 (57%) patients. Androgen deprivation therapy (ADT) was given to 4/48 (8%) ADJ patients and 9/82 (11%) SAL patients. Fiducials were placed in prostate bed for image guidance in 42 (32%) patients. Median follow up was 46 months. Total radiation dose did not significalntly affect QOL. SAL IMRT was associated with worse mean SHIM scores (3 points, p = 0.002) and ADJ IMRT was associated with lower mean IPSS scores (2 points, p = 0.03). Mean EPIC-26-bowel scores were lower without fiducial markers (16 points, p &lt; 0.0001). Conclusions: SAL IMRT was associated with worse sexual QOL, possibly due to less frequent usage of phosphodiesterase-5 inhibitors. ADJ IMRT was associated with worse urinary QOL, possibly due to a shorter post-operative recovery period. Fiducial marker resulted in better rectal QOL due to greater rectal sparing. Urinary and rectal QOL with post-prostatectomy, image-guided IMRT compare favorably with previous QOL reports involving three-dimensional conformal radiation therapy.
A phase II trial of concurrent radiochemotherapy with carboplatin (CBDCA) and weekly docetaxel (TXT) in locally advanced non-small cell lung cancer (NSCLC)
Authors: R. Suzuki, H. Taniguchi, Y. Kondoh, J. Shindoh, S. Matsumoto, T. Hiramatsu, H. Gonda, K. Baba, Y. Hasegawa, K. Shimokata
Journal: Journal of Clinical Oncology (2004)

7174 Background: Concurrent chemoradiation has been proposed as one of the best treatments for locally advanced NSCLC. However, the optimal therapy for locally advanced NSCLC continues to evolve. This phase II trial was carried out to evaluate the response and toxicity of the regimen of CBDCA and weekly TXT combined with concurrent radiotherapy for locally advanced NSCLC. Methods: In a recent phase I trial, we explored the feasibility of concurrent radiochemotherapy with CBDCA and weekly TXT. The recommended doses of CBDCA and TXT were determined as follows. CBDCA: AUC 5.0 d1, 29; TXT: 15 mg/m2 d1, 8, 15, 29, 36, 43, and concurrent radiation of a total of 60 Gy (2 Gy/day). Results: From 1999 to 2002, 47 patients with histologically confirmed NSCLC and who were deemed unresectable for stage IIIa/IIIb, were enrolled (37 PS 0 (ECOG): 10 PS 1, 42 M: 5 F, median age 60 (44–75), 15 IIIa: 32 IIIb, 17 adenocarcinoma: 28 squamous cell carcinoma: 1 large cell carcinoma: 1 other). We have observed only 2 events of grade 4 hematological toxicity (WHO criteria), no events of grade 3–4 non-hematological toxicity, except anorexia. Radiation-related esophagitis were mild (17 grade 0, 16 grade 1, 14 grade 2). Thirty-one/47 (66.0%) of treated patients showed a partial response (0 CR, 31 PR, 7 SD, 5 PD, 4 NE). The median survival time was 16.6 months. One-year, 2-year, and 3-year survival rates were 61.2%, 29.5%, and 14.8%, respectively. Conclusions: This regimen is a feasible and tolerable approach to treatment of locally advanced NSCLC patients with a modest prognosis for survival. No significant financial relationships to disclose.
American Society of Anesthesiologist Classification—Higher Incentives for Higher Scores
Authors: Deepak Agrawal
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Results of NEMO: A phase III trial of binimetinib (BINI) vs dacarbazine (DTIC) in <i>NRAS</i>-mutant cutaneous melanoma.
Authors: Reinhard Dummer, Dirk Schadendorf, Paolo Antonio Ascierto, Ana Maria Arance Fernández, Caroline Dutriaux, Michele Maio, Piotr Rutkowski, Michele Del Vecchio, Ralf Gutzmer, Mario Mandalà, Luc Thomas, Ernesto Wasserman, James Ford, Marine Weill, L. Andres Sirulnik, Valentine Jehl, Viviana Bozon, Georgina V. Long, Keith Flaherty
Journal: Journal of Clinical Oncology (2016)

9500 Background: NRAS mutation in melanoma occurs in ~20% of patients (pts). There are no specific therapies for NRAS melanoma. Despite emergence of immunotherapies (ITs) as effective treatments in melanoma, there is a high unmet need in these pts, particularly after failure of IT. Methods: In this open-label phase III study (ClinicalTrials.gov, NCT01763164), pts with advanced unresectable/metastatic cutaneous NRAS-mutant melanoma who were previously untreated or had progressed on/after prior IT were randomized 2:1 to BINI 45 mg PO BID or DTIC 1000 mg/m2 IV every 3 wk. Pts were stratified by stage, ECOG PS and prior IT for unresectable/metastatic disease. Progression-free survival (PFS) per independent central review was the primary endpoint. Overall survival (OS) was the key secondary endpoint; other secondary endpoints included confirmed overall response rate (ORR) and disease control rate (DCR). Results: 402 pts were randomized to BINI (n = 269) or DTIC (n = 133). The planned primary PFS analysis and prespecified analyses by IT strata and LDH level at screening (median mo and HR with 95% CIs) are presented in the table below. Confirmed ORR and DCR (95% CI) were 15% (11%–20%) and 58% (52%–64%) for BINI vs 7% (3%–13%) and 25% (18%–33%) for DTIC (P= 0.015 [ORR]; P< 0.001 [DCR]), respectively. Median duration of response on BINI was 6.9 mo. A prespecified interim analysis of OS favored BINI, with a point estimate for the HR of 0.81; mature OS analysis will be performed at 224 deaths. Grade 3/4 adverse events reported in ≥ 5% of pts in either group were increased CPK (19% BINI, 0% DTIC), hypertension (7% BINI, 2% DTIC), anemia (2% BINI, 5% DTIC) and neutropenia (1% BINI, 9% DTIC). Conclusions: BINI showed improvements over DTIC in several clinically relevant endpoints including PFS, ORR and DCR, was well tolerated and may offer a new treatment option for pts with NRAS-mutant melanoma before and after IT. Clinical trial information: NCT01763164.Progression-free survival. BINI DTIC HR P Primary, N = 402 2.8 (2.8–3.6) 1.5 (1.5–1.7) 0.62 (0.47–0.80) < 0.001 Prior IT, n = 85 5.5 (2.8–7.6) 1.6 (1.5–2.8) 0.46 (0.26–0.81) No prior IT, n = 317 2.8 (2.7–2.9) 1.5 (1.5–1.7) 0.70 (0.53–0.94) High LDH, n = 113 2.1 (1.5–2.8) 1.4 (1.1–1.5) 0.45 (0.28–0.71) Normal LDH, n = 269 3.9 (2.8–4.2) 1.7 (1.5–2.8) 0.65 (0.48–0.89)
Patient Experience and Health Care Quality—Reply
Authors: David Enze Wang, Yusuke Tsugawa, Ashish K. Jha
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
A report on the development and validation of first-ever perceptual speech evaluation tool for head and neck cancer (HNC) patients.
Authors: R. C. Dwivedi, S. St. Rose, C. Nutting, P. H. Rhys-Evans, K. J. Harrington, R. Kazi
Journal: Journal of Clinical Oncology (2010)

9116 Background: Although there are many perceptual voice evaluation scales available but to date there is no scale available for speech evaluation in HNC patients. The aim of this study was to develop and validate first ever speech-specific scale for perceptual evaluation of speech in HNC patients. Methods: Based on an extensive literature review and discussion in a multidisciplinary setting 5 speech parameters (intelligibility, articulation, speech rate, nasality and asthenia) and overall grade of speech impairment were selected and evaluated for the development and validation of this scale. Speech samples of 117 subjects (65 HNC patients and 52 age and sex matched healthy volunteers) were recorded using a standard protocol consisting reciting specific words and a standard text passage. All samples were independently judged and rated by 3 experienced raters (speech and language therapists) and were re-rated 12 weeks apart for establishing test-retest reliability. Internal consistency, test-retest reliability and Inter-rater reliability of different parameters of this scale and overall grade were determined using Cronbach's alpha and Spearman's rank correlation coefficients. Construct validity was tested using Spearman's rank correlation coefficient. Group validity was tested by Mann-Whitney U-test. Results: The Cronbach's alpha coefficients for internal consistency ranged from 0.87-0.90 for connected speech and 0.79-0.84 for words. The Spearman's correlation coefficients for test-retest reliability of these parameters for connected speech varied between 0.38-0.87 while for words the values ranged between 0.50-0.71. These values for inter-rater reliability of connected speech were between 0.55-0.99, while for words they ranged between 0.40-0.57. For construct validity, the Spearman's correlation coefficient between overall grade of connected speech and overall speech question of SHI, Speech domain of SHI and speech question of UWQOL ranged between 0.35- 0.55. Conclusions: GAAIN-R scale is a valid and reliable tool for speech evaluation in HNC patients. This scale may be used in other groups of patients' as well especially those with neurological diseases. No significant financial relationships to disclose.
Monitoring of somatic mutations in circulating cell-free DNA by digital PCR and next-generation sequencing during afatinib treatment in patients with lung adenocarcinoma positive for EGFR activating mutations
Authors: E. Iwama, K. Sakai, K. Azuma, T. Harada, D. Harada, K. Nosaki, K. Hotta, F. Ohyanagi, T. Kurata, T. Fukuhara, H. Akamatsu, K. Goto, T. Shimose, J. Kishimoto, Y. Nakanishi, K. Nishio, I. Okamoto
Journal: Annals of Oncology (2016)