tbuckley/cabot-search huggingface dataset:
Association between a 17-gene genomic prostate score and multiparametric prostate MRI in men with low- and intermediate-risk prostate cancer (PCa).
Authors: Michael S. Leapman, Antonio C. Westphalen, Niloufar Ameli, H. Jeffrey Lawrence, Phillip G. Febbo, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2015)

83 Background: A biopsy-based RT-PCR assay (Oncotype DX Prostate Assay) providing a Genomic Prostate Score (GPS) as a measure of tumor aggressiveness and multi-parametric prostate MRI (mpMRI) are clinically utilized predictors of adverse pathology at prostatectomy. These tests have not been directly compared and it remains to be determined whether they provide independent information. Methods: We evaluated the association between GPS results (scale 0-100) and baseline endorectal mpMRI in men with clinically localized PCa. MR studies were reviewed to a five-tier scale of increasing suspicion of malignancy. Mean apparent diffusion coefficient (ADC) was calculated from a single dominant lesion. Mean rank of the GPS (0-100) and GPS-predicted likelihood of favorable pathology among MRI strata were compared with the Kruskal-Wallis test. Regression analysis was performed between mean ADC and scaled GPS within CAPRA risk groups. Results: Of 332 patients who received GPS testing at a single institution, 94 were identified with low (n=59) and intermediate (n=35) CAPRA risk prostate cancer who received mpMRI within a two-year interval of prostate biopsy. A broad distribution of GPS was observed across categories defined by mpMRI criteria. Among intermediate risk patients both GPS and the GPS-predicted likelihood of favorable pathology were associated with MR score (p=0.01 and p&lt;0.01, respectively). For low risk patients, neither GPS nor likelihood of favorable pathology were significantly different across MR findings (p=0.12 and p=0.21, respectively). Mean ADC was not significantly associated with GPS or likelihood of favorable pathology for either low (p=0.24) or intermediate (p=0.91) risk categories. Conclusions: While a broad distribution of GPS was observed across mpMRI criteria, increasing GPS was associated with highly suspicious MRI findings in men with intermediate risk PCa. No significant associations were observed between MRI categories and either GPS or likelihood of adverse pathology in low risk patients.
Inhaled Nitric Oxide in Full-Term and Nearly Full-Term Infants with Hypoxic Respiratory Failure
Authors: The Neonatal Inhaled Nitric Oxide Study Group
Journal: New England Journal of Medicine (1997)

Neonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the initiation of extracorporeal membrane oxygenation in infants with hypoxic respiratory failure.
A phase I trial of SR271425 given as a one hour infusion every 3 weeks to patients with advanced solid tumors
Authors: S. Wadler, E. Loh, M. J. Pilat, L. Malburg, S. Holloway, N. Matthews, G. Shackleton, M. Valdivieso, P. Lorusso
Journal: Journal of Clinical Oncology (2005)

2030 Background: SR271425 is a novel cytotoxic antitumor agent with a broad spectrum of antitumor efficacy in murine tumor models. The study objective was to determine the dose limiting toxicity (DLT), recommended phase II dose (RPIID) and the PK/PD profile for SR271425 given over one-hour q 3 weeks. Methods: Escalating doses of SR271425 were given, starting at 17 mg/m2 based on mouse LD10. The trial started with an accelerated dose escalation phase. Patient selection used common Phase I criteria as well as additional cardiac criteria. Plasma levels of SR271425 were measured using a validated LC-MS/MS Method: Because SR233377, a previous generation thioxanthone agent, has been shown to prolong QTc and cause Torsade de pointes, careful monitoring of ECGs was done and the ECGs were read centrally. Results: 37 pts were enrolled to 15 dose levels up to 1320 mg/m2. The results are based on available data. Patient characteristics: 23 male, 14 female; age 35 -78, mean 54 yrs; ECOG PS 0 (10 pts), 1 (26) and 2 (1). No tumor types are highly represented among the 17 different diagnoses. The maximum administered dose is 1320 mg/m2 with 2 DLT’s (QTc grade 3 prolongation using CTCAEv3 criteria based on 3 consecutive QTcB readings). No drug related hepatic or hematologic toxicity has been reported, although a grade 3 hyperbilirubinemia occurred in a patient with progressive liver metastasis. Grade 1 toxicities include rash, flushing, pruritis, weight decrease, diarrhea, hypertension, and fatigue. At higher doses, patients had yellow discoloration of the skin and nausea/vomiting (grade 2). No confirmed tumor response has been seen, but a hepatocellular carcinoma had a minor response and a prostate cancer had declining PSA levels. In terms of exposure, both Cend and AUC increased in a dose related manner with no obvious deviation from linearity. Plasma drug concentrations declined in a biphasic manner with a mean terminal elimination t1/2 of 7.1 (±1.3) h. There was no change in clearance or volume of distribution over the dose range studied. Conclusions: SR271425 given as a one-hour infusion has QTc prolongation as the dose limiting factor. Slowing the infusion or splitting the dose will likely allow greater cumulative exposure to SR271425. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
Emerging solutions: Clinical trial informed consent collaborative model
Authors: P. Devine, C. Brady
Journal: Journal of Clinical Oncology (2005)

8228 Background: In today’s clinical trial arena, interest in accrual and retention is extremely high among investigators. A 2001 study by Lara et al, at U.C. Davis, reported that the consent process, with its legalistic and confusing forms, is itself a barrier to patient participation. This work began on a small scale at UCSF where patient advocates with the UCSF Breast SPORE, created explanatory letters about specific clinical trials. Under Ms Devine, the work developed into an advocate component for the MRI Correlative Science clinical trial 15007, sponsored by CALBG, ACRIN and NCI SPORE. A suite of materials where created to assist patients as they underwent the informed consent process. CISN principals are currently working with ACOSOG and UCSF researchers, to assess the potential for clinical trial decision aids to improve the quality of the informed consent process, trial participation and retention, for ACOSOG clinical trial Z1031. CISN and ACRIN are working together to develop an educational piece for a large multi-site Lung Screening Study. Although these studies provide a bold new blueprint for advocate involvement in the informed consent process, there is much work yet to be done. Methods: CISN is introducing the medical community to an array of issues affecting patients considering participation in clinical trials: lack of literacy about research requirements; tissue donation; understanding the informed consent process; the importance of meaningful and full disclosure to patients, and strategies for promoting research integrity. Unique educational materials are being developed to capture the acceptance of the patient. Results: Two and a half years later, accrual rates and a retention rate of 100% for CALGB/ACRIN/SPORE 150007 are much higher than historical numbers. Since this work was not conducted within a clinical study, these ideas will be translated to a research study, ACOSOG Z1031. Conclusions: Patient-centered, study specific, educational materials included as part of the informed consent process may enhance patient literacy, improve patient satisfaction, and advance public trust in the research enterprise, leading to responsible increased accrual and retention. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
New fields in the patient record: A tool or a nuisance?
Authors: Ioanna Theodorakopoulou, Kalliope Stathaki, Theodore Poufos, Frosso Vlachou, Olympia Spyri, Lina Hatziyiasemi, Georgios Rigakos, Stefanos V. Labropoulos, Ioanna Prasini, Evangelia Razis
Journal: Journal of Clinical Oncology (2016)

235 Background: The Contemporary Oncology Team was the first practice in Greece to participate in the Quality in Oncology Practice Initiative (QOPI). As a result, several corrective measures were designed and implemented to improve the quality of the services provided to patients. Methods: The plan-do-check-act approach was used to implement changes, primarily in the follow up form, over a period of 18 months. Several improvement opportunities were identified. 1.) A numerical scale for pain intensity quantification became a required field. 2.) Emotional well-being fields were added so the patient’s state could be documented by providers. 3.) Fertility assessment and counseling was added as a required field in the patient record. For this report we evaluated retrospectively the effect of these changes on our QOPI scores. Results: Contemporary Oncology Team QOPI scores after the implementation of the new forms have shown increased compliance, compared to QOPI aggregate scores for all participating US practices, in the areas related to the changes made. Specifically, pain assessment documentation improved from -54.56% to +9.96%. The use of a numerical tool proved invaluable to comparing pain intensity between different visits. Emotional well-being documentation improved from -42.55% to +18.26%. Fertility assessment documentation has not improved but this finding could be due to a decrease in patient chart sample size. Providers seemed to adapt quickly and without difficulty. Conclusions: Developing new fields in the patient record is an evolving process because it requires provider education and acquaintance with the new method of documentation. However, in this retrospective analysis it proved to be an effective method to improve provider compliance with assessment of pain and emotional well-being, and it is likely to be useful in other areas in need of improved documentation.
Converting a clinical indicator on patient missed treatments into a functional quality improvement metric.
Authors: Amy S. Harrison, Laura A. Doyle, Mark Hurwitz, Lilya Babinski, Jamie Williamson, Adam Dicker, Yan Yu, Rani Anne', Robert Benjamin Den
Journal: Journal of Clinical Oncology (2014)

101 Background: Extended time to complete a course of radiation can be detrimental to a patient’s overall local tumor control and survival. The American College of Radiology (ACR) Radiation Oncology Practice Guideline requires review of any unplanned interruptions during treatment. However, factors that impact missed treatments are neither required to be reviewed nor well characterized within the literature. We sought to understand the variables contributing to missed treatments by generating a functional metric for quality improvement. Methods: The departmental electronic medical record (EMR) was modified to create sub-sets of classifications for missed treatments. These categories were divided into intended and unintended breaks, with intended classification of physician prescribed break and eight subcategories of unintended breaks: patient preference, physician mandated, patient feels ill, transportation/social services, cancelled, no-show, weather, and machine downtime. Missed treatments were documented real-time by the treating radiation therapists using one of these eight categories. A custom report was generated to extract and separate missed treatments by category. Results: Over three years of ACR tracking, our department missed treatment rate ranged from 5-10%, out of 64,000 patient treatments. The new subcategory metric has been in place for the past six months. Overall compliance with documentation by therapists was 100%. The new metric yielded a six month total rate of missed treatments of 8% with detailed analysis showing the main reasons as: patient preferences (14%), inclement weather (14%), and machine down time (9%). Transportation was only a minor issue for the patient population. Conclusions: This stratification of a simple clinical indicator has identified the major factors influencing the total time to complete a course of treatment. Based on this analysis, our departmental quality committee is focusing on engaging and educating patients about the negative impact of missed treatments on their overall cancer care. Future research will attempt to identify patient characteristics that may predict individuals more likely to miss treatments.
Impact of 36 months of androgen-deprivation therapy (ADT) on physical function and quality of life (QOL) in men with nonmetastatic prostate cancer.
Authors: Shabbir M.H. Alibhai, Henriette Breunis, Narhari Timilshina, George A. Tomlinson, Sarah Duff Canning, Neil Eric Fleshner, Murray Krahn, Ian Tannock, Padraig Richard Warde, Gary Naglie
Journal: Journal of Clinical Oncology (2012)

16 Background: Use of ADT has been shown to adversely affect physical function and QOL within 3 months of initiation; declines persist at 12 months. Few studies have examined physical function with ongoing ADT use beyond 12 months. Methods: In this extension of our prior study, men age 50 or older with non-metastatic prostate cancer (PC) who were on continuous ADT were followed along with two control groups (PC, no ADT; healthy controls) matched on age, education, and baseline function. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and the Timed Up and Go (TUG) test, representing endurance, upper extremity strength, and lower extremity strength, respectively. Aggregate physical and mental QOL were measured with the Medical Outcomes Study SF-36. Assessments were done at baseline and at 3, 6, 12, 18, 24, 30, and 36 months. Mixed effects regression models were used, adjusting for age, baseline function, and other covariates. Results: 87 patients on ADT, 86 PC controls, and 86 healthy controls were enrolled (mean age 69.4 y, range 50-87). At baseline, all three groups were similar in age and physical function (all ANOVA p&gt;0.05) and most subjects were otherwise quite healthy. 6MWT distance improved in both control groups but remained unchanged in ADT users (p=0.0379). Grip strength declined sharply in the ADT group by 3 months and remained stable up to 36 months (p&lt;0.001), whereas both control groups were stable over time. There was a slight worsening of TUG scores in the ADT group over 36 months (p=0.0003) but were unchanged in both control groups (p&gt;0.10). Aggregate physical QOL continued to decline in ADT users over time (p=0.0002) but remained stable in both control groups over 36 months, whereas aggregate mental QOL was stable in all groups over time. Most declines were evident within 3-6 months of ADT initiation. Conclusions: Initial declines with continuous ADT use in both physical function and aggregate physical QOL persist for 36 months but generally did not decline further beyond one year despite ongoing ADT use. Early exercise interventions and/or intermittent ADT use may improve these outcomes.
RECORD-4 multicenter phase II trial of second-line everolimus (EVE) in patients (pts) with metastatic renal cell carcinoma (mRCC): Anti-VEGF cohort subanalysis.
Authors: Thomas Cosgriff, Lin Yang, Anna Alyasova, Dingwei Ye, Andrey Karpenko, Hanzhong Li, Boris Alekseev, Li-ping Xie, Ruben Dario Kowalyszyn, Oleg Karyakin, Yeni Verónica Neron, LaTonya Collins, Thomas Brechenmacher, Chinjune Lin, Liza Morgan, Robert J. Motzer
Journal: Journal of Clinical Oncology (2016)

611 Background: RECORD-4 assessed EVE in pts with mRCC who progressed after only 1 prior therapy and enrolled pts into 3 cohorts based on first-line sunitinib (cohort 1), other anti-VEGF agents (cohort 2) or cytokines (cohort 3) (J Clin Oncol2015;abstr 4518). Median PFS in cohort 2 was 7.8 mo (95% CI, 5.7-11). This RECORD-4 subanalysis assessed EVE outcomes after individual first-line anti-VEGF agents in cohort 2. Methods: Pts received EVE 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. Primary end point was PFS per investigator review. Data cutoff was Sept 1, 2014. In this analysis, efficacy and safety were analyzed for pts in cohort 2 (n=62) who received sorafenib (Sor, n=23), bevacizumab (Bev, n=16), pazopanib (Paz, n=13), tivozanib (Tiv, n=5), or axitinib (Ax, n=3); missing information for 2 pts. Results: In groups Sor/Bev/Paz/Tiv/Ax, respectively, 96/81/100/80/33% of pts had good/intermediate MSKCC prognosis, 30/94/54/100/100% were white, 70/0/38/0/0% were Asian, and 83/75/77/100/67% were &lt;65 years of age. Median duration of exposure in groups Sor/Bev/Paz/Tiv/Ax, respectively, was 5.5/6.7/6.2/8.1/11 mo. Median PFS (95% CI) was 5.7 (3.6-11.3) mo in group Sor, 9.2 (2.2-NE) mo in group Bev, and 9.2 (1.9-18.0) mo in group Paz. Overall rate of grade 3/4 adverse events (AEs), rates of discontinuation due to AEs, and rates of dose adjustments due to AEs are presented in the table. Conclusions: Results of this RECORD-4 subanalysis demonstrated a favorable benefit-risk profile of second-line EVE in pts whose disease progressed during or after first-line anti-VEGF therapies. Results should be interpreted with caution due to small patient numbers. Clinical trial information: NCT01491672. [Table: see text]
Pre-emptive skin toxicity treatment for anti-EGFR drugs: Evaluation of efficacy of skin moisturizers and limecicline—A phase II study.
Authors: R. Grande, F. Narducci, G. Mansueto, D. Gemma, I. Sperduti, S. Bianchetti, F. Angelini, G. Trombetta, T. Gamucci
Journal: Journal of Clinical Oncology (2011)

e19542 Background: Anti-EGFR target therapies like erlotinib (E) for metastatic lung cancer (mLC) and cetuximab (C)/panitumumab (P) for metastatic colorectal cancer (mCRC) cause skin reaction that seems to be related to treatment efficacy. STEPP study has shown that pre-emptive skin toxicity (ST) treatment reduces incidence of ≥ Grade 2 (G2) ST in mCRC treated with P. Aim of this study is to evaluate if pre-emptive ST treatment with a different schedule has the same efficacy in patients (pts) receiving anti-EGFR drugs E/C/P for mCRC and mLC. Methods: Treatment (T) included skin moisturizers with sunscreen and limecicline (L) 300mg/daily from day 1. Primary objective: incidence of ≥G2 ST during the first 3 months of therapy. Toxicities are reported with confidence interval (CI) at 95%.Quality of life (QoL) was assessed with Dermatology Life Quality Index (DLQI) every 2 weeks and evaluated with repeated measure ANOVA. Results: 51 pts with mCRC (60.8%) and mLC (39.2%) were enrolled. Median age 67 (34-82), M/F 29(56.9%)/22(43.1%), ECOG PS 0/1 33/18. Anticancer drugs E/C/P 20/30/1. Median time to first toxic event was 6 weeks (CI 95% 4-8). At 3 months evaluation 14 (27.4%; CI 95% 15.2-35.7) pts had G2 ST: 71.4% of them showed ST during the first month, 21.4% in the second month, 7.1% in the third month. ST was not related with age (p=0.67), sex (p=0.65), previous chemotherapy regimens (p=0.20) and current anti-EGFR T (p=0.34). No gastrointestinal or hematological toxicities related to L was observed. Only 6 (11.8%) pts required further drugs. QoL analysis didn’t show significant difference from the beginning and the end of T: data will be presented. Observations at a median follow-up of 8 months are shown in the table. Conclusions: Data show efficacy of pre-emptive T with a well-tolerated profile. A reduction of severe ST is shown with an increase of grade 1 toxicities, not leading to anti-EGFR dose reduction and with better QoL for the pts. Updated results will be presented. G0 G1 G2 G3-4 Skin toxicities 11 (21.6%) 22 (43.1%) 18 (35.3%)* 0 Pustular rush 23 (45.1%) 20 (39.2%) 8 (15.7%) 0 Xerosis 28 (57.9%) 11 (21.6%) 12 (23.5%) 0 Paronychia 39 (79.5%) 10 (19.6%) 2 (3.9%) 0 * CI 95% 22.2-48.4
Activity of new agents (NAs) as third-line treatment in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) after a long-term disease control (LTDC) with abiraterone acetate (AA) or enzalutamide (ENZ) post docetaxel (DOC): Preliminary results from a multicenter Italian study.
Authors: Antonello Veccia, Ugo De Giorgi, Gaetano Facchini, Lucia Fratino, Donatello Gasparro, Daniele Alesini, Umberto Basso, Marcello Tucci, Cinzia Ortega, Sarah Scagliarini, Francesco Verderame, Giovanni Lo Re, Giuseppe Procopio, Roberto Sabbatini, Enrico Campadelli, Paolo Andrea Zucali, Franco Morelli, Donata Sartori, Vincenza Conteduca, Orazio Caffo
Journal: Journal of Clinical Oncology (2016)

325 Background: Although the expected median progression free survival (mPFS) with AA and ENZ in DOC-pretreated pts is 6-8 mos, a quote of pts may experience a LTDC without progression of disease (PD) for more than 12 mos. Since the androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, some mechanisms of resistance could be common to all NAs. This may be crucial in planning their sequential use, mainly when a LTDC is observed in hormone NAs-based (HNAs) second line. The present study was aimed to assess the activity of NAs in pts who previously showed a LTDC with HNAs administered after DOC. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. For the study purpose, LTDC was defined as the absence of PD ≥ 12 mos in pts treated with second-line AA or ENZ. Results: A consecutive series of 291 mCRPC pts, median age 71 yrs (46-91), with bone (88%), nodal (53%) or visceral (18%) mets, was collected. All pts received NAs as second line after DOC: in particular 160 (55%) received AA and 32 (11%) ENZ, with 41 pts (21%) showing a LTDC (36 AA – 5 ENZ). Among LTDC pts, third line treatment was cabazitaxel (CABA) in 25 cases and one hormonal NA in the remaining (2 AA - 14 ENZ). The clinical outcomes of the third line therapy are detailed in the table. Conclusions: From this preliminary data, it appears that third line CABA could be slightly more active in pts achieving a LTDC with HNAs in second line LTDC, despite the clinical outcomes were not significantly different compared to HNAs. Analyses on larger patients populations are needed to confirm these findings. [Table: see text]