tbuckley/cabot-search huggingface dataset:
Incorporation of a patient question prompt list into a pancreatic cancer pathway.
Authors: Peter G. Ellis, Kathleen Lokay, Melinda Krebs
Journal: Journal of Clinical Oncology (2015)

20 Background: Metastatic pancreatic cancer is an aggressive disease affording a life expectancy of less than 6 months (Worni et al., 2013). Timely end-of-life discussions are critical. Patient question prompt lists (QPL) have been shown to facilitate discussions around distressing topics and increase patient satisfaction (Brandes et al., 2014; Clayton et al., 2007). We evaluated the use of a QPL embedded in a pancreatic pathway provided by Via Pathways (VP) to enhance communication between oncologists and patients with metastatic disease. Methods: VP are disease-specific decision support algorithms delivered in a web-based portal and used by oncologists at the point of care. Through a committee of oncologists and palliative care specialists, a QPL was developed and incorporated into the VP pancreatic pathway. The goal of the QPL was to empower patients to have informed discussions of available cancer therapies, treatment goals, and personal preferences. Users of the pathway were required to indicate if the QPL was used, then had to provide it to the patient. The QPL prompt was placed in the first line metastatic branch of the pancreatic pathway and piloted from 12/1/14 to 2/28/15. Following the pilot, users were surveyed through email. Results: Results are shown in the table. Conclusions: Based on the results, the pilot had limited success. Although there was an even distribution of those indicating the QPL was and was not provided to the patient, survey results suggested the majority of providers were unaware of the QPL. Our conclusion is that our approach must be less of a burden to the oncologist. Current focus is on automated delivery of advance care planning materials directly to the patient, removing that task from the oncologist workflow. [Table: see text]
Detection of prostate cancer by histoscanning.
Authors: R. Epplen, J. van Essen, T. van Erps, D. Thueer, R. Knuechel-Clarke, A. Heidenreich
Journal: Journal of Clinical Oncology (2011)

e15065 Background: HistoScanning is a tissue differentiation,visualization and quantification tool which identifies changes to solid organ tissues.It uses a specific three dimensional transrectal ultrasound device to acquire and transmit data to a computer program.Data is processed and suspicious areas in the prostate are projected in 3D.Our objective was to compare HistoScan with pathology of radical prostate specimens and to determine the sensitivity regarding to volume and localization. Methods: We analyzed the results of Histoscan in 85 patients that underwent radical prostatectomy.All patients had≥2 scans;scan with the largest suspicious volume was used for evaluation.Suspicious lesions measured ≥0,2 ml were considered positive.Specimens were processed according to the Stanford protocol.Findings were correlated with pathology according to localization and volume.A match was defined as a HistoScan positive lesion in a correspondent histopathologically positive area.Results were analyzed according to pT-stadium,Gleason Score(GS),PSA, cancerous tissue volume and volume of HistoScanlesions Results: Mean patient age was 62,8 years,mean PSA11,83ng/ml, mean prostate volume was 47,5ml and mean tumor volume was 4,80ml.44 patients had a pT2 tumor,38 a pT3 carcinoma.8 patients had salvage prostatectomy.9 patients had a final GS of 6, 50 and 18 pts had GS 7 and GS ≥8 respectively.HistoScan had 74% sensitivity in detecting and locating PCa.Only 55% of these cases showed a good correlation for tumor volume.Sensitivity was higher for pT3 tumors (92%) than for pT2 carcinoma (61,36%).HistoScan detected 55% of GS 6,74% of GS 7 and 83% of GS ≥8 carcinoma.HistoScan detected small tumors(<1 ml) in =50%,intermediate(1-5ml) in 57,5% and large(>5ml) in 86% respectively.Identical results are seen regarding the volume of suspicious lesions.For small (≤0,5 ml), intermediate(0,5-2ml) and large(>2ml) lesions,it correctly predicted prostate cancer localization in 33%,78,5 % and 64,7%,respectively. Conclusions: HistoScan has a great potential in detecting significant PCa.In particular,extracapsular,poor differentiated and large carcinomas show a high detection rate. However,larger prospective studies are needed to verify these preliminary results.
Phase II study of EZN-2208 (PEG-SN38) with or without cetuximab in patients with metastatic colorectal cancer (CRC).
Authors: Richard M. Goldberg, Chris R. Garrett, Noah C. Berkowitz, Tanios S. Bekaii-Saab, Theresa Ryan, George A. Fisher, Sally Clive, Petr Kavan, Einat Shmueli, Aby Buchbinder
Journal: Journal of Clinical Oncology (2012)

448 Background: EZN-2208 is a water-soluble, parenterally-delivered PEGylated conjugate of SN38 that increases solubility, exposure, and apparent half-life of SN-38. Methods: Patients with metastatic or locally recurrent CRC previously treated with fluoropyrimidines, oxaliplatin and irinotecan, and no more than 2 distinct progressions, were screened for K-Ras mutation and stratified accordingly. Patients with K-Ras tumor mutation (Mut) were treated with EZN-2208 (9mg/m 2 SN-38 equivalents) over 1-h IV on days 1, 8, 15 in 4-wk cycles (Arm A). Patients with K-Ras wild type (WT) tumors were randomized (2:1) to EZN-2208 (as above) and cetuximab (250mg/m 2 weekly following 400mg/m 2 on D1) (Arm B) or to irinotecan (125mg/m 2 ) over 90min IV days 1, 8 in 3 week cycles and cetuximab (as above) (Arm C). The primary objectives of the study were to determine the overall response rates (ORR) and progression free survival (PFS) (Arm A) and compare PFS (Arms B and C). A comparison of safety and toxicity of EZN-2208 and irinotecan was planned as well. Results: Demographic and efficacy parameters are summarized in the table . Common adverse events (Arms A%, B%, C%), observed in &gt; 25% of patients in at least one arm of the study, were diarrhea (45%, 64%, 55%), fatigue (56%, 56%, 39%), nausea (43%, 59%, 47%), vomiting (31%, 46%, 39%), constipation (27%, 26%, 37%), abdominal pain (25%, 28%, 32%), anemia (33%, 21%, 21%), dermatitis acneiform (0%, 28%, 26%), hypokalemia (17%, 28%, 26%), and alopecia (12%, 28%, 3%). Conclusions: EZN-2208 in combination with cetuximab is active in patients in the 3rd line setting of CRC and comparable to irinotecan in combination with cetuximab. EZN-2208 monotherapy did not result in responses in patients with CRC following progression on irinotecan. EZN-2208 has an acceptable safety and tolerability profile as monotherapy, and in combination with cetuximab. [Table: see text]
A phase II study of trebananib (AMG 386) and abiraterone in metastatic castration resistant prostate cancer.
Authors: Avani Atul Shah, Fatima Karzai, Ravi Amrit Madan, William Douglas Figg, Cindy H. Chau, James L. Gulley, Guinevere Chun, John Joseph Wright, Andrea Borghese Apolo, Howard L. Parnes, William L. Dahut
Journal: Journal of Clinical Oncology (2013)

TPS5102 Background: Preclinical studies support the use of an antiangiogenic approach in the treatment of prostate cancer. Trebananib is a novel peptide-Fc fusion protein that sequesters angiopoeitin 1 and angiopoeitin 2, thereby preventing their interaction with their common receptor Tie2, and inhibiting tumor endothelial cell proliferation and tumor growth. Trebananib is currently in Phase 3 trials for the treatment of ovarian carcinoma and has been shown to have clinical activity in multiple tumor types. Previous studies have demonstrated that in vivo alterations of testosterone levels regulate the expression of vascular endothelial growth factor, fibroblast growth factor, and angiopoietin associated factors. Dual inhibition of the androgen and angiogenic axis represents a novel strategy of combined targeted therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). We hypothesize that the addition of trebananib to CYP17 inhibitor abiraterone and prednisone will increase the median progression free survival (PFS) in chemotherapy-naïve mCRPC. Methods: This phase 2 study will evaluate the treatment effect as measured by progression free survival in patients treated with trebananib plus abiraterone/prednisone relative to abiraterone/prednisone alone. 72 patients with progressive, mCRPC will be randomized 1:1 to either study arm. Trebananib is administered intravenously every week, on days 1, 8, 15 and 22 of each 28-day cycle. Abiraterone acetate is taken once daily with prednisone 5 mg twice daily. We have completed the initial run-in phase of trebananib at 15mg/kg and 30mg/kg. The randomized phase of the study will use the 30 mg/kg dose of trebananib with the standard dose (1000 mg) of abiraterone. The primary end point is radiographic PFS. Secondary end points include overall survival, changes in genetic biomarkers related to the androgen and angiogenesis signaling axis, molecular markers of angiogenesis, circulating tumor cells and androgen receptor signaling status in circulating tumor cells before and after treatment. This combination of angiogenesis inhibition and abiraterone has the potential to improve clinical outcomes in front-line therapy for mCRPC. Clinical trial information: NCT01553188.
Inactivation of O<sup>6</sup>-methyguanine-DNA methyltransferase (MGMT) by promoter hyermethylation: A key factor of epithelial ovarian carcinogenesis in specific histologic types.
Authors: H. Roh, W. Joo, S. Lee, H. Yoo
Journal: Journal of Clinical Oncology (2010)

5103 Background: To evaluate promoter hypermethylation of O6-methyguanine-DNA methyltransferase (MGMT), expression of MGMT protein, and microsatellite instability (MSI), and also to investigate the clinical significance of these status in epithelial ovarian carcinogenesis. Methods: Ovarian cancer tissues (n = 86) were obtained after staging operation. MGMT gene was investigated by methylation-specific polymerase chain reaction (MSP) and MGMT protein expression status was analyzed using immunohistochemistry. MSI status was examined by the fluorescence-based PCR using five NCI markers. Results: Loss of MGMT expression was detected in 12 of 86 (14.0%) ovarian epithelial cancers. In 34 cases of MSP results available, MGMT promoter hypermethylation was detected in 5 cases (14.7%) with mucinous or clear cell carcinomas, but not in any of other histologic types (p = 0.028). 5 of 6 cases that lack of MGMT expression showed MGMT promoter hypermethylation, whereas all of 28 cases that retained expression of MGMT were unmethylated at MGMT CpG island (p = 0.000). In 41 cases of MSI results available, 7 (17.1%) cases showed MSI-H-phenotyped. Both MGMT promoter hypermethylation and loss of MGMT expression were noted in only cases of mucinous or clear cell carcinoma which MSI status were mostly MSS-S phenotyped. However, no significant correlation was found between MSI status and clinicopathological variables. Conclusions: Loss of MGMT expression was significantly correlated with MGMT promoter hypermethylation in MSS-S phenotyped tumors of mucinous or clear cell carcinoma. Although most clinicopathologic variables were not associated with MGMT hypermethylation, our results suggest that MGMT promoter hypermethylation was a key factor of ovarian carcinogenesis in specific histologic types of ovarian cancers. No significant financial relationships to disclose.
The effect of cytoreductive radiofrequency ablation (cRFA) on results of therapy with sunitinib or interferon-alpha (IFN) in metastatic renal cell carcinoma (RCC) patients with a small primary tumor.
Authors: Ilya Tsimafeyeu, Bin Chung, Janie S. Zart
Journal: Journal of Clinical Oncology (2012)

414 Background: At least 5% of the patients (pts) with small primary RCC initially present with metastasis. The main objective of this trial was to evaluate the role of cRFA in metastatic RCC pts with small primary tumor treated with immuno- or targeted therapy. Methods: Three parallel single-arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials, and included histopathologically confirmed RCC; metastatic measurable disease; size of primary tumor ≤5 cm; good prognosis by MSKCC model; no previous therapy. Study 1: Pts were treated with percutaneous cRFA under CT guide and following IFN, 9 MIU, s.c, 3 tiw. Study 2: Pts received cRFA and following sunitinib in repeated 6-week cycles of 50 mg/day for 4 weeks, followed by 2 weeks off. Study 3: Pts with unresected primary RCC received sunitinib alone. The primary endpoint was a 33% increase in progression-free survival (PFS) over expected 5 months in study 1 and over expected 11 months in studies 2-3 (power 80%; significance .05). Sample size was 38 pts for each study. Results: Studies were comparable by baseline patient characteristics (age, gender, histology, ECOG PS, number of metastatic sites, primary tumor size). Efficacy data for 114 evaluable pts showed an objective response rate (ORR) of 8% (95% CI 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3; median PFS of 9.1 (95% CI 6.9, 10.2), 13.4 (95% CI 9.8, 14), and 12.7 (95% CI 11.3, 13.5) months for studies 1-3, respectively. ORR and PFS were significantly higher in sunitinib trials comparing with study 1 (P&lt;.01 all differences); no differences were found between studies 2 and 3 (ORR, P=.1; PFS, P=.6). The study 1 met its primary end point, showing that PFS was significantly increased. There were no unexpected toxicities of medical treatment and complications of cRFA. Conclusions: cRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy. Cytoreductive ablative technique did not improve PFS in pts treated with sunitinib. Sunitinib was effective in metastatic RCC pts with unresected small primary tumor.
Using computerized chemotherapy ordering to improve performance and documentation of informed consent.
Authors: James F. Brandman, Carol Knop, Karen Giammicchio
Journal: Journal of Clinical Oncology (2012)

299 Background: Informed consent is the foundation of patient-centered care. In the context of clinical trials involving chemotherapy, rigorous adherence to this principle is required. However, for the large majority of patients treated with chemotherapy outside of clinical trials, adherence to obtaining consent is suboptimal. In the past five Quality Oncology Practice Initiative (QOPI) audits, Northwestern University Hematology/Oncology performed worse than other academic cancer centers and the aggregated QOPI cohort. Methods: Informatics devised three steps to transform the process from memory dependent to electronically driven: 1. Insertion of “InformedConsentChemotherapy” generates text documentation of the required elements of informed consent: Cancer/Stage, Goals, Dose/Schedule, Side effects, Alternatives. 2. Required completion of the following pop-up attestation before electronic orders can be signed: “Informed consent (including the required elements) has been discussed and documented.” 3. Display of the completed attestation statement when the patient’s chemotherapy module is accessed. Results: One month after implementation an audit showed 100% display of the attestation statement and 98% concordance with actual informed consent documentation. Conclusions: This innovative informatics process change yielded major improvement in adherence to the fundamental patient-centered standard that chemotherapy informed consent be discussed and documented. Potential weaknesses in this informatics solution include completion of the attestation without documentation of informed consent and completion of the attestation without an actual consent discussion. The audit demonstrated that the first occurs rarely while the second is impossible to measure without continuous direct observation. Minimizing dependence on memory, the advantages of electronic chemotherapy ordering provide the capacity to make doing the right thing—documenting informed consent—the easy thing. [Table: see text]
WNT6 mRNA Is Overexpressed in Variuos Non-Hodgkin’s Lymphoma Cases with No Apparent Relation to Cyclin D1 Level.
Authors: Pawel M. Swoboda, Monika Gos, Grzegorz Rymkiewicz, Katarzyna Blachnio, Jan Walewski, Przemyslaw Janik
Journal: Blood (2005)
Shifting patterns in the interpretation of phase III clinical trial outcomes in the treatment of advanced NSCLC.
Authors: A. G. Sacher, N. B. Leighl
Journal: Journal of Clinical Oncology (2011)

6105 Background: Advanced non-small cell lung cancer (NSCLC) continues to have a grim prognosis despite decades of trials involving novel agents. Over time, there appears to be an increasing willingness to study and adopt new treatments with very modest clinical benefit. We have sought to determine if the primary endpoint, outcome and interpretation of large scale clinical trials in advanced NSCLC are changing over time. Methods: A literature search for all phase III randomized controlled trials of systemic therapy for advanced NSCLC was performed. Publication date, primary endpoint, clinical outcomes, statistical significance and conclusions of eligible trials were recorded. Aggregate data were compiled by 10-year intervals. Significant differences were determined using a chi-square or Student’s t-test as appropriate. Results: A total of 238 trials were reviewed and 207 were eligible for inclusion in this study. The primary endpoint of phase III trials shifted significantly from median survival in 1980-1990 (97% of trials) and 1991-2000 (96%) towards progression free survival in 2001-2010 (15% progression-free survival, 80% median survival; p=0.04 for 1980s vs. 2000s). A similar shift was noted in trial outcomes (positive vs. negative) from uncommonly positive in 1980-1990 (21% of trials) to frequently positive in 1991-2000 (65%) and 2001-2010 (78%; p=0.009 for 1980s vs. 2000s). A decrease in the magnitude of median survival gains in positive studies between 1980-1990 (4.3 months), 1991-2000 (2.6 months) and 2001-2010 (2.4 months) was observed (p=0.016 for 1980s vs. 2000s). Lastly, the period before 1990 was the only time in which studies were reported as negative due to insufficient magnitude of median survival benefit despite statistical significance. Conclusions: A significant shift has occurred over the past 3 decades in the design and interpretation of phase III trials in advanced NSCLC. The use of median survival as the primary measure of benefit is declining alongside the magnitude of benefit deemed clinically relevant. This suggests a shift in the oncology community towards an increasing willingness to accept lesser benefit from new treatments.
External validation of a tumor-derived 5-gene prognostic signature for recurrence (R) of stages I/II colon and stage I rectal cancer following potentially curative resection.
Authors: P. F. Lenehan, L. A. Boardman, D. W. Fry, E. R. Heyman, J. Ohrnberger, W. P. Worzel
Journal: Journal of Clinical Oncology (2011)

437 Background: Optimizing post-operative clinical management for early-stage (I/II) colorectal cancer (CRC) patients (pts) is a significant unmet medical need. We hypothesized that a molecular prognostic test using primary CRC tissue would better predict the chances of tumor R within 36 months (mo) than current NCCN Clinical Practice Guidelines (NCCN). Methods: Pts had tumor R by 36 mo (n=46) or confirmed non-recurrence (NR) for ≥36 mo (n=69) after surgery; none had received neoadjuvant or adjuvant therapy. Archival formalin-fixed paraffin-embedded primary adenocarcinoma tissues (median storage 7 years; range 4-15) obtained at initial surgical resection with curative intent were retrieved for 86 stage I/II (pT1-4 pN0 M0) colon cancer and 29 stage I (pT1-2, pN0 M0) rectal cancer pts from 2 US and 2 European sites that were different from those previously used to generate the molecular test. Tumor gene expression was assessed by qRT-PCR with custom 384- well TaqMan Low Density Arrays (Applied Biosystems) using RNA that had satisfied a set of rigorous quality control parameters. Results: For stages I/II CRC (n=115), the dichotomous rule correctly classified 32/46 R and 38/69 NR pts: sensitivity (S) 0.70, specificity (SP) 0.55. High-risk pts had a significantly higher probability of R by 36 mo than low-risk pts: PPV 0.51, NPV 0.73; hazard ratio (HR) 2.06 (95% CI: 1.10 to 3.86; p=0.020). NCCN (V.1.2011) was not able to differentiate 36-mo R vs NR in this population: S 0.72, SP 0.42, PPV 0.45, NPV 0.69; HR 1.38 (95% CI: 0.73 to 2.63; p=0.315). The SP of the molecular test was significantly greater than that for NCCN (p=0.05). For stage I pts (n=29; 13R, 16NR), the prognostic accuracy of the test (0.79; 23/29) surpassed that for NCCN (0.55; 16/29). Conclusions: External validation of a 5-gene prognostic rule confirmed its ability to differentiate early stage CRC pts at high risk vs low risk for R within 36 mo after surgery better than current NCCN Guidelines, especially for stage I. The improved specificity and high sensitivity of the molecular test confirm its potential utility for optimizing post-op clinical management of early stage CRC. [Table: see text]
Prognostic and predictive blood-based biomarkers of overall survival (OS) in patients (pts) with advanced colorectal cancer (CRC) treated with cetuximab (C): Results from CALGB 80203 (Alliance).
Authors: Ace J. Hatch, Herbert Pang, Mark D. Starr, John C. Brady, Jingquan Jia, Donna Niedzwiecki, Alan Paul Venook, Stephanie M. Cushman, Herbert Hurwitz, Andrew B. Nixon
Journal: Journal of Clinical Oncology (2014)

448 Background: Previously, we identified potential predictive biomarkers of C sensitivity related to EGFR signaling from archived tumor tissue from CALGB 80203. Due to the fact that blood-based markers are more convenient and can be monitored over the course of treatment, baseline plasma samples were also collected and five (EGF, HB-EGF, sEGFR, sHER2, sHER3) of the 14 markers previously analyzed in archived tumor were evaluated in plasma. Methods: CALGB 80203 was a randomized (1:1) phase II trial of 238 pts with locally advanced or metastatic CRC comparing FOLFOX or FOLFIRI (chemo) vs. chemo combined with C. Baseline EDTA plasma samples from 154 pts were analyzed for the 5 candidate markers. The levels of each analyte were correlated with the primary endpoint of OS using univariate Cox proportional hazards models. Potential predictive markers were identified using a treatment by marker interaction term in the Cox model and the markers with significant p-values are reported. Hazard ratios between treatment groups are reported for low or high marker levels dichotomized at the median. Results: Univariate analyses indicated that plasma levels of EGF and sHER3 were negative prognostic markers (p&lt;0.05) that correlated with OS for the overall pt population. Across all pts (KRAS mutant and wild-type), sHER3 was identified as a potential predictive biomarker for C. Pts with higher sHER3 levels had significant OS benefit from C treatment (interaction p=0.03; HR=0.57, 95% CI 0.36-0.92). Low levels of EGF predicted for OS benefit from C in KRAS WT tumors (interaction p&lt;0.01; HR=0.39, 95% CI 0.18-0.87) and lack of benefit in the KRAS mutant pts (interaction p=0.03; HR=3.03, 95% CI 1.13-8.16), but were not predictive for C across all pts combined. Conclusions: Blood-based profiling of EGFR axis members identified sHER3 and EGF as candidate predictors for benefit from C. These data are consistent with our findings using mRNA expression from archived tumor samples and suggest a role for receptor shedding in HER3 biology. If further validated, these markers may help guide the development and use of anti-EGFR therapies and combination regimens.