tbuckley/cabot-search huggingface dataset:
Cost-effectiveness analysis (CEA) of bevacizumab (Bev) in first- and second-line treatment of metastatic colorectal cancer (mCRC).
Authors: Daniel A. Goldstein, Qiushi Chen, David H. Howard, Joseph Lipscomb, Turgay Ayer, Bassel F. El-Rayes, Christopher Flowers
Journal: Journal of Clinical Oncology (2014)

6502 Background: The addition of Bev to 5-Fluorouracil (5-FU)-based chemotherapy is the standard of care for previously untreated mCRC. A recent randomized trial demonstrated a 1.4 month increase in median overall survival (OS) when Bev is continued beyond the first progression, thus making it standard practice to use Bev with 5-FU based chemotherapy in both first- and second-line. International CEAs have evaluated Bev in the 1st-line setting. The objective of this study is to determine the cost effectiveness of Bev in the 1st line setting and when continued beyond progression from the US-payer perspective. Methods: We developed two Markov models to compare the cost and effectiveness of 5-FU, leucovorin and oxaliplatin (FOLFOX) with or without Bev in the first-line treatment, and subsequent chemotherapy with or without Bev in the second-line treatment of mCRC. Weibull models were fitted to the published survival curves, and were used to extrapolate the cause-specific mortality and progression risks. Costs for administration and management of adverse events were based on Medicare reimbursement rates for hospital and physician services, and drug costs based on the Medicare average sale prices (all in 2013 US $). Health outcomes were measured in life years (LY) and quality-adjusted life years (QALYS). The simulated OS and progression free survival (PFS) were validated by the fitted survival models. Model robustness was addressed by univariate and probabilistic sensitivity analyses (PSA). Results: Using Bev in first-line therapy provided an additional 0.289 QALYs (0.412 LYs) at a cost of $69,381. The incremental cost-effectiveness ratio (ICER) was $240,195/QALY. Continuing Bev beyond progression provided an additional 0.108 QALYs (0.167 LYs) at a cost of $23,788. The ICER was $219,742/QALY. In all one way sensitivity analyses, the ICER of Bev was > $100,000/QALY. The ICER of Bev was greater than $100,000/QALY in > 99.9% of PSAs. Conclusions: This is the first US based CEA of Bev in mCRC. Bev provides minimal incremental benefit at high incremental cost per QALY in both the first and second-line setting. The ICER of Bev could be improved by use of an effective biomarker to select patients most likely to benefit.
Antibody-mediated modulation of the IgM B-cell receptor (BCR) expression and signaling.
Authors: Sydney Welt, Rachel S Welt, Jonathan A Welt, Virginia Raymond, David Kostyal
Journal: Journal of Clinical Oncology (2014)

3050 Background: Targeting the BCR signaling pathway in B-cell malignancies has been shown to be therapeutic, but inhibition of the BCR itself has remained elusive due to serum IgM (sIgM) sequence homology. A unique sequence in the extracellular domain of membrane IgM (ECD-mIgM), designated proximal domain (PD), is not expressed in sIgM. Anti-PD monoclonal antibodies (mAbs) can be used to purify ECD-mIgM for mAb generation. Here we identify an ECD-mIgM conformational epitope not detected in sIgM. Methods: High affinity anti-PD monoclonal antibodies (mAbs) were generated by proprietary immunization techniques. These mAbs are shown by ELIZA, Western blots and Scanning Immuno-Electron Microscopy (SEM) to bind to mIgM protein and mIgM+ expressing cell lines (CA 46, SU-DHL-5, CRL-1596, CRL-1432, CRL-1642). Using these high affinity anti-PD mAbs, mIgM was immune-affinity purified. Second generation mAbs detecting mIgM conformational epitopes and not reacting with sIgM in ELIZA/Western/SEM assays were collected. Clonogenic assays were done by limiting dilution/MTT. Results: Cell surface binding assays demonstrated the specificity of these mAbs by testing against a panel of mIgM + vs mIgM- (mIgG+) cells. Normal sera failed to block or reduce mAb binding to mIgM+ cells. MAb1-1, mAb2-2b and mAb3-2b internalize mIgM but do not modulate cell growth inhibition. Second generation mAb4-2b mediates BCR internalization and in low density cultures, cell growth inhibition, anti-clonogenic activity and apoptosis are observed. Apoptosis is seen in a variety of malignant B-cell lines including high and low mIgM/Igα/β expressers. Conclusions: These data support the contention that BCR internalization is insufficient to interrupt the BCR signaling cascade despite the lack of detectable residual mIgM. Upon mAb4-2b binding to a non-ligand binding site on mIgM, it induces both BCR internalization and in another distinct event, apoptosis. These mAbs are candidates for development as drug/radioisotope targeting agents and/or as a mediator of inhibition of the BCR signaling pathway (mAb 4-2b). These mAbs have a high level of specificity as they do not bind to non-mIgM B-cells, normal lymphocytes and non-lymphatic tissue, thus reducing toxicity.
Prevention of palmoplantar erythrodysesthesia (PPE) with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (PLD), a placebo-controlled, double blinded, phase lll trial (SAKK 92/08).
Authors: Thomas Ruhstaller, Karin Ribi, Hong Sun, Shu-Fang Schmitz, Markus Borner, Annette Winkler, Andreas Mueller, Lukas von Rohr, Ralph C. Winterhalder, Christoph Rochlitz, Roger Von Moos, Sandro Anchisi, Clemens B. Caspar, Khalil Zaman, Alexandre Bodmer, Michael Beyeler, Simona Berardi, Beat J. K. Thurlimann, Arnoud Templeton
Journal: Journal of Clinical Oncology (2012)

9059 Background: PPE, also known as hand-foot syndrome, is a distinctive adverse drug reaction of PLD treatment. PLD has been detected in elevated concentrations in eccrine sweat glands in palms and soles. We postulated that prophylactic administration of an antiperspirant (F511 cream) prior and during treatment with PLD could decrease the incidence of PPE. Methods: Patients (pts) with metastatic breast cancer treated with PLD monotherapy ≥10mg/m 2 per week applied an antiperspirant to the left or right hand and foot and a corresponding placebo to the opposite site with double-blinding for the content of the cream applied to either side (intra-patient randomization). The creams were applied once daily during the first week, then three times per week. The primary endpoint was the rate of PPE grade (G) ≥ 2 in the antiperspirant or placebo treated side. Pts were evaluable if they developed PPE G ≥ 2 or had received cumulatively at least 160mg/m 2 PLD. Patient-reported extent of symptom burden was a secondary endpoint. Using McNemar’s matched pairs design 53 pts were needed to detect a difference of 20% between the sides with a significance level of 5% and power of 90%. Results: 52 of 90 pts from 11 Swiss centers included were evaluable. Median age was 64.5 years; median duration of PLD treatment was 12 weeks. 30 pts developed PPE G ≥ 2. In 3 pts PPE G ≥ 2 occurred on the placebo side but not on the antiperspirant side (p=0.097; table). PPE G ≥ 2 was borderline significantly more frequent in placebo foot than antiperspirant foot (p=0.048). Patient-reported extent of symptom burden showed a trend in favor of the antiperspirant side for skin problems (peeling, blistering, bleeding) in the group of pts with PPE G ≥ 2 (p=0.051). Conclusions: In this double-blind trial with intra-patient randomization we observed a trend towards less PPE G ≥ 2 with application of the antiperspirant cream F511 in pts treated with PLD as determined by the treating physician and reported by the pts. [Table: see text]
In Vivo modeling of Resistance to PI3Kδ Inhibitor Treatment Using EµTCL1-Tg Tumor Transfer Model
Authors: Annika Scheffold, Billy Michael Chelliah Jebaraj, Eugen Tausch, Anella Yahiaoui, Anna Dolnik, Tamara Jacqueline Blaette, Lars Bullinger, Christof Schneider, Daniel Mertens, Veerendra Munugalavadla, Shih-Shih Chen, Nicholas Chiorazzi, Stacey Tannheimer, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2016)
Telomerase RNA expression as a prognostic marker in patients with favorable histology Wilms tumor
Authors: J. S. Dome, C. A. Bockhold, S. M. Li, D. M. Green, S. Baker, E. J. Perlman, D. A. Hill, N. E. Breslow
Journal: Journal of Clinical Oncology (2004)

8519 Background: A primary objective of the fifth National Wilms Tumor Study (NWTS-5) was to identify novel prognostic indicators for patients with favorable histology (FH) Wilms tumor (WT). Telomerase is an enzyme that maintains telomeres and plays a key role in the cellular immortalization process. High expression of this enzyme correlates with unfavorable patient outcome in several pediatric and adult malignancies. We assessed whether levels of telomerase activity and RNA expression correlate with risk of recurrence in patients with FH WT. Methods: A case-cohort study was conducted involving 296 patients selected from NWTS-5 registrants who had pre-treatment frozen tumor samples available in the biology bank. Telomerase activity was measured using the telomeric repeat amplification protocol assay. Expression levels of TERT mRNA (encodes the telomerase catalytic component) and TERC/hTR (the telomerase RNA template) were measured using quantitative real-time PCR. Results: Forty-seven samples were excluded from the outcomes analysis due to lack of viable tumor, RNA degradation, or insufficient clinical information. The final analysis was conducted on 249 patients: 144 with relapse and 105 without relapse with follow-up of at least 2 years. Univariate analysis revealed a positive correlation between relative risk of recurrence (RR) and levels of TERT mRNA and TERC expression. For each 2-fold increase in TERT and TERC level, the RR increased by a factor of 1.12 (95% CI 1.01–1.24, p=0.04) and 1.33 (95% CI 1.09–1.61, p<0.01), respectively. Categorization of patients into equal groups representing high, medium, and low TERC expression revealed that the third of patients whose tumors had the highest TERC expression had a RR of 2.24 (95% CI, 1.25–4.02, p=0.01) compared to those at the low level. Expression level of TERC remained a significant prognostic indicator in a multivariate analysis adjusting for tumor stage and patient age. Telomerase activity level did not correlate with RR of recurrence. Conclusions: Telomerase RNA expression may provide a clinically useful adjunct to the current risk classification schema used for FH WT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NCI
Relative effects of antiretroviral therapy and harm reduction initiatives on HIV incidence in British Columbia, Canada, 1996–2013: a modelling study
Authors: Bohdan Nosyk, Xiao Zang, Jeong E Min, Emanuel Krebs, Viviane D Lima, M-J Milloy, Jean Shoveller, Rolando Barrios, P Richard Harrigan, Thomas Kerr, Evan Wood, Julio S G Montaner
Journal: The Lancet HIV (2017)
Use of flow cytometry during induction chemotherapy to determine outcomes in acute myeloid leukemia.
Authors: William Bruce Donnellan, Monalisa Ghosh Ghosh, Sunil Rangarajan, Bradley Jackson, Uma Borate, Harry P. Erba, James M. Foran
Journal: Journal of Clinical Oncology (2013)

7104 Background: The use of MRD to predict outcome in AML is controversial. We sought to determine concordance between FC and BM biopsy morphology on day 14 (D14BM) and CR bone marrow (CRBM) specimens and whether MRD detected by FC predicted for inferior outcomes. Methods: We performed a retrospective analysis of adult AML patients treated between 2005 and 2010 with standard induction chemotherapy. Based upon BM morphology and FC, patients were designated as BM+FC+, BM+FC-, BM-FC+, or BM-FC-. Outcomes assessed included induction failure, RFS and OS. Results were adjusted for age at diagnosis, NCCN risk classification, and secondary AML status. Results: Of 287 evaluable patients, 74 had D14 BM and FC results and 98 had CR BM and FC results. Using BM morphology as the gold standard, discordance rates for the presence and absence of disease for the D14 BM by FC were 29% and 23% respectively. Multivariate analysis revealed that patients categorized as BM-FC+ at D14 were more likely to experience induction failure (HR 8.62, CI 0.36-208) and had lower RFS and OS (HR 1.47, 1.95 CI 0.40-5.41, 0.52-7.36 respectively). Analysis of the CR BM samples showed similar results. Conclusions: In this retrospective study there was a high discordance rate between FC and BM morphology on D14 BM and CR BM. While there was a trend toward inferior patient outcomes when disease was detected by FC but not morphology, this was not statistically significant. Limitations of our study include the retrospective nature of the analysis, paucity of patient samples that had a FC evaluation, lack of data to see if positive FC at D14 or CR changed clinician therapy choices and interpretation bias by pathologists as a result of access to FC results during BM morphology interpretation. Larger prospective studies are needed to evaluate whether MRD detected by FC as early as D14 during AML therapy affects clinical outcomes.
Expression of GRP78 protein in pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm.
Authors: Asha R. Dhanarajan, Reginald Hill, Sam G. Pappas, Gerard J. Abood, Jennifer Lynn Gnerlich, Xianzhong Ding
Journal: Journal of Clinical Oncology (2017)

323 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to late detection, aggressive biology and resistance to chemotherapy. Markers for early detection of PDAC and mediators of chemoresistance are poorly understood. GRP78 is a major endoplasmic reticulum (ER) chaperone protein critical for protein quality control of the ER. Increased GRP78 expression promotes in vitro cancer cell survival, progression, and chemoresistance. This study aims to examine expression of GRP78 protein in PDAC and intraductal papillary mucinous neoplasm (IPMN) compared to normal pancreatic ducts using immunohistochemistry (IHC). Methods: The expression of GRP78 was assessed using IHC in 93 sections of formalin-fixed paraffin-embedded tissue: normal ducts (38), low grade IPMN (IPMN-LG, 26), high grade IPMN (IPMN-HG, 9), and PDAC (20). Immunostaining intensity of GRP78 protein was categorized as no or weak staining (0-1+) and strong staining (2-3+). Fisher’s exact test with two tails was performed using the GraphPad statistical software. Results: GRP78 expression was identified in the cytoplasm of normal pancreatic ducts, IPMN and PDAC with a fine granular pattern. All PDAC and IPMN-HG showed strong expression of GRP78 while the normal ductal cells showed only minimal expression of GRP78. 73% of IPMN-LG expresses GRP78 strongly. Statistical analysis revealed a significant difference in GRP78 expression level between normal ductal cells and all three pathological conditions including PDCA, IPMN-HG and IPMN-LG (all p &lt; 0.0001). Conclusions: This study shows that the expression level of GRP78 is significantly increased in PDAC, IPMN-HG and IPMN-LG compared to normal ductal cells. There appears to be a progressive increase in GRP78 expression from IPMN-LG to IPMN-HG and invasive PDAC. Increased GRP78 expression may be a marker for those at risk of developing PDAC. Changes in GRP78 expression over time and its role in PDAC chemoresistance should be further assessed. [Table: see text]
Overall survival according to tumoral clusterin expression in breast cancer.
Authors: Guillaume Mouillet, Loic Chaigneau, Thierry Michy, Cristian Villanueva, Fernando Bazan, Hamadi Almotlak, Elsa Curtit, Laurent Cals, Philippe Montcuquet, Nathalie Meneveau, Marie-Paule Algros, Xavier B. Pivot
Journal: Journal of Clinical Oncology (2013)

e11579 Background: Clusterin (CLU) is a glycoprotein expressed constitutively in many tissues and involved in various physiopathological processes. Despite CLU expression is dysregulated in many types of cancer, the specific role of CLU in tumorigenesis remains unclear. The identification of several forms of the protein, with multiple roles is an explanation for these conflicting results. Cytoplasmic CLU (cCLU) has a role in breast tumorigenesis, cancer progression and is associated with breast cancer cell lines death in vitro. However contradictory data are reported about prognostic value of cCLU on survival and clinical progression. Our objective was to estimate patient’s overall survival (OS) according to the expression of cCLU. Methods: Histological and clinical data of 158 patients diagnosed with breast cancer were retrospectively recorded. Every patients were treated in a single French university hospital between 1993 and 2001. Histological samples had been reviewed to determine hormonal status, HER2 and clusterin expression. Immunohistochemical techniques were based on standards and recommendations applied at the time of analysis. Tumors were defined as cCLU positive (cCLU +) if its expression was superior to 10%. Overall Survival rates along with standard deviations were estimated using the Kaplan-Meier method. Differences in OS according to cCLU expression were tested for significance using the log-rank test. Results: Patients had a median age of 56 years (31 – 82 years). Among the 158 patients analyzed, cCLU was overexpressed in 31 patients (19.62%). The histopathologic and clinical characteristics were not statistically different according to clusterin expression even if a trend favouring less favourable tumoural characteristics were observed in cCLU positive tumour. The median follow-up was 14.1 years (11.3 - 19.3). In univariate analysis, cCLU overexpession were not related to OS (HR = 0.86; CI95%: 0.43 - 1.70). Ten-year OS was 76% (± 4) among patients with cCLU - tumors vs 77% (± 7) in patients with cCLU + tumor (p = 0.66). Conclusions: cCLU expression does not seem to be a pronostic factor of overall survival.
Prior radiotherapy does not predict nivolumab response in non-small-cell lung cancer: a retrospective cohort study
Authors: Y. Kataoka, N. Ebi, D. Fujimoto, S. Hara, K. Hirano, T. Narabayashi, T. Tanaka, K. Tomii, H. Yoshioka
Journal: Annals of Oncology (2017)
A primary care education program regarding cancer survivorship care plans at the University of Wisconsin (UW).
Authors: James Edward Haine, Elizabeth R Trowbridge, Sandra A Kamnetz, David Feldstein, Lee G. Wilke, James Sosman, SarahMaria Hill Donohue, Mary E Sesto, Amye Tevaarwerk
Journal: Journal of Clinical Oncology (2017)

69 Background: Survivorship care plans (SCPs) have been recommended as a tool to improve cancer patients’ (pts) care coordination and outcomes. The UW routinely provides SCPs. However, a prior project indicated most PCPs were unaware of these SCPs, limiting SCPs potential benefits. Best methods for educating PCPs regarding SCP existence and content are needed. We developed an educational program to inform PCPs of SCP existence, content, and potential uses. Methods: The program - a 10 minute presentation with slides - was developed to make PCPs aware of the basics of SCPs as listed above. The program was presented at UW general internal medicine (GIM) and family medicine (FM) scheduled meetings and emailed to UW PCPs afterwards. Two anonymous online surveys were administered to evaluate PCP previous use and basic knowledge of SCPs. Baseline surveys were sent 1 week prior to the first presentation and a follow-up survey was sent 4 weeks later via UW GIM and FM listservs (n = 286 addresses). Results: 101 PCPs completed the baseline survey: 27% reported not knowing what SCPs were; 50% knew but reported never receiving one; 23% reported having received one. 66 PCPs that attended or reviewed the program completed the follow-up survey. 40 “matched” PCPs completed both surveys. See Table 1 for results. Conclusions: A brief educational program containing information about existence of, content, and location in electronic medical record (EMR) increased PCP knowledge in these areas, which are prerequisites for PCP use. Ongoing work will assess whether PCP review of SCPs at point of care influences clinical decision making. [Table: see text]
Prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with colorectal cancer.
Authors: Jae Hyun Kim, Seun Ja Park
Journal: Journal of Clinical Oncology (2017)

551 Background: Inflammatory response plays an important role in the pathogenesis of cancer. Some evidence has suggested that elevations in the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with decreased survival in various types of cancer. In this study, we aimed to evaluate the prognostic value of the NLR and PLR in patients with colorectal cancer (CRC). Methods: Between August 1995 and December 2010, medical records from a total of 2,004 patients with CRC were retrospectively reviewed. The values of simple inflammatory markers including NLR and PLR in predicting the long-term outcomes of these patients were evaluated using Kaplan-Meier curves and multivariate Cox regression models. Results: The median follow-up duration was 42 months (interquartile range, 19 – 69). The estimation of NLR and PLR was based on the time of diagnosis. In multivariate Cox regression analysis, high NLR ( ≥ 2.6) [hazard ratio (HR) 2.251, 95% confidence interval (CI) 1.570-3.228, p &lt; 0.001] and high PLR ( ≥ 155) [HR 1.473, 95% CI 1.019 – 2.128, p = 0.039] were independent risk factors predicting poor overall survival (OS) in CRC patients. Combined high NLR and PLR was also an independent risk factor predicting poor OS in patients with CRC [HR 2.316, 95% CI 1.529 – 3.508, p &lt; 0.001]. Conclusions: In this study, we identified that high NLR ( ≥ 2.6), high PLR ( ≥ 155), and combined high NLR and PLR are useful prognostic factors to predict OS in CRC patients.
A study of factors determining outcome of patients receiving third line chemotherapy for metastatic breast cancer: The Royal Marsden Hospital experience
Authors: A. Kuciejewska, U. Banerji, G. Walsh, S. Ashley, M. O’Brien, S. Johnston, I. Smith
Journal: Journal of Clinical Oncology (2006)

657 Background: Metastatic breast cancer is increasingly treated with multiple lines of chemotherapy. We studied the factors determining the outcome of patients receiving third line chemotherapy for metastatic breast cancer Methods: This is retrospective study of 149 consecutive patients from the Royal Marsden Hospital chemotherapy database recorded to have received third line chemotherapy for metastatic breast cancer. The chemotherapy regimens and best response to chemotherapy for all three lines of chemotherapy were recorded. The time to progression (TTP) and survival after third line chemotherapy were also studied. Chi square and log rank tests were used to analyse differences in response rates (RR) and (TTP)/survival respectively. Results: 149 patients were studied with a median age of 52 (range 25 -80). The median TTP and survival was 4 months (range 1–25) and 8 months (range 1–52) respectively. Eighteen different chemotherapy regimens were used. The RR for third line chemotherapy was 30.2% (45/149). There was no significant difference in the TTP and survival of patients treated with different chemotherapy regimens (p= 0.82 and 0.44) respectively. We identified a subgroup of patients who had a poor outcome after third line chemotherapy. These patients did not respond to the first two lines of chemotherapy and had a response rate of 20.2% (10/49) compared to the rest of the cohort, 35% (35/100), p= 0.068. The TTP (3 Vs 4 months, p = 0.033) and survival, (6 Vs 9 months, p = 0.027) of this subgroup was significantly shorter than the rest of the cohort. The median time to death after progression in this subgroup was 2 months. Conclusions: The chemotherapy regimen used does not influence RR, TTP or survival in patients receiving third line chemotherapy for metastatic breast cancer. Patients not responding to the first two lines of chemotherapy have a significantly shorter TTP and survival. Best supportive care or experimental chemotherapy should be considered as options for these patients. No significant financial relationships to disclose.