tbuckley/cabot-search huggingface dataset:
Graded prognostic assessment (GPA) of HER2 positive breast cancer patients with brain metastases.
Authors: Ming Chi, Vyshak Alva Venur, Alireza Mohammad Mohammadi, Samuel T. Chao, G. Thomas Budd, Alberto J. Montero, Halle C. F. Moore, Paul Elson, John H. Suh, Lilyana Angelov, Gene H. Barnett, Jame Abraham, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2015)

589 Background: Brain metastasis (BM) is a serious complication of HER2+ breast cancer (BC). We evaluated prognostic factors for overall survival (OS) in a contemporary cohort of patients (pts) with HER2+ BCBM treated at a tertiary care institution. Methods: The Cleveland Clinic’s IRB approved BM database was used to identify HER2+ BCBM pts treated between 2000 and 2013. OS from the diagnosis of BM was the primary endpoint. Breast-specific GPA (Sperduto et al, 2012), based on age at BM (< 60 vs >60), KPS (90-100 vs 70-80 vs 60 vs < 60), and BC subtype (luminal B versus Her2), was correlated with OS. Cox proportional hazards models with and without stepwise variable selection were used for data analysis. Recursive partitioning was used to identify cut points. Results: Data from 205 pts were analyzed. Median age was 52 (23-86); 51% of pts had KPS 90-100, 23% KPS < 80; 52% of pts were ER and/or PR+, and 82% had extracranial metastases at BM diagnosis. BM were initially treated with WBRT +/- surgery (62%), or WBRT + stereotatctic radiosurgery + /-surgery (17%). Median OS was 16.9 months (95% C.I. 13.0-22.5). Using breast specific GPA, 63% of pts had the most favorable profile (scores of 3.5-4), 37% had the second most favorable profile (scores 2.5-3) while a single patient scored 1.5-2. In univariate analysis, breast GPA was associated with OS (p = .004) as were 2 of its components, KPS (p < .0001) and age (p = .01); breast subtype was marginally significant (p = .09). Multivariable analysis again identified KPS (p < .0001) and age (p = .003), as independent predictors (with difference categorizations). Bone/lung metastases (p = .007) rather than BC subtype were predictive of OS. An updated HER2+-specific GPA was thus defined by assigning “points” to each factor: KPS > 70 = 2 points; 1 point each for age < 50 and no lung or bone metastases. Based on the cumulative number of points, 3 prognostic groups were identified: favorable (3-4 points, 49% pts), intermediate (2 points, 30% pts) and unfavorable (0-1 point, 21% pts) with median OS of 25.7, 13.7 and 5.4 months, respectively. Conclusions: This study confirms the prognostic value of the breast GPA, and proposes a modified HER2+ specific version.
Addition of bevacizumab to compensate for the negative influence of attenuated relative dose intensity of cytotoxic agents on the outcome in patients with metastatic colorectal cancer.
Authors: Goro Nakayama, Naomi Hayashi, Chie Tanaka, Tsutomu Fujii, Yuichi Ando, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2013)

e14614 Background: We reported that relative dose intensity (RDI) of key cytotoxic agents, irinotecan (IRI) and oxaliplatin (OX), is a significant predictor of disease control in patients with metastatic colorectal cancer (mCRC). However, in concomitant therapy with bevacizumab (BEV), the influence of adding BEV on the relation between RDI of cytotoxic agents and outcomes are unclear. In this study, we evaluate the impact of BEV on RDI of IRI and OX-based chemotherapy on the outcome of mCRC. Methods: A retrospective analysis of mCRC patients entered into three prospective clinical trials, testing FOLFIRI (CCOG-0502), mFOLFOX6 (CCOG-0704), FOLFIRI plus BEV and mFOLFOX6 plus BEV (CCOG-0801), was performed. RDI was calculated as the delivered dose intensity divided by standard dose intensity calculated for each regimen and compared to response rate (RR), disease control rate (DCR) and progression-free survival (PFS). Results: In FOLFIRI therapy, higher RDI (IRI, &gt;median: 80%) group achieved significant better RR, DCR and PFS than lower RDI (&lt;median) group (RR: 65 vs. 6% [p=0.001], DCR: 100 vs. 41% [p=0.003] and PFS: 9.9 vs. 5.6 months [p=0.002]). The other hand, in FOLFIRI plus BEV therapy, there were no difference between higher and lower RDI (IRI, median: 76%) group in ORR, DCR and PFS (RR: 31 vs. 27% [p=0.779], DCR: 75 vs. 53% [p=0.208] and PFS: 6.2 vs. 7.3 months [p=0.903]). In mFOLFOX6 therapy, higher RDI (OX, &gt;median: 79%) group achieved better disease control than lower RDI group (RR: 47 vs. 33% [p=0.456], DCR: 100 vs. 73% [p=0.032] and PFS: 8.5 vs. 6.2 months [p=0.064]). In addition of BEV, there were no difference between higher and lower RDI (OX, median: 76%) group in any outcomes (RR: 54 vs. 74% [p=0.159], DCR: 88 vs. 91% [p=0.672] and PFS: 11.6 vs. 11.7 months [p=0.797]). Conclusions: RDI of key cytotoxic agents is a significant predictor of disease control, especially in IRI-based regimen. Nevertheless, in concomitant therapy with BEV, there were no relations between RDI of cytotoxic agents and outcomes. These results suggest that BEV could have ‘covering effect’ to reduce the influence of dose modification of cytotoxic agents in mCRC patients.
The impact of question-listing on distress, anxiety, and question self-efficacy among cancer patients.
Authors: Christopher Gayer, Melissa F Miller, Anne Morris, Mitch Golant, Joanne S. Buzaglo
Journal: Journal of Clinical Oncology (2014)

e17668 Background: Open to Options (O2O) is a question listing intervention that provides one-on-one decision support to cancer patients. In a previous pilot project, blood cancer patients (n=77) reported decreased distress and anxiety and increased question self-efficacy. As part of an effort to disseminate O2O across a community-based cancer support network, the objective of this study was to test its effectiveness among survivors of any cancer. Methods: Facilitators provided support using an evidence-based decision-making model to prompt patients to list questions about diagnosis and treatment. Patients completed pre- and post-session surveys and a survey following consultation with their treatment provider. Distress, anxiety and question self-efficacy were measured using a 10-point scale. Results: Seven facilitators used O2O with 108 patients; 100 provided consent (11% ethnic minority, 80% female), 89 completed post-session outcomes, and 71 completed the post-consultation survey. Patients reported decreased distress (p<0.001) and anxiety (p<0.001) and increased question self-efficacy (p<0.001). After consult with their treatment provider, 69 of 71 patients (97%) reported bringing their question list to their appointment. Among those who brought their question list, 94% referred to it, and 67% showed it to their oncologist. On a scale from 0 to 10, participants thought the question list contributed to a more productive appointment (median=9), enhanced their understanding (median=8), and proved helpful (median=9); 86% reported their oncologist answered most of their questions. High post-session question self-efficacy was associated with enhanced provider-patient dialogue (understanding, p=0.006; productive, p=0.001; helpful, p=0.002), but change in distress was not. Nearly one-third (34%) reported discussing cancer clinical trials with their provider. Conclusions: The present findings replicated those reported among blood cancer patients and provide greater evidence to support the implementation and dissemination of O2O. Use of question-listing may improve coping and decision-making skills and lead to enhanced patient engagement in a shared treatment decision making process.
A prospective validation of plasma ddPCR for rapid <i>EGFR</i> and <i>KRAS</i> genotyping of advanced NSCLC patients (pts).
Authors: Adrian G. Sacher, Cloud Paweletz, Ryan Alden, Allison O'Connell, Stacy L. Mach, Pasi A. Janne, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2015)

11089 Background: Plasma genotyping of cell-free DNA (cfDNA) has the potential to allow for noninvasive genotyping while avoiding the inherent shortcomings of tissue genotyping and repeat biopsies. We have developed a quantitative droplet digital PCR (ddPCR)-based plasma genotyping assay capable of detecting common EGFR and KRAS mutations (Oxnard et al., CCR 2014). This is the first prospective study designed to validate the test characteristics of plasma ddPCR in advanced NSCLC. Methods: Pts with newly diagnosed or progressive advanced NSCLC were eligible. All pts were required to have a biopsy available or planned for tissue genotyping which was used for gold standard comparison; rebiopsy was required for pts with acquired resistance to EGFR TKI. Pts underwent an initial blood draw and immediate plasma ddPCR for EGFR exon 19 del, L858R, T790M and/or KRAS G12X. Test turnaround time (TAT) was measured in business days from date of blood draw until test reporting. Test characteristics were studied only in pts completing both plasma ddPCR and tissue genotyping for a given mutation. Results: 170 pts have been enrolled: 95 newly diagnosed, 43 with acquired resistance to EGFR TKIs and 32 others with progressive disease. Tumor genotype: 68 EGFR exon 19/L858R mutants, 27 KRAS G12X mutants, 75 others. Median TAT for plasma ddPCR was 3 days (range 1-5). Specificity of plasma ddPCR was 98% for 19 del/L858R (55/56) and 100% for KRAS (57/57), but lower for T790M at resistance (84%, 21/25; p = 0.03). Sensitivity of plasma ddPCR was 74% for 19 del/L858R (50/68) and 76% for T790M (19/25) but lower for KRAS (48%, 13/27; p = 0.03). Sensitivity for EGFR or KRAS was 78% in pts with extra-pulmonary disease (58/74) but 30% in pts with lung only disease (7/23; p < 0.01). Conclusions: Plasma ddPCR for driver mutations in EGFR and KRAS has a rapid TAT and high specificity suggesting it could be used to avoid biopsies for genotyping in some pts with advanced NSCLC. The false positive rate for T790M is likely related to tumor heterogeneity in resistant disease. This assay is currently being transitioned into the pathology laboratory for clinical use. Funding: US Department of Defense, Conquer Cancer Foundation of ASCO, Stading-Younger Cancer Research Foundation
Polyphenic trait promotes liver cancer in a model of epigenetic instability in mice
Authors: Marco Cassano, Sandra Offner, Evarist Planet, Alessandra Piersigilli, Suk Min Jang, Hugues Henry, Markus B. Geuking, Catherine Mooser, Kathy D. McCoy, Andrew J. Macpherson, Didier Trono
Journal: Hepatology (2017)

Hepatocellular carcinoma (HCC) represents the fifth‐most common form of cancer worldwide and carries a high mortality rate attributed to lack of effective treatment. Males are 8 times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28hep–/– mice display sex‐specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males. We now demonstrate that obesity and aging precipitate alterations of TRIM28‐dependent transcriptional dynamics, leading to a metabolic infection state responsible for highly penetrant male‐restricted hepatic carcinogenesis. Molecular analyses implicate aberrant androgen receptor stimulation, biliary acid disturbances, and altered responses to gut microbiota in the pathogenesis of Trim28hep–/– ‐associated HCC. Correspondingly, androgen deprivation markedly attenuates the frequency and severity of tumors, and raising animals under axenic conditions completely abrogates their abnormal phenotype, even upon high‐fat diet challenge. Conclusion : This work underpins how discrete polyphenic traits in epigenetically metastable conditions can contribute to a cancer‐prone state and more broadly provides new evidence linking hormonal imbalances, metabolic disturbances, gut microbiota, and cancer. (H epatology 2017;66:235–251).
A feasibility study of tamoxifen chemoprevention in Hodgkin's disease (HD) survivors
Authors: L. Diller, P. Mauch, C. Medeiros Nancarrow, L. Byrnes, M. A. Stevenson, A. Ng, J. Garber
Journal: Journal of Clinical Oncology (2004)

8551 Background: Female survivors of chest radiation (RT) for HD have an increased risk of breast cancer (BC) that develops at a relatively young age, often prior to menopause. Tamoxifen has not been studied in the prevention of radiogenic BC. In order to design a randomized BC prevention trial of tamoxifen for this cohort, we conducted a single-arm study, assessing enrollment, adherence, and toxicity. Methods: Eligible women were diagnosed with HD age ≤30, ≥5 years from mantle/chest RT, completed childbearing and had no history of thrombosis or second malignancy. Women were invited by letter to participate in this one-year study of tamoxifen, annual mammogram, breast exams at 6 and 12 months and other monitoring, (with the option of continuing tamoxifen for 5 years). In addition, patients could be referred by their MD. Results: Of 272 women identified, 67 were lost to follow-up and 14 were ineligible for medical reasons. Of the remaining 191 women, 164 (86%) declined. Reasons were “fear of side effects” (27%); “not completed childbearing”(18%); “too busy” (9%); “do not want to take medication” (8%); “MD advised against” (4%) and other (34%). Twenty-nine women (median age 41, range 34–55; median time since HD 19 years, range 6–36) enrolled on the study and began therapy. Median time of tamoxifen exposure is 18 months (range 2–24 months). Nine women (31%) discontinued tamoxifen prior to completing a full year of treatment. Reasons were side effects (4), other medical problems (2), BC (1), and other (2). There were no unusual or serious side effects. Conclusions: Despite their increased BC risk and tamoxifen's efficacy in other populations, female HD survivors were not eager to take tamoxifen. Because the risk of early onset BC is substantial in HD survivors, other prevention strategies, including novel agents should be considered. No significant financial relationships to disclose.
Adjuvant chemoradiation therapy for pancreatic adenocarcinoma: Impact of family history on outcome
Authors: J. M. Herman, T. J. Pawlik, M. Swartz, H. M. Yu, R. Schulick, J. Winter, D. Laheru, R. Hruban, A. P. Klein
Journal: Journal of Clinical Oncology (2007)

15044 Background: The objective of the current study was to examine the impact of a family history of pancreatic adenocarcinoma (PCA) on the outcome of patients receiving adjuvant chemoradiation therapy (CRT) following pancreaticoduodenectomy (PD). Patients and Methods: Between August 1993 and February 2005, 902 patients underwent PD for pancreatic adenocarcinoma. Following PD, 405 patients received no adjuvant CRT, while 346 patients received CRT. Another 151 patients were excluded because they received protocol treatment, neoadjuvant CRT, or were lost to follow-up. Patients who received adjuvant CRT were treated with 5-FU (97.4%) based CRT (median dose 50 Gy) and maintenance 5-FU or gemcitabine. Survival was estimated using the Kaplan-Meier method and differences in survival were examined using the log-rank test. Cox regression analysis was used to control for family history. Results: Of the 751 patients included in the study, 158 (21%) patients had a known family history of pancreatic adenocarcinoma (only one family member n=119; &gt;=2 either first or second degree relatives, n=39). Clinicopathologic characteristics of patients with a family history of PCA were similar to those of patients who did not have a family history (age, race, positive lymph node status, primary tumor size, and proportion receiving adjuvant CRT; all P&gt;0.05). In an analysis of the entire patient cohort, adjuvant CRT was associated with an improvement in median overall survival compared with no adjuvant CRT (21.0 months vs. 14.6 months, respectively; P= 0.001). Family history of PCA (&gt;=1 family member) was not associated with overall survival (positive family history, 20.0 months vs. negative family history, 17.3 months; P = 0.12). Family history of PCA also did not modify the effect of CRT on overall survival. Specifically, on multivariate analysis, after stratifying on family history (&gt;=1 family member), CRT remained significantly associated with an improved survival (Hazard ratio=0.71; P=0.001). Conclusion: Adjuvant 5-FU based CRT improves the median survival of patients with resected pancreatic adenocarcinoma. The improvement in median survival associated with adjuvant CRT was independent of a familial history of pancreatic adenocarcinoma. No significant financial relationships to disclose.
PSA values as a surrogate of overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC) treated with second-line (2L) chemotherapy (CT).
Authors: Martin Richardet, Matias Nicolas Cortes, Matias Molina, Patricia Hernandez, Romina Brombin, Aldo Alejandro Riso, Pablo Companys, Luciana Paola Acosta, Eduardo Richardet
Journal: Journal of Clinical Oncology (2014)

e16104 Background: Numerous reports confirmed that mCRPC patients with ≥ 50% decline in PSA in first-line therapy increase the OS compared with those who did not. This was not demonstrated in second-line treatment setting. In order to evaluate the decrease of PSA as surrogate of OS in men with mCRPC in 2L treatment, we analyzed and compared the decrease in PSA> 30% and its relation to OS. Methods: 72 patients treated at our institution with mCRPC relapsed to Docetaxel were analized, from 2005 to 2013. The primary objective was to determine whether the decrease in PSA ≥ 30% in the first 3 months from first dose CT, correlates with an increase in the OS, and if there are differences between treatment regimens. Results: 25% of patients were treated with Docetaxel, 26% with Mitoxantrone and 49% with Abiraterone. The most common sites of metastasis were bone (85%), liver (3%) and lung (2%). We evaluated OS in all patients and found that in those with PSA decline> 30%, the OS was 10.3 vs 8.0 months in those that did not decline PSA (p = 0.23). Abiraterone treated patients had an OS of 10.3 versus 5.9 months (p = 0.02). In the Docetaxel arm, OS was 9.8 vs 12.4 months (p = 0.838), and in the Mitoxantrone arm, OS of 8.6 vs 9.5 months (p = 0.87). Conclusions: Patients in the Abiraterone arm with a decrease in their PSA values of> 30%, had an increase of 4.4 months in OS. (p = 0.02). This leads us to conclude that the decline in PSA> 30% in the first three months of treatment with Abiraterone correlates with an increase in OS. For Mitoxantrone and Docetaxel, the differences were not statistically significant. We need a larger number of patients to confirm this data.
Assessing community hospital compliance with NCCN breast cancer guidelines in diagnosis and treatment of stage IIb and IIIa breast cancer: A Fox Chase Cancer Center Partners (FCCCP) initiative
Authors: E. Gitelson, M. O'Grady, R. F. Swaby, L. J. Goldstein, T. Li, P. F. Engstrom, S. J. Cohen
Journal: Journal of Clinical Oncology (2007)

6578 Background: The majority of cancer treatment occurs in community settings. NCCN guidelines are widely regarded as a marker for quality cancer care. We performed a retrospective review to assess compliance with NCCN guidelines at community medical oncology practices affiliated with FCCCP. Methods: Outpatient charts of 277 patients diagnosed with stage IIb/IIIa breast cancer between 2002–2005 from 16 medical oncology practices were assessed for the following documentation: charted pathology report with stage, ER, PR, and HER2/neu status noted, menopausal status, diagnostic mammogram, surgical evaluation, and radiation oncology consultation. The following treatments were evaluated: irradiation post-lumpectomy, sentinel and/or full axillary lymph node dissection (SLND and/or ALND), number of lymph nodes resected if ALND, use and type of chemotherapy, and accrual to a clinical trial. Results were compared with corresponding NCCN guidelines. Results: Percent compliance with NCCN guidelines by parameter for documentation were: pathology report (90.2%), staging (100%), ER/PR (92.4%), HER2/neu status (87.5%), menopausal status (92.3%), results of diagnostic mammogram (83.2%), and consultations of surgical (92.8%) and radiation oncologists (76%). For treatment, 85.1% of women had radiation post lumpectomy. SLND and/or ALND were performed in 96% of surgeries, with full ALND performed in 99% of cases with positive SLN. Eight or more lymph nodes were evaluated in 71.9% of patients. Overall, 83.7% of patients underwent chemotherapy, with 78.7% receiving regimens in compliance with NCCN guidelines. Clinical trial accrual was 6.2%, exceeding American College of Surgeons commendation standards for comprehensive community programs. Overall, mean percent compliance per NCCN parameter among practice groups was 87.8% (range 41.6 - 96%), with 15/16 hospitals achieving mean compliance above 80%. Conclusions: A comprehensive quality benchmark assessment of community medical oncology offices using NCCN guidelines is feasible. While overall compliance is high, areas deserving of education and improvement can be identified. No significant financial relationships to disclose.
Abstract 011: Transcriptional Basis Of Epicardial Progenitor Cell Activation During Heart Development, Regeneration And Repair
Authors: Guo N Huang, Jeffrey E Thatcher, John McAnally, Yongli Kong, Xiaoxia Qi, Wei Tan, J. Michael DiMaio, James F Amatruda, Robert Gerard, Joseph A Hill, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation Research (2013)

The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of epicardial progenitor cells, which reengages a developmental gene program, but the underlying transcriptional basis has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on C/EBP, HOX, MEIS, and GRAINYHEAD families of transcription factors. Furthermore, disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial progenitor cell activation during heart development and injury, providing a platform for enhancing cardioprotection and regeneration.