tbuckley/cabot-search huggingface dataset:
Differential response of factor VIII and protein C expression following multimodal therapy for esophageal carcinoma
Authors: M. Byrne, B. M, J. O’ Donnell, B. White, J. Kennedy, J. Reynolds
Journal: Journal of Clinical Oncology (2007)

15106 Background: Tumour growth is associated with development of a hypercoaguable state and increased risk of thrombosis. Factor VIII plasma concentration has been shown to be an independent and dose-dependant risk factor for venous thromboembolism. Von Willebrand factor, the carrier molecule of circulating FVIII is expressed by vascular endothelial cells and in vitro observations indicate that chemotherapy induces endothelial damage with subsequent dysfunction. This study assessed FVIII, Protein C and Protein S response following multi modal therapy for oesophageal carcinoma. Methods: Fifty oesophageal cancer patients were studied, (multimodal n= 25, surgery only, n=25), at time points 0 (pre-operatively, following the first and final cycles of chemoradiation, and on days 1, 3, 7, 14, 21 and 28 days, and at 3 and 6 months postoperatively. Blood samples were collected and centrifuged at 3000g for 20 minutes to botain platelet poor plasmad. Factor VIII levels were measured by one stage clotting assay with factor VIII-deficient plasma. Automated functional assays for Protein C and Protein S in plasma were performed. Results: Factor FVIII levels were significantly elevated in the multimodal cohort following the 1st (p&lt;0.008) and 2nd (p&lt;0.001) cycles of chemoradiotherapy and at all time points following surgery, compared to baseline readings (p&lt;0.001). Similar elevation was noted in the surgery only patients. No significant difference in factor FVIII levels between the multimodal group and surgery only patients was seen, except on day 21 (p &lt; 0.04). Preliminary findings indicate a significant difference between the multimodal and surgery only cohorts in Protein C (0.74–1.32 IU/ml) levels (p &lt; 0.05) at two timepoints. Conclusion: Factor VIII serum levels are significantly elevated following preoperative chemoradiotherapy. The pattern of response post oesophagectomy did not differ between the two cohorts. Elevated levels are a risk factor for both primary and recurrent venous thrombolism. The precise pathogenetic mechanism and cause of this elevation remains to be elucidated. Further studies investigating Protein C activity and, relating Factor VIII to thrombosis and inflammation in the oesophageal cancer patient are required. No significant financial relationships to disclose.
Relationship between surgical oncologic outcomes and publically reported hospital quality measures.
Authors: Jason Dennis Wright, Ana Tergas, Sharyn Nan Lewin, William M. Burke, Ling Chen, Alfred I. Neugut, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2014)

6504 Background: Hospital-level measures of patient satisfaction and process measures of quality are now reported publically by the Centers for Medicare and Medicaid Services. There are currently no metrics specific to cancer patients. We examined whether publically reported hospital satisfaction and quality data correlate with surgical oncologic outcomes. Methods: The Nationwide Inpatient Sample was utilized to identify patients with solid tumors who underwent surgical resection in 2009-2010. The hospitals in which patients were treated were then linked to: 1) publically reported measures of patient satisfaction (Hospital Consumer Assessment of Healthcare Providers and Systems, HCAHPS), 2) perioperative quality (Surgical Care Improvement Project, SCIP), and 3) mortality measures for medical conditions (risk adjusted mortality for pneumonia, MI, and CHF). The risk-adjusted hospital-level rates of morbidity and mortality were then calculated for each hospital and the means compared between the highest and lowest performing hospital quartiles for each of the measures. Data is reported as absolute reduction in risk (ARR) for each outcome. Results: A total of 63,197 patients treated at 448 hospitals were identified. The ARR in perioperative morbidity was 0.0020 for patients at high vs. low performing hospitals based on the overall HCHPS score of hospital satisfaction. Similarly, the ARR for mortality based on the same measure was 0.0038 for high vs. low performing centers. High performance on perioperative quality measures based on SCIP resulted in an ARR of 0.0056 for perioperative morbidity and 0.0049. Lastly hospitals with the lowest mortality for myocardial infarction, heart failure, and pneumonia and ARR for perioperative mortality of 0.0054, 0.0062, and 0.0011 compared to higher mortality hospitals for the respective conditions. Conclusions: Currently available measures of patient satisfaction and quality are poor predictors of outcomes for cancer patients undergoing surgery. Specific metrics for oncologic outcomes and quality are needed.
Development of phase-specific breast cancer survivorship care plans (SCPs).
Authors: Susan K. Parsons, Tracey Weisberg, Lauren Boehm, Arlene O'Rourke, Angie Mae Rodday, Nadine Linendoll, John Kalil Erban
Journal: Journal of Clinical Oncology (2017)

61 Background: There are nearly 3 million breast cancer (BC) survivors in the US. Among the recently diagnosed, accrediting organizations (e.g., Commission on Cancer) now require SCPs at the completion of curative therapy. Within the Oncology Care Model, the preparation and delivery of SCPs is recognized as one of the 13 quality metrics. SCPs, combining treatment summaries (TS) and follow-up care plans (FUCPs), assist patients and providers in the delivery of high quality long-term care. BC presents a unique challenge, as the risk of recurrence extends decades past initial treatment; adjuvant risk reduction may extend up to 15 years. Periodic FUCPs provide a mechanism to review updated information and may allow providers to catch up with longer term BC survivors whose care was delivered prior to SCPs. We explored the role of phase-specific SCPs within the heterogeneous BC survivor population. Methods: Oncologists and nurse practitioners (NPs) from the Breast Health and Survivorship Programs at Tufts MC, an academic medical center in Boston, and New England Cancer Specialists, a community-based private oncology practice in Maine--together caring for more than 2,000 BC survivors--convened to develop and test phase-specific survivorship tools. Using an adapted ASCO template for BC, TS were completed at the end of initial therapy by trained NPs. FUCPs for initial, 5-year, and 10-year visits were designed with clinical input, literature reviews, and existing guidelines. Results: FUCPs were pilot tested and refined before incorporation into the electronic health record. Further testing is planned to identify barriers to effective survivorship care, particularly involving documentation of changes in recommendations and the transition from oncologist to primary care physician. Conclusions: SCPs are critical for providing quality health care to BC survivors, but a single SCP, written at the conclusion of curative treatment, might not be sufficient to address changing needs of individuals as they progress through survivorship. Thus, phase-specific SCPs enable providers to focus on salient aspects of care that may change over time. Despite growing recognition of the value of SCPs, implementation remains a challenge across cancer programs.
High-dose 3D chemoradiotherapy trials in stage III non-small cell lung cancer (NSCLC) at the University of North Carolina: Long-term follow up and late complications
Authors: C. B. Lee, M. A. Socinski, L. Lin, D. T. Moore, D. E. Morris, J. S. Halle, J. G. Rosenman
Journal: Journal of Clinical Oncology (2006)

7145 Background: Combined modality treatment is the standard of care for patients (pts.) with unresectable stage III NSCLC. Dose escalation of radiotherapy and the use of concurrent chemotherapy are two strategies attempting to improve survival and locoregional control. The intensification of therapy increases the risk of both early and late treatment related toxicities. Methods: From 5/1996 to 8/2004, 112 stage III NSCLC pts. were entered into 4 Phase I/II trials to assess the safety and feasibility of high-dose (74–90 Gy) thoracic conformal radiotherapy (TCRT) in QD or BID fractions. All pts. were treated with platinum-based induction chemotherapy; 3 of the trials also used concurrent chemotherapy. Results: The median follow up of survivors (29/112) on these trials was 4.9 years. The overall response rate after combined modality therapy was 47% (53/112) (CR 4%, 5/112; PR 43%, 48/112). 27% (30/112) had stable disease. The median survival (with 95% CI) was 24 months (18–31 months). 1-, 3-, and 5-year overall survival was 69% (60–77%), 36% (27–45%), and 24% (16–33%) respectively. Late complications of therapy (defined as &gt;90 days post radiotherapy reported to date) are displayed in the table. Two pts. developed a second primary (1 lung, 1 liver carcinoid). In total, 22% (25/112) had late complications. These patients appear to have a significantly better overall survival (p = .007). 12% (13/112) had a brain-only recurrence, although this did not seem to significantly impact overall survival (p = .82). Conclusions: 1) High-dose TCRT is feasible and results in promising survival outcomes. 2) Late complications occur in a minority of patients suggesting the potential benefit of more aggressive TCRT is not outweighed by its risk. 3) Interestingly, brain-only recurrences did not significantly impact survival in these trials. [Table: see text] [Table: see text]
Natural killer cell response is a predictor of good outcome in MCPyV + Merkel cell carcinoma: A case series of 23 patients
Authors: Valerie Laniosz, Oluwakemi Onajin, Sindhuja Sominidi-Damodaran, Alexander Meves, Lawrence E. Gibson, Christian L. Baum
Journal: Journal of the American Academy of Dermatology (2017)
Alterations of molecular pattern in clinical biospecimen by pre-analytical conditions.
Authors: Florian Tobias Unger, Nicole Lange, Philipp Uhlig, Hartmut Juhl, Kerstin David
Journal: Journal of Clinical Oncology (2015)

e22263 Background: Biomarker analysis and patient stratification in the clinical situation is highly affected by the quality of biospecimen, which strongly depends on the pre-analytical conditions in which they were acquired. Warm and cold ischemia time that tissues are exposed to is of critical importance. Insufficient quality of such tissues may lead to spurious results and data misinterpretation resulting in biased stratification of patients. The present study was conducted to gain a better understanding of the molecular effects of warm and cold ischemia and consequences for clinical decision making. Methods: Normal and colorectal cancer (CRC) tissues from patients (n = 50) were analyzed by comparing endoscopy samples with samples fixed within 10, 20 and 45 minutes post surgery (cold ischemia). In addition, normal liver tissue (n = 43) before and after 10 minutes of warm ischemia were collected and compared to normal and metastatic liver tissue samples. Gene expression was analyzed using Affymetrix GeneChip technologies and protein expression/phosphorylation was examined by IHC, MSD and NanoPro1000 technology. Results: The gene expression profiling showed significant changes in individual patients in up to 690 genes due to warm ischemia in normal liver tissue and in up to 4,116 genes in primary CRC tissue due to cold ischemia. Strongly regulated genes as well as stable genes were identified and further validated. Clinically highly relevant was the finding that, the phosphorylation of EGFR-pathway proteins was affected by pre-analytical conditions. This was validated using the NanoPro1000 technology, to also information on the level of distinct isoform phosphorylation. Conclusions: Pre-analytical conditions had a significant impact on gene expression and phosphorylation of proteins. An understanding of pre-analytical influences is mandatory when testing surgical specimens in the clinical, while drug development, or identification of predictive biomarkers. To obtain reliable data, tissue processing for research and diagnostic purposes needs to be highly standardized. Molecular alterations identified in this study have to be analyzed with caution in clinical decision making, research and development programs.
BRAF mutation testing in cell-free DNA from plasma of patients with advanced cancers using a novel, rapid, automated molecular diagnostics platform (Idylla).
Authors: Helen J. Huang, Bart Claes, Gerald Steven Falchook, Aung Naing, Sarina Anne Piha-Paul, Apostolia Maria Tsimberidou, Ralph Zinner, Daniel D. Karp, Siqing Fu, Vivek Subbiah, David S. Hong, Jennifer J. Wheler, Rajyalakshmi Luthra, Bryan K. Kee, Michael J. Overman, Kevin Kim, Geert G. Maertens, Razelle Kurzrock, Funda Meric-Bernstam, Filip Janku
Journal: Journal of Clinical Oncology (2014)

e22139 Background: Cell-free (cf) DNA from the plasma of cancer patients offers an easily obtainable source of biologic material for analysis and monitoring of molecular aberrations. Novel technologies are needed for implementation of plasma cfDNA testing in personalized therapy. Methods: cfDNA from plasma of patients with advanced cancers who progressed on systemic therapy was purified and 100 ng was used for testing for V600 BRAF mutation using the fully integrated real-time PCR-based prototype platform (Idylla, Biocartis, Mechelen, Belgium) with a quick turnaround time (< 90 minutes). Results were compared to mutation analysis of archival primary or metastatic tumor tissue from a CLIA-certified laboratory if available (n=98). Results: cfDNA was extracted from plasma samples of 109 patients with advanced cancers (colorectal, n=46; melanoma, n=24; non-small cell lung, n=12; breast, n=6, Erdheim-Chester histiocytosis, n=4; thyroid, n=4; appendiceal, n=3; ovarian, n=3; other cancers, n=7). BRAF mutations were detected in 28% (30/109) of plasma samples and in 41% (40/98) of available archival tumor samples, resulting in concordance for patients who had plasma and tissue tested in 88% (86/98) of cases (kappa=0.74, 95% confidence interval 0.60- 0.87). In all 12 discrepant cases identical plasma cfDNA samples were tested using an alternative cfDNA BRAF mutation PCR-based method (BEAMing, Sysmex Inostics, Baltimore, MD), which yielded 100% agreement. Longitudinally collected plasma samples were available in 4 patients (appendiceal, n=1; melanoma, n=2; papillary thyroid cancer, n=1) treated with BRAF targeting combinations and changes in the amount of BRAF-mutant cfDNA corresponded with changes in tumor markers or subsequent responses to therapy visualized via imaging. Conclusions: Detecting V600 BRAF mutations in cfDNA from plasma using the Idylla platform is a fast and noninvasive alternative to mutation testing of tumor tissue with an acceptable level of concordance and sensitivity, and should be investigated further for testing and monitoring of BRAF mutation status in patients with cancer.
Willingness to pay for new hormone-refractory prostate cancer (HRPC) therapies: Experience from Ontario hospitals
Authors: D. Milliken, C. Sawka, M. E. Trudeau
Journal: Journal of Clinical Oncology (2007)

6559 Background: The New Drug Funding Program (NDFP) is an IV-based government funded provincial formulary that reimburses over 90 Ontario hospitals for new and expensive anti-cancer and supportive care drugs. An expert committee considers clinical and economic evidence, including a hierarchy of benefits and evidence to inform decisions. There can be extended unpredictable delays from the time evidence is available to funding, during which hospitals decide whether to pay for therapies. This report assesses hospitals’ willingness to pay for HRPC therapies prior to a funding decision. Methods: Patterns of uptake for docetaxel (D) and zoledronic acid (Z) were analyzed from the NDFP database and compared to publication dates, hierarchy of benefits and evidence, and costs for these new HRPC therapies. Results: Analysis of NDFP data for patterns of uptake revealed an apparent cost shift from hospitals to the NDFP for D but not for Z once funding was in place. This cost shift demonstrated that despite a higher cost, shorter time from publication to funding and equivalent levels of evidence that hospitals paid for D but not for Z. The only factor that favored payment for D over Z was that D ranked higher than Z in the NDFP hierarchy of benefits: Survival was the primary outcome for D versus prevention of skeletal related events (SRE) for Z. Publication of provincial practice guidelines supporting these therapies occurred after NDFP funding was in place and would not have impacted hospitals’ decisions to pay. Despite immediate uptake of Z once NDFP funding was introduced, hospitals did not absorb the cost when funding was temporarily suspended for a 5 month period. Conclusions: Survival benefit appeared to be the primary factor impacting hospitals’ willingness to pay for unfunded HRPC therapies. This observation is consistent with the ranking of clinical benefits used to inform NDFP formulary decisions. The higher cost of D did not appear to impact hospitals’ willingness to pay. No significant financial relationships to disclose. [Table: see text]
Prognostic value of incidental betablockers use in metastatic colorectal cancer patients receiving first-line treatment.
Authors: Michela Del Prete, Riccardo Giampieri, Mario Scartozzi, Elena Maccaroni, Luca Faloppi, Maristella Bianconi, Alessandro Bittoni, Luca Cecchini, Stefano Cascinu
Journal: Journal of Clinical Oncology (2013)

e14610 Background: Preclinical and retrospective studies suggested antitumor activity for the incidental use of betablockers in various tumour types. Data regarding colorectal cancer are lacking. We assessed the correlation between the incidental use of betablockers and clinical outcome in colorectal cancer patients receiving first-line therapy. Methods: 235 patients treated with first-line chemotherapy alone (128 patients) and with Bevacizumab (107 patients) were analysed. Patients were stratified for betablockers use, age, sex, site of metastases, previous adjuvant chemotherapy and ECOG performance status. Results: 29 patients (12%) were on treatment with betablockers at the time of first-line therapy: 20 (16%) in the chemotherapy alone group and 9 in the bevacizumab group (8%). In both groups patients receiving or not betablockers were similar for all main clinical characteristics. In the chemotherapy alone group, patients receiving betablockers showed an improved response rate (60% vs. 33%, p=0.044) and overall survival (mOS 41.3 vs 25.7 months, p=0.03, HR:2.26, 95% CI: 1.05-3.24). Only a trend for improved progression free survival was noticed. In the 107 patients receiving chemotherapy with bevacizumab a trend towards a worse overall survival was seen for patients receiving betablockers, although this was not statistically significant (mOS 16 vs 23.7 months, p=0.26, HR:0.64, 95% CI: 0.22-1.49). No significant differences were seen in regards of progression free survival or different response rate patterns between the two groups. Conclusions: Our analysis confirms a potential prognostic role for the use of betablockers in colorectal cancer patients treated with chemotherapy. Our findings are in line with preclinical studies suggesting that beta-adrenergic signalling may regulate cancerogenesis and tumor invasiveness. Our analysis suggests a potential worse outcome for patients on betablockers receiving Bevacizumab-based treatment, although the small number of patients precludes any definitive conclusion. We suggest that in future prospective trials the incidental use of betablockers will be considered a stratification factor for clinical outcome.
Gain of ALK gene copy number to predict lack of response to anti-EGFR treatment in advanced chemorefractory colorectal cancer (CRC) with KRAS/NRAS/BRAF/PI3KCA wild-type status.
Authors: Filippo Pietrantonio, Anna Tessari, Rosalba Miceli, Pamela Biondani, Federica Perrone, Adele Testi, Elena Tamborini, Giuseppe Pelosi, Luigi Mariani, Giuseppe Fanetti, Arpine Gevorgyan, Ilaria Bossi, Maria Di Bartolomeo, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2013)

3641 Background: KRAS, BRAF, NRAS and exon 20 PIK3CA quadruple wild-type CRC is associated with 41.2% response rate to anti-EGFR treatments. Even in molecular characterized patients, there is still a subset of non responders. The identification of additional predictive biomarkers is an unmet clinical need for treatment personalization. Alterations of ALK oncoprotein may interfere with the biological activity of EGFR through cross-talk of downstream signalling pathways. Methods: This retrospective analysis aimed to investigate the correlation between ALK gene copy number (GCN), assessed by fluorescence in situ hybridization (FISH), and clinical outcome in KRAS/NRAS/BRAF/PI3KCA wild-type chemorefractory advanced CRC patients receiving cetuximab or panitumumab. FISH was perfomed with break-apart ALK (2p23) probes and gain of ALK GCN was defined as a mean of 3 to 5 signals in ≥10% of cells and amplification as ≥6 signals. Association of ALK status with RECIST response was performed by Fisher’s exact test. Results: Forty-one patients were identified, of whom 17 (41%) were ALK GCN positive, whereas the remaining 24 cases (59%) were ALK GCN negative. No ALK translocations were detected. Overall response rate was 19/41 (46%). We observed a partial response in 3/17 patients with ALK GCN positive versus 16/24 patients with ALK GCN negative (18% versus 67%, respectively; P=0.0036). Kaplan-meier curves for comparison of median progression-free and overall survival, as well as correlation with ALK expression by immunohistochemistry, will be presented at the Meeting exploring the whole National Cancer Institute data-set. Conclusions: In this study population with KRAS/NRAS/BRAF/PI3KCA wild-type tumors, the response rate greater than 40% is in line with literature data. ALK GCN may be a biomarker for clinical outcome prediction in advanced chemorefractory CRC patients treated with cetuximab or panitumumab.
An Engineered Cell‐Instructive Stroma for the Fabrication of a Novel Full Thickness Human Cervix Equivalent In Vitro
Authors: Vincenza De Gregorio, Giorgia Imparato, Francesco Urciuolo, Maria L. Tornesello, Clorinda Annunziata, Franco M. Buonaguro, Paolo A. Netti
Journal: Advanced Healthcare Materials (2017)

There is a growing interest for developing organotypic cervical models by using primary cervical cells that are able to reproduce the physiological relevant stromal microenvironment and the distinctive histology of the native cervical epithelium. Here for the first time it is reported the production of an organotypic cervical model featured by a scaffold-free stromal tissue resembling the extracellular matrix (ECM) composition and organization of the native counterpart as well as a completely well-differentiated epithelium. To reach this aim, human cervical microtissue precursors have been produced, characterized, and used as functional building units to fabricate a cell-synthesized cervical stroma equivalent by means of a bottom-up approach. Immunotypization, and molecular and morphological analyses reveal the extent of fundamental epithelial biomarkers and the presence of collagen and noncollagenous molecules, demonstrating that the natural tissue architecture and biological characteristics of cervical tissues are reproduced. The results of this study suggest that the bottom-up technology used to produce these 3D human cervical equivalents provides a fully functional organotypic cervical model that may be used as a valuable tool to investigate the epithelial-stromal interactions as well as for testing new therapeutics in vitro.