tbuckley/cabot-search huggingface dataset:
Prognosis of patients with very thin cutaneous melanoma: The good, the bad, and the miscoded.
Authors: Phyllis A. Gimotty, Ronald D Shore, DuPont Guerry
Journal: Journal of Clinical Oncology (2014)

e20044 Background: Several studies have focused on identification of patients with very thin (VT) melanomas who are nevertheless at “high risk” of metastasis and who might be considered as candidates for sentinel lymph node biopsy. Methods: We compared published studies reporting on patients with VT melanomas (≤0.25 or ≤0.20 mm in thickness) from 4 non-US population-based registries (Germany, Sweden, Queensland, Wales/Sydney) and examined VT incidence and survival outcomes in the US SEER registry (2004-2010) and an institution-based registry (Penn 1973-2008). Pathology reports for all VT lesions (≤0.25 mm) were re-reviewed in one SEER region (SEER-R). Results: 10-year disease-specific survival rates (DSS) for patients with VT melanomas were 0.1% to 0.9% lower than for slightly thicker lesions (0.26-0.50 or 0.21-0.40 mm) in published studies. While VT lesions were 4.5%-8.9% of thin melanomas (≤1 mm) in published studies and 13% at Penn, in SEER and SEER-R they were 21% and 23%. These high percentages prompted a re-review of the SEER-R VT melanomas. 27% of the VT lesions (n=447) had coding errors not caught by SEER edits. 17% of corrected thin lesions were VT with median thickness of 0.2 mm. SEER-R 5-year DSS for VT lesions was revised from 97.4% to 99%, similar to 2 published studies (99.2% and 99.4%). 75% (6/8) of those who died of melanoma had been re-coded as non-VT; median corrected thickness was 4 mm. Among Penn’s 3,328 thin melanomas, 407 (12%) were VT with median thickness of 0.22 mm. These were associated with a 15-year DSS of 99.3%. Characteristics of 9 patients who recurred (n=7) or died of melanoma (n=2) were not significantly different from disease-free patients for standard melanoma prognostic factors. Conclusions: Significant miscoding of thickness of VT lesions is likely in SEER. Characterizing and coding information about VT lesions is challenging and demands quality assessment of the data by comparison to similar cohorts and checking internal consistency. Additionally, we have observed consistently among the published cohorts a slightly lower survival rate for patients with VT melanomas. This may reflect the uncommon presence of “usual” poor prognostic factors or yet to be characterized adverse biomarkers.
Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage
Authors: Mohammad Shadab Siddiqui, Goro Yamada, Raj Vuppalanchi, Mark Van Natta, Rohit Loomba, Cynthia Guy, Danielle Brandman, James Tonascia, Naga Chalasani, Brent Neuschwander-Tetri, Arun J. Sanyal, Daniela Allende, Srinivasan Dasarathy, Arthur J. McCullough, Revathi Penumatsa, Jaividhya Dasarathy, Joel E. Lavine, Manal F. Abdelmalek, Mustafa Bashir, Stephanie Buie, Anna Mae Diehl, Cynthia Guy, Christopher Kigongo, Mariko Kopping, David Malik, Dawn Piercy, Naga Chalasani, Oscar W. Cummings, Samer Gawrieh, Linda Ragozzino, Kumar Sandrasegaran, Raj Vuppalanchi, Elizabeth M. Brunt, Theresa Cattoor, Danielle Carpenter, Janet Freebersyser, Debra King, Jinping Lai, Brent A. Neuschwander-Tetri, Joan Siegner, Susan Stewart, Susan Torretta, Kristina Wriston, Maria Cardona Gonzalez, Jodie Davila, Manan Jhaveri, Kris V. Kowdley, Nizar Mukhtar, Erik Ness, Michelle Poitevin, Brook Quist, Sherilynn Soo, Brandon Ang, Cynthia Behling, Archana Bhatt, Rohit Loomba, Michael S. Middleton, Claude Sirlin, Maheen F. Akhter, Nathan M. Bass, Danielle Brandman, Ryan Gill, Bilal Hameed, Jacqueline Maher, Norah Terrault, Ashley Ungermann, Matthew Yeh, Sherry Boyett, Melissa J. Contos, Sherri Kirwin, Velimir A.C. Luketic, Puneet Puri, Arun J. Sanyal, Jolene Schlosser, Mohammad S. Siddiqui, Leslie Yost-Schomer, Elizabeth M. Brunt, Kathryn Fowler, David E. Kleiner, Edward C. Doo, Sherry Hall, Jay H. Hoofnagle, Jessica J. Lee, Patricia R. Robuck, Averell H. Sherker, Rebecca Torrance, Patricia Belt, Jeanne M. Clark, John Dodge, Michele Donithan, Erin Hallinan, Milana Isaacson, Mariana Lazo, Jill Meinert, Laura Miriel, Jacqueline Smith, Michael Smith, Alice Sternberg, James Tonascia, Mark L. Van Natta, Annette Wagoner, Laura A. Wilson, Goro Yamada, Katherine Yates
Journal: Clinical Gastroenterology and Hepatology (2019)
A prognostic test to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC): A cost-effectiveness analysis.
Authors: David D. Stenehjem, Brandon Kyle Bellows, Rajesh R. Kaldate, Joshua Timothy Jones, Uwe Siebert, Diana I. Brixner
Journal: Journal of Clinical Oncology (2014)

e18509 Background: Uncertainty exists in identifying patients with early stage NSCLC that will benefit from ACT. High-risk patients may go untreated and low-risk patients may be unnecessarily burdened with the toxicity and cost of ACT. This study compared the cost-effectiveness of a prognostic test based on cancer stage and a cell cycle progression expression signature vs. standard of care (SoC) in guiding ACT decisions in stage I/II NSCLC. Methods: The lifetime costs (2011 US$) and effectiveness (quality-adjusted life-years, QALYs) of ACT treatment decisions were examined using a Markov microsimulation model from a US third-party payer perspective. Cancer stage distribution and probability of receiving ACT with SoC were based on data from an academic cancer center. High and low risk classifications were made based on the prognostic score calculating the 5-year cancer-specific mortality. Probability of receiving ACT with the prognostic test was estimated from a physician survey. Treatment benefit with ACT was based on the prognostic score stratified by cancer stage. Other model parameters were derived from the published literature or were based on defined assumptions. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way sensitivity analyses examined parameter uncertainty. Results: In the simulation, more patients received ACT with the prognostic test (42.6%) than with SoC (27.3%). The average lifetime cost with the prognostic test was $131,528 compared to $121,914 with SoC. The average QALYs gained were 5.45 with the prognostic test vs. 5.17 with SoC. The incremental cost-effectiveness ratio (ICER) for the prognostic test compared to SoC was $34,334 per QALY gained. The ICER varied by stage of cancer: stage Ia $37,215/QALY, stage Ib $26,530/QALY, and stage IIa $58,844/QALY. One-way sensitivity analyses indicated the model was most sensitive to the ACT treatment benefit and the utility after ACT in patients without recurrence. Conclusions: This study suggests using the prognostic test evaluated herein to guide ACT decisions in early stage NSCLC is cost-effective compared to SoC based on globally accepted willingness-to-pay thresholds.
Potential value of rapid prostate-specific antigen (PSA) decline, in identifying primary resistance (PRes) to abiraterone acetate (AA) and enzalutamide (ENZ), in pre-treated castration resistant prostate cancer (CRPC) patients (pts).
Authors: Antonello Veccia, Orazio Caffo, Francesca Maines, Alberto Bonetta, Gilbert Spizzo, Enzo Galligioni
Journal: Journal of Clinical Oncology (2014)

e16044 Background: AA and ENZ are new generation hormonal agents (NHA) which demonstrated a survival gain in CRPC pts, pre-treated with docetaxel. Although all responsive patients eventually become resistant to these NHAs, some pts show PRes, defined as an early progression within the first 3 mos, which leads to an early treatment interruption. In the present analysis we have tried to identify which factor, if any, may predict PRes to AA and ENZ. Methods: We evaluated a consecutive series of 57 pts, treated in our Hospital in two subsequent named patient programs, between September 2011 and March 2013 . Twenty six pts received AA (1,000 mg po + prednisone 10 mg po daily) and 31 ENZ (160 mg po daily). For each pt we have recorded the pre and post-NHA clinical history, the treatment details and outcomes. We have also assessed the ability of a series of 24 selected clinical factors to predict NHAs PRes, through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: Among the 24 factors, the presence of pain at baseline, high baseline lactate dehydrogenase levels and PSA levels after one month of treatment were predictive of NHA PRes at the univariate analysis. However only PSA levels at 1 month were confirmed at the multivariate analysis [exp(beta) 0.115; p = 0.007], as patients failing to achieve a 50% or more reduction, compared to baseline, were more likely to show NHA PRes (48% vs 15%). Moreover, a clear difference in both PFS [median 9 vs 2 mos (p < 0.00001)] and OS [median 17 vs 7 mos ( p = 0.0009)] was observed, between patients who achieved at least a 50% PSA reduction at 1-month and those who did not. Conclusions: Our results seem to suggest that PSA trend may represent a simple and rapid method of identifying patients with PRes to NHAs, as patients failing to achieve a ≥50% reduction within the first month of treatment should received a more intensive monitoring. These data need to be confirmed in a larger patient population.
DEB40µm-TACE: Early single-center results in 23 patients.
Authors: Ali Seif Amir Hosseini, Jan Slotta, Babak Panahi, Peter Jenzewski, Joachim Lotz, Otto Kollmar, Christoph Engelke
Journal: Journal of Clinical Oncology (2014)

e15136 Background: Transarterial chemoembolization (TACE) is used as palliative treatment of patients with intermediate-stage hepatocellular carcinoma (HCC). However this method is limited by its difficulties in obtaining a complete necrosis of the treated lesion. To increase the efficacy of TACE new very small drug-eluting beads (DEB) are being developed. The microsphere Embozene Tandem 40µm induces permanent occlusion down to subarteriolar/sinosoidal tumour vascular level. We present our early results on 23 patients with hepatic malignancies treated with DEB-TACE (Tandem 40µm) microspheres. Methods: A total of 23 patients with histology-confirmed malignant liver tumours (n=20 HCC, n=2 CCC, n=1 FLC) were included. Eligibility criteria were normal LFT’s, Stage BCLC < D, Child < C, normal renal function. All patients underwent DEB-TACE using 30-150 mg doxorubicin per TACE-session with highly subselective catheterization of tumour-feeding arteries. TACE was performed in all 23 patients with 75 sessions using doxorubicine-loaded Tandem 40µm. We compared the chemoembolization side effects, complications and disease remission or progression as evaluated by RECIST 1.1 criteria. Results: The median age was 64 years (range 42-83). BCLC was 0 (n=1), A (n=9), and B or C (n=13). Follow-up was 3-12 months (median: 6 months). No extrahepatic non-target embolisation occurred. Tumour response was CR n=1, PR n=10, SD n= 6 and PD n=3, respectively (follow-up pending n=2). Time to local progression was 18-590 days (median=313). Complications during follow-up occured in 3 out of 20 patients (1 portal vein thrombosis (at 6 months), 1 intrahepatic abscess under subsequent sorafenib-therapy (at 7 months), 1 subsegmental peritumoral liver necrosis (at 3 months). No tharapy-related mortality appeared during follow-up. 3 patients underwent liver transplantation. Conclusions: Our studies using DEB-40 µm microsphere showed good tolerability, safety and a high rate of local tumour necrosis. This data justify a subsequent clinical randomized trial.
Real-time identification of tumor lesions and response to vintafolide treatment.
Authors: Wael A. Harb, Siu-Long Yao, Binh Nguyen, Robin Mogg
Journal: Journal of Clinical Oncology (2014)

5533 Background: In treating cancer, companion diagnostics are most useful when they can identify patients who cannot benefit from treatment. However, existing tests suffer from inaccuracy due to dependence on single specimens of a multifocal tumor or dependence on historically obtained specimens that may not represent the current tumor state. This analysis evaluates the performance characteristics of etarfolatide (EC20), a technetium-folate imaging diagnostic designed to provide real-time information on all patient tumor lesions that may respond to treatment with vintafolide (desacetylvinblastine-folate conjugate, EC145). Methods: 209 baseline lesions from 44 patients were evaluated in a phase 2 open-label, multicenter study of vintafolide in advanced ovarian cancer (EC-FV-02, NCT00507741). Data from 9 patients (52 lesions) without follow-up were excluded. 21 lesions were categorized as not evaluable, and 6 lesions were categorized as not imaged. 8 lesions that did not meet minimal size criteria were also excluded. The final analysis set included 107 lesions from 33 patients. Results: Etarfolatide correctly identified 24 of 26 lesions whose tumor size numerically decreased following vintafolide treatment (sensitivity for numerical decrease=92%). The corresponding negative predictive value (NPV=percent of EC20– lesions that did not numerically decrease) was 86% with a specificity of 15% and a positive predictive value (PPV=percent of EC20+ lesions that numerically decreased) of 26%. Among the etarfolatide negative lesions, 0 decreased by at least 30%. Among the etarfolatide positive lesions, 5 decreased by at least 30%. Therefore, among the 5 lesions that decreased by at least 30%, 5 were etarfolatide positive (sensitivity=100%). Among 102 lesions that did not decrease by at least 30%, 14 were etarfolatide negative (specificity=14%), corresponding to PPV and NPV of 5% and 100%, respectively. Conclusions: Etarfolatide identified nearly all tumor lesions that responded to vintafolide treatment in a phase 2 ovarian cancer study. Lesions that do not demonstrate etarfolatide uptake will not demonstrate major shrinkage (>30%) following vintafolide treatment. Clinical trial information: NCT00507741.
Excess Mortality in Polycythemia Vera and Essential Thrombocythemia
Authors: Arturo Pereira, Carlos Besses Raebel, Juan Carlos Hernandez Boluda, Francisca Ferrer Marin, Carmen Garcia-Hernandez, María Teresa Gómez-Casares, Manuel Pérez-Encinas, María-Soledad Noya, Beatriz Cuevas, Gonzalo Caballero, Maribel Mata, Francisco Cervantes, Alberto Alvarez-Larrán
Journal: Blood (2018)
SIX2 Mediates Late-Stage Metastasis via Direct Regulation of <i>SOX2</i> and Induction of a Cancer Stem Cell Program
Authors: Michael U.J. Oliphant, Melanie Y. Vincent, Matthew D. Galbraith, Ahwan Pandey, Vadym Zaberezhnyy, Pratyaydipta Rudra, Katherine R. Johnson, James C. Costello, Debashis Ghosh, James DeGregori, Joaquin M. Espinosa, Heide L. Ford
Journal: Cancer Research (2019)

Abstract The capacity for tumor cells to metastasize efficiently is directly linked to their ability to colonize secondary sites. Here we identify Six2, a developmental transcription factor, as a critical regulator of a breast cancer stem cell program that enables metastatic colonization. In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs. Six2 directly bound the Sox2 Srr2 enhancer, promoting Sox2 expression and downstream expression of Nanog, which are both key pluripotency factors. Regulation of Sox2 by Six2 enhanced cancer stem cell properties and increased metastatic colonization. Six2 and Sox2 expression correlated highly in breast cancers including TNBC, where a Six2 expression signature was predictive of metastatic burden and poor clinical outcome. Our findings demonstrate that a SIX2/SOX2 axis is required for efficient metastatic colonization, underscoring a key role for stemness factors in outgrowth at secondary sites. Significance: These findings provide novel mechanistic insight into stemness and the metastatic outgrowth of triple-negative breast cancer cells.
Abstract 14609: Fibronectin Surface Coating Accelerates the Autologous in vivo Recellularization of Decellularized Aortic Conduits in a Rat Implantation Model
Authors: Alexander Assmann, Christofer Delfs, Kim Horstkötter, Hiroshi Munakata, Khon Huynh, Volker Stoldt, Hiroyuki Kamiya, Udo Boeken, Artur Lichtenberg, Payam Akhyari
Journal: Circulation (2012)

Objectives Decellularization is a promising option to diminish immune and inflammatory response against cardiovascular implants. In order to accelerate the autologous in vivo recellularization of a...
Use of crowdsourcing for cancer clinical trial development.
Authors: Amanda Leiter, Tomasz Sablinski, Michael Diefenbach, Marc Foster, Alex Greenberg, John Holland, William K. Oh, Matt D. Galsky
Journal: Journal of Clinical Oncology (2014)

e16019 Background: Only 2-7% of cancer patients enroll in cancer clinical trials. Multiple reasons for poor accrual to trials have been cited including: lack of clinician/patient enthusiasm for a particular experimental intervention, lack of trial awareness, and unnecessarily restrictive eligibility criteria. Yet, trials are typically conceived of, and designed by small teams of researchers with minimal patient input. Crowdsourcing is the completion of a task by obtaining input from a large number of individuals. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians and patients could be harnessed to improve the clinical trial design process. We sought to evaluate the feasibility and utility of this approach. Methods: We first developed a clinical trial protocol for a study exploring metformin in prostate cancer. We then used a secure web-based platform to obtain input (based on 30 open- and closed-ended questions) from physicians/researchers and patients/advocates regarding important design elements of the proposed trial. Feasibility was prospectively defined as collecting input from at least 20 patients/advocates and 20 physicians/researchers. Utility was prospectively defined as the input resulting in at least 1 major (eligibility, dose, primary endpoint, statistical plan) or 3 minor (any changes not qualifying as major) protocol changes. Results: Over a 6-week period, crowdsourced input was collected from 60 physicians/researchers (>700 discrete responses) and 42 patients/advocates (>500 discrete responses) leading to 9 total changes (4 major and 5 minor) to the original protocol. Changes included modifications to eligibility criteria, data collection, and study procedures. Importantly, input from both physicians/researchers and patients/advocates led to protocol modifications. 91% of physicians/researchers and 76% of patients/advocates agreed or strongly agreed with the statement, “I would participate in a similar clinical trial crowdsourcing effort in the future.” Conclusions: Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct.
Tumor heterogeneity revealed by drug-induced apoptosis (MiCK) assays in lung cancer.
Authors: Dennis A. Wigle, Cary A. Presant, Allan Hallquist, Mathieu Perree, James Rutledge, Julian R. Molina
Journal: Journal of Clinical Oncology (2014)

e19115 Background: Evidence suggests that drug-induced apoptosis testing may facilitate individualized chemotherapeutic regimens, and may correlate with patient survival when using the MiCK assay (Cancer Res 2012; 72: 3901). Given recent demonstrations of tumor heterogeneity from genome sequencing, we explored inter-tumoral heterogeneity for tumors sampled from different sites with the MiCK assay. Methods: Patients with non-small cell lung cancer (NSCLC) or mesothelioma had tumors from different sites sent independently for drug-induced apoptosis testing. Purified tumor cells were cultured for 48 hours with individual drugs, and apoptosis was measured optically using light-scattering. Results from paired tumor sites in individual patients were compared and analyzed statistically. Active apoptosis (sensitivity) was defined as >= 1.0 kinetic units (KU), and no apoptosis (resistance) was < 1.0 KU, and 2 standard deviations (SD) in the assay were 1.14 KU. Results: 10 paired specimens were obtained from 5 NSCLC pts and 1 mesothelioma pt. The mean number of individual drug apoptosis tests analyzed per pt was 20.6 (range 3 to 39). There was concordance (within 2 SD) of drug-induced apoptosis in 97/103 assays (94%; 95% confidence interval [CI] 84% - 100%). Paired specimens analyzed for sensitivity or resistance showed concordance (within 2 SD) in 95% of assays (CI 85% - 100%). The best chemotherapy from specimen A was also shown to be the best chemotherapy from specimen B (within 2 SD) in 72% of 57 best drug assays (CI 36% – 100%). The best chemotherapy from specimen B was identical to the best chemotherapy for specimen A in 58% of 71 best drug assays (CI 27% – 89%). Conclusions: Significant inter-tumoral heterogeneity is not present in individual paired measurements of drug-induced apoptosis in the MiCK assay for lung cancer. However, since in 28% to 42% of assays the best chemotherapy from one site is not the same as best chemotherapy from an alternate site, analysis of multiple specimens may be appropriate in individual patients. Selection of metastases for apoptosis assays may be more desirable. In NSCLC, the DiaTech MiCK assay may identify chemotherapy regimens which produce the highest apoptosis.
Evaluation of prostate specific antigen (PSA) response following abiraterone in metastatic, castration resistant prostate cancer (mCRPC) previously treated with ketoconazole compared to ketoconazole naïve patients: A retrospective review.
Authors: Sofia Ghani, Kristopher Attwood, Angie Elefante, Kanza Khalid, Donald L. Trump
Journal: Journal of Clinical Oncology (2014)

e16067 Background: There is persuasive evidence that castration resistant prostate cancer (CRPC) remains AR dependent. Ketoconazole and abiraterone, block adrenal/intratumoral androgen biosynthesis; abiraterone has become the preferred choice for therapy in such men in view of its favorable toxicity profile and documented survival improvement in men with mCRPC. Direct comparisons of these two agents are unlikely and physicians now are faced with the question appropriate sequencing of such agents. The utility of ketoconazole in men who have previously received abiraterone is unknown. We evaluated PSA response rate to abiraterone among men with mCRPC previously treated with ketoconazole and compared this response rate to that seen in ketoconazole- naïve patients. We hypothesized that prior ketoconazole therapy would be associated with a substantially reduced PSA reponse following abiraterone. Methods: 32 men with mCRPC were identified between 2006-2013 who received abiraterone after treatment with ketoconazole. 46 men received abiraterone without prior ketoconazole. PSA response was defined as >50% reduction in serum PSA (Working Group Criteria) Results: Among men who had received ketoconazole first, the PSA response rate to abiraterone was 9.7% [95% CI:2-26%] In contrast, among men who received abiraterone without prior ketoconazole the PSA response rate was 54.3% [95%CI:40-70%]. (p<0.001) Conclusions: In this hypothesis-generating analysis, patients treated with abiraterone with prior ketoconazole had a much less favorable PSA response than patients unexposed to prior ketoconazole. These findings suggest that the mechanisms of action of ketoconazole and abiraterone in the management of mCRPC are similar. Further study of this question in a prospective fashion would provide a more rigorous evaluation of this question. However, based on this analysis it appears that men who have received ketoconazole as treatment for mCRPC are unlikely to benefit from abiraterone, at least as assessed by PSA response.