tbuckley/cabot-search huggingface dataset:
Advance care planning preferences in Hispanic population with cancer in the Bronx.
Authors: Jhosselini Cardenas Mori
Journal: Journal of Clinical Oncology (2016)

6 Background: We aim to explore medical information-sharing and decision-making preferences of Hispanic patients in the Bronx. Methods: We are recruiting cancer patients who self-identify as Hispanic and are waiting at the oncology clinic at Montefiore Medical Center Cancer Center before an appointment. Results: To date we have interviewed 110 patients. The majority (60, 52.6%) preferred shared decision-making with their doctors, families or both, while 45 (39.5%) had an active decision-making style. A minority (9, 7.9%) had a passive decision-making style, deferring to their families and only 1 (0.9%) had a passive decision-making style deferring to the physician. The only demographic characteristic that was associated with decision-making preference was language; those who are English-speaking were more likely to endorse an active decision-making style (Chi2 = 7.06, p = 0.029) and less likely to endorse shared decision-making (Chi2 = 6.33, p = 0.042). The majority of patients agreed or strongly agreed that they wanted to hear all of the information regarding their diagnosis, treatment options, treatment expectation and treatment risks and benefits. Conclusions: These results confirm our hypothesis that most Hispanic patients prefer either an active or shared decision-making process rather than a passive decision-making process. Most patients prefer disclosure of diagnosis, prognosis and plan.
Thioredoxin reductase RNA levels in expressed prostatic secretions as prognostic indicators of prostate cancer.
Authors: J. A. Linehan, R. Torrey, J. P. Clark, G. Babilonia, D. D. Smith, K. Chan, C. Lau, D. Y. Josephson, M. H. Kawachi, T. G. Wilson, S. S. Smith
Journal: Journal of Clinical Oncology (2011)

4623 Background: Thioredoxin reductases (TXNRD1, TXNRD2 and TGR) are involved in multiple cell functions: protection from oxidative stress, control of apoptosis, and synthesis of DNA. Like TMPRSS2:ERG, the thioredoxin system has been shown to play a role in more advanced prostate cancer. We have used nanotechnology to demonstrate that TXNRD1 and TXNRD2 are strongly up regulated in intratumoral reactive stroma (Singer et al., In Press). Using expressed prostatic secretions (EPS) we evaluated TXNRD1, along with other biomarkers as predictors of positive surgical margins in patients undergoing radical prostatectomy. Methods: We collected EPS prior to surgery in a blinded prospective study from 82 men undergoing radical prostatectomy for prostate cancer. 200ng of RNA from each specimen was used to prepare cDNA for TaqMan qPCR analysis of RNA levels. Specimens were analyzed for expression of RNA from PSA, PCA3, TXNRD1, and Type III plus VI TMPRSS2:ERG gene fusions. The capacity of these biomarkers to improve characteristic performance for predicting positive surgical margins (PSM), over baseline pre-surgical parameters: age, pre-biopsy serum PSA, biopsy Gleason sum and digital rectal exam (DRE) was analyzed. Results: The addition of assays for TXNRD1, PSA, PCA3, and TMPRSS2:ERG (type III+VI) RNA to baseline presurgical parameters for positive surgical margin prediction improved the area under the curve (AUC) from 0.728 (95%CI 0.6313728-0.8240672) to 0.862 (95%CI 0.7870411-0.9364589). At 80% specificity for positive margins, the baseline sensitivity using only DRE,PSA and biopsy Gleason sum was 56%. However, when TXNRD1, PSA, PCA3, and TMPRSS2:ERG (type III+VI), were added as predictors, the sensitivity was increased to 80% at 80% specificity. Based on these data, this test provides an 81% negative predictive value, compared to 75% for PSA, DRE and biopsy Gleason sum alone. Conclusions: The combination of biopsy Gleason sum and PSA correlate strongly with positive surgical margins. The addition of TXNRD1, PSA, PCA3, and TMPRSS2:ERG(type III+VI), markers as predictors improves the sensitivity and negative predictive value in predicting positive surgical margins prior to surgery.
Cost-effectiveness of <i>nab</i>-paclitaxel plus gemcitabine versus erlotinib plus gemcitabine in metastatic pancreatic cancer.
Authors: E. Gabriela Chiorean, Scott Whiting, Gary Binder, George Dranitsaris, Victoria Manax
Journal: Journal of Clinical Oncology (2014)

353 Background: In a recent phase III trial nab-paclitaxel (albumin-bound paclitaxel) + gemcitabine (nab-P/G) demonstrated a 1.8 month, or 27%, improvement in median overall survival (OS) (HR = 0.72, P &lt; 0.001) vs gemcitabine (G) in first-line metastatic pancreatic cancer (mPC). nab-P/G had higher 1 year OS (35% vs 22%) and improved PFS by 1.8 months (HR = 0.69, P &lt; 0.01). nab-P/G is the first taxane based therapy to show a significant OS improvement in a phase III mPC trial. Erlotinib + gemcitabine (E/G) has also demonstrated activity in mPC, with a 0.3 month OS benefit vs G (HR = 0.82, P = 0.04), a 1 year OS of 23% vs 17%, and 0.2 months PFS benefit (HR = 0.77, P = 0.004) vs G. A cost-effectiveness analysis measuring the cost per life year (LY) gained for nab-P/G and E/G was conducted from the US payer perspective. Methods: Costs and clinical outcomes were evaluated fromnab-P/G vs G and E/G vs G trials of mPC. Health care resource use and the management of grade III/IV adverse events (AE) were collected from a large multisite US oncology clinic, expert opinion, and literature (2012 US dollars). Drug cost per cycle was multiplied by the median cycles delivered from the trials for nab-P/G and E/G. Results: Duration of therapy was 4 months for nab-P/G vs 3.9 months for E/G. Total cost for nab-P/G was $24,984 vs $23,044 for E/G, including drug, administration and AE management. AE costs were similar between the two therapies (Table). Differences of &gt; 5% were noted in neutropenia (rates: nab-P/G = 33%; E/G = 24%), neuropathy (nab-P/G = 17%; E/G = 1%), and rash (nab-P/G = 0%; E/G = 6%). The net survival advantage for nab-P/G vs E/G was 1.5 incremental life months gained. Nab-P/G was cost-effective relative to E/G, at a cost of $15,522 per incremental life year gained. Conclusions: nab-P/G is a cost-effective alternative to E/G in mPC, bringing more months of OS at &lt; $16,000 cost per incremental life year gained. [Table: see text]
Pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU RU221408I.
Authors: Deirdre R. Pachman, Travis J. Dockter, Patricia J. Zekan, Briant Fruth, Kathryn Jean Ruddy, Lauren E. Ta, Todor Dentchev, Nguyet Le-Lindqwister, William M. Sikov, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2016)

220 Background: Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Preliminary animal data suggest that minocycline may be effective for the prevention of chemotherapy-induced neurotoxicity. The purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and P-APS. Methods: Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks. They were randomized to receive minocycline 200mg on day 1 followed by 100mg twice daily or a placebo, with the same dosing schedule. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy, and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment. The primary goal was to obtain pilot data regarding the possible effect of minocycline on the prevention of paclitaxel-induced CIPN and P-APS, to determine if conducting a larger phase III placebo-controlled trial was indicated. Scores obtained from patient questionnaires were converted to a 0-100 scale, where higher scores = better quality of life. Results: Forty-seven patients were randomized, 45 of which were evaluable, with a mean age of 55. There were no remarkable differences noted between the two groups for the overall sensory score of the EORTC-CIPN 20 or its individual sub-questions, which evaluated tingling, numbness, or shooting burning pain in hands and feet. However, there was a significant difference in the daily average AUC pain score attributed to P-APS, favoring minocycline (median 96.0 vs 84.3; p = 0.02). Correspondingly, patients receiving minocycline used less opioid pain medications for control of P-APS (0% vs 23%, P = 0.05). Not only were no increased toxicities reported with minocycline, but there was an apparent improvement in fatigue (median AUC 76.7 vs 59.0; P = 0.02). Conclusions: Based on the results of this pilot study, minocycline did not appear to be beneficial for the prevention of CIPN, but did look promising for reducing P-APS. Further study of this effect may be warranted. Clinical trial information: NCT02297412.
Small Molecule Inhibition of Cdc7, a Key Cell Cycle Regulator and Novel Therapeutic Target, Successfully Inhibits Leukemia Cell Growth in Vitro and in Vivo
Authors: Mark G. Frattini, David Shum, Kristen M O’Dwyer, Renier J. Brentjens, Ray Yeh, Peter Maslak, Mark Lawrence Heaney, Joseph Jurcic, Hakim Djaballah, Thomas J Kelly
Journal: Blood (2008)
Prognostic effect of the sixth and seventh American Joint Committee on Cancer TNM staging systems on esophageal cancer patients treated with chemoradiotherapy.
Authors: M. Nomura, K. Shitara, T. Kodaira, S. Hatooka, A. Mizota, C. Kondoh, T. Yokota, D. Takahari, T. Ura, K. Muro
Journal: Journal of Clinical Oncology (2011)

e14659 Background: The new seventh edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the sixth and seventh staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between stages I to III (P < 0.01) according to both editions. However, the seventh edition poorly distinguishes the prognoses of stages III and IV (P = 0.36 by multivariate analysis), in comparison to the sixth edition (P = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (P < 0.05). For the stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the seventh TNM staging system regarding prognostic factors in patients undergoing CRT.
Phase II study of thalidomide and celecoxib in androgen independent prostate cancer (AIPC)
Authors: G. Philips, K. Kinaman, M. Plante, M. Bunnell, P. Unger, P. Kantoff, M. Rincon
Journal: Journal of Clinical Oncology (2005)

4732 Background: Prostate cancer, a tumor dependent upon angiogenesis, frequently expresses vascular endothelial growth factor (VEGF), cyclo-oxygenase 2 (COX2) as well as interleukin 6 (IL-6) receptors. Thalidomide (T) manifests its anti-angiogenic activity via both basic fibroblast growth factor (bFGF) and VEGF pathways and can also down regulate the production of IL-6. Thalidomide has been shown to effect PSA responses in AIPC. COX2 inhibitors can ablate bFGF mediated angiogenesis and cause apoptosis of prostate cancer cell lines. We sought to identify possible synergistic clinical activity against AIPC of low dose T and celecoxib (C) and also examined effects on serial plasma VEGF and IL 6 levels. Methods: Eligibility criteria included asymptomatic AIPC progressing after antiandrogen withdrawal; ECOG PS 0–2; adequate liver, renal and hematologic function and no grade 2 or greater neuropathy. All patients (pts) received T 200 mg/day PO and if a > 50% PSA reduction was achieved by 3 months, they continued on T alone. Patients with a lesser response or progression additionally received C 200 mg/day for 3 months. Results: A total of 16 patients (13 with metastases, 4 had prior chemotherapy) initiated treatment. With T alone, 2 (13%) patients had a > 90% PSA decline, 10 (63%) had a transient < 50% decline and 4 (25%) progressed. Of the 9 patients who subsequently received C, 3 (33%) had a transient < 25% PSA decline, 1 (6%) had a 62% decline (possibly from an ongoing T effect), and 5 (56%) progressed. Four patients had PSA responses lasting 5.5 to 10 months (range 0–10 months for all patients). Expected grade 1/2 toxicities were observed with only 2 cases of grade 3 dyspnea and edema. Based on limited data points, changes in serum IL 6 levels and plasma VEGF levels did not correlate with PSA responses to T alone. Conclusions: Although the combination was well tolerated, low dose C did not significantly add to the known activity of low dose T as measured by PSA responses in AIPC No significant financial relationships to disclose.
Improving quality of pediatric cancer survivor care: Providers’ support of and experience with survivor care plans.
Authors: Echo L. Warner, Claire C Hacking, Yelena Wu, Anne C. Kirchhoff
Journal: Journal of Clinical Oncology (2014)

190 Background: Clinical integration of Survivor Care Plans (SCPs) varies. This study assessed pediatric oncology providers’ familiarity with and preferences for providing survivor care and SCPs. This research aims to inform efforts to improve the quality of pediatric cancer survivorship care through increased implementation of SCPs. Methods: From November 2013-April 2014 oncology providers (physicians n=18; nurses n=23) were recruited from the Pediatric Oncology clinic at Primary Children’s Hospital in Salt Lake City, UT. Participants completed a 25-item survey (N=41). A subset participated in a 45 minute focus group (n=17). Participants reported their familiarity with and training on survivorship care, opinions on SCP efficacy, and barriers to using SCPs. To evaluate differences in survey responses for physicians and nurses, we generated Fischer’s exact tests. Focus group transcripts and open-ended survey responses were content analyzed. Results: More oncologists reported familiarity with SCPs (94% vs. 30%, p&lt;0.01) than nurses. Top sources of training for cancer late effects included colleagues (66%), conferences (54%) and medical journals (37%). More oncologists (35%) than nurses (5%) reported ever providing a patient with an SCP (p=0.03). Oncologists also prioritized the clinical integration of SCPs more than nurses (69% vs. 29%, p=0.02). Top perceived barriers to using SCPs in clinical practice included: not knowing enough about SCPs (67%), using SCPs not expected (54%) and no champion (49%). In the qualitative comments, providers expressed that patient age variation made timing of SCP delivery difficult. Most participants were supportive of testing an SCP intervention program (95%) and felt this effort should be done within the context of the multidisciplinary healthcare team. Conclusions: As of now, this clinic has no standard procedures for disseminating SCP and survivorship care, yet the providers we surveyed supported testing an SCP program to improve the quality of their patients’ care. The implementation of coordinated pediatric cancer survivor care should include provider training and testing strategies to implement SCPs more consistently within clinical care.
EGFR mutation and response to chemotherapy in non-small-cell lung cancer (NSCLC) patients
Authors: K. H. Lee, S. W. Han, S. Jeong, D. W. Kim, D. H. Chung, S. A. Im, T. Y. Kim, D. S. Heo, Y. J. Bang, N. K. Kim
Journal: Journal of Clinical Oncology (2005)

7084 Background: EGFR mutation is associated with response and prolonged survival in NSCLC patients treated with gefitinib. However, its relevance in terms of response to conventional chemotherapeutics has not been investigated. We have retrospectively analyzed response to prior chemotherapies in NSCLC patients treated with gefitinib. Methods: EGFR mutation (mt) in exons 18, 19, 21, and 23 were identified by direct sequencing of PCR products of DNA extracted from archival paraffin embedded tissue. P-Erk (E) and p-Akt (A) expression was determined by immunohistochemistry. Response rate (RR) and time-to-progression (TTP) of prior chemotherapies of paclitaxel, platinum, and gemcitabine were analyzed in respect to EGFR mt and E and A expression. Results: 38 patients received paclitaxel in 1st-line chemotherapy (CRx). RR was not affected by EGFR mt (50% in mt(+) vs. 47% in mt(-), p=0.59), E (44% in E(+) vs. 45% in E(-), p=0.61) or A (46% in A(-/+) vs. 50% in A(2+), p=0.55). TTP was not affected by EGFR mt, E, or A. 54 patients received platinum in 1st-line CRx. RR was not affected by EGFR mt (50% in mt(+) vs. 37% in mt(-), p=0.59), E (37% in E(+) vs. 36% in E(-), p=0.60) or A (38% in A(-/+) vs. 41% in A(2+), p=0.52). TTP was not affected by EGFR mt, E, or A. 50 patients received gemcitabine in 1st- or 2nd-line CRx. RR was not affected by EGFR mt (25% in mt(+) vs. 18% in mt(-), p=.69), or A (19% in A(-/+) vs. 21% in A(2+), p=1.00). TTP was not affected by EGFR mt, E, or A. Of note, all responders to gemcitabine exhibited (+) E expression (RR 29% in E(+) vs. 0% in E(-), p=0.044). Conclusions: EGFR mutation was not associated with response to chemotherapies which included paclitaxel, platinum, or gemcitabine. These results support the use of gefitinib prior to other chemotherapeutics in patients with EGFR mutation. In addition, our results suggest the possibility that gefitinib resistant E (+) patients may benefit from gemcitabine. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Androgen receptor (AR) based biomarker association with response to abiraterone acetate/prednisone (AA/P) in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Manish Kohli, Liguo Wang, Hugues Sicotte, Rui Qin, Rachel Carlson, Jeanette Eckel-Passow, Winston Tan, Kevin Wu, Scott Dehm, Patrick W Eiken, Rafael E. Jimenez, Joseph Cernigliaro, Fernando Quevedo, Brian Addis Costello, Henry Clement Pitot, Timothy J. Moynihan, Thai Huu Ho, Roxana Stefania Dronca, Alan Haruo Bryce, Liewei Wang
Journal: Journal of Clinical Oncology (2015)

174 Background: AA/P is an FDA approved treatment for mCRPC. Since markers of early resistance to AA/P are unknown, we report initial findings of androgen receptor (AR) based associations with short term (12 week) progression on AA/P. Methods: mCRPC stage patients (pts) initiating pre-chemotherapy AA/P underwent metastatic site biopsies at baseline (pre AA/P) and after 12 weeks. Baseline somatic whole exome DNA, tumor gene expression for AR full length (ARFL), AR splice variant 7 (ARV7) and ARV7/ARFL ratios were compared in progessors versus non-progressors. Progression at or within 12 weeks of AA/P therapy was defined as death or disease progression by PCWG2 “composite progression (CP)” and/or “radiographic progression” endpoints. Wilcoxon rank-sum tests were used to test for differences in the two groups for comparing ARFL, ARV7 expressions and ARV7/ARFL ratios and chi square tests were used for differences in copy number variation. Results: Between 1/2013 and 6/2014, 59 pts were enrolled of which 44 have disease assessment data at the12-week time point. CP was observed in 17/44 patients. DNA seq and clinical data was available for 42/44 pts. Using radiographic progression at 12 weeks, AR Amplification/Gain was observed in 20/26 non-progressors (13 with Amplification) and in 9/16 progressors (P-value = 0.19; OR 2.5). ARFL and ARV7 gene expressions in both groups is provided in table. Conclusions: A trend towards higher ARV7/ARFL gene expression ratio in metastases was observed with early progression on AA/P. AR gain/amplification is observed less often in pts with early progression. Validation of these findings is on-going in this prospective trial. Clinical trial information: NCT# 01953640. [Table: see text]
Single arm phase II study of docetaxel and lapatinib in metastatic urothelial cancer: USC trial 4B-10-4.
Authors: Sujie Tang, Tanya B. Dorff, Denice D Tsao-Wei, Kristy Massopust, Charlean Ketchens, James Hu, Amir Goldkorn, Sarmad Sadeghi, Jacek K. Pinski, Monica Averia, Susan G. Groshen, Michael F. Press, Anne K. Schuckman, David I. Quinn
Journal: Journal of Clinical Oncology (2016)

424 Background: Advanced urothelial cancer progressing after first line systemic therapy is fatal. No agent in the second line or later setting has demonstrated improved survival although taxanes, pemetrexed, gemcitabine &amp; vinflunine have activity &amp; are used as palliative therapy. The Her2 pathway is up-regulated in some urothelial cancers and Her2 targeted therapy has enhanced chemotherapy effect in other cancers. We tested docetaxel with lapatinib, a Her1/Her2 TKI in urothelial cancer patients. Methods: Pts with measurable or evaluable urothelial cancerentered a single arm 2-stage phase II clinical trial, with PFS rate at 12 weeks as the primary endpoint in a Simon 2-stage design of 14+26 patients. The goal was a 12 week non progression rate of 60% - seen as promising compared to a rate of &lt; 40% seen as not. In a 2-stage design if ≥ 6 of 14 patients had not progressed by 12 weeks the trial would continue to 40 pts. Secondary endpts: ORR, safety &amp; OS. First 6 patients were given lapatinib 1250mg PO daily &amp; docetaxel 60mg/m2 IV q3wk; docetaxel dose then increased to 75mg/m2 q3wk. Tumor tissue &amp; circulating microenvironment were evaluated. Results: From July 2011 to July 2013, 15 pts were accrued. Median age 65 y, male 80%, ECOG 0 73%, Caucasian 73%, Mets: Liver 20%, Lung 20%, Bone 20%. PFS at 12 weeks 40%+/-13% - the trial was terminated after first stage. Reason off therapy: PD 10 (67%), toxicity 4 (27%). RECIST 1.1 best response: CR 1 (8%), SD 4 (31%), PD 8 (62%). Median OS: 6.3 (2.2, 12.7), PFS 2.0 (1.3, 6.6) months; 2 pts alive, follow up at 6.9 &amp; 8.1 months. Common toxicities: diarrhea 80% (gr3 33%), vomiting 40% (gr3 26.7%), nausea 67% (gr3 26.7%) &amp; fatigue 73.3% (gr3 6.7%). Conclusions: This phase II study of docetaxel with lapatinib in advanced urothelial cancer patients failed to provide sufficient efficacy for us to complete full accrual. One patient had a complete response and molecular correlatives may shed light on what may have predisposed to this. Intercurrently, another trial of maintenance lapatinib or placebo after chemotherapy in Her2+ patients reports no benefit (Powles ASCO 2015). Lapatinib alone or in combination is not recommended as therapy in urothelial cancer patients unless new tractable markers of response are developed. Clinical trial information: NCT01382706.