tbuckley/cabot-search huggingface dataset:
BrainMetsBC.org: Evaluation of a new resource for breast cancer patients with brain metastases
Authors: M. Mayer, P. S. Steeg, H. Schiff
Journal: Journal of Clinical Oncology (2008)

20711 Background: As improved treatments extend survival, more women with metastatic breast cancer (MBC) face a diagnosis of brain or other CNS metastases (BM). An estimated 20% of all breast cancer patients (pts) whose disease has spread develop BM; for HER2- positive pts, a BM incidence of 25% to 48% has been reported. As part of a Center of Excellence on BM of breast cancer, patient advocates launched a new consumer website, BRAINMETSBC.ORG, to offer information and support about BM to pts and caregivers. The present survey assesses how well the website meets this need. Methods: Visitors to BRAINMETSBC.ORG were invited to fill out an 18-question survey examining the helpfulness, clarity and design of this website. Responses were elicited from pts and caregivers dealing with brain BM, metastatic pts without BM, patient advocates, and healthcare providers. Results: The 84 respondents were young, with 52% aged 50–59, 19% aged 40–49, and 24% aged 30–39. 47% were pts or caregivers dealing with BM. Of these, 46% had been living with metastatic breast cancer for 3 to 5 years (46%), while 43% had been dealing with brain metastases < 1 year. 89% of pts and caregivers said they would have found the website helpful when first diagnosed with BM. Disease and treatment information was most helpful, followed by pt experiences. 90% said they knew more about BM after visiting the website. 64% of pts and caregivers found it reassuring to know that some women can live with brain mets. 52% felt less worried, and 41% more in control after reading the website. All patient advocates and health care providers felt the website would be helpful to them in working with pts and families. 93% of survey respondents found the medical information clearly presented, and 89% said the website was well-organized and easy to navigate. 43% asked for more treatment information. Conclusions: Patients and caregivers, advocates and healthcare providers highly rated BRAINMETSBC.ORG. The in-depth information provided and the stories from pts living with the disease were cited as valuable, as was learning that research is being actively pursued. Treatment updates and refinements will be crucial to the ongoing success of this website. Supported by the Department of Defense Breast Cancer Research Program. No significant financial relationships to disclose.
Phase II trial of gemcitabine (G), oxaliplatin (O), and erlotinib (T) for the treatment of hepatocellular carcinoma (HCC) and biliary tree cancers (BTC).
Authors: Y. Z. Patt, A. D. Baron, V. A. Parks, A. Small, M. Roach, S. Lee, F. Lee
Journal: Journal of Clinical Oncology (2010)

4153 Background: HCC is increasing in the USA; BTC, less common in the USA, is not rare in New Mexico. G-O is active in HCC and BTC. Both express EGFR. T, a TKI has activity against BTC and HCC. Therefore, this Western IRB-approved phase II trial of G- O+T in HCC and BTC was launched. Methods: Eligibility: Histologic confirmation and CT/MRI (C/M) measurable HCC. In hepatitis/alcoholic cirrhosis, AFP of ≥ 400 ng/mL and a typical C/M of HCC sufficed. A platelet (Plt) count of ≥ 100,000, Child-Pugh (C-P) class ≤ B cirrhosis, adequate renal function, and ECOG PS of ≤ 2 were required. BTC pts required measurable and histologically confirmed disease, and a decreasing bilirubin of ≤ 3.5 mg/dL post decompression of biliary obstruction and adequate bone marrow, renal, and hepatic reserve. Simon's 2 stage optimal phase II trial design was used. A disease-control rare (DCR), (CR+PR+ SD) at 24 weeks of ≤ 20% and > 40% (P0 and P1 of 0.2 and 0.4 respectively ) were set as undesirable (null) and desirable results. Treatment consisted of G 1,000 mg/m2 on day 1, O 100 mg/m2 on day 2, and daily T 150 mg PO. Dose levels -1 and -2 were 750 mg and 75 mg/m2 and 650 and 65 mg/m2 of G and O respectively and T 100 mg and 50 mg daily. G-O was repeated Q 15 days; 2 repetitions constituted 1 cycle. HCC pts with C-P B cirrhosis were started at dose level -1. T dose adjusted based on skin toxicity. BTC pts started T 100 mg/day. Simultaneous warfarin and T disallowed due to an initial fatal adverse event. Results: 26 HCC and 5 BTC pts were accrued. In HCC 1 durable PR, 10 SD and 9 PDs were seen; 6 were inevaluable for response. DCR in HCC was 42%. All 5 BTC pts had SD. Median number of treatment cycle was 2 (1-23 range) in HCC and 5 (2-6 range) in BTC. Median overall survival times (OST) and progression-free survivals (PFS) were 196 and 149 days in HCC and 1-year survival rate was 40%. In BTC, median PFS times was 238 and median OST was not reached. PFS at 21 and 26 wks in HCC were 47.5% and 41% respectively, and 21 wk PFS in BTC was 60%. Grade 3 toxicities in > 5% of pts were fatigue (12.9%), neutropenia (9.6%), thrombopenia (9.6%), and diarrhea (6.4%). Conclusions: G-O +T exceeded both pre-set P0 a and P1 of the primary objective with a PFS of 41% at 26 wks, warranting continuation of the HCC trial. Preliminary BTC data are promising to warrant continuation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Lilly Genentech, sanofi-aventis
Code status documentation in the electronic medical record for patients with stage IV pancreatic cancer.
Authors: Daniel Kronenberg, Janet M Armstrong, Joseph D. Ma, Carolyn Revta, Eric Roeland
Journal: Journal of Clinical Oncology (2016)

125 Background: Improving incidence of code status documentation in the electronic medical record (EMR) has been suggested a better guidance for clinical care compared with a traditional advance directive. We have previously reported that in the absence of a template in the EMR, code status documentation was 36% and inconsistent in patients with advanced cancer. Utilizing a different cohort of patients with metastatic pancreatic cancer, we examined the prevalence of EMR code status documentation. Methods: A retrospective analysis in patients with analytic metastatic pancreatic cancer (2008-2014) was conducted at a single, academic medical center. The primary objective was to determine prevalence of code status documentation in the EMR. Secondary objectives were to determine documentation author, location in the EMR, and time from documentation until death. Patients were identified from a tumor registry and code status documentation was identified in the scanned media, demographics tab, problem list, or using key search terms in the EMR. Results: 169 patients with stage IV pancreatic cancer were identified. Seventy-five percent (n = 127) had a code status documented. Of those with documented code status, 44.9% (n = 57) were full code/full care, 22.0% (n = 28) were DNR/comfort care, 18.9% (n = 24) were DNR/full care, 13.4% (n = 17) were DNR/not specified, and 0.8% (n = 1) was limited DNR/full code. EMR locations for code status documentation included: 71.7% (n = 91) discharge summary, 10.2% (n = 13) inpatient encounter, 10.2% (n = 13) history &amp; physical, 6.3% (n = 8) media tab, 0.8% (n = 1) telephone encounter, and 0.8% (n = 1) admission note. Code status documentation was completed by hospitalists (42.5%, n = 54), medicine residents (21.3%, n = 27), and primary oncologists (4.7%, n = 6). Mean difference for date of code status documentation and death was 67±145 d. Conclusions: Code status documentation was higher for patients with metastatic pancreatic cancer compared to patients with advanced cancer from a previous study at our institution. Research is needed to determine if full code/full care is a default selection or a true representation of a patient’s wishes. Future efforts need to consider a standardized location for code status documentation in the EMR.
Extended survival in second-line pancreatic cancer after therapeutic vaccination
Authors: T. Schuetz, H. L. Kaufman, J. L. Marshall, H. Safran
Journal: Journal of Clinical Oncology (2005)

2576 Background: Therapeutic vaccines represent a novel approach for the treatment of pancreatic cancer. The generation of cytotoxic T cells requires at least 2 signals: antigen presentation to the T cell receptor and T cell costimulation. PANVAC-VF contains the genes for CEA, MUC-1, and 3 costimulatory molecules (B7.1, LFA-3, and ICAM-1) in 2 viral vectors to optimize presentation of antigen to T cells. Previous studies utilizing this approach have demonstrated a correlation between the generation of tumor-specific cytotoxic T cells and overall survival (OS) following administration of pox virus-based therapeutic anti-tumor vaccines. Here, we update the previously reported results of two Phase I studies of related vaccines in patients with advanced pancreatic cancer. Methods: Safety was the primary objective of both studies. Twenty-two patients with pancreatic cancer (Stage III or IV) were enrolled (20 with metastatic disease; all had received prior therapy). Based on preclinical and clinical studies, an optimized regimen of a priming dose on day 0 followed by boosting doses on days 14, 28, and 42 was utilized. GM-CSF (100 μg) was given on the day of each injection and for 3 consecutive days. Patients who were clinically stable were able to continue vaccinations monthly. All patients continue to be followed for survival. Results: The most common adverse event (AE) related to the vaccines was grade 1 injection site reaction (erythema, swelling, pruritis, blister, induration, and pain). Other common AEs were fatigue, anorexia, nausea, vomiting, fever, headache, and myalgia. No serious adverse events related to vaccine occurred. Median OS in the two studies was 7.9 and 6.3 months. One year survival was 33% and 30%. 18 month survival in the first study is 25% and has not been reached in the second trial. Conclusions: Historical control data suggest that the expected median OS in patients with metastatic pancreatic cancer in the second-line setting is approximately 3 months. Although these studies were small and uncontrolled, these data suggest that treatment with PANVAC-VF is well tolerated and results in prolonged OS in this patient population. A randomized, controlled Phase III trial is underway to test this hypothesis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics Therion Biologics
Clinical benefit of imatinib in patients (pts) with metastatic gastrointestinal stromal tumors (GIST) negative for the expression of CD117 in the S0033 trial
Authors: M. E. Blackstein, C. Rankin, C. Fletcher, M. Heinrich, R. Benjamin, M. von Mehren, C. Blanke, J. A. Fletcher, E. Borden, G. Demetri
Journal: Journal of Clinical Oncology (2005)

9010 Background: IM is effective in the majority of pts with GIST, but limited data exist on KIT- GIST. S0033 aimed to evaluate differences between two initial dose levels of IM (400 vs. 800 mg/day) in pts with GIST expressing CD117 (KIT+), a subset of pts with KIT- GIST were treated. This abstract describes the outcomes of these pts and compares them with the KIT+ pts treated. Methods: Central pathology review was performed by a single pathologist on tumor specimens retrospectively, and data from S0033 (746 pts randomized) was analyzed. Pre-treatment tumor samples from 344 pts were also examined for mutations of KIT or PDGFRA. Results: Pathology has been reviewed on 414 pts: 377 (91%) had KIT+ GIST, 14 (3%) KIT- GIST, and 16 (4%) leiomyosarcoma/other subtype. Eight of the KIT- GISTs were genotyped and mutations in KIT or PDGFRA were noted in 4 and 3, respectively. (mutation frequency 87.5% for KIT- GISTs). Twelve non-GIST sarcomas had no mutations. The response rate and PFS in the pts with KIT- GISTs was not significantly different than that seen in KIT+ GISTs (43% vs. 49%, estimated PFS at 2 yrs). Pts with leiomyosarcoma or other histology have a significantly worse outcome than either KIT+ or KIT- GIST pts, with PFS 13% at 2 yrs and a median survival of about eight months compared to GIST pts for whom median survival has still not been reached. A significant difference in overall survival was noted in favor of the KIT+ GIST vs. KIT- GIST (77% vs. 57%, estimated OS at 2 yrs, p<0.01), although this was an unplanned subset analysis. Toxicities of all grades were similar across in the various histological groups. Conclusion: Our results indicate that IM therapy can provide clinical benefit for pts with KIT- GIST. The high incidence of kinase mutations in KIT- GIST support a therapeutic trial of IM for all GIST pts regardless of CD117 expression. There is no evidence of significant activity with IM for the non-GIST malignancies treated on this study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
Survival differences in patients (pts) with resected rectal cancer who received neoadjuvant therapy with or without postoperative chemotherapy (CT).
Authors: Christina Sing-Ying Wu, Lai Wei, Katherine Glass, John Wilson, Sherif Abdel-Misih, Ludmila Katherine Martin, Sigurdis Haraldsdottir, Alan Harzman, Syed Husain, Carl Richard Schmidt, Mark Arnold, Richard M. Goldberg, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2013)

518 Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University, and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August 2005 to July 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two pt groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19%, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]
MicroRNA polymorphisms and esophageal cancer outcome.
Authors: Olusola Olusesan Faluyi, Lawson Eng, Xin Qui, Dangxiao Cheng, Daniel John Renouf, Sharon Marsh, Sevtap Savas, Jennifer J. Knox, Gail Elizabeth Darling, Rebecca Wong, Wei Xu, Abul Kalam Azad, Geoffrey Liu
Journal: Journal of Clinical Oncology (2013)

32 Background: Better understanding of the biology of esophageal cancer may help improve its treatment. MicroRNAs (miRs) regulate mRNA and can exert some influence on carcinogenesis. Identification of the microRNAs which regulate esophageal cancer development could potentially yield alternative therapeutic options. Objectives: We evaluated polymorphisms in miRs, miR biogenesis, binding sites of miR and their role in the survival of esophageal cancer patients. Methods: 324 esophageal cancer patients of all stages and histological subtypes were evaluated. Using Illumina Custom GoldenGate, 43 polymorphisms in miR pathways were evaluated. Cox proportional hazards models adjusted for clinical prognostic variables and determined the association of polymorphisms with overall survival (OS) and progression free survival (PFS). Adjusted hazard ratio (aHR) and 95% confidence intervals (CI) were calculated. Results: Among our patients, 83% were male while the mean age was 65 years. 73% had adenocarcinomas while 33.6% had advanced tumors (Stage IV). The median PFS was 1.20 years, while median OS was 2.17 years. After adjustment for clinical variables, a 5’UTR polymorphism in pri-mir26a-1 (rs7372209) was significantly associated with reduced PFS [aHR=0.78, CI:0.62-0.98, p=0.04] and OS [aHR 0.71 (0.56-0.89), p=0.003]. Three other polymorphisms were significantly associated with OS but not PFS: these included two polymorphisms of miR processing genes, DDX20 (rs197412) [aHR 1.31 (1.04-1.64), p=0.02] and EIF2C1 (rs595961) [aHR 0.76 (0.60-0.97), p=0.03] as well as the CD86 3’UTR C&gt;G (rs17281995) polymorphism, which has been predicted to affect the binding of miR337, miR582, miR200a, miR184, and miR212 [aHR 1.38 (1.03-1.85), p=0.03]. Conclusions: We report the initial association of miR related polymorphisms with survival in esophageal cancer. We plan to explore additional relationships and validate these findings in other datasets.
Predictive value of eTag dimerization assay in patients with metastatic colorectal cancer treated with erlotinib
Authors: A. M. Oza, C. A. Townsley, G. Pond, S. Singh, L. L. Siu
Journal: Journal of Clinical Oncology (2005)

9618 Prediction of response to therapy based on tumor biology, which would allow rational selection of treatment remains the goal of anticancer drug therapy. This study reports on an in-vitro assessment of tumor/skin biopsies using a novel method to assess receptor dimerization and protein-protein interactions. This study evaluated a novel technology for the measurement of stable protein complexes by a colorimetric dimerization assay in tissue samples from patients with colorectal cancer who participated in a Phase II clinical trial of erlotinib. Formalin fixed paraffin embedded (FFPE) tissues were treated with an antibody conjugated to a unique fluorescent tag, that is distinguishable from other markers by capillary electrophoresis (CE). Each specific antibody was coupled to a molecular scissor, which generates reactive oxygen upon illumination by red light. Tumor and skin samples were obtained from patients with metastatic colorectal cancer who were treated with a continuous oral dose of erlotinib, taken prior to and after 7 days of treatment. Analysis of patients FFPE skin and tumor samples was performed with observer blinded to treatment outcome. Samples were analyzed in three different assays a HER1/1 dimerization assay, a HER 1/2 dimerization assay and a HER 1/1 phosphorylation assay. Results of eTag predictive assay and outcome were subsequently analyzed. Thirteen tumor and skin samples were analyzed. Four patients had stable disease and 9 patients had progressive disease as their best response. A cutpoint was found which optimized sensitivity and specificity for three different analyses. This cutpoint resulted in a sensitivity/specificity of 100%/88.9% when using a combination of HER 1/1 dimerization reduction and HER 1/2 dimerization increase, a sensitivity/specificity of 100%/88.9% when using a reduction in HER 1 phosphorylation and a sensitivity/specificity of 85.7%/100% when using a reduction of HER 1 phosphorylation in skin samples. The results indicate high specificity and sensitivity with eTag assay. This may be an effective method of predicting outcome with targeted therapy, but needs to be validated in prospective clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ACLARA ACLARA
Engraftment of resected pancreatic adenocarcinoma in SCID mice and patient survival following surgical resection: Roswell Park's experience.
Authors: Jose Luis Aranez, Potjana Jitawatanarat, Bonnie Hylander, Rose Pitoniak, Charles Levea, Elizabeth S Repasky, Wen Wee Ma
Journal: Journal of Clinical Oncology (2014)

185 Background: Preclinical models developed by implanting resected pancreatic cancer from human donors into immunocompromised (SCID) mice have been valuable in understanding the disease’s biology and developing therapies. The ability of resected tumors to engraft successfully has previously been reported to be a poor prognostic marker. This study was conducted to investigate the relationship between successful engraftment and clinical outcome by analyzing such a model developed at Roswell Park over the last decade. Methods: A retrospective review of 48 donor patients (27 males and 21 females) whose resected pancreatic adenocarcinoma was xenografted in SCID mice between 1999-2009 was conducted. The clinical outcome and baseline information were correlated with engraftment outcome. The expression of potential biomarkers correlating with engraftment was evaluated by performing immunohistochemistry on the initial donor surgical specimens. The expression was scored, assigned an average index value and categorized into groups (High vs Low expression) based on a median cutoff of values. Results: Resected tumors from 21 of the 48 donors successfully engrafted when implanted subcutaneously in SCID mice (44%). The baseline demographics and disease characteristics were balanced between engrafters versus non-engrafters. All of the engrafters and 26 (of 27) of non-engrafters received adjuvant treatment. The 2-year overall survival (OS) of patients whose tumors successfully engrafted was 17% compared to 39% in those whose tumors failed to engraft (P=0.09; hazard ratio 1.305 [95% CI 0.717-2.375]). Analysis to identify potential biological markers associated with engraftment success is underway. Conclusions: A review of the clinical outcome of patients whose tumors were procured and used for the patient-derived primary pancreatic cancer xenograft program at Roswell Park showed that successful engraftment in SCID mice is potentially a poor prognostic marker in patients with resectable pancreatic cancer. Our analysis did not reach statistical significance which is likely due to a smaller sample size but the potential link is consistent with that reported by others.