tbuckley/cabot-search huggingface dataset:
The time trends of gallbladder cancer and cholangiocarcinoma in 1,047 patients.
Authors: Shuichi Mitsunaga, Masafumi Ikeda, Satoshi Shimizu, Izumi Ohno, Hideaki Takahashi, Hiroyuki Okuyama, Akiko Kuwahara, Atsushi Ochiai
Journal: Journal of Clinical Oncology (2014)

376 Background: Gallbladder cancer (Gb ca) and cholangiocarcinoma (CC ca) are major primary sites in biliary tract cancer. Progresses of diagnosis and anti-cancer therapy for Gb and CC ca lead to the changes of patients’ characteristics and overall survival time, but is not fully understood. This study aimed to identify the time trends in patients with Gb and CC ca. Methods: The inclusive criteria in this study was the patients receiving initial treatment including surgery (Op), chemotherapy (Chemo), radiotherapy (RT), or best supportive care (BSC) for Gb or CC ca in our institution, and 1047 patients were reviewed. Patient who received initial treatment at 1992-2005 were in 54.1 % of the study subjects and was defined as Group 1. Patients with initial treatment at 2006-2012 were categorized to Group 2 and were in 45.9% of all patients. The differences between two groups were evaluated, and the features of Group 2 were identified. Results: Age more than 60 years (Odd ratio [OR]: 2.37), the absence of distant metastasis (OR: 2.13), and ECOG performance status score (PS) = 0 (OR: 1.70) were identified as the independent features of Group 2. The rates of Op, Chemo, RT, and BSC were 38.5, 24.7, 14.9, and 21.7% in Group 1, and 40.8, 49.9, 1.5, and 6.0% in Group 2. The rate of Chemo in Group 2 was higher than that in Group 1 (P &lt; 0.01). The median times of overall survival (OS) in Op, Chemo, RT, and BSC were 21.1, 5.2, 6.9, and 2.4 months in Group 1 and 60.6, 9.2, 10.5, 2.8 months in Group 2. The OS in Op or Chemo of Group 2 was longer than that in Group 1 (P &lt; 0.01, P &lt; 0.01). The independent poor prognostic factors were distant metastasis (HR: 3.91), Group 1 (1.81), and PS &gt; 0 (1.72) in all patients, distant metastasis (HR: 3.56), Group 1 (2.12), biliary drainage (1.75) in Op, and PS&gt;0 (HR: 1.97), Group 1 (1.74), and distant metastasis (1.64) in Chemo. Conclusions: The recent trends in patients with Gb and CC ca were aging, low rates of distant metastasis, good PS, increased cases with chemotherapy, and the prolonged survival times in surgery and chemotherapy. The presence of distant metastasis, the worsened PS, and the previous treatment group were the independent poor prognostic factors.
High-Dose Melphalan and Autologous Stem Cell Transplantation In AL Amyloidosis and Monoclonal Immunoglobulin Deposition Disease Associated End-Stage Renal Disease Requiring Dialysis
Authors: Vaishali Sanchorawala, Karen Quillen, Kathleen T Finn, Nancy T Andrea, J. Mark Sloan, Laura Dember, Adam Segal, Gheorghe Doros, Martha Skinner, David Seldin
Journal: Blood (2010)
A dose-finding clinical trial of mushroom powder in postmenopausal breast cancer survivors for secondary breast cancer prevention.
Authors: M. R. Palomares, J. Rodriguez, S. Phung, F. Z. Stanczyk, S. F. Lacey, T. W. Synold, S. Denison, P. H. Frankel, S. Chen
Journal: Journal of Clinical Oncology (2011)

1582 Background: We have shown that extract from Agaricus bisporus, the common white button mushroom (WBM), contains phytochemicals that suppress aromatase activity, inhibit breast cancer (BC) cell proliferation, and decrease mammary tumor formation in vivo. We now report a translational clinical trial to determine the optimal dose to induce this effect in humans. Methods: WBM were freeze-dried and pressed into a tablet containing 500mg of powdered extract, each roughly equivalent to 5g of whole WBM. Postmenopausal women diagnosed with BC at least 5 years prior, who were at least 3 months off therapy and recurrence-free, were treated with a 12-week course of 5, 8, 10, or 13g of mushroom extract daily. Aromatase inhibition was evaluated with serial serum sex steroid hormone and ex vivo plasma aromatase activity (AA) assays. Response was defined as a ≥50% decrease in free estradiol (FE2). Because immunologic effects have been reported with medicinal mushrooms, cytokines were also measured. Results: WBM extract up to 13g per day was well tolerated, with a median adherence of 95%, 96%, 95%, and 98% on the four escalating doses, respectively (n==6 each). Although no patients met the pre-defined response criterion, FE2 was observed to trend upward over the 12-week treatment course for the 5g and 8g dose groups and remain stable among the 10g and 13g dose groups (p==.05). AA measurements were able to detect a consistent post-prandial peak in activity in the 5g and 8g dose groups (p==.003 and <.001, respectively), which diminished in the 10g group and disappeared in the 13g group. Among patients with detectable baseline cytokine levels, IL-1β, IL-2, and IL-6 decreased on treatment, but there was no clear dose effect. Conclusions: High doses of WBM extract are well tolerated. An ex vivo assay of aromatase activity developed in our lab is sensitive to short-term changes and demonstrated suppression of post-prandial fluctuations with a 10g or 13g daily dose of WBM extract. These results suggest that anti-aromatase phytochemicals are present in plasma with daily consumption of 100-130g whole WBM, but not at high enough concentrations to significantly reduce estrogen levels from baseline in 12 weeks.
The use of minimally invasive thoracic surgical techniques eliminates the increased operative risk normally seen with increasing age
Authors: J. R. Roberts
Journal: Journal of Clinical Oncology (2005)

8110 Background: Thoracic incisions are the most painful incisions made by surgeons. This increased pain leads directly to the increased perioperative morbidity and mortality seen in older patients–elderly patients who develop pneumonia are much less likely to recover. We postulated that consistent application of minimally invasive thoracic surgical techniques would lessen, and perhaps eliminate, the increased perioperative risk seen with increasing age. Methods: Consecutive patients undergoing resection, regardless of technique, were available for consideration in this prospective study. We did not compare complications between techniques, as patients who required open procedures might be different than those who underwent thoracoscopic resections, but instead analyzed complications with respect to age. Our goal was to determine whether the consistent application of minimally invasive techniques would affect the overall risk in elderly patients. Only major perioperative complications (life-threatening complications, such as ARDS, cardiac arrest; and death) were analyzed–these complications were included if they occurred within 30 days of surgery, or within the hospital stay, if the stay was longer than 30 days. Length of stay and ICU stay were compared. Student’s t test was used to compare means, and chi-square was used to compare proportions. A univariate analysis was used to analyze for effect of increasing age. Results: The data for 1044 patients (647 lesser resections, 397 lobectomies) are included in this study and are summarized in the table below. No significant differences were seen in any compared variable. Conclusions: The consistent use of minimally invasive thoracic surgical techniques eliminated the expected increased operative risks and mortality in this large cohort of patients undergoing thoracic resections. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration US Surgical
Phase II study of sunitinib malate following hepatic artery embolization for metastatic neuroendocrine tumors.
Authors: J. R. Strosberg, A. Cheema, T. Campos, T. Valone, L. K. Kvols
Journal: Journal of Clinical Oncology (2011)

244 Background: Neuroendocrine tumors (NETs) frequently metastasize to the liver. Hepatic arterial embolization is an important therapeutic modality in treating patients with liver-predominant metastases. NETs are highly vascular and are known to express both VEGF and VEGFR. We hypothesize that administration of sunitinib, a VEGFR inhibitor, following hepatic artery embolization will delay tumor revascularization and extend progression-free survival. Methods: Patients with metastatic neuroendocrine tumors to the liver underwent a series of selective arterial embolizations followed by sunitinib (one week after each embolization, and continued until disease progression or up to a maximum of 8 cycles). Radiographic response rates were assessed by RECIST criteria. PFS and OS were calculated using Kaplan-Meier methodology. Results: 39 patients with metastatic NETs were enrolled. Primary tumor sites included the small intestine (26), pancreas (10), rectum (2), and lung (1). The initial starting dose of sunitinib was 50 mg; however, all five patients enrolled at this dose required dose reductions, and the starting dose was subsequently lowered to 37.5 mg. The majority of patients required further dose reductions to 25 mg. Twenty-eight patients (72%) experienced a partial radiographic response (PR), eight patients (20%) had stable disease, and three patients (8%) had progressive disease as their best response. Median PFS was 18 months and the rate of 1-year PFS was 72%. The rates of overall survival (OS) at 1 year and 2 years were 94% and 78%. Serum VEGF levels increased by an average of 51 pg/ml (34%) after embolization. Conclusions: Hepatic artery embolization is a highly active treatment option for patients with metastatic neuroendocrine tumors to the liver. Embolization stimulates release of VEGF into the circulation. Sunitinib can be administered following hepatic artery embolization. The high rates of progression-free survival and overall survival associated with this sequence of therapies are encouraging. [Table: see text]
Chemotherapy costs associated with receipt of the adoption of oncotype DX in early-stage breast cancer within the SEER-Medicare population.
Authors: Michaela Ann Dinan, Xiaojuan Mi, Shelby D. Reed, Gary H. Lyman, Lesley H Curtis
Journal: Journal of Clinical Oncology (2016)

32 Background: The Oncotype DX (ODX) multigene assay has been previously suggested to result in an overall reduction in the use of adjuvant chemotherapy and associated costs for women with early stage, estrogen receptor (ER)-positive breast cancer. However, the association between adoption of ODX and chemotherapy costs has only previously been considered in theoretical models and has not been examined using actual patient outcomes in real world clinical practice. Methods: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) -Medicare data of the association between overall and chemotherapy-specific costs associated with adoption of ODX testing in patients diagnosed with invasive, non-metastatic, ER-positive breast cancer between 2005 and 2009. We limited our primary analysis to women ages 66 to75 to include women in which adjuvant chemotherapy would be most likely to be considered. Total Medicare payments were used to calculate direct costs in the year following diagnosis. NCCN guidelines were used to stratify patients on the basis of clinical and pathologic features into low ( &lt; 1.0 cm), intermediate, and high risk (node positive) disease. Results: A total of 21,272 women met study criteria. Average costs in the year following diagnosis were $31,532 in the overall cohort, and was highest for women with NCCN high risk ($45,192) vs. intermediate ($28,642) or low ($23,662) risk disease. Chemotherapy costs followed similar trends ($4,819, $1,157, and $226 respectively). In multivariable analyses, ODX was associated with a relative decrease in chemotherapy costs among high risk women (RR 0.54, 0.37-0.77), but increased costs among low and intermediate risk women (RR1.36, 1.13-1.26 and RR 3.73, 2.13-56.54). Women with high risk disease had significantly lower absolute chemotherapy costs associated with receipt of ODX (-$2,298, -$3,049 to -$1,547; All P &lt; 0.001). Conclusions: Receipt of ODX testing was associated with relative and absolute decreases in chemotherapy costs, but only in women with high NCCN risk disease. Further research is needed to disentangle correlative vs. causative association of ODX testing with patient outcomes and costs.
Micro- and macroarteriolar blockade of hepatocellular carcinoma (HCC): Ramping up the dose of sorafenib over two weeks before hepatic arterial chemoembolization (HACE) for liver cancer.
Authors: Andrew N de la Torre, Ismael Castaneda, Sohail Contractor
Journal: Journal of Clinical Oncology (2015)

472 Background: Multiple sessions of hepatic artery chemo-embolization (HACE) are usually necessary to achieve partial or complete ablation of a hepatoma (HCC). Blocking the pro-angiogeneic environment and re-establishment of tumor microvasculature with the tyrosine kinase inhibitor sorafenib administered prior to HACE may enhance tumor necrosis and possibly patient survival. Methods: Twenty patients with inoperable HCC were subject to 2 weeks of sorafenib, followed by HACE using Adriamycin and mitomycin C. The first 10 patients were treated with a sorafenib 400 mg twice a day. The second 10 patients had their dose of sorafenib ramped up from 200 mg twice a day to 400 mg twice a day over 1-2 weeks according to tolerability. Patients were continued on sorafenib during as many HACE procedures needed to achieve no evidence of enhancement on multi-phase imaging. Results: The mean length of treatment for the ramped up group was significantly longer that the non-ramped up group as shown in table 2. (3.90 vs 3.05, N &lt; 0.05). There was no significant difference in survival, nor adverse events between groups. Three patients (5, 12, 13) ultimately went on to receive a liver transplant. Conclusions: Use of sorafenib prior to HACE is feasible and safe. Ramping up the dose over 2 weeks allows more patient to stay on treatment longer. Further studies are needed to determine how best to combine sorafenib with HACE in order to increase survival and eligibility of patients to be listed for liver transplant. Clinical trial information: NCT00949182.
Hypothesis-free biomarker discovery platform evolving into a companion diagnostic using bioinformatics.
Authors: Gitte Pedersen
Journal: Journal of Clinical Oncology (2012)

52 Background: Cancer drug discovery is hypothesis driven focused on addressing specific mechanisms; however the patient’s individual tumor harbor much more diversity and therefore the biomarkers behind the hypothesis are often insufficient in explaining the differences in individual drug response. A Danish Private Public Partnership is developing biomarkers for cancer prognostics under a $30 million grant. The Danish National Biobank was established by another $20 million grant and hosts approximately 15 million biological samples associated with cradle-to-grave electronic medical records. Methods: Proposing a hypothesis-free biomarker-discovery platform using intelligent target-filtering technology integrated with sequencing short reads on a small chip addressing the sample prep and data analysis bottlenecks in current sequencing platforms. By using bioinformatics on existing sequence data it is possible to optimize the proposed strategy and develop novel diagnostic applications. The intelligent target-filtering process generates a single-stranded tag library. Because the tags are single stranded, it is possible to detect all possible tags using a universal high-throughput platform. The cost per sample is low, the content/test very high, and hypotheses free. This approach represents a paradigm shift in the biomarker-discovery process, saving significant time and money while increasing the probability of success. The diagnostic becomes a bioinformatics exercise that allows the drug discovery company to optimize the definition of responders. Results: The result of the digital gene expression experiment was compared to RNA-seq and Affymetrix whole genome array. Conclusions: The platform offers a more cost-effective way of providing an open and hypothesis free platform compared to sequencing. The platform also offers cost-effective open-ended solution for such diverse applications as expression profiling, genome wide methylation profiling, genome wide duplication/deletion analysis, environmental microbiome profiling, and single gene mutation detection with only relatively minor adjustments in how the single stranded tags are extracted from the sample.
Eculizumab Is An Effective Long-Term Treatment In Patients with Atypical Hemolytic Uremic Syndrome (aHUS) Previously Receiving Chronic Plasma Exchange/Infusion (PE/PI): Extension Study Results,
Authors: Christoph Licht, Petra Muus, Christophe Legendre, Kenneth W Douglas, Maryvonne Hourmant, Yahsou Delmas, Maria Herthelius, Antonella Trivelli, Timothy H. J. Goodship, Camille L Bedrosian, Chantal Loirat
Journal: Blood (2011)
Psycho-oncological screening in patients with newly diagnosed or relapsing breast cancer.
Authors: Meinolf Karthaus, I. C. Schuth
Journal: Journal of Clinical Oncology (2012)

80 Background: Breaking news in breast cancer (BC) pts often has to be supported by psychological help. It remains unclear which and how many BC pts need supportive psycho-oncological care, since pts may react in different ways. Some pts show high risk profiles for anxious reactions or depressions after breaking bad news and should be detected for interventions. Need for pychological intervention was screened with a simple 14-point item test (HADS). A scoring of &lt;15 points was assumed to be at low risk for anxiousness and depression, a scoring of 15-21 points was considered medium risk while a score of &gt;21 was assumed to describe high-risk pts. Pts considered to be at low risk, did not receive further intervention. Pts detected to be at medium or high risk received further psychological intervention. The aim was to evaluate efficacy of psychological support in pts with newly diagnosed BC or relapse of cancer &gt;1 yr after a curative approach. Methods: Psycho-oncological screenings and interventions were analyzed in a tertiary cancer within a two-year period. Results: Out of a total of 611 cancer pts, 202 pts had BC. 63 pts had a newly diagnosis of cancer or a relapse of &gt;1 year since primary diagnosis or therapy and signed informed consent. Pts assumed to be at low risk had a mean score of 6,97 (SD 3.71) prior and 7,03 (SD4.97) after the end of cancer therapy. In this group of low risk pts there was no further psychological intervention. In pts detected with a medium risk (15-21) mean HADS score prior therapy was 16.63 (SD 1.38) and fell down during cancer treatment and supportive psychotherapeutically intervention to 13.58 post therapy (SD 6.16). Pts with the highest risk at diagnosis had a mean of 28.25 (SD 4.41) and decreased to a mean HADS of 16.83 (SD 4.84) at the end of cancer therapy while being under supportive psychotherapeutically care. Mean number of psychotherapeutic sessions was 3.86/patient with a mean duration of intervention time of 1.38 h. Conclusions: BC pts with a HADS &lt;15 should not be considered to be candidates for routine psychotherapeutically supportive care. Pts being at high-risk gained most benefit. A simplified scoring system for anxiousness and depression is recommended to detect pts with a need for further therapeutic treatment.
Equity of access: Consent interpretation program at Princess Margaret Cancer Centre (PM) in Canada.
Authors: Jasmine Grant, Lindsay Philip, Grace Eagan, Elizabeth Abraham, Pamela Degendorfer, Amit M. Oza
Journal: Journal of Clinical Oncology (2014)

189 Background: Toronto is a multicultural city with over 160 languages spoken by patients. Since 2010, institutional policy requires that professional medical interpreters are used when obtaining informed consent from patients with limited English proficiency (LEP). The availability and cost of these interpreters can be a deterrent for clinical trial participation, particularly when funding is limited. In order to ensure that patients facing language barriers have equitable access to trials, to protect the rights and safety of LEP patients involved in trials, and to improve patient outcomes, adherence to this policy needs to be ensured. Methods: Through a collaboration with the PM Cancer Clinical Research Unit (CCRU) and Interpretation and Translation Services (ITS) supported by the Princess Margaret Cancer Foundation, a 6-month pilot was initiated with full access to interpretation services for all trial patients in November 2012. The CCRU provided training to interpreters on clinical trials and GCP and interpreters reviewed template consent forms provided by ethics boards to cut back on preparation time and costs when delivering a sight translation of study specific consent forms. Trials staff were trained on the process and given badge tags with instructions. Metrics were collected to monitor the use of professional interpreters. Results: Utilization of professional interpreters in trials increased by 16% during the 6-month pilot and 286 requests have been logged to date. Staff were surveyed and indicate this has streamlined the consent process with 83% of respondents saying the new process is easy/very easy. Care providers feel this has allowed them to approach more patients than before this project. Conclusions: This project ensures that accurate information is provided to all patients contemplating participating in or already enrolled in trials, that all patients have the same level of access to treatment, and that there is equity of access for all patients irrespective of their English proficiency. The increased use of professional interpreters in consent discussions indicates better adherence to policy which has allowed the pilot to continue for another year.