tbuckley/cabot-search huggingface dataset:
Evaluation of the performance of breast cancer cell line–derived multigene predictors of chemotherapy response in multiple clinical trials.
Authors: N. Song, S. D. Rice, D. Gingrich, D. Wang, C. Tian, Z. Ding, S. L. Brower, P. Ervin, M. J. Gabrin, K. Shen
Journal: Journal of Clinical Oncology (2011)

64 Background: While various multi-gene predictors (MGPs) of chemotherapy response have been developed based on cancer patient primary tissues or cancer cell-lines, the accuracy and consistency of these predictors remain a concern in clinical validation studies. In this study we developed four unique MGPs for chemotherapy response from breast cancer cell lines and performed a systematic evaluation of the performance of these MGPs using data from five distinct clinical trials. Methods: Forty-six immortalized breast cancer cell-lines were exposed to various concentrations of drug combinations [paclitaxel, 5-fluorouracil, doxorubicin, cyclophosphamide (TFAC); 5-fluorouracil, doxorubicin, cyclophosphamide (FAC); 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and epirubicin, cyclophosphamide (EC)] using an in vitro chemosensitivity assay. Utilizing publicly available breast cancer cell-line microarray data, genes highly associated with in vitro chemosensitivity were selected as candidate MGPs. Five independent and publicly available clinical trials were used for validation. In three of these clinical trials patients were treated by TFAC, while EC, FAC or FEC were used in the other two trials. All five studies involved neoadjuvant chemotherapy treatment, and pathologic complete response (pCR) was used as the endpoint. The association of MGPs with pCR was assessed using receiver-operator curve (ROC) analysis and area under the ROC (AUC) was used to evaluate the performance of prediction. Results: In five independent clinical trials, the MGPs predicted patient pCR to EC, FAC/FEC and three TFAC treatments with an AUC of, 0.671, 0.632, 0.735, 0.738 and 0.647 respectively. Conclusions: In the five independent clinical trials in which patients were treated by various chemotherapy agents, the performance of MGPs is promising. These results demonstrate the feasibility of using breast cancer cell-line derived MGPs to predict breast cancer patients’ chemotherapy responses.
PROCHE: A program to monitor side effects among patients treated in a medical oncology outpatient unit.
Authors: F. Scotte, M. Berhoune, S. Marsan, H. Aboudagga, A. Morel, J. Fouque, C. Nedelec, J. Stevens, B. Bonan, S. Oudard
Journal: Journal of Clinical Oncology (2010)

9152 Background: The increasing number of cancer patients (pts) treated in an outpatient setting impacts significantly on their quality of care and monitoring of treatment side effects. A pilot program (PROCHE: Chemotherapy Optimization Program) to pre-emptively confirm scheduled chemotherapy was conducted, and was approved by the French CNIL (the authority in charge of database confidentiality). Methods: Side effect data for each patient were collected two days prior to each scheduled in-hospital chemotherapy treatment by nurses in a specialized call center who contacted pts and completed a CTC-NCI version 3.0 questionnaire. Laboratory test results were also entered into the database (which used data encryption software). Based on these data, oncologists confirmed, postponed or cancelled the scheduled treatment the day before. If confirmed, the hospital pharmacy prepared the chemotherapy drugs a day in advance of the visit. Study endpoints included the time between scheduled treatment administration and actual administration (treatment delay) on the day of the visit and patient satisfaction, and were recorded the months prior to, and during, the program. Results: Between October 2008 and Oct 2009, 593 pts participated and 3531 questionnaires were completed (i.e. 86% of pts had at least two completed questionnaires). The most common side effects were fatigue (562 pts, 94.8%), pain (414 pts, 69.8%), nausea (329 pts, 55.5%) and neuropathy (297 pts, 50.1%). Most side effects were of grade I (70.3% of pts with nausea and 64.2% with fatigue) or grade II (48.8% of pts with neuropathy) severity. Comparing before and after program initiation,treatment delay was reduced by a mean (±SD) of 40 (±10) minutes per patient (p<0.001), and patient satisfaction with their time spent in the hospital ward improved by 42% (from 54% to 96%). Conclusions: The pilot program reduced the waiting time to receive treatment because chemotherapy agents were prepared the day ahead. It allowed oncologists to retrospectively assess chemotherapy-related side effects for each pt recorded in the database. Access to such a database may lead to improved pro-active management of treatment-related side effects. No significant financial relationships to disclose.
Genetic Association of Non Hodgkin’s Lymphoma Susceptibility to Polymorphisms in the CTLA-4 Gene on Chromosome 2q33.
Authors: Giovanna Piras, Maria Monne, Uras Antonella, Patrizia Fancello, Andrea Maulu, Calvisi Anna, Curreli Luigi, Gaviano Eleonora, Murgia Alessandro, Gabbas Attilio
Journal: Blood (2004)
Integrating palliative care services in oncology clinics: An application of the Edmonton Symptom Assessment System (ESAS).
Authors: Sherri L. Rauenzahn, Susanne Schmidt, Jessica Jones, Ifeoma Aduba, Laura LaNiel Tenner
Journal: Journal of Clinical Oncology (2016)

168 Background: Research inpalliative care has shown improvements in overall survival, quality of life, symptom management, care satisfaction and reductions in the cost of care. Therefore, the American Society of Clinical Oncology has recommended early concurrent palliative care in patients with advanced cancer and with high symptom burden. Despite this recommendation, integrating palliative services at our NCI-designated cancer center has been challenging. The aims of this project were to quantitatively describe the symptom burden of patients in ambulatory oncology clinics; facilitate the establishment of an effective referral system by detecting discrepancies between symptom burden and referral practices; and improve the integration of palliative care services by implementing the Edmonton Symptom Assessment System (ESAS) tool into 5 of our oncology clinics. Methods: ESAS forms consist of 10 questions assessing patient symptom burden and quality of life. Total scores range from 0 to 100. This tool was distributed to patients at two breast, two gastrointestinal and the thoracic clinics at each visit. The provider reviewed the forms and decided if a palliative care referral was appropriate based on patient responses. The forms as well as referral decisions were entered into REDCap. Over a 5 month period, 607 patients completed the initial assessment and 430 follow up forms were collected, resulting in a total of 1,037 scores collected. Results: The mean ESAS score for all patient visits was 20.7 (SD = 18.7). Only 3.5% (n = 21) of all patients were initially referred to palliative care and 2.6% (n = 11) of patients were referred on follow up visits. Those with an initial referral had an initial mean score of 39.0 (SD = 19.0) and a mean follow up score of 31.9 (SD = 19.5). Conclusions: This project highlights the low palliative care consultation rate and the under-utilization of services by most oncologists at the cancer center despite using the ESAS tool. However, those who received a referral had lower ESAS scores at follow-up. We propose utilizing a trigger that would capture a preset percentage of patients who indicated scores reflective of high symptom burden and distress.
The mitochondrial metabolism inhibitor CPI-613 in combination with mFOLFIRINOX for pancreatic adenocarcinoma.
Authors: Angela Tatiana Alistar, Rodwige Desnoyer, Ralph D'Agostino
Journal: Journal of Clinical Oncology (2016)

264 Background: Stage IV pancreatic cancer is a lethal disease with limited treatment options. Current standard practice is combination chemotherapy with FOLFIRINOX or Gemcitabine + Abraxane. Despite these two new treatment options, the response rate and survival are limited in stage IV pancreatic cancer. The glycolic and mitochondrial metabolisms are aberrant in pancreatic cancer and translate into chemo-resistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species such as chemotherapy. CPI -613 is a novel anti-mitochondrial developed by Cornerstone Pharmaceuticals. Methods: A phase I clinical trial with mFOLFIRINOX+ CPI-613 in never treated for stage IV pancreatic cancer patients was initiated. The goals of this phase 1trial are: (1) To determine the Maximum Tolerated Dose (MTD) of CPI-613, when used in combination with mFOLFIRINOX, in patients with metastatic pancreatic cancer, (2) To assess the safety of CPI-613/ mFOLFIRINOX combination in patients with metastatic pancreatic cancer, and (3) To obtain preliminary data on efficacy of treatment with CPI-613/ mFOLFIRINOX Results: The MTD for CPI 613 was identified at 500mg/m2. The treatment combination is feasible and well-tolerated. The combination treatment was not found to have higher toxicity than FOLFIRINOX alone. The objective response rate was 53.9 % which is higher than FOLFIRINOX alone (reported as 31.6%). One patient has a complete radiologic and clinical response and two other patients have near complete responses. Conclusions: The preliminary efficacy data of this phase I clinical trial will inform a multi-institutional randomized phase II study of FOLFIRINOX vs. m FOLFIRINOX+ CPI613 in the near future. Clinical trial information: NCT01835041.
Safety and efficacy of CYT387, a JAK-1/2 inhibitor, for the treatment of myelofibrosis.
Authors: A. D. Pardanani, D. Caramazza, G. George, T. L. Lasho, W. J. Hogan, M. R. Litzow, K. Begna, C. A. Hanson, R. F. McClure, L. M. Bavisotto, G. Smith, M. Kowalski, S. Sirhan, A. W. Roberts, V. Gupta, J. Gotlib, A. Tefferi
Journal: Journal of Clinical Oncology (2011)

6514 Background: CYT387 is a potent JAK-1/2 inhibitor. In an ongoing phase-1/2 multi-center study, 108 patients with myelofibrosis (MF) have so far been accrued. We present updated interim results for 60 patients who have completed a minimum of 3 cycles of treatment. Additional information for the entire study cohort will be presented at the meeting. Methods: Patients with high/intermediate-risk MF were included. CYT387 was administered orally once daily in 28-day cycles. Responses were assessed by International Working Group (IWG) criteria. Results: Dose-limiting toxicities were grade 3 hyperlipasemia and grade 3 headache. The maximum tolerated dose was 300 mg/day. The study retention rate after a median of 6.4 months was 92%. About half of the patients experienced a first-dose effect (transient lightheadedness and hypotension), which was self-limited and generally resolved within hours with rare recurrence. Grade 3/4 hematologic and non-hematologic adverse events were infrequent with the exception of thrombocytopenia, which occurred in approximately 25% of patients. Forty-two patients were evaluable for anemia response per IWG criteria (Blood 2006;108:1497) and 33 were red cell transfusion-dependent. In the latter group, anemia response required a transfusion-free period of ≥12 weeks, while on protocol drug therapy, and capped by a hemoglobin level of ≥8 g/dL. Accordingly, the overall anemia response rate was 50% and 58% in transfusion-dependent patients. The median duration of anemia response was 20 weeks (range 12-54) and only 2 (11%) of the 19 patients who achieved transfusion-independency required single episodes of PRBC transfusions. Responses in anemia were not affected by leukocyte count (p=0.39), platelet count (p=0.35), circulating blast count (p=0.35), circulating CD34 cell count (p=0.78), karyotype (p=0.67) or JAK2V617F mutational status (p=0.17). Spleen response rate by IWG criteria was approximately 45% whereas the majority of patients experienced resolution of constitutional symptoms including pruritus, night sweats and bone pain. Conclusions: CYT387 is unique among JAK inhibitors because of its ability to induce durable anemia responses in a significant number of patients with myelofibrosis.
Eribulin treatment patterns in patients with and without prior anthracycline use.
Authors: Ali McBride, Claudio Faria, Xuan Li, Annette Powers
Journal: Journal of Clinical Oncology (2014)

292 Background: Eribulin mesylate is indicated for patients with metastatic breast cancer after treatment with ≥2 prior chemotherapeutic regimens for metastatic disease. Prior therapy should have included an anthracycline and a taxane. Evidence examining the effects of prior exposure to anthracyclines on eribulin therapy is limited. The purpose of this study was to compare demographic characteristics and treatment patterns for anthracycline-experienced patients vs. anthracycline-naïve patients treated with eribulin. Methods: A retrospective analysis using electronic medical record (EMR) data from 1/1/08 to 3/1/14 was conducted. Chemotherapy drugs were identified by the treatment name field in the EMR. Index date was defined as the first eribulin treatment. Patients with ≥2 eribulin administrations, continuous eligibility including a 6 month pre-period prior to the index date, and no treatment gaps more than 6 months were included. Patients were stratified into an anthracycline experienced cohort (treated prior to eribulin therapy) or without anthracycline cohort (never treated with this drug class prior to eribulin therapy). Demographics (gender, age, receptor status) and treatment characteristics (number and days of eribulin therapy) were compared between the cohorts. Results: 190 patients received eribulin; 46 (24%) with prior anthracycline use, 144 (76%) without. The majority of patients were female (87% for prior anthracycline, 97% without), and the average age of both groups was 59 yrs. Most patients were HR+/HER2- (56% overall; 70% for prior anthracycline, 51% for without), followed by TNBC (29% overall; 24% prior anthracycline, 31% without). Some patients had been treated previously with trastuzumab (15% overall; 7% for prior anthracycline, 17% for without). The number of eribulin administrations did not differ significantly between cohorts (8.2 administrations for anthracycline vs. 9.6 without, p=0.268). Likewise the number of days of therapy did not differ significantly (88.1 days for prior anthracycline vs. 104 without, p=0.369). Conclusions: There was no significant difference detected for prior anthracycline use impacting the number of eribulin administrations or days of therapy.
The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in first-in-human phase I study: The START Center experience.
Authors: T. Shimizu, A. W. Tolcher, K. P. Papadopoulos, M. Beeram, D. W. Rasco, L. S. Smith, S. Gunn, L. Smetzer, T. A. Mays, B. Kaiser, C. Alvarez, G. L. Mangold, A. Patnaik
Journal: Journal of Clinical Oncology (2011)

2502 Background: The dual targeting strategy involving PI3K and MAPK pathways is compelling, as it has become increasingly clear that both pathways are interconnected. Nevertheless, the clinical impact of this strategy remains uncertain. Methods: A pooled analysis of advanced cancer patients (pts) treated with phase I study drugs targeting PI3K/MAPK pathways from 06/07 to 11/10 was conducted. Pts treated with either single pathway inhibition (S) or dual pathway inhibition (D) were evaluated for safety, efficacy, and correlations between tumor genetic alterations and response. Response was assessed by using waterfall plot analysis (WPA) which included both average enlargement in tumor burden (AETB) and median enlargement in tumor burden (METB). Tumor genetic alterations were analyzed using DNA array-based CGH/PCR-based DNA sequencing. Results: A total of 225 pts in 11 first-in-human phase I clinical trials were analyzed; 66 pts (30%) received D, while 122 (54%) and 37 (16%) received inhibitors of either PI3K or MAPK pathways (S); 159 (71%) had measurable disease. The rates of drug-related grade 3/4 adverse events (AEs) were 17% (28/159) for S and 46% (30/66) for D (p<0.0001); rates of DLTs were 10% (16/159) for S and 17% (11/66) for D (p=0.17). The most frequent grade 3/4 AEs were rash and transaminase elevation. WPA displayed AETB(%) / METB(%): 21/17(S) and 13/14(D). Ninety-two of the 225 (41%) pts had available tumor genomic profiling data. PI3K pathway genetic alterations were detected in 17 of the 92 pts (18%; PTEN deletion, n=11; Akt2 amplification, n=5; PIK3CA mutation, n=1). Nine of the 17 (53%) pts with PI3K pathway genetic alterations had simultaneous KRAS or BRAF mutations (colorectal, n=8; melanoma, n=1). Of these 9 pts, all 5 pts who treated with D had tumor regression ranging from -2% to -64%. Conclusions: These preliminary results suggest that D of PI3K/MAPK pathways exhibits favorable efficacy compared to S of either pathway, at the expense of higher rates of Gr 3/4 AEs. This strategy may be especially important in pts with coexisting PI3K pathway genetic alterations and KRAS/BRAF mutations. Validation in the context of larger studies is recommended.
Influence of prostate cancer disease state and therapeutic selection on peripheral whole-blood RNA signature.
Authors: Bobby Chi-Hung Liaw, Uma Chippada-Venkata, Yixuan Gong, Li Wang, Jun Zhu, Matthias Michael Heck, Che-Kai Tsao, Matt D. Galsky, William K. Oh
Journal: Journal of Clinical Oncology (2015)

166 Background: Prostate cancer is a heterogeneous disease with differences in tumor stromal interactions contributing to variability in treatment response and outcome. Gene expression of peripheral blood cells is altered by interactions with neoplastic tissue. We previously developed a peripheral whole blood six-gene signature prognostic for survival in mCRPC. Here we evaluate how different clinical disease states and treatment with different therapeutic agents impact this signature. Methods: Whole blood was collected in PAXgene Blood RNA tubes in two cohorts of prostate cancer patients, one at Mount Sinai (n=135), the other in Munich (n=59), in the context of prospective clinical studies. Whole blood RNA was extracted and the six target genes were amplified using qPCR. Scores were derived using normalized cycle threshold (ΔCT) values of the six genes, according to the model: 2 x ABL2 + SEMA4D + ITGAL – C1QA – TIMP1 – CDKN1A. Patients were categorized by disease state in the Mount Sinai cohort, and by treatment received in the Munich cohort, for data analysis. Results: CRPC is the only disease state with a mean six-gene score (18.06) above the high-risk cutoff (17.9), and is significantly higher than localized or hormone sensitive advanced disease (16.07, 16.52, respectively; p=0.0002). Among patients with localized disease, there was no significant difference in the mean six-gene scores for patients with low-, intermediate-, and high-risk disease (16.07, 15.33, 16.66, respectively; p=0.27). In CRPC patients treated with docetaxel, there are significant changes to the six-gene score over the course of treatment (p=0.002), with a notable percentage decrease (-6.2%) at the 2-8 week timepoint that is not observed in patients treated with abiraterone or enzalutamide. Conclusions: Gene expression profiling of whole blood is influenced by the clinical state of prostate cancer as seen by differences to the six-gene score from localized to castrate resistant disease. Cytotoxic chemotherapy appears to modulate the six-gene score, something not seen with AR-directed therapies. Further investigation will be needed to understand the significance of these changes.
Prevalence of recognized bone metastases in the U.S. adult population.
Authors: S. Li, Y. Peng, E. D. Weinhandl, A. H. Blaes, K. Cetin, V. M. Chia, S. Stryker, J. J. Pinzone, J. F. Acquavella, T. J. Arneson
Journal: Journal of Clinical Oncology (2011)

1534 Background: Bone metastases (BM) are a significant cause of morbidity for cancer patients. Reliable population-based estimates of BM prevalence are lacking. Methods: All available claims from 2004-2008 were studied in 2 point-prevalent cohorts with insurance coverage on Dec 31, 2008: 1) persons age 18-64 years enrolled in commercial plans (MarketScan) and 2) persons age ≥65 years enrolled in traditional Medicare (Medicare 5% sample). Presence of BM was defined by 1 inpatient or 2 outpatient claims in any 1-year interval with a diagnosis of BM or 1 claim for zoledronic acid or pamidronate with a qualifying diagnosis for cancer. BM prevalence was extrapolated to the national commercially insured population age 18-64 years and to the traditional Medicare population age ≥65 years. Applying age/sex-specific rates to the 2008 U.S. census population, we estimated BM prevalence in the U.S. adult population overall and for select cancers. Results: In the commercially insured and Medicare cohorts, we identified 9,502 (in 18.2 million) and 6,427 (in 1.3 million) BM cases, respectively. Among the commercially insured, 29%, 28%, and 43% were identified from diagnosis code only, drug codes only, or both diagnosis and drug codes, respectively. The corresponding distribution was 37%, 20%, and 43% in the Medicare cohort. We estimated there were 279,679 U.S. adults with recognized BM on Dec 31, 2008. Estimates by cancer type are shown in the table [N (95% CI), in thousands]. Conclusions: Approximately 280,000 U.S. adults had recognized BM at the end of 2008. This estimate is likely conservative because not all cohort members were continuously insured from 2004-2008. Estimates do not include persons with BM who were not diagnosed or who, though diagnosed, were not assigned the codes required for defining BM in this study. Female breast Prostate Lung Multiple myeloma Other All cancers Commercially insured 25.6 (24.7, 26.4) 4.8 (4.4, 5.1) 7.8 (7.3, 8.2) 10.8 (10.3, 11.4) 11.5 (10.9, 12.0) 60.4 (59.1, 61.7) Medicare 35.4 (33.8, 37.0) 36.3 (34.6, 37.9) 15.7 (14.6, 16.8) 22.5 (21.2, 23.8) 18.6 (17.5, 19.8) 128.5 (125.5, 131.6) U.S. adults 89.8 (87.0, 92.6) 61.1 (58.6, 63.7) 34.8 (33.0, 36.6) 49.2 (47.1, 51.4) 44.7 (42.7, 46.7) 279.7 (274.6, 284.8)