tbuckley/cabot-search huggingface dataset:
Anti-VEGF drugs combined with gemcitabine-based chemotherapy in treatment of metastatic collecting duct carcinoma.
Authors: J. Guo, C. L. Cui, Z. H. Chi, L. Si
Journal: Journal of Clinical Oncology (2011)

403^ Background: Collecting duct carcinoma (CDC), accounting for less than 1% of kidney cancer, demonstrates an aggressive course and extremely poor prognosis. There are still no standard treatment regimens for this disease at present. Sunitinib and sorafenib, two protein tyrosine kinase inhibitors, have been used in treatment of renal cell carcinoma mainly by inhibiting vascular endothelial growth factor receptor (VEGFR). However, the combination of anti-VEGF drugs with gemcitabine-based chemotherapy has not been tested in CDC treatment. Methods: From Jun 2008 to Aug 2010, six patients (5 males and 1 female) with metastatic CDC, ECOG PS ≤ 2 and adequate organ function were enrolled in the trial. Four patients received sorafenib (400mg bid) and two received sunitinib (37.5mg Qd), all in combining with gemcitabine (1.0 g/m2 d1,8) and cisplatin (40 mg d1-3) Q28d. A mean of 2.3 cycles (range 1-4 cycles) was given. Performance status 0-2 was allowed. Tumor assessments and radiological evaluations were conducted every 4 weeks. Results: The median age was 41.5 years (range 28-60 years). All patients received prior nephrectomy. The sites of metastases included lung (4/6), skeleton (3/6), mediastinal lymph node (2/6), and liver (1/6). The therapy was well tolerated with grade 3-4 toxicities: neutropenia (4/6), thrombocytopenia (2/6), hand-foot syndrome (1/6) and rash (1/6). One patient had partial response, four had stable disease, and the disease control rate was 83.3% (5/6). The median progression-free survival was 3.5 months (range 1-6+ months), and the median overall survival was 6.5 months (1-15+ months) with the median follow-up of 6.5 months. No drug related deaths occurred. Conclusions: The combination of anti VEGF drugs and gemcitabine based chemotherapy are well tolerated. This treatment regimen demonstrates modest antitumor activity and may cause progression-free survial benefit in patients with CDC. [Table: see text]
Long- and short-acting opioids in cancer pain management: What is the best ratio?
Authors: Alison Wiesenthal, Natalie Moryl, Paul A. Glare
Journal: Journal of Clinical Oncology (2014)

206 Background: Many cancer patients experience chronic and breakthrough pain necessitating the use of both immediate release (IR) and extended release (ER) opioids. The common strategy in treating chronic cancer pain is using ER opioids with the addition of IR opioids for breakthrough pain. The National Comprehensive Cancer Network recommends IR dosing at 0.1-0.2 times the daily ER dose as needed every 1 hour for breakthrough pain, though data is lacking to validate this recommendation. The aim of this exploratory study was to review the current practice in prescribing IR and ER opioids and the IR/ER ratio used in cancer pain management at one comprehensive cancer center (CCC). Methods: We performed a retrospective chart review of 54 consecutive patients at a CCC over a 6 month period. IR/ER doses, dose adjustments and satisfaction with analgesia were recorded. Adjustments in treatment plans were made based on patients' report of effectiveness and side effects associated with ER and IR opioids. Results: 19 of 54 (35%) patients reported adequate analgesia, with the average daily prescribed IR/ER ratio of 0.6 (range 0 to 3.75). In this group, IR opioids were unchanged during the clinic visit. The ER opioids, on average, were also unchanged, though decreased by 25% and increased by 50% in a few cases over serial clinic visits. Of those patients reporting suboptimal analgesia during the clinic visit (65%), 80% had their ER opioids increased, 6% had IR opioids increased, and 9% had both IR and ER increased. The ER opioids were increased by 40% on average and IR by 11% with the average IR/ER ratio changing from 0.5 (range 0-2) to 0.37 (range 0-1.13). Conclusions: These preliminary data highlight the great variability between patient preferences and clinician decisions in terms of IR/ER opioid ratios. In this retrospective study, analgesia was better in the group using higher IR doses with a higher IR/ER ratio. At the same time, patients with suboptimal analgesia had their ER opioids titrated faster and higher than the IR opioids. More studies are needed to determine best practice in the prescribing of long and short acting opioids for management of chronic cancer pain.
Assessment of Early Molecular Response As a Predictor of Long-Term Clinical Outcomes in the Phase 3 BELA Study
Authors: Tim H Brümmendorf, Hagop M. Kantarjian, Carlo Gambacorti-Passerini, Francois Guilhot, Luke Akard, Vaishali Doshi, Jeff H Lipton, Dmitri Pavlov, Karin Gogat, Ladan Duvillie, Mark Shapiro, Jorge E Cortes
Journal: Blood (2012)
Recognition of viral and self-antigens by T H 1 and T H 1/T H 17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses
Authors: Moira Paroni, Virginia Maltese, Marco De Simone, Valeria Ranzani, Paola Larghi, Chiara Fenoglio, Anna M. Pietroboni, Milena A. De Riz, Maria C. Crosti, Stefano Maglie, Monica Moro, Flavio Caprioli, Riccardo Rossi, Grazisa Rossetti, Daniela Galimberti, Massimiliano Pagani, Elio Scarpini, Sergio Abrignani, Jens Geginat
Journal: Journal of Allergy and Clinical Immunology (2017)
Chemotherapy-induced nausea and vomiting (CINV) in a naturalistic setting.
Authors: J. G. Lundberg, S. Borjeson, V. Fomichov, J. Lyth, C. Petersson
Journal: Journal of Clinical Oncology (2011)

e19614 Background: In 1999, researchers and clinicians at Linköping University Hospital, Sweden, designed an assessment tool for patient-reported CINV. Patient demographics, chemotherapy regimen, antiemetics use, CINV and well being outcomes are gathered in a database. The purpose of this study was to retrospectively describe CINV outcomes in a naturalistic setting in one center in Sweden. Methods: An ordinal assessment scale whereby nausea is described as “No”, “Mild”, “Moderate”, or “Severe” was used. The last day of combination chemotherapy administration plus four days were described for patients receiving one of four common chemotherapy regimens; epirubicin plus cyclophosphamide plus fluorouacil (FEC 60), leucovorin plus fluorouracil plus oxaliplatin (FOLFOX), bleomycin plus etoposide plus cisplatin (BEP) or cisplatin plus 5-FU. The absolute and relative frequencies and corresponding confidence intervals (CI) of patients reporting “No nausea” were described on a per day basis. Patient reported use of 5HT3 receptor antagonist was 85.4%-98.0% and corticosteroid 74.0%-87.8%. Results: See table. Conclusions: Control of nausea, both on the day when chemotherapy is given and on subsequent days, is not optimal. Frequencies of reported “No Nausea.” Chemotherapy Day of the cycle Number of events Number at risk Frequency of reported “No Nausea” (95% CI) Relative frequency (95% CI) FEC – 60 1 627 1,131 0.55 (0.51-0.60) Reference 2 683 1,118 0.61 (0.57-0.66) 1.10 (0.99-1.23) 3 655 1,119 0.59 (0.54-0.63) 1.06 (0.95-1.18) 4 691 1,107 0.62 (0.58-0.67) 1.13 (1.01-1.25) 5 779 1,085 0.72 (0.67-0.77) 1.30 (1.17-1.44) FOLFOX 1 733 968 0.76 (0.70-0.81) Reference 2 714 997 0.72 (0.67-0.77) 0.95 (0.85-1.05) 3 645 982 0.66 (0.61-0.71) 0.87 (0.78-0.96) 4 617 958 0.64 (0.60-0.70) 0.85 (0.76-0.95) 5 669 934 0.72 (0.66-0.77) 0.95 (0.85-1.05) Cisplatin plus 5-FU 1 198 224 0.88 (0.70-0.81) Reference 2 146 226 0.65 (0.55-0.76) 0.73 (0.59-0.91) 3 126 224 0.56 (0.47-0.67) 0.64 (0.51-0.80) 4 130 221 0.59 (0.50-0.70) 0.67 (0.53-0.83) 5 136 217 0.63 (0.53-0.74) 0.71 (0.57-0.88) BEP 5 17 50 0.34 (0.21-0.55) Reference 6 18 50 0.36 (0.23-0.57) 1.06 (0.55-2.05) 7 22 49 0.45 (0.30-0.68) 1.32 (0.70-2.49) 8 25 45 0.56 (0.38-0.82) .1.63 (0.88-3.03) 9 32 45 0.71 (0.50-1.01) 2.09 (1.16-3.77)
The Role of the Human Visual Cortex in Assessment of the Long-Term Durability of Retinal Gene Therapy in Follow-on RPE65 Clinical Trial Patients
Authors: Manzar Ashtari, Elena S. Nikonova, Kathleen A. Marshall, Gloria J. Young, Puya Aravand, Wei Pan, Gui-shuang Ying, Aimee E. Willett, Mani Mahmoudian, Albert M. Maguire, Jean Bennett
Journal: Ophthalmology (2017)
Peroxisome proliferator-activated receptor gamma (<i>PPARG</i>) gene amplifications in urothelial carcinoma (UC).
Authors: Richard M. Bambury, Gopa Iyer, Markus Riester, Lillian Werner, Nikolaus Schultz, Edward C. Stack, Rachel Park, Massimo Loda, Irina Ostrovnaya, Philip W. Kantoff, Dean F. Bajorin, David B. Solit, Franziska Michor, Joaquim Bellmunt, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2013)

279 Background: PPARy is a steroid hormone receptor encoded by the PPARG gene (Chr 3p25). Data are conflicting regarding its role in UC. Some studies suggest activation has antiproliferative effects, and preclinical data indicate a potential role for PPARy agonists in cancer treatment. However, recent findings show that use of the PPARy agonist thiazolidinones (TZD) in type 2 diabetes is associated with increased risk of developing UC. To define the spectrum of PPARy aberrations in UC, DNA was evaluated to detect copy number gains/losses (CNG/CNL) of PPARG in three clinically annotated UC cohorts. Methods: Cohort A contained 97 patients with high-grade UC. Cohort B contained 94 patients with primary bladder tumors who developed metastatic UC. Cohort C had 33 patients with metastatic UC, including both primary and paired metastatic tissue for 14 patients. DNA from all tumors was subjected to copy number analysis (array comparative genomic hybridization for cohorts A and B and molecular inversion probe array for cohort C) to identify focal areas of CNG/CNL. Statistical analysis using RAE (cohort A) or GISTIC 2.0 (with CNG defined as log2 copy number ratio &gt;0.8) in cohorts B/C was used to identify significant alterations. Results: The region containing PPARG showed CNG in 7%, 10%, and 15% of cohorts A, B and C, respectively. In cohort A, RAE p value was 5.36E-05 at the amplicon containing PPARG. In cohorts B and C GISTIC 2.0 q values were 9.75E-12 and 6.04E-10. PPARG CNG had no impact on survival in the cohorts with available survival data (A and B). Paired biopsies from primary and metastatic sites showed discordance in PPARG CNG in 2 cases. In 1 case CNG was present in the metastasis but not in the primary and in 1 case the opposite occurred. Conclusions: PPARG shows significant CNGs in 7-15% of UC. Notably the RAF1 locus (a known oncogene) lies close to PPARG and could also represent the driver alteration within this amplicon. Investigation of the functional relevance of these CNGs is clearly warranted as it may be a driver of bladder cancer growth and progression. Determination of PPARG CNG status in UCs in a TZD treated population may provide mechanistic insights into the increased incidence of UC in patients treated with these agents.
Construction and validation of a practical prognostic index for patients with metastatic pancreatic adenocarcinoma.
Authors: C. Morizane, T. Okusaka, S. Morita, K. Tanaka, H. Ueno, S. Kondo, M. Ikeda, K. Nakachi, S. Mitsunaga, T. Yamaguchi
Journal: Journal of Clinical Oncology (2011)

285 Background: The aim of the present study was to determine prognostic factors in patients with metastatic pancreatic adenocarcinoma (PC) receiving systemic chemotherapy and to construct and validate a prognostic index for metastatic PC. Methods: The relationship between patient characteristics and outcome was examined by multivariate regression analyses of data from 409 consecutive patients with metastatic pancreatic adenocarcinoma who had been treated with a gemcitabine- containing regimen (GEM alone: 302 patients, GEM + cisplatin (CDDP): 39, GEM + 5-flurorouracil (5-FU): 27, GEM + S-1:41), and we stratified the patients into three risk groups according to the number of prognostic factors they had for a poor outcome. A validation data set obtained from 145 patients who had been treated with agents other than GEM (5-FU + CDDP, MTX+5- FU, docetaxel, UFT, S-1, CPT-11) was analyzed. The prognostic index was applied the each of the patients. Results: The multivariate regression analyses revealed that the presence of pain (hazard ratio (HR): 1.692), peritoneal dissemination (HR:1.756), liver metastasis (HR:1.423), and an elevated serum CRP level by &gt; 1.0 mg/dl (HR:1.540) significantly contributed to a shorter survival time. The patients were stratified into three groups according to their number of risk factors and their outcomes of the three groups were significantly different. The median survival times (MSTs) of the low-, intermediate-, and high-risk groups were 11.1, 7.3, and 3.2 months, respectively. When the prognostic index was applied to the validation data set, the respective outcomes of the three groups were found to be significantly differed from each other. The MSTs of the low-, intermediate-, and high-risk groups were 8.6, 5.2, and 2.3 months, respectively. Conclusions: Pain, peritoneal dissemination, liver metastasis, and an elevated serum CRP value are important prognostic factors for patients with metastatic pancreatic adenocarcinoma. No significant financial relationships to disclose.
Comparison of safety and efficacy between squamous and non-squamous non-small cell lung cancer (NSCLC) patients in phase II studies of DMXAA (ASA404)
Authors: M. J. McKeage, M. B. Jameson
Journal: Journal of Clinical Oncology (2008)

8072 Background: DMXAA (ASA404) is a tumor vascular disrupting agent recently evaluated in phase II trials in NSCLC. A randomized trial compared DMXAA 1,200 mg/m2 plus carboplatin and paclitaxel (CP) with CP alone (median survival 14.0 vs 8.8 months). A single-arm study evaluated DMXAA 1,800 mg/m2 plus CP (median survival 14.9 months). Both trials included squamous and non-squamous patients. We examined whether the safety or efficacy of DMXAA varied with histology. Methods: Patients had chemotherapy-naïve stage IIIb/IV NSCLC. Phase II data were pooled by histology and treatment, with aggregation of the two DMXAA doses. We compared efficacy and safety between squamous and non-squamous patients receiving the same treatment. Then for each histology we compared patients receiving and not receiving DMXAA. Results: Numbers of patients evaluable for safety (efficacy) were: in the CP arm of the randomized study, 11 (11) squamous and 25 (25) non-squamous; in the CP + DMXAA 1,200 mg/m2 arm of the randomized study, 11 (11) squamous and 26 (23) non-squamous; and in the CP + DMXAA 1,800mg/m2 single arm study, 11 (10) squamous and 20 (20) non-squamous. Pooling data from the two DMXAA dose groups should not introduce bias because they contain similar proportions of squamous patients. Conclusions: Addition of DMXAA to CP was generally well tolerated in both squamous and non- squamous patients. There was no evidence that DMXAA induced hemoptysis in either group. In both squamous and non-squamous patients, efficacy findings including survival were consistently better with DMXAA plus CP than with CP alone. The forthcoming phase III trial will therefore include both squamous and non-squamous patients. Safety and Efficacy Squamous Non-squamous All histologies CP CP + DMXAA CP CP + DMXAA CP CP + DMXAA % patients with ≥1 adverse event NCI-CTC grade ≥3/severe 72.7% (n=11) 68.2% (n=22) 64.0% (n=25) 60.9% (n=46) 66.7% (n=36) 63.2% (n=68) Response rate* 14.3% (n=7) 40.0% (n=20) 25.0% (n=20) 31.7% (n=41) 22.2% (n=27) 34.4% (n=61) Median time to tumor progression (months) 1.6 (n=11) 5.6 (n=21) 4.8 (n=25) 5.5 (n=43) 4.4 (n=36) 5.5 (n=64) Median survival (months) 5.5 (n=11) 10.2 (n=21) 11.0 (n=25) 14.9 (n=43) 8.8 (n=36) 14.5 (n=64) * 12 patients evaluable for other efficacy parameters were not evaluable for response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Antisoma
Evaluation of major histocompatibility complex class I expression in clear cell renal cell carcinoma as a prognostic tool.
Authors: Claire M. de la Calle, Sarah A. Holzman, Umer Sheikh, Jonathan H. Huang, Haydn T. Kissick, Adeboya O. Osunkoya, Brian P. Pollack, Dattatraya Patil, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2015)

469 Background: After nephrectomy for clear cell renal cell carcinoma (ccRCC) approximately one-third of patients develop metastases. Yet, with currently used prognostic tools such as the TNM staging and the Fuhrman nuclear grade (FNG) system, it is difficult to accurately assess prognosis for each patient. Here, we evaluated Major Histocompatibility Complex Class I (MHCI) expression as a potential prognostic immune marker in ccRCC. Methods: Fifty-five post-nephrectomy patients that presented with localized ccRCC were included. All patients had four or more years of follow up. MHCI was stained in the tumor sections via immunohistochemistry. Then, via an automated image analysis algorithm MHCI expression was quantitated with the Positivity score, the ratio of positively stained pixels over the total number of pixels. Results: Mean MHCI positivity score of the cohort was 0.75 (SE= ±0.20). At the end of the follow-up period, the patients who were alive had higher MHCI expression (0.80 positivity score; SE ±0.14) than those who died of disease (0.62 positivity score; SE= ±0.16; t test, p&lt;0.0001). MHCI positivity scores above the mean were associated with increased cancer specific survival (Mantel-Cox, p=0.0021). MHCI expression was higher among patients with no recurrence (0.80; SE= ±0.16) compared to those that recurred during the study period (0.70; SE= ±0.22; t test, p=0.017); and time-to-recurrence was longer in patients with above mean MHCI positivity scores (Mantel-Cox, p=0.017). Patients who were alive with recurrence had increased MHCI expression (0.81; SE= ±0.10) compared to those who succumbed to disease recurrence (0.62; SE= ±0.25; t-test, p=0.0009). No correlation was detected between FNG and tumor expression of MHCI (ANOVA, p=0.655, F=0.423) or between stage at presentation and MHCI tumor expression (ANOVA, p=0.734, F=0.311). Conclusions: With an automated high-throughput image analysis, this cohort shows that increased MHCI expression in ccRCC is associated with improved prognosis after curative nephrectomy.
Economic evaluation of denosumab compared with zoledronic acid in patients with hormone-refractory prostate cancer with bone metastases.
Authors: A. P. Yu, M. Namjoshi, J. Xie, K. Parikh, E. Q. Wu, A. Guo, K. W. Culver
Journal: Journal of Clinical Oncology (2011)

e15115 Background: A Phase III clinical trial (NCT00321620) recently demonstrated that denosumab delayed time to 1st skeletal-related event (SRE) and subsequent SREs longer than zoledronic acid (ZA), but showed no difference in either survival or disease progression between the two products. The objective of this study was to conduct an economic evaluation of denosumab compared to ZA in the treatment of bone metastases in men with hormone-refractory prostate cancer. Methods: A Markov model was developed to assess the one-year costs and effectiveness associated with the two treatments. Transition probabilities associated with experiencing the first SRE, subsequent SREs, disease progression, and death were primarily derived from the results of the Phase-III clinical trial, and, supplemented with published literature. Costs associated with progression, SREs, adverse events, and death were obtained from the literature and estimated as paid amounts in 2010 dollars. The model results include theincremental cost per SRE avoided. One-way sensitivity analyses were performed to test the robustness of the model. Results: The total costs incurred over one year were estimated at $37,854 for denosumab and $30,499 for ZA, with an incrementally higher cost of $7,355 for denosumab. The estimated number of SREs during the one-year period was 0.56 for denosumab and 0.67 for ZA, where the denosumab patients had 0.11 fewer SREs. The incremental cost per SRE avoided with the use of denosumab was $66,864. The one-way sensitivity analysis indicated that the cost per SRE avoided was driven by the differences in the drug costs, risk of progression, and risk of first SRE. Conclusions: Although denosumab was shown to be more effective than zoledronic acid in delaying SREs in the recently completed Phase III trial, its use is associated with high costs. Health plans need to carefully consider these high costs prior to making decisions regarding formulary inclusion and reimbursement.
Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation
Authors: Weiming Lai, Yingying Cai, Jinfeng Zhou, Shuai Chen, Chaoyan Qin, Cuixia Yang, Junling Liu, Xin Xie, Changsheng Du
Journal: Cellular and Molecular Immunology (2017)
Phase I trial of total androgen blockade, weekly docetaxel, and image-guided intensity-modulated radiotherapy for localized high-risk prostate adenocarcinoma.
Authors: Stephen J. Ramey, Ali Reza Golshayan, Thomas E. Keane, Andrew S. Kraft, Uzair Bashir Chaudhary, David T. Marshall
Journal: Journal of Clinical Oncology (2013)

96 Background: High-risk prostate cancer patients have high rates of treatment failure and improved outcomes are needed. Docetaxel has shown efficacy in hormone-resistant prostate cancer and can act as a radiosensitizer. Dose escalation studies with radiation therapy have found improved freedom from failure rates. The addition of androgen deprivation therapy (ADT) improves overall survival. Therefore, this phase I study was designed to find the maximum tolerable dose (MTD) of weekly docetaxel when combined with high-dose image-guided intensity-modulated radiotherapy (IGRT) and ADT in patients with high-risk prostate cancer. Methods: Men with high-risk adenocarcinoma of the prostate (≥T2c, or PSA ≥20ng/ml, or Gleason ≥8) were treated with weekly docetaxel (given at 10-30 mg/m 2 , increasing by 5 mg/m 2 until the MTD was reached) concurrently with IGRT of 77.4 Gy in 43 fractions to the prostate and 45 Gy in 25 fractions to the proximal seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before chemoradiation and continuing 2 months concurrently. The GnRHa was then continued for an additional 24 months. Results: 19 patients began combined chemoradiation between April 2006 and December 2010. Median follow-up is 32 months. No dose-limiting toxicities (DLTs) were seen in patients treated with docetaxel doses up to 25 mg/m 2 . However, at the 30 mg/m 2 level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and grade 3 upper GI toxicity, indicating the MTD had been exceeded. At last follow-up, 2 patients had died, one from metastatic prostate cancer and the other from heart failure. A second patient demonstrated biochemical failure by the Phoenix criteria at 46 months, giving an actuarial biochemical disease-free survival (bDFS) at 3 years of 94.7%. All patients had ≥grade 2 erectile dysfunction but no other ≥grade 2 long-term toxicities were identified. Conclusions: Weekly docetaxel may be combined with high-dose IGRT and long-term ADT up to a MTD of 25 mg/m 2 . Long-term side effects with this regimen were minimal, and bDFS rate is encouraging. Clinical trial information: NCT00099086.