tbuckley/cabot-search huggingface dataset:
Genetic polymorphisms of PDGFR/VEGFR2/VEGFR3/RET and their relevance to thrombocytopenia in mRCC patients treated with sunitinib.
Authors: Xi Nan Sheng, Yan Kong, Zhihong Chi, Chuan Liang Cui, Lu Si, Li Li Mao, Bin Lian, Si Ming Li, Bixia Tang, Xuan Wang, Xieqiao Yan, Jie Dai, Jun Guo
Journal: Journal of Clinical Oncology (2015)

481 Background: Since Asian are more susceptible to hematologic toxicity caused by sunitinib. The adverse effect difference differs from that of Caucasian may be related to genetic polymorphism. This study is to explore the characteristics of gene phenotypes and potential relationship between genetic polymorphisms and thrombocytopenia in Chinese patients with metastatic clear-cell renal cell carcinoma (mcc-RCC) treated with Sunitinib. Methods: Ninety-three mcc-RCC patients treated with sunitinib were enrolled in this study. Genotype analyses were done before treatment and thrombocytopenia was recorded on the first three cycles of treatment. Genetic polymorphisms of PDGFR (rs35597368, rs1800810, rs1800813, rs1800812) AVEGFR2 (rs2071559, rs1531289, rs7692791, rs1870377) AVEGFR 3 (rs307826) ARET (rs1799939) were analyzed for a possible association with thrombocytopenia (grade 3/4) incidences. Results: Gene types of total of 10 single nucleotide polymorphisms in 4 candidate genes were according with Hardy-Weinberg law. Grade 3/4 thrombocytopenia incidence is 29%. Test results demonstrated that the incidence of grade 3/4 thrombocytopenia was increased when CG genotype in PDGFR 1171C/G (rs1800810) (p=0.048) or when GA genotype in PDGFR 735G/A (rs1800813) (p=0.050) or when AA genotype in VEGFR2 1718T/A (rs1870377) (p=0.001) were present. Conclusions: The mutation in locus of rs1800810, rs1800813 and rs1870377 may intensify the inhibition of PDGFR or VEGFR2 by sunitinib, causing the increase thrombocytopenia incidence. It is help to look for the biomarker about side effect for the patients with metastatic clear-cell renal cell carcinoma treated with sunitinib.
Phase I trial of CCL21 gene modified dendritic cells in non-small cell lung cancer.
Authors: J. M. Lee, E. B. Garon, F. Baratelli, D. Schaue, P. S. Pak, W. D. Wallace, R. Suh, F. Abtin, G. Zeng, S. M. Dubinett
Journal: Journal of Clinical Oncology (2010)

TPS157 Background: Intratumoral administration of autologous dendritic cells (DC), transduced with a replication-deficient adenoviral (Ad) vector to express the secondary lymphoid organ chemokine (SLC/CCL21) gene, may stimulate anti-tumor immune responses. Objectives: 1) To determine the safety and maximum tolerated dose (MTD) of CCL21 gene-modified DC (Ad-CCL21-DC) when administered as an intratumoral injection into a tumor site of patients with advanced non-small lung cancer (NSCLC). 2) To determine the local and systemic biologic activity of Ad-CCL21-DC when administered intratumorally to patients with advanced NSCLC. 3) To determine the clinical activity (i.e. reduction in tumor burden) of Ad-CCL21-DC when administered intratumorally to patients with advanced NSCLC. Methods: Study Population: Patients with pathologically confirmed and radiographically measurable NSCLC, stage IIIb/IV, who have tumor accessible by CT-guided intervention or bronchoscopy, and are refractory to standard therapy. Sample Size: 21 patients will be evaluated, 3 patients at each dose level; and an additional 12 patients at the MTD. Study Design: Phase I, nonrandomized, dose escalating, multicohort trial will be conducted to enroll patients at a single institution in a modified 3+3 design. Three patients will be assigned to each cohort (A, B, or C) and receive the same Ad-CCL21-DC dose (1×106, 5×106, or 1×107 cells/injection, respectively) by CT-guided or bronchoscopic intratumoral injection (days 0 and 7). Dose escalation may proceed only if all 3 patients enrolled in the lower dose cohort experience no dose limiting toxicity (DLT) over a 28-day period or 1 of 6 patients in a cohort has a DLT. All subjects will be monitored for 56 days. Eligible patients will be assigned to a cohort and will receive monitoring. Outcome Measures: Tumor biopsy on days 0 and 7: 1) Immunohistochemistry for T cell and DC infiltrates. 2) Quantitative real-time RT-PCR for cytokines. 3) Flow cytometry for T cells, DC, and CCL21. Peripheral blood: 1) Nested PCR for detection of free Ad-CCL21. 2) Quantification of anti-Ad antibody by ELISA. 3) Antigen-specific ELISPOT assays. 4) Quantitate circulating tumor cells. Enrollment: 4 Subjects. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tragara Pharmaceutical
The recurrence patterns and post-recurrence survivals in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with preoperative paclitaxel/cisplatin-based chemoradiotherapy.
Authors: Hung-Yang Kuo, Jhe-Cyuan Guo, Ta-Chen Huang, Chia-Chi Lin, Min-Shu Hsieh, Jang-Ming Lee, Jason C. Cheng, Hsiu-Po Wang, Kun-Huei Yeh, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2016)

80 Background: More than half of patients (pts) with locally advanced ESCC would have disease recurrence after curative preoperative chemoradiation (CRT) followed by surgery. Whether recurrence pattern correlates with the post-recurrence survival remains uncertain. Methods: We included 131 pts with locally advanced ESCC (clinical T3N0-1M0 or T1-3N1M0 or M1a according to AJCC 6 th edition) who were enrolled in 3 phase II clinical trials of preoperative CRT followed by surgery and had successfully completed CRT and surgery. These pts received preoperative twice weekly paclitaxel/cisplatin-based CRT with radiotherapy 40Gy given in 20 fractions followed by esophagectomy. When pts had first disease recurrence, we divided them into three groups according to their recurrence patterns: loco-regional recurrence (LRR), distant metastasis only (DM), and both LRR and DM (LRR+DM). Survival outcomes were compared using the Kaplan-Meier curves. Results: With a median follow-up of 34.8 months, 75 pts (57.3%) had disease recurrence (Table 1) and the median post-recurrence survival of these pts is 6.7 months (m). Among them, 24 pts (32.0%) had LRR, 19 (25.3%) pts had DM, and 32 pts (42.7%) had LRR+DM. There is no statistical difference of the post-recurrence survivals (Fig. 1) among 3 groups (5.4, 7.5, 4.9m, p = 0.43 in LRR, DM, and LRR+DM group respectively). It is noteworthy that 4 pts in the DM group with limited distant metastasis (1 had brain metastasis, 3 had lung metastasis) had long post-recurrence survival (56.2+, 51.6+, 13.8+, 13.1+m) after receiving metastasectomy with or without chemotherapy. Conclusions: The post-recurrencesurvival of locally advanced ESCC pts who received preoperative CRT followed by surgerywere similar regardless of recurrence pattern (loco-regional recurrence or both loco-regional and distant failure). However, in pts with limited metastasis, curative metastasectomy might provide the opportunity of achieving long-term survival. (The work was supported by the Grant of MOST 103-2314-B-002-092, MOST 104-2314-B-002-111- and HCH104-024)
Real-world utilization of the novel AR-targeted therapies in mCRPC management: An electronic medical records retrospective study.
Authors: A. Oliver Sartor, Jyotsna Mehta, Eileen Fonseca, Catherine Balderston McGuiness, Allison Petrilla, Zhen Su
Journal: Journal of Clinical Oncology (2014)

176 Background: New androgen receptor (AR) targeted therapies, including abiraterone (AA) and enzalutamide (EZ), have recently been approved for mCRPC management. This study examined use of AA in community oncology practices to understand real world practice patterns. Methods: Deidentified EMRs were retrospectively analyzed for cancer staging, tumor histology, metastatic coding, lab results and drug orders from 78 practices (300+ locations; 37 states; &gt;500,000 cancer patients) to identify mCRPC patients initiating AA between May 2011-Jan 2013, provided there was one year of baseline data prior to starting AA and 3 mos of data after initiating AA. Patients were excluded if participating in clinical trials, diagnosed with other primary neoplasms, or from practices inconsistently reporting data. Key outcomes were changes in systemic anti-cancer therapy, discontinuation of AA, and death during the first 3 mos after AA initiation. Results: Of 3,930 mCRPC patients observed with an oncology visit during study period, 356 met criteria for analysis (mean age at AA initiation 73.3 yrs); 37% of patients (n=131) received prior docetaxel (D) and 16% of patients (n=56) received prior cabazitaxel (C) before starting AA. Of these 356 patients, 153 (43%) experienced a change of therapy or death in the 3 mos post-starting AA. Of the total patients, 19% (n=66) discontinued AA, while 17% (n=62) changed systemic therapy. Of those changing therapy, 5 patients started EZ, 20 CBZ, 24 D. A total of 11% of the total patients (n=39) died within 3 mos of starting AA. Conclusions: Real-world treatment data suggests more than 57% of patients were alive and continuing AA while 43% discontinued AA/changed treatments, or died within 3 mos of starting AA. EMR data provide important insights into real world practice; limitations include inconsistency in data entry and difficulty in aligning prescription start dates with actual dispensed medication. [Table: see text]
Health-related quality-of-life (HRQoL) reporting by randomized cancer trials (RCT): Pitfalls for interpretation.
Authors: L. Testa, C. C. Barbosa, A. C. Chaves, P. M. Hoff, R. P. Riechelmann
Journal: Journal of Clinical Oncology (2011)

6102 Background: Overall survival and HRQoL are well-recognized direct measures of patient benefit. While survival is an easily defined endpoint, the definition and measure of quality of life is less clear. Hence, the reporting of HRQoL may impact on result interpretation. Here, we evaluated the quality of reporting of HRQoL by RCT of anticancer therapy. Methods: We performed a systematic review of phase III RCT of cancer-directed therapy published in PubMed in the last 10 years, whose primary or secondary endpoint was HRQoL. Data on study characteristics were extracted and authors’ conclusions were independently analyzed and classified (positive, negative, neutral, not reported) by two blinded investigators. Articles were analyzed for HRQoL methodological quality, using a checklist previously published (Tannock et al. Ann Oncol 2004). Summary statistics were used to describe the results. Results: 347 of 922 trials were eligible. 136 (39%) cited HRQoL as a study endpoint. In such studies, the most common tumor site was Lung, 84% were superiority and 16% were non-inferiority RCT, and 52 (38%) trials were positive with respect to primary endpoint. 47 (34%) presented HRQoL results, 29 (21%) reported positive results, 30 (22%) clearly defined HRQoL as a study endpoint, 36 (26%) had a-priori hypothesis testing, and only 9 (7%) computed a sample size based on HRQoL hypothesis. Most studies reported negative conclusions on HRQoL (73; 53%), while 30 (22%) were considered positive, 17 (12%) neutral and in 66 (48%), no results were presented. There was a positive association between positive conclusions and authors’ declared financial conflict of interest with industry (p< .05). Despite the fact that 95 (70%) presented negative results on HRQoL, only 75 (55%) actually reported negative conclusions. Conclusions: The quality of reporting HRQoL data by RCT in oncology is poor, with the majority not presenting sufficient information for results interpretation. Also, authors' conclusions not always reflect HRQoL results. Improvement in conducting and reporting patient-reported outcomes are urgently needed to help clinicians to put such information in context and decide what is best for their patients.
Impact of Rapid Lymphocyte and Monocyte Recovery on Overall Survival Post-Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine/Melphalan Conditioning
Authors: Lori DeCook, Mary Thoma, Tanya Huneke, Nicole Johnson, Robert Wiegand, Mark R. Litzow, William J Hogan, Luis F. Porrata, Shernan G. Holtan
Journal: Blood (2011)
The Disease-Related Bone Marrow Microenvironment Alters Hematopoietic Stem and Progenitor Function in Multiple Myeloma Patients
Authors: Ingmar Bruns, Ron-Patrick Cadeddu, Ines Brückmann, Sebastian Buest, Julia Fröbel, Thomas Schroeder, Stefanie Geyh, Ali-Nuri Hünerlitürkoglu, Guido Kobbe, Roland Fenk, Andreas Trumpp, Akos Czibere, Rainer Haas
Journal: Blood (2011)
Molecular testing for colorectal and lung cancer at an academic cancer center satellite site: Opportunities for improvement.
Authors: Melina Marmarelis, Lawrence N. Shulman, Joseph O. Jacobson, Andrew David Norden
Journal: Journal of Clinical Oncology (2016)

229 Background: Given their prevalence, colorectal and lung cancer are treated in both academic and community settings. Appropriate use of targeted therapies in these diseases is challenging given the need for biomarker testing prior to use. Rapidly changing practice standards, limited resources, and barriers to tissue processing make this particularly challenging in the community. We examined the use of biomarker testing and targeted therapies in colorectal and lung cancer at one of the Dana-Farber Cancer Institute satellite sites. Methods: Patients who had their first visit for colorectal cancer between 2011 and 2014 or for lung cancer in 2014 at one site were identified using ICD-9 codes. Notes and reports were reviewed for pathology, staging, molecular testing, and treatment. Results: In 2014, 46 patients had their first visit for colon cancer. MMR testing was done in 48% (22/46) of these patients. Of the 23 patients under 70 years old (NCCN guideline), 75% (17/23) were tested. From 2011 to 2014 there were 30 patients with newly diagnosed metastatic colorectal cancer. KRAS testing was done in 73% (22/30) of these patients and three were subsequently treated with EGFR targeted therapy (all 3 KRAS/BRAF wild type). In 2014, 90 patients were seen with a new diagnosis of lung cancer. Among the 36 patients with adenocarcinoma, 21 were stage IV at diagnosis and 57% (12/21) were tested for EGFR and ALK. The most common reason cited for not testing was tissue sample size (e.g. cytology from pleural fluid, CT-guided biopsy). Among the 9 patients not tested, 6 were noted to have insufficient material and in 3, testing was not requested. Conclusions: The largest discrepancy between guidelines and clinical practice was seen in EGFR and ALK testing in lung cancer. In colorectal cancer there was high concordance with NCCN guidelines and importantly these results appropriately guided EGFR directed therapy. Possible interventions to increase utilization include educational events, reflex testing on pathology, and an algorithm to pursue additional tissue when biomarker testing could significantly change therapy.
Docetaxel and cisplatin combination chemotherapy in Chinese patients with anthracycline-resistant advanced breast cancer
Authors: B. Xu, L. Zhao, J. Wang, P. Yuan
Journal: Journal of Clinical Oncology (2008)

12018 Background: The resistance to anthracyclines frequently emerges in patients with metastatic breast cancer, which makes further treatment difficult. The aim of this study was to determine the efficacy and safety of combination chemotherapy of Docetaxel combined with cisplation for anthracycline - resistant advanced breast cancer. Methods: From April 2000 to March 2005, 31 patients with anthracycline-resistant advanced breast cancer were treated with combination chemotherapy of docetaxel and cisplatin. Docetaxel 75 mg/m2 and cisplatin 75 mg/m2 were used on day 1 every three weeks. The median number of cycles was 4 (rang2∼8 cycles). Results: The overall combination chemotherapy response rate was 54.9% with a median time to progression of 5 months. One- year survival rate was 66.7%. The main side effects were gastrointestinal and hematologic toxicities, including grade 3 to 4 nausea and vomiting in 3 patients (9.7%), leukopenia in 6 (19.3%), and neutropenia in 3 (9.7%). Conclusions: Docetaxel and cisplatin combination is active in the treatment for anthracycine-resistant advanced Chinese breast cancer patients with an acceptable toxicity, and may be a therapeutic alternative after anthracycline regimen has failed. No significant financial relationships to disclose.
Patient evaluation of community nurse-led follow-up clinics for colon cancer.
Authors: Leslie M. Samuel, Bernice West
Journal: Journal of Clinical Oncology (2013)

587 Background: Health services face an ever increasing demand for quality patient focussed healthcare with limited financial resources. Our group has designed and implemented, using non-specialist community nurses, a nurse led follow up service for patients with potentially cured colon and prostate cancers in 4 community hospitals in North East Scotland. Nurses use a structured questionnaire, take tumour specific blood tests &amp; order some imaging. Results communicated to patients via letter from oncologist. Methods: A user-group &amp; professionals were consulted and a customised questionnaire designed. Topic sections were-basic demographic data; mode of transport; perceptions of parking; travel; continuity of care; timing of appointments; satisfaction with service attributes; any concerns; suggestions for improvement and an overall rating score. Details of the evaluation were considered by the ethics committee as 'service evaluation'. Results: The questionnaire was successfully piloted in 5 patients. The main study targetted 100 patients, &amp; data-collection ran from August 2010 until July 2011, the 4th year of the service. 103 questionnaires returned, all useable, from 216 sent out across 4 community clinic sites. The 48% return rate was consistent across all sites. The findings were grouped together rather than presented by clinic, due to lack of response variation by site. Verbatim comments were recorded. Returns from colon cancer patients were 75% of the total (47% M, 28% F) &amp; 25% prostate patients. Median age 71, range 41 - 90 years. Travel was by car 87%, foot 8% &amp; public transport 5%. Topics covered included, own health 96%, appt times 79%, tests &amp; results 75%, patient support 37%, carer support 12% &amp; 'other' 16%. Ranking of statements suggests 90% satisfaction with administration &amp; 94% quality of clinic, and 85% prefer local proximity of clinic. Only 36% accompanied to clinic, less than when at central clinic. Only 8% expressed concerns, usually about scan results. Conclusions: an overwhelmingly positive patient evaluation provides evidence that non-specialist community nurses can deliver a follow up service in the community for potentially cured colon (&amp; prostate) cancer patients.
Safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HGS1029, an inhibitor of apoptosis protein (IAP) inhibitor, in patients (Pts) with advanced solid tumors: Results of a phase I study.
Authors: B. I. Sikic, S. G. Eckhardt, G. Gallant, H. A. Burris, D. R. Camidge, A. D. Colevas, S. F. Jones, W. A. Messersmith, H. A. Wakelee, H. Li, P. G. Kaminker, S. Morris, J. R. Infante
Journal: Journal of Clinical Oncology (2011)

3008 Background: IAPs are key regulators of cancer cell survival, which makes them appealing targets for cancer therapy. HGS1029 is a small molecule IAP inhibitor which directly kills tumor cells as a single-agent or in combination. Methods: The safety, PK and PD (various cytokines and apoptotic markers) of HGS1029, given as a 15 min IV infusion with Schedule (Sch) A (Day 1, 8 and 15 every 28D) and then Sch B (continuous weekly) were evaluated in pts with advanced solid tumors. Results: 44 pts (20 females, 24 males) with a median age of 62 years (range: 41-88) have been enrolled in 10 cohorts (Sch A: 0.1, 0.2, 0.4, 0.6, 0.9, 1.4, 2.1 and 3.2 mg/m2; Sch B: 3.2 and 4.8 mg/m2). Dose-limiting toxicities (DLTs) were observed in 1/9 pts at 1.4 mg/m2 (Grade (G) 3 AST, G3 amylase, G4 lipase, and G3 fatigue) and in 2/6 pts at 4.8 mg/m2 (G3 fatigue, prolonged asymptomatic G4 amylase and lipase). The most frequent adverse events (typically mild to moderate in severity), reported to be at least possibly related to HGS1029, include nausea (33%), anorexia (21%), pyrexia (21%), vomiting (19%), diarrhea (17%), fatigue (17%), and rash (12%). HGS1029 produced a dose-dependent short-lived lymphocytopenia and a transient neutrophilia. Confirmed tumor regression has been observed in a pretreated pt with colon cancer and 2 pts (NSCLC, adrenocortical carcinoma) had stable disease for > 6 months. Plasma HGS1029 concentration-time profiles suggest a linear PK across the dose range. At ≥ 1.4 mg/m2, the disposition of HGS1029 follows a 3 compartment model with a terminal half life ≥ 4.8 hrs. The levels of cIAP-1, an IAP family member, were profoundly reduced in PBMC's after a single administration of HGS1029. The greatest elevations of the cytokine MCP-1 were observed in the highest dose cohorts. Two-fold increases in baseline M30 levels, indicating a possible apoptotic response, were also observed in the serum of several pts. Conclusions: HGS1029 has been well tolerated in pts with advanced solid malignancies. DLTs include severe fatigue, elevated amylase and lipase. Based on this favorable safety profile, combination studies with mapatumumab and chemotherapies are warranted.
Could the PD-1 pathway be a potential target for treating small intestinal adenocarcinoma?
Authors: Chanjuan Shi, Ramya Thota, Jordan Berlin
Journal: Journal of Clinical Oncology (2016)

233 Background: The programmed death 1 (PD-1) pathway is up-regulated in the immune microenvironment of many cancers. PD-1 blockage has been shown to be effective in treating some malignancies. In colorectal cancers, inhibition of PD-1 pathway appears to be selectively efficacious in microsatellite instable (MSI) tumors. In this study, we examined the immune microenvironment of small intestinal adenocarcinoma by immunohistochemistry. Methods: Twenty two small intestinal adenocarcinomas were identified from our Pathology Archives from 01/01/2002 to 05/01/2014. Immunohistochemical studies were employed to evaluate expression of CD3, CD4, CD8, CD20, CD56, PD-1 and programmed death ligand 1 (PD-L1). CD3+, CD4+, and CD8+ T cells were estimated under high power fields (HPF) and compared between PD-L1+ and PD-L1- tumors. Results: The 22 cases included 9 females and 13 males, with age ranging from 38 to 92 years. PD-1 was expressed in 18 of 22 (82%) cases, by tumor surrounding lymphocytes and lymphoid aggregates as well as tumor infiltrating lymphocytes if present. PD-L1 expression was observed in 10 of 22 (45%) cases, including 2 MSI, 2 microsatellite stable (MSS) and 6 tumors with unknown MSI status. PD-L1 was mainly expressed by histiocytes capping cancerous glands/nests at the infiltrating front. Expression of PD-L1 was also seen in tumor cells surrounding by the histiocytic caps. All the 10 cancers also expressed PD-1. The tumors expressing PD-L1 contained more CD3+ (440±22/HPF versus 238±31/HPF, p &lt; 0.01), CD4+ (172±26/HPF versus 287±25/HPF, p &lt; 0.01) and CD8+ T cells (58±17/HPF versus 153±33/HPF, p = 0.013) than those without expression of PD-L1. CD20+ cells were mainly seen in lymphoid aggregates. There were rare or none C56+ inflammatory cells. Conclusions: PD-1 and PD-L1 are expressed by inflammatory cells (mainly histiocytes) and tumors cells in most small intestinal adenocarcinoma. Blockage of the PD-1 pathway should be evaluated in the treatment of small intestinal adenocarcinomas.