6 results on '"Kristen Ciombor"'
Search Results
2. Data from Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer
- Author
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Gregory B. Lesinski, Tanios Bekaii-Saab, Miguel Villalona-Calero, Anne M. Noonan, Daniel Ahn, Sanaa Tahiri, Kristen Ciombor, Christina Wu, Sameh Mikhail, Susan Geyer, Thomas A. Mace, and Matthew R. Farren
- Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate Experimental Design: Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.Results: Higher baseline levels of the immunosuppressive cytokines IL6 and IL10 were strongly associated with poorer OS (P = 0.008 and 0.026, respectively; HR = 1.16 and 1.28, respectively), whereas higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS (P = 0.045; HR = 0.69). Patients with a greater proportion of antigen-experienced T cells (CD45RO+) had longer OS (CD4 P = 0.032; CD8 P = 0.036; HR = 0.36 and 0.61, respectively). Although greater expression of the T-cell checkpoint molecule CTLA-4 on CD8+ T cells was associated with significantly shorter OS (P = 0.020; HR = 1.53), the TIM3 molecule had a positive association with survival when expressed on CD4+ T cells (P = 0.046; HR = 0.62).Conclusions: These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-naïve metastatic PDAC patients to date. Clin Cancer Res; 22(10); 2565–74. ©2015 AACR.
- Published
- 2023
3. Supplementary Materials from Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer
- Author
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Gregory B. Lesinski, Tanios Bekaii-Saab, Miguel Villalona-Calero, Anne M. Noonan, Daniel Ahn, Sanaa Tahiri, Kristen Ciombor, Christina Wu, Sameh Mikhail, Susan Geyer, Thomas A. Mace, and Matthew R. Farren
- Abstract
Table S1. Antibodies used for flow cytometry Table S2. Monte Carlo cross-validation of continuous measure markers. Table S3. Monte Carlo cross-validation of dichotomous measure markers. Table S4. Pancreatic cancer patient circulating immune cell frequencies Figure S1. Overall survival does not predict plasma MCP-1 levels
- Published
- 2023
4. Next generation sequencing survey of biliary tract cancer (BTC) reveals the association between tumor somatic variants and chemotherapy resistance
- Author
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Daniel H, Ahn, Milind, Javle, Chul W, Ahn, Apurva, Jain, Sameh, Mikhail, Anne M, Noonan, Kristen, Ciombor, Christina, Wu, Rachna T, Shroff, James L, Chen, and Tanios, Bekaii-Saab
- Subjects
Adult ,Aged, 80 and over ,Male ,Organoplatinum Compounds ,Middle Aged ,Prognosis ,Deoxycytidine ,Gemcitabine ,Cyclin-Dependent Kinases ,Disease-Free Survival ,Article ,Young Adult ,Biliary Tract Neoplasms ,Treatment Outcome ,Drug Resistance, Neoplasm ,Surveys and Questionnaires ,Antineoplastic Combined Chemotherapy Protocols ,Mutation ,Humans ,Female ,Aged - Abstract
Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS).When genes with an incidence 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached.In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.
- Published
- 2016
5. Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma.
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Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, Ramanathan RK, Goyal L, Sadeghi S, Macarulla T, El-Khoueiry A, Kelley RK, Borbath I, Choo SP, Oh DY, Philip PA, Chen LT, Reungwetwattana T, Van Cutsem E, Yeh KH, Ciombor K, Finn RS, Patel A, Sen S, Porter D, Isaacs R, Zhu AX, Abou-Alfa GK, and Bekaii-Saab T
- Subjects
- Administration, Oral, Adult, Aged, Antineoplastic Agents adverse effects, Bile Duct Neoplasms genetics, Bile Duct Neoplasms mortality, Bile Duct Neoplasms pathology, Cholangiocarcinoma genetics, Cholangiocarcinoma mortality, Cholangiocarcinoma secondary, Disease Progression, Drug Administration Schedule, Gene Amplification, Gene Fusion, Genetic Predisposition to Disease, Humans, Middle Aged, Mutation, Phenotype, Phenylurea Compounds adverse effects, Progression-Free Survival, Prospective Studies, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Receptor, Fibroblast Growth Factor, Type 2 antagonists & inhibitors, Time Factors, Antineoplastic Agents administration & dosage, Bile Duct Neoplasms drug therapy, Biomarkers, Tumor genetics, Cholangiocarcinoma drug therapy, Phenylurea Compounds administration & dosage, Protein Kinase Inhibitors administration & dosage, Pyrimidines administration & dosage, Receptor, Fibroblast Growth Factor, Type 2 genetics
- Abstract
Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.
- Published
- 2018
- Full Text
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6. Adjuvant Chemoradiotherapy With Epirubicin, Cisplatin, and Fluorouracil Compared With Adjuvant Chemoradiotherapy With Fluorouracil and Leucovorin After Curative Resection of Gastric Cancer: Results From CALGB 80101 (Alliance).
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Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, Enzinger PC, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Gunderson LL, Goldberg RM, Venook AP, Ilson D, O'Reilly E, Ciombor K, Berg DJ, Meyerhardt J, and Mayer RJ
- Subjects
- Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, Cisplatin administration & dosage, Combined Modality Therapy, Epirubicin administration & dosage, Female, Fluorouracil administration & dosage, Humans, Leucovorin administration & dosage, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Risk Factors, Stomach Neoplasms pathology, Survival Rate, Treatment Outcome, United States, Adenocarcinoma therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemoradiotherapy, Adjuvant, Esophagogastric Junction, Stomach Neoplasms therapy
- Abstract
Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma, Intergroup Trial 0116 (Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction adenocarcinoma: Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil (FU) and leucovorin (LV) compared with surgery alone. CALGB 80101 (Alliance; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival. Patients and Methods Between April 2002 and May 2009, 546 patients who had undergone a curative resection of stage IB through IV (M0) gastric or gastroesophageal junction adenocarcinoma were randomly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy (FU plus LV arm) or postoperative epirubicin, cisplatin, and infusional FU (ECF) before and after combined FU and radiotherapy (ECF arm). Results With a median follow-up duration of 6.5 years, 5-year overall survival rates were 44% in the FU plus LV arm and 44% in the ECF arm ( P
logrank = .69; multivariable hazard ratio, 0.98; 95% CI, 0.78 to 1.24 comparing ECF with FU plus LV). Five-year disease-free survival rates were 39% in the FU plus LV arm and 37% in the ECF arm ( Plogrank = .94; multivariable hazard ratio, 0.96; 95% CI, 0.77 to 1.20). In post hoc analyses, the effect of treatment seemed to be similar across all examined patient subgroups. Conclusion After a curative resection of gastric or gastroesophageal junction adenocarcinoma, postoperative chemoradiotherapy using a multiagent regimen of ECF before and after radiotherapy does not improve survival compared with standard FU and LV before and after radiotherapy.- Published
- 2017
- Full Text
- View/download PDF
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