Circulating free tumor DNA copy number index (CNI) as a predictor of therapeutic response in pancreatic ductal adenocarcinomas (PDAC)
| العنوان: | Circulating free tumor DNA copy number index (CNI) as a predictor of therapeutic response in pancreatic ductal adenocarcinomas (PDAC) |
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| المؤلفون: | Jana Bergelin, Ekkehard Schütz, Tomislav Dragovich, Howard B. Urnovitz, Patricia Lucente, Madappa N. Kundranda, Boris G. Naraev, Marie Conn, Julia Beck, John Chang |
| المصدر: | Journal of Clinical Oncology. 37:261-261 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, business.industry, Tumor burden, Patient specific, chemistry.chemical_compound, chemistry, Internal medicine, medicine, Pancreatic carcinoma, business, DNA |
| الوصف: | 261 Background: Cell-free tumor DNA (cfDNA) has potential to provide minimally invasive patient specific biomarkers to monitor tumor burden. Tumor-specific copy number instability (CNI) are used to quantify tumor-derived cfDNA in the plasma. We prospectively computed CNI Scores of cfDNA to compare with radiological and Ca 19-9 responses. Methods: In a laboratory blinded, prospective single-institution study, 119 plasma samples from 33 patients (pts) with PDAC were analyzed. Time-points were at baseline (C1), 2nd (C2) and 3rd (C3) cycle of systemic therapy. Tumor cfDNA was measured with a CNI scoring assay that quantifies cfDNA with somatic macro-alterations. CNI Score (CNIs) of 31 was defined as ref. range (97.5 % - control group; N = 135), pts below this threshold were censored. Progression of disease (PD) defined as C3 CNIs > 93 (3-fold threshold) and difference to the baseline > 31 (dispersion of reference population). Mutant KRAS in plasma was measured using ddPCR in a subset 22 pts. Pts with an increase of > 0.06% (critical difference) were classified PD. Radiologic imaging results were compared with CNIs and CA19-9 changes from baseline to C3, respectively. Results: By standard radiological imaging 33 pts were classified as: 14 PR/CR, 10 SD, 9 PD. 27/33 pts (81%) were evaluable by CNIs which ranged from decrease of 2017 - increase of 645. The C3 CNI classifier yielded a sensitivity of 86% for predicting PD and 95% for SD/PR/CR. KRAS classification yielded an accuracy of 72%, and only 3/9 PD were accurately predicted (33%). 26/33 pts were secretors evaluable by CA19-9. Only 2/8 PD pts showed increasing values in CA19-9 and 6/8 of evaluable by CNI; 5/6 showed increasing CNI scores. 3/20 deemed as SD on imaging with increasing values of CA19-9 were noted to have decreasing CNIs. CNI Score classification was significantly better than CA19-9 (P = 0.001 and 0.63, respectively). Conclusions: Our evaluation of a comparative study on cfDNA and CA19-9 versus imaging suggest that CNI quantification is potentially a more reliable blood-based marker for early assessment of efficacy to systemic therapy in PDAC. Furthermore, for patients not expressing CA19-9 it could serve as an alternative monitoring aid. |
| تدمد: | 1527-7755 0732-183X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::05a78d7e11b8b813f0d9ec5eea10e1d1 https://doi.org/10.1200/jco.2019.37.4_suppl.261 |
| رقم الأكسشن: | edsair.doi...........05a78d7e11b8b813f0d9ec5eea10e1d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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