Prognostic value of baseline and early changes of circulating-free (cf) and circulating tumor (ct) DNA in the neoadjuvant (NA) setting of early stage colon cancer (CC)
العنوان: | Prognostic value of baseline and early changes of circulating-free (cf) and circulating tumor (ct) DNA in the neoadjuvant (NA) setting of early stage colon cancer (CC) |
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المؤلفون: | Jos Janssens, Giacomo Bregni, Patrick Flamen, Chiara Senti, Lionel D'Hondt, Marylene Clausse, Stéphane Holbrechts, Karen Geboes, Thierry De Grez, Francesco Sclafani, Caroline Vandeputte, T. Besse-Hammer, Alain Hendlisz, Philippe Vergauwe, Jean-Luc Van Laethem, Paraskevas Gkolfakis, Françoise Rothé, Marc Van den Eynde, Elena Acedo Reina, Gauthier Demolin |
المصدر: | Journal of Clinical Oncology. 39:3600-3600 |
بيانات النشر: | American Society of Clinical Oncology (ASCO), 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, Prognostic factor, Stage colon cancer, Oncology, business.industry, Adjuvant chemotherapy, Internal medicine, medicine, Stage (cooking), business, Minimal residual disease, Gastroenterology |
الوصف: | 3600 Background: ctDNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy (CT). No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with NACT. We sought to evaluate the prognostic value of baseline and early changes of cf/ctDNA in stage II-III CC pts who were treated with one cycle of NA FOLFOX CT followed by surgery +/- adjuvant FOLFOX CT in the PePiTA trial. Methods: PePiTA was a multicentre, single-arm, prospective phase II trial testing in vivo tumour chemosensitivity of early stage CC (as assessed by 18F-FDG PET/CT-based metabolic response to one cycle of NA FOLFOX) and its association with long-term outcome (NCT00994864). Plasma samples were prospectively collected at baseline, 2 weeks after one cycle of NA FOLFOX CT, and before surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft v1.6 software (Bio-Rad). Survival outcome measures were 5-year disease-free survival (DFS) and 6-year overall survival (OS). ROC curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with SPSS v25.0 (SPSS Inc.). Results: 80 pts were included (44 ypStage I-II and 36 ypStage III). After a median follow-up of 52.5 months, 5-year DFS and 6-year OS were 68% (95%CI 52-84) and 84% (95%CI 74-94), respectively. Pts with high (≥1600 ng/ml) baseline cfDNA had worse 6-year OS (HR 6.45, 95%CI 1.61-25.84; p = 0.008). Early changes of cfDNA after one cycle of NA FOLFOX CT failed to predict survival (HR DFS 0.96, 95%CI 0.38-2.43; p = 0.92; HR OS 0.62, 95%CI 0.16-2.50; p = 0.50). At baseline, 25 out of 60 (42%) ctDNA-assessable patients were positive. Detectable ctDNA at baseline (HR DFS 2.06, 95%CI 0.65-6.49; p = 0.22; HR OS 3.11, 95%CI 0.57-16.99; p = 0.19) or at any timepoint before surgery (HR DFS 1.65, 95%CI 0.54-5.04; p = 0.38; HR OS 2.80, 95%CI 0.54-14.44; p = 0.22) was not significantly associated with survival. A trend toward a significant association between ctDNA increase at surgery and 5-year DFS was found (HR 3.66, 95%CI 0.81-16.44; p = 0.09). Data on the correlation between early changes of cf/ctDNA and 18F-FDG PET/CT-based metabolic response will be presented at the meeting. Conclusions: For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with NACT. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from FOxTROT-like, NACT treatment strategies. While analysis of ctDNA in this setting did not appear useful to predict prognosis, these results might be secondary to the small sample size. |
تدمد: | 1527-7755 0732-183X |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::d29cd7fc9c63ecb7746fb8b86019ffbe https://doi.org/10.1200/jco.2021.39.15_suppl.3600 |
رقم الأكسشن: | edsair.doi...........d29cd7fc9c63ecb7746fb8b86019ffbe |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15277755 0732183X |
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