10.3389/fonc.2019.00622.s003
Alessio Amatu
Alessio
Amatu
Marta Schirripa
Marta
Schirripa
Federica Tosi
Federica
Tosi
Sara Lonardi
Sara
Lonardi
Katia Bencardino
Katia
Bencardino
Erica Bonazzina
Erica
Bonazzina
Laura Palmeri
Laura
Palmeri
Damiano Alfio Patanè
Damiano Alfio
Patanè
Elio Gregory Pizzutilo
Elio Gregory
Pizzutilo
Benedetta Mussolin
Benedetta
Mussolin
Francesca Bergamo
Francesca
Bergamo
Giulia Alberti
Giulia
Alberti
Rossana Intini
Rossana
Intini
Letizia Procaccio
Letizia
Procaccio
Marco Arese
Marco
Arese
Silvia Marsoni
Silvia
Marsoni
Michele Nichelatti
Michele
Nichelatti
Vittorina Zagonel
Vittorina
Zagonel
Salvatore Siena
Salvatore
Siena
Alberto Bardelli
Alberto
Bardelli
Fotios Loupakis
Fotios
Loupakis
Federica Di Nicolantonio
Federica
Di Nicolantonio
Andrea Sartore-Bianchi
Andrea
Sartore-Bianchi
Ludovic Barault
Ludovic
Barault
Table_1_High Circulating Methylated DNA Is a Negative Predictive and Prognostic Marker in Metastatic Colorectal Cancer Patients Treated With Regorafenib.pdf
Frontiers
2019
regorafenib
DNA methylation
metastatic colorectal cancer
cell free circulating DNA
liquid biopsy
digital PCR
biomarkers
prognosis
2019-07-12 12:49:39
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_1_High_Circulating_Methylated_DNA_Is_a_Negative_Predictive_and_Prognostic_Marker_in_Metastatic_Colorectal_Cancer_Patients_Treated_With_Regorafenib_pdf/8864237
<p>Background: Regorafenib improves progression free survival (PFS) in a subset of metastatic colorectal cancer (mCRC) patients, although no biomarkers of efficacy are available. Circulating methylated DNA (cmDNA) assessed by a five-gene panel was previously associated with outcome in chemotherapy treated mCRC patients. We hypothesized that cmDNA could be used to identify cases most likely to benefit from regorafenib (i.e., patients with PFS longer than 4 months).</p><p>Methods: Plasma samples from mCRC patients were collected prior to (baseline samples N = 60) and/or during regorafenib treatment (N = 62) for the assessment of cmDNA and total amount of cell free DNA (cfDNA).</p><p>Results: In almost all patients, treatment with regorafenib increased the total cfDNA, but decreased cmDNA warranting the normalization of cmDNA to the total amount of circulating DNA (i.e., cmDNA/ml). We report that cmDNA/ml dynamics reflects clinical response with an increase in cmDNA/ml associated with higher risk of progression (HR for progression = 1.78 [95%CI: 1.01–3.13], p = 0.028). Taken individually, high baseline cmDNA/ml (above median) was associated with worst prognosis (HR for death = 3.471 [95%CI: 1.83–6.57], p < 0.0001) and also predicted shorter PFS (<16 weeks with PPV 86%). In addition, high cmDNA/ml values during regorafenib treatment predicted with higher accuracy shorter PFS (<16 weeks with a PPV of 96%), therefore associated with increased risk of progression (HR for progression = 2.985; [95%CI: 1.63–5.46; p < 0.0001).</p><p>Conclusions: Our data highlight the predictive and prognostic value of cmDNA/ml in mCRC patients treated with regorafenib.</p>