Cell-free DNA in newly diagnosed patients with glioblastoma – a clinical prospective feasibility study

// Dorte Schou Nørøxe 1 , 2 , Olga Østrup 3 , Christina Westmose Yde 3 , Lise Barlebo Ahlborn 3 , Finn Cilius Nielsen 3 , Signe Regner Michaelsen 1 , Vibeke Andrée Larsen 4 , Jane Skjøth-Rasmussen 5 , Jannick Brennum 5 , Petra Hamerlik 6 , Hans Skovgaard Poulsen 1 , 2 and Ulrik Lassen 2 1 Department of Radiation Biology, Rigshospitalet, 2100 Copenhagen, Denmark 2 Department of Oncology, Rigshospitalet, 2100 Copenhagen, Denmark 3 Center for Genomic Medicine, Rigshospitalet, 2100 Copenhagen, Denmark 4 Department of Neuroradiology, Rigshospitalet, 2100 Copenhagen, Denmark 5 Department of Neurosurgery, Rigshospitalet, 2100 Copenhagen, Denmark 6 Danish Cancer Society, 2100 Copenhagen, Denmark Correspondence to: Dorte Schou Nørøxe, email: anne.dorte.schou.noeroexe@regionh.dk Keywords: glioblastoma; liquid biopsy; cell-free DNA; fragment length; base-pair Received: March 10, 2019 Accepted: May 29, 2019 Published: July 09, 2019 ABSTRACT Background: Glioblastoma (GB) is an incurable brain cancer with limited treatment options. The aim was to test the feasibility of using cell-free DNA (cfDNA) to support evaluation of treatment response, pseudo-progression and whether progression could be found before clinical and/or radiologic progression. Results: CfDNA fluctuated during treatment with the highest levels before diagnostic surgery and at progression. An increase was seen in 3 out of 4 patients at the time of progression while no increase was seen in 3 out of 4 patients without progression. CfDNA levels could aid in 3 out of 3 questionable cases of pseudo-progression. Methods: Eight newly diagnosed GB patients were included. Blood samples were collected prior to diagnosis, before start and during oncologic treatment until progression. Seven patients received concurrent radiotherapy/Temozolomide with adjuvant Temozolomide with one of the patients included in a clinical trial with either immunotherapy or placebo as add-on. One patient received radiation alone. CfDNA concentration was determined for each blood sample. Conclusions: It was feasible to measure cfDNA concentration. Despite the limited cohort size, there was a good tendency between cfDNA and treatment course and -response, respectively with the highest levels at progression.