Fernando Carceller1,2, Neil P Jerome3,4, Lucy A Fowkes5, Komel Khabra6,7, Andrew Mackinnon5, Francisco Bautista8, Lynley V Marshall1,2, Sucheta Vaidya1,2, Henry Mandeville9, Veronica Morgan5, Martin O Leach3, Dow-Mu Koh5. 1. a Paediatric Neuro-Oncology and Drug Development Teams, Children & Young People's Unit , The Royal Marsden NHS Foundation Trust , London , UK. 2. b Division of Clinical Studies and Cancer Therapeutics , The Institute of Cancer Research , London , UK. 3. c Cancer Research UK Cancer Imaging Centre , The Institute of Cancer Research , London , UK. 4. d Department of Circulation and Medical Imaging , NTNU - Norwegian University of Science and Technology , Trondheim , Norway. 5. e Department of Radiology , The Royal Marsden NHS Foundation Trust , London , UK. 6. f The Royal Marsden NHS Foundation Trust , Research Data Management and Statistics Unit , London , UK. 7. g MRC Clinical Trials Unit, University College London , London , UK. 8. h Paediatric Oncology Unit, Hospital Niño Jesús , Madrid , Spain. 9. i Department of Radiotherapy , The Royal Marsden NHS Foundation Trust , London , UK.
Abstract
Objectives: Diffusion-weighted magnetic resonance imaging (DW-MRI) offers potential to monitor response and predict survival in high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). We hypothesized that post-radiotherapy DW-MRI may provide prognostic imaging biomarkers in children and young adults with these tumors. Methods: Patients aged ≤21 years diagnosed between 2005 and 2012 were eligible. The tumor median apparent diffusion coefficient (ADC) and its 5th percentile (C5-ADC) were determined at the first post-radiotherapy scan and at the time of radiological progression. DW-MRI parameters were correlated with survival endpoints, temozolomide use and pseudoprogression, when it occurred. Results: Out of 40 patients (20 HGG, 20 DIPG), 23 had evaluable DW-MRI post-radiotherapy and 25 at radiological progression. There were 6 episodes of pseudoprogression. Hazard ratios (95%CI) for progression-free survival were 0.998 (0.993-1.003) for median ADC and 1.003 (0.996-1.010) for C5-ADC. Hazard ratios (95%CI) for overall survival were 1.0009 (0.996-1.006) for median ADC and 0.998 (0.992-1.004) for C5-ADC. Post-radiotherapy median and C5-ADC values were not significantly different between patients treated with radiotherapy alone versus radiotherapy/temozolomide. The median and C5-ADC values were not significantly different at the time of pseudoprogression compared to those at tumor progression. Conclusions: Post-radiotherapy median ADC and C5-ADC were not prognostic, nor able to differentiate radiosensitization with temozolomide or occurrence of pseudoprogression in this cohort of HGG and DIPG patients. Further exploration of alternative DW parameters, study timepoints or data modeling may contribute to the development of prognostic/predictive imaging biomarkers for children and young adults with HGG or DIPG.
Objectives: Diffusion-weighted magnetic resonance imaging (DW-MRI) offers potential to monitor response and predict survival in high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). We hypothesized that post-radiotherapy DW-MRI may provide prognostic imaging biomarkers in children and young adults with these tumors. Methods:Patients aged ≤21 years diagnosed between 2005 and 2012 were eligible. The tumor median apparent diffusion coefficient (ADC) and its 5th percentile (C5-ADC) were determined at the first post-radiotherapy scan and at the time of radiological progression. DW-MRI parameters were correlated with survival endpoints, temozolomide use and pseudoprogression, when it occurred. Results: Out of 40 patients (20 HGG, 20 DIPG), 23 had evaluable DW-MRI post-radiotherapy and 25 at radiological progression. There were 6 episodes of pseudoprogression. Hazard ratios (95%CI) for progression-free survival were 0.998 (0.993-1.003) for median ADC and 1.003 (0.996-1.010) for C5-ADC. Hazard ratios (95%CI) for overall survival were 1.0009 (0.996-1.006) for median ADC and 0.998 (0.992-1.004) for C5-ADC. Post-radiotherapy median and C5-ADC values were not significantly different between patients treated with radiotherapy alone versus radiotherapy/temozolomide. The median and C5-ADC values were not significantly different at the time of pseudoprogression compared to those at tumor progression. Conclusions: Post-radiotherapy median ADC and C5-ADC were not prognostic, nor able to differentiate radiosensitization with temozolomide or occurrence of pseudoprogression in this cohort of HGG and DIPGpatients. Further exploration of alternative DW parameters, study timepoints or data modeling may contribute to the development of prognostic/predictive imaging biomarkers for children and young adults with HGG or DIPG.
Authors: S Vajapeyam; D Brown; C Billups; Z Patay; G Vezina; M S Shiroishi; M Law; P Baxter; A Onar-Thomas; J R Fangusaro; I J Dunkel; T Y Poussaint Journal: AJNR Am J Neuroradiol Date: 2020-04-02 Impact factor: 4.966