Non-invasive intravoxel incoherent motion MRI in prediction of histopathological response to neoadjuvant chemotherapy and survival outcome in osteosarcoma at the time of diagnosis.

ABSTRACT

BACKGROUND: Early prediction of response to neoadjuvant chemotherapy (NACT) is important to aid personalized treatment in osteosarcoma. Diffusion-weighted Intravoxel Incoherent Motion (IVIM) MRI was used to evaluate the predictive value for response to NACT and survival outcome in osteosarcoma. METHODS: Total fifty-five patients with biopsy-proven osteosarcoma were recruited prospectively, among them 35 patients were further analysed. Patients underwent 3 cycles of NACT (Cisplatin + Doxorubicin) followed by surgery and response adapted adjuvant chemotherapy. Treatment outcomes were histopathological response to NACT (good-response ≥ 50% necrosis and poor-response < 50% necrosis) and survival outcome (event-free survival (EFS) and overall survival (OS)). IVIM MRI was acquired at 1.5T at baseline (t0), after 1-cycle (t1) and after 3-cycles (t2) of NACT. Quantitative IVIM parameters (D, D*, f & D*.f) were estimated using advanced state-of-the-art spatial penalty based IVIM analysis method bi-exponential model with total-variation penalty function (BETV) at 3 time-points and histogram analysis was performed. RESULTS: Good-responders Poor-responders ratio was 13 (37%)22 (63%). EFS and OS were 31% and 69% with 16.27 and 25.9 months of median duration respectively. For predicting poor-response to NACT, IVIM parameters showed AUC = 0.87, Sensitivity = 86%, Specificity = 77% at t0, and AUC = 0.96, Sensitivity = 86%, Specificity = 100% at t1. Multivariate Cox regression analysis showed smaller tumour volume (HR = 1.002, p = 0.001) higher ADC-25th-percentile (HR = 0.047, p = 0.005) & D-Mean (HR = 0.1, p = 0.023) and lower D*-Mean (HR = 1.052, p = 0.039) were independent predictors of longer EFS (log-rank p-values 0.054, 0.0034, 0.0017, 0.0019 respectively) and non-metastatic disease (HR = 4.33, p < 10-3), smaller tumour-volume (HR = 1.001, p = 0.042), lower D*-Mean (HR = 1.045, p = 0.056) and higher D*.f-skewness (HR = 0.544, p = 0.048) were independent predictors of longer OS (log-rank p-values < 10-3, 0.07, < 10-3, 0.019 respectively). CONCLUSION: IVIM parameters obtained with a 1.5T scanner along with novel BETV method and their histogram analysis indicating tumour heterogeneity were informative in characterizing NACT response and survival outcome in osteosarcoma.