Assessment of the influence of preoperative chemotherapy in patients with osteosarcoma by dynamic contrast- enhanced MRI using pharmacokinetic modeling M. Egmont-Petersen * , P.C.W. Hogendoorn ** , R.J. van der Geest * , J.L. Bloem *** , J.H.C. Reiber * *) Division of Image Processing, Dept. of Radiology, **) Dept. of Pathology, ***) Dept. of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands Email: michael@lkeb.azl.nl Abstract. A novel method is introduced for predicting the effect of preopera- tive chemotherapy in patients with osteosarcoma. The method is based on the histogram of wash-in rates as estimated by fitting a pharmacokinetic model to each voxel within a region of interest. The 80-percentile of this histogram is the best predictor for the effect of chemotherapy; among 7 good and 13 poor responders solely 4 were predicted wrongly. The kappa measure is 0.560, and is significantly different from zero with a p-value smaller than, p<0.01. Our gold standard is the pathologic specimen from which the response to chemo- therapy is assessed, above/below 10% viable remnant tumor. 1 Introduction The effect of preoperative (neoadjuvant) chemotherapy on high-grade bone tumors is an important prognostic indicator for the expected survival rate of patients. Patients for whom the preoperative chemotherapy resulted in less than 10% viable tumor - so-called good responders - have significantly better prospects for five-year survival than patients with more than 10% viable remnant tumor. An earlier study indicated a high correspondence between the presence of viable remnant bone tumor and a fast up-take of paramagnetic tracer (Gd-DTPA) in pa- tients with Ewing’s sarcoma [1]. This is caused by the disposition of Ewing’s sar- coma to form isolated islands (remnants), which can clearly be distinguished on a macroscopic level in histologic specimen of the postoperative tumor due to their intense basophilic properties. Osteosarcoma, on the other hand, exhibits a different reaction to preoperative chemotherapy resulting in microscopic nests with viable remnant tumor that interwove areas with necrosis, granulation tissue and normal bone cortex. It is hard to assess quantitatively the amount of viable remnant tumor in preoperative MR-images of patients with osteosarcoma because of this intermingling pattern of viable and necrotic areas. To circumvent this problem, we introduce dif- ferent aggregate measures for the effect of preoperative chemotherapy in patients with osteosarcoma.