Fig. 2

– Response, recurrence, and CED analysis. (A) Relative tumor volume normalized to the moment of study inclusion of all treated patients with available data. (B, D, F) Individual patient data showing tumor volume in the three patients showing response or stable disease (patient 1, 2, and 15), before and after hrBMP4 treatment. The dotted line indicates the moment of treatment with hrBMP4. (C, E, G) Representative images of the three patients with the best therapeutic response before study inclusion and at 3, 6- and 9-month follow-up. (H) Illustration of hrBMP4 CED concept. (I, J) Preoperative drug distribution planning, planning the simulated drug distribution over time (concentric green rings). (K, L) Postoperative 3D reconstructions showing tumor (red), CED catheters (white), and the ventricular system (blue). (M) Vd/Vi at 24 h of hrBMP4 infusion (gray) and at the end of infusion (black). (N) Coverage of tumor and peritumoral volume at the end of hrBMP4 infusion. (O) Analysis of recurrence location in relation to the volume of hrBMP4 infusion, showing the limited overlap (white) between hrBMP4 treated parenchymal volume (yellow) and recurrence volume (light blue). (P) Representative examples of overlap (white) between gadolinium/hrBMP4 distribution volume (yellow) and recurrence volume (blue), showing that the recurrent tumors largely grew outside of the hrBMP4 treated volume (colors match those in Fig. 2O).