Figure 2.

Illustrative case patient 11, a 48-year-old female, who was treated 21 months after GBM diagnosis for a second recurrence at dose level 4 with 1 × 10¹⁰ vp. After 2 weeks, MRI showed a large area with cavity formation suggestive of tumor lysis in the target area of one of the intratumoral catheters used for virus administration [A, T1 after gadolinium prior to treatment and 2 weeks after treatment; B, postoperative neuronavigation screenshot demonstrating the relation of the CED catheter (trajectory in blue) and the necrotic area]. Six weeks after virus infusion her preexisting paresis of the left leg deteriorated due to increasing mass effect of the treated tumor for which she underwent subtotal re-resection. After initial improvement, she deteriorated again 6 weeks later, at this point she declined further diagnostic tests and treatment. She died 106 days after virus infusion. PCR analysis of CSF samples demonstrated increasing virus titers 3 months post-infusion (Fig. 5). The resected tumor material contained besides tumor cells also viral proteins and immune cell infiltrates (Fig. 4B). Our routine tumor cell culture protocol of this tumor failed due to virus-induced lysis of tumor cells. Unfortunately, we were unable to discriminate between true tumorprogression or an inflammatory reaction known as pseudoprogression.