Treatment Response
One patient died of tumor progression and tumor bleeding within 6 weeks of initiation of IREC. As the best overall response for the remaining 42 patients, partial response (PR), stable disease, progressive disease (PD) were observed in 1 (2%), 37 (86%), and 4 (9%) patients, respectively (Table 2 ). In one patient (UPN4) who achieved PR, Iodine 123 (123I) metaiodobenzylguanidine (MIBG) scintigraphy showed disappearance of MIBG uptake in the bone marrow metastases after the first cycle of IREC, and remained negative until the end of three cycles (Figure 1 ).
In 34 of 43 (79%) patients, bone marrow minimal residual disease (MRD) was measured by quantitative PCR for TH and PHOX2B genes using bone marrow specimens; at baseline (before IREC therapy), 14 patients were MRD positive and 20 were MRD-negative. Five of the 14 patients who were MRD positive at baseline became MRD-negative after IREC therapy. Of the 20 patients who were MRD-negative at baseline, 17 remained negative and 3 patients became MRD positive during IREC therapy.