Reply to K. Satharasinghe et al

In our report, we did not discuss how relapses were documented— we assumed it would be self-evident that they must be confirmed unequivocably before salvage therapy is initiated. Satharasinghe et al raise concern about the 27% of patients whose relapse was detected only by iodine-123 (I) metaiodobenzylguanidine (MIBG) scan. Among those 25 patients, 24 had abnormal radiotracer uptake in one or more osteomedullary sites and one patient had new uptake in a small postoperative paraspinal site. Relapse was deemed unequivocal when multiple skeletal sites of abnormal MIBG uptake were present (n 7). In contrast, with a single new abnormal MIBG-avid osteomedullary site (n 17), the finding was judged as indicative of relapse only after magnetic resonance imaging revealed a corresponding lesion and follow-up MIBG scan remained abnormal (by which time other staging studies often also showed new disease). The paraspinal relapse was confirmed by disease resection after follow-up I-MIBG scintigraphy remained abnormal. None of the above patients had the most common form of I-MIBG false positivity, that is, uptake in the abdomen after retroperitoneal tumors are resected and renal function is impaired, leading to delayed or altered excretion of the radiotracer. Uncertainty in these situations is rare with tomographic (SPECT) imaging techniques or fusion MIBG/computed tomography (CT) that correlate uptake to anatomy; hybrid [F]fluorodeoxyglucose-positron emission tomography/CT can also be helpful in clarifying disease status. Relapse of high-risk neuroblastoma (NB) has long been viewed as a systemic event and tantamount to eventual death from disease or toxicity of retrieval therapy. Developments in the past decade, however, raise the welcome possibility that the absolute equivalence between relapse in these patients and a lethal outcome may no longer hold true. Thus, close monitoring using sensitive techniques may now be detecting focal or well-localized relapses. These might be controlled by surgery and/or radiotherapy, supplemented by relatively nontoxic systemic therapies that are noncrossresistant with prior treatments. For patients with no evidence of disease after treatment of highrisk NB, we continue to advocate close monitoring for recurrence. Despite being the most common study to reveal unsuspected relapse, I-MIBG scan was falsely negative in 16% of cases. Clearly, this scintigraphic evaluation cannot serve as a “stand-alone surveillance test” but should be part of a battery of tests required for accurately assessing relapse-free survival.