Originally published as JCO Early Release 10.1200/JCO.2008.17.6107 on January 26 2009

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Sensitivity of Surveillance Studies for Detecting Asymptomatic and Unsuspected Relapse of High-Risk Neuroblastoma

From the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY.

Corresponding author: Brian H. Kushner, MD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: kushnerb{at}mskcc.org.

Purpose Relapse-free survival (RFS) is a powerful measure of treatment efficacy. We describe the sensitivity of standard surveillance studies for detecting relapse of neuroblastoma (NB).

Patients and Methods The patients were in complete/very good partial remission of high-risk NB; routine monitoring revealed asymptomatic and, therefore, unsuspected relapses in 113 patients, whereas 41 patients had symptoms prompting urgent evaluations. Assessments every 2 to 4 months included computed tomography, iodine-131–metaiodobenzylguanidine ¹³¹I-MIBG; through November 1999) or iodine-123–metaiodobenzylguanidine (¹²³I-MIBG) scan, urine catecholamines, and bone marrow (BM) histology. Bone scan was routine through 2002.

Results ¹²³I-MIBG scan was the most reliable study for revealing unsuspected relapse; it had an 82% detection rate, which was superior to the rates with ¹³¹I-MIBG scan (64%; P = .1), bone scan (36%; P < .001), and BM histology (34%; P < .001). Among asymptomatic patients, ¹²³I-MIBG scan was the sole positive study indicating relapse in 25 (27%) of 91 patients compared with one (4.5%) of 22 patients for ¹³¹I-MIBG scan (P = .04) and 0% to 6% of patients for each of the other studies (P < .001). Patients whose monitoring included ¹²³I-MIBG scan were significantly less likely than patients monitored by ¹³¹I-MIBG scan to have an extensive osteomedullary relapse and had a significantly longer survival from relapse (P < .001) and from diagnosis (P = .002). They also had significantly longer survival than patients with symptomatic relapses (P = .002).

Conclusion ¹²³I-MIBG scan is essential for valid estimation of the duration of RFS of patients with high-risk NB. Without monitoring that includes ¹²³I-MIBG scan, caution should be used when comparing RFS between institutions and protocols.

Supported in part by Grants No. CA61017 and CA72868 from the National Cancer Institute, Bethesda, MD; Hope Street Kids, Alexandria, VA; the Justin Zahn Fund, New York, NY; the Katie's Find a Cure Fund, New York, NY; and the Robert Steel Foundation, New York, NY.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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