Sensitivity of surveillance studies for detecting asymptomatic and unsuspected relapse of high-risk neuroblastoma

Abstract

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 (131)I-MIBG; through November 1999) or iodine-123-metaiodobenzylguanidine ((123)I-MIBG) scan, urine catecholamines, and bone marrow (BM) histology. Bone scan was routine through 2002.

Results: (123)I-MIBG scan was the most reliable study for revealing unsuspected relapse; it had an 82% detection rate, which was superior to the rates with (131)I-MIBG scan (64%; P = .1), bone scan (36%; P < .001), and BM histology (34%; P < .001). Among asymptomatic patients, (123)I-MIBG scan was the sole positive study indicating relapse in 25 (27%) of 91 patients compared with one (4.5%) of 22 patients for (131)I-MIBG scan (P = .04) and 0% to 6% of patients for each of the other studies (P < .001). Patients whose monitoring included (123)I-MIBG scan were significantly less likely than patients monitored by (131)I-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: (123)I-MIBG scan is essential for valid estimation of the duration of RFS of patients with high-risk NB. Without monitoring that includes (123)I-MIBG scan, caution should be used when comparing RFS between institutions and protocols.

Fig 1.

Iodine-123–metaiodobenzylguanidine scan showing focal tracer activity in left distal femur of an asymptomatic 7.2-year-old girl who was 34 months from diagnosis. Concurrent routine surveillance studies, including bone marrow histology and urine catecholamines, showed no evidence of neuroblastoma. Magnetic resonance imaging demonstrated an intramedullary lesion. She is in second complete remission 17+ months later. L, left; R, right.

Fig 2.

Survival from time of relapse of patients with unsuspected relapse detected by monitoring that included iodine-123–metaiodobenzylguanidine (¹²³I-MIBG) scans (blue line), unsuspected relapse detected by monitoring that included iodine-131–metaiodobenzylguanidine (¹³¹I-MIBG) scans (gray line), and symptomatic relapse (gold line; P < .001).

Fig 3.

Survival from diagnosis of patients in first complete remission/very good partial remission with unsuspected relapse detected by monitoring that included iodine-123–metaiodobenzylguanidine (¹²³I-MIBG) scans (blue line), unsuspected relapse detected by monitoring that included iodine-131–metaiodobenzylguanidine (¹³¹I-MIBG) scans (gray line), and symptomatic relapse (gold line; P = .002).