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

Abstract

A B S T R A C T PurposeRelapse-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 MethodsThe 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 ϭ .1), bone scan (36%; P Ͻ .001), and BM histology (34%; P Ͻ .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 ϭ .04) and 0% to 6% of patients for each of the other studies (P Ͻ .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 Ͻ .001) and from diagnosis (P ϭ .002). They also had significantly longer survival than patients with symptomatic relapses (P ϭ .002). Conclusion123 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.

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2immunotherapy and isotretinoin: a prospective Phase II study

“…Achieving a minimal disease state (CR/ VGPR) after relapse remains a challenge but may be facilitated through close monitoring of disease status: asymptomatic, limited relapse may be more amenable to control than symptomatic, widespread, and bulky relapsed disease. 44 Greater anti-NB activity is a possibility with new generations of antibody-based immunotherapy 26,45,46 and other targeted therapies. 40 47 Major organ toxicity had to be grade 2 by Common Terminology Criteria for Adverse Events Version 2.0 (CTCAEv2.0), although neutrophil count 500/ml and platelet count 10,000/ml were acceptable.…”

“…32 Extent-of-disease evaluations Disease status was assessed every 3 months for 24 months by histology of BM aspirates and biopsies obtained from bilateral posterior and bilateral anterior iliac crests, 123 I-MIBG scan, and computed tomography or magnetic resonance imaging of chest/abdomen/pelvis and head. 44 Disease status was defined by INRC, 47 modified to incorporate 123 I-MIBG findings as follows: CR: no evidence of NB, including normal 123 I-MIBG scan; VGPR: volume of primary mass reduced >90%, normal 123 I-MIBG scan, BM(¡) by histology, normal catecholamine levels; PD: new lesion or >25% increase in an existing lesion.…”

Recurrent Neuroblastoma

“…In a recent study of 91 high-risk patients with asymptomatic relapse, 123 I-MIBG scan was reported to have the highest sensitivity (82%) of detecting unsuspected relapse, compared with bone scan, bone marrow examination, CT (head), CT (chest/abdomen/pelvis), and urine catecholamines, with sensitivities of 27%, 28%, 22%, 29%, and 18%, respectively (Kushner et al, 2009). 123 I-MIBG scan was the sole indicator of unsuspected relapse in 27% of patients, whereas CT chest/abdomen/pelvis was the only positive test in 6% of patients, CT head in 3% of patients, bone marrow histology in 4.5% of patients, bone scan in 3% of patients, and urine catecholamines in none of the patients.…”

“…Patients can present with nausea, vomiting, headaches, seizures, drowsiness, cranial nerve symptoms, motor weakness/paralysis, and back pain (Matthay et al, 2003a). Fifty percent of relapses present within 18 months from diagnosis and 77% by 24 months (Kushner et al, 2009;Lau et al, 2004;London & Castel et al, 2011;Santana et al, 2008). For CNS recurrence, the median time of relapse was 12 to 20 months (Kellie et al, 1991;Kramer et al, 2001;Matthay et al, 2003a;Shaw & Eden, 1992).…”

“…Other symptoms from distant metastases include lethargy, irritability, soft tissue mass arising from bony involvement of the calvarium, periorbital ecchymosis (raccoon eye), pallor and bruising from bone marrow infiltration and cytopenia, and soft tissue mass from lymph node metastases. Depending on the frequency of follow-up and the type of investigations used to monitor relapse, 30 to 73% of patients are asymptomatic at relapse (Kushner et al, 2009;Lau et al, 2004 Table 1. Characteristics of 31 relapsed NB patients from a single institution (Lau et al, 2004) While central nervous system (CNS) disease is very rare at diagnosis, CNS recurrence has been reported in 1 to 5% of all patients with Stage 4 NB (Kellie et al, 1991;Kramer et al, 2001;Matthay et al, 2003a;Shaw & Eden, 1992).…”