Pediatr Blood Cancer Evaluation of Semi-Quantitative Scoring System for Metaiodobenzylguanidine (mIBG) Scans in Patients With Relapsed Neuroblastoma

Neuroblastoma, the most common extra-cranial solid tumor in children, originates as a primary tumor of the sympathetic nervous system but metastasizes often to bone and bone marrow, resulting in a poor prognosis. Approximately 15% of patients who present with metastatic disease at diagnosis are refractory to induction chemotherapy while 40%will eventually relapse after having a complete response (CR) or partial response (PR) [1]. Intravenous administration of radiolabeled metaiodobenzylguanidine (mIBG), a norepinephrine analog that specifically targets malignant cells of the sympathetic nervous system, is an effective therapy for patients with refractory disease, with response rates of 30–40% [2–8]. Many of the patients who undergo therapy with I-mIBG or other treatments for relapsed neuroblastoma have sites of disease only apparent onmIBG scans or in bonemarrow biopsies and cannot be evaluated by standard response criteria for solid tumors, such as the RECIST criteria [9]. Therefore, a standardized scoring system to predict the clinical response and progression-free survival (PFS) with I-mIBG treatment is needed to help quantitate therapeutic efficacy of agents used in treatment of refractory neuroblastoma. In recent analyses of high-risk, metastatic neuroblastoma, semi-quantitative scoring systems that divide the body into anatomical sections were developed to assign numeric scores to patients’ diagnostic I and I-mIBG scans [10–14]. Assessing extent of disease before, during, and after induction chemotherapy, three studies have shown a correlation between semi-quantitative scores either at diagnosis or during induction with response at the end of induction chemotherapy [10,12,13] while another showed good concordance among scan readers but poor correlation with response [14]. Although some of these studies showed a significant correlation between the change in semi-quantitative score Background. The purpose of this study was to determine the accuracy of two semi-quantitative scoring systems to assess response to I-metaiodobenzylguanidine (mIBG) therapy in recurrent neuroblastoma. Procedures. Diagnostic mIBG scan pairs (n1⁄457) were collected for patients who underwent I-mIBG therapy for relapsed neuroblastoma. Two scoring systems were designated: Method 1, which divided the body into nine segments to view osteomedullary lesions with an additional tenth segment to assess soft tissue involvement; and Method 2, which divided the body into seven segments without a corresponding compartment for soft tissue involvement. Four nuclear medicine physicians independently assigned extension and intensity scores utilizing both methods, and separately recorded their impression of whether the post-therapy scan had improved, not changed, or worsened. Interand intraobserver concordance and correlation with overall response and progression-free survival (PFS) were performed. Results. Method 1 produced the highest inter-observer concordance and was used to calculate the relative extension scores (post-therapy score divided by pre-therapy score), which correlated significantly with overall response. Patients who achieved complete response (CR) or partial response (PR) (n1⁄421) had lower relative extension scores, compared to those without response (P<0.001). The readers’ overall impression associated highly (P< 0.001) with the relative extension scores though results were less quantitative. Concordance was higher if initial scores were >5. Relative extension score did not predict PFS. Conclusion. Semi-quantitative scoring of mIBG scans provides a more reliable method of assessing response in patients with relapsed neuroblastoma than qualitative impression. The reproducibility and high inter-observer concordance makes mIBG score an important component of overall response criteria in patients with recurrent neuroblastoma.Pediatr Blood Cancer 2006 Wiley-Liss, Inc.