Criteria for evaluation of disease extent by (123)I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force

Abstract

Background: Neuroblastoma is an embryonic tumour of the sympathetic nervous system, metastatic in half of the patients at diagnosis, with a high preponderance of osteomedullary disease, making accurate evaluation of metastatic sites and response to therapy challenging. Metaiodobenzylguanidine (mIBG), taken into cells via the norepinephrine transporter, provides a sensitive and specific method of assessing tumour in both soft tissue and bone sites. The goal of this report was to develop consensus guidelines for the use of mIBG scans in staging, response assessment and surveillance in neuroblastoma.

Methods: The International Neuroblastoma Risk Group (INRG) Task Force, including a multidisciplinary group in paediatric oncology of North and South America, Europe, Oceania and Asia, formed a subcommittee on metastatic disease evaluation, including expert nuclear medicine physicians and oncologists, who developed these guidelines based on their experience and the medical literature, with approval by the larger INRG Task Force.

Results: Guidelines for patient preparation, radiotracer administration, techniques of scanning including timing, energy, specific views, and use of single photon emission computed tomography are included. Optimal timing of scans in relation to therapy and for surveillance is reviewed. Validated semi-quantitative scoring methods in current use are reviewed, with recommendations for use in prognosis and response evaluation.

Conclusions: Metaiodobenzylguanidine scans are the most sensitive and specific method of staging and response evaluation in neuroblastoma, particularly when used with a semi-quantitative scoring method. Use of the optimal techniques for mIBG in staging and response, including a semi-quantitative score, is essential for evaluation of the efficacy of new therapy.

Figure 1

(A)¹²³I-mIBG scoring method 1: method 1 divides the skeleton into nine segments to view osteomedullary involvement, and adds a tenth sector that counts any soft tissue involvement to the score. The extension score for method 1 is graded as: 0, no sites per segment; 1, one site per segment; 2, more than one site per segment; and 3, diffuse involvement (>50% of the segment). (B) ¹²³I-mIBG scoring Frappaz-method 2: method 2 divides the skeleton into seven segments. The intensity score for method 2 is graded as: 0, no uptake; 1, doubtful uptake; 2, obvious but mild uptake; 3, strong uptake, with a maximum score of 21. Soft tissue involvement is noted separately from the score. (C) ¹²³I-mIBG scoring SIOPEN-method 3: method 3 divides the skeleton into 12 anatomic segments. The extension score for method 3 is graded as: 0, no sites per segment, 1, one discrete site per segment; 2, two discrete lesions; 3, three discrete lesions; 4, >3 discrete foci or a single diffuse lesions involving <50% of a bone; 5, diffuse involvement of >50–95% whole bone; 6, diffuse involvement of the entire bone.

Figure 2

¹²³I-mIBG scans and semi-quantitative scores on an 8 ½ -year-old female with widespread skeletal involvement of stage 4 neuroblastoma. Injection artefact from the portacath site in the left chest is observed in all images. The scores according to the three different methods most used are given; the Curie score (method 1) is currently the standard of comparison for other scoring variations. (A) At diagnosis: method 1 (Curie)= 26 (by segment 3, 3, 3, 3, 3, 3, 1, 3, 3, 1); method 2 (Frappaz)= 21 (by segment: 3, 3, 3, 3, 3, 3, 3); method 3 (SIOPEN)= 61 (by segment: 5, 5, 5, 5, 4, 4, 6, 6, 6, 6, 4, 5). (B) During induction: method 1= 1 for the soft tissue; method 2= 0; method 3= 0. (C) End therapy. Note the disappearance of soft tissue involvement because of surgical resection of primary tumour: method 1= 0; method 2= 0; method 3= 0. (D) At relapse: method 1= 13 (by segment: 2, 1, 1, 1, 1, 1, 0, 3, 3, 0); method 2=9 (by segment: 2, 0, 2, 1, 1, 2, 1); method 3=29 (by segment: 3, 1, 1, 1, 0, 0, 1, 4, 5, 5, 4, 4).