Neuroblastoma Therapy Clinical Applications
Neuroblastoma and Metastasis (Stage III and IV). (*)
(*) Provided a diagnostic MIBG procedure demonstrates significant increased uptake in lesions.
Neuroblastoma (NB) treatment with high doses of 131-I-MIBG is still a promise, despite the extensive experience in this area. The treatment of stages I and II is fully established, consisting of surgical excision and combined chemotherapy, achieving survival rates above 90% at 2 years, which precluded the use of MIBG as a treatment option in these cases. However, in advanced stages the prognosis remains extremely poor, with survival at 2 years of diagnosis, from 7% to 23%. The selection of patients for treatment with MIBG has been, in practice, that of advanced stages of disease with bone metastases, and failure or lack of response to chemotherapy. Still, Troncone et al. obtained in 276 patients, some sort of favorable response in 35% of them. Other authors, report good results in stages III and IV administering therapeutic doses only at the initial diagnosis of the disease. This procedure has been criticized for raising some issues unresolved, including the potential risk of developing multidrug-resistant malignant clones or that the tumor may become radioresistant and continue to proliferate.
Other protocols, taking advantage of the synergy between cisplatin and radiation, have also obtained good results with a single dose administration of 131-I-MIBG before surgery when the tumor uptake is maximal, to achieve reduction of tumor mass, reserving the multidrug therapy for residual tumor, which presumably reduces the risk of resistance.
The criteria for selection of patients for inclusion in treatment protocols of 131-I-MIBG varies depending on the institution. Due to clinical and economic reasons, most of the selected groups of patients are restricted. Generally, these patients pertain to advanced stages of the disease, III and IV, refractory to induction chemotherapy protocols.
In
general, side effects are few, limited to a certain gastric intolerance with
nausea and sometimes vomiting, diarrhea and hypertension, although they all tend
to be temporary.
According to international response criteria (INRC), treatment response
is assessed as follows:
• Complete Response: No tumor or metastasis.
• Very good partial response: tumor reduction between 90%-100%. MIBG no uptake
in bone. Lesion uptake may persist on the bone scan.
• Partial response: tumor reduction between 50-90%. No new lesions. Reduction of
metastases detected in more than 50%.
• Stable disease: No new lesions. Reduction of over 50% of any measurable
lesion (primary or metastases).
• Progressive disease): Any new lesion; increase of over 25% of any pre-existing
lesion. Previous negative marrow becomes positive.
The assessment of the number of lesions has to be made by standard procedures at each evaluation: CT or MRI and MIBG. The dimensions of the lesion were assessed by CT or MRI preferentially.
Currently, treatment with 131-I-MIBG is still subjected to numerous tests and
modifications to improve performance in terms of prolonging survival in advanced
stages of disease.
References:
1 Hoefnagel CA, De Kraker J, Voute PA et al. Preoperative 131I metaiodobenzylguanidine therapy in neuroblastoma at diagnosis (“MIBG de novo”). J Nucl Biol Med 1991; 35: 248-251.
2 Mairs RJ, Cunningham RS, O´Donogue JA et al. Enhanced tumor uptake and in vitro radiotoxicity of no-carrier-added I131-metaiodobenzylguanidine: implications for the targeted radiotherapy of neuroblastoma. Eur J Cancer 1995; 31 A.576-581.
3 Troncone L, Galli G. Proceeding of international workshop on the role of 131-metaiodobenzylguanidine in the treatment of neural crest tumors. J Nucl Biol Med 1991; 35: 177-363.
4 Brodeur GM, Pritchard J Berthold F et al. Revision of the International Criteria for Neuroblastoma diagnosis, staging and response to treatment. J Clin Oncol 1993; 11: 1466-1477.
5 Hoefnagel CA. Metaiodobenzylguanidine and somatostatin in Oncology: role in the management of neural crest tumors. Eur J Nucl Med 1994; 21: 561-581.
6 Diez L, Mitjavila M, Tumores Neuroendocrinos: estudios con meta-yodo-bencil-guanidina, p: 549-561 in: Medicina Nuclear Aplicaciones Clínicas. Eds: I. Carrio - P. González. Editorial Masson, Barcelona España, 2003.