Clinical impact of primary tumour 123ImIBG response to induction chemotherapy in children with high-risk neuroblastoma.

ABSTRACT

BACKGROUND: More than 50% children with high-risk neuroblastoma (HR-NBL) experience disease progression, which we hypothesise is due to non-response of primary tumour to treatment. Current imaging techniques are unable to characterise response in primary tumour (necrotic versus viable tissue) at diagnosis or follow-up. OBJECTIVES: Compare clinico-histological characteristics between primary 123ImIBG-avid tumours that became entirely 123ImIBG-non-avid (responders) after induction chemotherapy (IC) versus primary 123ImIBG-avid tumour that remained 123ImIBG-avid (non-responders). METHODS: Retrospective review of clinico-radiological data of children diagnosed with 123ImIBG-avid HR-NBL at our centre (2005-2016). Patients received Rapid COJEC IC and two additional courses of TVD if metastatic response was inadequate. Primary tumour 123ImIBG response was assessed qualitatively as positive, negative or intermediate at diagnosis and after IC. Post-surgical histopathology slices were marked considering percentage of viable tissue. RESULTS: Sixteen of 61 patients showed complete primary tumour 123ImIBG response, 20 partial response, while 25 no response. There was no statistically significant difference between clinical demographics of complete responders and group of non- or partial responders. Mean percentage of viable tumour cells was higher in non-responders than in complete responders (44.6% vs 20.6%; p = 0.05). Five-year EFS was significantly higher in complete responders than non-responders (43 ± 15% vs 7 ± 6%; p < 0.005). CONCLUSIONS: 123ImIBG response in primary HR-NBL correlates with amount of necrotic tissue, skeletal metastatic 123ImIBG response and outcome. An entirely 123ImIBG non-avid tumour can still harbour viable tumour cells. Therefore, our findings do not support utility of primary tumour 123ImIBG response in decision making regarding residual tumour surgery. Combining both, primary and metastatic 123ImIBG response will improve interpretability of clinical trial results.