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

Elwira Szychot; Daniel Morgenstern; Mark Chopra; Stefania Sorrentino; Owen Arthurs; Neil Sebire; Farrukh Arfeen; Andrzej Brodkiewicz; Paul Humphries; Lorenzo Biassoni

doi:10.1007/s10147-021-02039-y

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

Int J Clin Oncol. 2022 Jan;27(1):253-261. doi: 10.1007/s10147-021-02039-y. Epub 2021 Oct 9.

Authors

Elwira Szychot^{1

2

3}, Daniel Morgenstern^{4

5}, Mark Chopra⁶, Stefania Sorrentino^{6

7}, Owen Arthurs⁶, Neil Sebire⁸, Farrukh Arfeen⁶, Andrzej Brodkiewicz⁹, Paul Humphries⁶, Lorenzo Biassoni⁶

Affiliations

¹ Clinical Studies, The Institute of Cancer Research, Sutton, UK. e.szychot@nhs.net.
² Oak Centre for Children and Young People, Royal Marsden Hospital, Sutton, SM2 5PT, UK. e.szychot@nhs.net.
³ Department of Paediatrics, Paediatric Oncology and Immunology, Pomeranian Medical University, Szczecin, Poland. e.szychot@nhs.net.
⁴ Departments of Haematology/Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁵ Hospital for Sick Children, Toronto, Canada.
⁶ Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁷ Unit of Paediatric Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
⁸ Department of Pathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁹ Department of Paediatrics, Child's Nephrology, Dialysis Therapy and Acute Poisoning, Szczecin, Poland.

PMID: 34626287
DOI: 10.1007/s10147-021-02039-y

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.

Keywords: 123ImIBG; Children; High-risk neuroblastoma; Primary tumour.

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Humans
Induction Chemotherapy*
Infant
Neuroblastoma* / drug therapy
Retrospective Studies