The evaluation of induction chemotherapy regimens for high-risk neuroblastoma in South African children^*

Abstract

Achieving remission after induction therapy in high-risk neuroblastoma (HR-NB) is of significant prognostic importance. This study investigated remission after induction-chemotherapy using three standard neuroblastoma protocols in the South African (SA) setting. Retrospective data of 261 patients with HR-NB diagnosed between January 2000 and December 2016, who completed induction chemotherapy with standard treatment protocols were evaluated. The treatment protocols were either OPEC/OJEC or the St Jude NB84 protocol (NB84) or rapid COJEC (rCOJEC). The postinduction metastatic complete remission (mCR) rate, 2-year overall survival (OS) and 2-year event free survival (EFS) were determined as comparative denominators. The majority (48.3%; n = 126) received OPEC/OJEC, while 70 patients received (26.8%) rCOJEC and 65 (24.9%) NB84. Treatment with NB84 had the best mCR rate (36.9%), followed by OPEC/OJEC (32.5%) and rCOJEC (21.4%). The 2-year OS of treatment with NB84 was 41% compared to OPEC/OJEC (35%) and rCOJEC (24%) (p = 0.010). The 2-year EFS of treatment with NB84 was 37% compared to OPEC/OJEC (35%) and rCOJEC (18%) (p = 0.008). OPEC/OJEC had the least treatment-related deaths (1.6%) compared to rCOJEC (7.1%) and NB84 (7.5%) (p = 0.037). On multivariate analysis LDH (p = 0.023), ferritin (p = 0.002) and INSS stage (p = 0.006) were identified as significant prognostic factors for OS. The induction chemotherapy was not significant for OS (p = 0.18), but significant for EFS (p = 0.08) Treatment with NB84 achieved better mCR, OS and EFS, while OPEC/OJEC had the least treatmentrelated deaths. In resource-constrained settings, OPEC/OJEC is advised as induction chemotherapy in HR-NB due to less toxicity as reflected in less treatment-related deaths.

The implementation of a national paediatric oncology protocol for neuroblastoma in South Africa

“…Yet, in the South African context, none proved superior when considering post-induction remission and outcomes. However, the toxicity profile of OPEC/OJEC had a more favourable outcome than the Rapid COJEC protocol and doxorubicin-containing protocols [27].…”

“…Historically, POUs in South Africa were self-determining entities. The NB management protocols were based on evidence from international protocols, systematic reviews and clinical practice guidelines [27]. In the national NB protocol, a deviation from known local practices was required to achieve a single standard of care that would be feasible in all POUs regardless of unequal access to resources.…”

“…In general, established clinical practice is slow to change, referred to as 'clinical inertia' [28], which was present especially in determining the standard induction chemotherapy for HR-NB. The retrospective review showed numerous induction regimes that were used from 2000 to 2014 [10,27]. Yet, in the South African context, none proved superior when considering post-induction remission and outcomes.…”

“…To date, treatment strategies for NB in South Africa have been diverse, based on the experience of individual paediatric oncologists [ 10 ]. The treatment of NB was managed according to the available resources and multiple international protocols were used [ 11 ]. The SACCSG encouraged the development of a national NB management protocol in 2016, which led to the SACCSG NB-2017 study.…”

Mapping Pediatric Oncology Clinical Trial Collaborative Groups on the Global Stage

“…105 Several other cooperative groups emerged from the SIOP Africa Continental Conference in Cairo, Egypt, in 2019, including the Pediatric Oncology Group of East Africa (whose formalization has been delayed because of the COVID-19 pandemic; Dr J. Balagadde Kambugu, Uganda Cancer Institute, Personal communication (e-mail), November 2021), 99 the South African Children's Cancer Study Group, 106 the African Pediatric Neuro-Oncology Society, 107 and the aforementioned POEM Group, which includes the Middle East and North Africa. 99,107 The South African Children's Cancer Study Group was founded to coordinate pediatric cancer care and plays a strong advocacy role in the region, 106,108 with ongoing collaborative trials for retinoblastoma, HL, GCT, neuroblastoma, and nutrition in childhood cancer. There are numerous twinning initiatives throughout Africa aiming to build foundational infrastructure, 99,109,110 including twinning between the Moroccan Society of Pediatric Oncology and Hematology and SJCRH, which resulted in the execution of a prospective HL treatment protocol.…”