The impact of response to induction chemotherapy on the event-free and overall survival in patients with high-risk neuroblastoma: a systematic review and meta-analysis

   Neuroblastoma (NB) is one of the most common embryonal tumors of childhood. About 40 % of all NB patients are stratified into the high-risk group and require multimodal therapy. The goal of induction treatment is a maximum reduction of the primary tumor and metastases. Response to induction therapy is an important prognostic factor affecting long-term survival. The protocol of our meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO): ID-CRD42022311162. The PubMed, Google Scholar and Cochrane Library databases were searched for relevant studies published over the last 15 years (2007–2022). A total of 12 studies were selected for analysis where response to induction therapy was assessed in patients with high-risk NB in accordance with the International NB Response Criteria, and an analysis of the impact of response on overall (OS) and event-free (EFS) survival was carried out. The meta-analysis included 3431 patients: a good response to induction therapy (complete response / very good partial response) was achieved in 1702 patients, a poor response (partial response / mixed response / stable disease) – in 1729 patients. The patients with a good response had a 28 % lower relative risk (RR) of relapse / progression within 5 years of diagnosis compared with the patients with a poor response: RR = 0.72 (0.64 to 0.80), p-value for effect < 0.001, p-value for heterogeneity < 0.001, I2 = 65 %. The relative risk of death within 5 years of diagnosis was 31 % lower in the patients with a good response: RR = 0.69 (0.57 to 0.83), p-value for effect < 0.001, p-value for heterogeneity < 0.001, I2 = 78 %. A separate analysis of results of international cooperative groups (GPOH, COG and SIOPEN) also revealed a statistically significant relationship between partial response / mixed response / stable disease response to induction therapy and EFS (p < 0.001). The highest level of evidence was obtained for separate subgroups – GPOH (a moderate level of evidence for EFS) and SIOPEN (a moderate level of evidence for EFS and OS) – due to low clinical inconsistency (standardized response criteria and therapy) as well as low statistical inconsistency. The study had certain limitations that are described in detail in the article. Response to induction chemotherapy is an important factor that affects EFS and OS in patients with high-risk NB.