# Induction Regimens in High‐Risk Neuroblastoma: Systematic Review of Response Rates and Toxicities

## TL;DR

This paper reviews chemotherapy regimens for high-risk neuroblastoma, finding that while response rates have not improved over 30 years, regimens with anthracyclines show better results.

## Contribution

The study systematically compares induction regimens for high-risk neuroblastoma, revealing no improvement in response rates over time despite regimen variations.

## Key findings

- Anthracycline-containing regimens had higher end-induction response rates.
- Dose cisplatin intensity was negatively associated with response rates.
- Only 16.7% of regimens included novel agents, and toxic death rates remained low.

## Abstract

Numerous induction therapies have been evaluated for high‐risk neuroblastoma (HRNBL). It is not known how these regimens' response rates nor toxicities compare. We aimed to describe and compare key features of HRNBL induction regimens and their associations with study‐level end‐induction response (EIR).

We performed a systematic review (PubMed) of prospective trials of frontline HRNBL therapy published January 1, 1995–October 31, 2024 that reported EIR. EIR was measured as partial response or better (PR+) per protocol response criteria.

1395 unique titles were screened, yielding 95 abstracts. Of these, 29 publications evaluating 36 induction regimens met inclusion criteria, with a median of 64.5 patients (range: 7–652) per regimen. Median cycle number was 6 (range: 2–9), cycle length was 21 days (10–28), and total duration of induction was 18 weeks (11.4–36). An alkylator and a platinum agent were used in all regimens. Only six regimens (16.7%) included a novel agent. The median study level EIR rate (PR+) was 84.4% (64.3–100), with a weighted average by the number of participants of 79.4%. Study level EIR did not vary over time. Anthracycline‐containing regimens had higher EIRs. Dose cisplatin intensity was negatively associated with EIR. The median toxic death rate was 0% (0–4.1).

Over the past 30 years, induction regimens have relied heavily on conventional chemotherapy. Despite differences in agents, doses, and duration, study‐level EIR rates have not improved over time. Future induction regimens incorporating novel agents will be crucial to improve EIR and reduce toxicities.