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A systematic review of re-induction chemotherapy for children with relapsed high-risk neuroblastoma.

ABSTRACT: BACKGROUND:Despite aggressive multimodal therapy, >50% of children with high-risk neuroblastoma (HRNB) relapse. Survival after relapse is rare, and no consensus currently exists on the most effective therapy. OBJECTIVE:To conduct a systematic review of the literature on effectiveness of re-induction chemotherapy in children with relapsed HRNB. METHODS:Database searches were performed to identify studies looking at response to 1st line chemotherapy for children >12 months at diagnosis with first relapse of HRNB. Studies not reporting separate outcomes for HRNB patients or of refractory patients only were excluded. Two independent reviewers extracted the data and assessed study quality using a modified Newcastle-Ottawa tool. RESULTS:Nine studies were identified fitting the inclusion criteria. All except one were single arm cohorts, and two were retrospective database reviews from single centres. One was a multicentre randomised controlled trial. All used a version of the validated International Neuroblastoma Response Criteria with 8 recording best ever response and 1 at a specified time, and 5 had central review. The proportion of relapsed patients varied from 24 to 100% with 30-93% receiving upfront myeloablative therapy. The response rate varied from 6 to 64%; however, because of heterogeneity, studies were not directly comparable, and no single treatment emerged as the most effective re-induction therapy. CONCLUSIONS:To date, there is no clear superior re-induction therapy for 1st relapse of HRNB. Randomised controlled trials with separate arms for relapsed versus refractory disease are needed to determine optimal re-induction chemotherapy to act as a backbone for testing newer targeted agents.

SUBMITTER: Herd F

PROVIDER: S-EPMC6458963 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: Neuroblastoma is the most common extracranial solid tumor in children, and most patients are at high risk when they are initially diagnosed. The roles of surgery and induction chemotherapy in patients with high-risk neuroblastoma have been a subject of much controversy and debate. The objective of the current study was to assess the roles of surgery in high-risk neuroblastoma. Method: The review protocol was prospectively registered (PROSPEROID: CRD42021253961). The PubMed, Embase, Cochrane, and CNKI databases were searched from inception to January 2020 with no restrictions on language or publication date. Clinical studies comparing the outcomes of different surgical ranges for the treatment of high-risk neuroblastoma were analyzed. The Mantel-Haenszel method and a random effects model was utilized to calculate the hazard ratio (95% CI). Results: Fourteen studies that assessed 1,915 subjects met the full inclusion criteria. Compared with the gross tumor resection (GTR) group, complete tumor resection (CTR) did not significantly improve the 5-year EFS [p = 1.0; HR = 0.95 (95% CI, 0.87-1.05); I 2 = 0%], and the 5-year OS [p = 0.76; HR = 1.08 (95% CI, 0.80-1.46); I 2 = 0%] of patients. GTR or CTR resection had significantly better 5-year OS [p = 0.45; HR = 0.56 (95% CI, 0.43-0.72); I 2 = 0%] and 5-year EFS [p = 0.15; HR = 0.80 (95% CI, 0.71-0.90); I 2 = 31%] than subtotal tumor resection (STR) or biopsy only; however, both CTR or GTR showed a trend for more intra and post-operative complications compared with the STR or biopsy only [p = 0.37; OR = 1.54 (95% CI, 1.08-2.20); I 2 = 0%]. The EFS of the patients who underwent GTR or CTR at the time of diagnosis and after induction chemotherapy were similar [p = 0.24; HR = 1.53 (95% CI, 0.84-2.77); I 2 = 29%]. Conclusion: For patients with high-risk neuroblastoma, complete tumor resection and gross tumor resection of the primary tumor were related to improved survival, with very limited effects on reducing intraoperative and postoperative complications. It is necessary to design strong chemotherapy regimens to improve the survival rate of advanced patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPEROID [CRD42021253961].

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A systematic review of re-induction chemotherapy for children with relapsed high-risk neuroblastoma.

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