Approximately half of children with neuroblastoma—a childhood cancer that develops from immature nerve cells—have an aggressive, hight-risk form of the disease with a high likelihood of recurrence.

During the last 3 decades, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. These treatment approach es have resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments.[1]

New findings published online in CANCER, a peer-reviewed journal of the American Cancer Society, demonstrates that a news ‘bridge therapy’ used between induction and consolidation treatments may benefit patients with this high-risk neuroblastoma.[2]

Surgical removal
can often be cured by surgical removal of tumors followed by chemotherapy. These patients often receive induction therapy composed of various chemotherapy drugs and surgery, followed by consolidation therapy (given to kill any cancer cells that may be left in the body) involving high-dose chemotherapy plus stem cell transplants.

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Unfortunately, these standard treatments are unsuccessful in many children. In these cases, a bridge therapy, which might include immunotherapy drugs that have demonstrated anti-neuroblastoma activity combined with chemotherapy, radiolabeled MIBG (a therapy that delivers targeted radiation to neuroblastoma), or combinations of chemotherapeutic agents, could offer some benefit.

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To examine the benefits of a bridge therapy strategy for patients with high-risk neuroblastoma whose cancer was still evident after induction therapy, Ami V. Desai, MD, MSCE, of the University of Chicago and her colleagues examined data from 201 patients diagnosed at various hospitals from 2008–2018 with neuroblastoma who had residual disease after completing induction therapy.

Ami V. Desai, MD, MSCE is Assistant Professor of Pediatrics and Assistant Professor of Comprehensive Cancer Research Center at the University of Chicago. Photo courtesy: © 2022 The University of Chicago Medical Center. Used with permission.

Participating patients were treated in three groups with different approaches based on physician, institutional, or family preferences. Treatment included (1) no bridge therapy prior to consolidation therapy, (2) bridge therapy prior to consolidation therapy, and (3) additional post-induction therapy without consolidation therapy.

Evaluation
The investigators were especially interested in evaluating if the addition of bridge therapy prior to consolidation with stem cell transplant improved the event-free survival, or the time after treatment that cancer did not come back or get worse in patients with residual neuroblastoma at the end of induction therapy.

Patients who directly underwent consolidation (group 1) had better responses to induction therapy than patients who received bridge therapy prior to consolidation (group 2). Event-free survival was similar in these two groups, however, suggesting that the addition of bridge therapy prior to consolidation therapy may benefit patients with a poor response to induction therapy.

Among patients with stable cancer at metastatic sites after induction therapy, those who received bridge therapy (group 2) had significantly improved event-free survival compared with those who directly underwent consolidation therapy (group 1).

Patients treated with post-induction therapy who did not receive consolidation therapy (group 3) experienced inferior event-free survival than patients in groups 1 or 2; however, those in group 3 with no signs of metastatic cancer following post-induction therapy had significantly better 3-year event-free survival than those with residual metastatic disease. Prospective studies are needed to confirm these findings and to help identify which patients may have long-term survival without consolidation with autologous stem cell transplant.

“Response to induction therapy is known to be prognostic of survival, and our study suggests that bridge therapy prior to consolidation therapy benefits patients with high-risk neuroblastoma with a poor response to induction,” Desai said.

“Also, response to bridge therapy prior to consolidation therapy is associated with outcome, and patients with less than a partial response may benefit from alternative treatment approaches,” she concluded.

Reference
[1] Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, Nakagawara A, Berthold F, Schleiermacher G, Park JR, Valteau-Couanet D, Pearson AD, Cohn SL. Advances in Risk Classification and Treatment Strategies for Neuroblastoma. J Clin Oncol. 2015 Sep 20;33(27):3008-17. doi: 10.1200/JCO.2014.59.4648. Epub 2015 Aug 24. PMID: 26304901; PMCID: PMC4567703.
[2] Desai AV, Applebaum MA, Karrison TG, Oppong A, Yuan C, Berg KR, MacQuarrie K, Sokol E, Hall AG, Pinto N, Wolfe I, Mody R, Shusterman S, Smith V, Foster JH, Nassin M, LaBelle JL, Bagatell R, Cohn SL. Efficacy of post-induction therapy for high-risk neuroblastoma patients with end-induction residual disease. Cancer. 2022 Jun 6. doi: 10.1002/cncr.34263. Epub ahead of print. PMID: 35665495.

Featured image: Human neuroblastoma cells: nuclei are stained in red, microfilaments are in green.

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