The results of therapy in patients with high-risk neuroblastoma: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

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Abstract

   Treatment of patients with high-risk neuroblastoma (NB) is a complex challenge, and it is based on response to certain elements of therapy. The development and introduction of new treatment approaches, such as GD2-targeted immunotherapy (IT), leads to improved survival in this cohort of patients.

   The aim of the study was to retrospectively assess the effectiveness of therapy in patients with high-risk NB before the introduction of IT into clinical practice.

   We retrospectively analyzed the data of 151 NB patients stratified into a high-risk group who had received treatment in accordance with the modified NB2004 protocol of the German Society for Pediatric Oncology and Hematology (GPOH) at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology from 01.2012 to 12.2017. This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All the study subjects (or their legal representatives) signed a voluntary informed consent form indicating their agreement to treatment and use of their data for research purposes. Overall survival (OS), event-free survival (EFS), and risk factors were analyzed in the patients with high-risk NB including those who had completed multimodal therapy with autologous hematopoietic stem cell transplantation and post-consolidation therapy with isotretinoin and had achieved a satisfactory response to induction therapy (complete response (CR), very good partial response (VGPR), partial response (PR)) (population of special interest). The main unfavorable prognostic clinical and molecular genetic factors affecting survival in the high-risk NB patients were older age, MYCN gene amplification, and stage 4 of the disease. The use of the modified GPOH NB2004 protocol resulted in a satisfactory response (CR/VGPR/PR) to the induction therapy in most patients: 124/151 (82.1 %). Surgery (other than primary tumor biopsy) led to improved survival, with no statistical difference between macroscopic radical surgery and macroscopic residual tumor. At the same time, radiation therapy (RT), as the second element of local control, had a significant impact on EFS in the group of the patients with stage 4 disease: the 3-year EFS was 39.4 % (95 % confidence interval (CI) 23.1–55.4) in the patients with RT versus 25.7 % (95 % CI 17.5–34.7) in the patients without RT (p = 0.0295). The introduction of a new high-dose TreoMel chemotherapy regimen did not result in worse survival rates but led to a decrease in transplant-related toxicity. The 5-year OS and 5-year EFS were 49.4 % (95 % CI 40.9–57.3 %) and 33.3 % (95 % CI 25.9–40.9) respectively for all the study subjects, and 81.6 % (95 % CI 70.3–88.9) and 55.1 % (95 % CI 43.1–65.5) respectively for the patients from the population of special interest. The analysis of the results of therapy in the high-risk NB patients who had received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, yielded results comparable to those of the original GPOH NB2004 protocol. The patients with CR/VGPR/PR to the induction therapy who had completed the protocol treatment with autologous hematopoietic stem cell transplantation and isotretinoin post-consolidation therapy demonstrated higher 5-year EFS rates. However, there remains a need to develop more effective treatment regimens for high-risk NB.

About the authors

T. V. Shamanskaya

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: shamanskaya.tatyana@gmail.com
ORCID iD: 0000-0002-3767-4477

Tatyana V. Shamanskaya, Cand. Med. Sci., Head of the Department

Institute of Oncology, Radiology and Nuclear Medicine

Department for Embryonal Tumor Research

117997

1 Samory Mashela St.

Moscow

Россия

S. R. Varfolomeeva

Research Institute of Pediatric Oncology and Hematology of the N. N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-6131-1783

Moscow

Россия

D. Yu. Kachanov

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-3704-8783

Moscow

Россия

R. A. Moiseenko

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-9654-084X

Moscow

Россия

M. V. Teleshova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-4042-0125

Moscow

Россия

D. M. Konovalov

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-7732-8184

Moscow

Россия

V. Yu. Roshchin

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-9375-7517

Moscow

Россия

A. N. Kazakova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-1085-4646

Moscow

Россия

L. V. Zemtsova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-0993-9183

Moscow

Россия

A. E. Drui

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-1308-8622

Moscow

Россия

M. Ya. Yadgarov

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-3792-1682

Moscow

Россия

G. V. Tereshchenko

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-7317-7104

Moscow

Россия

A. P. Shcherbakov

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-8129-0545

Moscow

Россия

Yu. N. Likar

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-6158-2222

Moscow

Россия

M. N. Sukhov

Russian Children's Clinical Hospital of the N. I. Pirogov Russian National Research Medical University of Ministry
of Healthcare of the Russian Federation

ORCID iD: 0000-0003-4412-3056

Moscow

Россия

N. S. Grachev

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-4451-3233

Moscow

Россия

D. G. Akhaladze

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-1387-209X

Moscow

Россия

M. A. Maschan

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-1735-0093

Moscow

Россия

A. V. Nechesnyuk

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2537-6157

Moscow

Россия

A. V. Pshonkin

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2057-2036

Moscow

Россия

E. E. Kurnikova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-4767-5382

Moscow

Россия

E. V. Skorobogatova

Russian Children's Clinical Hospital of the N. I. Pirogov Russian National Research Medical University of Ministry
of Healthcare of the Russian Federation

ORCID iD: 0000-0003-4431-1444

Moscow

Россия

L. A. Khachatryan

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-7265-0414

Moscow

Россия

D. K. Fomin

Russian Scientific Center of Roentgenology and Radiology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-7316-3519

Moscow

Россия

A. A. Maschan

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-0016-6698

Moscow

Россия

A. G. Rumyantsev

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-1632-4822

Moscow

Россия

G. A. Novichkova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2322-5734

Moscow

Россия

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