Full text

Turn on search term navigation

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Approximately 50% of high-risk neuroblastomas (NB) relapse within two years after the end of treatment. The prognosis for relapsed or refractory patients is poor, and additional therapeutic options are needed. The identification of ALK somatic mutations or amplification plays an important role in the treatment of relapsed/refractory patients. The aim of our study was to evaluate the genomic status of patients with relapsed/refractory NB and to employ ALK Tyrosine Kinase Inhibitors (TKIs) in patients with targetable ALK mutations. In the era of precision medicine, ALK inhibitors may play an important role in the treatment of high-risk, ALK-mutated, NB patients.

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relapsed/refractory disease have a poor prognosis, and additional therapeutic options are needed. Mutations and amplifications in the ALK (Anaplastic Lymphoma Kinase) gene constitute a key target for treatment. Our goal, within the Italian project of PeRsonalizEdMEdicine (PREME), was to evaluate the genomic status of patients with relapsed/refractory NB and to implement targeted therapies in those with targetable mutations. From November 2018 to November 2021, we performed Whole Exome Sequencing or Targeted Gene Panel Sequencing in relapsed/refractory NB patients in order to identify druggable variants. Activating mutations of ALK were identified in 8(28.57%) of 28 relapsed/refractory NB patients. The mutation p.F1174L was found in six patients, whereas p.R1275Q was found in one and the unknown mutation p.S104R in another. Three patients died before treatment could be started, while five patients received crizotinib: two in monotherapy (one with p.F1174L and the other with p.S104R) and three (with p.F1174L variant) in combination with chemotherapy. All treated patients showed a clinical improvement, and one had complete remission after two cycles of combined treatment. The most common treatment-related toxicities were hematological. ALK inhibitors may play an important role in the treatment of ALK-mutated NB patients.

Details

Title
Therapeutic Targeting of ALK in Neuroblastoma: Experience of Italian Precision Medicine in Pediatric Oncology
Author
Pastorino, Fabio 1   VIAFID ORCID Logo  ; Capasso, Mario 2   VIAFID ORCID Logo  ; Brignole, Chiara 1   VIAFID ORCID Logo  ; Lasorsa, Vito A 3   VIAFID ORCID Logo  ; Bensa, Veronica 1   VIAFID ORCID Logo  ; Perri, Patrizia 1   VIAFID ORCID Logo  ; Cantalupo, Sueva 2 ; Giglio, Serena 4 ; Provenzi, Massimo 5 ; Rabusin, Marco 6 ; Pota, Elvira 7 ; Cellini, Monica 8 ; Tondo, Annalisa 9 ; De Ioris, Maria A 10   VIAFID ORCID Logo  ; Sementa, Angela R 11 ; Garaventa, Alberto 12 ; Ponzoni, Mirco 1   VIAFID ORCID Logo  ; Amoroso, Loredana 12   VIAFID ORCID Logo 

 UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy 
 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy; CEINGE Biotecnologie Avanzate, Via G. Salvatore, 486, 80145 Napoli, Italy 
 CEINGE Biotecnologie Avanzate, Via G. Salvatore, 486, 80145 Napoli, Italy 
 UO Pediatria-Neonatologia/Nido PO A. Ajello ASP Trapani, 91100 Trapani, Italy 
 Pediatric Oncology, Ospedale Papa Giovanni XXIII, Piazza Organizzazione Mondiale Sanità 1, 24127 Bergamo, Italy 
 Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137 Trieste, Italy 
 UOSD di Ematologia ed Oncologia Pediatrica, Università Degli Studi Della Campania “Luigi Vanvitelli,” Piazza Luigi Miraglia 2, 80138 Napoli, Italy 
 Division of Paediatric Hemato-Oncology, University Hospital Azienda Policlinico di Modena, Via del Pozzo 71, 41124 Modena, Italy 
 Department of Hematology-Oncology, Anna Meyer Children’s Hospital, VialePieraccini 24, 50139 Firenze, Italy 
10  Department of Paediatric Haematology/Oncology, and Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy 
11  Dipartimento di Patologia, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy 
12  UOC Oncologia, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy 
First page
560
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2774892374
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.