Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene
| Autor: | Ondrej Rohleder, Jaroslav Sterba, Renata Veselská, Ondrej Slaby, Jana Šoukalová, Peter Múdry, Elleni Michu, Marta Jezova, Kristyna Melicharkova, Jakub Neradil, Anna Seehofnerová |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Heterozygote Cancer Research Indoles PDGFR medicine.medical_treatment Population Infantile myofibromatosis Tyrosine kinase inhibitor Case Report Vinblastine Targeted therapy Receptor Platelet-Derived Growth Factor beta 03 medical and health sciences 0302 clinical medicine Germline mutation Low-dose chemotherapy Antineoplastic Combined Chemotherapy Protocols Sunitinib Genetics medicine Humans Chemotherapy Missense mutation Pyrroles Molecular Targeted Therapy education Germ-Line Mutation Family Health education.field_of_study business.industry Infant Newborn Myofibromatosis Theranostics medicine.disease 3. Good health Treatment Outcome 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Female business Nijmegen breakage syndrome medicine.drug |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| Popis: | Background Infantile myofibromatosis belongs to a family of soft tissue tumors. The majority of these tumors have benign behavior but resistant and malignant courses are known, namely in tumors with visceral involvement. The standard of care is surgical resection. Observations suggest that low dose chemotherapy is beneficial. The treatment of resistant or relapsed patients with multifocal disease remains challenging. Patients that harbor an actionable mutation in the kinase domain are potential subjects for targeted tyrosine kinase inhibitor therapy. Case presentation An infant boy with inborn generalized infantile myofibromatosis that included bone, intracranial, soft tissue and visceral involvement was treated according to recent recommendations with low dose chemotherapy. The presence of a partial but temporary response led to a second line of treatment with six cycles of chemotherapy, which achieved a partial response again but was followed by severe toxicity. The generalized progression of the disease was observed later. Genetic analyses were performed and revealed a PDGFRB gene c.1681C>A missense heterozygous germline mutation, high PDGFRβ phosphokinase activity within the tumor and the heterozygous germline Slavic Nijmegen breakage syndrome 657del5 mutation in the NBN gene. Targeted treatment with sunitinib, the PDGFRβ inhibitor, plus low dose vinblastine led to an unexpected and durable response without toxicities or limitations to daily life activities. The presence of the Slavic NBN gene mutation limited standard chemotherapy dosing due to severe toxicities. Sister of the patient suffred from skull base tumor with same genotype and histology. The same targeted therapy led to similar quick and durable response. Conclusion Progressive and resistant incurable infantile myofibromatosis can be successfully treated with the new approach described herein. Detailed insights into the biology of the patient’s tumor and genome are necessary to understand the mechanisms of activity of less toxic and effective drugs except for up to date population-based chemotherapy regimens. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3115-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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