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

J 2017

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

MÚDRY, Peter, Ondřej SLABÝ, Jakub NERADIL, Jana ŠOUKALOVÁ, Kristýna MELICHÁRKOVÁ et. al.

Základní údaje

Originální název

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

Autoři

MÚDRY, Peter (203 Česká republika, domácí), Ondřej SLABÝ (203 Česká republika, domácí), Jakub NERADIL (203 Česká republika, domácí), Jana ŠOUKALOVÁ (203 Česká republika, domácí), Kristýna MELICHÁRKOVÁ (203 Česká republika, domácí), Ondřej ROHLEDER (203 Česká republika, domácí), Marta JEŽOVÁ (203 Česká republika, domácí), Anna SEEHOFNEROVÁ (203 Česká republika, domácí), Elleni PONECHAL MICHU (203 Česká republika, domácí), Renata VESELSKÁ (203 Česká republika, domácí) a Jaroslav ŠTĚRBA (203 Česká republika, garant, domácí)

Vydání

BMC Cancer, London, UK, BioMed Central, 2017, 1471-2407

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.288

Kód RIV

RIV/00216224:14110/17:00095701

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1186/s12885-017-3115-x

UT WoS

000393842000001

Klíčová slova anglicky

Infantile myofibromatosis; tyrosine kinase inhibitor; PDGFR; chemotherapy; theranostics; case report

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 1. 2021 14:40, Mgr. Tereza Miškechová

Anotace

V originále

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. 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 PDGFR beta phosphokinase activity within the tumor and the heterozygous germline Slavic Nijmegen breakage syndrome 657del5 mutation in the NBN gene. Targeted treatment with sunitinib, the PDGFR beta 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. 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.

Návaznosti

LM2015090, projekt VaV

Název: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Akronym: CZECRIN)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CZECRIN - Český národní uzel Evropské sítě infrastruktur klinického výzkumu

NV16-33209A, projekt VaV

Název: Sekvenování nové generace a expresní profilování jako diagnostický podklad pro návrhy individualizovaných léčebných plánů pro děti se solidními nádory

NV16-34083A, projekt VaV

Název: Receptorové tyrozinkinázy a navazující signální dráhy jako potenciální cíle léčby refrakterních solidních nádorů dětského věku

Citovat

MÚDRY, Peter, Ondřej SLABÝ, Jakub NERADIL, Jana ŠOUKALOVÁ, Kristýna MELICHÁRKOVÁ, Ondřej ROHLEDER, Marta JEŽOVÁ, Anna SEEHOFNEROVÁ, Elleni PONECHAL MICHU, Renata VESELSKÁ a Jaroslav ŠTĚRBA. 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. BMC Cancer. London, UK: BioMed Central, 2017, roč. 17, č. 119, s. nestránkováno, 7 s. ISSN 1471-2407. Dostupné z: https://dx.doi.org/10.1186/s12885-017-3115-x.

@article{1404973,
   author = {Múdry, Peter and Slabý, Ondřej and Neradil, Jakub and Šoukalová, Jana and Melichárková, Kristýna and Rohleder, Ondřej and Ježová, Marta and Seehofnerová, Anna and Ponechal Michu, Elleni and Veselská, Renata and Štěrba, Jaroslav},
   article_location = {London, UK},
   article_number = {119},
   doi = {http://dx.doi.org/10.1186/s12885-017-3115-x},
   keywords = {Infantile myofibromatosis; tyrosine kinase inhibitor; PDGFR; chemotherapy; theranostics; case report},
   language = {eng},
   issn = {1471-2407},
   journal = {BMC Cancer},
   title = {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},
   url = {https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3115-x},
   volume = {17},
   year = {2017}
}

TY  - JOUR
ID  - 1404973
AU  - Múdry, Peter - Slabý, Ondřej - Neradil, Jakub - Šoukalová, Jana - Melichárková, Kristýna - Rohleder, Ondřej - Ježová, Marta - Seehofnerová, Anna - Ponechal Michu, Elleni - Veselská, Renata - Štěrba, Jaroslav
PY  - 2017
TI  - 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
JF  - BMC Cancer
VL  - 17
IS  - 119
SP  - nestránkováno
EP  - nestránkováno
PB  - BioMed Central
SN  - 14712407
KW  - Infantile myofibromatosis
KW  - tyrosine kinase inhibitor
KW  - PDGFR
KW  - chemotherapy
KW  - theranostics
KW  - case report
UR  - https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3115-x
L2  - https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3115-x
N2  - 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. 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 PDGFR beta phosphokinase activity within the tumor and the heterozygous germline Slavic Nijmegen breakage syndrome 657del5 mutation in the NBN gene. Targeted treatment with sunitinib, the PDGFR beta 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. 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.
ER  -

MÚDRY, Peter, Ondřej SLABÝ, Jakub NERADIL, Jana ŠOUKALOVÁ, Kristýna MELICHÁRKOVÁ, Ondřej ROHLEDER, Marta JEŽOVÁ, Anna SEEHOFNEROVÁ, Elleni PONECHAL MICHU, Renata VESELSKÁ a Jaroslav ŠTĚRBA. 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. \textit{BMC Cancer}. London, UK: BioMed Central, 2017, roč.~17, č.~119, s.~nestránkováno, 7 s. ISSN~1471-2407. Dostupné z: https://dx.doi.org/10.1186/s12885-017-3115-x.

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