J 2019

Individualization of Treatment Improves the Survival of Children With High-Risk Solid Tumors: Comparative Patient Series Analysis in a Real-Life Scenario

KÝR, Michal, Kristýna POLÁŠKOVÁ, Zuzana KUTTNEROVÁ, Tomáš MERTA, Jakub NERADIL et. al.

Basic information

Original name

Individualization of Treatment Improves the Survival of Children With High-Risk Solid Tumors: Comparative Patient Series Analysis in a Real-Life Scenario

Authors

KÝR, Michal (203 Czech Republic, guarantor, belonging to the institution), Kristýna POLÁŠKOVÁ (203 Czech Republic, belonging to the institution), Zuzana KUTTNEROVÁ (703 Slovakia, belonging to the institution), Tomáš MERTA (203 Czech Republic, belonging to the institution), Jakub NERADIL (203 Czech Republic, belonging to the institution), Jitka BERKOVCOVÁ (203 Czech Republic), Ondřej HORKÝ (203 Czech Republic), Marta JEŽOVÁ (203 Czech Republic, belonging to the institution), Renata VESELSKÁ (203 Czech Republic, belonging to the institution), Giannoula Lakka KLEMENT (124 Canada), Dalibor VALÍK (203 Czech Republic) and Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution)

Edition

Frontiers in Oncology, Lausanne, Frontiers Media S.A. 2019, 2234-943X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.848

RIV identification code

RIV/00216224:14110/19:00108598

Organization unit

Faculty of Medicine

UT WoS

000475875500001

Keywords in English

cancer; children; personalized medicine; targeted therapy; comparative effectiveness research; clinical trials; metronomic

Tags

International impact, Reviewed
Změněno: 26/4/2021 12:55, Mgr. Tereza Miškechová

Abstract

V originále

Introduction: The individualization of treatment is attractive, especially in children with high-risk cancer. In such a rare and very heterogeneous group of diseases, large population-based clinical randomized trials are not feasible without international collaboration. We therefore propose comparative patient series analysis in a real-life scenario. Methods: Open cohort observational study, comparative analysis. Seventy patients with high-risk solid tumors diagnosed between 2003 and 2015 and in whom the treatment was individualized either empirically or based on biomarkers were analyzed. The heterogeneity of the cohort and repeated measurements were advantageously utilized to increase effective sample size using appropriate statistical tools. Results: We demonstrated a beneficial effect of empirically given low-dose metronomic chemotherapy (HR 0.46 for relapses, p = 0.017) as well as various repurposed or targeted agents (HR 0.15 for deaths, p = 0.004) in a real-life scenario. However, targeted agents given on the basis of limited biological information were not beneficial. Conclusions: Comparative patient series analysis provides institutional-level evidence for treatment individualization in high-risk pediatric malignancies. Our findings emphasize the need for a comprehensive, multi omics assessment of the tumor and the host as well whenever molecularly driven targeted therapies are being considered. Low-dose metronomic chemotherapy or local control of the disease may be a more rational option in situations where targeted treatment cannot be justified by robust evidence and comprehensive biological information. "Targeted drugs" may be given empirically with a realistic benefit expectation when based on robust rationale.

Links

LM2015090, research and development project
Name: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Acronym: CZECRIN)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1586/2018, interní kód MU
Name: Personalizovaná léčba v dětské onkologii: na cestě k "liquid dynamic medecine" a "N-of-1 clinical trials" (Acronym: Personalizovaná léčba v dětské onkologii)
Investor: Masaryk University, Category A
NV16-33209A, research and development project
Name: Sekvenování nové generace a expresní profilování jako diagnostický podklad pro návrhy individualizovaných léčebných plánů pro děti se solidními nádory
NV16-34083A, research and development project
Name: Receptorové tyrozinkinázy a navazující signální dráhy jako potenciální cíle léčby refrakterních solidních nádorů dětského věku
90089, large research infrastructures
Name: BBMRI-CZ II