Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers - proof-of-principle prospective observational study

Q: What problem does functional precision medicine aim to address in pediatric cancers?

It addresses limited treatment options and the scarcity of predictive biomarkers for personalized recommendations when standard care is exhausted.

Q: How was feasibility assessed in this prospective study?

Feasibility was measured by the ability to return FPM-based treatment recommendations to the FPM tumor board within a clinically actionable timeframe of less than 4 weeks.

Q: What results were reported regarding treatment recommendations and patient outcomes?

FPM recommendations were generated for most patients, with therapeutic interventions given to a subset. Patients receiving FPM-guided treatments showed improved progression-free survival compared with their prior therapy, and results suggested higher progression-free survival and objective response rate versus non-guided patients.

Sep 21, 2026

Upload by Emma Wilson

Children and teenagers with rare relapsed or refractory cancers often face limited options and few predictive biomarkers for personalized treatment recommendations. Functional precision medicine (FPM), combining genomic profiling with drug sensitivity testing (DST) on patient-derived tumor cells, may identify therapies after standard care is exhausted. A prospective observational study evaluated feasibility of returning FPM-based recommendations to an FPM tumor board within <4 weeks and assessed clinical outcomes. Among 25 enrolled patients, turnaround times were within 10 days for DST and 27 days for genomics.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages33

Reading Time1 h 23 min

AccessFree to download

Introduction

Rationale and background for functional precision medicine

Study design and objectives

Primary feasibility objective

Secondary clinical outcomes objective

Results summary

Turnaround times and patient cohort

Treatment recommendations and FPM-guided therapies

Discussion and implications

Potential impact and need for further validation

nature medicine Article [https://doi.org/10.1038/s41591-024-02848-4](https://doi.org/10.1038/s41591-024-02848-4) Feasibility of functional precision medicine for guiding treatment of relapsedor refractory pediatric cancers | Received: 2 July 2023
Accepted: 31 January 2024
Published online: 11 April 2024 Check for updates | A list of authors and their affiliations appears atthe end of the paper
Children with rare, relapsedor refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsedor refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in realtime totheFPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsedor refractory solid and hematological cancers were enrolled; 21 patients underwent DSTand 20 also completed genomic profiling. Median turnaround times forDSTand genomics were within
10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienceda greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to
those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPMto positively impact clinical care for pediatric and adolescent patients with relapsedor refractory
cancersand warrant further validation in large prospective studies.
ClinicalTrials.gov registration: NCT03860376. | | | --- | --- | --- | | Cancer is the leading cause of disease-related death for children and teenagers in the United States. Despite improvements in survival for patients with cancers like acute lymphoblastic leukemia, progress for other high-risk, relapsed or refractory pediatric cancers | | remains challenging1. These patients typically have few established treatment options, in spite of advancements in standard therapy2,3. Genomics-guided precision oncology4 aims to provide pediatric and adolescent patients with matched treatments based on molecular | | [e-mail:](e-mail: dazzam@fiu.edu)[ dazzam@fiu.edu](e-mail: dazzam@fiu.edu) | | | Nature Medicine | Volume 30 | April 2024 | 990–1000 990 Fig. 1 | Flow diagram showing FPM workflow. FPM workflow including patient enrollment, sample collection, functionalex vivo drug sensitivity testing and molecular tumor profiling, and report delivery to the FPMTB for clinical decision-making. Numbers at each exit and endpoint represent patient numbers. [Created with](Created with BioRender.com)[ BioRender.com](Created with BioRender.com). changes in their tumors to improve survival and quality of life. The widespread availability of different sequencing approaches has resulted in multiple pediatric cancer precision medicine programs around the world such as the Zero Childhood Cancer Program in Australia, PROFYLE in Canada andiTHERin the Netherlands5–7. Despite the substantial clinical benefit, these trials revealed several constraints in using genomics-driven therapy only, particularly for cancers that lack actionable driver mutations and matched treatments, which is often the case in pediatric cancers are oft

FAQs

What problem does functional precision medicine aim to address in pediatric cancers?

It addresses limited treatment options and the scarcity of predictive biomarkers for personalized recommendations when standard care is exhausted.

How was feasibility assessed in this prospective study?

Feasibility was measured by the ability to return FPM-based treatment recommendations to the FPM tumor board within a clinically actionable timeframe of less than 4 weeks.

What results were reported regarding treatment recommendations and patient outcomes?

FPM recommendations were generated for most patients, with therapeutic interventions given to a subset. Patients receiving FPM-guided treatments showed improved progression-free survival compared with their prior therapy, and results suggested higher progression-free survival and objective response rate versus non-guided patients.

Sep 21, 2026

Upload by Emma Wilson