# Personalized prediction of chemotherapy efficacy in osteosarcoma through patient-derived organoids: correlation with survival and tumor proliferation potential

## TL;DR

This study shows that patient-derived organoids can predict chemotherapy response and survival in osteosarcoma patients more accurately than traditional methods.

## Contribution

The study introduces patient-derived organoids as a novel tool for predicting chemotherapy efficacy and survival in osteosarcoma.

## Key findings

- PDO-based CIWS predicted 5-year DFS with 84.6% accuracy, outperforming RECIST.
- CIWS and OFP were significantly associated with 5-year DFS and OS.
- PDOs reflected tumor viability and resistance, offering a potential complement to existing evaluation methods.

## Abstract

Neoadjuvant chemotherapy (NAT) is the standard treatment for osteosarcoma (OS), but patient responses vary, and conventional imaging or pathology offers limited predictive accuracy. Patient-derived organoids (PDOs) are promising models for assessing drug sensitivity and tumor viability ex vivo. This study evaluated the potential of PDO-based drug sensitivity testing and organoid formation potential (OFP) to predict therapeutic outcomes in OS.

Tumor samples from OS patients collected before and after NAT were cultured as 3D PDOs. Chemosensitivity to first-line agents was quantified via a cell inhibition weighted score (CIWS), whereas OFP was used to reflect residual tumor viability. Clinical response was assessed via RECIST 1.1 and, for the primary analysis, dichotomized as responder (CR+PR+SD) versus nonresponder (PD); survival (OS/DFS) was tracked for up to 5 years. Correlations between PDO metrics and clinical outcomes were analyzed.

PDOs were established from 31 samples (18 pre-NAT samples and 13 post-NAT samples), including 8 paired pre/post-NAT samples. CIWS predicted NAT response assessed by RECIST 1.1 with 83.3% accuracy (pre-NAT, 15/18; 95% CI 58.6–96.4) and 5-year DFS with 84.6% accuracy (post-NAT, 11/13; 95% CI 54.6–98.1). With predefined CIWS/OFP cutoffs, Kaplan–Meier analyses showed longer DFS/OS in CIWS-sensitive and OFP-II/III (low growth) groups (P<0.05).

PDOs demonstrated promise as an ex vivo approach to evaluate whether ex vivo chemosensitivity and residual tumor viability measured by PDOs are associated with imaging response and 5-year survival. Their correlation with clinical outcomes highlights the potential of PDO testing to complement existing evaluation methods and to inform individualized treatment strategies.

• Patient-derived organoids (PDOs) were successfully established from 31 osteosarcoma samples (18 pre- and 13 post-neoadjuvant chemotherapies) collected from 23 patients.

• PDO-based drug sensitivity and organoid formation potential reflect tumor viability and resistance.

• CIWS based on PDOs achieved 84.6% (11/13) accuracy, outperforming RECIST evaluation.

• CIWS and OFP were significantly associated with 5-year DFS and OS.