A new perspective on the BO06 trial in osteosarcoma: short- and long-term prognostic value of histologic response and intensified chemotherapy

Purpose Cure rate models accounting for cured and uncured patients, provide additional insights into long and short term survival. We aim to better understand the prognostic value of histologic response and chemotherapy intensification on cure fraction and progression-free survival (PFS) for the uncured patients. Methods A logistic model is assumed for the effect of histologic response and intensified chemotherapy on the cure status, while a Cox regression model is estimated only for the uncured patients on PFS. The mixture cure model is used to simultaneously study these two effects. Results Histologic response is a strong prognostic factor for the cure status (OR: 3.00 [1.75-5.17]), but it has no clear effect on PFS for the uncured patients (HR: 0.78 [0.53-1.16]). The cure fractions are 55% [46%-63%] and 29% [22%-35%] among patients with good histologic response (GR) and poor responders (PR) respectively. The intensified regimen was associated with higher cure fraction among PR (OR: 1.90 [0.93 – 3.89]), with no evidence of effect for GR (OR: 0.78 [0.38 – 1.59]). Conclusions Accounting for cured patients is valuable in distinguishing the covariate effects on cure and PFS. Estimating cure chances based on these prognostic factors is relevant for counseling patients and can affect treatment decisions.