Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial

• Published in: BMJ open 2022-05, Vol.12 (5), p.e052941-e052941
• Main Authors: Musta, Eni, van Geloven, Nan, Anninga, Jakob, Gelderblom, Hans, Fiocco, Marta
• Format: Article
• Language: English
• Subjects: Bone cancer; Cancer therapies; Chemotherapy; Drug dosages; Medical prognosis; Oncology; paediatric oncology; Patients; Pediatrics; Sarcoma; statistics & research methods; Surgery; Toxicity
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2021-052941

ObjectivesCure rate models accounting for cured and uncured patients, provide additional insights into long and short-term survival. We aim to evaluate the prognostic value of histological response and chemotherapy intensification on the cure fraction and progression-free survival (PFS) for the uncured patients.DesignRetrospective analysis of a randomised controlled trial, MRC BO06 (EORTC 80931).SettingPopulation-based study but proposed methodology can be applied to other trial designs.ParticipantsA total of 497 patients with resectable highgrade osteosarcoma, of which 118 were excluded because chemotherapy was not started, histological response was not reported, abnormal dose was reported or had disease progression during treatment.Intervention(s)Two regimens with the same anticipated cumulative dose (doxorubicin 6×75 mg/m2/week; cisplatin 6×100 mg/m2/week) over different time schedules: every 3 weeks in regimen-C and every 2 weeks in regimen-DI.Primary and secondary outcome measuresThe primary outcome is PFS computed from end of treatment because cure, if it occurs, may happen at any time during treatment. A mixture cure model is used to study the effect of histological response and intensified chemotherapy on the cure status and PFS for the uncured patients.ResultsHistological response is a strong prognostic factor for the cure status (OR 3.00, 95% CI 1.75 to 5.17), but it has no clear effect on PFS for the uncured patients (HR 0.78, –95% CI 0.53 to 1.16). The cure fractions are 55% (46%–63%) and 29% (22%–35%), respectively, among patients with good and poor histological response (GR, PR). The intensified regimen was associated with a higher cure fraction among PR (OR 1.90, 95% CI 0.93 to 3.89), with no evidence of effect for GR (OR 0.78, 95% CI 0.38 to 1.59).ConclusionsAccounting 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 counselling patients and can have an impact on treatment decisions.Trial registration numberISRCTN86294690.