Abstract
Objectives
Cure 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.
Design
Retrospective analysis of a randomised controlled trial, MRC BO06
(EORTC 80931).
Setting
Population-based study but proposed methodology can be applied to
other trial designs.
Participants
A 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 measures
The 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.
Results
Histological 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).
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 counselling patients and can
have an impact on treatment decisions.
Trial registration number
NCT86294690.
Cited by
1 articles.
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