骨肉瘤组织学反应和强化化疗的短期和长期预后价值：BO06 试验的回顾性重新分析。

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

机构信息

Korteweg-de Vries Institute for Mathematics, University of Amsterdam, Amsterdam, The Netherlands

Department of Biomedical Data Science, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

BMJ Open. 2022 May 10;12(5):e052941. doi: 10.1136/bmjopen-2021-052941.

DOI:10.1136/bmjopen-2021-052941

PMID:35537786

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9092180/

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.

INTERVENTIONS

Two regimens with the same anticipated cumulative dose (doxorubicin 6×75 mg/m/week; cisplatin 6×100 mg/m/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

ISRCTN86294690.

摘要

目的

考虑到已治愈和未治愈患者的治愈率模型可提供对长期和短期生存的更深入了解。我们旨在评估组织学反应和化疗强化对未治愈患者的治愈率和无进展生存期（PFS）的预测价值。

设计

随机对照试验 MRC BO06（EORTC 80931）的回顾性分析。

设置

基于人群的研究，但提出的方法可应用于其他试验设计。

参与者

共 497 例可切除的高级骨肉瘤患者，其中 118 例因未开始化疗、未报告组织学反应、报告异常剂量或在治疗期间疾病进展而被排除在外。

干预措施

两种方案具有相同的预期累积剂量（阿霉素 6×75mg/m/周；顺铂 6×100mg/m/周），但时间安排不同：方案-C 每 3 周一次，方案-DI 每 2 周一次。

主要和次要结果测量

主要结果是从治疗结束时开始计算的 PFS，因为如果发生治愈，则可能在治疗期间的任何时间发生。使用混合治愈模型来研究组织学反应和强化化疗对未治愈患者的治愈状态和 PFS 的影响。

结果

组织学反应是治愈状态的一个强有力的预后因素（OR 3.00，95%CI 1.75 至 5.17），但对未治愈患者的 PFS 没有明显影响（HR 0.78，95%CI 0.53 至 1.16）。在组织学反应良好（GR，PR）和较差的患者中，治愈率分别为 55%（46%-63%）和 29%（22%-35%）。强化方案与 PR 患者的治愈率更高相关（OR 1.90，95%CI 0.93 至 3.89），但对 GR 患者没有影响（OR 0.78，95%CI 0.38 至 1.59）。