评估骨肉瘤组织学反应的预后意义：儿童肿瘤学组骨肿瘤委员会关于CCG-782和INT0133-A结果的比较报告
Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133-A Report From the Children's Oncology Group Bone Tumor Committee.
作者信息
Bishop Michael W, Chang Yu-Chen, Krailo Mark D, Meyers Paul A, Provisor Arthur J, Schwartz Cindy L, Marina Neyssa M, Teot Lisa A, Gebhardt Mark C, Gorlick Richard, Janeway Katherine A, Chou Alexander J
机构信息
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
出版信息
Pediatr Blood Cancer. 2016 Oct;63(10):1737-43. doi: 10.1002/pbc.26034. Epub 2016 Apr 29.
BACKGROUND
The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery.
METHODS
Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event-free survival (EFS-DS) were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan-Meier methodology.
RESULTS
Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1).
CONCLUSION
We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.
背景
骨肉瘤组织学反应的预后价值可能随诱导化疗方案的时间推移而发生变化。我们推测，与儿童癌症组研究CCG - 782相比，INT0133方案中诱导治疗强度的增加会降低组织学反应对根治性手术后事件风险的影响。
方法
对参加CCG - 782和INT0133研究的年龄小于22岁、新诊断为非转移性骨肉瘤的患者进行回顾性分析。评估临床因素与反应及结局的相关性。良好反应定义为切除时存活肿瘤小于5%。使用Cox比例风险模型确定反应、研究和根治性手术后无事件生存期（EFS - DS）之间的关联。EFS - DS采用Kaplan - Meier方法进行估计。
结果
有814例患者的数据（206例CCG - 782，608例INT0133）。对于反应良好者，CCG - 782组的10年EFS - DS（±标准误）为75.4%±7.7%，INT0133组为70.8%±3.1%。对于反应较差者，CCG - 782组的10年EFS - DS为39.9%±4.9%，INT0133组为58.4%±3.1%。组织学反应在各项研究中均能预测结局（P < 0.0001）。观察到EFS - DS在研究与组织学反应之间存在显著交互作用（P = 0.011）。使用比例风险回归分析，与CCG - 782组反应较差者相比，INT0133组反应较差者发生事件的风险较低（相对风险比（RHR）= 0.6:1），但与CCG - 782组反应良好者相比，INT0133组反应良好者发生事件的风险较高（RHR = 1.53:1）。
结论
我们观察到肿瘤坏死的预测价值与诱导治疗强度之间呈负相关，这引发了关于组织学反应真正预后价值的疑问。这凸显了在未来试验中开发治疗策略时需要新的标志物。
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