骨来源恶性肿瘤临床疗效的评估

Clinical evaluation of drug efficiency in primary malignant bone tumors

目的:通过现有实体瘤临床评估体系,对骨来源恶性肿瘤术前化疗前后的影像学资料进行总结,对比病理学评估结果,进一步提出并完善适合骨来源恶性肿瘤疗效的临床评估体系。方法:回顾性分析自2014年6月至2017年3月就诊于北京大学人民医院的190例连续病例,最后纳入研究157例,通过病理学Huvos分级将病例进行分组,对术前化疗前后的临床资料(肿瘤最大径变化、代谢参数的变化,以及一些公认的描述性参数)进行差异性检验及通过受试者工作曲线(receiver operating characteristic curve,ROC)计算肿瘤各项参数的变化率对术前化疗病理反应的ROC曲线下面积,并判断病理学分级的截点。结果:对原发肢体骨包含软组织包块的病例,判断坏死率为100%、90%及50%的最大径变化率截点分别为86%、50.7%和0.02%,骨扫描的T/B值变化率对坏死率预测效果不好,而PET/CT的SUVmax变化率对应坏死率为90%和50%的截点分别为60.7%和31.4%;而骨性边界变清晰及骨性密度增高为90%以上的病理学特异性表现形式。对不含软组织包块的原发纯骨内病变的病例,尚未发现有意义的临床评估指标。对中轴骨(包括颌面骨、脊柱及骨盆等)的病灶,由于病例数少,临床评估的截点目前区分度不大。结论:本研究对骨来源肿瘤的疗效临床评估提出了更具体的定义和不同病理学分级的界值,该临床评估体系的完善需通过前瞻、多中心、大宗数据进一步验证和讨论。

Objective: To evaluate whether clinical imaging findings of sarcomas after preoperative chemotherapy correlate with tumor responses by pathological evaluation using the rate of necrosis, so as to develop reliable and quantitative evaluation of clinical response. Methods: We retrospectively reviewed the medical records of 190 patients with high-grade sarcomas(mainly osteosarcomas and Ewing’s sarcomas) that originated from the bone and who received neoadjuvant chemotherapy from June 1,2014 to March 1,2017 at Peking University People’s Hospital. Finally, 157 lesions were evaluated by clinical imaging, including X-ray, computed tomography, magnetic resonance imaging, and bone scans or PET/CT. All patients underwent surgery at our center and pathological evaluation by tumor necrosis rates, which were graded by Huvos’ classification, where grade Ⅰ is 0 to 49%, gradeⅡ is 50% to 89%, grade Ⅲ is 90% to 99%, and grade Ⅳ is 100% necrosis. Statistical diversity analysis was performed by different pathological groups and receiver operating characteristic(ROC) curves. ROC curves were generated to determine the dividing clinical parameters(cut-off values) to distinguish different pathological groups. Results: The cut-off values of the rate change in maximum diameters of tumors located in the extremities were 86%, 50.7%, and 0.02% for Huvos’ Ⅳ, Ⅲ, Ⅱ, and Ⅰgroups, respectively. The differentiation was not obvious using bone scans to distinguish different pathological responses. The cut-off value for SUVmax for Huvos’ Ⅲ, Ⅱ, andⅠ groups were 60.7% and 31.4%, respectively. We did not identify any valuable clinical parameters to evaluate the lesion restricted inside the bone. For sarcomas that originated from the axial skeleton, because of the small size of the sample, the differentiation was not so obvious. Conclusions: This study clearly defined the measuring methods for sarcomas primarily originating from the bone and attempted to determine meaningful cut-off values for multiple pathological response groups. A prospective multicenter trial is warranted to expand the sample size to make this clinical evaluation more precise and practical.