|
2021年6月，英国《肿瘤内科治疗进展》（IF：8.168）在线发表复旦大学附属肿瘤医院林明曦、金奕滋、杨子怡、胡夕春和张剑（通讯作者）的研究报告，在国际上首次提出并定义了乳腺癌内分泌治疗期间出现的“骨假性进展（bone psedo progression）”，引起广泛关注。 骨是乳腺癌的主要转移部位，39.0%～71.4%的晚期乳腺癌患者可发生骨转移，尤其是激素受体阳性的乳腺癌。然而在内分泌±靶向治疗期间，骨病灶作为非靶病灶准确判断疗效一直存在着困难和争议。该文作者既往工作中发现，出现骨的新病灶（骨扫描筛查、CT或MR证实）并不一定意味着无效，相反，部分患者在延续原方案治疗中得到持续的获益，甚至获益超过没有出现骨新病灶的患者。骨新发病灶一律判定为疾病进展，可能引起过早停止治疗并对临床结局产生不利影响。 文中举出了如下案例（详见原文），并利用复旦大学附属肿瘤医院于2015年9月1日～2020年9月30日临床研究和真实世界中规则随访，具有完备骨扫描、CT/MR定期报告的48例激素受体阳性HER2阴性晚期乳腺癌一线内分泌治疗患者进行回顾分析，部分患者参与了CDK4/6抑制剂的临床试验或临床治疗。在研究和实践中，因为均允许经治医生依据个人经验判断患者是否可能继续获益而继续给予原有内分泌±靶向治疗，因而产生了本文分析的可能性。事实上，根据是否出现骨新病灶，参与者被回顾性分为两组，两组患者在出现骨新病灶后仍继续原有方案治疗，直至出现明确的病变进展（骨外病变进展或溶骨病变进展，以此来定义无进展生存的事件终点）。作者对两组患者的无进展生存和骨外客观缓解率进行了分析。 经过中位随访25.4个月，骨扫描新病灶患者（经CT/MR证实）与未发现骨新病灶患者相比：中位无进展生存相似：26.57比29.57个月（95%置信区间：15.46～37.68、19.24～39.90，风险比：1.098，95%置信区间：0.482～2.503，P=0.818）。 值得注意的是，未发现骨新病灶患者与骨扫描新病灶患者（经CT/MR证实）相比：骨外客观缓解率相似：82.9%比85.7%（比值比：0.806，95%置信区间：0.061～5.682，P=0.999）。 骨新病灶出现（成骨改变）至真实疾病进展的中位间隔为21.26个月（95%置信区间：10.11～32.42）。 该分析结果提示，骨“假性进展”这一现象真实存在，需要关注和良好定义。事实上，这一现象容易出现在CDK4/6抑制剂使用的患者中。 免疫治疗中同样存在着“假性进展”的概念，笔者认为，从机制上讲有异曲同工之处，免疫治疗中假性进展主要来源于免疫细胞的浸润（原有病灶因为小或其他原因未被CT/MR检测到）造成治疗后CT/MR上显示出可检测的“从无到有”征象。乳腺癌内分泌治疗骨假性进展，同样也是如此，骨的早期转移未必立刻产生溶骨性的改变和成骨修复力量的激活，在经过治疗后，溶骨/成骨平衡被打破，当溶骨为主时并被检测到时（局部密度减低、信号变化），一般临床判定为骨“真性进展”，符合我们的临床实践；当成骨为主并检测到时（局部密度增加、信号变化），则有必要综合评估“假性进展”的可能性。 张剑教授在开展此项工作后，认为还有如下几点值得关注：
Ther Adv Med Oncol. 2021 Jun 15;13:17588359211022881. Determination and clinical significance of bone pseudoprogression in hormone receptor-positive metastatic breast cancer. Lin M, Jin Y, Yang Z, Hu X, Zhang J. Fudan University Shanghai Cancer Center, Shanghai, China. BACKGROUND: 99mTechnetium labeled methylene diphosphonate bone scans (BSs) are commonly used to monitor disease progression in bone for patients with metastatic breast cancer (MBC). However, new BS lesions may represent osteoblastic bone healing, which we now define as bone pseudoprogression. In this study, we aimed to assess the clinical significance and determination methods of bone pseudoprogression. METHODS: This retrospective analysis was conducted among 48 patients with hormone receptor-positive MBC treated with first-line endocrine therapy. Four months after initiating therapy, all the participants did not show extraosseous disease progression. Participants were divided into two groups according to the presence of new BS lesions. All the patients continued on treatment until explicit disease progression (extraosseous disease progression or progressive lysis on bone lesions). Explicit progression-free survival (PFS) and extraosseous objective response rate were analyzed between the two groups. RESULTS: New BS lesions were observed in 11 of 48 (22.9%) patients. All the new BS lesions appeared as osteoblastic bone lesions on computed tomography. For patients with new BS lesions, the median PFS was 26.57 months [95% confidence interval (CI) 15.46-37.68], which was similar to that (29.57 months; 95% CI 19.24-39.90) in patients without new BS lesions [hazard ratio: 1.098 (95% CI 0.482-2.503), p = 0.818]. Notably, 82.9% of patients without new BS lesions showed an extraosseous objective response, whereas 85.7% of patients with new BS lesions demonstrated an extraosseous objective response [odds ratio: 0.806 (95% CI 0.061-5.682), p = 0.999]. The median interval between bone pseudoprogression and true disease progression was 21.26 months (95% CI 10.11-32.42). CONCLUSIONS: Osteoblastic new BS lesions detected on follow-up BSs may represent bone pseudoprogression. Clinicians should raise awareness of bone pseudoprogression, thereby avoiding premature discontinuation of therapy and maximizing the opportunity to benefit from endocrine therapy. Due to the small sample size and retrospective nature of the study, large prospective clinical trials are needed to confirm our findings. KEYWORDS: bone metastasis; breast cancer; cyclin-dependent kinase 4/6 inhibitor; endocrine therapy; pseudoprogression PMID: 34188696 PMCID: PMC8209838 DOI: 10.1177/17588359211022881
|
|
|
