肺腺癌骨转移治疗中出现骨耀斑现象的临床研究

Clinical research of bone flare phenomenon in lung adenocarcinoma patients with bone metastases

目的探讨肺腺癌骨转移患者在治疗过程中出现骨耀斑现象的时间、发生率及其临床意义,同时观察血清碱性磷酸酶(ALP)和钙离子(Ca^(2+))水平在判断骨耀斑现象中的参考价值。方法回顾性分析山东省临沂市肿瘤医院自2017年12月至2019年12月57例参加药物临床试验的晚期肺腺癌患者在抗肿瘤治疗过程中的CT影像学表现及血清ALP、Ca^(2+)水平变化。结果57例患者中,基线有骨转移者30例。有46例表皮生长因子受体(EGFR)阴性患者接受含铂双药化疗或联合贝伐珠单抗或联合PD-1抑制剂治疗,11例EGFR阳性患者接受表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)靶向治疗。治疗后有7例发生骨耀斑现象(化疗联合组5例,靶向治疗组2例),均为基线有骨转移的患者,发生率为23.33%(7/30),中位发生时间44天(36~126天),且多在治疗的早期出现。基线有骨转移的30例患者中,收集到5个月以上血清ALP及Ca^(2+)数值的有25例,包括骨耀斑患者7例、获益(PR/SD)患者13例、进展(PD)患者5例。结果显示,治疗过程中疗效不同的患者ALP较基线的中值百分比显示出明显的变化,其中,骨耀斑组和获益组呈下降趋势,且骨耀斑组下降趋势更显著,而进展组患者的ALP数值呈持续升高趋势;血清Ca^(2+)在治疗过程中较基线的中值百分比变化则不明显。结论在抗肿瘤治疗过程中,有些肺腺癌骨转移患者会出现骨耀斑现象,且多在治疗的早期发生,这是对恶性肿瘤全身治疗有效的表现,可结合血清ALP数值变化及临床特征综合判断,避免误诊为骨转移癌病情进展而过早终止有效治疗。

Objective To investigate the time,incidence and clinical significance of bone flare in lung adenocarcinoma patients with bone metastases,at the same time,to observe the reference value of the serum alkaline phosphatase(ALP)and serum calcium(Ca^(2+))in judging bone flare phenomenon.Methods The CT imaging findings,serum ALP and Ca^(2+) levels of 57 patients with advanced lung adenocarcinoma who participated in the anti-tumor clinical trials from December 2017 to December 2019 in Linyi Cancer Hospital were retrospectively analyzed.Results Of the 57 patients,30 had bone metastases at baseline.Forty-six patients with epidermal growth factor receptor(EGFR)negative received platinum-based dual-drug chemotherapy or combined with bevacizumab or PD-1 antibody inhibitors,and 11 EGFR positive patients received targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI).Bone flare occurred in 7 patients with bone metastases at baseline(5 patients in combined chemotherapy group and 2 patients in targeted treatment group)after treatment.The incidence of bone flare was 23.33%(7/30).The median time was 44 days(from 36 days to 126 days),and most often occurred in the early stages of the treatment.Of the 30 patients with bone metastases at baseline,25 patients with ALP and Ca^(2+) levels over 5 months were observed,including 7 patients with bone flare,13 patients with benefit(PR/SD),and 5 patients with progression(PD).The results indicated that the median percentage of ALP of patients with different curative effects showed significant changes compared with baseline,and the bone flare group and benefit group showed a decreasing trend,and the decreasing trend was more significant in the bone flare group,while the ALP values of patients in the progression group increased continuously,but the median percentage change of serum Ca^(2+) during treatment was not significant compared with baseline.Conclusion During the process of anti-tumor treatment,some patients with bone metastasis of lung adenocarcinoma appeard bone flare phenomenon.It mostly occured in the early stage of treatment,and it was an effective manifestation of systemic treatment of malignant tumors.It could be comprehensively judged in combination with the changes of serum ALP value and clinical characteristics to avoid misdiagnosis as the progress of bone metastasis and premature termination of effective treatment.