Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, PR China.
Cancer Rep (Hoboken). 2023 Jan;6(1):e1628. doi: 10.1002/cnr2.1628. Epub 2022 May 25.
With more and more target medicine application in lung cancer, lots of patients take medicine at home, the treatment bone metastasis and screen of bone metastasis always has been neglected until skeletal-related events (SREs) such as bone pain, hypercalcemia of malignancy and pathologic fractures emerging which significantly impairs the patients' daily activity ability, seriously lower quality of life.
To identify the clinical characteristics of patients which influence the overall survival (OS) of EGFR-TKIs effective in EGFR-mutant NSCLC with bone metastasis (BM) and the bone metastatic image features.
We conducted a retrospective study in patients (treated with EGFR-TKIs ≥6 months) of lung adenocarcinoma with BM in our hospital from October 2014 to October 2017. The Kaplan-Meier survival curves were calculated using the log-rank univariate test. Multivariate regression analysis was conducted using Cox's regression model. Comparison between the different subgroups of bone metastasis was conducted using Pearson Chi-Square test.
A total of 79 patients were diagnosed as EGFR-mutant lung adenocarcinoma with bone metastases. At univariate analysis, age < 65 years (p = .024), heavy smoking (p = .005), Osteolytic BM (p = .034), number of bone metastasis ≥3 (p = .032), EGFR-L858R mutated (p = .018) and bisphosphonate times <6 (p = .046), were significantly associated with worse overall survival (OS). At multivariate analysis, EGFR 19del was an independent predictor of better OS (p = .035). Osteolytic BM was more likely to occur in EGFR-mutant patients (osteolytic vs. sclerotic vs. mixed: 45.57% vs. 34.18% vs. 20.25%). Patients who had received bisphosphonate ≥6 times were less suffer from SRE compared to those treated with bisphosphonate <6 times (p = .019).
In conclusions, this retrospective study suggests that for the patients, treated with EGFR-TKIs ≥6 months, EGFR exon 19 del, osteogenic bone metastasis, bisphosphonate application times ≥6, smoking <400/day and the number of BM <3 were predictors of better OS (p < .05). Bisphosphonate times ≥9 should be considered to the patients with BM. SPECT-CT would be an effective correction of SPECT in the patient's bone metastasis examination. During the whole follow-up process, we found by chance that the change of bone mineral density in the follow-up process suggested that bisphosphonates need to be used for more than 1 year or more, and we can use local CT in the follow-up clinical practice to confirm the bone density changes to decide when we could stop or reduce bisphosphonate application.
随着越来越多的靶向药物应用于肺癌，许多患者在家中服药，治疗骨转移和筛选骨转移一直被忽视，直到出现骨骼相关事件（SREs），如骨痛、恶性高钙血症和病理性骨折，这显著影响了患者的日常活动能力，严重降低了生活质量。
确定影响 EGFR 突变型非小细胞肺癌伴骨转移（BM）患者表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）总生存期（OS）的临床特征，以及骨转移的影像学特征。
我们对 2014 年 10 月至 2017 年 10 月在我院接受 EGFR-TKIs 治疗≥6 个月的肺腺癌伴 BM 患者进行了回顾性研究。采用对数秩检验对 Kaplan-Meier 生存曲线进行单因素分析。采用 Cox 回归模型进行多因素回归分析。采用 Pearson Chi-Square 检验比较不同骨转移亚组之间的差异。
共诊断 79 例 EGFR 突变型肺腺癌伴骨转移患者。单因素分析结果显示，年龄<65 岁（p=0.024）、大量吸烟（p=0.005）、溶骨性 BM（p=0.034）、骨转移≥3 个（p=0.032）、EGFR-L858R 突变（p=0.018）和双膦酸盐治疗次数<6 次（p=0.046）与总生存期（OS）显著相关。多因素分析结果显示，EGFR 19 缺失是 OS 的独立预测因子（p=0.035）。溶骨性 BM 更易发生在 EGFR 突变型患者中（溶骨性比硬化性比混合性：45.57%比 34.18%比 20.25%）。与接受双膦酸盐治疗<6 次的患者相比，接受双膦酸盐治疗≥6 次的患者发生 SRE 的可能性较小（p=0.019）。
总之，这项回顾性研究表明，对于接受 EGFR-TKIs 治疗≥6 个月的患者，EGFR 外显子 19 缺失、成骨性骨转移、双膦酸盐应用次数≥6 次、吸烟<400/天和 BM<3 个是 OS 的预测因子（p<0.05）。对于有 BM 的患者，应考虑使用双膦酸盐治疗 9 次以上。SPECT-CT 可作为 SPECT 骨转移检查的有效校正。在整个随访过程中，我们偶然发现，在随访过程中骨密度的变化表明需要使用双膦酸盐治疗 1 年以上，我们可以在随访临床实践中使用局部 CT 来确认骨密度的变化，以决定何时停止或减少双膦酸盐的应用。
