Retrospective Study of EGFR-mutant Lung Adenocarcinoma with Bone Metastatic Clinical Features

Background: 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.

Aim: 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.

Methods: 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.

Results: 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).

Conclusion: 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.