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. 2024 Oct 31;13(10):2603-2616.
doi: 10.21037/tlcr-24-441. Epub 2024 Oct 18.

Prognostic significance of bone metastasis and clinical value of bone radiotherapy in metastatic non-small cell lung cancer receiving PD-1/PD-L1 inhibitors: results from a multicenter, prospective, observational study

Huiling Dong #  1   2 , Aihua Lan #  1   2 , Jie Gao  1   2 , Yulin An  1   2 , Li Chu  1   2 , Xi Yang  1   2 , Xiao Chu  1   2 , Jie Hu  3 , Qian Chu  4 , Jianjiao Ni  1   2 , Zhengfei Zhu  1   2   5   6
Affiliations

Prognostic significance of bone metastasis and clinical value of bone radiotherapy in metastatic non-small cell lung cancer receiving PD-1/PD-L1 inhibitors: results from a multicenter, prospective, observational study

Huiling Dong et al. Transl Lung Cancer Res. .

Abstract

Background: Bone metastasis (BoM) is a prevalent occurrence in patients with non-small cell lung cancer (NSCLC), significantly impacting prognosis and diminishing both survival rates and patients' quality of life. More and more studies have demonstrated that immunotherapy can improve the prognosis of NSCLC patients with bone metastases. Previous investigations pertaining to BoM in NSCLC have generally suffered from small sample sizes, absence of propensity score matching (PSM) to equate baseline characteristics, and an omission of the examination of patterns of treatment failure. This study aims to evaluate the prognostic significance of BoM and potential clinical value of bone radiation in metastatic NSCLC patients receiving immunotherapy.

Methods: Metastatic NSCLC patients receiving programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors from three academic centers were enrolled in a prospective, observational trial (https://clinicaltrials.gov/study/NCT04766515) and those with measurable disease and adequate follow-up were retrospectively reviewed. Propensity score matched (PSM) patients with and without BoM were included in this study. Treatment efficacy, pattern of failure and clinical value of bone radiotherapy were extensively evaluated.

Results: A total of 544 out of 1,451 immunotherapy-treated NSCLC patients were included after PSM, including 272 with BoM and 272 without. Patients with baseline BoM had a median progression-free survival (PFS) of 7.8 months [95% confidence interval (CI): 7.0-8.7], lower than those without it (9.5 months; 95% CI: 8.9-10.0) (P<0.001). Patients with baseline BoM had a median overall survival (OS) of 14.5 months (95% CI: 12.6-16.4), lower than those without 27.6 months (95% CI: 25.1-30.1) (P<0.001). Patients with BoM also had lower objective response rate than those without it (11.1% vs. 15.8%, P<0.001). Initial disease progression in the bone was more common in those with BoM (56.5%) compared to those without it (31.7%) (P<0.001). Meanwhile, among patients with BoM, no significant difference of PFS was found between those receiving bone radiation or not, possibly due to a dominant use of palliative radiotherapy.

Conclusions: Baseline BoM correlated with worse prognosis and palliative bone radiation did not improve PFS in metastatic NSCLC patients receiving PD-1/PD-L1 inhibitors.

Keywords: Non-small cell lung cancer (NSCLC); bone metastasis (BoM); bone radiotherapy; programmed cell death protein 1/programmed cell death-ligand 1 inhibitors (PD-1/PD-L1 inhibitors); progression-free survival (PFS).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-441/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Flowchart of patient enrollment. NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1; PSM, propensity score matching.
Figure 2
Figure 2
Kaplan-Meier analysis of progression-free survival and overall survival. (A) Kaplan-Meier plots of PFS in patients with BoM and non-BoM. (B) Kaplan-Meier plots of OS in patients with BoM and non-BoM. BoM, bone metastasis before immunotherapy; non-BoM, no bone metastasis before immunotherapy; PFS, progression-free survival; OS, overall survival.
Figure 3
Figure 3
Treatment failure and cumulative incidence of bone metastasis. (A) PD pattern of immunotherapy failure in patients with baseline bone metastasis and no bone metastasis. (B) Kaplan-Meier analysis of cumulative incidence of bone metastasis following immunotherapy in patients without bone metastasis at baseline. PD, progressive disease; OPD, metastasis to other sites outside the bone leads to disease progression; OBPD, metastasis of bone and other parts leading to disease progression; BPD, bone metastasis led to disease progression; BoM, bone metastasis before immunotherapy; non-BoM, no bone metastasis before immunotherapy.
Figure 4
Figure 4
Kaplan-Meier analysis of progression-free survival in those with baseline bone metastasis. (A) Kaplan-Meier plots of PFS in patients with bone radiotherapy and no bone radiotherapy. (B) Kaplan-Meier plots of PFS in patients with SBRT, PBT and no bone radiotherapy. SBRT, stereotactic body radiotherapy; PBT, palliative bone radiotherapy; RT, radiotherapy; PFS, progression-free survival.
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