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. 2022 Apr 7:12:812358.
doi: 10.3389/fonc.2022.812358. eCollection 2022.

Predicting Bone Metastasis Risk Based on Skull Base Invasion in Locally Advanced Nasopharyngeal Carcinoma

Bo Wu  1   2 , Yu Guo  2 , Hai-Hua Yang  3 , Qian-Gang Gao  2 , Ye Tian  1
Affiliations

Predicting Bone Metastasis Risk Based on Skull Base Invasion in Locally Advanced Nasopharyngeal Carcinoma

Bo Wu et al. Front Oncol. .

Abstract

Objective: To develop and validate a bone metastasis prediction model based on skull base invasion (SBI) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

Methods: This retrospective cohort study enrolled 290 patients with LA-NPC who received intensity-modulated radiation therapy in two hospitals from 2010 to 2020. Patient characteristics were grouped by SBI and hospital. Both unadjusted and multivariate-adjusted models were used to determine bone metastasis risk based on SBI status. Subgroup analysis was performed to investigate heterogeneity using a forest graph. Cox proportional hazard regression analysis was used to screen for risk factors of bone metastasis-free survival (BMFS). A nomogram of BMFS based on SBI was developed and validated using C-index, receiver operating characteristic curve, calibration curves, and decision curve analysis after Cox proportional hazard regression analysis.

Results: The incidence of bone metastasis was 14.83% (43/290), 20.69% (24/116), and 10.92% (19/174) in the overall population, SBI-positive group, and SBI-negative group, respectively. In the unadjusted model, SBI was associated with reduced BMFS [HR 2.43 (1.32-4.47), P = 0.004], and the results remained stable after three continuous adjustments (P <0.05). No significant interaction was found in the subgroup analyses (P for interaction >0.05). According to Cox proportional hazard regression analysis and clinical value results, potential risk factors included SBI, Karnofsky performance status, TNM stage, induction chemotherapy, concurrent chemoradiotherapy, and adjuvant chemotherapy. Using a training C-index of 0.80 and a validation C-index of 0.79, the nomogram predicted BMFS and demonstrated satisfactory prognostic capability in 2, 3, and 5 years (area under curve: 83.7% vs. 79.6%, 81.7% vs. 88.2%, and 79.0% vs. 93.8%, respectively).

Conclusion: Skull base invasion is a risk factor for bone metastasis in patients with LA-NPC. The SBI-based nomogram model can be used to predict bone metastasis and may assist in identifying LA-NPC patients at the highest risk of bone metastasis.

Keywords: bone metastasis; bone metastasis-free survival; intensity modulated radiation therapy; nasopharyngeal carcinoma; nomogram; prediction model; skull base invasion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the study selection process.
Figure 2
Figure 2
Kaplan–Meier Survival Curves for bone metastasis-free survival (A), distant metastasis-free survival, (B) and overall survival (C) of locally advanced nasopharyngeal carcinoma patients based on skull base invasion.
Figure 3
Figure 3
Hazard risk of bone metastasis in subgroup analyses after adjustment for hospital, age, sex, Karnofsky performance status, smoking index, and histological type.
Figure 4
Figure 4
Nomogram predicting 24, 36, and 60 months of bone metastasis-free survival.
Figure 5
Figure 5
ROC curves of the training dataset (A) and the validation dataset (B) in 24 months (AUC: 83.7% vs. 79.6%), 36 months (AUC: 81.7% vs. 88.2%) and 60 months (AUC: 79.0% vs. 93.8%).
Figure 6
Figure 6
Calibration curves of the training dataset (A–C) and the validation dataset (D–F) in 24, 36, and 60 months.
Figure 7
Figure 7
Usefulness evaluation of the training dataset (A–C) and the validation dataset (D–F) in 24, 36, and 60 months.
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