Development and Validation of a Nomogram for Assessing Survival in Patients With Metastatic Lung Cancer Referred for Radiotherapy for Bone Metastases

Key Points

Question

What are the optimal factors to use for constructing a nomogram to assess the probability of survival in patients with bone metastases arising from lung cancer?

Findings

This prognostic study of 477 patients with metastatic lung cancer found that age, histological type, smoking status, epidermal growth factor receptor mutation status, body mass index, and neutrophil to lymphocyte ratio were ideal parameters to construct a nomogram for potentially indicating 3-, 6-, and 12-month survival. This nomogram was successfully validated in a separate cohort of 235 patients at another institution.

Meaning

The study’s nomogram can guide radiation oncologists in making treatment decisions and determining the proper timing for end-of-life discussions and/or hospice referrals.

Abstract

Importance

A survival prediction model for patients with bone metastases arising from lung cancer would be highly valuable.

Objective

To develop and validate a nomogram for assessing the survival probability of patients with metastatic lung cancer receiving radiotherapy for osseous metastases.

Design, Setting, Participants

In this prognostic study, the putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression analysis with backward elimination and model selection based on the Akaike information criterion. The nomogram was subjected to internal (bootstrap) and external validation; its calibration and discriminative ability were evaluated with calibration plots and the Uno C statistic, respectively. The training and validation set cohorts were from a tertiary medical center in northern Taiwan and a tertiary institution in southern Taiwan, respectively. The training set comprised 477 patients with metastatic lung cancer who received radiotherapy for osseous metastases between January 2000 and December 2013. The validation set comprised 235 similar patients treated between January 2011 and December 2017. Data analysis was conducted May 2018 to July 2018.

Main Outcomes and Measures

The nomogram end points were death within 3, 6, and 12 months.

Results

Of 477 patients in the training set, 292 patients (61.2%) were male, and the mean (SD) age was 62.86 (11.66) years. Of 235 patients in the validating set, 113 patients (48.1%) were male, and the mean (SD) age was 62.65 (11.49) years. In the training set, 186 (39%), 291 (61%), and 359 (75%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 4.21 (95% CI, 3.68-4.90) months. In the validating set, 84 (36%), 120 (51%), and 144 (61%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 5.20 (95% CI, 4.07-7.17) months. Body mass index (18.5 to <25 vs ≥25: hazard ratio [HR], 1.42; 95% CI, 1.14-1.78 and <18.5 vs ≥25: HR, 2.31; 95% CI, 1.56-3.44), histology (non–small cell vs small cell lung cancer: HR, 0.59; 95% CI, 0.41-0.86), epidermal growth factor receptor mutation (positive vs unknown: HR, 0.66; 95% CI, 0.46-0.93 and negative vs unknown: HR, 0.98; 95% CI, 0.66-1.45), smoking status (ever smoker vs never smoker: HR, 1.50; 95% CI, 1.24-1.83), age, and neutrophil to lymphocyte ratio were incorporated. The HRs of age and neutrophil to lymphocyte ratio were modeled nonlinearly with restricted cubic splines (both P < .001). The nomogram’s discriminative ability was good in the training set (C statistic, ≥0.77; P < .001) and was validated using both an internal bootstrap method (C statistic, ≥0.76; P < .001) and an external validating set (C statistic, ≥0.75; P < .001). The calibration plots for the end points showed optimal agreement between the nomogram’s assessment and actual observations.

Conclusions and Relevance

The nomogram (with web-based tool) can be useful for assessing the probability of survival at 3, 6, and 12 months in patients with metastatic lung cancer referred for radiotherapy to treat bone metastases, and it may guide radiation oncologists in treatment decision making and engaging patients in end-of-life discussions and/or hospice referrals at appropriate times.

Abstract

This prognostic study develops and validates a nomogram to assess the probability of survival at 3, 6, and 12 months in patients from Taiwan with metastatic lung cancer who were referred for radiotherapy to treat osseous metastases.