Predictors of bone metastasis, skeletal events in lung cancer identified

Researchers have identified a range of factors that are associated with the likelihood that a patient with advanced lung cancer will develop bone metastases or skeletal-related events.

They say these predictive factors – which include cancer stage, performance status, and various biochemical measures – should be taken into consideration when stratifying patients in future clinical trials.

Nobuyuki Katakami (Institute of Biomedical Research and Innovation, Kobe, Japan) and team recruited 274 patients with newly diagnosed lung cancer from 12 centres in Japan. In all, 77 patients had small-cell lung cancer (SCLC) of any stage and 197 had stage IIIB/IV non-small-cell lung cancer (NSCLC).

Patients were reviewed every 4 weeks to see if they had developed skeletal-related events. Treatment for lung cancer and use of zoledronate for bone metastases was at the discretion of the investigator.

Bone metastases were detected in 78 (28.5%) patients at enrolment into the study and in a further 34 (12.4%) during a median 13.8 months of follow-up, report the researchers in the Journal of Thoracic Oncology.

Meanwhile, skeletal-related events occurred in 52 (19.0%) patients and included pathological fracture, radiation to bone, spinal cord compression and hypercalcaemia of malignancy.

The median time from lung cancer diagnosis to bone metastasis was 19.0 months and from metastasis to skeletal-related events was 9.5 months.

Among the patients with NSCLC, multivariate analysis identified three factors that predicted bone metastasis – namely, stage IV disease, performance status 1 or greater and higher bone alkaline phosphatase levels – and three factors that predicted skeletal-related events – namely, stage IV disease, aged 64 years or below and lower albumin levels.

In patients with SCLC, the predictors of bone metastasis were higher levels of lactate dehydrogenase and lower levels of parathyroid hormone–related peptide. The numbers were insufficient to identify any predictors of skeletal-related events in this group with certainty.

Katakami and co-authors say that while some of the predictive factors they identified are as expected, others – such as age below 65 years and use of zoledronate after metastasis – are surprising. Also surprising was the absence of cross-linked N-telopeptide of type I collagen levels as a baseline predictor of skeletal-related events.

They conclude: “Predictive factors should be taken into consideration in future randomized studies evaluating [bone metastasis] and [skeletal-related events].”

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