Urinary Markers May Predict Response to Re-irradiation of Bone Metastases

In a recently published study, patients who did not respond to initial radiation or re-irradiation of symptomatic bone metastases had significantly higher urinary markers of bone turnover at baseline and follow-up.

Patients who responded to re-irradiation of bone metastases had significant differences in certain urinary markers of osteoclasts at baseline compared with patients who did not respond to re-irradiation, results of a National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control.20 companion study indicated.

In fact, Edward Chow, MBBS, MSc, PhD, of Sunnybrook Odette Cancer Centre, University of Toronto, and colleagues found that those patients who did not respond to either initial radiation or re-irradiation of bone metastases had markedly higher urinary markers of bone turnover both at baseline and follow-up.

“In the era of personalized medicine, for patients with painful bone metastases from solid tumors such as breast and prostate, with markedly elevated bone markers who have not been treated with bone-modifying agents, it may be worthwhile to reduce or normalize the levels of the bone markers with bone-modifying agents before the palliative radiotherapy,” wrote Chow and colleagues in Radiotherapy and Oncology.

The NCIC CTG Symptom Control.20 evaluated the use of re-irradiation for reduction in pain related to bone metastases and found that 45% of patients receiving a single 8-Gy treatment and 51% of those receiving with a 20-Gy treatment in multiple fractions had an overall pain response. This benefit was seen in patients regardless of response to initial radiation.

In this companion study, Chow and colleagues examined urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1 month after re-irradiation. These markers were then correlated to response to re-irradiation and initial radiation. Based on these markers, patients were classified as frequent responders (n = 34; response to both initial radiation and re-irradiation), eventual responders (n = 6; response to re-irradiation only), eventual non-responders (n = 59; response to initial radiation only), or absolute non-responders (n = 10).

Looking at these urinary markers, the researchers observed a significant difference between responders and non-responders to re-irradiation for baseline PYD levels (55.5 vs 66.4 in nmol/mmol creatinine; P = .03) and DPD (10.6 vs 14.6 in nmol/mmol creatinine; P = .04). However, at 1 month, no difference between the groups was noted for any of the five markers.

“Comparing the four groups at baseline for the five markers, the mean values for the frequent responders and eventual non-responders were very similar,” the researchers wrote. “The mean values for the eventual responders tended to be lower than the first two groups but the difference did not reach statistical significance.”

The mean values of the urinary markers in absolute non-responders were close to or at least double those for the other three groups, the data showed, and were significantly different for DPD at baseline (P = .03).

Those patients considered to be responders had a median survival of longer than 12 months compared with 8.9 months in non-responders (P = .02).

“Our data demonstrate that a biologic relation exists between bone markers and response to re-irradiation,” the researchers wrote. “Further research is required to determine whether these biomarkers can be developed to provide patients with prognostic information and/or can provide radiation oncologists with predictive information to assist in making treatment decisions.”