An intra-patient dose-escalation study of disodium pamidronate plus radiotherapy versus radiotherapy alone for the treatment of osteolytic metastases. Monitoring of recalcification using image-processing techniques

Objective: To evaluate the clinical benefit and mainly to monitor quantitatively the recalcification of osteolytic lesions after radiotherapy with or without intravenous infusion of disodium pamidronate (DP) in different doses. Patients and Methods: 42 patients with solitary lytic metastasis in weight-bearing bones were studied. Primary endpoints were the mean value and energy of gray-level histogram in plain radiographs (MVGLH and EGLH) and relative electron density (RED) of CT scans in bone lesions. In eleven patients (group A) the DP dose was increased stepwise from 90 up to 180 mg (flat dose), while in other 15 patients (group B) a flat dose of 180 mg was administered intravenously in 2 h. In both groups, the first session of DP was given concurrently with local radiotherapy (30 Gy in ten fractions, 5 days a week). Another 16 patients (group C) underwent radiotherapy only. Results: Morbidity related to pamidronate was mild. Significant differences from the baseline (p < 0.05, Wilcoxon test) were recorded for MVGLH, EGLH and RED values, regarding all groups. Improvement was significantly higher in patients of group B versus A, while the results of pamidronate groups (A and B) were superior to group C, concerning the above indices (p < 0.05, Mann-Whitney test). Additionally, pamidronate groups had significantly lower skeletal morbidity than group C. Conclusion: The 2-h infusional flat dose of 180 mg every 4 weeks seems to be tolerable and superior to 90 mg regarding palliation and mainly recalcification of osteolytic lesions. Radiotherapy alone is effective but inferior to the combined treatment. Last but not least, the findings of MVGLH, EGLH and RED indicate an important increase in bone mass and bone formation, which was difficult to be identified visually by the experts. (orig.)