Risk of radiation-induced malignancy after low-dose radiotherapy for non-malignant musculoskeletal disorders: A long-term retrospective analysis of n=4699 patients.

Abstract

Musculoskeletal disorders are conditions with substantial medical and economic consequences. Low-dose radiotherapy is re-gaining large-scale global significance as a cost-effective conservative treatment that can provide significant symptomatic relief, due to its anti-inflammatory and anti-proliferative effects. The aim of this study is to appraise the potential risk of secondary malignant neoplasms following functional low-dose radiotherapy for non-malignant musculoskeletal disorders in a long-term analysis. Single-center retrospective observational analysis. All patients that received LDRT for non-malignant musculoskeletal disorders between January 1, 1994 and December 31, 2011 were included. Data on newly diagnosed malignant neoplasms, overall survival, and cause of death were documented. Overall survival was estimated using Kaplan-Meier analysis. Solid malignancies were considered secondary malignant neoplasms if they occurred within the irradiated field. For hematologic malignancies, treatment regions were categorized by the presence or absence of active red bone marrow based on International Commission on Radiological Protection data for adults. n=4699 patients underwent low-dose radiotherapy (mean age 64 years); n=5614 treatment series were conducted. Kaplan-Meier estimates showed an expected post-LDRT life expectancy of 21 years. Treatment sites were classified as distal joints (62%), proximal joints (37%), and others (1%). Three solid malignancies were observed within previously irradiated regions, corresponding to an incidence of 0.064%. At 12.5 years, hematologic malignancy-free survival was 99.0% in the non-marrow-adjacent group compared to 97.7% in the marrow-adjacent group, corresponding to an absolute difference of 1.3 percentage points (p=0.002; Relative risk 1.013). Hematologic malignancy-free survival, was significantly different when comparing non-marrow-adjacent regions to the shoulder (p=0.001) and trunk/pelvic region (p=0.003). The greatest theoretical risk of secondary malignant neoplasms arises from low-dose radiotherapy of central trunk regions, where potential risks for systemic and solid cancers overlap. Overall, contemporary low-dose radiotherapy appears safe for peripheral indications, while treatments near marrow-rich or central trunk structures should be applied judiciously.