Risk of Late Toxicity After Radiotherapy in Patients With Connective Tissue Disorders: Association With Connective Tissue Disorder Severity

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There is no way to reliably identify which patients with connective tissue disorders (CTDs) are at greatest risk of radiotherapy-related complications. Building on our prior experience, we have postulated that CTD severity, as measured by the number of organ systems involved, may be predictive of chronic radiation toxicity risk. Medical records of 43 patients with CTDs (20 patients with scleroderma and 23 patients with systemic lupus erythematosus) who received radiotherapy at Mayo Clinic were reviewed. Risk of radiotherapy-related late toxicity was analyzed for patients as a function of CTD severity. The division of patients into high- and low-severity CTD groups was made at the 50th percentile of the number of organ systems involved with the CTD (low-severity CTD included patients with 2 to 3 organ systems involved for scleroderma and 2 to 4 organ systems for lupus; high-severity CTD included patients with 4 to 5 organ systems involved for scleroderma and 5 to 6 organ systems involved for lupus). All 20 scleroderma patients, and 17 of 23 lupus patients, were evaluable for long-term complications. For patients with low-severity CTD, the 5- and 10-year chronic toxicity rates of any grade were 41% (95% CI, 19%–67%) and 52% (95% CI, 26%–88%), respectively. For patients with high-severity CTD, 5- and 10-year chronic toxicity rates of any grade were 79% (95% CI, 52%–93%) and 79% (95% CI, 52%–93%), respectively. Univariate analysis revealed a significant difference in the risk of late toxicity of any grade for patients with high-severity CTD when compared to patients with low-severity CTD (Figure; p = 0.006). No significant difference between the two groups could be demonstrated when analyzing risk of grade 3 or higher late toxicity (p = 0.56), possibly because relatively few patients experienced grade ≥3 late toxicity events (3 patients among the 20 with scleroderma, 4 patients among the 17 with lupus). This study suggests that the severity of the CTD, as estimated by the number of organ systems involved, is one piece of information the clinician may use in evaluating the risk of radiotherapy-related late toxicity in patients with scleroderma or lupus.