Impact of Collagen Vascular Disease on Radiation-Related Toxicity in Breast Cancer Patients: A Matched Pair Analysis

Abstract

To evaluate the impact of collagen vascular disease (CVD) on treatment-related toxicity in women undergoing radiotherapy (RT) for breast cancer. We queried a prospective institutional database for women with CVD treated with RT for breast cancer between 1981 and 2016. Each patient was matched to 3 controls without CVD using the following match criteria: age ± 5 years, race, treatment year ±5 years, RT field, laterality, RT dose ± 2Gy. Medications used for CVD at time of RT were recorded as requirement for disease-modifying antirheumatic drugs (DMARDs) might indicate more active CVD. RT toxicity was graded using CTCAE 4.0. We defined acute toxicity as events occurring during RT to within 90 days of completion of RT and late toxicity as events occurring >90 days of RT completion. Acute toxicity included radiation dermatitis (skin erythema, desquamation, edema, skin necrosis/ulceration), and pain; late toxicity included edema, telangiectasia, fibrosis, hyperpigmentation, tissue necrosis, skin infection, lymphedema, pain, radiation pneumonitis. Grade 2+ (G2+) acute and late toxicities were compared between patients with CVD and those matched controls using generalized estimating equation (GEE). No multivariable analysis was performed because all covariates were used as matching factors. Forty three patients with documented CVD at time of RT (40-rheumatoid arthritis, 2-lupus, 1-polymyositis) were matched to 129 controls without CVD. The median dose of RT was 60 Gy and the median follow up was 87 months (1-354 m). The majority of patients received breast only RT (81%). Among these 43 patients, 25 (58%) were taking DMARDs and 18 (42%) were taking either no medication (n=8) or non-DMARDs (n=10). In patients with CVD, 25.6% had G2+ acute toxicity (18.6% Grade 2; 7.0% Grade 3; 0% Grade 4) and 7.0% had G2+ late toxicity (7.0% Grade 2; 0% Grade 3; 0% Grade 4). When comparing the patients with CVD to the matched control patients, there was no significant difference in the rates of G2+ acute toxicity (25.6% vs 25.6%, OR=1.0, CI 0.49-2.04) or G2+ late toxicity (7.0% vs 10.1%, OR=0.67, CI 0.19-2.38). When patients on DMARDs (n=25) were compared to those on no medication or non-DMARDs (n=18) there was also no significant difference in the rates of G2+ acute toxicity (p=0.42) or G2+ late toxicity (p=0.42). In this matched pair analysis, radiation for breast cancer was well-tolerated among women with CVD (with majority having rheumatoid arthritis) without significantly increased risk of toxicity. Counseling for standard acute and late toxicities for breast radiation seems to be appropriate among this group of patients.