Toxicity After Radiotherapy in Patients with Historically Accepted Contraindications to Treatment (CONTRAD): An International Systematic Review and Meta-analysis

BACKGROUND AND PURPOSE To investigate the incidence of radiotherapy-related acute and late toxicities among patients with pro-inflammatory comorbidities. MATERIAL AND METHODS PICOS/PRISMA/MOOSE methods were used to identify studies on PubMed and MEDLINE, 1970-2018. The following were extracted: location, cancer, sample size, age, follow-up duration, medical contraindication, treatment, and toxicity. A weighted random effects model with the DerSimonian and Laird method was used in the meta-analysis. The primary endpoint was the grade ≥ 3 acute toxicity, and the secondary endpoint was late toxicity. RESULTS There were 1137 articles screened and 18 included, assessing 621 patients. Among the 18 articles, 10 had collagen vascular disease (n = 417) and 8 had inflammatory bowel disease (n = 204). Median follow-up was 52.8 months. 457 patients received radiotherapy alone, and 153 received concurrent chemo-radiotherapy. The random effects estimate for incidence of grade ≥ 3 toxicity in collagen vascular disease patients (95% confidence interval) was 11.7% (5.4-19.6%) and 6.1% (1.4-12.6%) for acute and late toxicities, respectively. Incidence of grade ≥ 3 toxicity in inflammatory bowel disease patients was 14.0% (7.1-22.4%) and 10.2% (3.2-19.7%) for acute and late toxicities, respectively. Average grade 4 toxicity across both diseases was 1.5% and 4.5% for acute and late toxicities, respectively. Average grade 5 toxicity across both diseases was negligible (<1%). CONCLUSIONS Patients with historically accepted contraindications to radiation therapy have a 10-15% risk of any grade ≥ 3 toxicity, <5% risk of grade 4 toxicity, and <1% risk for grade 5 toxicity, suggesting that collagen vascular disease and inflammatory bowel disease are not absolute contraindications to radiotherapy.