Background/Purpose: In the era of modern medicine, radiotherapy remains a cornerstone for the multi-modality cancer treatment.

Methods: We conducted a comprehensive search for any study describing patients with a connective tissue disorder (CTD) who received radiotherapy and reported adverse events (AEs) in electronic databases (MEDLINE, EMBASE, Web of Science, and The Cochrane Library) from inception through March 2013. Our search strategy was restricted to human subjects and studies published in English, French, or Spanish.  Study selection, data collection and quality assessment were independently performed by two pairs of investigators.  Our primary outcome was the incidence of AEs from radiotherapy in patients with CTDs.  Secondary outcomes included: i) predictive factors of AEs ii) effects of radiotherapy on underlying CTD either flares or increased organ damage; and iii) incidence of de novo CTD in patients receiving radiotherapy and iv) Incidence of recurrent malignancies in patients with CTD receiving radiotherapy.  Meta-analyses were performed when there were two or more studies with similar outcomes. AEs were recollected and classified in acute (<90 days) and late (>90 days).

Results: 46 publications were included (5 retrospective cohorts, 6 case series (7 publications), and 34 case reports). Study quality raged from fair to moderate. 832 patients received radiation at palliative or curative doses; 558 patients with a CTD and 274 controls. The age of the included patients ranged from 16-72.  Pooled incidence of significant AEs was 8% (95%CI: 4%, 14%) for acute and 13% (95%CI 9%, 17%) for late. Patients with a CTD had 2.4 greater odds of developing a significant late AEs compared with patients without a CTD (95%CI 1.1, 3.9). No differences were found in the rate of significant acute AEs. AEs rates were affected by radiation site (abdominal, pelvic and CNS), concurrent CTD therapy (use of DMARDs, NSAIDs, or steroids versus no treatment), and type of CTD. Compared to patients without CTD, increased risk of severe AEs were observed in patients with rheumatoid arthritis (late AEs: Peto OR 3.8; 95%CI 1.4, 10.3) and scleroderma (acute AE: Peto OR 16.5; 95% CI 1.5, 186.2 and late AEs: Peto OR 6.8; 95%CI 4.0, 46.1). Regarding, the effects of radiation on underlying disease 19 out of 25 patients with scleroderma had exacerbation of symptoms, 2 patients improved with steroids and penicillamine. The pooled incidence of de novo CTD was 18% (95%CI 9%, 28%) and malignancy recurrence was observed in 3% of the patients.

Conclusion: We observed statistically significant increased rates of severe late AEs in patients with CTD undergoing radiotherapy. Although, radiotherapy is an essential component of cancer therapy, oncologists should be aware that patients with rheumatic diseases requiring radiotherapy as a part of the treatment regimen might be at a greater risk of developing severe adverse events.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adverse-events-with-the-use-of-radiotherapy-in-patients-with-connective-tissue-diseases-and-cancer-a-systematic-review-and-meta-analysis/