Severe toxicity risk from radiotherapy ‘may not be trivial’ in systemic sclerosis
Click Here to Manage Email Alerts
Key takeaways:
- Most patients with SSc undergoing radiotherapy saw no increase in skin thickening or SSc-related pulmonary events.
- Risks for severe toxicities “may not be trivial” and call for careful monitoring.
Radiotherapy poses no significant risks for worsening disease in patients with systemic sclerosis, but entails “variable risk” for both acute and late toxicities, according to data published in The Journal of Rheumatology.
“The use of radiotherapy in patients with SSc has raised concerns due to the risk of triggering severe skin thickening or the development of localized scleroderma in patients without prior disease,” Aos Aboabat, MBBS, quality lead in the rheumatology unit at King Saud University, in Riyadh, Saudi Arabia, and colleagues wrote. “Additionally, case reports have suggested that patients with SSc who undergo radiotherapy might develop exaggerated skin and visceral fibrosis extending beyond the radiation field, leading to significant radiotherapy morbidity and potential death.”
To examine the effects of radiotherapy on patients with SSc, in the face of conflicting data, Aboabat and colleagues conducted a systematic review of 26 articles gathered from MEDLINE, Embase, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials. The documents included 13 case reports, three case series, five retrospective cohort studies and five case-control studies.
The main outcomes were manifestations of SSc, including flares, skin thickening and pulmonary fibrosis; as well as toxic adverse effects related to radiotherapy, both acute — within 3 months — and late — defined as 3 months after radiotherapy. The researchers used the Common Terminology Criteria for Adverse Events to assess the toxic adverse effects, with toxicities of grade 1 and 2 categorized as non-severe, and grade 3 through 5 categorized as severe.
The review covered a total of 121 patients with SSc undergoing radiotherapy (mean age, 56.4 years; median radiotherapy dose, 50 Gy). Eleven of the studies, representing 51 patients, reported SSc outcomes post-radiotherapy, according to the researchers.
Of those 51 patients, 74.5% (n = 38) demonstrated no worsening of skin thickening, determined by change in modified Rodnan skin score or physician clinical assessment. Also, 74% (n = 37) did not develop SSc-related pulmonary complications after radiotherapy.
Meanwhile, an analysis of the retrospective studies showed an average 57.3% rate of acute severe adverse effects, and a rate of 25.8% for non-severe effects. For late adverse effects, the rates were 32.4% for non-severe and 24% for severe.
“The outcomes of radiotherapy in patients with SSc represent a multifaceted issue that requires careful consideration,” Aboabat and colleagues wrote. “The findings of this study suggest that radiotherapy may be used cautiously in patients with SSc, as the risk of severe toxicity may not be trivial. The occurrence of severe late radiotherapy-related adverse effects underlines the need for vigilant monitoring and appropriate risk management.
“Collaboration between radiation oncologists and rheumatologists is paramount to assess the risks and benefits of radiotherapy on a case-by-case basis, considering the unique aspects of each patient’s condition,” they added. “The journey toward fully understanding the implications of radiotherapy in patients with SSc is still underway.”
Perspective
Back to Top
David A. McLain, MD, MACR, FACP, FRCP
The use of radiotherapy in systemic autoimmune rheumatic diseases (SARDs) has been controversial.
Radiotherapy can be problematic for patients with SARDs because it can increase the risk for treatment toxicity. As the number of patients with cancer and SARDs needing radiotherapy is likely to rise due to advancements in medical treatment and longer life expectancy, the interactions between radiotherapy and SARDs need to be better understood.
Radiotherapy is a cornerstone of cancer treatment, with an estimated 50% of patients with cancer receiving it alone or in combination with other modalities during their treatment odyssey. There is a strong relationship between chronic inflammation and oxidative damage after exposure to ionizing radiation. Cytokines, including interleukin (IL)-1, tumor necrosis factor (TNF-α), and interferon gamma (IFN-γ), play a key role in chronic oxidative damage following exposure to ionizing radiation.
Studies have found that patients with rheumatoid arthritis undergoing radiotherapy for cancer did not show a significant increase in RA reactivation or exacerbation of symptoms. A flare of lupus with radiotherapy has been considered a relative contraindication due to early and late complications. Although multiple studies have indicated that this is not the case, and that lupus patients can tolerate radiotherapy, they are often denied radiation therapy in breast cancer cases.
One study showed that 65% of patients with lupus and cancer could have received curative or symptomatic radiotherapy, but only 10% did. No patient developed any toxicity, leading to the conclusion that radiotherapy is possibly being inappropriately withheld from patients with lupus alongside cancer.
In the present study on patients with scleroderma receiving radiotherapy, most did not show worsened SSc skin thickening or pulmonary complications post-treatment. However, there were uncommon cases of increased skin thickening, acro-osteolysis of digits, new pulmonary fibrosis, new esophageal dysmotility and pulmonary hemorrhage following radiotherapy. Due to these potential adverse effects, careful rheumatologic monitoring is suggested for these patients. In general, radiotherapy is not contraindicated in SARDs, but patients should be monitored by a rheumatologist afterward.
Collapse
Read more about
Click Here to Manage Email Alerts