The report is a product of the VA/HSR Evidence Synthesis Program.

Radiation Therapy for Benign Conditions: A Systematic Review

Takeaway: Evidence for use of low-dose radiation therapy (RT) was reviewed for 9 benign conditions. RT may reduce heterotopic ossification (abnormal bone growth) and improve function in plantar fasciitis. There was no significant difference in pain for keloids (scarring). There was either insufficient or no evidence for the effect of RT for people with keloids, pterygium (fleshy eye growth), osteoarthritis, Peyronie's disease (inner penis scarring), Dupuytren's contracture (a hand condition), and hidradenitis suppurativa (a painful skin condition). However, there is no indication that RT should not be used after conventional therapy fails.

Veterans are at increased risk for certain benign inflammatory and degenerative musculoskeletal, orthopedic, and soft tissue conditions that can cause physical limitations and decreased quality of life. Low-dose radiation therapy (RT; a dose of <60 Gray units) has been explored as a treatment for benign inflammatory and degenerative musculoskeletal disease, typically when conventional therapy fails. Outside of Germany, RT is rarely used to treat benign diseases.

In response to a request from VA’s National Radiation Oncology Program, HSR’s Evidence Synthesis Program (ESP) Center in Providence, RI, conducted a systematic review on the evidence of RT for 9 benign conditions: heterotopic ossification (abnormal bone growth), keloids (scarring), plantar fasciitis, pterygium (fleshy eye growth), osteoarthritis, Ledderhose disease (a foot condition), Dupuytren’s contracture (a hand condition), Peyronie’s disease (inner penis scarring), and hidradenitis suppurativa (a painful skin condition). ESP investigators sought to answer the following question:

What are the benefits and harms of low-dose radiation therapy for the treatment or prevention of benign hyperproliferative and degenerative skin/epithelial, and musculoskeletal disorders such as keloid scars, hidradenitis suppurativa, Dupuytren’s contracture, Ledderhose disease, Peyronie’s disease, plantar fasciitis, heterotopic ossification, pterygium, or osteoarthritis in adults?

Investigators searched for relevant peer-reviewed articles in Medline (via PubMed), Embase, and ClinicalTrials.gov from inception to April 1, 2023. One included study was identified by the peer reviewers and was published in May 2023. Investigators excluded studies where participants were <18 years of age, where the majority of patients received re-irradiation of the same anatomic site, where brachytherapy cancer treatment (except for pterygium) was used, and where the majority of patients were treated before 1980. In all, investigators identified 48 studies on the use of low-dose RT for the 9 prioritized diseases.

Summary of Findings

Across all 48 studies, there was wide variation in the total dose of RT (in 47 studies range = 0.5 to 40 Gray units and in 1 study <5% of patients received up to 70 Gray units), sample size (range = 17 to 2,164), and follow-up (range = 1 to 144 months). Five of nine diseases did not have enough comparative data to evaluate the certainty of evidence.

• RT may reduce heterotopic ossification and improve function in plantar fasciitis. There was no significant difference in pain for keloids. There was either insufficient or no evidence for the other diseases.
• Low-dose RT may be safe. Local skin reactions were the most common side effect, but studies did not consistently report adverse events and it was not always clear whether an adverse event was due to RT, a co-occurring intervention (e.g., surgery), or a natural feature of the lesion.
• No study reported cases of radiation-induced malignancies—a concern of patients and providers—but sample sizes were too small or follow-up time was too short to detect this rare outcome.
• Single group studies predominantly informed the synthesis for most of the diseases. Findings (especially causal inference) from single group studies need to be interpreted with caution because it is challenging to differentiate treatment effect from symptom resolution that could have occurred naturally over the study observation period.
• Few studies reported patient satisfaction, experience of care, or quality of life.

Implications

RT may reduce the occurrence of heterotopic ossification and improve function in plantar fasciitis. There was no significant difference in pain for people with keloids. The investigators had low confidence in these findings due to methodological limitations and imprecise and inconsistent estimates. One randomized controlled trial (RCT) showed that symptoms improved for people with Ledderhose disease after RT compared to sham RT (certainty of evidence was not evaluated). Aside from these, there was either insufficient or no evidence for the effect of RT on disease-related outcomes, side effects, or patient satisfaction, experience, or quality of life for people with pterygium, osteoarthritis, Peyronie’s disease, Dupuytren’s contracture, and hidradenitis suppurativa. Despite the gaps in the evidence, investigators found no indication that RT should not be used after conventional therapy fails for the 9 prioritized diseases and conclude equipoise about the clinical utility of RT in patients failing conventional therapies.

Limitations

None of the articles focused on Veterans, but the clinical findings likely translate to the VA population. Given the large number of diseases and published studies, the review team prioritized comparative designs (i.e., a best-evidence approach). Nevertheless, this design decision may have excluded non-comparative studies with important data on the benefits and harms of RT for benign conditions. The reviewers were unable to investigate potential sources of heterogeneity of treatment effects. Finally, sometimes it was unclear whether an adverse event was a negative consequence of the treatment.

Future Research

There is a need for well-designed, adequately powered comparative studies evaluating the effect of RT for the prioritized diseases. RCTs should consider employing sham radiation as the comparison group or other conservative modalities such as steroid injections. Future observational studies should at a minimum conduct causally explicit analyses to counter confounding bias. There is also a need to better understand patient quality of life, experience, and satisfaction, including treatment-related burden. Finally, there is a need for a registry to collect data on radiation-induced secondary malignancies.

Citation: Jutkowitz E, Rieke K, Caputo E, et al. Radiation Therapy for Benign Conditions: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Systems Research, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #22-116; 2024.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/Radiation-Benign-Conditions.cfm . (This report is available via Intranet only.)

ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

This Management Brief is provided to inform you about recent HSR findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR Resource Center charged with disseminating important HSR findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers; and to disseminate these reports throughout VA.

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