(Vienna, 08-07-2025) – Immune checkpoint inhibitors (ICI) are currently revolutionising the treatment of numerous cancers. A recent study by MedUni Vienna, conducted at the Comprehensive Cancer Centre (CCC) of MedUni Vienna and Vienna General Hospital, now shows for the first time that patients with rectal cancer who receive immunotherapy in combination with chemoradiotherapy (CRT) surprisingly often develop severe muscle damage (myositis).
‘We found an unexpectedly high incidence of this side effect,’ emphasise study leaders Johannes Längle and Michael Bergmann (Clinical Department of Visceral Surgery, University Clinic for General Surgery, CCC). Specifically, 6 out of 50 patients (12%) developed histologically confirmed myositis. This frequency is significantly higher than previously known: normally, the incidence of myositis with ICI is less than 1%.
The results come from the prospective CHINOREC study, which was conducted jointly by experts in visceral surgery, rheumatology, cardiology, neuropathology, pathology and radiation oncology. The study has now been published in the leading journal ‘MedComm’ (IF 10.7).
Early diagnosis possible with specialised biomarkers
The scientists showed that early identification of myositis is possible through specific blood values. Together with the team led by cardiologist Jutta Bergler-Klein (Clinical Department of Cardiology, University Clinic for Internal Medicine II), they were able to demonstrate for the first time that cardiac troponin cTnI can reliably distinguish between cardiac involvement and pure skeletal muscle involvement. This represents a decisive advance, as previously used biomarkers (such as cTnT) did not have sufficient specificity and often led to unnecessary cardiac investigations.
Cytotoxic T cells identified as the main cause
Another key finding of the study was that this form of myositis is mediated by cytotoxic T cells. Using immunohistology of muscle biopsies, the scientists led by first author Rebecca Zirnbauer (Clinical Department of Visceral Surgery, University Clinic for General Surgery, CCC) together with neuropathology (Simon Hametner, Clinical Department of Neuropathology and Neurochemistry, University Clinic for Neurology) were able to prove that CD8-positive T cells in particular cause muscle damage. This distinguishes ICI-induced myositis significantly from other immune-mediated muscle diseases and enables targeted treatment for the first time.
Early treatment prevents serious complications
Due to the potentially life-threatening complications of ICI-induced myositis, which can have a mortality rate of up to 40–50% if left untreated, early diagnosis and treatment are essential. Together with the rheumatology team led by Stephan Blüml and the recently deceased Klaus Machold (Clinical Department of Rheumatology, University Clinic for Internal Medicine III), the scientists were able to show that only through the timely use of immunomodulatory therapies could serious consequences such as respiratory failure be prevented and, at the same time, the tumour surgery be performed successfully.
The authors of the study therefore recommend that regular screenings be carried out in future when neoadjuvant immunotherapy is combined with CRT, and that diagnostic and therapeutic measures be taken quickly even in cases of mild symptoms and elevated biomarker levels.
Service: MedComm
Incidence and Immunopathology of Myositis in Rectal Cancer Patients Treated With Neoadjuvant Immune Checkpoint Inhibitors and Chemoradiotherapy: Findings From the CHINOREC Trial. Zirnbauer R, Hametner S, Bergler-Klein J, Kuehrer I, Kulu A, Ammon D, Kabiljo J, Stift A, Schmid R, Müllauer L, Bittermann C, Laengle F, Machold K, Blüml S, Bergmann M, Laengle J. MedComm, 6: e70275. doi: 0.1002/mco2.70275