Ultrasound Can Identify Subclinical Musculoskeletal Toxicity of Cancer Checkpoint Inhibitor Therapy
Key findings
- This retrospective study describes the benefits of rheumatologist-performed ultrasound in evaluating 34 cancer patients who had musculoskeletal symptoms associated with immune checkpoint inhibitor therapy
- Musculoskeletal ultrasound identified inflammatory features in all 20 patients who had clinically evident synovitis and in 10 of the 14 who did not
- Ultrasound also identified inflammatory synovial and tenosynovial tissue features in seven patients whose synovial fluid cell counts were in the traditionally accepted non-inflammatory range
- Point-of-care musculoskeletal ultrasound has a key role in evaluating suspected musculoskeletal toxicity of cancer immunotherapy
Immune-related adverse events (irAEs), including musculoskeletal complications, are common when cancer is treated with an immune checkpoint inhibitor (ICI). Musculoskeletal irAEs can range from nonspecific arthralgias to inflammatory arthritis, and their presentations can be subtle, particularly early in disease evolution.
Subscribe to the latest updates from Rheumatology, Allergy and Immunology Advances in Motion
Physicians at Massachusetts General Hospital have been using ultrasound at the point-of-care to evaluate patients suspected of having musculoskeletal irAEs associated with ICI. In a retrospective study, they found this novel application enhanced identification of inflammatory features, particularly when the clinical examination was ambiguous or did not suggest clinical synovitis.
The findings are reported in Seminars in Arthritis and Rheumatism by Minna J. Kohler, MD, RhMSUS, director of the Rheumatology Musculoskeletal Ultrasound Program and director of the Oncorheumatology Program in the Division of Rheumatology, Allergy and Immunology at Mass General, Mazen Nasrallah, MD, formerly of the Division now a Mass General Brigham-affiliated rheumatologist at Salem Hospital, and colleagues. The Oncorheumatology Program is part of the Mass General Cancer Center Severe Immunotherapy Complications Service, a multidisciplinary team of clinicians and researchers working to address the urgent need to understand how and why immune-related adverse events occur.
Rheumatology Consultation Was Crucial
The researchers reviewed data on 55 adults treated with ICI for solid cancer who were referred with suspected musculoskeletal irAEs between 2010 and 2019. All had ultrasound performed and interpreted by the same rheumatologist, who is certified in musculoskeletal ultrasound through the American College of Rheumatology. The imaging findings were confirmed by a blinded second reader who has the same certification.
Three patients had pre-existing inflammatory disease, and 11 had equivocal findings or incomplete follow-up data. In seven patients, ultrasound identified alternative etiologies: seven patients had osteoarthritis, Lyme arthritis, gout, or tendinopathy. Making these diagnoses significantly improved cancer care by allowing continuation of ICI therapy.
Ultrasound Facilitated Earlier Clinical Diagnosis of Arthritis
The 34 other patients were classified as having definite irAE (pathology unequivocally correlating with ICI therapy and no alternative etiology). 20 of them had definite clinical signs of synovitis, and ultrasound confirmed inflammatory pathology in all 20 patients. The most common ultrasound features were grade ≥2 synovial proliferation, hyperemia, and tenosynovitis.
Among the 14 patients who did not have definite clinical synovitis, ultrasound identified inflammatory features in 10. Again, the most common findings were grade ≥2 synovial proliferation, hyperemia, and tenosynovitis.
Patients without appreciable synovitis or tenosynovitis on physical examination will benefit from ultrasound, as early identification of inflammation may allow for improved treatment strategies for symptom control to allow for continuation of cancer immunotherapy treatment.
Ultrasound Was Additive to Synovial Fluid Analysis
15 of the 34 patients with definite musculoskeletal irAEs had synovial fluid sampled from the same joint evaluated by ultrasound:
- 8 patients had a synovial fluid cell count ≥2000 cells/µL — All had synovitis detected by clinical examination and all had inflammatory features on ultrasound
- 7 patients had a cell count <2000 cells/µL — Only four had clinically detected synovitis, but all had inflammatory features on ultrasound. Six required intra-articular or systemic steroids, and five required initiation of a disease-modifying anti-rheumatic drug.
There was no difference between groups in the interval from the time of irAE symptom onset to rheumatology evaluation, suggesting the difference was not due to early versus delayed presentation. When examining patients with suspected musculoskeletal irAEs, rheumatologists should not dismiss the possibility of inflammatory pathology even if synovial fluid cell counts are outside the conventionally accepted inflammatory range.
view original journal article Subscription may be required
Learn about the Oncorheumatology Program and the Severe Immunotherapy Complications team