Ultrasonographic findings can identify ‘pseudoprogression’ under nivolumab therapy

• Published in: British journal of dermatology (1951) Vol. 177; no. 6; pp. 1726 - 1731
• Main Authors: Imafuku, K., Hata, H., Kitamura, S., Yanagi, T., Shimizu, H.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-12-2017
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents, Immunological - administration & dosage; Blood flow; Cancer; Cancer immunotherapy; Cell death; Computed tomography; Disease Progression; Drug Administration Schedule; Female; Humans; Immune checkpoint inhibitors; Immunotherapy; Lymph nodes; Lymphatic Metastasis; Melanoma; Melanoma - diagnostic imaging; Melanoma - drug therapy; Metastases; Metastasis; Monoclonal antibodies; Neoplasm Metastasis; Nivolumab - administration & dosage; Positron emission tomography; Skin cancer; Skin Neoplasms - diagnostic imaging; Skin Neoplasms - drug therapy; Targeted cancer therapy; Treatment Outcome; Tumors; Ultrasonography; Ultrasound
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.15198

Summary
‘Pseudoprogression’ is often seen in patients with melanomas who are treated with immune checkpoint inhibitors such as nivolumab or ipilimumab. We sometimes evaluate metastatic lesions by imaging tests such as computed tomography (CT) or positron emission tomography‐CT. ‘Pseudoprogression’ usually occurs upon the initial administration, which may make it difficult for the physician to determine the disease condition. In our two cases of metastatic melanoma treated with nivolumab (antiprogrammed cell death‐1 antibody), we examined the ultrasonography (US) of target lesions that could be accessed from the body surface, such as those of the regional lymph node or subcutaneous metastasis. In both cases, the US revealed a lesion approximately 10% greater in size after 40–50 days of nivolumab administration, even though the blood flow inside the tumour was reduced by about 20% within 50 days. From about 100 days after blood flow reduction was detected by US, the tumours began to decrease in size. However, contrast CT was unable to detect the association between tumour size and tumour blood flow. The present cases suggest that US could be a powerful tool for differentiating between ‘pseudoprogression’ and real progressive disease in patients treated with cancer immunotherapies such as those involving immune checkpoint inhibitors. The misdiagnosis of progressive disease can lead to unnecessary alterations to the current treatment. Therefore, the US findings in our study could be clinically useful and educational for physicians.
What's already known about this topic?
Nivolumab is effective for unresectable malignant melanoma. However, a lesion targeted with nivolumab therapy will sometimes enlarge in the initial phase of treatment, a phenomenon known as ‘pseudoprogression’.
It is difficult but important to differentiate pseudoprogression from actual progressive disease. To date, no reports have addressed the diagnostic challenge of determining blood flow inside metastatic tumours in cases of suspected pseudoprogression.
What does this study add?
A phenomenon was observed in which metastatic lesions that initially developed in size were subsequently found by ultrasonography (US) to have clear decreases in blood flow followed by decrease in tumour size.
It was difficult to identify internal metastatic lesions using computed tomography. Therefore, the evaluation of blood flow of the tumour using US could be useful in differentiating pseudoprogression from true progressive disease.
Linked Comment: Akiyama. Br J Dermatol 2017; 177:1483–1484.