Imaging of tumour response to immunotherapy

Abstract

A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2-10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria-so-called immune-related response criteria and then immune-related RECIST (irRECIST)-were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of "unconfirmed progression", into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.

Interim [18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma

“…Moreover, the results of survival analysis, exhibiting a lower PFS for patients with early PMD (no-MB) compared to those with early MB, are another indirect proof of the rather low incidence of the phenomenon in this cohort. This is in line with previous results published in the literature documenting non-negligible, but not higher than 10% rates of the phenomenon in melanoma immunotherapy [36,44,45], and provides supporting evidence to the standpoint that an increase in tumor burden observed during ICI treatment more likely reflects true progression rather than pseudoprogression [41,46,47].…”

“…irAEs represent another source of false-positive findings on imaging. Radiologic manifestations of irAEs have been reported with variable incidences, reaching up to 31% of patients under ICIs [47][48][49]. Although the specific characteristics of individual patients play a significant role, the emergence of these toxicities is mainly dependent on the agents used, with the combination of an anti-CTLA-4 antibody and an anti-PD-1 antibody increasing both their incidence and severity [50].…”

The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

“…Pseudo-progression is defined as a transient increase followed by a decrease in apparent total tumor burden. Its incidence is highly variable between studies, ranging between 2 and 10%, depending on tumor type, treatment, and patients ( 52 , 53 ). Pseudo-progression incidence rates have been reported as ranging between 1.5 and 17% of patients with advanced urothelial carcinoma on immunotherapy ( 54 ).…”

MRI characteristics in treatment for cerebral melanoma metastasis using stereotactic radiosurgery and concomitant checkpoint inhibitors or targeted therapeutics

“…Pseudoprogression generally is indistinguishable from true progression in a single MRI study. It is It is known that MM may possibly show a delayed response after immunotherapy, especially after administration of ipilimumab, thus immune-related Response Criteria (irRC) were introduced [23,24]. These require the initial increase of at least 25% in lesion load to be confirmed by follow-up imaging at least 4 weeks later to diagnose progressive disease and exclude pseudoprogression.…”