Cancer immunotherapy is presenting new challenges in the imaging evaluation of treatment response and the diagnosis of treatment-related complications. Accurate and reproducible assessment of response requires familiarization with the emerging patterns following immunotherapy. The underlying mechanisms of immunotherapy expose the patient to the risk of immune-related adverse events (irAEs). Timely and comprehensive assessment of irAEs is important for prompt and appropriate clinical management.
Assessment of disease response
Assessment of disease response following immunotherapy requires specific knowledge for accurate radiological interpretation.
Treatment response may be associated with a significant delay in the decrease of the tumour burden. This delay is attributable to the time interval required for the immune system to mount the desired response through activation and expansion of effector cell populations.
Clinically significant stabilization of disease describes a tumour burden that may remain static for a prolonged period after treatment and may or may not eventually demonstrate a decrease in volume. This is thought to be more significant in terms of responses to immunotherapy compared with similar findings following conventional cytotoxic therapy.
Pseudo-progression, or flare effect, may herald a delayed response to treatment after an initial increase in tumour volume. It occurs immediately after treatment within the so-called flare time window and may be a transient increase in tumour size or the emergence of ‘new’ metastases due to immune cell infiltration of existing deposits, with or without significant associated oedema. Current thinking suggests this phenomenon is over-reported. It is more likely that apparent pseudo-progression, be it of existing disease or emerging metastases, reflects true tumour growth in the lag time before the effective immune response.
These patterns of response are reflected in the recommended radiological surveillance following treatment with immunotherapy. Imaging assessment after completion of treatment should be made with two consecutive follow-up studies performed at least 4 weeks apart, mainly to negate the effect of a delayed response. If new or enlarging disease is observed immediately after the completion of treatment, repeat imaging should be undertaken at least 4 weeks later to assess further changes. This addresses the potential confusion of pseudo-progression.
It is important to be able to assess treatment response both accurately and reproducibly. For conventional cytotoxic agents the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) are currently used. These have their own inherent shortcomings but significantly so in the context of immunotherapy. To reflect the differences between traditional RECIST and the concepts discussed above, specific immune-based response criteria (iRECIST) have been published. The most recent uses unidimensional measurements to provide a standardized approach to treatment response.1
Future developments in the assessment of treatment response will not only include the refinement of these criteria but also a change in the way tumour burden is measured. At present we use anatomically measurable disease to assess treatment efficacy. Simple measurements of tumour burden do not take into consideration ...