Immune-Related Response Assessment in Solid Tumors

Immunotherapy has transformed the management of solid tumours by harnessing the patient’s own immune system to recognise and attack cancer cells. Unlike conventional cytotoxic therapies, immune checkpoint inhibitors and other immunomodulatory agents can provoke atypical patterns of response, including initial enlargement of lesions followed by regression, or the appearance of new lesions before overall tumour control. These phenomena, termed pseudoprogression and hyperprogression, pose challenges for clinical decision-making and trial design. To address these issues, modified response criteria have been developed that build upon the established Response Evaluation Criteria in Solid Tumours (RECIST), introducing features such as the measurement of new lesions within total tumour burden and mandatory confirmation of progression. The accurate assessment of immune-related responses requires integration of radiological evaluation, biomarker analysis and clinical context, with the goal of distinguishing true treatment failure from transient inflammatory changes. Refining these criteria has global significance for optimising patient outcomes, guiding continuation or cessation of therapy, and informing regulatory endpoints for novel agents.

Research from Nature Portfolio

Recent studies have proposed evidence-based refinements to immune-related response criteria, outlining the steps required to validate a modified RECIST framework (iRECIST) in prospective settings. These analyses emphasise the need for standardised definitions of unconfirmed and confirmed progression, integration of new-lesion measurements into total tumour burden calculations, and harmonisation across trial sites. Early efforts have focused on developing statistical models to compare these novel criteria with conventional RECIST1.1, highlighting the potential for improved detection of true responses and reduction of premature treatment discontinuation.

Immune-Related Response Assessment in Solid Tumors publication trend

The graph below shows the total number of articles in immune-related response assessment in solid tumors across all publications each year (not limited to Nature Index journals).

Technical terms

RECIST (Response Evaluation Criteria in Solid Tumours): Standardised guidelines using tumour size measurements to classify response to therapy.

irRECIST (immune-related RECIST): Modified RECIST that incorporates new lesion measurements and requires confirmation of progression to account for immune effects.

Pseudoprogression: Apparent increase in tumour size or new lesions due to immune cell infiltration rather than true tumour growth.

Hyperprogression: Accelerated tumour growth observed in a subset of patients following immunotherapy.

Tumour burden: Quantitative assessment of the total amount of cancer in the body, often measured by imaging.

Immune checkpoint inhibitor: A class of drugs that block regulatory pathways in T cells to enhance anti-tumour immunity.

References

1. Towards evidence-based response criteria for cancer immunotherapy. Nature Communications (2023).
2. Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients. Journal for ImmunoTherapy of Cancer (2016).
3. Monitoring of KRAS -mutated ctDNA to discriminate pseudo-progression from true progression during anti-PD-1 treatment of lung adenocarcinoma. Oncotarget (2017).
4. Imaging of tumour response to immunotherapy. European Radiology Experimental (2020).