# Incidence and Clinical Features of Pseudoprogression in Brain Metastases After Immune-Checkpoint Inhibitor Therapy: A Retrospective Study

## TL;DR

This study finds that about 9% of brain metastases show pseudoprogression after immune-checkpoint inhibitor therapy, with neurological symptoms being a key sign of true tumor progression.

## Contribution

The study reports the first lesion-specific incidence rate of pseudoprogression in brain metastases following immune-checkpoint inhibition.

## Key findings

- Pseudoprogression occurs in at least 9.4% of brain metastases lesions after immune-checkpoint inhibitor therapy.
- Pseudoprogression typically occurs at a median of 2.7 months after starting therapy.
- Patients with true tumor progression were more likely to require dexamethasone for neurological symptoms.

## Abstract

There are currently no studies reporting on the incidence of pseudoprogression in brain metastases at the point of initial change in contrast enhancement suspected for tumour progression after the start of immune-checkpoint inhibition. This study addresses this question and also investigates the associated clinical features of pseudoprogression of brain metastases in this context. This study reports that the lesion-specific incidence rate of pseudoprogression is at least 9.4% in brain metastases after immune-checkpoint inhibition. The sole clinical feature distinguishing pseudoprogression from true tumour progression was that patients with tumour progression were more likely to need dexamethasone for neurological symptoms. These findings give an initial suggestion to clinicians concerning the likelihood of pseudoprogression when confronted with imaging changes suspicious for intracranial progression after initiating immune-checkpoint inhibition in melanoma and non-small cell lung cancer.

Background: Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was conducted to address this. Materials and Methods: Brain metastasis patients showing progression on MRI according to response assessment in neuro-oncology brain metastases criteria after starting ICI therapy were included, irrespective of prior irradiation. Lesions were classified as tumour progression (TP) or pseudoprogression based on three-month radiological follow-up or histopathology. TP was assigned if progression was again shown at three months. Pseudoprogression was assigned if lesions showed stability, partial, or complete response at three months. ‘Non-classified’ lesions were those with new or changed treatment during follow-up. Results: A cohort of 98 patients with 233 lesions was included over an 11-year period; 170 lesions were considered non-classified, and 41 and 22 lesions were classified as TP and pseudoprogression respectively. This resulted in a lesion- and patient-specific incidence for pseudoprogression of 9.4% and 17.3% respectively. Due to the large number of lesions that could not be classified, as is the case in clinical practice, the reported incidence in this study is likely an underestimation and can be seen as a ‘minimum’ incidence rate. Ten pseudoprogression (45.5%) and 13 (31.7%) TP lesions were previously irradiated. Pseudoprogression occurred at a median of 2.7 months after starting ICI therapy. The only clinical feature distinguishing patients with TP from pseudoprogression was that TP patients were more likely to need dexamethasone for neurological symptoms. Conclusions: Pseudoprogression has a lesion-specific incidence rate of at least 9.4% and occurs at a median of 2.7 months after starting ICI therapy. Severe neurological symptoms requiring dexamethasone may be a clinical feature typical for TP.