Imaging changes following stereotactic radiosurgery for metastatic intracranial tumors: differentiating pseudoprogression from tumor progression and its effect on clinical practice

Abstract

Stereotactic radiosurgery has become standard adjuvant treatment for patients with metastatic intracranial lesions. There has been a growing appreciation for benign imaging changes following radiation that are difficult to distinguish from true tumor progression. These imaging changes, termed pseudoprogression, carry significant implications for patient management. In this review, we discuss the current understanding of pseudoprogression in metastatic brain lesions, research to differentiate pseudoprogression from true progression, and clinical implications of pseudoprogression on treatment decisions.

Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial

“…Considering the higher SRS doses in our study, especially in patients with small surgical cavity volumes, some of the declared surgical bed recurrences might simply have been post-radiosurgery changes (ie, pseudoprogression), which could have falsely elevated the frequency of recurrence in our trial. 27 Finally, the patient populations differed substantially between the trials, including primary tumour histology (eg, lung primary 59% in the current multi-institutional trial vs 20% in the single institutional trial), making comparisons very difficult. However, taking these two randomised, controlled trials in context provides evidence that more than half of patients will have recurrences in the surgical bed even after gross total resection, that postoperative SRS substantially improves surgical bed control compared with resection alone, and SRS did not result in a difference in overall survival, suggesting resection cavity SRS is an effective strategy to delay WBRT and the associated cognitive, functional, and quality of life decreases.…”

Treatment of MRI‐Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dogs

“…It is possible that these tumors were not responsive to radiation and grew during the time between examinations. However, in human medicine where repeat MRI imaging is commonplace, it is difficult to differentiate tumor progression from pseudprogression caused by tumor necrosis, edema, and secondary inflammation resulting in an apparently larger region of contrast uptake . The edema seen after SRT is not specific for a particular pathological process and could be because of tumor progression, tumor necrosis, or radiation treatment.…”

Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases

“…Awareness of the potential interaction between the effect of SRS and PD-1 mAbs is imperative to avoid the misinterpretation of radiologic changes as tumor progression, which could otherwise lead to inappropriate re-irradiation or cessation of an effective therapy and potentially harmful consequences (6). If this significant interaction between SRS and immunotherapy is confirmed at other centers, changes in management options such as first-line surgical management of brain metastases or lower-dose SRS may need to be considered in patients with brain metastases being offered immunotherapy.…”

“…Classically, these changes manifest clinically months to years after SRS (5,6). The addition of immune-modulating therapies to systemic treatment paradigms is becoming standard of care in some malignancies that tend to metastasize to the brain, in particular melanoma and non-small cell lung cancer (NSCLC; refs.…”