Lung brain metastasis pseudoprogression after nivolumab and ipilimumab combination treatment

Abstract

Immunotherapy has revolutionized the treatment of non‐small cell lung cancer; however, its role in the treatment response of lung brain metastasis is unknown. Understanding immunotherapy activity in the central nervous system is important in order to avoid additional toxicity, such as that associated with the use of cerebral radiotherapy. We present two cases with clinical and radiological progression with increases in size and perilesional edema of brain lesions after treatment with a combination of ipilimumab and nivolumab. The increasing use of immunotherapy in lung cancer requires increased knowledge of new patterns of radiological response, such as pseudoprogression.

Anlotinib combined with durvalumab in a patient with recurrent multifocal brain metastases of small cell lung cancer after definitive concurrent chemoradiotherapy and palliative radiotherapy of the lung and brain: a case report

“…In the present case study, the patient developed secondary BMs approximately 2 weeks after initiation of durvalumab treatment. With reference to similar reports from previous studies, we considered this could reflect a case of pseudoprogression (14,15). Given the lack of supporting data in the treatment of BMs of SCLC, anlotinib was added into the ongoing immunotherapy as a trial, and the dose of durvalumab was adjusted correspondingly.…”

Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

“…Pseudoprogression involves a transient enlargement of existing lesions or the appearance of new lesions mimicking tumor progression, which resolves on longitudinal imaging [ 57 ]. ICIs (particularly anti-CTLA-4 agents) have been known to result in pseudoprogression when used to treat BMs [ 58 ]. Imaging studies in patients with pseudoprogression often show an increased contrast enhancement and vasogenic edema (which can be small and asymptomatic), which usually occur within the first 3 months.…”

“…For minimally symptomatic lesions, close follow-up with serial imaging can avoid unnecessary tumor-directed therapies. Sometimes, a biopsy is needed to distinguish treatment-related changes from progressive tumors and to guide further therapy [ 58 ].…”

Clinical case of lung spindle cell carcinoma markedly responsive to pembrolizumab

“…In retrospect, brain edema and chest wall tumor exacerbation after initial pembrolizumab administration may suggest a pseudoprogression given the remarkable therapeutic effect observed thereafter. Although it is difficult to distinguish the contribution of abscopal effect by palliative irradiation therapy to chest wall, exacerbation of brain edema could be explained adequately by pseudoprogression of ICI 16,17,20 . Although brain edema exacerbation frequently induces PS decline, a pseudoprogression would usually exhibit a subsequent improvement.…”

“…Initial ICI treatment for brain metastases often shows a pseudoprogression within the first three months 9 . Pseudoprogression of brain metastases has been explained histologically by inflammatory cell infiltration, edema, and necrosis, and radiologically by frequent exhibition of perilesional brain edema 16–18 . A careful therapeutic response evaluation is thus recommended to avoid progressive disease six months or less after ICI administration initiation 9,19 .…”