Prognostic value of MRI volumetric parameters in non-small cell lung cancer patients after immune checkpoint inhibitor therapy: comparison with response assessment criteria

BackgroundAccurate response parameters are important for patients with brain metastasis (BM) undergoing clinical trials using immunotherapy, considering poorly defined enhancement and variable responses. This study investigated MRI-based surrogate endpoints for patients with BM receiving immunotherapy.MethodsSixty-three non-small cell lung cancer patients with BM who received immune checkpoint inhibitors and underwent MRI were included. Tumor diameters were measured using a modification of the RECIST 1.1 (mRECIST), RANO-BM, and iRANO adjusted for BM (iRANO-BM). Tumor volumes were segmented on 3D contrast-enhanced T1-weighted imaging. Differences between the sum of the longest diameter (SLD) or total tumor volume at baseline and the corresponding measurement at time of the best overall response were calculated as changes in SLDs (for each set of criteria) and change in volumetry, respectively. Overall response rate (ORR), progressive disease (PD) assignment, and progression-free survival (PFS) were compared among the criteria. The prediction of overall survival (OS) was compared between diameter-based and volumetric change using Cox proportional hazards regression analysis.ResultsThe mRECIST showed higher ORR (30.1% vs. both 17.5%) and PD assignment (34.9% vs. 25.4% [RANO-BM] and 19% [iRANO-BM]). The iRANO-BM had a longer median PFS (13.7 months) than RANO-BM (9.53 months) and mRECIST (7.73 months, P = 0.003). The change in volumetry was a significant predictor of OS (HR = 5.87, 95% CI: 1.46-23.64, P = 0.013). None of the changes in SLDs, as determined by RANO-BM or iRANO-BM, were significant predictors of OS, except for the mRECIST, which exhibited a weak association with OS.ConclusionQuantitative volume measurement may be an accurate surrogate endpoint for OS in patients with BM undergoing immunotherapy, especially considering the challenges of multiplicity and the heterogeneity of sub-centimeter size responses. The change in volumetric measurement was a significant predictor of overall survival compared with response assessment guidelines.Treatment response can be objectively measured using volumetric MRI measurement of brain metastases.Volumetric MRI measurement is particularly useful in brain metastases, challenged by sub-centimeter size and multiplicity.

Automated summary

The study suggests that quantitative volume measurement can be an accurate surrogate endpoint for OS in patients with brain metastasis undergoing immunotherapy, especially considering the challenges of sub-centimeter size responses and multiplicity. Volumetric MRI measurement is particularly useful in brain metastases.