In ion beam radiotherapy, PET-based treatment verification provides a consistency check of the delivered treatment with respect to a simulation based on the treatment planning. In this work the region-based MLEM reconstruction algorithm is proposed as a new evaluation strategy in PET-based treatment verification. The comparative evaluation is based on reconstructed PET images in selected regions, which are automatically identified on the expected PET images according to homogeneity in activity values. The strategy was tested on numerical and physical phantoms, simulating mismatches between the planned and measured β+ activity distributions. The region-based MLEM reconstruction was demonstrated to be robust against noise and the sensitivity of the strategy results were comparable to three voxel units, corresponding to 6 mm in numerical phantoms. The robustness of the region-based MLEM evaluation outperformed the voxel-based strategies. The potential of the proposed strategy was also retrospectively assessed on patient data and further clinical validation is envisioned.