These cases were identified through the first author’s routine clinical practice at a tertiary level oncologic hospital. Institutional ethics committee approval was received for a waiver of patient consent. SRS was delivered either using a Varian TrueBeam linear accelerator with dynamic conformal arc therapy (DCAT) or with the Gamma Knife radiosurgery machine. The SRS schedules used in each case are specified in the respective figure legends.
Anatomical boundaries
IM generally enlarge in one of two ways. Most commonly, IM enlarge in a relatively concentric manner, with progressive enlargement of a nodular lesion. Less commonly, metastases may extend along an anatomical surface, such as along the cortex or pial surface of the brain, or along the ependymal surface of the ventricular system. The frequency with which metastases enlarge in these two ways depends, in part, on the histology. For example, intracranial metastases from melanoma have a particular predilection to developing at the interface between the pia mater and the cortex [12], and curvilinear extension along the pial surface is a common occurrence. As such, the pattern of IM progression or recurrence is affected by the local anatomy. In contrast, the distribution of the radiation dose administered with SRS in general does not respect these anatomical boundaries, but rather is largely concentric around the treated lesion. This is illustrated by the isodose distributions as depicted in Figs. 3 and 6.
Several such anatomical boundaries exist in the brain. Firstly, this includes the major dural reflections: the falx cerebri (Figs. 1 and 2) and the tentorium cerebelli (Fig. 3). In our experience, the development of new enhancement on the other side of a dural reflection after SRS is strongly suggestive of RN rather than PD. A sulcus and CSF may provide a similar barrier (Figs. 4 and 5). In our experience of both above scenarios, the new enhancement occurring with RN preferentially involves the subcortical white matter, sparing the intervening cortex, and thus the new lesion can be anatomically distinct from, or non-contiguous with, the originally treated lesion. It is important, however, to ensure that there is no contiguous involvement of the intervening meninges, which would otherwise raise concern for PD.
Similar considerations exist for IM located close to the ventricular system (Figs. 6 and 7), though the MRI appearances differ to a degree, related to the anatomical differences compared to the more peripheral lesions discussed above. In contrast to more peripheral lesions, there is often no intervening grey matter between the treated IM and the white matter on the other side of the ventricle. As a result, in our experience, such RN lesions tend to develop in continuity, wrapping around the ventricle. Of note, and in contrast to metastatic disease, there is often no enhancement along the ventricle surface, producing an “open ring” appearance. This open ring appearance can also occur with treated metastases located away from the ventricular surface (see Fig. 1), related to the lower differential radiosensitivity of the cortex and the effect this in turn has on the MRI appearances (the ring potentially being open on the side of the cortex). Notably, in all our illustrated cases, the area of enhancement correlates geographically with the high radiation dose regions, as highlighted in Figs. 3 and 6.
Change in shape
The progression and evolution of IM tends to occur in a relatively simple manner. Prior to treatment, or if not responding to treatment, the entirety of an IM will enlarge, without regression of any particular components. While subsequent recurrence (and hence enlargement) may occur within only a portion of the initial lesion, often at its margin, any post-treatment regression will have already occurred. Thus, it would be very uncommon for different components of the same IM to enlarge and regress simultaneously. In contrast, RN is a more variable and dynamic process, affected by a variety of factors inherent to that particular part of the brain (or voxel), such as the dose received and the sensitivity to radiation effects. These factors vary from voxel to voxel, often leaving to a complex evolution of RN lesions. Radiologically, this can manifest as a change in the shape of the lesion, with different portions of the given lesions simultaneously enlarging and regressing (Figs. 7, and 8). Given that such evolution would not be expected for recurrent IM, such an appearance can be more confidently attributed to RN.