Generalized white matter changes on MRI after conventional RT have been previously described (5
). This is the first report of MRI changes after IMRT. Typically, changes in the posterior fossa with associated enhancement are suspicious for recurrent or progressive disease. The MRI findings after IMRT as described in our study () can be mistaken for leptomeningeal disease () or a combination of changes due to IMRT and late demyelination (). When leptomeningeal disease is suspected, biopsy is not uniformly performed. Also, patients might be removed from their original treatment protocols and enrolled in investigational studies.
White matter changes visible on MRI can be visualized after RT or chemotherapy (12
). In a study of patients with acute lymphoid leukemia who were treated with chemotherapy with or without RT, the acute MRI changes noted included widening of the sulci or ventricles, hyper- or hypo-intense areas, and gray matter changes—findings believed to indicate cerebral atrophy, leukoencephalopathy, and brain necrosis (3
). The MRI changes observed in our study differed from other treatment-related white matter changes in their combination of features: primarily posterior fossa location, subacute onset, transient nature, and lack of associated neurologic symptoms.
One proposed explanation for the radiographic changes we observed in some of our patients after IMRT is that these were white matter changes that might reflect areas in the posterior fossa that received the greater dose to the target. The greater target dose could result in a transient breakdown of the blood–brain barrier with or without concurrent transient demyelination and/or radiation-related small vessel damage. However, we observed a discordance between the prescribed radiation dose to the posterior fossa and the occurrence of white matter changes. In comparing the IMRT dose map and the MRI images, we would have expected the regions with the MRI changes to coincide with the greater radiation dose. However, we do not observe this association ( and ). Although the white matter changes did not directly match the IMRT high-dose regions, we could not dismiss the radiation dose level as an influential factor associated with the transient MRI changes occurring after IMRT. The radiographic changes were seen in 27% of the patients who had received the larger radiation dose (>50 Gy) compared with 11% of patients who received the intermediate dose (36–45 Gy). The same patients who underwent IMRT had also undergone craniospinal RT, which can affect the homogeneity of the dose in the thinner portions of the head such as the posterior fossa region. The integral dose to the surrounding planning target volume could explain some of the white matter changes in the cerebellar hemispheres, brainstem, and temporal and occipital lobes, which received a greater dose than that delivered by craniospinal RT. In some patients, two IMRT plans were performed to cover the entire posterior fossa followed by a third IMRT plan for the tumor bed. Because of dose heterogeneity of the IMRT plans, the additive dose distribution just adjacent to the planning target volume or within the target volume of the plans could have affected the white matter changes seen. However, the number of patients receiving the greater vs. intermediate radiation dose (11 vs. 37) was too small to draw a definitive conclusion. Additionally, 1 of 5 patients who received the lowest dose (23.4 Gy) of IMRT to the posterior fossa and 3 of 11 patients who received the greatest dose (≥50 Gy) had transient MRI changes. The similar numbers in the two groups suggest that the MRI changes had no relation to the radiation dose received. However, the numbers were too small to draw a definitive conclusion. Therefore, we hypothesize that other undefined patient susceptibility factors contributed to the MRI changes we observed.
In our patients, the radiographic effects of IMRT consisted of a combination of changes on FLAIR images and parenchymal enhancement within the posterior fossa that occurred after a median of 6 months. In contrast, the MRI changes seen with leptomeningeal disease in our patient population occurred outside the conformal field of the posterior fossa, with enhancement and FLAIR changes occurring at a median of 19.5 months and 22 months, respectively, after IMRT completion. In the future, magnetic resonance spectroscopy performed when the MRI changes are noted might help to distinguish between radiation-related changes and recurrences early in the evolution of these changes. Although we do not have histologic proof that the areas of enhancement after IMRT were not tumor recurrence, the lack of progression of these abnormalities without therapeutic intervention strongly suggests that they did not represent neoplasm. Also, we did not observe an increase in local relapse in patients treated with IMRT.