MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma

Abstract

Purpose: MRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound.

Methods: Twenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline.

Results: Pre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 × 10^-3mm²/s increase 12 months after treatment (p = 0.15).

Conclusion: MR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound.

Keywords: Brachytherapy; Magnetic resonance imaging; Proton beam therapy; Ultrasound; Uveal melanoma.

Fig. 1

Patient inclusion flowchart

Fig. 2

MRI of a UM of the right eye (a, e, i) before, and (b, f, j) 3, (c, g, k) 7 and (d, h, l) 13 months after ruthenium plaque brachytherapy. Favourable evolution of the UM was observed in terms of size (red lines in a–d), ADC value and TIC at dynamic contrast-enhanced MR perfusion (DCE). a–d Axial oblique multi-slice (MS) turbo spin echo (TSE) contrast-enhanced T1 with fat signal suppression. Progressive decrease in size of the UM, indicated by red lines, already noticed 3 months after radiotherapy. e–h Axial oblique ADC. Progressive increase of the UM ADC value, except 13 months after radiotherapy where there is a decrease. Regions of interests used to derive the ADC values are delineated in red circles. i–l DCE TICs. Progression of the initial washout TIC profile into a plateau and progressive TIC, corresponding to a lower (more negative) outflow percentage

Fig. 3

MRI of a UM of the right eye (a, e, i) before, and (b, f, j) 2, (c, g, k) 5 and (d, h, l) 11 months after PBT. Pseudo progression of the UM 2 months after radiotherapy: slight increase in size, indicated by red lines (a–d), but what seems a more favourable TIC in terms of perfusion outflow reduction at DCE MR Perfusion. a–d Coronal oblique MS TSE contrast-enhanced T1 with fat signal suppression. Slight increase in size of the UM 2 months after radiotherapy followed by a slow progressive decrease of its size. e–h Coronal oblique ADC. Slight increase of the UM ADC value at 2 months which remained stable. i–l DCE TIC. Favourable perfusion characteristics after PBT, with progressive smaller peak intensity and outflow percentage. ROIs used to derive the ADC values are delineated in red circles

Fig. 4

Overview of prominence regression on MRI after radiotherapy. a The regression of the tumour prominence measured on MRI for patients treated with brachytherapy (orange) or PBT (blue). b The distribution of UM measured prominence (top) before treatment and (bottom) 12 months after treatment. c MRI-based relative change in prominence (mm) measured at (left) 3, (middle) 6 and (right) 12 months after treatment compared to pre-treatment. d Table shows the comparison between prominence measurements on ultrasound and MRI at different timepoints. Significant (p ≤ 0.05) changes compared to pre-treatment are marked by an asterisk

Fig. 5

a, b Ultrasound and c, d MRI of a UM of the right eye a, c before and b, d 3 months after ruthenium plaque brachytherapy. Post-treatment changes, accounting for less accurate ultrasound measurements of the UM after radiotherapy, but not interfering with the MR measurements. The tumour prominence measured 1.2 mm thicker on ultrasound as compared to MRI (red lines) after brachytherapy, which could likely be attributed to structural changes of the extra-ocular tissue due to radiation reactions or due to the temporary surgical detachment of the extra-ocular muscle adjacent to the tumour needed to facilitate the placement of the ruthenium applicator. a, b Ultrasound images with the identification of the limits of the UM, of the sclera (green arrow) and of the medial rectus (blue dashed arrow) being easy before and difficult after radiotherapy. c, d Axial oblique MS TSE contrast-enhanced T1 with fat signal suppression. Although there is post-radiotherapy peri-scleral enhancement (orange arrow with double chevron), and thickening of the tendon of the medial rectus due to its intraoperative detachment during the ruthenium plaque insertion (red dashed arrow with double chevron), the limits of the tumour and of the sclera remain clearly visible, allowing accurate measurements

Fig. 6

Overview of PWI metrics before and after ocular radiotherapy. a The TIC profiles show a gradual progression from primarily washout to plateau/progressive curves. b Pre-treatment and c 3-month post-treatment (left) relative peak intensity and (right) outflow percentage for brachytherapy (orange) and PBT (blue) patients. d Summary of the distribution in TIC profile, outflow percentage, relative peak intensity percentage and treatment response at all timepoints for the different treatments. Significant (p ≤ 0.05) outflow percentage and relative peak intensity changes are marked by an asterisk

Fig. 7

Overview of DWI data before and after radiotherapy. a Before treatment, the brachytherapy (orange) patients showed a significant (p = 0.01) higher ADC compared to the PBT (blue)-treated patients. b ADC changes (left) 3, (middle) 6 and (right) 12 months after treatment compared to pre-treatment. c Table with mean ADC values and standard deviations at different timepoints. Significant (p ≤ 0.05) differences compared to baseline are marked by an asterisk

Fig. 8

A side-by-side comparison of treatment response of (left) brachytherapy and (right) PBT-treated patients, based on MRI and ultrasound at each timepoint. Treatment response in terms of tumour prominence was defined as a decrease in tumour prominence of more than 0.6 mm. In addition, a reduction in outflow percentage of at least 5% on PWI was also considered a sign of treatment response on MRI. At 3 months, 69% of brachytherapy patients showed treatment response on ultrasound as compared to 92% patients on MRI. For PBT patients, however, only 23% of patients showed treatment response on ultrasound while this was 77% on MRI. Furthermore, 60% of those patients who showed treatment response on MRI were based on favourable PWI changes, when no prominence decrease was yet apparent