Normal tissue complication probability (NTCP) models could aid the understanding of dose dependence of radiation-induced toxicities after eye-preserving radiotherapy of choroidal melanomas. We ...performed NTCP-modeling and established dose-response relationships for visual acuity (VA) deterioration and common late complications after treatments with proton therapy (PT).
Retrospective study from single, large referral center.
We considered patients from Nice, France, diagnosed with choroidal melanoma and treated primarily with hypofractionated PT (52 Gy physical dose in 4 fractions). Complete VA deterioration information was available for 1020 patients, and complete information on late complications was available for 991 patients.
Treatment details, dose-volume histograms (DVHs) for relevant anatomic structures, and patient and tumor characteristics were available from a dedicated ocular database. Least absolute shrinkage and selection operator (LASSO) variable selection was used to identify variables with the strongest impact on each end point, followed by multivariate Cox regressions and logistic regressions to analyze the relationships among dose, clinical characteristics, and clinical outcomes.
Dose-response relationship for VA deterioration and late complications.
Dose metrics for several structures (i.e., optic disc, macula, retina, globe, lens, ciliary body) correlated with clinical outcome. The near-maximum dose to the macula showed the strongest correlation with VA deterioration. The near-maximum dose to the retina was the only variable with clear impact on the risk of maculopathy, the dose to 20% of the optic disc had the largest impact on optic neuropathy, dose to 20% of cornea had the largest impact on neovascular glaucoma, and dose to 20% of the ciliary body had the largest impact on ocular hypertension. The volume of the ciliary body receiving 26 Gy was the only variable associated with the risk of cataract, and the volume of retina receiving 52 Gy was associated with the risk of retinal detachment. Optic disc-to-tumor distance was the only variable associated with dry eye syndrome in the absence of DVH for the lachrymal gland.
VA deterioration and specific late complications demonstrated dependence on dose delivered to normal structures in the eye after PT for choroidal melanoma. VA deterioration depended on dose to a range of structures, whereas more specific complications were related to dose metrics for specific structures.
Ruthenium-106 (Ru-106) brachytherapy is an established modality for eye-preserving treatment of choroidal melanoma. To achieve optimal treatment outcomes, there should be a balance between tumour ...control and the risk of healthy tissue toxicity. In this retrospective study, we examined normal tissue complication probability (NTCP) for visual acuity deterioration and late complications to aid the understanding of dose-dependence after Ru-106 treatments. We considered consecutive patients diagnosed with choroidal melanoma and primarily treated at a single institution from 2005-2014. Treatment plans were retrospectively recreated using dedicated software and image guidance to contour the tumour and determine the actual plaque position. Dose distributions were extracted from each plan for all relevant anatomical structures. We considered visual acuity deterioration and late complications (maculopathy, optic neuropathy, ocular hypertension, vascular obliteration, cataract and retinal detachment). Lasso statistics were used to select the most important variables for each analysis. Outcomes were related to dose and clinical characteristics using multivariate Cox regressions analysis. In total, 227 patients were considered and 226 of those were eligible for analysis. Median potential follow-up time was 5.0 years (95% CI: 4.5-6.0). Visual acuity deterioration was related to optic disc-tumour distance and dose metrics from the retina and the macula, with retina V10Gy showing the strongest correlation. Macula V10Gy was the only dose metric impacting risk of maculopathy, while optic disc-tumour distance also proved important. Optic disc V50Gy had the largest impact on optic neuropathy along with optic disc-tumour distance. Optic disc V20Gy was the only variable associated with vascular obliteration. Lens D2% had the largest impact on the risk of cataract along with older age and the largest base dimension. We found no variables associated with the risk of ocular hypertension and retinal detachment. Visual acuity deterioration and most late complications demonstrated dependence on dose delivered to healthy structures in the eye after Ru-106 brachytherapy for choroidal melanomas.
Background
Current standard treatment procedures for Ruthenium‐106 (Ru‐106) brachytherapy for choroidal melanomas do not use 3D image‐guided treatment planning. We evaluated the potential impact of ...introducing 3D treatment planning and quantified the theoretical clinical benefits in terms of tumour control probability (TCP) and normal tissue complication probability (NTCP).
Materials and methods
Treatment plans for thirty‐two patients were optimized using 3D image‐guided treatment planning and compared to the original 2D clinical plans. Optimization of plans was done in an image‐based treatment planning system by optimizing the plaque position and treatment time such that the entire tumour received the prescribed dose of 100 Gy. TCP and NTCP for 2D clinical plans and optimized 3D image‐guided plans were estimated from published outcome prediction models and compared within patients using Wilcoxon signed‐rank test.
Results
The median minimum tumour dose (D99%) for 2D clinical plans was 93 Gy (range: 23–158 Gy), corresponding to 5‐year TCP of 75% (IQR 61–86%), while median tumour D99% for optimized 3D image‐guided plans was 115 Gy (range 103–141 Gy), corresponding to TCP of 82% (IQR 80–84%). This was a statistically significant increase in estimated TCP (median increase in TCP 8% (IQR: −5–23, p = 0.006). While the dose to normal tissue increased somewhat, there was no significant change in NTCP.
Conclusion
3D treatment planning theoretically allows for improved tumour dose delivery for Ru‐106 brachytherapy of choroidal melanomas, resulting in a significant increase in expected tumour control compared to traditional approaches using 2D calculations. The deliverability of optimized plans, and potential increased risk of late complications, will have to be confirmed in future clinical studies.
Purpose: Ruthenium-106 (Ru-106) brachytherapy is a common eye-preserving treatment for choroidal melanomas. However, a dose-response model describing the relationship between the actual delivered ...tumour dose and tumour control has, to the best of our knowledge, not previously been quantified for Ru-106 brachytherapy; we aimed to rectify this.
Material and methods: We considered consecutive patients with primary choroidal melanomas, treated with Ru-106 brachytherapy (2005-2014). Dosimetric plans were retrospectively recreated using 3D image-guided planning software. Pre-treatment fundus photographies were used to contour the tumour; post-treatment photographies to determine the accurate plaque position. Patient and tumour characteristics, treatment details, dose volume histograms, and clinical outcomes were extracted. Median follow-up was 5.0 years. The relationship between tumour dose and risk of local recurrence was examined using multivariate Cox regression modelling, with minimum physical tumour dose (D
99%
) as primary dose metric.
Results: We included 227 patients with median tumour height and largest base dimension of 4 mm (range 1-12, IQR 3-6) and 11 mm (range 4-23, IQR 9-13). The estimated 3 year local control was 82% (95% CI 77-88). Median D
99%
was 105 Gy (range 6-783, IQR 65-138); this was the most significant factor associated with recurrence (p < .0001), although tumour height, combined TTT and Ru-106 brachytherapy, and sex were also significant. The hazard ratio (HR) for a 10 Gy increase in D
99%
was 0.87 (95% CI 0.82-0.93). Using biological effective dose in the model resulted in no substantial difference in dose dependence estimates. Robustness cheques with D
1-99%
showed D
99%
to be the most significant dose metric for local recurrence.
Conclusion: The minimum tumour dose correlated strongly with risk of tumour recurrence, with 100 Gy needed to ensure at least 84% local control at 3 years.
Purpose
The use of planar ultra‐widefield fundus photography (UWF) may result in distortions and inaccurate measurement. The aim of the study was to evaluate the accuracy of UWF instead of the ...standard narrow field (SF) for the treatment planning phase of ocular tumours.
Methods
Distortions between conformal SF and UWF were assessed in 43 patients with choroidal melanoma treated with either proton therapy or brachytherapy. imagej software was used to measure distortion.
Results
The median interquartile range (IQR) distortion for all cases was 3.7% 1.7–10.8. For cases with tumours within 6 mm of the optic disc, distortions appeared clinically nonsignificant. For peripheral and/or large tumours, significantly larger distortions were observed on UWF (median 4.4% 2.7–22.6 for tumours ≥6 mm from the optic disc versus 3.3% 1.6–9.9 for those <6 mm, p = 0.04). Images can be subdivided into three groups: minimal distortion (79.1% of eyes), similar level of major distortion for both measured distances (11.6%) and distortion with unequal level of distortion between the measured distances (9.3%).
Conclusion
Distortions with UWF appeared minimal in posterior regions of the fundus and increased with the distance from the posterior pole. UWF could therefore be used for treatment planning of ocular tumours as the planned radiation dose to the macula and optic disc are not impacted.
To present a new method to determine dose depth and the distance from the concave side of the plaque to the tumour base in patients with uveal melanoma treated with ruthenium-106 based on ultrasonic ...mirror image.
We used the mirror image associated with ultrasound during plaque brachytherapy to determine intraobserver reproducibility and interobserver agreement between two surgeons. 230 eyes with primary uveal melanoma were included in a retrospective analysis to determine the distance from the plaque to the tumour base using ultrasound. A phantom study was used to illustrate the effects on radiation dose to apex of the tumour when the dose depth was incorrectly determined. Doses to apex of the tumour were determined using Plaque Simulator.
The intraobserver variation in dose depth measurement
plaque was significantly lower than for measures
plaque (p<0.001). Agreement between the surgeons was better with a plaque in place. Distances from the plaque to the tumour base were distributed with mean=0.99 (median: 1, range: 0.1-2.9 mm). From the phantom study, it was clear that the tumour did not receive the prescribed 100 Gy if the dose depth was incorrectly determined.
The dose depth in patients with uveal melanoma must be measured accurately for correct calculation of the radiation dose to the apex of the tumour. Repeated in vivo and in vitro ultrasound measurements of dose depth showed higher variance than measurements using the mirror image produced from a ruthenium plaque. Using the mirror image thus help to improve the dose calculation.
Eye-preservation using brachytherapy (BT) and proton therapy (PT) are commonly used as primary treatments for uveal melanomas (UM). Choice of modality generally depends on local availability rather ...than direct assessment of the two techniques. We conducted a comparative dose planning study, estimating biologically effective doses (BED) to the tumour, macula and optic nerve head (ONH).
We retrospectively included 70 patients with primary UM: 35 treated with Ruthenium-106 (Ru-106) BT, and 35 who underwent PT. Only PT patients whose tumour was small enough to be treatable by BT were included. Prescriptions were 100 Gy (continuously delivered in a single session) for BT and 52 Gy (in 4 fractions) for PT to the entire tumour. Both planning techniques aimed to minimize doses to macula and ONH without compromising tumour coverage. Dual image-guided planning with 3D dose calculation was carried out for each patient. Dose volume histograms for tumour, macula, and ONH were extracted. BED was calculated using well-established models: Gagne et al. (Med Phys, 2012) for BT and Holloway and Dale (Br J Radiol, 2013) for PT, correcting for fractionation effects, overall treatment time and relative biological effectiveness. Wilcoxon signed-rank test was used to evaluate differences in BED.
Minimum tumour BEDs (BED99%) were larger for BT with median 159 Gy (interquartile range (IQR): 149–168) compared to 128 Gy (128–128) for PT. The median difference was 31 Gy (21–41) with p<0.0001. Median macula BED50% was 72 Gy (22–587) for BT compared to 155 Gy (0–374) for PT. However, the median of the individual patient difference was 23 Gy (1–248, p = 0.0002), favoring PT. Median ONH BED50% was 46 Gy (15–291) for BT compared to 3 Gy (0–525) for PT but the difference was not statistically significant (p = 0.1). PT spared the macula for smaller tumours <2 mm from the macula, while the ONH received less dose with BT in juxtapapillary cases.
Ru-106 brachytherapy delivered larger tumour doses, larger macula doses, and comparable optic nerve head doses compared to proton therapy. Large individual variations were seen, emphasizing the need for prospective comparative planning to guide the choice of treatment modality.
Introduction: The aim of this study was to investigate the incidence of deep vein thrombosis (DVT) in patients immobilized in plaster cast and the possible efficacy of prophylaxis with low molecular ...weight heparin (LMWH).
Material and methods: The study was a randomized, assessor-blinded, open multicenter (three centers) study. All patients over 18 years of age with planned plaster cast on a lower extremity of at least 3 weeks were eligible for participation. Written informed consent was obtained from 300 patients and they were randomized to either 3.500 IU anti-Xa of tinzaparin (Innohep) subcutaneously once daily or no prophylaxis. On the day the cast was removed, ascending unilateral venography was performed. Two experienced radiologists, unaware of treatment, assessed the pictures independently. The radiologist had to obtain consensus as to whether DVT was present or not.
Results: 300 patients were included (148 in the treatment group and 152 in the control group). Ninety-five were subsequently withdrawn. DVT was diagnosed in 10/99 patients in the treatment group and in 18/106 patients in the control group. This difference is not significant (
P=.15,
χ
2 test) and the odds ratio was 0.55 (95% confidence interval=0.34–1.26).
Conclusion: DVT in legs after plaster casting is a big problem, with an incidence of almost 20%. An effective prophylactic regime is required. Once-daily dose of 3.500 IU anti-Xa of tinzaparin was not sufficient.
PDF
![[OA057] Comparative dose pl...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1120-1797_1724-191X/small "[OA057] Comparative dose planning for Ru-106 brachytherapy and proton therapy for choroidal melanomas")
