Commissioning and validation of a novel commercial TPS for ocular proton therapy.

BACKGROUND: Until today, the majority of ocular proton treatments worldwide were planned with the EYEPLAN treatment planning system (TPS). Recently, the commercial, computed tomography (CT)-based TPS for ocular proton therapy RayOcular was released, which follows the general concepts of model-based treatment planning approach in conjunction with a pencil-beam-type dose algorithm (PBA). PURPOSE: To validate RayOcular with respect to two main features: accurate geometrical representation of the eye model and accuracy of its dose calculation algorithm in combination with an Ion Beam Applications (IBA) eye treatment delivery system. METHODS: Different 3D-printed eye-ball-phantoms were fabricated to test the geometrical representation of the corresponding CT-based model, both in orthogonal 2D images for X-ray image overlay and in fundus view overlaid with a funduscopy. For the latter, the phantom was equipped with a lens matching refraction of the human eye. Funduscopy was acquired in a Zeiss Claus 500 camera. Tantalum clips and fiducials attached to the phantoms were localized in the TPS model, and residual deviations to the actual position in X-ray images for various orientations of the phantom were determined, after the nominal eye orientation was corrected in RayOcular to obtain a best overall fit. In the fundus view, deviations between known and displayed distances were measured. Dose calculation accuracy of the PBA on a 0.2 mm grid was investigated by comparing between measured lateral and depth-dose profiles in water for various combinations of range, modulation, and field-size. Ultimately, the modeling of dose distributions behind wedges was tested. A 1D gamma-test was applied, and the lateral and distal penumbra were further compared. RESULTS: Average residuals between model clips and visible clips/fiducials in orthogonal X-ray images were within 0.3 mm, including different orientations of the phantom. The differences between measured distances on the registered funduscopy image in the RayOcular fundus view and the known ground-truth were within 1 mm up to 10.5 mm distance from the posterior pole. No clear benefit projection of either polar mode or camera mode could be identified, the latter mimicking camera properties. Measured dose distributions were reproduced with gamma-test pass-rates of >95% with 2%/0.3 mm for depth and lateral profiles in the middle of spread-out Bragg-peaks. Distal falloff and lateral penumbra were within 0.2 mm for fields without a wedge. For shallow depths, the agreement was worse, reaching pass-rates down to 80% with 5%/0.3 mm when comparing lateral profiles in air. This is caused by low-energy protons from a scatter source in the IBA system not modeled by RayOcular. Dose distributions modified by wedges were reproduced, matching the wedge-induced broadening of the lateral penumbra to within 0.4 mm for the investigated cases and showing the excess dose within the field due to wedge scatter. CONCLUSION: RayOcular was validated for its use with an IBA single scattering delivery nozzle. Geometric modeling of the eye and representation of 2D projections fulfill clinical requirements. The PBA dose calculation reproduces measured distributions and allows explicit handling of wedges, overcoming approximations of simpler dose calculation algorithms used in other systems.

Estimation of radiation exposure of children undergoing superselective intra-arterial chemotherapy for retinoblastoma treatment: assessment of local diagnostic reference levels as a function of age, sex, and interventional success.

PURPOSE: This study aims to determine local diagnostic reference levels (LDRLs) of intra-arterial chemotherapy (IAC) procedures of pediatric patients with retinoblastoma (RB) to provide data for establishing diagnostic reference levels (DRLs) in pediatric interventional radiology (IR). METHODS: In a retrospective study design, LDRLs and achievable dose (AD) were assessed for children undergoing superselective IAC for RB treatment. All procedures were performed at the flat-panel angiography systems (I) ArtisQ biplane (Siemens Healthineers) and (II) Allura Xper (Philips Healthcare). Patients were differentiated according to age (A1: 1-3 months; A2: 4-12 months; A3: 13-72 months; A4: 73 months-10 years; A5: > 10 years), sex, conducted or not-conducted chemotherapy. RESULTS: 248 neurointerventional procedures of 130 pediatric patients (median age 14.5 months, range 5-127 months) with RB (68 unilateral, 62 bilateral) could be included between January 2010 and March 2020. The following diagnostic reference values, AD, and mean values could be determined: (A2) DRL 3.9 Gy cm2, AD 2.9 Gy cm2, mean 3.5 Gy cm2; (A3) DRL 7.0 Gy cm2, AD 4.3 Gy cm2, mean 6.0 Gy cm2; (A4) DRL 14.5 Gy cm2, AD 10.7 Gy cm2, mean 10.8 Gy cm2; (A5) AD 8.8 Gy cm2, mean 8.8 Gy cm2. Kruskal-Wallis-test confirmed a significant dose difference between the examined age groups (A2-A5) (p < 0.001). There was no statistical difference considering sex (p = 0.076) and conducted or not-conducted chemotherapy (p = 0.627). A successful procedure was achieved in 207/248 cases. CONCLUSION: We report on radiation exposure during superselective IAC of a pediatric cohort at the German Retinoblastoma Referral Centre. Although an IAC formally represents a therapeutic procedure, our results confirm that radiation exposure lies within the exposure of a diagnostic interventional procedure. DRLs for superselective IAC are substantially lower compared with DRLs of more complex endovascular interventions.

Quantitative detection of circulating tumor cells in cutaneous and ocular melanoma and quality assessment by real-time reverse transcriptase-polymerase chain reaction.

PURPOSE: Inconsistent reports on the detection of melanoma cells in peripheral blood by reverse transcriptase-PCR (RT-PCR) have resulted in uncertainty on the prognostic value of circulating melanoma cells. EXPERIMENTAL DESIGN: We developed real-time RT-PCR assays for quantitation of tyrosinase, MelanA/MART1, and gp100 and for porphobilinogen deaminase housekeeping gene. Melanoma tissue (n = 18), peripheral blood samples from healthy donors (n = 21), and patients with cutaneous (n = 122) and uveal (n = 64) melanoma from our institution were analyzed. For quality control, an additional 251 samples from ongoing multicenter studies were compared with in-house samples. RESULTS: Tyrosinase was not detected in healthy donor blood samples. For the two other markers, cutoff values had to be defined to distinct patient samples from controls. Patients with stage IV uveal and cutaneous melanoma expressed all three markers more frequently and at higher levels in peripheral blood as compared with earlier stages. The variation of expression was 4 logs and correlated with tumor load and serum lactate dehydrogenase. In 2 of 3 uveal melanoma patients, detection of circulating tumor cells preceded the development of liver metastases. The diagnostic sensitivity was optimal in blood samples containing >0.1pg/ microl porphobilinogen deaminase (95.7% of in-house samples and 57.4% of multicenter samples). CONCLUSIONS: Real-time RT-PCR is able to quantitatively define the quality of a sample and provides quantitative data for melanoma markers. Disparities in the results of previous studies may be attributable to undetected differences in sample quality. The prognostic relevance of this assay is currently under evaluation in several prospective randomized trials.