Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison

Abstract

Purpose: Eye-dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed.

Material/methods: The HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye-dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in-house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice for absolute dose measurement, and the IAEA TRS-398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread-out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor-specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated.

Results: A pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm² in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall-offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm² , and 0.80 mm, respectively. Average distal fall-offs of the HollandPTC eyeline were 0.20 g/cm² , and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source-to-axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165-350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%.

Conclusions: HollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation-related toxicities. This interinstitutional comparison could support further research on ocular post-PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.

Keywords: eyeline; proton therapy; uveal melanoma.

FIGURE 1

A schematic drawing of the HollandPTC eye nozzle, including its main components with respect to their position. SF, scattering foil; VRS, variable range shifter; RMW, range modulator wheel; IC, set of two ionization chambers; p+, proton; n, neutron; LFM, light field mirror. Not to scale. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Geant4‐simulated energy spread determination. Interinstitutional comparison of the measured vs Geant4‐simulated pristine Bragg peaks with the maximal beam energy and normalized at their maxima. Commissioned range R_90% of every institution is marked by a cross. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Distal and proximal characteristics of measured modulated and collimated beams. (A) Clinical spread‐out Bragg peaks (SOBPs) of 1.10 g/cm² measured at HollandPTC with a FS‐35 mm for five residual ranges. (B) Zoomed‐in distal fall‐off for the same configurations. (C) Interinstitutional comparison of the distal fall‐off of fully modulated beams measured with a FS‐25 mm (a FS‐35 mm was considered at HollandPTC) and along the central axis of the proton beam. (D) Proximal dose distributions as a function of SOBP width measured at HollandPTC with a FS‐35 mm. (E) Interinstitutional comparison of the proximal region of small and medium modulation widths: small SOBP <1.00 g/cm² in solid line and medium SOBP </> 1.00–2.00 g/cm² in dashed line. Data were not available at UFHPTI, Florida, and CPT PSI, Villigen. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Lateral dose profiles of measured modulated and collimated beams. (A) Lateral profiles of the HollandPTC nozzle as a function of field size. All profiles were measured at the isocenter and middle of the fully modulated SOPB. (B) Dependency of the lateral penumbra on spread‐out Bragg peak (SOBP) modulation width of the HollandPTC nozzle. All profiles were measured at the isocenter and middle of each SOPB. (C) Dependency of the lateral profile of the HollandPTC nozzle on the point of measurement in water. All profiles were measured with a FS‐35 mm and the fully modulated SOBP at eight different depths. (D) Lateral penumbra dependency on air gap distance between the surface of the water phantom and the snout exit of the HollandPTC nozzle. All profiles were measured with a FS‐35 mm and the fully modulated SOBP. Zero corresponds to the isocenter. Confidence interval is given at 95%. (E) Interinstitutional comparison of the lateral profiles measured at the isocenter with a fully modulated SOBP. The SOBP width was chosen as close as technically possible to 3.00 g/cm² in all the institutions. (F) Lateral profiles of a FS‐10 mm and of a FS‐20 mm (a FS‐25 mm was considered at UFHPTI, Florida). (G) Lateral penumbra LP 20% to 80% values as a function of the water equivalent depth and measured with a FS‐25 mm (a FS‐35 mm was considered at HollandPTC). Confidence interval is given at 95%. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

Dependency of output factor on field size and spread‐out Bragg peak modulation of the HollandPTC eye nozzle. Error bar function indicates 2.30% of measurement uncertainties. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 6

From technical differences to clinical discrepancies in terms of depth dose distributions: clinical simulations for three scenarios (AJCC staging¹⁷): (A) T1 UM, (B) T2 UM, and (C) T3 UM. Tumors were located anteriorly (ciliary body tumor), at the equator, or posteriorly. Tumor height (TH) and largest basal diameter (LBD) in straight gazing angle direction were used for spread‐out Bragg peak (SOBP) modulation. The dose was prescribed at the isocenter. Simulations were performed with the individual pristine Bragg peak of every institution and the HollandPTC library of range modulator wheels. SOBP region was defined between 90% distal to 90% proximal doses; 2.50 mm distal and proximal margins were used. [Color figure can be viewed at wileyonlinelibrary.com]