A generalized model for monitor units determination in ocular proton therapy using machine learning: A proof-of-concept study.

Objective.Determining and verifying the number of monitor units is crucial to achieving the desired dose distribution in radiotherapy and maintaining treatment efficacy. However, current commercial treatment planning system(s) dedicated to ocular passive eyelines in proton therapy do not provide the number of monitor units for patient-specific plan delivery. Performing specific pre-treatment field measurements, which is time and resource consuming, is usually gold-standard practice. This proof-of-concept study reports on the development of a multi-institutional-based generalized model for monitor units determination in proton therapy for eye melanoma treatments.Approach.To cope with the small number of patients being treated in proton centers, three European institutes participated in this study. Measurements data were collected to address output factor differences across the institutes, especially as function of field size, spread-out Bragg peak modulation width, residual range, and air gap. A generic model for monitor units prediction using a large number of 3748 patients and broad diversity in tumor patterns, was evaluated using six popular machine learning algorithms: (i) decision tree; (ii) random forest, (iii) extra trees, (iv) K-nearest neighbors, (v) gradient boosting, and (vi) the support vector regression. Features used as inputs into each machine learning pipeline were: Spread-out Bragg peak width, range, air gap, fraction and calibration doses. Performance measure was scored using the mean absolute error, which was the difference between predicted and real monitor units, as collected from institutional gold-standard methods.Main results.Predictions across algorithms were accurate within 3% uncertainty for up to 85.2% of the plans and within 10% uncertainty for up to 98.6% of the plans with the extra trees algorithm.Significance.A proof-of-concept of using machine learning-based generic monitor units determination in ocular proton therapy has been demonstrated. This could trigger the development of an independent monitor units calculation tool for clinical use.

Study of the responses and calibration procedures of neutron and gamma area and environmental detectors for use in proton therapy.

Ambient dose equivalent measurements with radiation protection instruments are associated to large uncertainties, mostly due to the energy dependence of the instrument response and to the dissimilarity between the spectra of the standard calibration source and the workplace field. The purpose of this work is to evaluate its impact on the performance of area and environmental detectors in the proton therapy environment, and to provide practical solutions whenever needed and possible. The study was carried out at the Centre Antoine Lacassagne (CAL) proton therapy site, and included a number of commercially available area detectors and a home-made environmental thermoluminescent dosimeter based on a polyethylene moderator loaded with TLD600H/TLD700H pairs. Monte Carlo simulations were performed with MCNP to calculate, first, missing or partially lacking instrument responses, covering the range of energies involved in proton therapy. Second, neutron and gamma spectra were computed at selected positions in and outside the CAL proton therapy bunkers. Appropriate correction factors were then derived for each detector, workplace location and calibration radionuclide source, which amounts to up to 1.9 and 1.5 for neutron and photon area detectors, respectively, and suggest that common ambient dose equivalent instruments might not meet IEC requirements. The TLD environmental system was calibrated in situ and appropriate correction factors were applied to account for the cosmic spectra. Measurements performed with this system from 2014 to 2017 around the installation were consistent with reference natural background dose data and with pre-operational levels registered at the site before the construction of the building in 1988, showing thus no contribution from the site clinical activities. An in situ verification procedure for the radiation protection instruments was also implemented in 2016 at the low energy treatment room using the QA beam reference conditions. The method presents main methodological, practical and economic advantages over external verifications.

Cataract Avoidance With Proton Therapy in Ocular Melanomas.

Purpose: The lens is a radiosensitive organ. Any dose of cephalic irradiation can give rise to radiation-induced cataracts. Contrary to other forms of radiotherapy, proton therapy (PT) can spare all or part of the lens due to accurate dose deposition. We investigated whether a lens-sparing approach was relevant to avoid cataracts in uveal melanoma patients. Methods: Patients were referred for PT from onco-ophthalmologists of private and academic institutions. Patients without preexisting cataracts or implants were entered in a prospective database. Dose thresholds responsible for cataracts were investigated in volumes of lens or lens periphery. Lens opacifications and de novo vision-impairing cataracts (VICs) had biannual follow up by ophthalmologists blinded to lens dose. Correlations between dose-volume relationships and VICs were assessed using univariate/multivariate regressions. Results: Between 1991 and 2015, 1696 uveal melanoma patients were consecutively treated with PT. After a median follow up of 48 months, 14.4% and 8.7% of patients had cataracts and VIC within median times of 19 and 28 months, respectively. Median values of mean lens and lens periphery doses were 1.1 (radiobiologically effective [RBE] dose in photon-equivalent grays [GyRBE]) and 6.5 GyRBE, respectively. The lens received no dose in 25% of the patients. At an irradiated lens volume of ≤5%, there was no significantly increased risk for VIC below a dose of 10 GyRBE. Conclusions: A lens-sparing approach is feasible and results not only in reduced need for cataract surgery but also in better fundus-based tumor control. Reassessment of radioprotection rules for lens dose thresholds may follow.

Visual Outcomes of Parapapillary Uveal Melanomas Following Proton Beam Therapy.

PURPOSE: In parapapillary melanoma patients, radiation-induced optic complications are frequent and visual acuity is often compromised. We investigated dose-effect relationships for the optic nerve with respect to visual acuity after proton therapy. METHODS AND MATERIALS: Of 5205 patients treated between 1991 and 2014, those treated using computed tomography (CT)-based planning to 52 Gy (prescribed dose, not accounting for relative biologic effectiveness correction of 1.1) in 4 fractions, with minimal 6-month follow-up and documented initial and last visual acuity, were included. Deterioration of ≥0.3 logMAR between initial and last visual acuity results was reported. RESULTS: A total of 865 consecutive patients were included. Median follow-up was 69 months, mean age was 61.7 years, tumor abutted the papilla in 35.1% of patients, and tumor-to-fovea distance was ≤3 mm in 74.2% of patients. Five-year relapse-free survival rate was 92.7%. Visual acuity was ≥20/200 in 72.6% of patients initially and 47.2% at last follow-up. A wedge filter was used in 47.8% of the patients, with a positive impact on vision and no impact on relapse. Glaucoma, radiation-induced optic neuropathy, maculopathy were reported in 17.9%, 47.5%, and 33.6% of patients, respectively. On multivariate analysis, age, diabetes, thickness, initial visual acuity and percentage of macula receiving 26 Gy were predictive of visual acuity. Furthermore, patients irradiated to ≥80% of their papilla had better visual acuity when limiting the 50% (30-Gy) and 20% (12-Gy) isodoses to ≤2 mm and 6 mm of optic nerve length, respectively. CONCLUSIONS: A personalized proton therapy plan with optic nerve and macular sparing can be used efficiently with good oncological and functional results in parapapillary melanoma patients.

Influence of Ionizing Radiation on Two Generations of Cochlear Implants.

The purpose of the present study was to test the behavior of two different generations of cochlear implant systems subjected to a clinical radiotherapy scheme and to determine the maximal acceptable cumulative radiation levels at which the devices show out-of-specification behaviors. Using stereotactic irradiation (Cyberknife, 6 MV photon beam), three Digisonic SP and three Neuro devices were submitted to 5 Gy doses that cumulated to 60 Gy (12 sessions) and 80 Gy (16 sessions), respectively. A follow-up series of irradiation was then applied, in which Digisonic SP devices received two additional fractions of 50 Gy each, cumulating to 160 Gy, and Neuro devices three additional fractions of 20, 40, and 150 Gy, cumulating to 290 Gy. Output current values were monitored during the treatment. At clinical doses, with 60 or 80 Gy cumulative radiation exposure, no single measurement showed more than 10% divergence from the reference measure. The cochlear implants tested in this study showed high resistance to clinically relevant cumulative radiation doses and showed no out-of-bounds behavior up to cumulative doses of 140 or 160 Gy. These observations suggest that cochlear implant users can undergo radiotherapy up to cumulative doses well above those currently used in clinical situations without risk of failure.

Effects and consequences of Digisonic SP cochlear implant on radiotherapy planning.

The aim of this study was to assess dose attenuation by a Digisonic SP cochlear implant (CI) and evaluate its impact on treatment planning. The Digisonic CI was irradiated with 6 MV photons. Overall dose attenuation was assessed with MOSFET dosimeters and Gafchromic films. In addition, we evaluated the attenuation of separate CI components. Dose attenuation was also calculated using different radiation treatment planning systems (TPS) softwares and dose calculation algorithms. The CI was placed on a head phantom. Single-beam and multiple-beam plans were evaluated for dose attenuation using two radiation techniques (Conformal and Stereotactic radiotherapy) and four different algorithms (Clarkson, Point Kernel-Superposition, Ray Tracing and Monte Carlo). MOSFET and Gafchromics film showed maximal 6-7.5% radiation dose attenuation, at the center of the CI. Computerized TPS-based dose attenuation by the implant was 4-8.1%, using a single ipsilateral field. No clinically meaningful dose attenuation was found in multiple field plans owing to the contribution of various beam paths with only a couple going through the implant using either conventional conformal or stereotactic treatment plans. Dose attenuation induced by a Digisonic SP CI is about 6%, for single 6 MV photon field. This dose reduction is unlikely to be clinically significant, as single-field radiotherapy plans to this anatomic region are uncommon.

Proton beam therapy for presumed and confirmed iris melanomas: a review of 36 cases.

BACKGROUND: To report the clinical features and outcomes of iris melanomas treated by proton beam therapy. MATERIALS AND METHODS: A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon, Department of Ophthalmology, in 36 patients treated by proton beam therapy for presumed (n = 29) and confirmed (n = 7) iris melanomas between July 1997 and October 2010. Ciliary body melanomas with iris involvement were excluded. The patients' mean age was 54.4 years (range, 22-82 years). The average tumor diameter was 3.8 mm (range, 2.5-8.0). The iridocorneal angle was invaded by the tumor in 47% of cases (n = 17), the ciliary body in 17% of cases (n = 6), and the sclera in 3% (n = 1). Raised intraocular pressure was present before treatment in 11.1 % of cases (n = 4). Tumor biopsy was performed in 19% of cases (n = 7). Four patients had undergone an initial incomplete surgical excision of tumor before radiotherapy. Surgical preparation of the eye with tantalum ring positioning had been performed in all cases 3-4 weeks before irradiation. The prescribed dose was 60 Cobalt Gray Equivalent (CGE) of proton beam radiotherapy delivered in four fractions on four consecutive days. RESULTS: The median follow-up was 50 months (mean 60.5, range 15-136). One patient (2.7%) was lost to follow-up. None of the patients showed tumor progression, local recurrence, or metastasis. None of the patients required secondary enucleation. Cataract was developed in 62% of patients, glaucoma in two cases (6%) after irradiation, and hyphema with the aggravation of pre-existing glaucoma in one patient. No patients developed neovascular glaucoma. CONCLUSIONS: Proton beam therapy appears to be the treatment of choice for the conservative treatment of iris melanomas with excellent tumor control and an acceptable rate of complications. Longer follow-up studies on a larger series is necessary to consolidate these results.

[Advances in radiation oncology for metastatic bone disease]. / Métastases osseuses : les nouvelles techniques d'irradiation et traitements combinés ablatifs décalent-ils les standards ?

INTRODUCTION: Irradiation of bone metastases primarily aims at alleviating pain, preventing fracture in the short term. The higher doses and more conformal dose distribution achievable while saving healthy tissue with new irradiation techniques have induced a paradigm shift in the management of bone metastases in a growing number of clinical situations. MATERIALS AND METHODS: A search of the English and French literature was conducted using the keywords: bone metastases, radiotherapy, interventional radiology, vertebroplasty, radiofrequency, chemoembolization. RESULTS-DISCUSSION: Stereotactic irradiation yields pain relief rates greater than 90% in Phase I/II and retrospective studies. IMRT (static, rotational, helical) and stereotactic irradiation yield local control rates of 75-90% at 2 years. Some situations previously evaluated as palliative are currently treated more aggressively with optimized radiation sometimes combined modality interventional radiology. CONCLUSION: A recommendation can only be made for stereotactic irradiation in vertebral oligometastases or reirradiation. In the absence of a sufficient level of evidence, the increasing use of conformal irradiation techniques can only reflect the daily practice and the patient benefit while integrating economic logic care. The impact of these aggressive approaches on survival remains to be formally demonstrated by interventional prospective studies or observatories including quality of life items and minimal 2-year follow-up.