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1.
Sci Rep ; 10(1): 7025, 2020 04 27.
Article in English | MEDLINE | ID: mdl-32341427

ABSTRACT

Proton minibeam radiation therapy (pMBRT) is a novel dose delivery method based on spatial dose fractionation. pMBRT has been shown to be promising in terms of reduced side effects and superior tumour control in high-grade glioma-bearing rats compared to standard irradiation. These findings, together with the recent optimized implementation of pMBRT in a clinical pencil beam scanning system, have triggered reflection on the possible application to patient treatments. In this context, the present study was designed to conduct a first theoretical investigation of the clinical potential of this technique. For this purpose, a dedicated dose engine was developed and used to evaluate two clinically relevant patient treatment plans (high-grade glioma and meningioma). Treatment plans were compared with standard proton therapy plans assessed by means of a commercial treatment planning system (ECLIPSE-Varian Medical systems) and Monte Carlo simulations. A multislit brass collimator consisting of 0.4 mm wide slits separated by a centre-to-centre distance of 4 or 6 mm was placed between the nozzle and the patient to shape the planar minibeams. For each plan, spread-out Bragg peaks and homogeneous dose distributions (±7% dose variations) can be obtained in target volumes. The Peak-to-Valley Dose Ratios (PVDR) were evaluated between 9.2 and 12.8 at a depth of 20 mm for meningioma and glioma, respectively. Dose volume histograms (DVHs) for target volumes and organs at risk were quantitatively compared, resulting in a slightly better target homogeneity with standard PT than with pMBRT plans, but similar DVHs for deep-seated organs-at-risk and lower average dose for shallow organs. The proposed delivery method evaluated in this work opens the way to an effective treatment for radioresistant tumours and will support the design of future clinical research.


Subject(s)
Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy/methods , Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Humans , Linear Energy Transfer , Monte Carlo Method , Protons , Radiotherapy Dosage
2.
Cancer Radiother ; 23(6-7): 677-681, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31494038

ABSTRACT

In radiation therapy, a renewed interest is emerging for the study of spatially fractionated irradiation. In this article, a few applications using spatial fractionation of the dose will be discussed with a focus on proton minibeam radiation therapy. Examples of calculated dose (1D profiles and 2D dose distributions) and biological evidence obtained so far will be presented for various spatially fractionated techniques GRID, micro- and minibeam radiation therapy. Recent results demonstrating that proton minibeam radiation therapy leads to an increase in normal tissues sparing will be discussed, which opens the door to a dose escalation in the tumour and a possibly efficient treatment of very radioresistant tumours.


Subject(s)
Dose Fractionation, Radiation , Neoplasms/radiotherapy , Organs at Risk/radiation effects , Proton Therapy/methods , Animals , Humans , Radiation Injuries/prevention & control , Radiation Tolerance , Rats
3.
Cancer Radiother ; 22(5): 411-416, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30064829

ABSTRACT

PURPOSE: We report the patient outcomes of a treatment combining proton therapy and Tomotherapy in sinonasal adenoid cystic carcinoma involving skull base. MATERIALS AND METHODS: We included patients treated at Curie Institute, Paris, France, between March 2010 and February 2014 for an advanced adenoid cystic carcinoma involving skull base. Patients received Tomotherapy, proton therapy or both. We evaluated treatment toxicity (according to CTCAE V4), local control, distant metastasis-free survival and overall survival. RESULTS: Thirteen patients were included, with a median follow-up of 34 months. Radiation therapy followed surgery for 77% of the patients and margins were positive in all those cases. Median dose was 73.8Gy. Local control, distant metastasis-free survival and overall survival at 3 years were respectively 60%, 48% and 60%. One-sided grade 3 hearing impairment occurred in 46% of the patients. CONCLUSION: Combining high-dose proton therapy and Tomotherapy is effective and has moderate toxicity in the treatment of T4 sinonasal adenoid cystic carcinoma involving skull base.


Subject(s)
Carcinoma, Adenoid Cystic/radiotherapy , Paranasal Sinus Neoplasms/radiotherapy , Proton Therapy , Radiotherapy, Conformal , Radiotherapy, Intensity-Modulated , Skull Base Neoplasms/radiotherapy , Carcinoma, Adenoid Cystic/diagnostic imaging , Carcinoma, Adenoid Cystic/mortality , Female , Follow-Up Studies , France/epidemiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Organs at Risk/diagnostic imaging , Paranasal Sinus Neoplasms/diagnostic imaging , Paranasal Sinus Neoplasms/mortality , Radiotherapy Dosage , Radiotherapy, Adjuvant , Radiotherapy, Image-Guided , Retrospective Studies , Skull Base Neoplasms/diagnostic imaging , Skull Base Neoplasms/mortality
4.
Rev Sci Instrum ; 88(11): 113301, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29195357

ABSTRACT

Responses of Fuji Imaging Plates (IPs) to proton have been measured in the range 1-200 MeV. Mono-energetic protons were produced with the 15 MV ALTO-Tandem accelerator of the Institute of Nuclear Physics (Orsay, France) and, at higher energies, with the 200-MeV isochronous cyclotron of the Institut Curie-Centre de Protonthérapie d'Orsay (Orsay, France). The experimental setups are described and the measured photo-stimulated luminescence responses for MS, SR, and TR IPs are presented and compared to existing data. For the interpretation of the results, a sensitivity model based on the Monte Carlo GEANT4 code has been developed. It enables the calculation of the response functions in a large energy range, from 0.1 to 200 MeV. Finally, we show that our model reproduces accurately the response of more complex detectors, i.e., stack of high-Z filters and IPs, which could be of great interest for diagnostics of Petawatt laser accelerated particles.

5.
Life Sci Space Res (Amst) ; 10: 23-8, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27662784

ABSTRACT

Particle therapy provides an opportunity to study the human response to space radiation in ground-based facilities. On this basis, a study of light flashes analogous to astronauts' phosphenes reported by patients undergoing ocular proton therapy has been undertaken. The influence of treatment parameters on phosphene generation was investigated for 430 patients treated for a choroidal melanoma at the proton therapy centre of the Institut Curie (ICPO) in Orsay, France, between 2008 and 2011. 60% of them report light flashes, which are predominantly (74%) blue. An analysis of variables describing the patient's physiology, properties of the tumour and dose distribution shows that two groups of tumour and beam variables are correlated with phosphene occurrence. Physiology is found to have no influence on flash triggering. Detailed correlation study eventually suggests a possible twofold mechanism of phosphene generation based on (i) indirect Cerenkov light in the bulk of the eye due to nuclear interactions and radioactive decay and (ii) direct excitation of the nerve fibres in the back of the eye and/or radical excess near the retina.


Subject(s)
Choroid Neoplasms/radiotherapy , Melanoma/radiotherapy , Phosphenes/physiology , Proton Therapy , Radiation Exposure , Space Simulation , Choroid Neoplasms/metabolism , Choroid Neoplasms/pathology , Cosmic Radiation , Humans , Melanoma/metabolism , Melanoma/pathology , Vision, Ocular/radiation effects
6.
Phys Med Biol ; 61(17): 6413-29, 2016 09 07.
Article in English | MEDLINE | ID: mdl-27499356

ABSTRACT

Small diamond detectors are useful for the dosimetry of high-energy proton beams. However, linear energy transfer (LET) dependence has been observed in the literature with such solid state detectors. A novel synthetic diamond detector has recently become commercially available from the manufacturer PTW-Freiburg (PTW microDiamond type 60019). This study was designed to thoroughly characterize four microDiamond detectors in clinical proton beams, in order to investigate their response and their reproducibility in high LET regions. Very good dosimetric characteristics were observed for two of them, with good stability of their response (deviation less than 0.4% after a pre-irradiation dose of approximately 12 Gy), good repeatability (coefficient of variation of 0.06%) and a sensitivity of approximately 0.85 nC Gy(-1). A negligible dose rate dependence was also observed for these two microDiamonds with a deviation of the sensitivity less than 0.7% with respect to the one measured at the reference dose rate of 2.17 Gy min(-1), in the investigated dose rate range from 1.01 Gy min(-1) to 5.52 Gy min(-1). Lateral dose profile measurements showed the high spatial resolution of the microDiamond oriented with its stem perpendicular to the beam axis and with its small sensitive thickness of about 1 µm in the scanning profile direction. Finally, no significant LET dependence was found with these two diamond dosimeters in comparison to a reference ionization chamber (model IBA PPC05). These good results were in accordance to the literature. However, this study showed also a non reproducibility between the devices in terms of stability, sensitivity and LET dependence, since the two other microDiamonds characterized in this work showed different dosimetric characteristics making them not suitable for proton beam dosimetry with a maximum difference of the peak-to-plateau ratio of 6.7% relative to the reference ionization chamber in a clinical 138 MeV proton beam.


Subject(s)
Proton Therapy/methods , Radiation Dosimeters/standards , Diamond/chemistry , Diamond/radiation effects , Linear Energy Transfer , Proton Therapy/instrumentation , Proton Therapy/standards , Radiometry/instrumentation , Radiometry/methods
7.
Phys Med Biol ; 61(4): 1532-45, 2016 Feb 21.
Article in English | MEDLINE | ID: mdl-26816191

ABSTRACT

Collimators are used as lateral beam shaping devices in proton therapy with passive scattering beam lines. The dose contamination due to collimator scattering can be as high as 10% of the maximum dose and influences calculation of the output factor or monitor units (MU). To date, commercial treatment planning systems generally use a zero-thickness collimator approximation ignoring edge scattering in the aperture collimator and few analytical models have been proposed to take scattering effects into account, mainly limited to the inner collimator face component. The aim of this study was to characterize and model aperture contamination by means of a fast and accurate analytical model. The entrance face collimator scatter distribution was modeled as a 3D secondary dose source. Predicted dose contaminations were compared to measurements and Monte Carlo simulations. Measurements were performed on two different proton beam lines (a fixed horizontal beam line and a gantry beam line) with divergent apertures and for several field sizes and energies. Discrepancies between analytical algorithm dose prediction and measurements were decreased from 10% to 2% using the proposed model. Gamma-index (2%/1 mm) was respected for more than 90% of pixels. The proposed analytical algorithm increases the accuracy of analytical dose calculations with reasonable computation times.


Subject(s)
Algorithms , Proton Therapy/methods , Protons , Radiotherapy Planning, Computer-Assisted/methods , Humans , Proton Therapy/instrumentation , Proton Therapy/standards , Radiotherapy Dosage , Scattering, Radiation
8.
Med Phys ; 42(12): 7108-13, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26632064

ABSTRACT

PURPOSE: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy (RT) approach that allies the inherent physical advantages of protons with the normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams. This dosimetry work aims at demonstrating the feasibility of the technical implementation of pMBRT. This has been performed at the Institut Curie - Proton Therapy Center in Orsay. METHODS: Proton minibeams (400 and 700 µm-width) were generated by means of a brass multislit collimator. Center-to-center distances between consecutive beams of 3200 and 3500 µm, respectively, were employed. The (passive scattered) beam energy was 100 MeV corresponding to a range of 7.7 cm water equivalent. Absolute dosimetry was performed with a thimble ionization chamber (IBA CC13) in a water tank. Relative dosimetry was carried out irradiating radiochromic films interspersed in a IBA RW3 slab phantom. Depth dose curves and lateral profiles at different depths were evaluated. Peak-to-valley dose ratios (PVDR), beam widths, and output factors were also assessed as a function of depth. RESULTS: A pattern of peaks and valleys was maintained in the transverse direction with PVDR values decreasing as a function of depth until 6.7 cm. From that depth, the transverse dose profiles became homogeneous due to multiple Coulomb scattering. Peak-to-valley dose ratio values extended from 8.2 ± 0.5 at the phantom surface to 1.08 ± 0.06 at the Bragg peak. This was the first time that dosimetry in such small proton field sizes was performed. Despite the challenge, a complete set of dosimetric data needed to guide the first biological experiments was achieved. CONCLUSIONS: pMBRT is a novel strategy in order to reduce the side effects of RT. This works provides the experimental proof of concept of this new RT method: clinical proton beams might allow depositing a (high) uniform dose in a brain tumor located in the center of the brain (7.5 cm depth, the worst scenario), while a spatial fractionation of the dose is retained in the normal tissues in the beam path, potentially leading to a gain in tissue sparing. This is the first complete experimental implementation of this promising technique. Biological experiments are needed in order to confirm the clinical potential of pMBRT.


Subject(s)
Proton Therapy/methods , Feasibility Studies , Phantoms, Imaging , Proton Therapy/instrumentation , Radiometry/instrumentation , Radiometry/methods , Radiotherapy Dosage , Water
9.
Phys Med Biol ; 59(11): 2747-65, 2014 Jun 07.
Article in English | MEDLINE | ID: mdl-24800943

ABSTRACT

Monte Carlo calculations are increasingly used to assess stray radiation dose to healthy organs of proton therapy patients and estimate the risk of secondary cancer. Among the secondary particles, neutrons are of primary concern due to their high relative biological effectiveness. The validation of Monte Carlo simulations for out-of-field neutron doses remains however a major challenge to the community. Therefore this work focused on developing a global experimental approach to test the reliability of the MCNPX models of two proton therapy installations operating at 75 and 178 MeV for ocular and intracranial tumor treatments, respectively. The method consists of comparing Monte Carlo calculations against experimental measurements of: (a) neutron spectrometry inside the treatment room, (b) neutron ambient dose equivalent at several points within the treatment room, (c) secondary organ-specific neutron doses inside the Rando-Alderson anthropomorphic phantom. Results have proven that Monte Carlo models correctly reproduce secondary neutrons within the two proton therapy treatment rooms. Sensitive differences between experimental measurements and simulations were nonetheless observed especially with the highest beam energy. The study demonstrated the need for improved measurement tools, especially at the high neutron energy range, and more accurate physical models and cross sections within the Monte Carlo code to correctly assess secondary neutron doses in proton therapy applications.


Subject(s)
Monte Carlo Method , Neutrons , Proton Therapy/methods , Radiation Dosage , Humans , Phantoms, Imaging , Proton Therapy/instrumentation , Radiotherapy Dosage
10.
Radiat Prot Dosimetry ; 161(1-4): 363-7, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24222710

ABSTRACT

Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma. MCNPX calculations of out-of-field doses were done for ∼20 different organs considering realistic treatment plans and using computational phantoms representative of an adult male individual. Simulations showed higher secondary neutron doses for intracranial treatments, ∼14 mGy to the salivary glands, when compared with ocular treatments, ∼0.6 mGy to the non-treated eye. This secondary dose increase is mainly due to the higher proton beam energy (178 vs. 75 MeV) as well as to the impact of the different beam parameters (modulation, collimation, field size etc.). Moreover, when compared with published data, the assessed secondary neutron doses showed similar trends, but sometimes with sensitive differences. This confirms secondary neutrons to be directly dependent on beam energy, modulation technique, treatment configuration and methodology.


Subject(s)
Craniopharyngioma/radiotherapy , Eye Neoplasms/radiotherapy , Melanoma/radiotherapy , Neutrons , Proton Therapy/adverse effects , Proton Therapy/methods , Adult , Computer Simulation , Eye/radiation effects , Humans , Male , Models, Theoretical , Monte Carlo Method , Phantoms, Imaging , Radiation Dosage , Radiometry , Radiotherapy Dosage , Reproducibility of Results , Salivary Glands/radiation effects
11.
Phys Med Biol ; 54(8): 2377-94, 2009 Apr 21.
Article in English | MEDLINE | ID: mdl-19321923

ABSTRACT

This paper presents the main results of a Monte Carlo simulation describing the Orsay Proton Therapy Center (CPO) beam line. The project aimed to obtain a prediction of the dose distribution in a water phantom within 2% accuracy in the dose value and a 2 mm of range. The simulation tool used was MCNPX, version 2.5.0, and included all the elements of the CPO beam line. A new algorithm of multiple Coulomb scattering has been incorporated in MCNPX, resulting in a better prediction of the spatial dose distribution and absolute values of the deposited energy. The simulations of 3D dose profiles in water show a very good agreement with measured data to within 2%. We first performed a comparative analysis of the dosimetry in heterogeneous phantoms between the pencil beam algorithm and MCNPX. The simulations give a better agreement with experimental data compared to the pencil beam approach. In a second phase, we simulated the patient-dependent fields along with the spatial dose distributions in a water phantom. The simulated response of a Pixel chamber located 2 m upstream of the water phantom revealed a good agreement with the measured data to within 1%. The results presented herein support the applicability of Monte Carlo models for absolute dosimetry and for design purposes regarding existing and new beam lines at CPO. This work completes a series of publications reporting the progress in the development of a Monte Carlo simulation tool for the CPO beam line dedicated for the treatment of head and neck tumours.


Subject(s)
Models, Biological , Monte Carlo Method , Proton Therapy , Algorithms , Benchmarking , Calibration , France , Humans , Phantoms, Imaging , Radiation Dosage , Reproducibility of Results , Sensitivity and Specificity , Uncertainty , Water
12.
Ophthalmic Res ; 38(5): 255-60, 2006.
Article in English | MEDLINE | ID: mdl-16888407

ABSTRACT

INTRODUCTION: Exudation from the tumour scar and glaucoma can be major problems after proton beam irradiation of uveal melanoma and can sometimes lead to secondary enucleation. We conducted a randomized study to determine whether systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy could have a beneficial effect. PATIENTS AND METHOD: Between February 1999 and April 2003, all the patients treated by proton beam radiotherapy for uveal melanomas >/=7 mm thick or >/=15 mm in diameter were included in this study after giving their informed consent. One half of the patients received proton beam radiotherapy alone (60 Gy in 4 fractions) and the other half received the same dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the information concerning the initial tumour parameters, treatments and follow-up was recorded and a statistical analysis was performed. RESULTS: We randomized 151 patients. The median follow-up was 38 months. The 2 groups of patients were similar in terms of age, gender and tumour characteristics. The patients treated with TTT showed a greater reduction of tumour thickness (p = 0.06), less retinal detachment at the latest follow-up (p = 0.14) and a lower secondary enucleation rate (p = 0.02). DISCUSSION: The present study is the first randomized analysis to demonstrate a significant decrease in the secondary enucleation rate in patients treated with TTT after proton beam radiotherapy. Further studies should be performed to determine whether TTT could be beneficial to smaller tumours and to define its optimal dose.


Subject(s)
Hyperthermia, Induced , Melanoma/radiotherapy , Radioisotope Teletherapy , Uveal Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Cobalt Radioisotopes/therapeutic use , Combined Modality Therapy , Dose Fractionation, Radiation , Eye Enucleation/statistics & numerical data , Female , Humans , Male , Melanoma/therapy , Middle Aged , Pupil , Retinal Detachment/prevention & control , Treatment Outcome , Uveal Neoplasms/therapy
13.
Eye (Lond) ; 20(11): 1300-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16294207

ABSTRACT

AIMS: To describe the results in terms of local control, eye preservation and systemic evolution of iris melanomas treated by proton beam irradiation. METHODS: Retrospective review of the charts of patients with iris melanoma treated by proton beam therapy between April 1998 and September 2002. Ciliary body melanomas with iris involvement or tumours with extrascleral invasion were excluded. Treatment consisted of 60 Gy of proton beam irradiation delivered in four fractions to the tumour volume. RESULTS: A total of 21 patients were treated, median follow-up of 33 months (8-72 months). 15 patients presented a lesion with documented growth. The median clinical diameter was 5 mm (2-8 mm), the median ultrasound diameter 4.8 mm (2-7.7 mm) The patients were 6% T1, 57.1% T2, and 14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of patients. At the end of follow-up, all patients were alive with no proven metastatic disease except one patient with suspicious liver lesions. None of the patients showed tumour progression or ocular relapse. The tumour response at 2 years was a flat lesion for 6.3% of cases, partial regression in 75% and stable in 18.8%. None of the patients required secondary enucleation. The main complication was cataract (45% within 24 months of treatment). Raised intraocular pressure was observed in 15% of patients but no neovascular glaucoma. CONCLUSIONS: Proton beam therapy shows potential utility for selected cases of localised iris melanomas allowing excellent local tumour control and eye preservation. Further follow-up on larger series is needed to confirm these results.


Subject(s)
Iris Neoplasms/radiotherapy , Melanoma/radiotherapy , Proton Therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cataract/etiology , Dose Fractionation, Radiation , Follow-Up Studies , Humans , Iris Neoplasms/pathology , Melanoma/pathology , Middle Aged , Protons/adverse effects , Radiation Injuries/etiology , Retrospective Studies , Treatment Outcome
14.
J Fr Ophtalmol ; 28(8): 833-9, 2005 Oct.
Article in French | MEDLINE | ID: mdl-16249762

ABSTRACT

PURPOSE: We analyzed the long-term results of uveal melanoma treatment with proton beam irradiation in a series of patients with a follow-up of at least 10 years. PATIENTS AND METHODS: The patients were treated with proton beam radiation between September 1991 and December 1992. They had an initial examination including visual acuity, funduscopy, A and B scan ultrasonography of the eye, fundus photographs and fluorescein angiography. General examination included chest radiography and B scan ultrasonography of the liver. All tumors received a total dose of 60 cobalt-Gray equivalents (applied in four daily fractions) at the Orsay proton therapy center. RESULTS: A total of 167 patients were treated with a median follow-up of 116 months. Their median age was 59 years. Thirteen tumors were anterior to the equator, 76 overlapped the equator and 78 were posterior to the equator. An initial retinal detachment was present in 41 cases. The optic disk was invaded in 10 cases. The median tumor diameter was 12 mm and the median tumor thickness was 5.8 mm. The mean initial acuity was 20/50. The survival rate was 62.93% at 10 years; 72.9% of deaths resulted from metastasis. Statistically significant risk factors for death identified in the multivariate analysis were tumor diameter greater than 12 mm (p=0.0004) and age over 60 years (p=0.0001). The metastasis rate at 10 years was 31%. The liver was affected in 97.8% of these patients. Risk factors for metastasis were the anterior site of the tumor, its volume greater than 0.4 cc and the presence of retinal detachment at diagnosis. The secondary enucleation rate at 10 years was 13.23%, mainly attributable to secondary neovascular glaucoma. The local recurrence rate was 6%. The visual acuity rate in 42.1% of patients was better than 20/100 at 10 years. Visual loss was mainly due to postradiation maculopathy and neuropathy. CONCLUSION: Our study confirms the long-term results found in the literature on proton beam radiation. This therapy allows good tumor control, an excellent eye retention rate, and good final visual acuity for approximately half of the patients.


Subject(s)
Melanoma/radiotherapy , Uveal Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Radiotherapy/adverse effects , Retrospective Studies , Time Factors
15.
Cancer Radiother ; 9(3): 161-74, 2005 May.
Article in French | MEDLINE | ID: mdl-15979920

ABSTRACT

OBJECTIVE: To define prognostic factors for local control and survival in 100 consecutive patients treated by fractionated photon and proton radiation for chordoma of the skull base and upper cervical spine. PATIENTS AND METHODS: Between December 1995 and August 2002, 100 patients (median age: 53 years, range: 8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons and protons. The proton component was delivered by the 201 MeV proton beam of the Centre de Protonthérapie d'Orsay (CPO). The median total dose delivered to the gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A complete surgery, incomplete surgery or a biopsy was performed before the radiotherapy in 16, 75 and 9 cases, respectively. RESULTS: With a median follow-up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, less than 95% of the tumour volume encompassed by the 95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic factors of local control. Ten patients died. The 2 and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely independent favourable prognostic factor for overall survival. CONCLUSION: In chordomas of the skull base and upper cervical spine treated by surgical resection followed by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose-uniformity within the gross tumour volume. Special attention must be paid to minimise underdosed areas due to the close proximity of critical structures and possibly escalate dose-constraints to tumour targets in future studies, in view of the low toxicity observed to date.


Subject(s)
Chordoma/radiotherapy , Skull Base Neoplasms/radiotherapy , Spinal Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Chordoma/pathology , Female , Humans , Male , Middle Aged , Photons/therapeutic use , Prognosis , Proton Therapy , Radiometry , Skull Base Neoplasms/pathology , Spinal Neoplasms/pathology , Treatment Outcome
16.
Cancer Radiother ; 8(2): 108-19, 2004 Apr.
Article in English, French | MEDLINE | ID: mdl-15132144

ABSTRACT

Goal of radiotherapy is to treat patient with the best therapeutic ratio, i.e. the highest local control and the lowest toxicity rates. The conformal approach, three-dimensional conformal radiotherapy or intensity-modulated radiotherapy, is based on imageries, up-dated 3-D treatment planning systems, immobilization systems, restricted quality assurance and treatment verification. The aim is to ensure a high dose distribution tailored to the limits of the target volume, while reducing exposure of normal tissues. The evaluation tools used for optimizing treatment are the visual inspection of the dose distribution in various planes, and the dose-volume histograms, but they do not fully quantify the conformity of dose distributions. The conformal index is a tool for scoring a given plan or for evaluating different treatment plans for the same patient. This paper describes the onset and evolution of conformal index and his potential application field.


Subject(s)
Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Conformal , Forecasting , Humans , Imaging, Three-Dimensional , Immobilization , Models, Theoretical , Neoplasms/pathology , Quality Assurance, Health Care , Radiotherapy, Conformal/adverse effects , Stereotaxic Techniques
18.
J Fr Ophtalmol ; 25(3): 290-7, 2002 Mar.
Article in French | MEDLINE | ID: mdl-11941255

ABSTRACT

PURPOSE: To evaluate the results of proton beam irradiation of choroidal melanomas on a large series of patients. PATIENTS AND METHODS: Retrospective analysis of a series of patients treated with proton beam irradiation between 1991 and December 1998. The data were analyzed to evaluate the local tumor control as well as the general progression and metastatic rate of the patients. Statistical analysis served to isolate risk factors for relapse or metastasis. RESULTS: We treated 1062 patients during the study period, with a median follow-up of 38 months. Local control was obtained for 97.1% of the patients. Tumors anterior to the equator were at risk for relapse. The survival rate was 92% at 2 years and 78% at 5 years. 73.1% of the 1062 patients died from metastasis, 6.1% of living patients presented with metastatic disease. The risk factors for death were the initial diameter, the age of the patient, and large tumor volume at diagnosis. Metastasis were essentially hepatic (94.6%). Risk factors for metastasis were: a large tumor volume, a lesion anterior or straddling the equator and the age of the patient. Ocular complications may induce a visual loss of 0.1 and less in 47% of the patients, due to optic nerve head and macular ischemia. 6% of the patients required secondary enucleation due to local complications (neovascular glaucoma). CONCLUSION: Proton beam irradiation of choroidal melanoma allows good tumor control and eye retention. The survival prognosis is associated with the initial volume of the tumor. The functional results may be improved and new therapeutics are needed to treat metastatic disease.


Subject(s)
Choroid Neoplasms/radiotherapy , Melanoma/radiotherapy , Proton Therapy , Adolescent , Adult , Aged , Aged, 80 and over , Choroid Neoplasms/diagnosis , Choroid Neoplasms/surgery , Eye Enucleation , Female , Fluorescein Angiography , Humans , Male , Melanoma/diagnosis , Melanoma/surgery , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Radiography , Radiotherapy Dosage , Retina/diagnostic imaging , Retrospective Studies , Survival Analysis , Treatment Outcome
19.
Br J Ophthalmol ; 85(11): 1305-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11673294

ABSTRACT

AIM: To describe the inflammatory reaction that can occur following proton beam irradiation of uveal melanomas based on a large series of patients and to try to determine the risk factors for this reaction. METHODS: Data from a cohort of patients with uveal melanoma treated by proton beam irradiation between 1991 and 1994 were analysed. The presence of inflammation was recorded and evaluated. Kaplan-Meier estimates and statistical analysis of general and tumour related risk factors were performed. RESULTS: 28% of patients treated during this period presented with ocular inflammation (median follow up 62 months). Risks factors were essentially tumour related and were correlated with larger lesions (height > 5 mm, diameter > 12 mm, volume > 0.4 cm(3)). Multivariate analysis identified initial tumour height and irradiation of a large volume of the eye as the two most important risk factors. Ocular inflammation usually consisted of mild anterior uveitis, resolving rapidly after topical steroids and cycloplegics. The incidence of inflammation after proton beam irradiation of melanomas seems higher than previously reported and is related to larger lesions. Evidence of inflammation associated with uveal melanoma has been described and seems to be associated with tumour necrosis (spontaneous or after irradiation). The appearance of transient inflammation during the follow up of these patients may be related to the release of inflammatory cytokines during tumour necrosis. CONCLUSION: Inflammation following proton beam irradiation is not unusual. It is correlated with larger initial tumours and may be related to tumour necrosis.


Subject(s)
Melanoma/radiotherapy , Radiation Injuries/complications , Uveal Neoplasms/radiotherapy , Uveitis, Anterior/etiology , Analysis of Variance , Anti-Inflammatory Agents/therapeutic use , Female , Humans , Male , Melanoma/complications , Melanoma/pathology , Mydriatics/therapeutic use , Proportional Hazards Models , Radiation Injuries/drug therapy , Retrospective Studies , Risk Factors , Steroids , Survival Analysis , Treatment Outcome , Uveal Neoplasms/complications , Uveal Neoplasms/pathology , Uveitis, Anterior/drug therapy
20.
Med Phys ; 28(6): 975-87, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11439494

ABSTRACT

We present an experimental procedure for the determination and the verification under practical conditions of physical and computational parameters used in our proton pencil beam algorithm. The calculation of the dose delivered by a single pencil beam relies on a measured spread-out Bragg peak, and the description of its radial spread at depth features simple specific parameters accounting individually for the influence of the beam line as a whole, the beam energy modulation, the compensator, and the patient medium. For determining the experimental values of the physical parameters related to proton scattering, we utilized a simple relation between Gaussian radial spreads and the width of lateral penumbras. The contribution from the beam line has been extracted from lateral penumbra measurements in air: a linear variation with the distance collimator-point has been observed. Analytically predicted radial spreads within the patient were in good agreement with experimental values in water under various reference conditions. Results indicated no significant influence of the beam energy modulation. Using measurements in presence of Plexiglas slabs, a simple assumption on the effective source of scattering due to the compensator has been stated, leading to accurate radial spread calculations. Dose measurements in presence of complexly shaped compensators have been used to assess the performances of the algorithm supplied with the adequate physical parameters. One of these compensators has also been used, together with a reference configuration, for investigating a set of computational parameters decreasing the calculation time while maintaining a high level of accuracy. Faster dose computations have been performed for algorithm evaluation in the presence of geometrical and patient compensators, and have shown good agreement with the measured dose distributions.


Subject(s)
Algorithms , Proton Therapy , Radiotherapy Planning, Computer-Assisted/statistics & numerical data , Radiotherapy, Conformal/statistics & numerical data , Biophysical Phenomena , Biophysics , Humans , Models, Theoretical , Neoplasms/radiotherapy , Scattering, Radiation
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