30 years of ocular proton therapy, the Nice view.

PURPOSE: Radiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization. MATERAIAL AND METHODS: MEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991-2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (∼95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract). RESULTS: Although demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice. CONCLUSIONS: Some of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.

A 60 MeV proton beam-line dedicated to research and development programs.

A new proton beam-line dedicated to R&D programs has been developed at CentreAntoine Lacassagne (CAL), in Nice (France), in collaboration with the Centrenational d'études spatiales (CNES). This is the second beam-line of the MEDICYC 65 MeV cyclotron that is currently in operation, the first being the clinical 'eye-line' used for ocular proton therapy. The R&D beam-line is proposed with two configurations, the first producing a Gaussian narrow beam of a few mm width, the second a 100 mm diameter flat beam with a homogeneity better than ±3%. The energy range is (20 - ∼60) MeV, where the exact upper limit depends on the beam configuration being used. The energy spread of the non-degraded beam is (0.3 ± 0.1) MeV. A beam current between 10 pA and 10 µA can be produced with a stability better than 0.2% above 100 pA, and 2% below. The beam can be monitored online at a precision better than 5% in the flux range 1E5 (1E6) - 1E9 (1E10) p/cm2/s for a flat (Gaussian) configuration, although work is in progress to extend this range. Targeted applications for the R&D beam-line are instrumentation research, radiation tolerance tests of components and radiobiology.

[Cyberknife robotic stereotactic radiotherapy: technical aspects and recent developments]. / La radiothérapie stéréotaxique avec Cyberknife (R) : aspects pratiques et développements technologiques récents.

Cyberknife (Accuray Inc. Sunnyvale, USA) stereotactic body radiation therapy (SBRT) involves the delivery of a small number of large doses of radiation to a target volume using continuously evolving advanced technology. It has emerged as a novel treatment modality for cancer and modified some concepts of cancer treatment. It is indicated in early-stage primary cancer, sometimes as an alternative to surgery. It is also indicated for patients with oligometastatic disease who have relatively long survival with the aim to optimize disease control with a good quality of life. Although there remain some uncertainties regarding the radiobiology of hypofractionation, local control and tolerance have been promising. Indications are increasing under strict quality assurance programs worldwide and prospective clinical evaluation.

Innovative image-guided CyberKnife stereotactic radiotherapy for bladder cancer.

CyberKnife stereotactic body radiation therapy is used to treat extracranial tumour sites that move with respiration. It has also been employed for the successful treatment of prostate cancer, using the image-tracking CyberKnife system to compensate for intrafraction movements resulting from peristaltic motion and bladder filling. Large sporadic motions can be compensated for using an online target motion monitoring and cybernetic correction strategy. Radio-opaque gold markers can be implanted in the bladder during transurethral resection and used for online image-tracking during radiation to compensate for bladder filling and target movements. Transurethral bladder resection followed by chemoradiation and a stereotactic CyberKnife radiotherapy boost seems a promising approach for the treatment of invasive bladder cancer in heavily pre-treated patients or patients eligible for preservation strategies. In this case study of a patient with a previously irradiated pelvis, CyberKnife radiotherapy was feasible and well tolerated, with disease control and non-altered functional results two years after treatment completion. CyberKnife irradiation may also be considered for the conservative treatment of locally advanced T2-T4a N(0) M(0) bladder cancer with incomplete or uncertain transurethral resection.

[Current indications and ongoing clinical trials with CyberKnife stereotactic radiotherapy in France in 2009]. / Indications du CyberKnife et essais cliniques en cours en 2009.

Image-guided frameless fractionated stereotactic radiotherapy can be performed with millimetric accuracy using the CyberKnife (Accuray Inc. Sunnyvale, USA) equipped with an integrated tracking system for intra- and extracranial lesions. Highly conformal hypofractionated irradiation has been used to treat lesions with curative or palliative intent. It is advantageous for radioresistant tumors, re-irradiating lesions, boosting small volumes and treating tumors that move with respiration. It also limits travel costs and improves the quality of life. Over 60,000 patients have been treated worldwide using CyberKnife including 600 patients in the three French cancer centres of Nice, Nancy and Lille. These expert Cyberknife centres follow quality assurance programs and work together with the "Haute Autorité de santé" and the French National Cancer Institute (INCa) to promote clinical developments. The CyberKnife has been used to treat intracranial lesions including (but not limited to) meningiomas, acoustic schwannomas, brain oligometastases, as well as skull base tumors like chordomas, or para- or intraspinal tumors, and extracranial tumors such as lung cancers. Currently, extracranial stereotactic radiotherapy is particularly attractive for tumors moving with respiration and is being evaluated in liver, prostate and re-irradiation including head and neck tumors.