A. Mazal

Intraocular inflammation after proton beam irradiation for uveal melanoma

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 cm3). 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.

Proton dosimetry comparison involving ionometry and calorimetry

A comparison of the absorbed dose to tissue determined by various ionization chambers, Faraday cups, and an A-150 plastic calorimeter was performed in the 200 MeV proton beam of Orsay, France. Four European proton-therapy centers (Clatterbridge, UK, Louvain la Neuve, Belgium, and Nice and Orsay, France) participated in the comparison. An agreement of better than 1% was observed in the absorbed dose to A-150 measured with the different chambers of the participating groups. The mean ratio of the absorbed dose to A-150 determined with the calorimeter to that determined by the different ionization chambers in the different irradiation conditions was found to be 0.952 +/- 0.007 [1 standard deviation (SD)] according to the code of practice used by all the participating centers, based on Jannis tables of stopping powers and a value of 35.2 J/Coulomb for (W(air)/e)p. A better agreement in the mean ratio calorimeter/chamber, 0.985 +/- 0.007 (1 SD) is observed when using the proton stopping power ratio values recently published by the International Commission on Radiation Units and Measurements in Report no. 49. The mean ratio of these doses determined in accordance with the American Association of Physicists in Medicine protocol and using the new recommended stopping power tables becomes 1.002 +/- 0.007 (1 SD). Two Faraday cups agree in measured charge to within 0.8%; however, the calculation of dose is underestimated by up to 17%; compared with ion chamber measurements and seems to be very sensitive to measurement conditions, particularly to the distance to the collimator.

Potential benefits of using cardiac gated images to reduce the dose to the left anterior descending coronary during radiotherapy of left breast and internal mammary nodes.

PURPOSE To assess the benefits of using cardiac gated images for treatment planning of breast and internal mammary nodes. PATIENTS AND METHODS Inspiration breath hold computed tomography (CT) series acquired at prospectively gated diastolic phase were used for planning. Three different techniques were compared. Technique A used tangents and an internal mammary nodes field covering the three first inter-rib spaces; technique B used an extended internal mammary nodes including part of the medial breast in junction with tangential fields; the 3(rd) technique used helical tomotherapy. For each technique, two treatment plans were performed: one plan (plan-01) where mean dose and V(25) to the heart were considered for plan evaluation and a second plan (plan-02) where the irradiation of the left anterior descending artery was minimized. RESULTS V(25) to the heart was found to be less than 5% for all six plans. Mean doses to the heart were within 4.8 to 7.2 Gy. By attempting to lower the dose to the left anterior descending artery, heart D(mean) was decreased by 20-30% for the two techniques A and B while being unchanged for tomotherapy. Regarding target coverage, there was no marked difference between plans where only heart dose was considered (plans-01) and plans where the left anterior descending artery dose was minimized (plans-02). When the left anterior descending artery dose was part of plan evaluation, D(mean) to the left anterior descending artery could be decreased by 24, 19 and 9% for techniques A, B and tomotherapy respectively. The three techniques exposed segments of the left coronary to different levels of dose. CONCLUSION This study showed that evaluation of the dose to the left anterior descending artery coronary may change the treatment strategy. Cardiac gated images without IV contrast permitted a good visualization of the coronaries in order to optimize the dose on these structures. In addition to heart V(25,) the dose to the coronaries should be included in prospective studies on radiotherapy related heart toxicity in association with all additional risk factors.

La protonthérapie : bases, indications et nouvelles technologies

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.

Clinical applications of proton therapy.

Proton therapy offers considerable potential advantages in the management of poorly resectable, radio-resistent tumors close to critical anatomical structures. So far over 15,000 patients have been treated worldwide with two major indications: conservative management of ocular melanomas in which local control exceeds 95% at 5 years and curative irradiation of sarcomas at the base of the skull and cervical canal, with a survival rate between 84 and 94% at 5 years. The different protocols tested currently worldwide are discussed.

Preliminary results with one-year minimum follow-up of the first 146 patients with a uveal melanoma treated with protons at CPO (Orsay)

Summary Proton therapy began at the ‘Centre de Protontherapie d’Orsay’ (CPO) in September 1991. Our treatment protocol and the preliminary results have been presented on the first 146 irradiated patients with one-year minimal follow-up. The subsequent developments have also been mentioned.

Physical Rationale for Proton Therapy and Elements to Build a Clinical Center

In this chapter we present: I. The physical bases of proton therapy, going from microscopic concepts to macroscopic features II. The technology and the logistics, which evolve to more and more compact and cheaper facilities with the capability to perform adaptive radiation therapy III. The most usual clinical indications, moving toward (nearly) all indications of radiation therapy IV. Some research orientations, rediscovering physics, and radiation biology V. Basic elements to conceive and build a clinical center VI. Conclusions: The need to learn from others and also to innovate

La protonthérapie : bases, indications et nouvelles technologiesProtontherapy: basis, indications and new technologies

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.

The use of aSi EPID for in vivo dosimetry in photon beams: clinical experience

In vivo dose verification is used to prevent major deviations between the prescribed dose and the dose really delivered to the patient. This work presents a quick and simple alternative method for verification of dose delivered to the patient using photon beams. During the treatment session, a transit dose is measured with the EPID and the dose in the patient is estimated from back projection of the portal dose. This method was validated by phantom measurement using an ionisation chamber. Central axis doses estimated by this formalism were compared with measured dose. The feasibility of the method and its applicability in clinical use has been evaluated on patients treated with conformal therapy (18 patients, 325 treatment beams over 8 months) and with IMRT (9 patients, 165 treatment beams). Using this amount of data, the definition of action levels became possible. The uncertainties are within the accepted tolerance of classical in vivo dosimetry (1SD = 3.5% for conformational beams and 1SD = 3.6% for IMRT). The proposed method for in vivo dose verification is very simple to implement and to use in clinics. Measurements can be repeated during several sessions giving the opportunity to built new strategies for the validation by statistical evaluation of the data. The trending of in vivo dose along the treatment becomes also possible.

La protonthérapie : aspects technologiques, applications cliniques et perspectives

Protontherapy certainly presents a ballistic advantage with in-depth dose distribution following a Bragg peak. Some fifteen health-care centres are presently applying this technique in the U.S. Europe and Japan. - Low-energy systems allow the treatment of tumours of the eye while higher energies are able to reach tumours deep in the trunk. - The present two major indications are the conservative treatment of ocular melanomas and the post-operative irradiation of sarcomas of the skull base and of the spinal canal. - Other treatments are presently being explored : carcinomas of the prostate ; tumours of the head and neck, of the central nervous system and of the liver.