Double scattering and pencil beam scanning Monte Carlo workflows for proton therapy retrospective studies on radiation-induced toxicities.

PURPOSE: Monte Carlo (MC) simulations can be used to accurately simulate dose and linear energy transfers (LET) distributions, thereby allowing for the calculation of the relative biological effectiveness (RBE) of protons. We present hereby the validation and implementation of a workflow for the Monte Carlo modelling of the double scattered and pencil beam scanning proton beamlines at our institution. METHODS: The TOPAS/Geant4 MC model of the clinical nozzle has been comprehensively validated against measurements. The validation also included a comparison between simulated clinical treatment plans for four representative patients and the clinical treatment planning system (TPS). Moreover, an in-house tool implemented in Python was tested to assess the variable RBE-weighted dose in proton plans, which was illustrated for a patient case with a developing radiation-induced toxicity. RESULTS: The simulated range and modulation width closely matches the measurements. Gamma-indexes (3%/3mm 3D), which compare the TPS and MC computations, showed a passing rate superior to 98%. The calculated RBE-weighted dose presented a slight increase at the necrosis location, within the PTV margins. This indicates the need for reporting on the physical and biological effects of irradiation in high dose regions, especially at the healthy tissues and increased LET distributions location. CONCLUSION: The results demonstrate that the Monte Carlo method can be used to independently validate a TPS calculation, and to estimate LET distributions. The features of the in-house tool can be used to correlate LET and RBE-weighted dose distributions with the incidence of radiation-induced toxicities following proton therapy treatments.

[New indications of protontherapy for adults intracranial tumours]. / Nouvelles indications de protonthérapie et essais cliniques en cours : tumeurs intracrâniennes.

Considering intracranial tumours, only few indications of protontherapy, such as chordoma, chondrosarcoma or uveal melanoma, are uniformly approved in the world. Other indications, excluding paediatric pathologies, are still debated. The aim of this article is to describe the rationale for the use of protonbeam irradiation for meningioma, pituitary adenoma, craniopharyngioma, paraganglioma, glioma, and schwannoma, and to inform the radiation oncologists if prospective studies or randomized studies are opened for inclusions. This article deals only with indications for adults.

First proton minibeam radiation therapy treatment plan evaluation.

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.

Spatial fractionation of the dose in proton therapy: Proton minibeam radiation therapy.

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.

[Boost in proton for locally advanced nasopharyngeal carcinoma: A Curie Institute experience]. / Complément de dose de protons pour les cancers du nasopharynx localement évolués : une expérience de l'institut Curie.

PURPOSE: The aim of this study was to assess the treatment outcome and toxicity for patients with locally advanced nasopharyngeal carcinoma treated with a complementary dose with proton. PATIENTS AND METHODS: Between November 1999 and September 2016, 17 patients have been treated for a stage III-IVa nasopharyngeal carcinoma in the proton therapy centre of Curie Institute. Bilateral lymph node in the neck (I-V levels) received from 40 to 54Gy with photon beam. The primary tumor volume including microscopically extensions received a complementary dose with proton in order to reach the dose of 70 to 78Gy. All the patients received a concomitant chemotherapy. The end-points of the study were loco-regional control, survival, and treatment-related toxicity. RESULTS: Patients characteristics were: median age 49, 71 % male, 88% stage IVa, with a majority (82%) of T4N0M0. The median follow-up was 99 months. The 2-, 5- and 10-year actuarial locoregional free survival and overall survival were 94% and 88%, 86% and 74%, and 86% and 66%, respectively. The grade≥3 late adverse events were sphenoid bone radionecrosis (5.9%) and hearing loss (23.5%). CONCLUSION: This study showed that a complementary dose with proton seems to be a good option for the treatment of locally advanced nasopharyngeal carcinoma, particularly for T4N0M0.

[Conformal radiotherapy to 76Gy in localized prostate cancer. Therapeutic modalities and preliminary results]. / Radiothérapie conformationnelle à 76Gy des cancers localisés de la prostate. Modalités thérapeutiques et résultats préliminaires.

PURPOSE: To describe therapeutic modalities for localized prostate cancer treated by conformal radiation to 76Gy with or without androgen ablation. To evaluate the preliminary results in terms of survival, biological control and toxicity. PATIENTS AND METHOD: Between January 1998 and June 2001, 321 patients with localized prostate cancer were irradiated at institut Curie. Tumors were stratified into the three Memorial Sloan-Kettering Cancer Center prognostic groups (1998) for analysis: favorable risk group (FG) 23%, intermediate risk group (IG) 36.5%, unfavorable risk group (UG) 40.5%. Androgen deprivation, mainly neoadjuvant, less or equal to one year was prescribed to 93.8% of patients (72.6% less or equal to six months). Planning target volume prescription doses were: prostate: 76Gy, seminal vesicles: 56 to 76Gy, and pelvic lymph nodes: 44Gy to 16.8% of patients. RESULTS: The five-year actuarial overall survival was 94% (95% IC: 90-97%). The median post-therapeutic follow-up was 36 months (nine to 60 months). The 48-month actuarial rates of biochemical control for the three prognostic groups were statistically different according to both the American Society for Therapeutic Radiology and Oncology consensus (ASTRO 1997) and the Fox Chase Cancer Center definitions of biochemical failure (FCCC 2000) with respectively 87 and 94% for FG, 78 and 84% for IG, 54 and 58% for UG (P<10(-6) and P<10(-8)). At time of our analysis, late post-treatment rectal and bladder bleedings were 17,4 and 13,6%, respectively. According to a 1-4 scale adapted from M.D. Anderson Cancer Center criteria: rectal bleedings were grade 1 (9.6%), grade 2 (6.2%) and grade 3 (1.6%). Bladder bleedings were grade 2 (13%) and grade 3 (0.6%). Analysis of rectal bleeding risk factors showed significant correlations with pelvic lymph nodes irradiation for grade 2 and 3, (P=0.02), and for all grades, a correlation with smaller rectal wall volumes (P=0.03), and greater percentages of rectal wall irradiated to higher doses: 65, 70, 72 and 75Gy (P=0.02, P=0.01, P=0.0007 and P=0.003, respectively). CONCLUSIONS: These results are comparable to those previously reported with the same follow-up. Impact of dose escalation with short androgen deprivation on local control, survival and complications needs longer follow-up and further analysis.

[Chordomas of the base of the skull and upper cervical spine. 100 patients irradiated by a 3D conformal technique combining photon and proton beams]. / Les chordomes de la base du crâne et du rachis cervical haut. A propos d'une série de 100 patients irradiés selon une technique conformationnelle 3D par une association de faisceaux de photons et de protons.

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.

Possibility of conservative local treatment after combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer.

PURPOSE: The aims of this prospective study were to evaluate the outcome and the possibility of breast conservation therapy for patients with locally advanced noninflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation. METHODS AND MATERIALS: Between April 1982 and June 1990, 97 patients with locally advanced nonmetastatic and noninflammatory breast cancer were treated. The median follow-up was 93 months from the beginning of treatment. The induction treatment consisted of four courses of chemotherapy (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative irradiation (45 Gy to the breast and nodal areas). A fifth course of chemotherapy was given after irradiation therapy. Three different loco-regional approaches were proposed, depending on the tumoral response. In 37 patients (38%) with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumors, mastectomy and axillary dissection were performed. Sixty other patients (62%) benefited from conservative treatment: 33 patients (34%) achieved complete remission and no surgery was done but additional radiation boost was given to the initial tumor bed; 27 patients (28%) who had a residual mass less than or equal to 3 cm in diameter were treated by wide excision and axillary dissection followed by a boost to the excision site. After completion of local therapy, all patients received a sixth course of chemotherapy. A maintenance adjuvant chemotherapy regimen without anthracycline was prescribed (12 monthly cycles). RESULTS: The 5-year actuarial loco-regional relapse rate was 16% after radiotherapy alone, 16% following wide excision and radiotherapy, and 5.4% following mastectomy. The 5-year loco-regional relapse rate was significantly higher after conservative local treatment (wide excision and radiotherapy, and radiotherapy alone) than after mastectomy (p= 0.04). After conservative local treatment, the 5-year breast conserving rate of patients with loco-regional disease-free status was 84%. For all patients included in this study, the 5-year breast-conserving rate of those who were loco-regional disease-free was 52%. In multivariate analysis, the possibility of breast conservative treatment was significantly related to the initial tumor size and age (more conservative treatment for tumor size < 6cm and age < 50 years). Five- and 10-year overall survival rates and disease-free survival rates were 80, 69, 73, and 61% respectively. Five- and 10-year overall survival rates were not influenced by the local treatment (conservative vs. nonconservative local treatment, p = 0.9). On the other hand, local failure significantly decreased the 5- and 10-year overall survival rates (p , 0.0001). In multivariate analysis, three factors had a significant impact on overall survival and disease-free survival: tumor response after induction chemotherapy, initial tumor size, and clinical stage. Arm lymphedema was noted in 12.5% (8 out of 64) of the patients treated with axillary dissection and in 3% (1 out of 33) without axillary dissection. Cosmetic results were satisfactory in 79% of patients after wide excision and radiotherapy and in 71% of patients treated by radiotherapy alone. CONCLUSIONS: Induction chemotherapy followed by preoperative irradiation may permit the selection of some patients with locally advanced breast cancer for conservative treatment. However, the impact of this treatment modality on long-term survival remains to be established.

Single-fraction stereotactic radiotherapy: a dose-response analysis of arteriovenous malformation obliteration.

PURPOSE: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. METHODS AND MATERIALS: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 +/- 230 mm3 (median 968 mm3; range 62-11, 250 mm3). The mean minimum target dose (Dmin) was 19 +/- 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 +/- 300 mm3 (median 1200 mm3; range 75-14 900 mm3). The mean maximum dose (Dmax) was 34.5 +/- 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 +/- 2.3 months (median 37.5; range 7-117). RESULTS: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 +/- 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), Dmin by steps of 5 Gy (p = 0.005), targeted volume of the nidus (< or = 968 mm3 vs. >968 mm3; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the Dmin [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p = 0.010). Delayed complications were observed in eight patients. The 5-year actuarial rate of delayed complications was 7.4%. CONCLUSION: After stereotactic radiotherapy delivered in a single high dose using a single-isocenter technique, the success rate for complete obliteration is independently correlated to Dmin but does not seem to be influenced by Dmax and the targeted volume of the nidus.

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience.

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS: Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.

Linac radiosurgery for cerebral arteriovenous malformations: results in 169 patients.

PURPOSE: To present the SALT group results using Linac radiosurgery (RS) for AVM in 169 evaluable patients treated from January 1990 thru December 1993. METHODS AND MATERIALS: Median age was 33 years (range 6-68 years). Irradiation was the only treatment in 55% patients. Other treatment modalities had been used prior to RS in 45%: one or more embolizations in 36%, surgery in 6%, and embolization and surgery in 3% patients. Nidus were supratentorial in 94% patients, infratentorial in 6% patients. Circular 15 MV x-ray minibeams (6-20 mm) were delivered in coronal arcs by a GE-CGR Saturne 43 Linac. Patient set-up included a Betti arm-chair, a Talairach frame. Prescribed peripheral dose was 25 Gy on the 60%-70% isodose (max dose 100%). Arteriographic results were reassessed in December 1997 at 48 to 96 months follow-up. RESULTS: The overall obliteration rate (OR) was 64% (108/169). AVM volumes ranged from 280 to 19,920 mm(3), median 2460 mm(3). OR was 70% for AVM

A preliminary comparative treatment planning study for radiotherapy of age-related maculopathy.

PURPOSE: We present a comparative planning of different approaches for external radiotherapy in age-related maculopathies. MATERIALS AND METHODS: Calculated dose distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV photons, (b) a single lateral-oblique beam using either photons, electrons or protons and (c) an anterior circular proton beam. RESULTS: For lateral photon or electron beams the dose to the lens is usually lower than 10% of the dose to the macula. The entrance doses for bilateral photon beams are about 50% which increase up to 100% at the orbital bone. About 5 mm of optic nerves are irradiated at the maximal dose while the optic chiasma is spared. A single photon beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow eye but gives a rather inhomogeneous dose to the target volume. For a lateral proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at least 70% of the dose to the macula and the lens and the fellow eye are spared. An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50% isodose approaches the periphery of the lens. CONCLUSION: Doses to the critical structures can be dramatically diminished for all the techniques by reducing the beam size, but only if very precise set-up techniques are used. Proton beams are an attractive solution, but the impact of such a choice on the use of proton facilities and on the national health system should be carefully evaluated, as well as the risk of radio-induced secondary neoplasias.

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 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.

[Initial results of proton therapy in choroidal melanoma at the d'Orsey Center for Proton Therapy; the first 464 cases]. / Résultats préliminaires de la protonthérapie du mélanome de la choroïde au centre de protonthérapie d'Orsay (CPO): les 464 premiers cas.

PURPOSE: Retrospective analysis of the treatment of choroidal melanoma with protontherapy at the Centre de protonthérapie d'Orsay, France. PATIENTS AND METHODS: Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by protontherapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow-up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. RESULTS: Univariate analysis showed that the actuarial local recurrence rate was 5%, the 3-year survival rate 88%, and the overall metastasic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. CONCLUSION: Protontherapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor.

[Radiotherapy using a combination of photons and protons for locally aggressive intracranial tumors. Preliminary results of protocol CPO 94-C1]. / Radiothérapie des tumeurs intracrâniennes localement agressives par une combinaison de photons et de protons. Résultats préliminaires du protocole CPO 94-C1.

PURPOSE: From October 1993 through July 1998, 48 assessable adult patients with non-resectable aggressive intracranial tumors were treated by a combination of high dose photon + proton therapy at the Centre de Protonthérapie d'Orsay. PATIENTS AND METHODS: Grade 1 and 4 gliomas were excluded. Patients benefited from a 3D dose calculation based on high-definition CT and MRI, a stereotactic positioning using implanted fiducial markers and a thermoplastic mask. Mean tumor dose ranged between 63 and 67 Gy delivered in five weekly sessions of 1.8 Gy in most patients, according to the histological types (doses in Co Gy Equivalent, with a mean proton-RBE of 1.1). RESULTS: With a median 18-month follow-up (range: four-58 months), local control in tumors located in the envelopes and in the skull base was 97% (33/34), and in parenchymal tumors, 43% (6/14) only. Two patients (5%) presented with a clinically severe radiation-induced necrosis (temporal lobe and chiasm). CONCLUSION: In our experience, high-dose radiation combining photons and protons is a safe and highly efficient procedure in selected malignancies of the skull base and envelopes.

[Optic neuropathy after proton-beam therapy for malignant choroidal melanoma]. / Neuropathie optique après protonthérapie pour mélanome malin de la choroïde.

Proton-beam irradiation is a conservative therapy commonly used for the treatment of uveal malignant melanomas. Some adverse effects such as optic neuropathy can compromise the visual outcome. We were interested in determining the risk factors for radiation papillopathy. Since there is currently no effective therapy, this is an interesting way to improve prevention of optic neuropathy. Six hundred sixty-two eyes had more than 24 month follow-up after proton-beam irradiation for uveal melanoma. In five hundred twenty-two cases, the clinical examination of the optic nerve head by ophthalmoscopy was possible. One-hundred eleven optic discs were pathologic, whereas 411 remained disease-free. Retrospective study of these two groups allowed to quantify the risk factors for optic neuropathy. The irradiation of more than 2mm of optic nerve at 30 Grays-equivalents appeared to be the major risk factor for optic neuropathy. For a given irradiation dose, the observed pattern of clinical responses was heterogeneous. These results are discussed and compared to the previous published reports. Visual results and life prognosis are also discussed, considering the optic nerve head status. Proton-beam therapy can preserve the optic nerve when the tumor location allows to keep it away from the irradiation-field. Patients must be informed about the risk of optic neuropathy after proton-beam irradiation.

[Results of proton beam irradiation for treatment of choroidal melanoma]. / Résultats du traitement du mélanome de la choroïde par faisceau de protons.

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.

[Re-irradiation of cerebral arteriovenous malformations. Experience of the Sainte-Anne-Tenon Group]. / Ré-irradiation de malformations artério-veineuses cérébrales. Expérience du Groupe Sainte-Anne-Tenopn.

BACKGROUND AND PURPOSE: Between 20 to 50% of cerebral arteriovenous malformations treated with radiosurgery (RS) fail to obliterate 2 to 5 years after irradiation. Patients are not protected against the risks leading to treatment. Two therapeutic options can be used to eradicate the persisting nidus: micro-surgery and a second irradiation. Our group has reirradiated 39 such patients. MATERIAL: From 1989 to 2000, 39 patients have been reirradiated (14 females and 25 males; median age 31 years). There were more left lesions: 59% than right (35%) and 5% on midline. The most frequent locations were: temporal 12 cases; parietal 8 cases; frontal 7 cases; thalamus 7 cases. The predominant first symptoms were hemorrhage (68.5%) and seizure (15.8%). Prior RS, 21/39 patients had embolization (53.8%) and 3 surgery. Method. Treatment has been performed with the same system for the first and the second radiosurgery for 37 patients. Planification and dosimetry improved during that period. The level of dose was similar for the 2 RS. MRI has been used as a non invasive follow-up tool. RESULTS: Only 28 patients were evaluable because 7/39 patients had the second radiosurgery in 1999 or in 2000 and data were lacking at the time of writing for 4 patients. Obliteration rate was 17/28 (60.7%). Nine patients bled between the two radiosurgery procedures. COMPLICATIONS: 4 new regressive deficits occurred after the second radiosurgery. The rate of parenchymal changes were higher, after the second radiosurgery. Except one patient who died of a non-related affection 2 years after obliteration of his cerebral arteriovenous malformation, thus 38/39 patients were alive. CONCLUSION: This series was small compared to the potential number of candidates suffering from failure of the first radiosurgery, but the results are promising.

[Reirradiation of spine and lung tumor with CyberKnife]. / Réirradiation des tumeurs du rachis et du poumon par CyberKnife).

We present the results of two retrospective studies, one regarding reirradiation of spinal tumours and the second, concerning lung tumours. In the first case, primary or secondary tumours were located in or in contact with the vertebrae and spinal cord. The first irradiation has given a full dose to the spinal cord. In the second case, primary or secondary lung tumours have already been treated by irradiation alone or by radiochemotherapy. No grade 3 or 4 early toxicity has been found. Preliminary clinical results are encouraging. The use of CyberKnife represents a major therapeutic advance in the management of irradiated spinal or lung lesions. The possibility of sparing organs at risk and increasing the dose in the tumour target volume are the main advantages.

[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.