[Comparison with dose-volume histograms of two conformal irradiation techniques used for the treatment of T2N0M0 nasopharyngeal cancer, one with association of photons and protons and another with photons alone]. / Comparaison par les histogrammes dose-volume de deux techniques d'irradiation conformationnelle des cancers du nasopharynx classés T4N0M0, l'une par photons et protons et l'autre par photons seuls.

Purpose- There is a relationship between the local control rate of the nasopharyngeal cancer and the total dose delivered within the tumoral volume. In contrast, the relation between the dose and the irradiated volume and the risk of complication is not clearly defined. That is why, in patients presenting with a locally advanced nasopharyngeal cancer, we compared the dose-volume distribution of irradiated tissues, obtained from two 3D conformal irradiation techniques. Patients and methods- Between January 2000 and June 2001, 5 patients, 3 males and 2 females, with a median age of 32 years and presenting with a T4N0M0 nasopharyngeal cancer received a chemoradiotherapy. Radiotherapy combined photons and protons beams and the platin-based chemotherapy was delivered in three intravenous injections at d1, 22, 43 of the irradiation. To calculate the dosimetry, a CT scan and a MRI were performed in all the patients. The gross tumor volume (GTV) was delineated from the imagery, three clinical tumor volumes were defined, the CTV1 was the GTV and the whole nasopharynx, the CTV2 was the CTV plus a 10 mm-margin and the CTV3 was the CTV2 and the nodes areas (cervical and subclavicular). Prophylactic dose within node areas was 44 Gy. Prescribed doses within CTV2 and GTV or CTV1 were 54 Gy/CGE (Cobalt Gy Equivalent, for an EBR = 1,1) and 70 Gy/CGE, respectively. Irradiation was delivered with fractions of 1.8 or 2.0 Gy/CGE, with 44 Gy or 54 Gy by photons and with 16 or 26 CGE by protons. According to dose-volume histograms obtained from the dosimetry planning by protons and photons and from the theoretical dosimetry by photons lonely, for the different volumes of interest, GTV, CTV2, and organs at risk (optic nerves, chiasm, internal ears, brainstem, temporal lobes), we compared the averages of the maximum, minimum and mean doses and the averages of the volumes of organs of interest encompassed by different isodoses.Results- Calculated averages of minimum, maximum and mean doses delivered within GTV were superior for the treatment with combined photons and protons than with photons alone. The average GTV encompassed by the 70 Gy/CGE isodose was larger by 65% with the association compared to photons alone. The conformation ratio (tissue volume encompassed by the 95% isodose/GTV encompassed by the 95% isodose) was 3.1 with the association compared to 5.7 with photons alone. For the CTV2, there were no differences in different criteria according to the both irradiation techniques. For the critical, radiosensitive organs, the comparison of the majority of the criteria was in favour of the association of protons and photons. Overall, 78% of the criteria were in favour of the association.Conclusion- For locally advanced nasopharyngeal cancer without clinical adenopathy, irradiation by photons and protons increases the tumor volume irradiated at the prescribed dose and decreases the volume or critical organs irradiated and the total dose delivered within them.

[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.

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.

[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.