Melanoma: Chauvel P

Bensadoun RJ, Allavena C, Chauvel P, Dassonville O, Demard F, Dieu-Bosquet L, Lacau St Guily J, Ettore F, Gory-Delabaere G, Marcy PY, Reyt E, Anonymous00028, Anonymous00029, Anonymous00030, Anonymous00031, Anonymous00032, Anonymous00033. · Centre Antoine Lacassagne, Nice, France. · Bull Cancer. · Pubmed #12957805 links to  free full text

Abstract: CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPG s according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concern the place of fine needle aspiration biopsy in preoperative diagnosis, the place of cervical lymph node area surgical treatment, the place of postoperative irradiation and neutron therapy in the treatment of unresectable tumors and also the place of medical imaging, especially RMI, for the diagnosis of these tumors.

Bensadoun RJ, Allavena C, Chauvel P, Dassonville O, Demard F, Dieu-Bosquet L, Lacau St Guily J, Ettore F, Gory-Delabaere G, Marcy PY, Reyt E, Anonymous00452, Anonymous00453, Anonymous00454, Anonymous00455, Anonymous00456, Anonymous00457. · Centre Antoine-Lacassagne, Nice. · Cancer Radiother. · Pubmed #12914861 No free full text.

Abstract: CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers. and specialists from French public universities,general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, treatment and follow-up of patients with these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been defined, the document is submitted for review by independent reviewers. RESULTS: This article presents the updated clinical practice guidelines concerning irradiation of patient with salivary gland tumors. The main recommendations are: 3 dimensional conformal radiotherapy (with or without intensity modulation) or 2D irradiation can be used; for surgical complete resected patients, postoperative photon radiotherapy should not be used in case of low grade stage I and 11 tumors(standard, level of evidence B2) but should be used for high grade stage II, II and IV tumors and for low grade stage III and IV tumors(standard, level of evidence B2). Neutron therapy should not be used in all of these cases (standard, level of evidence D); for patients presenting an incomplete macroscopic or microscopic surgical residual disease, postoperative irradiation must be delivered(standard). Neutron or photon therapy can be either delivered (options); for non operable patients neutron or photon therapy can be either delivered (options, level of evidence B2); for unresectable tumors or in case of recurrent neoplasms, exclusive neutron therapy or surgical tumor reduction combined with postoperative photon beam irradiation can be proposed (options, level of evidence C).

Kodjikian L, Nguyen K, Lumbroso L, Gauthier-Villars M, Chauvel P, Plauchu H, Sterkers M, Devouassoux M, Grange JD. · Hospices Civils de Lyon, Université Claude Bernard, University Eye Clinic, Croix Rousse Hospital, Department of Ophthalmologie, 103 Grande rue de la Croix Rousse, 69004 Lyon, France. · Acta Ophthalmol Scand. · Pubmed #12859267 No free full text.

Abstract: PURPOSE: A total of 69 families affected by uveal melanoma have been reported in the literature. This report describes two additional families. In addition to presenting these cases, which constitute exceptions, the paper reviews the literature. MATERIAL AND METHODS: Two families, each with two affected members, were analysed in this retrospective study. The pedigree of each family has been pieced together. RESULTS: Considering the low incidence of familial uveal melanoma in the general population, it seems unlikely that inherited genetic factors are responsible for the condition; this question remains difficult to resolve. DISCUSSION: The characteristics of each family history are described and compared with the literature data. The mode of possible inheritance is discussed. Both the histopathology and anatomical location are studied, after which we discuss the body of evidence to establish whether there is an inherited cancer predisposition syndrome in patients with familial uveal melanoma. CONCLUSION: The statistical likelihood of such an uncommon tumour occurring independently in two or more family members leads us to believe that some cases of familial uveal melanoma may go unrecognized, and that reports on too few families have been published worldwide to prove the existence of a single mendelien gene. However, appropriate tissue samples, such as blood and tumour samples, should be obtained and conserved for present or future cytogenetic and molecular genetic studies.

Westekemper H, Anastassiou G, Sauerwein W, Chauvel P, Bornfeld N, Steuhl KP, Meller D. · Zentrum für Augenheilkunde, Universitätsklinikum, Hufelandstrasse 55, 45122 Essen. · Ophthalmologe. · Pubmed #16721565 No free full text.

Abstract: BACKGROUND: In cases of large, diffuse or multilocular growth pattern of conjunctival melanoma, proton beam irradiation can serve as an alternative therapy to exenteration. In extended tumours, ocular surface problems can result after therapy. In this study we examined ocular surface integrity of ten patients who underwent proton beam radiation between 1996 and 2002. METHODS: The patients were examined during their follow-up. Eight of the ten cases who underwent proton radiotherapy were recurrent tumours, which were previously treated with other adjuvant therapies. We performed a standard ophthalmological examination and detailed tear film diagnostics. RESULTS: The follow-up was 17-87 months (mean: 40.9+/-20.1). In six cases more than 50% of the upper and lower eyelids were included in the radiation field. All of these cases showed moderate to severe sicca symptoms. The impression cytology revealed squamous metaplasia of conjunctival cells in nine of ten cases. CONCLUSIONS: Squamous metaplasia of conjunctival epithelia indicates a radiogenic, persisting disturbance of differentiation of the conjunctival epithelial cells. The tear film instability correlates with the loss of mucin-secreting goblet cells and meibomian gland dysfunction.

Mosci C, Mosci S, Barla A, Squarcia S, Chauvel P, Iborra N. · National Institute for Cancer Research, Genova - Italy. · Eur J Ophthalmol. · Pubmed #19551683 No free full text.

Abstract: PURPOSE. To evaluate the results of 15 years of experience with proton beam radiotherapy in the treatment of intraocular melanoma, and to determine univariate and multivariate risk factors for local failure, eye retention, and survival. METHODS. A total of 368 cases of intraocular melanoma were treated with proton beam radiotherapy at Centre Lacassagne Cyclotron Biomedical of Nice, France, between 1991 and 2006. Actuarial methods were used to evaluate rate of local tumor control, eye retention, and survival after proton beam radiotherapy. Cox regression models were extracted to evaluate univariate risk factors, while regularized least squares algorithm was used to have a multivariate classification model to better discriminate risk factors. RESULTS. Tumor relapse occurred in 8.4% of the eyes, with a median recurrence time of 46 months. Enucleation was performed on 11.7% of the eyes after a median time of 49 months following proton beam; out of these, 29 eyes were enucleated due to relapse and 16 due to other causes. The univariate regression analysis identified tumor height and diameter as primary risk factors for enucleation. Regularized least squares analysis demonstrated thehigher effectiveness of a multivariate model of five risk factors (macula distance, optic disc distance, tumor height, maximum diameter, and age) in discriminating relapsed vs nonrelapsed patients. CONCLUSIONS. This data set, which is the largest in Italy with relatively long-term follow-up, demonstrates that a high rate of tumor control, survival, and eye retention were achieved after proton beam irradiation, as in other series.

Fauquembergue M, Kodjikian L, Chauvel P, Bacin F. · Clinique Ophtalmologique Universitaire, Centre Hospitalier de la Croix Rousse, Lyon. · J Fr Ophtalmol. · Pubmed #18046278 links to  free full text

Abstract: We report the case of a single-eyed patient with a small (2.2 mm thick with largest tumor diameter 7.6 mm) choroidal melanoma involving the entire macular surface with few functional signs. Visual acuity was 20/63. The patient was informed of the side effects and so was followed regularly at the oncology unit over 4 years. During this period, the tumor volume increased fourfold (the thickness reached 4.3 mm and the LTD 10.4 mm), with visual acuity decreasing to 20/250: proton beam therapy was therefore performed. The patient showed no metastasis more than 2 years after the treatment. This unusual case raises the question of small choroidal melanoma management, especially if the patient is single-eyed, in good general health, middle-aged and if the tumor is retrofoveal with just a few functional signs: when, why and who should be treated?

Wuestemeyer H, Sauerwein W, Meller D, Chauvel P, Schueler A, Steuhl KP, Bornfeld N, Anastassiou G. · Department of Ophthalmology, University of Essen, Hufelandstr. 52, 45122, Essen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #16133022 No free full text.

Abstract: BACKGROUND: Diffuse and multifocal patterns of conjunctival melanoma may not be treatable with standard eye-sparing methods. The purpose of this study was to evaluate the usefulness of proton beam radiation therapy as an alternative to exenteration. METHODS: Twenty patients with extended conjunctival melanoma were treated by proton beam irradiation. Most cases were T3 tumours which were not accessible to brachytherapy due to their extension, localisation with fornical or caruncular involvement. Only 2 patients had a tumour limited to the bulbar conjunctiva. Both were recurrent tumours with multiple lesions. Sixteen cases were recurrences after various pre-treatments. The area of the conjunctiva which was suspected to have microscopic disease was treated by 31 Gy in 6 fractions. The "high risk" areas with a clinically detectable tumour (primary target volume) were treated by an additional boost using a smaller beam size and applying 2 fractions up to 45 Gy. An individually shaped compensator was brought into the beam to modify the range of the protons so that the eye was irradiated only at a depth of 2 mm. RESULTS: The mean follow-up time was 38.1+/-26.6 months (median 34 months). Recurrent disease occurred in 6 cases (30%); 2 of them outside the irradiated volume, 3 within the target volume treated by 31 Gy, and just one in the primary target volume treated by 45 Gy. An exenteration followed only in two patients (10%). 6 patients (30%) suffered from metastatic disease and 4 (20%) of them have died by now. During follow up we found no statistically significant association between the occurrence of local recurrence after proton radiotherapy and the development of metastases. Best corrected visual acuity remained stable in 12 cases (60%); in 14 patients the best corrected visual acuity was 0.25 or better. A sicca-syndrome developed in 19/20 patients. However, only 10/20 patients used artificial tears more than 5x/d. A focal cataract developed in 7 patients (35%). There was eyelash loss in the area of irradiated eyelids. In 4 cases a limbal stem cell deficiency occurred with the consequence of corneal vascularisation. CONCLUSIONS: Proton radiotherapy may serve as an alternative to exenteration in case of T3 and diffuse T1 or T2 conjunctival melanomas.

Chauvel P, Iborra N, Hérault J, Courdi A, Gérard JP. · Centre Antoine-Lacassagne, Biomedical Cyclotron, 227 Avenue de la Lanterne 06200 Nice, France. · Radiother Oncol. · Pubmed #15971302 No free full text.

Abstract: The organization of a networking for patient recruitment is a main concern for a new facility using charged particles. The experience of choroidal melanoma in Nice demonstrates the possibility to create "de novo" a protontherapy center treating a sufficient number of patients. The influence of the opening of new facilities is analyzed.

Hérault J, Iborra N, Serrano B, Chauvel P. · Centre Antoine Lacassagne, Cyclotron Biomedical, 227 Avenue de la Lanterne, 06200 Nice, France. · Med Phys. · Pubmed #15895573 No free full text.

Abstract: Patients with ocular melanoma have been treated since June 1991 at the medical cyclotron of the Centre Antoine Lacassagne (CAL). Positions and sizes of the ocular nozzle elements were initially defined based on experimental work, taking as a pattern functional existing facilities. Nowadays Monte Carlo (MC) calculation offers a tool to refine this geometry by adjusting size and place of beam modeling devices. Moreover, the MC tool is a useful way to calculate the dose and to evaluate the impact of secondary particles in the field of radiotherapy or radiation protection. Both LINAC and cyclotron producing x rays, electrons, protons, and neutrons are available in CAL, which suggests choosing MCNPX for its particle versatility. As a first step, the existing installation was input in MCNPX to check its aptitude to reproduce experimentally measured depth-dose profile, lateral profile, output-factor (OF), and absolute dose. The geometry was defined precisely and described from the last achromatic bending magnet of our proton beam line to the position of treated eyes. Relative comparisons of percentage depth-dose and lateral profiles, performed between measured data and simulations, show an agreement of the order of 2% in dose and 0.1 mm in range accuracy. These comparisons, carried out with and without beam-modifying device, yield results compatible to the required precision in ocular melanoma treatments, as long as adequate choices are made on MCNPX input decks for physics card. Absolute dose and OF issued from calculations and measurements were also compared. Results obtained for these two kinds of data, carried out in the simplified situation of an unmodulated beam, indicate that MC calculation could effectively complement measurements. These encouraging results are a large source of motivation to promote further studies, first in a new design of the ocular nozzle, and second in the analysis of the influence of beam-modifying devices attached to the final patient collimator, such as wedge or compensators, on dose values.

Kodjikian L, Roy P, Rouberol F, Garweg JG, Chauvel P, Manon L, Jean-Louis B, Little RE, Sasco AJ, Grange JD. · Department of Ophtalmology, Croix-Rousse Hospital, and Laboratory of Biomaterials and Matrix Remodelling, Claude Bernard University, Lyon, France. · Am J Ophthalmol. · Pubmed #15183783 No free full text.

Abstract: PURPOSE: To evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DESIGN: Interventional case series. METHODS: In this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: The 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P =.045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. CONCLUSION: Our results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

Gambrelle J, Kodjikian L, Rouberol F, Donate D, Duquesne N, Jean-Louis B, Chauvel P, Gérard JP, Romestaing P, Grange JD. · Service d'Ophtalmologie, Hôpital de la Croix-Rousse, Lyon. · J Fr Ophtalmol. · Pubmed #14968076 links to  free full text

Abstract: INTRODUCTION: Our main goals were to study the survival of patients with uveal melanomas involving the ciliary body 5 and 10 years after treatment and to review prognosis. MATERIAL AND METHODS: This study investigated 106 tumors (27 ciliary body melanomas and 79 choroidal-ciliary melanomas) of patients treated between June 1983 and April 1998. Seventy-two patients were treated with 106-ruthenium applicators and 34 were treated with proton therapy. Some large tumors or recurrences required a second treatment. The mean follow-up period was 91 months. RESULTS: The mean tumor sizes before treatment were 6,6mm for melanoma thickness and 10.3mm for mean largest basal melanoma diameters (LTD). Of the patients studied, 71% were still alive at 5 years, 35% had metastasis and 27.7% developed recurrences. Multivariate analysis showed that the risk factors for melanoma-related death were LTD greater than 13mm, presence of exudative retinal detachment, macroscopic iris root involvement at the time of diagnosis, and choroidal-ciliary location. DISCUSSION AND CONCLUSION: With 71% of patients still alive at 5 years, this review shows that melanomas involving the ciliary body do not seem less severe than more posterior uveal tumors. Because of size differences between ciliary body melanomas and choroidal-ciliary melanomas, we cannot come to the conclusion that choroidal-ciliary melanomas have a poorer prognosis than ciliary body melanomas. Largest tumor diameter over 13mm, presence of exudative retinal detachment, and macroscopic iris root involvement at the time of diagnosis are important risk factors for melanoma-related death, as shown by the multivariate analysis.

Grange JD, Duquesne N, Roubeyrol F, Branisteanu D, Sandon K, Fleury J, Gerard JP, Chauvel P, Pinzaru G, Jean-Louis B, Bievelez B. · Clinique Ophtalmologique Universitaire, Hôpital de la Croix-Rousse, 93, grande rue, 69004 Lyon. · J Fr Ophtalmol. · Pubmed #10617843 links to  free full text

Abstract: We describe two comparative series of patients treated with double-dose betaraysbrachytherapy (106 Ruthenium) between 1983 and 1994, and double-dose proton beam therapy between 1991 and 1996. The indications for double-dose irradiation with the same radio-element corresponded to "macroscopically abnormal" situations: immediate and prolonged radioresistance, recurrence or secondary radioresistance. Thirteen cases are called series 1 (Ruthenium) and 6 cases are called series 2 (protons). The series 1 allows a more reliable study as far as follow-up is higher (5.8 to 7.5 years) than in series 2 where the follow-up is shorter (13.6 to 29 months). Although double-dose irradiation was macroscopically efficient in 11 out of 13 cases in series 1, and in 3 out of 6 cases in series 2 (stabilization or decrease of tumour height measured before the second therapeutic session), 2 patients are deceased and 1 has a metastatic disease in the group "recurrence" of Ruthenium serie. Another one has also a metastatic disease in the group "recurrence" of protons series. Nevertheless double-dose radiotherapy allows a complementary decrease or stabilization of tumour height after a first session. It also decreases the indications for enucleation if there is no severe anatomic complications, when a tumour does not regress or recurs after a first session of radiations.

Chiquet C, Grange JD, Ayzac L, Chauvel P, Patricot LM, Devouassoux-Shisheboran M. · Department of Ophthalmology, Croix-Rousse Hospital, University of Lyons, France. · Br J Ophthalmol. · Pubmed #10611107 links to  free full text

Abstract: AIMS: To assess the cellular proliferation using the monoclonal antibody Ki-67, in paraffin embedded uveal melanomas irradiated by proton beam, as well as in non-irradiated uveal melanomas. METHODS: 30 enucleated eyes were included for histopathological study and Ki-67 immunostaining. Patients were enucleated between 1991 and 1996 for uveal melanoma, 14 after proton beam irradiation and 16 without treatment (control group). The mean follow up period was 2.5 years after diagnosis and 1 year after enucleation. RESULTS: A significant relation was found between Ki-67 score and mitotic index (r = 0.56, p = 0.001), histological largest tumour diameter (r = 0.38, p = 0. 03), fibrosis (r = -0.35, p = 0.05), absence of tumoral pigmentation (p = 0.05), and presence of vascular thrombosis (p = 0.03). The Ki-67 score was significantly higher in the non-irradiated group (p = 0.01) and in the group of patients whose cause of enucleation was tumoral evolution (p = 0.005) compared with the group of patients enucleated after neovascular glaucoma. The Ki-67 score was very high in a case of orbital recurrence of uveal melanoma and metastatic death. 70% of metastasised tumours showed a Ki-67 score higher than the median value. CONCLUSION: Ki-67 labelling is a reliable method of estimating the proliferative activity in uveal melanomas after proton beam irradiation. The Ki-67 score is significantly correlated with prognostic variables (mitotic index and histological largest tumour diameter), and with radiation effects after proton beam irradiation.

Courdi A, Caujolle JP, Grange JD, Diallo-Rosier L, Sahel J, Bacin F, Zur C, Gastaud P, Iborra-Brassart N, Hérault J, Chauvel P. · Centre A. Lacassagne, Nice, France. · Int J Radiat Oncol Biol Phys. · Pubmed #10477000 No free full text.

Abstract: PURPOSE: To present the first results of uveal melanomas treated with the Medicyc Cyclotron 65 MeV proton beam facility in Nice, analyzing the factors that affect the cause-specific survival (CSS), metastatic rate, and reporting the visual outcome. METHODS AND MATERIALS: This study concerns 538 patients referred by French institutions between June 1991 and December 1996. The eye and tumor parameters were measured using ultrasonography and angiography. Since 1994, CT scans were performed in most patients to help determine the axial length and the shape of the ocular globe. Tantalum clips were inserted around the tumor by the referring ophthalmologist. There were 349 posterior pole tumors (64.9%), 130 equatorial tumors (24.1%), and 59 ciliary body tumors (11%). Two hundred four patients (37.9%) had T1 or T2 tumors, and 334 patients (62.1%) had T3 or T4 tumors. The median tumor diameter was 14.6 mm, and the median tumor height was 5.1 mm. All patients received 52 Gy (57.20 Gy Co-equivalent dose) on 4 consecutive days. The data were analyzed by December 1997. RESULTS: The CSS was 77.4% at 78 months, the overall survival was 73.8% and the local control was 89.0%. The CSS was not influenced by the patient age or the site of the tumor. It was 81.5% for T1 and T2 tumors, versus 75% for T3 and T4 tumors (P = 0.035). It was found that the tumor diameter, rather than the height, was the most important parameter affecting outcome. The metastatic rate was 8%. It depended on the T stage, tumor diameter and thickness, but not the tumor site. Thirty-eight enucleations were performed, most of them due to tumor progression and/or glaucoma. One-third of the patients in whom visual acuity was adequately scored before and after treatment had a stable, if not improved vision, and half the patients retained useful vision after treatment. CONCLUSION: The outcome of patients suffering from uveal melanoma and treated with high-energy protons compares favorably with other techniques of treatment. The tumor dimensions affected CSS and metastatic rate. Even though two-thirds of patients had posterior pole tumors, half of them retained useful vision.