C. Plancher

Surgical management of liver metastases from uveal melanoma: 16 years' experience at the Institut Curie

BACKGROUND Uveal melanoma is characterised by a high prevalence of liver metastases and a poor prognosis. AIM To review the evolving surgical management of this challenging condition at a single institution over a 16-year period. PATIENTS AND METHODS Between January 1991 and June 2007, among 3873 patients with uveal melanoma, 798 patients had liver metastases. We undertook a detailed retrospective review of their clinical records and surgical procedures. The data was evaluated with both uni- and multivariate statistical analysis for predictive survival indicators. RESULTS 255 patients underwent surgical resection. The median interval between ocular tumour diagnosis and liver surgery was 68 months (range 19-81). Liver surgery was either microscopically complete (R0; n = 76), microscopically incomplete (R1; n = 22) or macroscopically incomplete (R2; n = 157). The median overall postoperative survival was 14 months, but increased to 27 months when R0 resection was possible. With multivariate analysis, four variables were found to independently correlate with prolonged survival: an interval from primary tumour diagnosis to liver metastases >24 months, comprehensiveness of surgical resection (R0), number of metastases resected (< or = 4) and absence of miliary disease. CONCLUSIONS Surgical resection, when possible, is able to almost double the survival and appears at present the optimal way of improving the prognosis in metastatic uveal melanoma. Advances in medical treatments will be required to further improve survival.

Prophylactic salpingo-oophorectomy in a series of 89 women carrying a BRCA1 or a BRCA2 mutation†

Prophylactic salpingo‐oophorectomy (SO), which is recommended in BRCA1/2 mutation carriers, still needs to be reappraised.

Preoperative staging of liver metastases from uveal melanoma by magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET)

BACKGROUND Microscopically complete (R0) resection of metastases from uveal melanoma prolongs median overall survival compared to incomplete surgery. The aim of this study was to compare the sensitivity of dynamic-enhanced magnetic resonance imaging (MRI) with fluorodeoxyglucose-positron emission tomography (FDG-PET) in the preoperative diagnosis of liver metastases from uveal melanoma. PATIENTS AND METHODS Fifteen consecutive patients (mean age: 56 years) underwent FDG-PET and liver MRI. Extrahepatic metastatic disease was excluded by whole body computed tomography and bone scintigraphy. MRI and FDG-PET were performed with a mean of 19 days (range: 1-30) before surgery. Imaging findings were compared with surgical (including intraoperative ultrasonography) and histological findings on a lesion by lesion analysis. RESULTS R0 resection was performed in 12 patients. A total of 28 lesions were resected with 27 histologically proven metastases. Nine lesions were smaller than 5mm, 7 measured 5-10mm and 11 were larger than 10mm. Sensitivity and positive predictive value were 67% and 95% for MRI compared to 41% and 100% for FDG-PET. The difference between the two modalities was statistically significant (p=0.01; McNemar test). In remaining 3 patients, diffuse miliary disease (>10 capsular lesions) was discovered intraoperatively, and was suspected on preoperative MRI in 2 cases. Only one extrahepatic lesion identified by FDG-PET was falsely positive. CONCLUSIONS In this preliminary study, MRI was superior to FDG-PET for staging of liver metastases from uveal melanoma. Although miliary disease was suggested by MRI in some cases, preoperative confirmation remains imperfect.

Combined Proton Beam Radiotherapy and Transpupillary Thermotherapy for Large Uveal Melanomas: A Randomized Study of 151 Patients

Introduction: Exudation from the tumour scar and glaucoma can be major problems after proton beam irradiation of uveal melanoma and can sometimes lead to secondary enucleation. We conducted a randomized study to determine whether systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy could have a beneficial effect. Patients and Method:Between February 1999 and April 2003, all the patients treated by proton beam radiotherapy for uveal melanomas ≧7 mm thick or ≧15 mm in diameter were included in this study after giving their informed consent. One half of the patients received proton beam radiotherapy alone (60 Gy in 4 fractions) and the other half received the same dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the information concerning the initial tumour parameters, treatments and follow-up was recorded and a statistical analysis was performed. Results: We randomized 151 patients. The median follow-up was 38 months. The 2 groups of patients were similar in terms of age, gender and tumour characteristics. The patients treated with TTT showed a greater reduction of tumour thickness (p = 0.06), less retinal detachment at the latest follow-up (p = 0.14) and a lower secondary enucleation rate (p = 0.02). Discussion: The present study is the first randomized analysis to demonstrate a significant decrease in the secondary enucleation rate in patients treated with TTT after proton beam radiotherapy. Further studies should be performed to determine whether TTT could be beneficial to smaller tumours and to define its optimal dose.

Facteurs pronostiques du mélanome malin de l’uvée: Étude rétrospective sur 2 241 patients et apport recent de la recherche de la monosomie 3

Introduction Nous avons realise une etude retrospective des facteurs cliniques influencant le pronostic local et general chez des patients atteints de melanome choroidien. Nous avons effectue une analyse preliminaire de la valeur pronostique de la monosomie 3. Patients et methode Les patients adresses a l’Institut Curie pour un melanome de l’uvee ont un bilan initial complet, un traitement conservateur radiotherapique ou une enucleation et un suivi a long terme local et general. Depuis 5 ans, les tumeurs traitees par enucleation ont une etude du statut du chromosome 3 par FISH. Les donnees concernant le bilan initial, le traitement et le suivi sont enregistrees systematiquement de maniere prospective. Nous avons realise une etude retrospective avec analyse multivariee des facteurs cliniques influencant la recidive locale, la conservation oculaire, les metastases et la survie, et en particulier des effets de la monosomie 3. Resultats Deux mille deux cent quarante et un patients ont ete traites avec un recul median de 72 mois. 92,8 % des patients ont eu un traitement conservateur par curietherapie a l’iode 125 ou par protontherapie, et 7,2 % des patients ont eu une enucleation (n = 160). Parmi les patients enuclees, 120 ont eu une etude genetique de leur tumeur par FISH. La survie globale a ete de 76,3 %, et le taux de metastases, de 19,5 %. Les facteurs cliniques influencant la survie en analyse multivariee sont la taille et la localisation de la tumeur, l’âge, le sexe et le traitement initial. Les facteurs influencant le risque metastatique sont identiques, avec en plus, l’existence d’un decollement de retine initial et la recidive locale. La monosomie 3 influence de facon significative le risque metastatique. Discussion Cette etude retrouve les facteurs de risque habituels, mais differe legerement des precedentes series car la localisation a cheval sur l’equateur apparait plus pejorative que la localisation au niveau du corps ciliaire pour les metastases et la survie. Par ailleurs, le decollement de retine initial apparait comme un facteur de risque significatif pour la recidive locale et les metastases. Actuellement, la recherche de la monosomie 3 n’est possible que sur des pieces d’enucleation ; mais, il est probable qu’elle puisse etre applicable aux biopsies a l’aiguille. Cette recherche pourrait etre proposee en meme temps que le traitement conservateur. Conclusion Cette etude confirme les resultats precedents sur les facteurs pronostiques du melanome uveal et la valeur pronostique de la monosomie 3. L’identification de plus en plus precise d’un groupe de patients a haut risque devrait permettre prochainement de proposer des therapeutiques adjuvantes a ces patients et d’adapter le suivi a long terme.INTRODUCTION We conducted a retrospective study on the clinical factors influencing the local and general prognosis of patients treated for uveal melanoma with a preliminary analysis of the prognostic value of monosomy 3. PATIENTS and method: The patients sent to Curie Institute for uveal melanoma have a complete initial clinical evaluation, conservative management by radiotherapy or enucleation, and local and general long-term follow-up. Over the last 5 years, the status of chromosome 3 has been assessed by FISH in the tumors of enucleated patients. Findings concerning the initial workup, treatment, and follow-up are recorded prospectively. We conducted a retrospective study with multivariate analysis of the clinical factors influencing local recurrence, ocular conservation metastasis, and survival and studied the effect of monosomy 3. RESULTS A total of 2241 patients were registered with a median follow-up of 72 months. Of these patients, 92.8% had conservative management with iodine 125 brachytherapy or proton beam therapy and 7.2% of the patients had enucleation (n=160). Tumors from 120 patients were studied for the status of chromosome 3 by FISH. The overall survival rate was 76.3% and the metastatic rate was 19.5%. The clinical factors influencing survival were the size and location of the tumor, age of the patient, gender, and initial treatment. The factors influencing the metastatic risk were the same plus retinal detachment and local recurrence. Monosomy 3 was a significant risk factor for metastatic disease. DISCUSSION This study found the usual risk factors with the difference that location on the equator seems to be of worse prognosis than ciliary body involvement for survival and metastasis. In addition, the initial retinal detachment appears to be a risk factor for local recurrence and metastasis. At present, the evaluation of chromosome 3 is available for enucleated tumors but it could probably be done on needle biopsy performed during conservative management as well. CONCLUSION This study confirms previous results on the prognostic factors of uveal melanoma and on the value of monosomy 3. The increasingly precise identification of a group of high-risk patients should allow us to propose adjuvant therapy and to adapt follow-up.

Proton beam therapy for iris melanomas

AimsTo describe the results in terms of local control, eye preservation and systemic evolution of iris melanomas treated by proton beam irradiation.MethodsRetrospective review of the charts of patients with iris melanoma treated by proton beam therapy between April 1998 and September 2002. Ciliary body melanomas with iris involvement or tumours with extrascleral invasion were excluded. Treatment consisted of 60 Gy of proton beam irradiation delivered in four fractions to the tumour volume.ResultsA total of 21 patients were treated, median follow-up of 33 months (8–72 months). 15 patients presented a lesion with documented growth. The median clinical diameter was 5 mm (2–8 mm), the median ultrasound diameter 4.8 mm (2–7.7 mm) The patients were 6% T1, 57.1% T2, and 14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of patients. At the end of follow-up, all patients were alive with no proven metastatic disease except one patient with suspicious liver lesions. None of the patients showed tumour progression or ocular relapse. The tumour response at 2 years was a flat lesion for 6.3% of cases, partial regression in 75% and stable in 18.8%. None of the patients required secondary enucleation. The main complication was cataract (45% within 24 months of treatment). Raised intraocular pressure was observed in 15% of patients but no neovascular glaucoma.ConclusionsProton beam therapy shows potential utility for selected cases of localised iris melanomas allowing excellent local tumour control and eye preservation. Further follow-up on larger series is needed to confirm these results.

Long-term results of low-dose proton beam therapy for circumscribed choroidal hemangiomas.

Purpose: To evaluate the long-term efficacy and outcome of low-dose proton beam irradiation in the treatment of symptomatic circumscribed choroidal hemangioma. Patients and Methods: Retrospective review of 71 patients with symptomatic circumscribed choroidal hemangiomas treated by proton beam irradiation between September 1994 and October 2002 using a total dose of 20 Cobalt Gray Equivalent. Results: The median follow-up was 52 months (8–133 months). Retinal reattachment was obtained in all cases. Tumor thickness decreased in all cases and a completely flat scar was obtained in 65 patients (91.5%). Visual acuity was improved by two lines or more in 37 of the 71 patients (52%), and in 30 of the 40 patients (75%) treated within 6 months after onset of the first symptoms. The main radiation complications detected during follow-up were cataract (28%) and radiation-induced maculopathy (8%). None of the 71 patients developed eyelid sequelae or neovascular glaucoma. Conclusion: Proton beam irradiation with a total dose of 20 Cobalt Gray Equivalent appears to be a valid treatment for circumscribed choroidal hemangiomas, inducing definitive retinal reattachment and decreasing tumor thickness. However, delayed radiation-induced maculopathy may occur. A successful functional outcome is dependent on a short interval between onset of the first symptoms and initiation of therapy.

Outcome of residual mediastinal masses of thoracic lymphomas in children : impact on management and radiological follow-up strategy

Background. Following treatment with chemotherapy and radiotherapy, patients with thoracic lymphomas may demonstrate benign residual mediastinal masses, composed of inflammatory, fibrous or necrotic tissue. Because of the potential risk of viable tumour cells within the mass, histological verification of the nature of these masses may be requested. Objective. To study the outcome of thoracic lymphomas in children in order to optimise the radiological follow-up strategy of residual mediastinal masses (RMM). Materials and methods. A retrospective study of 39 children [24 with Hodgkins disease (HD), 10 with non-Hodgkins lymphoma (NHL), and 5 with anaplastic lymphoma (AL)]. The results of chest X-rays (CXR) and thoracic CT performed at the time of re-assessment were compared with the histology of the residual masses (n = 11) or the clinical course (n = 28). Results. At the time of re-evaluation, 16/39 patients had residual mediastinal enlargement (RME) on CXR, and 18/39 patients had RMM on CT. Good concordance was observed between the two imaging modalities (K = 0.69). Two children with a RMM died from extra-mediastinal progression. Two children with NHL had active residual mediastinal lesions but neither had RMM. Sixteen cases of RMM were observed in the remaining 35 children and 9 of these masses were histologically verified as benign. A favourable course was observed in these 35 cases. Conclusions. RMM are frequent and generally benign. They are well shown on CXR and have a non-specific appearance on CT. Except when required by a treatment protocol, they could be submitted to further radiological follow-up before contemplating surgical verification.

Uveal metastasis revealing lung cancer

BACKGROUND Uveal metastases (UM) are the most common intraocular malignancies and can be the first manifestation of a disseminated disease. The purpose of this study is to determine the frequency with which uveal metastasis results in a diagnosis of lung cancer, to describe the clinical characteristics of patients with lung cancer metastatic to the uvea, as well as diagnostic difficulties that may be encountered. PATIENTS AND METHODS We carried out a single-center retrospective study of the medical records of all patients who presented with a UM between 1999 and 2010 at the institut Curie in Paris. From these patients, we retrospectively studied UM secondary to lung cancer. A work-up including thoracic-abdominal-pelvic CT was performed for each patient in whom the primary source of choroidal metastasis was unknown. RESULTS Of 109 patients presenting with UM, 43 were diagnosed with primary lung cancer (39.4%). Of those 43 patients, the UM was observed prior to the lung cancer in 31 patients (72.1%). Demographic data included 61% male and 39% female, mean age 59.1 years (range: 31-78), and mean life expectancy after diagnosis of UM was 7.5 months (range: 0.7-29). Other metastatic sites were associated with UM in 90.7% of the patients. In all, 90.7% of the patients presented with blurred vision, and 25.6% with pain or inflammation. UM were located within the choroid for 39 patients (90.7%), the iris for three patients (7.3%) and the vitreous for one patient. Seventy percent of patients had a solitary lesion, 76.7% had unilateral involvement, and 23.3% of cases were bilateral. Mean thickness on B-scan ultrasonography was 3.61 mm (range: 1-8.5 mm). In all, 81.4% of UM were unpigmented, while 18.6% showed pigment mottling. In all, 20.9% of patients were referred with the diagnosis of choroidal melanoma from their regular ophthalmologist, and three of the 43 patients (6.9%) were initially misdiagnosed and treated for melanoma at Curie. Chest X-ray was unremarkable in 18.9% of patients. CONCLUSION UM is often the first manifestation of disseminated disease and requires a search for the primary tumor, in particular lung cancer. Standard chest X-ray cannot rule out the diagnosis. Metastases may be solitary with heterogenous pigmentation, and the differential diagnosis from uveal melanoma may be difficult, requiring the expertise of a referral center.

Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: A ten-year follow up of 257 patients treated at a single institution

OBJECTIVE To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. METHODS 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. RESULTS 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). CONCLUSIONS Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.