Familial retinoblastoma: fundus screening schedule impact and guideline proposal. A retrospective study.

AIMS: To assess if systematic fundus screening according to an 'intensive' schedule alters ocular outcome and to propose fundus screening schedule guidelines for children related to a retinoblastoma patient. METHODS: For children with a positive family history of retinoblastoma, we perform fundus exams shortly after birth under general anaesthesia and then at regular intervals according to schedules based on the risk. Familial retinoblastoma cases seen at our institution from January 1995 to December 2004 were retrospectively classified as 'screened' or 'non-screened' (NS) and, among the 'screened' patients, as 'intensively screened' (IS) if screening matched our recommendations or 'non-intensively screened' (S). Groups were compared by Fisher exact test for categorical variables and Kruskal-Wallis test for continuous variables. RESULTS: Among the 547 retinoblastoma patients managed at our institution during this period, 59 were familial cases. In all, 20 were in the NS group, 23 in the S group, and 16 in the IS group. The number of children enucleated was, respectively, 13, 2, and 0 (P<10(-4)); external beam radiation (EBRT) was required for, respectively, 6, 0, and 2 children (P<0.009). Chemotherapy burden and visual acuity were not significantly different between groups. CONCLUSION: An 'intensive' fundus screening schedule decreased the need for enucleation and EBRT. Therefore, despite the heavy burden of the screening schedule, we recommend physicians and health-care professionals to better inform and refer children with a family history of retinoblastoma for genetic counselling and proper fundus screening in specialized centres.

From childhood to adulthood: long-term outcome of medulloblastoma patients. The Institut Curie experience (1980-2000).

Medulloblastoma patients treated at the Institute Curie between 1980 and 2000 were reviewed. Only patients whose primary treatment included craniospinal radiation were considered. Surviving patients were identified and evaluated by means of self-report questionnaires using the Health Utility Index (HUI). Psychosocial functioning, employment, and other health-related indicators were recorded. Seventy-three patients were treated during the study period. At a median follow-up from diagnosis of 14.4 years, 49 patients were alive and 45 surviving patients could be contacted. Late sequelae were frequent, particularly neurological deficits (71%) and endocrine complications (52%). Impairments of psychosocial functioning, including employment, driving capacity, independent living, and marital status, were identified in most patients. Most long-term medulloblastoma survivors suffer persistent deficits in several domains, with a significant impact on their psychosocial functioning. These findings reinforce the importance of early intervention programs for all survivors in order to reduce the psychosocial impacts of their disease.

Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP study.

AIM: Improvement of EFS of children older than 3 years with high risk medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment.

[Functional results of retinoblastoma treatment with local treatment used in isolation or associated with chemotherapy]. / Résultats fonctionnels du traitement du rétinoblastome par les traitements locaux en utilisation isolée ou associés à une chimiothérapie.

INTRODUCTION: Because of long-term complications of external beam radiation in retinoblastoma, a new therapeutic modality using chemotherapy and local treatments is used whenever possible. We conducted a retrospective study to evaluate visual results. PATIENTS AND METHOD: We studied visual acuity and ocular side effects in children presenting uni- or bilateral retinoblastoma in whom we were able to achieve conservative management without external beam treatment. The treatments that were used included chemotherapy, chemothermotherapy, diode laser, iodine 125 plaque brachytherapy, and cryotherapy. The initial characteristics (diameter, subretinal or vitreous seeding, and location) of each tumor, the treatments used, their results, and the visual function after age 4 years were recorded. RESULTS: We treated 429 children for retinoblastoma at the Curie Institute between October 1994 and December 2002. Two hundred twenty-seven eyes had conservative treatment without external beam. We were able to study the visual function in 102 eyes at a median age of 67 months. The median follow-up after the end of the treatment was 5 years. The mean visual acuity was 20/37 and 60% of the children had visual acuity of more than 20/40. Macular alteration was observed in 34 eyes. Statistical analysis showed that a larger tumor diameter of the retinal surface (p<0.0003) and location close to the macula (p<0.0001) were the most significant risk factors for vision loss. CONCLUSION: The visual results of the treatment of retinoblastoma by chemotherapy and local treatments is good when the tumors are not located close to the macula. Larger tumors also have a worse prognosis for vision.

Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study.

OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.

[Diode laser thermotherapy and chemothermotherapy in the treatment of retinoblastoma]. / Thermothérapie et thermochimiothérapie au laser diode dans le traitement du rétinoblastome.

INTRODUCTION: The use of transpupillary thermotherapy alone or associated with systemic chemotherapy is a therapeutic modality of ocular retinoblastoma that allows ocular preservation without external beam irradiation of the eye. We present our experience with thermotherapy in the treatment of selected cases of retinoblastoma. MATERIAL AND METHODS: This paper reports a retrospective case series of patients treated for retinoblastoma by thermotherapy or chemothermotherapy (carboplatin IV followed by thermotherapy) in a single institution from October 1994 to December 2000. Data collected include general characteristics of the treated children, tumor characteristics, and the results of the treatments on local tumor control. Transpupillar thermotherapy was delivered with a diode laser through an operating microscope. Each tumor was treated separately and laser intensity, spot size, and duration were adapted to the size of the tumor and the clinical response. Chemothermotherapy consisted in thermotherapy delivered shortly after an intravenous injection of carboplatin (560 mg/m(2)) at day 1, followed by thermotherapy alone at day 8 if the lesion was 6mm or more in diameter. This cycle was administered every 28 days. The choice between thermotherapy and chemothermotherapy depended on the initial size of the lesions. Thermotherapy was used when the lesion measured 3mm or less. Lesions measuring more than 15 mm, or associated with substantial vitreous seeding, retinal detachment, or optic nerve head involvement are not suitable for these techniques. RESULTS: During the study period, 239 children were treated in our institution and 109 of them (147 eyes, 372 tumors) could be treated conservatively without external beam radiation. The median tumor diameter at the moment of thermotherapy or chemothermotherapy was 2mm (range, 0.2-15.0mm). One hundred and ninety-four tumors were treated by chemothermotherapy and 18 by thermotherapy alone. In 75% of the cases, the treatment was administered after two courses of chemotherapy (etoposide and carboplatin). After a mean follow-up of 55 months (range, 16-89 months), tumor control was obtained in 87.1% of lesions after chemothermotherapy and 77.8% after thermotherapy. Salvage enucleation was necessary for seven lesions (seven eyes) but none in the cases where thermotherapy was used alone. No severe systemic side effects were noted. DISCUSSION: Diode laser delivers hyperthermia on the tumor bed and its use alone or in association with systemic administration of carboplatin makes it possible to preserve the eye without external beam irradiation, with few side effects and less cumulative doses of chemotherapy. CONCLUSION: Thermotherapy and chemothermotherapy provide excellent local tumor control and eye preservation in selected cases of retinoblastoma.

Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Société Française d'Oncologie Pédiatrique.

Childhood malignant brain stem tumours have a very poor prognosis with a median survival of 9 months despite radiotherapy. No chemotherapy has improved survival. However, carboplatin has been reported to have activity in glial tumours as well as antitumour synergy with radiation. Our aims were to test the response rate of these tumours to carboplatin alone and to evaluate the efficacy on survival of carboplatin alone followed by concurrent carboplatin and radiotherapy. Patients younger than 16 years with typical clinical and radiological presentation of infiltrating brain stem tumour, as well as histologically-documented cases in the atypical forms, were eligible. Two courses of carboplatin (1050 mg/m2 over 3 days) were administered initially. This treatment was followed by a chemoradiotherapy phase including five weekly carboplatin courses (200 mg/m2) and conventional radiotherapy. 38 eligible patients were included. No tumour response was observed after the initial phase. This schedule of first-line carboplatin followed by concurrent carboplatin and radiotherapy did not improve survival.

[Current treatment of retinoblastoma. 153 children treated between 1995 and 1998]. / Le traitement actuel du rétinoblastome. 153 enfants traités entre 1995 et 1998.

PURPOSE: Treatment of retinoblastoma has changed significantly over the past few years. There are fewer indications for external beam radiation and a new treatment modality, chemotherapy, has appeared. MATERIAL: and methods: We reviewed a series of 153 children treated for retinoblastoma between 1995 and 1998. There were 67 boys and 86 girls: 76 unilateral and 77 bilateral retinoblastomas. Indications for treatments and outcome were reviewed for 230 eyes and for each tumor. Age at diagnosis varied from 0 to 94 months with a median age of 12 months. A family history of retinoblastoma was found in 24 cases. Three children were seen for treatment of recurrence. RESULTS: Among the 76 cases of unilateral retinoblastoma, 56 were enucleated and 20 were treated conservatively (5 with external beam radiation). Among the 154 eyes with bilateral retinoblastoma, 48 were enucleated and 106 were treated conservatively (49 by external beam radiation). Local treatments included chemothermotherapy, laser alone, cryotherapy, and (125)I plaques. Conservative management other than external beam radiation was used for 81 eyes and was successful in 72 (89%). CONCLUSION: We discuss the indications and results of primary chemotherapy and local treatments. External beam radiation is still often indicated in bilaterally advanced cases. In other forms of retinoblastoma, chemothermotherapy is a very reliable and useful treatment.