Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004.

BACKGROUND: Retinoblastoma is an eye tumour of childhood that occurs in heritable and non-heritable forms. In the heritable form, there is a predisposition to the development of non-ocular subsequent primary tumours (SPTs). METHODS: This study included 1927 retinoblastoma patients diagnosed in Britain from 1951 to 2004. Ascertainment was through the (UK) National Registry of Childhood Tumours; cases were followed-up for the occurrence of SPTs. Standardised incidence ratios (SIRs) were calculated. RESULTS: We identified 169 SPTs in 152 patients. The SIR analysis included 145 SPTs with cancer registrations from the years 1971 to 2009. These tumours occurred in 132 patients: 112 of the 781 heritable and 20 of the 1075 (presumed) non-heritable cases under surveillance at the start of this period developed at least one registered SPT. The SIRs for all tumours combined were 13.7 (95% confidence interval 11.3-16.5) in heritable cases and 1.5 (0.9-2.3) in non-heritable cases. The main types of SPT in the heritable cases were leiomyosarcoma, (31 cases; SIR 1018.7 (692.2-1446.0)), osteosarcoma (26 cases; SIR 444.6 (290.4-651.4)), and skin melanoma (12 cases; SIR 18.6 (9.6-32.4)). CONCLUSION: The risk of SPTs in heritable retinoblastoma is extremely high. This has important implications for the clinical follow-up and counselling of survivors and their families.

Heritable retinoblastoma and accelerated aortic valve disease.

Heritable retinoblastoma is associated with a germline mutation in the tumour suppressor gene RBI. The Rb protein (pRb) arises from the RB1 gene, which was the first demonstrated cancer susceptibility gene in humans. Second primary malignancies are recognised complications of retinoblastoma. Furthermore, pRb is implicated in valve remodelling in calcific aortic valve disease. We report a family with hereditary retinoblastoma and associated secondary primary malignancies. There are two interesting aspects to this family. The first is the concept of 'cancer susceptibility genes'; the RBI gene being the first reported in humans. A further feature of note is that two family members also have bicuspid aortic valves. We discuss a potential association between the gene defect responsible for retinoblastoma (with its associated propensity for further malignancies) and accelerated deterioration of the bicuspid aortic valve in the proband carrying this gene defect.

Non-ocular tumours following retinoblastoma in Great Britain 1951 to 2004.

BACKGROUND: Retinoblastoma occurs in both a heritable and a non-heritable form. In the heritable form, there is a predisposition to the development of non-ocular tumours. OBJECTIVES: To identify the types of non-ocular tumour occurring in retinoblastoma survivors and to produce estimates of risk for these tumours. METHODS: We carried out a cohort study that included 1927 cases of retinoblastoma diagnosed in Great Britain between 1951 and 2004. Cases were ascertained through the National Registry of Childhood Tumours and followed up for the occurrence of non-ocular tumours using the routine notification system based on the National Health Service Central Registers in Britain. RESULTS: Of the 1927 cases, 809 were known to have the heritable form of the disease and 1118 assumed to have the non-heritable form. 102 of the heritable and 13 of those classified as non-heritable developed a non-ocular tumour. The cumulative risk of developing such a tumour 50 years after retinoblastoma diagnosis was 48.3% (95% confidence interval: 38.1 to 59.7%) in the heritable and 4.9% (1.9 to 12.4%) in the non-heritable cases. The main categories of non-ocular tumours observed in the heritable cases were soft-tissue sarcomas (36 of which 21 were leiomyosarcoma), osteosarcoma (32), carcinoma (13), brain and central nervous system tumours (10), melanoma (9), leukaemia (4) and others (4). There were a total of 108 non-ocular tumours in 102 cases. CONCLUSIONS: There is a high risk of non-ocular tumours occurring in survivors of heritable retinoblastoma. These results have important implications for the clinical follow-up and counselling of survivors.

Salvage external beam radiotherapy after failed primary chemotherapy for bilateral retinoblastoma: rate of eye and vision preservation.

BACKGROUND: Radiation is implicated in the induction of second malignancies in children with bilateral retinoblastoma. There is a need to determine whether this risk can be justified by good visual outcome when external beam radiotherapy (EBRT) is used as a salvage treatment. AIM: To study the effectiveness of EBRT as a salvage treatment after failed primary chemotherapy and focal treatment in bilateral retinoblastoma. METHODS: This is a retrospective observational case series. The outcome measures after EBRT are: rate of eye preservation, rate of tumour control, visual potential, visual acuity and radiation-induced side-effects. RESULTS: Thirty-six eyes (22 patients) were included. The median follow-up after EBRT was 40 months (19-165 months). Thirty-two eyes received lens-sparing radiotherapy, and four received whole-eye radiation. The rate of eye preservation was 83.3% (30/36 eyes). Twenty-four eyes (66.7%) were controlled by EBRT and required no further treatment. Of the 30 preserved eyes, 20 eyes (66.7%) had extramacular tumours without retinal detachment and therefore potential for central vision. The final visual acuity was recorded for 19 eyes. Ten eyes (52.6%) read 6/9-6/5, three eyes (15.8%) read 6/18-6/36, and six eyes (31.6%) read 6/60 or worse. Significant radiation- induced side effects were limited to cataracts and dry eyes with whole-eye radiation. There were no second cancers or deaths. CONCLUSION: Salvage EBRT is highly effective in preserving eyes with useful vision in bilateral retinoblastoma after failed chemotherapy and focal treatments. These results will help the parents and ophthalmologists of such patients to reach an informed decision when weighing up the benefits of EBRT against its potential oncogenic effect.

Retinoblastoma in Great Britain 1963-2002.

AIM: This paper describes the epidemiology and family history status of 1601 children with retinoblastoma in Great Britain diagnosed 1963-2002 and summarises the practical consequences for diagnosis and counselling of developments in molecular genetics. METHODS: Incidence rates were analysed according to year of diagnosis and tumour laterality. Cases were classified as heritable or non-heritable on the basis of laterality and family history of the disease. RESULTS: There were 998 unilateral cases, 581 bilateral and 22 of unknown laterality. Bilateral cases tended to be diagnosed at a younger age than unilateral. All bilateral cases are regarded as heritable, and 35% had a family history of the disease. 7% of the unilateral cases had a family history and are therefore heritable. Thus, at least (41%) of our cases are heritable. This is an underestimate, since these data on family history are incomplete. For unilateral cases aged below 1 year, the reported incidence rate increased significantly (p<0.0001) by about 2.5% per year; for the age group 1-4 years, the average increase was about 0.5% per year (not significant).

Retinoblastoma: treatment and survival in Great Britain 1963 to 2002.

AIM: This paper describes the treatment and survival of 1576 children with retinoblastoma in Great Britain diagnosed 1963-2002. METHODS: Survival rates were analysed according to period of diagnosis and tumour laterality. RESULTS: Survival was calculated by calendar period of diagnosis, 1963-1982 and 1983-2002. For both unilateral and bilateral retinoblastoma, survival improved between the two periods. The survival curves for the two periods were significantly different: for unilateral retinoblastoma p<0.00001, for bilateral p<0.01. For unilateral cases, the estimated 5-year survival rates rose from 85% for those diagnosed in 1963-1967 to 97% for those diagnosed in 1998-2002. The equivalent rates for bilateral cases were 88% and 100%. CONCLUSION: Survival rates were already high at the start of the study period. They increased with changes in treatment regimens.

Retinoblastoma incidence and survival in European children (1978-1997). Report from the Automated Childhood Cancer Information System project.

Based on 2283 cases of retinoblastoma diagnosed in children aged 0-14 years, incidence and survival in Europe during the period 1978-1997 are described. Data were provided to the Automated Childhood Cancer Information System (ACCIS) from 60 paediatric and general cancer registries. During 1988-1997, the cumulative incidence of retinoblastoma in the ACCIS regions was found to be between 44.2 and 67.9 per million births. The highest incidence was seen in the first year of life. The age-standardised (World standard) incidence rate for the age-range 0-14 years was 4.1 per million. Approximately one-third of cases had bilateral tumours. Overall incidence increased over the period 1978-1997 by 1% per year, as derived from a model adjusted for sex, age group and type of registry (general or paediatric). The 5-year survival rate improved from 89% to 95% during the period covered by the study. This improvement was seen in both unilateral and bilateral cases but was significant only for the unilateral tumours. Survival was lower in the East region, although smaller differences were also observed between the other four regions (British Isles, North, South and West). Availability and quality of registration data on retinoblastoma need to be improved for effective evaluation of incidence and survival.

Vitreous relapse following primary chemotherapy for retinoblastoma: is adjuvant diode laser a risk factor?

AIMS: To evaluate rates of vitreous relapse among retinoblastoma patients treated with primary chemotherapy and assess diode laser as a potential risk factor for relapse. METHODS: Retrospective review of all patients treated with primary chemotherapy at a large ocular oncology centre. Eyes that developed vitreous relapse were coded with regard to Reese-Ellsworth Group, laterality, time to relapse, type of relapse (vitreous base or non-vitreous base relapse), treatments used (including adjuvant diode laser), and ocular preservation. Individual tumour foci treated with laser hyperthermia were also coded for laser parameters including power settings, number of treatments, and concomitant administration of systemic chemotherapy (chemothermotherapy). RESULTS: 15 of 106 eyes (14.15%) developed vitreous relapse over a 6 year period. Mean time to relapse was 7.2 months after chemotherapy was completed. Five cases (33%) were of the vitreous base variety. Ocular salvage was attempted in 11 cases using a variety of methods; one patient was lost to follow up. Six of the remaining 10 eyes (60%) were salvaged. Eight of 38 eyes (21%) treated with systemic chemotherapy and laser hyperthermia developed vitreous relapse compared with seven of 68 eyes (10%) treated with primary chemotherapy alone (p<0.005). Laser settings, number of hyperthermia treatments, and the concomitant use of systemic chemotherapy (chemothermotherapy) were not associated with higher rates of vitreous relapse. CONCLUSION: Nearly one in seven eyes with retinoblastoma treated with primary chemotherapy may develop vitreous relapse. The administration of diode laser hyperthermia appears to increase this risk. Despite additional therapy a number of these eyes succumb to enucleation.

The impact of PET scanning on management of paediatric oncology patients.

PURPOSE: Limited information is available on the use of positron emission tomography (PET) in paediatric oncology. The aim of this study was to review the impact of PET on the management of paediatric patients scanned over a 10-year period. METHODS: One hundred and sixty-five consecutive oncology patients aged 11 months to 17 years were included. Two hundred and thirty-seven scans were performed. Diagnoses included lymphoma (60 patients), central nervous system (CNS) tumour (59), sarcoma (19), plexiform neurofibroma with suspected malignant change (13) and other tumours (14). A questionnaire was sent to the referring clinician to determine whether the PET scan had altered management and whether overall the PET scan was thought to be helpful. RESULTS: One hundred and eighty-nine (80%) questionnaires for 126 patients were returned (63 relating to lymphoma, 62 to CNS tumours, 30 to sarcoma, 16 to plexiform neurofibroma and 18 to other tumours). PET changed disease management in 46 (24%) cases and was helpful in 141 (75%) cases. PET findings were verified by histology, clinical follow-up or other investigations in 141 cases (75%). The returned questionnaires indicated that PET had led to a management change in 20 (32%) lymphoma cases, nine (15%) CNS tumours, four (13%) sarcomas, nine (56%) plexiform neurofibromas and four (22%) cases of other tumours. PET was thought to be helpful in 47 (75%) lymphoma cases, 48 (77%) CNS tumours, 24 (80%) sarcomas, 11 (69%) neurofibromas and 11 (61%) cases of other tumours. PET findings were verified in 44 (70%) lymphoma cases, 53 (85%) CNS tumours, 21 (70%) sarcomas, 12 (75%) neurofibromas and 11 (61%) other tumour cases. CONCLUSION: PET imaging of children with cancer is accurate and practical. PET alters management and is deemed helpful (with or without management change) in a significant number of patients, and the results are comparable with the figures published for the adult oncology population.

Pineal parenchymal tumours: II. On the aggressive behaviour of pineoblastoma in patients with an inherited mutation of the RB1 gene.

This report relates to a retrospective analysis of two non-randomised cohorts of patients with pineoblastoma, with some differences in presenting features and treatment characteristics. We have identified a large difference in survival depending on the possession or otherwise of the mutated RB (retinoblastoma) gene in the genome/karyotype. Eight children with familial retinoblastoma (non-metastatic at presentation) developed pineoblastoma and were treated by chemotherapy and radiotherapy. The survival of these patients was compared with the survival of nine non-metastatic sporadic cases of pineoblastoma similarly staged and treated. One out of eight children having the RB mutation in the genome survived compared with seven out of nine in the group with sporadic pineoblastoma (P = 0.002). It is suggested that the inheritance of the mutated retinoblastoma gene is not only causal in the generation of this tumour type but, in a way that is yet to be defined, renders such tumours more aggressive or less responsive to therapy. With the current interest in the role of RB mutations in other cancers (where the prognostic import of single genes is less easily identified), this observation may have wider relevance.

Globe conserving treatment of the only eye in bilateral retinoblastoma.

AIMS: To quantify the rates of eye preservation and patient survival, local tumour relapse and recurrence, and development of new tumours in the remaining eye of children with bilateral retinoblastoma with one eye already enucleated. Also, in the same children, to describe the types of primary and secondary treatment procedures, and to define the anatomical outcome. METHODS: This is a retrospective observational case series report. The study participants consisted of 107 patients with bilateral retinoblastoma with one eye enucleated within 1 month of baseline examination and had their remaining eye treated conservatively. The main outcome measure were: primary treatment failures, new tumours, enucleation of the only eye, death, remission, and anatomical outcomes (retinal detachment, vitreous haemorrhage, and cataract). RESULTS: The median age at diagnosis was 8.4 (range 0.2-44, SD 10.1) months with a median ophthalmic follow up of 44.3 (8.1-114, SD 10.1) months. In 22 of the 107 patients (21%) the treated eye was in Reese Ellsworth groups I or II and in the remaining 85 (79%) in groups III-V at diagnosis. The primary treatment was cryotherapy in 14% (15/107) of eyes, radioactive plaque brachytherapy in 3.7% (4/107), and chemotherapy in 10% (11/107). It was lens sparing radiotherapy in 37% (40/107), whole eye radiotherapy in 29% (31/107), combined radiotherapy and chemotherapy in 2.8% (3/107), chemothermotherapy in 0.9% (1/107), and combined focal therapy in 1.8% (2/107). The primary treatment failed to achieve local tumour control during the follow up period in 37% (40/107) of eyes. In 17 eyes failure was due to inadequate control of the presenting tumour, in 16 to development of a new tumour, and in eight eyes to a combination of both. 35 (88%) of the 40 failures were managed by secondary conservative treatment and the remaining five were treated by enucleation of the only eye. There were eight (7.4%) deaths and the 3 year survival rate was 93% (100/108). Anatomical results included vitreous haemorrhage in four cases, tractional retinal detachment also in four cases, and 24 children required cataract surgery. CONCLUSIONS: Aggressive conservative treatment achieved a good rate of globe salvage without impairing survival.

High level amplification of N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours.

Twenty-five primary retinoblastoma tumours were analysed by real-time quantitative polymerase chain reaction to determine the genomic copy number of the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization to contain variable copy number increases of chromosomal material mapping to 2p. High level amplification (>30-fold) of N-MYC was found in three tumours, none of which showed adverse histological features and all patients are surviving at between 54 and 108 months post enucleation. Furthermore, the three tumours associated with metastasis and adverse patient outcome showed normal N-MYC copy number. Although high level amplification of N-MYC is an unfavourable prognostic indicator in neuroblastoma, these data show no evidence of a correlation between amplification of N-MYC and adverse outcome in retinoblastoma.

Imaging-guided core biopsy for the diagnosis of malignant tumors in pediatric patients.

OBJECTIVE: We evaluated the ability of imaging-guided core biopsy to obtain sufficient tissue from pediatric tumors for a definitive diagnosis of malignancy on which treatment could be based. MATERIALS AND METHODS: Thirty-four biopsies (biopsies of the abdomen, 32; of the chest, 2) were performed on 34 children at presentation under CT or sonographic guidance using 14-, 18-, or both 14- and 18-gauge needles. A minimum of two tissue cores was obtained. Most biopsies were performed under general anesthesia, permitting other procedures to be performed. The biopsy results were confirmed by subsequent surgical pathology, bone marrow biopsy, biochemical or clinical features, and follow-up examination. RESULTS: The needle biopsy diagnoses were nephroblastoma (n = 11), neuroblastoma (n = 7), renal cell carcinoma (n = 2), synovial sarcoma (n = 1), non-Hodgkin's lymphoma (n = 2), clear cell sarcoma (n = 1), rhabdoid tumor (n = 1), pulmonary blastoma (n = 2), embryonal rhabdomyosarcoma (n 1), germ cell tumor (n = 1), adrenal carcinoma (n = 1), inflammatory tissue (n = 2), desmoplastic tumor of the mesentery (n = 1), and primitive neuroectodermal tumor (n = 1). In 28 patients, the results were confirmed as correct (22 with surgery and 6 with follow-up examination). Four patients required additional biopsy. In two of these patients, the core biopsy showed inflammatory tissue only, and an open biopsy of a different site was performed; the other two patients did not respond to therapy on the basis of needle biopsy results, and an open biopsy altered the diagnosis. Two patients with widespread disease were excluded because they did not respond to treatment and were too ill to undergo an open biopsy. Only one significant complication was recorded. CONCLUSION: Imaging-guided core biopsy is a safe and reliable means of obtaining sufficient tissue to make a confident histologic diagnosis of malignant pediatric tumors in a high percentage of patients.

Delay in diagnosis of retinoblastoma: risk factors and treatment outcome.

BACKGROUND: Delay in diagnosis of retinoblastoma causes considerable parental distress; however, the primary healthcare professional (PHP) may have difficulty detecting the most common presenting symptom-leucocoria. Alternatively, the PHP may not appreciate that retinoblastoma is the pathology underlying more common ocular symptoms in infants and young children. METHOD: The parents of 100 recently diagnosed patients with retinoblastoma were interviewed to establish the extent of diagnostic delay, ascertain any associated risk factors, and to determine whether or not delay influenced treatment outcome. RESULTS: Although nearly 50% of patients were referred to an ophthalmologist within 1 week of first consulting a PHP, one quarter waited more than 8 weeks. There was a significantly increased risk of diagnostic delay in younger patients, those presenting with squint rather than leucocoria, and those first presenting to a health visitor rather than to a general practitioner. The risk of local tumour invasion was significantly increased by diagnostic delay. Treatment with primary enucleation was not increased by diagnostic delay. There were no deaths during the study period. CONCLUSION: Primary healthcare professionals require education about the importance of ocular symptoms, especially squint, in paediatric patients.

Asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma.

PURPOSE: To determine the prevalence and severity of asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma and to compare the prevalence of carotid arterial disease following radiation therapy alone with that following radiation therapy and chemotherapy. MATERIALS AND METHODS: Forty-two survivors of childhood or early adult Hodgkin lymphoma aged 18-37 years who had undergone radiation therapy more than 5 years earlier underwent carotid arterial ultrasonography. Common carotid intima-media thickness was measured; carotid vessels were assessed for intima-media abnormalities. Results were compared with those from 33 control subjects. RESULTS: Patients had a significantly greater number of abnormal scans than did control subjects (11 [26%] vs one [3%]; P < .01). Ten patients (24%) had intima-media abnormalities that did not cause significant stenosis; one patient had diffuse bilateral intima-media thickening (mean, 1.99 mm) with greater than 70% stenosis of both common carotid arteries. Intima-media thickness was significantly greater in patients (0.51 mm) than in control subjects (0.43 mm; P < .005). The number of abnormalities in patients with radiation therapy plus chemotherapy (six [19%] of 31 patients) did not differ significantly from the number in patients with only radiation therapy (five [45%] of 11 patients; P = .12); there was no significant difference between median intima-media thicknesses (0.50 mm vs 0.51 mm, P > .2). CONCLUSION: Asymptomatic carotid arterial disease occurs frequently in young patients following neck radiation therapy for Hodgkin lymphoma. No difference in prevalence was shown between only radiation therapy and radiation therapy plus chemotherapy.

Thyroid nodular disease after radiotherapy to the neck for childhood Hodgkin's disease.

Patients who receive radiotherapy to the neck are at risk of developing thyroid dysfunction. This prospective study of patients whose treatment for Hodgkin's disease in childhood included radiotherapy to the neck aimed to investigate the incidence and natural history of thyroid dysfunction and the morphological changes of the gland demonstrated on ultrasound. Forty-seven patients were investigated by clinical examination, thyroid function tests and thyroid ultrasound. Only six patients had a clinically detectable abnormality, but 64% had abnormal thyroid function tests. All patients had an abnormal thyroid ultrasound scan and 42% had at least one focal abnormality. A significant association was found between the presence of a focal lesion on ultrasound and young age at radiotherapy, longer follow-up and the length of time that the thyroid-stimulating hormone (TSH) level had been elevated. During follow-up, 65% of patients not on thyroxine developed new focal abnormalities. The longest time interval between radiotherapy and an increase in TSH level was 94 months, and from radiotherapy to the appearance of a focal abnormality on thyroid ultrasound was over 18 years. Three patients were found to have a thyroid carcinoma. These findings indicate the importance of long-term follow-up for patients treated by neck irradiation for Hodgkin's disease in childhood.

Growth hormone deficiency following radiotherapy for orbital and parameningeal sarcomas.

Growth hormone deficiency (GHD) is a recognized late effect of successful treatment of tumors requiring cranial irradiation. Growth after treatment was assessed in 16 patients with sarcomas of the orbital and parameningeal regions. Median age at diagnosis was 6.35 years and median follow-up was 7.2 years. Treatment consisted of combination chemotherapy and radical radiotherapy, conventionally fractionated with a median dose 4500 cGy; the hypothalamic/pituitary region received a median dose of 4163 cGy. Height was measured every 6 months and 13/16 patients underwent tests of GH function. At GH testing median height standard deviation score (SDS) was -0.7, a median decrease of -0.55 since tumor diagnosis. Seven patients were treated with human GH (hGH) at a median of 3.7 years from tumor diagnosis and followed for a median of 2.7 years. Treatment with hGH resulted in a median increase in height SDS of 0.9. Careful surveillance with timely introduction of GH replacement is required for treatment of GHD following treatment of orbital and parameningeal sarcomas.

Ongoing assessment of nutritional status in children with malignant disease.

The nutritional status of a child on cancer therapy influences both tolerance of and response to treatment. However, it is difficult to assess nutritional status on a daily basis because an accurate quantitation of the calorie intake is difficult. Anthropometric and biochemical parameters are prone to error and often reflect past rather than current nutritional status. In practice, a subjective clinical assessment is usually relied upon. This study objectively appraises the value of such an assessment. Based on clinical symptoms that alter oral intake and absorption of food, a scoring system was designed to assess nutritional status on a day to day basis. A symptom score (SS) of 10 implied "normality"; 0 indicated maximum debility. Over a 2-year period 511 daily scores were recorded in 30 patients aged 0.7-17.5 years. Patients were studied at presentation and during treatment for acute lymphoblastic leukemia (ALL, n = 14; solid tumors receiving megatherapy with autologous bone marrow rescue (ABMR, n = 8), and chemotherapy for different tumors (miscellaneous, n = 8). The SS was compared with other nutritional parameters, including sequential anthropometric indices, serum albumin, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and whole-body protein turnover (WBPT) using [1-(13) C]leucine. The mean SS was reduced at diagnosis for all leukemic patients (median score = 8), improved during first remission (p < 0.002), fell to a minimum during febrile neutropenia (p = 0.0009), and improved with clinical and hematological recovery (p = 0.0009). A reduction in SS was related to fever (p < 0.001) and a fall in neutrophil count (p < 0.001). There was no correlation with anthropometric indices or IGF-I and IGFBP-3 levels. Paired WBPT studies in 9 patients showed that SS correlated well with protein breakdown (p = 0.026). The results suggest that the ongoing nutritional status of children with malignancy undergoing chemotherapy is best assessed using simple clinical parameters.

Treatment of retinoblastoma vitreous base seeding.

OBJECTIVE: The purpose of the study is to describe results of a new treatment for retinoblastoma vitreous base seeding. DESIGN: The study design was a retrospective review of patients treated at an ocular oncology referral center. PARTICIPANTS: Five eyes of five patients with vitreous base seeding that occurred after previous external beam radiation therapy were treated between October 1987 and December 1994. INTERVENTION: A customized plaque made from iridium-192/platinum wire was placed to deliver 4000 cGy to the tumor apex along its entire length and systemic chemotherapy (consisting of carboplatin, vincristine, and etoposide) was given. MAIN OUTCOME MEASURES: Eye preservation and tumor control were measured. RESULTS: Vitreous base seeding was controlled completely and the eye preserved in four of the five treated eyes with an average follow-up of 26.2 months. CONCLUSIONS: The combination of a customized iridium-192 plaque and systemic chemotherapy is an effective means of treating vitreous base seeding of retinoblastoma.

A limited role for VEEP (vincristine, etoposide, epirubicin, prednisolone) chemotherapy in childhood Hodgkin's disease.

The VEEP regimen (vincristine, etoposide, epirubicin, prednisolone), with or without involved field radiotherapy, has been shown to be an effective treatment in adult Hodgkin's disease. In an attempt to avoid the late sequelae of both alkylating agents and radiotherapy this regimen has been studied in a series of 54 children and young adults. Early analysis suggested that the relapse rate was higher with VEEP than with standard alkylating agent-based regimens. Sufficient follow-up has now been achieved to evaluate the likelihood of sustained remission following second-line treatment and therefore the overall long term survival with this treatment approach. The 5-year Overall Survival (OS) and 5-year Progression Free Survival (PFS) for patients with stage I-III disease was 93% and 82% respectively. However, the 5-year OS and PFS for stage IV patients was only 44% and 50%, respectively. Of 13 patients who were initial treatment failures on VEEP, 7 of whom had advanced disease, only 6 were salvaged with second-line therapy. 8 of 33 who attained a complete response (CR) relapsed and there were 2 relapses in those achieving a partial response (PR) (n = 8). All those relapsing from CR/PR were salvaged by second-line alkylating agent chemotherapy +/- radiotherapy, +/- high dose chemotherapy. In conclusion, patients with stage I-IIIA, non-bulky disease, the moderately high relapse rate did not adversely affect the overall high cure rate, although VEEP failures were subjected to a high total treatment burden. VEEP alone is inadequate in patients with stage IV disease, bulky mediastinal disease in/or those with B symptoms in whom there is a high primary failure rate and relatively poor results with second line therapy.