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[Changes of lipid peroxidation parameters in children being treated for cancer].

Lipid peroxidation (LP) occurring in pediatric cancer patients receiving polychemotherapy has been investigated. Plasma level of malonic dialdehyde in children with retinoblastoma (Rtb) was found to drop while it remained unchanged in patients with acute lymphoblastic leukemia (ALL). The treatment caused different changes in the red cell catalase levels in said groups: the enzyme concentration increased in the Rtb patients in the course of therapy and decreased in the ALL group. A slight decline in alpha-tocopherol and retinol levels the Rtb group was matched by a relevant rise in blood-plasma in the ALL group. To adjust LP regulation and improve resistance, antioxidants should be given to pediatric cancer patients suffering peroxidation-related stress.

Adolescent↗

Isolated lower extremity metastases, 9 years after initial diagnosis of retinoblastoma.

We report the development of isolated lower extremity metastases, in a child, 9 years after her initial diagnosis and treatment of bilateral infantile retinoblastomas. The radiographic, scintigraphic, computed tomographic, and magnetic resonance imaging findings are discussed. The dominant metastatic focus was blastic, involving the medial cuneiform. Additional occult lesions were found in the base of the second metatarsal, middle cuneiform, navicular and tibial diaphysis. An open biopsy confirmed the diagnosis. The occurrence of late distant metastases is rare in the USA.

Antineoplastic Agents↗

Multifocal osteosarcoma as second tumor after childhood retinoblastoma.

We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases.

Adolescent↗

Outcome of second malignancies after retinoblastoma: a retrospective analysis of 25 patients treated at the Institut Curie.

Retinoblastoma is usually curable in developed countries. The morbidity and mortality of patients with hereditary retinoblastoma is still threatened by the occurrence of secondary tumours. Between 1971 and 1988, 427 patients with retinoblastoma were treated in the ophthalmologic, paediatric and radiotherapy departments of the Institut Curie. In this study, we report the clinical and therapeutic features and the outcome of 25 patients treated for a second malignant neoplasm, diagnosed between 1997 and 1999 at the Institut Curie. The median time interval between the diagnosis of retinoblastoma and SMN was 11.2 years (range 3.8-20.6 years). Histopathological diagnoses included: 12 osteosarcomas, 12 soft tissue sarcomas and, 1 malignant oligodendroglioma. The second malignant neoplasm was located inside the radiation field in 21 cases and outside in 4. Twenty three patients received pre-operative chemotherapy. Surgery was performed in 16 patients. Post-operative chemotherapy was administered in 12 patients and external beam radiotherapy was used in 2 patients. Response to treatment was evaluable in 24 patients: complete remissions were observed in 14/24, partial remissions in 2/24 and progressive disease in 8/24. Nineteen patients died. Six are still alive, with 4 in complete remission (median follow-up 8.8 years; range 5.8-13.9 years). Despite aggressive therapy, the prognosis of patients with second malignant neoplasm occurring after retinoblastoma is very poor. It is important to provide information to retinoblastoma patients regarding the risk of a second tumour as this may facilitate an early tumour detection.

Child, Preschool↗

Sebaceous carcinoma of the eyelid associated with retinoblastoma.

OBJECTIVE: To analyze the association between retinoblastoma (Rb) and sebaceous carcinoma (SC) of the eyelid to improve surveillance of survivors of RB: DESIGN: Case report and systematic literature review. METHODS: Ten patients who had SC develop after Rb were identified by systematic literature review, and a child who died with lymph node, lung, and liver metastases 7 years after irradiation for Rb is described. The data were analyzed by univariate statistics, including cumulative frequency distribution plots and Kaplan-Meier analysis. RESULTS: Of 11 children with SC of the eyelid who all had hereditary RB, 9 (82%; 95% confidence interval, 48-98) received a median of 46 Gy (range, 21-89) of radiotherapy at a median age of 16 months (range, 0.5-15 years) and had SC develop within the field of radiation. Their median age at diagnosis of SC was 14 years (range, 8-30 years), median diagnostic delay 12 months (range, 6 months-3 years), and median interval from irradiation 11 years (range, 5-26 years); 7 of them (78%; 95% confidence interval, 40-97) were diagnosed between 5 and 15 years after radiotherapy. SC also developed at the age of 32 and 54 years in two nonirradiated Rb patients. Five patients had regional lymph node metastases after a median time of 12 months (range, 1 month-24 years). The 5-year cumulative probability of survival was 87%. CONCLUSIONS: SC of the eyelid may occur in patients with hereditary Rb regardless of primary treatment, especially within the field 5 to 15 years after radiotherapy.

Adenocarcinoma, Sebaceous↗

Unsual ocular metastasis from breast cancer.

Herein a clinical case of an unusual metastasis from breast cancer to the retina and vitreous confirmed by diagnostic vitrectomy is described. Further investigation also demonstrated the central nervous system metastasis.

Adenocarcinoma↗

Ocular metastases from breast carcinoma: A multicentric retrospective study.

Breast cancer may affect the eye and orbit by metastatic neoplastic infiltration, uvea being the most common site of presentation. Management of these cases with radiotherapy is usually gratifying with reported response rate of approximately 75%. A retrospective evaluation of cases treated in five Institutions participating in a collaborative radiation therapy group of north-Italy is reported. Fifty-four cases of metastases to the eye or orbit were referred for radiation therapy to the Departments participating in the survey in the period 1977-1995. There were 49 female patients aged between 28 and 75 years (median, 44 years) at presentation of orbital metastasis. Thirty-eight lesions (70%) were metastases to the choroid, 9 involved other parts of the eye, and 7 patients had orbital metastases. Five of the 49 patients had bilateral choroidal metastases. Radiotherapy was employed with megavoltage equipment. The median total dose delivered was 40 Gy (range, 16-60 Gy). All the patients were treated 5 times per week with fraction sizes ranging from 1.8 to 3.0 Gy (median, 2.0 Gy). Of the 43 evaluable eyes, 34 (79%) showed a definite improvement after radiotherapy. There was a stabilization of the process in 4 patients. The rest (11 lesions) were lost to detailed follow-up of the response of the eye metastases. Twelve patients experienced acute transient cheratoconjunctivitis and in a case a subconjunctival haemorrhage was observed; as late side effects, two cases of chataract were observed during a period of observation of 37 and 117 months. A median survival time of 17 months was observed. The goal of irradiation was to improve vision or at least prevent blindness and enucleation. The palliative effect of irradiation was confirmed with a response rate consistent with the data of the literature on this subject.

Adult↗

Efficacy of induction chemotherapy in retinoblastoma, alone or combined with other adjuvant modalities.

BACKGROUND: There are not much data available on the use of newer antimetabolites as an initial treatment modality in retinoblastoma, or their effect on vitreous seedings and de novo foci, especially in the Indian subcontinent. METHODS: To evaluate the efficacy of newer agents as induction chemotherapy, 34 tumors in 22 eyes of 19 children with bilateral retinoblastoma were treated with 2 cycles of carboplatin, etoposide, vincristine, and cyclophosphamide; each cycle was of 1 month duration. The tumor response was evaluated at 2 months and adjuvant salvage modalities (ie, cryotherapy, laser, and/or external beam radiotherapy) were added as needed. The cycles were continued and ophthalmoscopic and ultrasonographic monitorings were performed to determine further tumor response, tumor height regression, effect on vitreous seeds, and other ocular changes. RESULTS: Mean tumor height at presentation was 4.2 mm, which regressed to 2.61 mm at 6 months (P=0.000). The biggest tumor to respond was 12.5 mm, although smaller multiple tumors regressed better. Adjuvant modalities were used in 28 tumor foci in 16 eyes. A follow up of 6 to 24 months (mean, 12.8+/-6.21 months), showed complete regression in 12/34 tumors, partial regression in 15/34, stable disease in 6/34, and 1 tumor progressed despite all therapy. Results in all 6 eyes with vitreous seeds were most gratifying; at 1 year vitreous seeds disappeared in 4 eyes and showed complete calcification in 2. Fresh new lesions were not seen in any eye with complete response after the first 2 cycles of chemotherapy. Recurrences were nil and complications minor. CONCLUSIONS: The overall tumor response (complete and partial) of more than 80% indicates that chemoreduction is an effective modality alone and combined with adjuvant salvage modalities. The results with our treatment regime, even in cases with advanced intraocular retinoblastoma, are encouraging.

Antineoplastic Combined Chemotherapy Protocols↗

Third International Meeting on von Hippel-Lindau disease.

Five years after the identification of the von Hippel-Lindau (VHL) gene, physicians, scientists and concerned VHL family members met to review the current state of knowledge on the diagnosis and treatment of VHL and to summarize the latest information on the biochemistry of the VHL protein (pVHL). The NIH and University of Pennsylvania groups reported the detection of germ-line mutations in 100% (93 of 93) of VHL families studied. Several studies determined the frequency of VHL germ-line mutations in individuals with a single manifestation of VHL without a family history of VHL. National groups to improve the diagnosis and treatment of individuals with VHL disease have been established in Great Britain, Denmark, France, Holland, Italy, Japan, Poland, and the United States. Evidence for the existence of genes that modify the expression of VHL was presented. The VHL protein appears to have several distinct functions: (a) down-regulation of hypoxia-inducible mRNAs; (b) proper assembly of the extracellular fibronectin matrix; (c) regulation of exit from the cell cycle; and (d) regulation of expression of carbonic anhydrases 9 and 12.

Animals↗