Tumour angiogenesis as a prognostic factor for disease dissemination in retinoblastoma.

AIM: To evaluate tumour angiogenesis as a predictor of prognosis in retinoblastoma. METHODS: This was a retrospective, non-randomised comparative clinicopathological study. The histopathology from 24 cases of Reese-Ellsworth (RE) group V unilateral retinoblastoma treated by enucleation alone was reviewed. Group I consisted of five patients (four RE group Vb and one group Va) who developed disseminated disease at a mean of 10.4 months after enucleation. The remaining 19 patients constitute group II (18 RE group Vb and 1 group Va), none of whom had developed metastatic disease with a mean follow up of 54 months. None of the 24 patients had evidence of extraocular disease at enucleation. The surgical specimens from patients with unilateral retinoblastoma treated by enucleation at Hospital do Cancer AC Camargo between January 1992 and December 1995 were identified, reviewed and the clinical data recorded. Two subsequent histological sections were prepared. One stained with haematoxylin and eosin for assessment of choroidal and optic nerve invasion, and the other for immunoreaction with an endothelium specific marker (antibody anti-CD 34). The main outcome measures were choroidal and/or optic nerve invasion and quantification of the tumour's relative vascular area (TRVA) obtained by Chalkley counting. RESULTS: Choroidal invasion was present in three eyes of group I (all massive) and six eyes of group II (two focal and four massive). Optic nerve invasion was found in two eyes of group I (all post-laminar) and four eyes of group II (three prelaminar and one post-laminar). There was no statistical difference regarding choroidal or optic nerve between the two groups. The TRVA was the only independent variable found to predict disease dissemination (p = 0.008 by Cox analysis). A TRVA equal to or greater than 3.9% had 100% sensitivity and 79% specificity in predicting disease dissemination. CONCLUSIONS: Quantification of angiogenesis, through measurement of the TRVA, can help to identify patients with retinoblastoma at high risk for disease dissemination after enucleation.

Extraocular retinoblastoma: A 13-year experience

The current study was performed to evaluate two regimens of treatment and to describe clinical and epidemiologic characteristics in patients with extraocular retinoblastoma. Eighty-three patients with extraocular retinoblastoma according to Childrens Cancer Group (CCG) classification were admitted to the Pediatric Department of the A. C. Camargo between 1987-2000. The age, gender, race, lag time, first clinical presentation, staging, laterality, and treatment regimen were analyzed. Treatment was comprised of cisplatin, teniposide, vincristine, doxorubicin, and cyclophosphamide during the first treatment period (1987-1991) or cisplatin and teniposide with alternating courses of ifosfamide and etoposide during the second treatment period (1992-2000). The mean age of the patients was 32.9 months (range, 2-145 months). The mean lag time was 10.5 months. Forty-three patients were treated in the first period and 40 patients were treated in the second period. Locally advanced tumors (Class I-III) were present in 83.1% of the patients. There was a positive correlation between lag time and age for unilateral tumors (correlation coefficient [r] = 0.35; P = 0.006), whereas the correlation was negative for bilateral tumors (r = -0.12; P = 0.63). The 5-year overall survival was 55.1% in the first treatment period and 59.4% in the second treatment period (P = 0.69).

No significant differences with regard to survival rates were noted for unilateral tumors between the two treatment periods (44.6 noted for unilateral tumors vs. 59.1 noted for unilateral tumors). In the current study, the addition of ifosfamide and etoposide to a treatment regimen comprised of cisplatin, teniposide, vincristine, doxorubicin, and cyclophosphamide did not appear to improve the survival of patients with extraocular retinoblastoma. Patients with dissemination to the central nervous system or metastatic disease remain incurable and die of progressive disease, despite the aggressive treatment. A multicenter trial should be considered to evaluate the best strategy for these situations.