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Background: Few studies were reported from developing countries regarding patient outcome and ocular survival in children with bilateral retinoblastoma treated with chemoreduction compared to external beam radiotherapy (EBRT)., Procedure: We undertook a retrospective study of three treatment eras: (1) (1988-1995) n = 68 when EBRT was used as primary conservative therapy; (2) (1995-2003) n = 46 when carboplatin-based systemic chemoreduction was introduced and (3) (2003-2009) (n = 83) when additional periocular chemotherapy was added for advanced tumors and pre-enucleation chemotherapy was given for those with massive buphthalmia., Results: The probability of 5-year disease-free survival was 0.94 (95% confidence interval [CI] 0.91-0.98%) without significant differences among the three eras. Chemoreduction reduced the use of EBRT from 84.6% to 68.7% in eras 1 and 3, respectively (P = 0.008), which was more evident in cases with less advanced disease. Chemoreduction also significantly improved the 5-year probability of preservation of eyes with advanced disease from 0.13 (95% CI 0.04-0.27) during era 1 to 0.49 (95% CI 0.34-0.62) in era 3 (P < 0.0001). Chemoreduction was not associated with changes in the probability of extraocular relapse, which was reduced after the introduction of pre-enucleation chemotherapy. Second malignancies occurred in nine cases, acute myeloid leukemia being the most fatal one. Trilateral retinoblastoma occurred in three cases and all of them had been exposed to chemotherapy., Conclusions: Chemoreduction reduced the need for EBRT in eyes with less advanced disease and improved the preservation of eyes with advanced disease while its effects on secondary malignancies or trilateral disease remain unclear., (© 2013 Wiley Periodicals, Inc.)

Purpose: To evaluate the outcome of patients with retinoblastoma and postlaminar optic nerve invasion (PLONI)., Design: Retrospective interventional case series., Participants: Sixty-one consecutive patients included in 3 successive protocols were analyzed., Methods: Pathologic review was done in each case. Patients were stratified into 2 risk groups: the high-risk group included those with concomitant full choroidal and/or scleral invasion and were given adjuvant chemotherapy. Those without these features were considered low risk and chemotherapy was withheld after 1994., Main Outcome Measures: Extraocular relapse and survival according to stratification., Results: The probability of event-free survival (pEFS) was 0.91 and the probability of overall survival (pOS) was 0.94 at 5 years. Patients in the high-risk group (n = 22) had pEFS of 0.86. Three had extraocular relapse (involving the central nervous system; all died of disease). Microscopic scleral invasion was associated to extraocular relapse (P = 0.05). Lower risk patients (n = 39) had a pEFS of 0.94 and pOS of 1. Eighteen received postenucleation chemotherapy and none relapsed. Twenty-one received no adjuvant therapy and 2 had a systemic relapse but were successfully retrieved. Relapsing patients had a higher ratio of affected optic nerve (>25% of it overall length; P = 0.02)., Conclusions: Patients with PLONI have an excellent outcome with current therapy. Risk stratification according to the presence of concomitant choroidal and/or scleral invasion may help in the decision of giving adjuvant therapy.

Background: Although intra-retinal tumor has long been staged presurgically according to the Reese-Ellsworth (R-E) system, retinoblastoma differs from other pediatric neoplasms in never having had a widely accepted classification system that encompasses the entire spectrum of the disease. Comparisons among studies that consider disease extension, risk factors for extra-ocular relapse, and response to therapy require a universally accepted staging system for extra-ocular disease., Procedure: A committee of retinoblastoma experts from large centers worldwide has developed a consensus classification that can encompass all retinoblastoma cases and is presented herein. Patients are classified according to extent of disease and the presence of overt extra-ocular extension. In addition, a proposal for substaging considering histopathological features of enucleated specimens is presented to further discriminate between Stage I and II patients., Results: The following is a summary of the classification system developed-Stage 0: Patients treated conservatively (subject to presurgical ophthalmologic classifications); Stage I: Eye enucleated, completely resected histologically; Stage II: Eye enucleated, microscopic residual tumor; Stage III: Regional extension [(a) overt orbital disease, (b) preauricular or cervical lymph node extension]; Stage IV: Metastatic disease [(a) hematogenous metastasis: (1) single lesion, (2) multiple lesions; (b) CNS extension: (1) prechiasmatic lesion, (2) CNS mass, (3) leptomeningeal disease]. A proposal is also presented for substaging of enucleated Stages I and II eyes., Conclusions: The proposed staging system is the product of an international effort to adopt a uniform staging system for patients with retinoblastoma to cover the whole spectrum of the disease., ((c) 2005 Wiley-Liss, Inc.)

Background: Chemoreduction is used for the treatment of retinoblastoma in industrialized nations; however, there are fewer data from developing countries. Before the implementation of this program, radiotherapy was used in almost all preserved eyes., Methods: Retrospective evaluation from 1995 to 2001 at the Hospital Garrahan (Argentina). Carboplatin 18.7 mg/kg/day 1 and vincristine (0.05 mg/kg/day 1) were offered to patients with Reese-Ellsworth (RE) groups I-III and all unilateral cases. Etoposide (3.3 mg/kg/day 1 and 2) was added for groups IV and V. The number of cycles was tailored according to response., Results: Fifty-eight patients (78 eyes) were evaluated (39 bilateral, 19 unilateral). With a median follow-up of 47 months, 40 patients had unilateral enucleation, 14 were not enucleated, and 4 had bilateral enucleation. Nineteen patients had unilateral initial enucleation. Eye preservation at 5 years was: RE groups I-III (n = 24 eyes), 0.9 (SE: 0.095) IV-V (n = 54), 0.45 (SE 0.07). Patients received a median of four cycles of chemotherapy. Acute toxicity was mild. External beam radiotherapy was avoided in 41% of eyes with groups I-III. Etoposide was avoided in 24 patients. Two patients died of metastasis. No secondary malignancy occurred., Conclusions: Compared to our previous experience, eye preservation was better and even though less radiotherapy was used, it was prescribed more often than currently recommended in eyes with less advanced disease because of limited availability of sophisticated local therapy., (2004 Wiley-Liss, Inc.)

Purpose: To report our experience with topotecan in children with relapsed/refractory metastatic and intraocular retinoblastoma., Patients and Methods: Topotecan was administered intravenously as a 30-min infusion at a dose of 2 mg/m2/d for five consecutive days and repeated after three weeks. If obvious progression was detected by physical examination in patients with overt extraocular disease or if progressive disease was noted after fundoscopic examination in patients with intraocular disease, a second cycle was not administered. Response was evaluated at Week 6., Results: Nine patients (6 extraocular, 3 intraocular) were treated from November 1998 to March 2002. A total of 16 cycles were administered. In patients with extraocular disease, there were three partial responses, two cases of stable disease, and one case of progressive disease. Two patients with relapsed/resistant intraocular disease had partial response. allowing local therapy to be performed, and the third patient had progressive disease. The drug was well-tolerated. No patient developed fever or documented infections. No other serious toxicity was found., Conclusion: Topotecan is active in extraocular and relapsed/resistant intraocular retinoblastoma. The role of this drug in the treatment of retinoblastoma should be explored in further studies.

Background: The objectives of this prospective study were to avoid adjuvant treatment for patients with intraocular disease and patients with postlaminar optic nerve invasion (PL-ONI) without full choroidal or scleral invasion. Adjuvant chemotherapy (Regimen 1) was given to patients with scleral invasion, PL-ONI without cut section, and full choroidal and/or scleral invasion. A more intensive regimen of higher dose intravenous chemotherapy (Regimen 2) and local radiotherapy was given to patients with PL-ONI and compromise at the cut end and to patients with overt extraocular disease., Methods: Six-month intravenous chemotherapy included carboplatin plus etoposide alternating with cyclophosphamide plus vincristine (Regimen 1) and the same drugs at higher dosage plus idarubicin (Regimen 2). Chemoreduction with carboplatin and vincristine with or without etoposide was given to selected patients (n = 39 patients)., Results: From 1994 to 2001, 169 patients were evaluable at the Hospital Garrahan (Buenos Aires, Argentina). One hundred eighteen patients with intraocular disease had a 5-year disease free survival (DFS) rate of 0.98, including 54 patients with choroidal invasion. None of 22 patients with isolated PL-ONI developed recurrent disease, whereas 2 of 8 patients with concomitant risk factors had tumor recurrences and died. Three of 5 patients with scleral invasion survived, and 7 of 10 patients with cut-end ONI survived. The only patient with metastatic disease that survived (n = 6) had only lymph node invasion., Conclusions: Adjuvant therapy can be avoided in patients with intraocular and isolated PL-ONI. Patients with PL-ONI who also had other risk factors required intensive adjuvant therapy, such as patients with cut-end and overt extraocular disease. Metastatic disease was not found to be curable with this approach., (Copyright 2003 American Cancer Society.)

Background: Overt extraocular retinoblastoma is common in developing countries and little information about its treatment is available. The aim of this study is to report our experience in the treatment of these cases using a uniform approach., Procedure: Patients with overt extraocular retinoblastoma including orbital extension, preauricular lymph node invasion and/or metastatic disease on diagnosis or after extraocular relapse admitted to the Hospital JP Garrahan from August 1987 to December 2000 were retrospectively reviewed. Patients were treated according to two different protocols (1987-1993 and 1994-2000). Treatment included: neoadjuvant combination chemotherapy followed by limited surgery in case of orbital extension (enucleation or resection of residual orbital mass) and adjuvant chemotherapy and radiotherapy. Chemotherapy included cyclophosphamide, vincristine, etoposide, doxorubicin (in protocol 87), idarubicin (in protocol 94), cisplatin (in protocol 87), and carboplatin (in protocol 94)., Results: Forty-one patients were included. Fifteen of them had orbital or preauricular disease and had a 5-year event-free survival (pEFS) of 84%. Twenty-six had distant metastatic disease and non survived 5-years. One patient died of toxicity and one died in complete remission. One patient had a secondary leukemia. The remaining adverse events included CNS and/or systemic relapse., Conclusions: This treatment strategy was highly efficacious for patients with orbital and/or lymph node extension. Orbital exenteration is not necessary for these patients. Those patients with distant metastatic or CNS disease were not curable with this approach., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To define a subgroup of patients with retino-blastoma and low risk of extraocular relapse through histopathological and clinical variables., Patients and Methods: Inclusion criteria consisted of stage I (intraocular disease), stage IIb1 (without concomitant choroid and/or scleral invasion), and nonenucleated patients (according to the Grabowski-Abramson classification). A total of 112 consecutive patients admitted to Hospital JP Garrahan from 1987 to 1997 were evaluable. Treatment included enucleation or local therapy and no chemotherapy., Results: Forty-one patients had stage Ia (intraretinal), 8 stage Ib (prelaminar optic nerve invasion), 40 stage Ic (uveal invasion), and 12 stage IIb1 (postlaminar optic nerve invasion and cut end free of tumor). Eleven patients had neither eye enucleated. Median follow-up was 60 months. Only two events occurred: one patient had progressive disease in the contralateral globe and died of CNS metastasis and another had an orbital relapse that was successfully treated. Both had choroidal invasion. Five-year pEFS and pOS were 0.97 and 0.98, respectively. Neither length of the optic nerve stump, tumor size, anterior chamber invasion, degree of differentiation, nor degree of ocular coat invasion correlated with increased risk of metastasis., Conclusions: A subset of patients with retinoblastoma with low risk of relapse can be determined using histopathological evaluation of the invasion of ocular coats. Adjuvant chemotherapy is not warranted for patients with intraretinal extension and prelaminar optic nerve invasion. It is also probable that those patients with isolated choroidal invasion and those with postlaminar optic nerve extension with surgical margins clear of tumor do not need chemotherapy.

Four patients, followed at the Buenos Aires Cildren's Hospital are reported: one with a nephrotic syndrome and male pseudohermaphroditism, the second with nephrotic syndrome, male pseudohermaphroditism and Wilms' tumor, the third with pseudohermaphroditism and Wilms' tumor and the fourth with a nephrotic syndrome and Wilms' tumor. The cases presenting nephrotic syndrome, all had an early onset and a rapid and fatal course leading to death in renal failure or secondary to a related bacterial infection. The renal histology in all of the cases with nephrotic syndrome, was very similar: diffuse involvement of all glomeruli consisting in a severe increase of the mesangial matrix, with scarce mesengial proliferation.

One hundred twenty two children with non-Hodgkin's lymphoma were studied from January 1966 to December 1975. The first group (1966-1972) did not receive an uniform treatment. The second group (1973-1975) entered in a G.A.T.L.A. protocol consisting of: vincristine-prednisone plus surgery and/or radiotherapy as induction treatment, craniocervical radiotherapy and intrathecal methotrexate as CNS preventive treatment and anti-leukemia (6-mercaptopurine, methotrexate and vincristine-prednisone pulses) or anti-lymphoma (COPP) treatment as maintenance, in a randomized trial. Comparison of survival of the two groups are as follows: series 1966-1972, 22% and 20% at 12 and 24 months of evolution, respectively, and series 1973-1975, 33% and 26% at 12 and 24 months, respectively. After 2 years of complete remission we have not seen any relapse. We conclude that 1) this disease is highly malignant and must be treated with more intensive chemotherapeutic treatment, and 2) there is no difference between antileukemia or anti-lymphoma maintenance treatment, as yet.