RESUMO
Patients with retinoblastoma and central nervous system (CNS) involvement are rarely curable with available treatments. We designed a high-dose intra-arterial regimen targeting the ophthalmic artery and chiasm combined with intrathecal chemotherapy to treat a 4-year-old patient with retinoblastoma metastasized to the CNS. After three cycles of this regimen, including carboplatin, melphalan, and intrathecal topotecan, a partial response of the orbital tumor mass and chiasmatic lesion, and complete response in the cerebrospinal fluid and bone marrow were achieved. This new treatment strategy may be explored as a treatment component for patients with overt extraocular retinoblastoma and CNS dissemination.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Carboplatina/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/secundário , Pré-Escolar , Humanos , Infusões Intra-Arteriais , Injeções Espinhais , Masculino , Melfalan/administração & dosagem , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Topotecan/administração & dosagemRESUMO
IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site.
Assuntos
Predisposição Genética para Doença/epidemiologia , Proteínas de Homeodomínio/genética , Neoplasias da Retina/genética , Retinoblastoma/genética , Transativadores/genética , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Incidência , Lactente , Masculino , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Neoplasias da Retina/epidemiologia , Neoplasias da Retina/patologia , Retinoblastoma/epidemiologia , Retinoblastoma/secundário , Medição de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Fatores de Transcrição/genéticaRESUMO
IMPORTANCE: Different staging systems for extraocular retinoblastoma have been published, but to date they have not been validated in large cohorts. OBJECTIVE: To review 533 patients (and pathology slides) with retinoblastoma included in 4 protocols (January 1, 1988, to December 31, 2009) who received uniform treatment. DESIGN AND SETTING: Retrospective review in a hospital setting. A critical analysis for detecting inconsistencies and omissions was performed. PARTICIPANTS: Patients were reclassified according to the modified St Jude Children's Research Hospital staging system, Grabowski-Abramson staging system, International Retinoblastoma Staging System (IRSS), and American Joint Committee on Cancer TNM staging system. MAIN OUTCOME AND MEASURE: The main outcome measure was disease-free survival (DFS), considering only extraocular relapse as an event. RESULTS: In the IRSS and the St Jude system, higher stages correlated with poorer DFS. For intraocular disease, only the TNM system and the IRSS included pathological definitions, and all systems except for the IRSS included substages without differences in DFS. Omissions of factors significantly associated with lower DFS included scleral invasion by the TNM system and massive choroidal invasion by the Grabowski-Abramson system. The St Jude system omits postlaminar optic nerve involvement, but this omission did not correlate significantly with lower DFS because these patients received intensive therapy. No differences in DFS were observed among substages for metastatic disease except for the presence of central nervous system involvement. All staging systems had inconsistencies in definitions of extent of disease. No system provides guidelines for imaging. CONCLUSIONS AND RELEVANCE: Only the IRSS and the St Jude system allowed for grouping of patients with increasing risk of extraocular relapse. For lower stages, only the IRSS considers all unequivocal pathological prognostic factors. For higher stages, all systems had redundant information, resulting in an excess of substages.
Assuntos
Neoplasias da Medula Óssea/secundário , Neoplasias Encefálicas/secundário , Neoplasias do Nervo Óptico/secundário , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Neoplasias da Medula Óssea/terapia , Neoplasias Encefálicas/terapia , Pré-Escolar , Intervalo Livre de Doença , Enucleação Ocular , Seguimentos , Humanos , Lactente , Terapia Neoadjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias , Disco Óptico/patologia , Neoplasias do Nervo Óptico/terapia , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
AIM: To evaluate minimally disseminated disease (MDD) in cytologically negative cerebrospinal fluid (CSF) specimens of patients with high-risk retinoblastoma by the detection of the synthase of ganglioside GD2 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: The CSF was evaluated in 26 patients with high risk for CSF relapse: 14 with postlaminar optic nerve invasion, five of them with tumour at the resection margin, five with massive choroidal invasion, three with overt orbital extension and four patients with systemic metastasis. Serial CSF examinations were repeated at different time intervals according to stage and in the event of suspected relapse. GD2 synthase mRNA was evaluated by RT and nested PCR at each procedure. RESULTS: MDD was present at diagnosis in six cases (23%) and it was significantly associated to massive optic nerve involvement or history of glaucoma (p<0.05). Three of the children with positive MDD had a CSF relapse. Thirteen patients had negative MDD at diagnosis and one had a CSF relapse. In seven children no ARN could be obtained for PCR analysis and two subsequently relapsed. The probability of CSF relapse was 0.50 (95% confidence interval (CI) 0.13-0.88) for children with MDD and 0.08 (95% CI 0.02-0.46) for those with negative RT-PCR examination of the CSF at diagnosis (p=0.03). CONCLUSIONS: MDD in the CSF detected by RT-PCR for GD2-synthase mRNA occurred in 31.7% of evaluable high-risk children with retinoblastoma with no initial central nervous system (CNS) involvement. It was significantly associated to optic nerve involvement and glaucoma and increased risk of CSF relapse.
Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Biomarcadores Tumorais/genética , N-Acetilgalactosaminiltransferases/genética , RNA Mensageiro/líquido cefalorraquidiano , Neoplasias da Retina/líquido cefalorraquidiano , Neoplasias da Retina/genética , Retinoblastoma/líquido cefalorraquidiano , Retinoblastoma/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores Etários , Distribuição de Qui-Quadrado , Corioide/patologia , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Invasividade Neoplásica , Recidiva Local de Neoplasia , Nervo Óptico/patologia , Valor Preditivo dos Testes , Neoplasias da Retina/mortalidade , Neoplasias da Retina/patologia , Neoplasias da Retina/terapia , Retinoblastoma/mortalidade , Retinoblastoma/secundário , Retinoblastoma/terapia , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Few prospective studies about the management of unilateral retinoblastoma with pathology risk factors (PRFs) have been published. METHODS: Patients (n = 114) were divided into four groups: Group 1 (initial chemoreduction) (n = 17). Groups 2 and 3, included patients initially enucleated with no, or lower risk PRFs: (n = 65) and with higher risk PRFs (n = 30), respectively. The later included postlaminar optic nerve involvement (PLONI) (n = 23), tumor at resection margin of optic nerve (n = 5) or isolated scleral invasion (n = 2). Group 3 received adjuvant chemotherapy including a total eight cycles of carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Orbital radiotherapy (45 Gy) was given to patients with invasion to the resection margin. Group 4 included patients with metastatic disease (n = 2). They were given neoadjuvant therapy followed by surgery and high-dose chemotherapy and autologous stem cell rescue. RESULTS: Five-year event-free survival is 0.94 (1 for Group 1, 0.94 for Group 2, 0.96 for Group 3, and 0 for Group 4). Events included. Group 2: Systemic relapse (n = 2) and combined orbital and CNS relapse (n = 1). Relapsing patients had PLONI (n = 2) and isolated focal choroidal invasion (n = 1). Group 3: CNS relapse (n = 1) in a patient with tumor at the resection margin of optic nerve. Group 4: CNS relapse (n = 2). Only one relapsed patient survived. Eight of 17 eyes treated conservatively were preserved. CONCLUSIONS: The survival of patients with unilateral retinoblastoma was excellent and 60% were spared from adjuvant treatment. Our intensive regimen was likely to be effective for prevention of metastasis in patients with higher risk PRFs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Criança , Pré-Escolar , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Estudos Prospectivos , Recidiva , Reprodutibilidade dos Testes , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/secundário , Retinoblastoma/diagnóstico , Retinoblastoma/secundário , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the outcome and determine risk factors for extraocular relapse in patients with retinoblastoma who had been enucleated after failure of chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions. Pathological risk factors (PRF) were defined as invasion of the anterior segment, choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the local pathology report. Extraocular relapse was defined as an event. RESULTS: One hundred twenty-two patients were included (17 had bilateral enucleation). Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%), vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty-five also received external beam radiotherapy (28.7%). PRF included: 39 with choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post-laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given to eight patients (6.5%) because of scleral invasion. Four patients had an extraocular relapse after enucleation, two of whom survive after intensive treatment including stem cell rescue. Five-year probability of event-free survival is 0.96. Only scleral invasion and bilateral enucleation were significantly associated with extraocular relapse. CONCLUSIONS: The risk of extraocular relapse is low after enucleation following failure of chemoreduction. Patients who underwent bilateral enucleation and those with scleral invasion are at higher risk of extraocular relapse.
Assuntos
Enucleação Ocular , Neoplasias da Retina/cirurgia , Retinoblastoma/secundário , Retinoblastoma/cirurgia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Quimioterapia Adjuvante , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Invasividade Neoplásica , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/patologia , Retinoblastoma/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
There is general agreement that bone marrow (BM) examination for staging in patients with retinoblastoma should be limited to cases with advanced disease. However, there are limited data about the yield of sampling multiple sites with aspirations and biopsies and immunocytology. Our policy for BM examination included: 2 aspirates and 2 biopsies at the posterior iliac crest scheduled only for cases with postlaminar optic nerve extension (n=56), scleral invasion (n=10) or orbital (n=5) or metastatic disease at diagnosis (n=7) or at extraocular relapse (n=18). Immunocytology with the antibodies 3A7 or 3F8 for the ganglioside GD2 was performed. From 1/1994 to 3/2005, 277 newly diagnosed patients and 5 at extraocular relapse were included. BM invasion was not found in any of the 66 patients enucleated with disease confined to the globe, but was found in 11/27 of those with overt extraocular disease. There were 2/11 cases with at least 1 negative aspirate with positive biopsy and/or immunocytology for GD2. GD2 positivity was found in 9/9 cases. A more aggressive BM evaluation has a low yield in enucleated patients with high-risk features but disease limited to the globe. However, in cases with overt extraocular dissemination, the use of BM biopsy and immunocytology for GD2 allowed for the detection of cases that would have been missed by aspirations alone. GD2 was intensively expressed and it may also be used to monitor disease response and the presence of minimal residual disease.
Assuntos
Neoplasias da Medula Óssea/secundário , Medula Óssea/patologia , Gangliosídeos , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Biópsia , Exame de Medula Óssea , Neoplasias da Medula Óssea/imunologia , Gangliosídeos/imunologia , Humanos , Imuno-Histoquímica , Masculino , Monitorização Fisiológica , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias da Retina/imunologia , Retinoblastoma/imunologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Retinoblastoma (RB) is the most frequent malignant eye tumor in childhood. In developing countries advanced stages are common. The purpose of this paper is to present our 21-year clinical experience with metastatic extra ocular RB patients treated with 5 different chemotherapy schemas at a single Mexican Pediatric referral center. MATERIALS AND METHODS: A retrospective analysis was carried out reviewing the clinical characteristics of patients with metastatic RB. The information analyzed included the delay in diagnosis after first symptoms, age, sex, ocular staging, and anatomic site of metastases, treatment scheme, initial response and status at the last contact or date of death. RESULTS: Eighty-one patients were included; age range was from 3 to 80 months. The most common site of metastasis was central nervous system (83.9%). From those patients treated with chemotherapy (n = 74), 89.2% presented a complete initial response (n = 66). Early mortality occurred in 7 cases before any treatment. Fifty-six received treatment and died with progressive disease. All patients without radiotherapy died with tumor activity (n = 15). The use of cisplatin was related with longer disease free intervals; no other variable was related with survival. Four patients were alive and disease free at 33 to 144.3 months of follow up from diagnosis. The prevalent cause of death was tumor progression. CONCLUSIONS: In our experience, metastatic RB has a very high mortality rate in spite of the use of different chemotherapy regimens.
Assuntos
Neoplasias Oculares/mortalidade , Retinoblastoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/secundário , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Radioisótopos de Cobalto/uso terapêutico , Terapia Combinada , Irradiação Craniana , Progressão da Doença , Intervalo Livre de Doença , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Neoplasias Oculares/radioterapia , Neoplasias Oculares/cirurgia , Feminino , Seguimentos , Humanos , Lactente , Tábuas de Vida , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , México/epidemiologia , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Indução de Remissão , Retinoblastoma/tratamento farmacológico , Retinoblastoma/mortalidade , Retinoblastoma/patologia , Retinoblastoma/radioterapia , Retinoblastoma/cirurgia , Estudos Retrospectivos , Neoplasias Cranianas/tratamento farmacológico , Neoplasias Cranianas/mortalidade , Neoplasias Cranianas/radioterapia , Neoplasias Cranianas/secundário , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The current study was performed to evaluate two regimens of treatment and to describe clinical and epidemiologic characteristics in patients with extraocular retinoblastoma. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Retinoblastoma/tratamento farmacológico , Retinoblastoma/secundário , Pré-Escolar , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Enucleação Ocular , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Neoplasias da Retina/patologia , Neoplasias da Retina/cirurgia , Retinoblastoma/mortalidade , Retinoblastoma/patologia , Retinoblastoma/cirurgia , Teniposídeo/administração & dosagem , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
PURPOSE: The aim of this study was to evaluate in an upfront phase II study the response to idarubicin in children with extraocular retinoblastoma. PATIENTS AND METHODS: The starting dose of idarubicin was 15 mg/m(2)/d (days 1 and 2) weeks 0 and 3. After an interim evaluation, the dose was reduced to 10 mg/m(2)/d (days 1 and 2) weeks 0 and 3 because of hematopoietic toxicity. Response was evaluated at week 6. RESULTS: At the Hospital JP Garrahan (Buenos Aires, Argentina), 10 patients (five bilateral) were entered onto the study from 1995 to 1998. A total of 19 cycles were administered. Extraocular sites included orbit (n = 10), bone marrow (n = 3), bone (n = 1), lymph node (n = 1), and CNS (n = 1). The response rate was 60% (95% confidence interval, 30% to 90%). One complete response was achieved, in addition to five partial responses, two cases of stable disease, and two cases of progressive disease. All patients with bone marrow involvement achieved complete clearance of tumor cells. The patient with CNS disease had progressive disease. All patients had severe hematopoietic toxicity (grade 4 neutropenia and grade 3/4 thrombocytopenia after most cycles). Other toxicities included grade 2 diarrhea in 30%. No echocardiographic changes were detected. CONCLUSION: Idarubicin is active in extraocular retinoblastoma. The activity of this drug should be explored in future phase III studies.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Idarubicina/uso terapêutico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Orbitárias/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Medula Óssea/tratamento farmacológico , Neoplasias da Medula Óssea/mortalidade , Neoplasias da Medula Óssea/secundário , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/secundário , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Idarubicina/efeitos adversos , Lactente , Metástase Linfática , Masculino , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Neoplasias Orbitárias/mortalidade , Retinoblastoma/mortalidade , Retinoblastoma/patologia , Retinoblastoma/secundário , Resultado do TratamentoRESUMO
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.
Assuntos
Neoplasias da Retina/patologia , Retinoblastoma/patologia , Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/secundário , Criança , Pré-Escolar , Enucleação Ocular , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/radioterapia , Neoplasias Orbitárias/secundário , Neoplasias Orbitárias/cirurgia , Recidiva , Neoplasias da Retina/radioterapia , Neoplasias da Retina/cirurgia , Retinoblastoma/radioterapia , Retinoblastoma/secundário , Retinoblastoma/cirurgia , Fatores de RiscoRESUMO
We report an unusual case of a two-year-old girl with metastatic retinoblastoma and massive bone marrow involvement who showed the overt presence of circulating retinoblastoma cells in peripheral blood smears a few days before death. This extended disease developed after an early relapse that followed abandoned primary chemotherapy. To the best of our knowledge, there are no previous reports about the presence of circulating retinoblastoma cells in peripheral blood films. We conclude that the search for bone marrow invasion in patients with disseminated retinoblastoma should be exhaustive to achieve an accurate staging assessment. Peripheral blood smears should be examined cautiously to detect occasional circulating retinoblastoma cells when the bone marrow is massively involved.
Assuntos
Neoplasias da Medula Óssea/secundário , Células Neoplásicas Circulantes , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Pré-Escolar , Feminino , Humanos , Recidiva , Neoplasias da Retina/sangue , Retinoblastoma/sangueRESUMO
Thirty-seven patients with retinoblastoma were evaluated prospectively by clinical examination, lumbar puncture, and CT. Eight (22%) of the 37 were found to have meningeal dissemination. The tumor was bilateral in three patients. Two cases showed no CT signs of local recurrence. Headache, nausea/vomiting, and restlessness were the most common symptoms. CT scans in these patients showed diffuse meningeal contrast enhancement, nodular masses, ependymal-subependymal enhancement, and ventricular dilatation. Our series of eight patients with meningeal spread illustrates a considerable range of dissemination patterns referable to retinoblastoma. One case illustrated the CT finding of multiple epidural metastases.