Impact of chemoreduction for conservative therapy for retinoblastoma in Argentina.

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.

Results of a prospective study for the treatment of unilateral retinoblastoma.

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.

Twinning partnerships through International Atomic Energy Agency (IAEA) to improve radiotherapy in common paediatric cancers in low- and mid-income countries.

PURPOSE: The article summarises the current use of radiotherapy (RT) in childhood cancer and suggests methods to improve current practice in regions where outcomes of paediatric cancer patients are inferior to those of high-income countries. METHODS AND MATERIALS: The International Atomic Energy Agency (IAEA) is supporting low- and mid-income countries (LMICs) in upgrading cancer care where nuclear applications, particularly RT, are used. A consensus meeting of experts was invited to advise IAEA on the needs for RT in paediatric cancer patients. The current indications for RT were reviewed, together with regional differences in access, practice and outcome. RESULTS: Regional variations in the use of evidence-based multidisciplinary care including RT were associated with varying outcomes of paediatric cancer patients. The contribution of modern and investigational technology to these differences is uncertain and should be determined in clinical trials. Adequate resources are required to support children through the acute phase of treatment and to permit early recognition and management of late effects. An IAEA sponsored project for prospective data collection to assess the current and future status of radiation treatment in childhood cancer in LMICs has commenced. CONCLUSION: RT remains an essential component of the multidisciplinary management of many paediatric cancers. Excessive variations in outcome are inappropriate and call for action on harmonising training programmes and compliance with evidence-based recommendations. Training projects targeting paediatric cancer care are being implemented and clinical studies comparing new technologies against evidence-based approaches are needed to achieve this goal. The IAEA has an important role in these activities and has commenced prospective data collection in 13 LMICs to monitor trends in treatment techniques and outcomes.

Treatment results in patients with retinoblastoma and invasion to the cut end of the optic nerve.

BACKGROUND: There is little information on the outcome of patients with retinoblastoma and tumor at the resection margin of the optic nerve. PROCEDURE: Retrospective evaluation of three successive prospective protocols. Twenty-six consecutive patients were analyzed (International Staging System-IRSS-stage 2 = 21, stage 3 = 5) from three successive prospective protocols (1988-2006). Patients with stage 2 were enucleated upfront and those with stage 3 had neoadjuvant chemotherapy followed by enucleation and adjuvant therapy. Both groups received adjuvant chemotherapy and orbital radiotherapy after enucleation. Patients in protocol 1 received 1 year of the lower-dose chemotherapy regimen including cyclophosphamide, vincristine and doxorubicin along with intrathecal chemotherapy. Patients of protocols 2 and 3 received a more intense and shorter intravenous regimen including carboplatin and etoposide alternating with cyclophosphamide, idarubicin and vincristine with no intrathecal treatment. The components of protocol 2 and 3 were similar except for the dose of carboplatin which was 10% lower in protocol 3. RESULTS: Thirteen were treated in protocol 1 and 13 in protocols 2 and 3. The probability of event-free survival was 0.70 at 5 years. Events included: CNS relapse = 3, second malignancies = 3, death in complete remission = 2. There were no significant differences in outcome between protocols or stages. Endocrinological disturbances related to the hypothalamus-hypophysis axis were evident in 6/8 patients evaluated. Severe orbital sequelae occurred in 12 cases. CONCLUSIONS: A substantial number of patients with tumor at the resection margin of the optic nerve can be cured with current therapy; however, therapy related sequelae are frequent.

Experience with chemoreduction and focal therapy for intraocular retinoblastoma in a developing country.

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.

Results of a prospective study for the treatment of retinoblastoma.

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.

Treatment of overt extraocular retinoblastoma.

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.

Morbilidad en el tratamiento de los tumores óseos primitivos en la infancia: osteosarcoma (primera parte)

Se evalúa la morbilidad obtenida en el tratamiento de 24 niños portadores de osteosarcoma. De estos pacientes evaluados, 13 recibieron reemplazos endoprotésicos. Se analizan las complicaciones derivadas de la cirugía, así como las relacionadas con la quimioterapia (protocolo PIA). En el aspecto funcional se comparan los resultados obtenidos con la cirugía conservadora y los pacientes amputados

Morbilidad en el tratamiento de los tumores óseos primitivos en la infancia: osteosarcoma (primera parte)

Se evalúa la morbilidad obtenida en el tratamiento de 24 niños portadores de osteosarcoma. De estos pacientes evaluados, 13 recibieron reemplazos endoprotésicos. Se analizan las complicaciones derivadas de la cirugía, así como las relacionadas con la quimioterapia (protocolo PIA). En el aspecto funcional se comparan los resultados obtenidos con la cirugía conservadora y los pacientes amputados