A 20-year audit of retinoblastoma treatment outcomes.

OBJECTIVES: To evaluate the long-term treatment outcomes in intraocular retinoblastoma (RB) including the associated factors for eventual treatment with external beam radiotherapy (EBRT) and enucleation as well as to analyse the risk factors for metastasis and death in extraocular RB. METHODS: Retrospective analysis of 390 eyes from 256 (89.8%) intraocular RB and 29 (10.2%) extraocular RB cases diagnosed and treated between October 1998 and May 2018 at one of the largest tertiary care centers in Turkey. RESULTS: Of 351 intraocular RB eyes, 53.3% had group D/E disease at presentation. 75 (21.4%) of 351 eyes underwent primary enucleation. Of the remaining 276 eyes undergoing eye-conserving treatments, 201 (72.8%) were salvaged. Most of these eyes were treated using intravenous chemotherapy and/or focal treatments [transpupillary thermotherapy (TTT) and cryotherapy] initially. EBRT was eventually required in 48 (17.4%) eyes and secondary enucleation in 75 (27.2%) eyes. At mean follow-ups of 76.7 and 39.7 months for intraocular and extraocular RB cohorts, respectively, 180 (46.2%) eyes underwent primary/secondary enucleation and exenteration. Overall, 13 cases developed metastasis and 9 died. Two patients with trilateral RB also expired. Multivariable risk factors for enucleation were the presence of vitreous seeds (p < 0.001), absence of EBRT administration (p = 0.033), 5-9 TTT applications compared with no TTT (p = 0.031), and each 1 mm increase in tumour base diameter (p < 0.001). Univariate factors predictive of metastasis were the presence of extraocular RB detected by imaging methods (p < 0.001) and extrascleral/optic nerve cut end involvement at histopathological examination (p < 0.001). CONCLUSIONS: In our series, 72.8% of the intraocular RB eyes undergoing eye-conserving treatments were saved. The globe salvage rate for all intraocular and extraocular RB eyes was 53.8% and the overall survival rate was 96.1%.

A targeted salvage therapy with Brentuximab vedotin in heavily treated refractory or relapsed pediatric Hodgkin lymphoma patients before and after stem cell transplantation.

Taçyildiz N, Tanyildiz HG, Ünal E, Dinçaslan H, Asarcikli F, Adakli Aksoy B, Vatansever G, Yavuz G. A targeted salvage therapy with Brentuximab vedotin in heavily treated refractory or relapsed pediatric Hodgkin lymphoma patients before and after stem cell transplantation. Turk J Pediatr 2019; 61: 671-676. Hodgkin`s lymphoma (HL) is highly curable disease in its early stages, but in advanced stages, it presents a dilemma when it becomes refractory or relapses after several rounds of chemotherapy. Brentuximab vedotin (BV) is an antibody-drug conjugate that targets the tumor necrosis receptor family protein member CD30 positive malignancies via an anti-CD30 monoclonal antibody linked to monomethyl auristatin-E. In adult and pediatric studies, it has been shown to be an effective salvage therapy for primary refractory HL or relapse after autologous stem cell transplant (ASCT). Between July 2012 and August 2017, we administered BV (1.8 mg/m2 every three weeks; 12 cycles totally) with doxorubucin, vinblastin, dacarbazine (AVD), rituximab + ifosfamide + carboplatin + etoposide (RICE), or bendamustine combination treatment in pediatric HL patients, who were previosuly treated for refractory or relapsed advanced stage HL before (seven patients) or after (one patient) ASCT in our center. After eight BV courses, one patient was able to undergo match unrelated donor (MUD) SCT. Another seven pediatric HL patients, who were not able to go into remission with any other classical HL chemotherapy protocols, received 4-6 courses of BV-AVD and/or RICE/bendamustine. All were able to undergo ASCT after negative positron emission tomography (PET) imaging results. After ASCT, we switched to BV as consolidation therapy until a total of 12 cycles was completed. Patients went into remission after a median 34 (range: 12-42) months from the start of BV treatment. BV is an encouraging, well- tolerated, and effective targeted therapy especially when combined with AVD or when alternated with another targeted therapy combination, including RICE, when needed.

Selenium in the prevention of anthracycline-induced cardiac toxicity in children with cancer.

High cumulative doses of anthracyclines (300-500 mg/m(2)) used in the treatment of children with cancer may result in cardiotoxicity, a major long-term adverse effect that limits clinical usefulness of this class of chemotherapeutic agents. We assessed anthracycline-induced cardiotoxicity by measuring Pro-BNP levels and echocardiographic (ECHO) findings and investigated potential protective effect of selenium (Se) supplementation in a group of pediatric cancer patients. Plasma level of Pro-BNP was measured, and ECHO was performed in 67 patients (45 boys, 22 girls; ages 2-18 years; median age 12 years) after they completed anthracycline-containing chemotherapy. Serum Se level was measured in 37 patients. Eleven patients had high Pro-BNP levels and/or cardiac failure with Pro-BNP levels of 10-8,022 pg/mL (median 226.3 pg/mL; laboratory normal level is less than 120 pg/mL). Serum Se levels were low (20-129 mcg/L, median 62 mcg/L) in ten of these eleven patients. Eight of 10 patients with low Se and high Pro-BNP levels were supplemented with Se 100 mcg/day for a period of 4-33 months (median 6 months) which resulted in improvement in Pro-BNP and/or ECHO findings. These results suggest that Se supplementation may have a role in protection against anthracycline-induced cardiac toxicity.

Zinc and selenium status in pediatric malignant lymphomas.

Ninety-six untreated patients with malignant lymphoma (ML), 81 Hodgkin's disease, and 15 Burkitt's lymphoma were studied for zinc (Zn) status, and 21 patients also had selenium (Se) status analysis. Plasma and hair Zn and Se levels were measured by atomic absorption spectrophotometry. Chronic Zn and Se deficiencies (low plasma and low hair Zn and Se levels together) were found to be associated with ML in Turkish children. This was most likely due to the poor "nutritional environment" of the patients because majority of the ML patients were from families of low socioeconomic status. Supplementation of pediatric ML patients with Zn and Se, in addition to standard chemotherapy and radiotherapy regimen, is recommended.

Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation.

PURPOSE: To evaluate the causes of chemoreduction failure in retinoblastoma and to analyze the associated factors for eventual treatment with external beam radiotherapy and enucleation. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Seventy-one patients with 105 eyes with intraocular retinoblastoma that underwent chemoreduction therapy between October 1998 and January 2003. INTERVENTION: A 6-treatment cycle of chemoreduction therapy with vincristine, etoposide, and carboplatin was administered at monthly intervals. Unresponsive disease was defined as persistence of retinal tumors, vitreous seeds, or subretinal seeds after the second treatment cycle, with no appreciable sign of regression. Eyes with unresponsive disease were enucleated after the second treatment. Eyes that responded to chemoreduction therapy received focal treatment, including indirect laser photocoagulation, transpupillary thermotherapy, cryotherapy, and ruthenium 106 episcleral plaque radiotherapy after the second chemoreduction treatment, if necessary, to achieve complete tumor regression. Recurrence was defined as the regrowth of retinal tumors, vitreous or subretinal seeds after an initial favorable response, and regression. Recurrent retinal tumor, vitreous seeds, or subretinal seeds were treated with focal treatments and 2 to 3 additional chemoreduction treatments. When these methods failed or were not applicable, external beam radiotherapy and/or enucleation was administered. MAIN OUTCOME MEASURES: The use of external beam radiotherapy and enucleation for chemoreduction failure, which was defined as unresponsive or recurrent disease. RESULTS: The mean follow-up was 25.7 months (range: 6-49). Ten of 105 eyes (9.5%) with unresponsive disease were enucleated after the second treatment. Of the remaining 95 eyes, 42 (44.2%) developed recurrence after chemoreduction. Recurrent disease failing to be treated successfully by other methods was treated with external beam radiotherapy in 26 of 95 eyes (27.4%) and enucleation in 22 of 95 eyes (23.2%). External beam radiotherapy was successful in preventing enucleation in 20 of 26 eyes (76.9%). Overall, the globe salvage rate was 69.5%, ranging from 36.1% for Reese-Ellsworth group V disease to 87.0% for groups I to IV disease. Histopathologically, 29 of 31 enucleated eyes (93.5%) had poorly differentiated or moderately differentiated retinoblastoma. Using multivariate logistic regression analysis, factors predictive of eventual treatment with external beam radiotherapy were female gender (P = 0.010), presence of subretinal seeds (P = 0.023), and a greater number of chemoreduction treatments (P = 0.027). By multivariate analysis, the factors associated with the need for eventual treatment with enucleation were recurrence of retinal tumors (P = 0.004), presence of vitreous seeds (P = 0.008), greater tumor thickness (P = 0.015), presence of subretinal fluid (P = 0.040), and older patient age (P = 0.042). CONCLUSIONS: Chemoreduction failure in this article was defined as unresponsive or, more commonly, recurrent retinoblastoma. Older patient age, greater tumor thickness, presence of vitreous seeds and subretinal fluid at baseline, and retinal tumor recurrence after chemoreduction were factors associated with the need for enucleation.

Trace Element Analyses (Zinc and Selenium) in Pediatric Malignant Lymphomas.

Ninetysix untreated patients with Malignant lymphoma's, 81 Hodgkin's disease and 15 Burkitt's lymphoma were studied for zinc (Zn) and selenium (Se) status. Plasma and hair Zn, and Se levels were measured by atomic absorption spectrophotometry. Chronic Zn and Se deficiencies (low plasma and low hair Zn and Se levels together) were found to be associated with Malignant lymphoma's in Turkish children. This was most likely due to poor "nutritional environment" of the patients since majority of the Malignant lymphoma cases were from low socioeconomic class. Supplemention of the patients with physiological doses of Zn and Se, in addition to standard chemo radiotherapy regimen was proposed.