Recurrence and new tumor development after frontline intravenous chemotherapy for retinoblastoma: Risk factors and treatment results.

PURPOSE: To evaluate the risk factors leading to recurrence and new tumor (NT) development in patients with retinoblastoma after intravenous chemotherapy (IVC) and to review the treatment outcomes. MATERIALS AND METHODS: The records of 166 retinoblastoma cases (having 246 affected eyes) who underwent six-cycle IVC (vincristine, etoposide, and carboplatin) as primary treatment between October 1999 and August 2020 were reviewed retrospectively. RESULTS: The mean ages at presentation were 9.0 (median: 8.0) and 9.2 (median: 8.5) months in cases with recurrence and NTs respectively. Recurrence was detected in 40 (16.3%) eyes, NTs in 29 (11.8%), and both recurrence/NTs in 24 (9.8%). The mean time elapsed till recurrence and NT was 10.7 months. Multivariable analysis showed that the factors predictive of recurrence were largest tumor base diameter (LTBD) >12 mm (p = 0.039) and presence of subretinal seeds at diagnosis (p = 0.043). Multivariable risk factors for the development of NTs were bilateral familial retinoblastoma (p = 0.001) and presence of subretinal seeds at diagnosis (p = 0.010). Mean follow-up was 80.1 (median: 72.5) months. By Kaplan-Meier analysis, the 1-, 3-, and 6-year recurrence and NT rates were 21.2%, 28.1%, and 28.7% and 14.9%, 22.6%, and 23.9% respectively. The most common treatment methods used for recurrent and/or NTs included cryotherapy, transpupillary thermotherapy, and intra-arterial chemotherapy. Enucleation was eventually required in 24/93 (25.8%) eyes. No patient developed metastasis. DISCUSSION: Development of recurrence and/or NT after IVC was noted in 38% of all retinoblastoma eyes. Bilateral familial disease, LTBD >12 mm, and presence of subretinal seeds at baseline were risk factors for recurrence and NTs in this study.

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.