The role of three-component selective intra-arterial chemotherapy in the failure of standard organ-preserving treatment in children with intraocular retinoblastoma

Abstract

Introduction . Retinoblastoma (RB) is a malignant tumor of the retina, the survival rate for the intraocular form reaches 99 %. According to the researchers, the risk factors for the occurrence of refractory or recurrent forms of RB are the size of the tumor at primary diagnosis (more than 15 mm), the child s age at the onset of the disease (up to one year), bilateral RB, and the presence of subretinal and vitreal screenings. If methods of local destruction of the tumor are not applicable for the successful treatment of intraocular refractory or recurrent RB, then they resort to the second line of polychemotherapy as an alternative to enucleation. New versions of local chemotherapy and radiation therapy (gamma knife) are being developed and applied. Nowadays, researchers have a negative attitude towards traditional radiation therapy (EBRT) as a method of organ-preserving treatment due to serious consequences (asymmetry of the facial skeleton and second radio-induced tumors). Aim of the study — to increase the effectiveness of organ-preserving treatment in patients with refractory or recurrent intraocular RB. Materials and methods . In the period from 10.2018 to 12.2019 at the N.N. Blokhin National Medical Research Centre of Oncology it was received three-component selective intra-arterial chemotherapy (SIAC) in 15 patients (15 eyes) aged 11 to 52 months. Eyes initially affected by RB (n = 15), according to the IIRC (Murphree) classification, had the following groups: group B in 1 case, group C in 3, group D in 7, and group E in 4 eyes. It should be noted that all patients initially received intensive combined conservative therapy: in 11 (73 %) of 15 cases — systemic chemotherapy VEC; in 13 (86 %) of 15 — SIAC with melphalan, in all cases, additionally, two-component SIAC was used in combination with melphalan with topotecan. In some cases, local therapy in the form of intravitreal chemotherapy (IVIC) was added to the treatment of 6 (40 %) of 15 patients in the form of melphalan monotherapy and in one case (6 %) a doublet was used in combination with melphalan and topotecan. Also, in some patients, additional local ophthalmic therapy was used: transpupillary thermotherapy (TTT) in 6 out of 15 patients, including in combination with cryotherapy (CT) in 1 patient and in combination with brachytherapy (BT) in one case. At the same time, incomplete tumor regression (refractory form of the disease) was noted in 7 out of 15, and a recurrent course of the disease — in 8 out of 15 patients. Incomplete tumor regression and recurrent RB were the reasons for the appointment of a three-component SIAC using carboplatin, melphalan and topotecan, in combination with IVIC with pronounced endophytic growth of RB, as an alternative to irradiation and enucleation of the eye. Results . The average number of three-component SIAC courses was 1.46 ± 0.63 (rang 1—3). The combination of SIAHT with IVHT was performed in 3 out of 15 patients. All children (n = 15) are alive with a median period of follow-up of23.92 ± 15.68 (10—64) months. One in 15 patients was lost from observation due to their parents’ desire to be treated abroad. It is known that the child is alive, but there is no data on the condition of his eyes. 9 out of 14 patients needed additional treatment after SIAC intensification. To consolidate the resulting effect as a full regression in 2 cases, the final IVIC courses were conducted (n = 2). In connection with the presence of residual tumor and/or intraocular progression and/or appearance of new lesions in 1 of 9 patients were IVIC and TTT, 2 of 9 — IVIC, SIAC, CT, TTT. In 4 out of 9 cases, enucleation was performed, and in 2 out of 4 — the operation was performed after continuing the attempt of organ-preserving treatment: after CT and TTT (n = 1) and IVIC, CT, TTT and BT (n = 1). No child was given ERBT. There were no cases of stroke after SIAC. We managed to save 10 (71.4 %) of 14 eyes with visual acuity: object vision in 4 (40 %) out of 10, eye fixation in 3 (30 %) out of 10, and light perception in 3 (30 %) out of 10 cases. The average follow-up period from the end of three-component SIAC in 14 patients was 13.57 ± 5.27 (6—22) months. Conclusion . Thus, the three-component SIAC is effective and safe for patients with refractory and recurrent retinoblastoma, as evidenced by a high percentage of retained eyes and the presence of visual functions from light perception to object vision.