Unifocality as Prognostic Factor for Unilateral Retinoblastoma: Preliminary Results of 32 Eyes Treated with Intra-Arterial Chemotherapy Alone Factor for Unilateral Retinoblastoma: with

treatments allow good eye preservation rates and decrease the indications for external beam radiation (possible cause of second tumors in the irradiation area and beyond) but are not free of ocular and systemic toxicity. In order to improve ARTICLE INFO as Prognostic Preliminary Results of 32 Eyes Treated Intra-Arterial Chemotherapy Alone. Biomed J Sci Tech Res 38(4)-2021. Abbreviations: Diffusion Purpose: To evaluate the role of intra-arterial chemotherapy (IAC) in the management of unilateral, unifocal retinoblastoma (RB) as a single therapy, associated to neither focal nor systemic adjunctive therapies. Methods: Prospective, single center, interventional case series of 32 consecutive eyes diagnosed with unilateral unifocal RB and treated exclusively with selective ophthalmic intra-arterial chemotherapy, with no adjunctive systemic or focal treatments. Results: Full regression of the lesion was observed in 30 eyes (93.75%). 2 eyes were enucleated. Ophthalmoscopic remissions type I and III with higher calcific component were achieved. Additionally, neither recurrences nor new tumors appeared during the patient follow-up, which ranged from 10 months to 13 years. Conclusion: Selective intra-arterial chemotherapy has demonstrated to be highly effective in terms of disease control and anatomical preservation in case of unilateral unifocal disease, without requiring any additional systemic and/or focal therapy.


Introduction
Retinoblastoma (RB) is the most common intraocular malignancy of in childhood. Approximately 60% of cases are unilateral while 40% are bilateral. With respect to gender distribution, there is male predominance 1.2:1 with survival rate ranging from 86-92%. It is generally diagnosed in patients at an average age of 18 months, with 90% cases diagnosed younger than 5 years of age [1,2]. With recent advances in research and clinical trials, there has been a paradigm shift in the treatment protocols of RB. Enucleation is required for extensive RB. Initial treatment can be conservative when preservation of residual visual function, even minimal, appears to be possible. It usually comprises neoadjuvant Intravenous Chemotherapy (IVC) followed by local treatments of each tumor (Laser, Thermotherapy, Cryotherapy, Plaque radiotherapy) [3]. These treatments allow good eye preservation rates and decrease the indications for external beam radiation (possible cause of second tumors in the irradiation area and beyond) but are not free of ocular and systemic toxicity. In order to improve the efficacy of intraocular penetration of the chemotherapeutic agents and therefore local tumor control, it has been proposed to administer chemotherapy via the intra-arterial route directly into the ophthalmic artery [4,5]

Results
A total of 32 eyes from 32 patients were examined and treated.
All 32 eyes were treatment-naïve. No family history was referred. 6 cases out of 32 (18.75%) were de novo mutations. ABC classification of RB was used to assess the stage of the disease. Among thirty two eyes, 11 (31.25%) were diagnosed stage B, 4 (12.5%) were stage C, 8 (25%) stage D and 9 (28.12%) were stage E. Most of the lesions were localized at the posterior pole, while the others were localized in peripheral retina and only 1 (3%) was iuxtapapillary. Vitreous seeding, subretinal seeding and both vitreous plus subretinal seeding were present in respectively 5 (15.62%), 3 (9.37%) and 2 (6.25%) patients (Table 1) (Table 1). Most of the patients received 3 or more infusions (mean number 4.2, range 2 to 6). Full regression of the lesion was observed in 30 eyes (93.75%). Complete regression was seen in 30 eyes (93.75%).   2 infusions, remission pattern type I C.
Eyelid edema, frontal rush and D.
Permanent skin scar.

Discussion
New therapeutic paradigms significantly improved the chances of anatomical and, often, functional preservation of the globe even with advanced stage diseases [7][8][9]. The introduction of selective for eyes with subretinal and vitreous seeding, with the majority of patients receiving 3 or less cycles of IAC with one to three drugs [11]. This globe retention rates may be partially explained by the fact that 61% of the eyes had previous treatments. The lower responsiveness to IAC of previously-treated RB has been described by several authors [11,12]

Conclusion
Choosing the proper therapeutic approach in patients with RB could be challenging, with multiple factors to be considered. If on one hand the main goal remains life salvage, we can't forget the importance of anatomical and/or functional preservation and the impact of this disease, and of course of the treatment procedures, on the quality of life of the little patient and his/her family. From our experience it comes to light a more favorable prognosis in case of unilateral unifocal RB which may be related to peculiar histological/genetic features, explaining the greater sensitivity to selective chemotherapy delivery. The hope for the future is to customize the treatment protocol basing on the combination of clinical, neuro-radiological and genetic/epigenetic parameters [17] in order to rise the efficacy of therapeutic procedures, reduce overtreatment and its impact on patient's and parent's quality of life [18,19].