Survival and ocular preservation in a long-term cohort of Japanese patients with retinoblastoma

Tetsuro Ueda ,Koh Hei Sonoda ,Mitsuo Tanabe ,Yoshinao Oda,Hiroaki Ono,Shunji Hasegawa,Takuya Ichimura,Yuhki Koga,Hiroshi Yoshikawa,Utako Oba,K Yamana ,Tetsuko Kobayashi,Shigenobu Suzuki,Yasunari Sakai,Kentaro Nakashima,Hideki Nakayama,Wakako Kato,Tsuyoshi Yoshitake ,Shouichi Ohga

doi:10.1186/s12887-020-1923-7

Abstract

BackgroundRetinoblastoma is an ocular tumor in infants with cancer predisposition. Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM).MethodsWe studied the outcomes of all patients with retinoblastoma at a tertiary center in 1984–2016, when preservation method changed from radiotherapy (1984–2001) to systemic chemotherapy (2002–2016).ResultsOne-hundred sixteen infants developed unilateral- (n = 77), bilateral- (n = 38), or trilateral-onset (n = 1) tumor. Ten (8.6%) had a positive family history, despite a few studies on RB1 gene. Contralateral disease occurred in one unilateral-onset case. One-hundred eight of 155 eyes (70%) were enucleated. Nine binocular survivors were from 5 bilateral- and 4 unilateral-onset cases. Two survivors received bilateral enucleation. Six deaths occurred; brain involvement (including 3 trilateral diseases) in 4 bilateral-onset, systemic invasion in a unilateral-onset, and SPM (osteosarcoma) in a bilateral-onset case(s). Two others survived SPM of osteosarcoma or lymphoma. The 10-year overall survival (OS: 98.5% vs. 91.3%, p = 0.068) and binocular survivors (13.2% vs. 5.2%, p = 0.154) between bilateral- and unilateral-onsets did not differ statistically. The 10-year OS and cancer (retinoblastoma/SPM)-free survival (CFS) rates of all patients were 94.9 and 88.5%, respectively. The proportion of preserved eyes did not differ between radiotherapy and chemotherapy eras. The CFS rate of bilateral-onset cases in systemic chemotherapy era was higher than that in radiotherapy era (p = 0.042). The CFS rates of bilateral-onset patients with neoadjuvant chemotherapy (upfront systemic therapy for preservation) was higher than those without it (p = 0.030).ConclusionsSystemic chemotherapy and local therapy raised OS and binocular survival rates of bilateral-onset patients similarly to those of unilateral-onset patients. All but one death was associated with a probable germline defect of the RB1 gene. Neoadjuvant stratified chemotherapy may support the long-term binocular life with minimized risk of SPM.

Highlights

Retinoblastoma is an ocular tumor in infants with cancer predisposition
Non-surgical control became the mainstay for ocular preservation after 1980, in order to reduce the risk of late complications and second primary malignancy (SPM) after external beam radiotherapy [3]
To search for better practices for retinoblastoma, we retrospectively studied the final outcomes of patients in our tertiary institution over three decades, focusing on the survival and ocular preservation of survivors

Summary

Introduction

Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM). Retinoblastoma, which is the most common intraocular tumor of childhood, arises from a mutation in RB1 [1]. It usually affects young infants; the worldwide incidence of one case per 15,000–20,000 live births [2]. The first goal in the treatment of retinoblastoma is to prevent extraocular invasion and metastasis of the primary tumor. In developing countries, this tumor is still diagnosed at an advanced stage [9]. There is little information on the late effects of systemic chemotherapy on mortality and morbidity along with the risk of developing SPM in association with a germline mutation of RB1

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Results

Conclusion