Management of Recurrence in Retinoblastoma Based on the Source of Tumor Cells

Abstract

Purpose: The aim was to study the characteristics of recurrence patterns in the form of scar recurrence, new lesions, and vitreous seeds which is necessary in anticipating future events for the management of retinoblastoma (RB).

Methods: This retrospective analytical observational study was conducted in a tertiary care hospital in South India; we included 64 eyes of 45 patients having RB from January 2019 to July 2020. The inclusion criterion was treatment-naïve patients with > 12 months of follow-up period. Recurrence patterns were defined as Pattern 1a and Pattern 1b: local and diffuse dissemination of vitreous seeds, respectively. Pattern 2: Scar recurrences: these are new tumor growths over chemoreduced lesions. Pattern 3: New lesions: local dissemination of subretinal seeds leading to new lesions elsewhere in the retina.

Results: A noncomparative analysis of 64 eyes of 45 patients having 108 lesions was studied; of which 28/45 (62.22%) were male and 17/45 (37.78%) were female. The mean time of presentation since the first clinical sign was 40 days (range: 10-180). The most common sign at presentation was leukocoria 42/64 (65.6%), followed by squint 4/64 (6.34%). Nineteen patients (42.22%) had bilateral RB, while 26 patients (57.78%) had unilateral RB. Primary enucleation was done for 19/26 eyes with advanced unilateral disease. Out of the total 32 eyes with subretinal tumor seeds at presentation, 17/32 eyes had a recurrence in the form of new lesions (Pattern 3) and 22/32 eyes had scar recurrence (Pattern 2). All of these 32 eyes were salvaged by local tumor consolidation methods. Recurrence due to vitreous seed dissemination was found in 18/64 eyes, in which diffuse dissemination (Pattern 1b) was present in 8/18 eyes (44.4%); all required enucleation even after local and systemic chemotherapeutic measures. Rest 10/18 eyes with local vitreous seeds (Pattern 1a) were cured at the end of the follow-up. Globe salvage was more with Pattern 1a rather than Pattern 1b even after additional intravitreal chemotherapy.

Conclusion: All eyes with Patterns 2 and 3 were salvaged at the end of follow-up with local tumor consolidation methods, while the globe salvage rate with Pattern 1 was poor even with multiple doses of intravitreal chemotherapy. The rate of successful treatment for managing these recurrence patterns depends on early identification by regular follow-ups with detailed retina examination.

Keywords: Recurrence patterns; retinoblastoma; subretinal seeds; vitreous seeds.

Figure 1

Fundus picture of the eye with asterisk showing multiple scar recurrences on regressed tumor sites and arrowhead showing new lesion away from primary site disseminating due to their adherence-independent properties and Patterns 2 and 3

Figure 2

Fundus picture of the eye on systemic chemotherapy with arrowheads showing diffuse vitreous seeds recurrence (Pattern 1b) due to widespread dissemination of tumor cells and asterisks showing new lesions on sites away from the primary lesion (Pattern 3)

Figure 3

Fundus pictures of scar recurrences (Pattern 2). (a and c) Images with green asterisk showing regression after systemic chemotherapy, (b and d) showing white arrowheads are recurrences few months after the completion of systemic chemotherapy because of the persistence of subretinal tumor seeds due to failure of chemotherapy drugs to reach adequate mitotoxic levels (later on managed by local thermotherapy)

Figure 4

Image (a) showing three tumor lesions, image (b) showing respective scar sites after systemic chemotherapy while image (c) with arrowhead shows tumor recurrence on the margin of the scar seen 5 months after the completion of systemic chemotherapy, which was later on managed by transpupillary thermotherapy (Pattern 2)

Figure 5

Images (a and b) showing diffuse vitreous seed recurrence (Pattern 1b), while image (c) showing focal vitreous seed recurrence (Pattern 1a) around the localized area of the tumor

Figure 6

Flowchart of the classification system of recurrence patterns of retinoblastoma based on the source of tumor seeds with their outcomes and management. TTT: Transpupillary thermotherapy, ICG: Indocyanine green, EUA: Examination under anesthesia

Figure 7

Classification system of recurrence patterns of retinoblastoma based on the source of tumor seeds