Intra-arterial Chemotherapy for Retinoblastoma: Real-world Experience.

BACKGROUNDIntra-arterial chemotherapy (IAC) has become a first-line standard treatment for retinoblastoma (RB). However, studies describing its adverse events are sparse, especially from the developing world. Our study described the outcomes and adverse events from a single center in South India.AIMTo describe the challenges, treatment outcomes, and complications of selective IAC for RB in Indian eyes.METHODSThis study was a single center, retrospective study that included 17 patients with RB who underwent IAC using melphalan (5/7.5 mg) and topotecan (1/2 mg) (n = 12) or melphalan (5 mg) alone (n = 3) or triple therapy that included carboplatin (30 mg) along with these drugs (n = 2) between January 2018 and December 2023. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seed control, complications, and globe salvage rates.RESULTSOut of the 17 patients, 11 were diagnosed with unilateral RB and 6 were diagnosed with bilateral RB. The mean age at the time of diagnosis was 19.8 months. The mean interval between the first symptom and presentation was 6.5 months. IAC was employed as the primary (n = 9) or secondary (n = 8) modality of treatment. Each eye received a mean of 1.5 IAC sessions (median: 1 session; range: 1-3 sessions). Eyes were classified according to the international classification of RB as group B (n = 5), group C (n = 1), group D (n = 4), and group E (n = 7). Following IAC, complete regression of the main tumor was seen in 15 eyes (88%) and partial regression in 2 eyes (12%). Globe salvage was achieved in 15 eyes (88%). Adverse effects included vitreous hemorrhage (n = 3), rhegmatogenous retinal detachment (n = 2), choroidal ischemia (n = 1), isolated subretinal hemorrhage (n = 2), retinal pigment epithelium degeneration (n = 2), forehead pigmentation (n = 1), third nerve palsy with complete ptosis (n = 1), and 30-degree exotropia (n = 1). The mean follow-up period was 28.6 months (median: 24 months, range: 1–72 months).CONCLUSIONIAC is an effective way to control RB and globe preservation. In the Indian context we encountered many challenges highlighting the importance of case selection. Further studies in India are required to thoroughly understand IAC as a treatment for RB.

Background: There are limited reports of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) from developing world. Objectives: In this study, we report our 4-year experience of IAC for RB from India. Methods: Retrospective, interventional case series. Primary outcome measures included tumor regression, vitreous seeds and subretinal seeds control, and globe salvage. Secondary outcome measures were best-corrected visual acuity and treatment complications. Results: Fifteen eyes underwent 53 IAC procedures over mean 28.6 ± 13.8 months (range 10–51 months). IAC was employed as primary (n = 6) or secondary (n = 9) chemotherapy. Following IAC, complete regression of main tumor was seen in 7 eyes (47%) and partial regression in 3 (20%) eyes. Enucleation was done in 5(33%) eyes. Globe salvage rates were achieved in 1 eye (100%) in group B, 2 eyes (67%) in group C (n = 3), 6 eyes (67%) in group D (n = 9), and 1 eye (50%) in group E (n = 2). Following IAC, Kaplan-Meier survival curve showed 93% globe survival rate at 1 year, 76% at 2 years, and 66% at 3, and 4 years. Conclusion: IAC has enhanced globe salvage rates in eyes with RB. Multicenter studies with longer follow-up are necessary to better understand outcomes in the long term.

Purpose:Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB) however, little information exists regarding its use in older patients (>5 years). In the present study, we evaluate the use of IAC (2008–2018) for RB in older patients and compare the outcomes to those in the prechemotherapy (<1994) and intravenous chemotherapy (IVC) (1994–2007) eras.Methods:A retrospective analysis of all patients older than 5 years treated with IAC for RB from 2008–2018. Comparisons were made to 26 active RB cases in older children treated in the prechemotherapy era and to 12 active RB cases treated in the IVC era.Results:There were 13 eyes with RB in 13 older patients treated in the IAC era. The median patient age was 6.8 years. Tumor response was achieved in all 13 eyes at a median interval of 1.1 months from first IAC. Globe salvage was achieved in eight eyes with five eyes requiring enucleation. At 14 months, median follow-up after IAC, there was no metastasis or death. Compared to the prechemotherapy era, those in the IAC era demonstrated significant reduction in need for enucleation (P < 0.001) and EBRT or enucleation (P < 0.001). Compared to the IVC era, there was significant reduction in need for EBRT (P = 0.02) and EBRT or enucleation (P = 0.03) and similar avoidance of metastasis (P > 0.99) and death (P > 0.99).Conclusion:Older patients with RB managed in the IAC era demonstrated reduced need for EBRT or enucleation compared to those managed in the IVC or prechemotherapy eras, with no instance of metastasis or death.

We aimed to analyze our 4-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) and to examine the tumor response, globe salvage, mortality, and safety profile of IAC in the Malaysian profile. This was a retrospective, interventional case series. A total of 22 eyes of 20 patients with RB who underwent IAC using melphalan and topotecan from January 2018 to December 2021 in Hospital Kuala Lumpur were retrospectively reviewed. Tumor response, globe salvage, mortality, and safety profile of IAC were compared based on the International Classification of Retinoblastoma. The mean patient age at IAC was 21.3 months. An overall globe salvage rate of 63.6% was observed: more specifically, 100% for Group A, 75% for Groups B and C, 66.7% for Group D, and 42.9% for Group E. Poor tumor response after IAC was significantly associated with a lesser chance of globe salvage (P = 0.045). The overall rate of good tumor response following IAC was 77.3%. Specifically, rates of good tumor response in each group were 100%, 75%, 75%, 83.3% and 71.4% in group A, B, C, D and E, respectively. The mortality rate was 5%. Complications (per-catheterization) included cerebral infarct (2.2%), oxygen desaturation (2.2%), vomiting (26.1%), periorbital edema (8.8%), ptosis (6.5%), fever, femoral hematoma, and hyperpigmentation over lid (4.4% each). Four-year experience showed that IAC is a safe and effective method for RB management. Patients with a poor response after IAC may have a lower chance of globe salvage. Careful patient selection is of utmost importance to achieve the best outcome in a setting of limited health-care resources.

We congratulate the authors on an expounded study on intra-arterial chemotherapy (IAC) for retinoblastoma (RB) published in your esteemed journal.[1] Although the authors write an illustrative series, we believe that there are certain questions unanswered on the topic. In the handful of studies on IAC for RB, the rate of successful catheterization reported is 98%.[2] Did the authors ever find the ophthalmic artery inappropriate for selective catheterization? What were the alternative routes taken if the ophthalmic artery was not fully developed, or if the access from the internal carotid artery was too acute? Did the authors document the visual acuity or encounter any case of foveal/choroidal atrophy? Long-term visual outcomes after intravenous chemotherapy (IVC) are well known, but despite the efficacy of the IAC; we are yet unaware of its visual outcomes. Could the potentially high dose of focused chemotherapy be causing more ischemic complications leading to an overall poor visual outcome despite a globe salvage? The protocols followed for advanced RB are imprecise, largely influenced by personal choice and technical resources. Since the patients received 1–11 cycles of IVC, the indications of IAC are not reflected from the study. Only two cases treated by authors were unilateral, but we should remember that unilateral nongermline advanced diseases are best treated by IAC.[2] Furthermore, the authors were unable to compare the outcomes of primary and secondary IAC due to smaller numbers. Successfully running a separate RB clinic for the past 20 years,[3] we share our experience in IAC for RB in Table 1. Although literature does not address this issue, three patients developed new lesions after IAC in our series.Table 1: Details of patients receiving intra-arterial chemotherapyWe endorse IAC in selective cases of RB but until well-established indications are laid down; we should use this modality with caution. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Intra-arterial chemotherapy for retinoblastoma in 341 consecutive eyes (1,292 infusions): comparative analysis of outcomes based on patient age, race, and sex

Aim:To describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC) for retinoblastoma (RB) in Indian eyes.Materials and Methods:Single center, retrospective interventional case series of 6 eyes with RB who underwent IAC using Melphalan (3 mg/5 mg/7.5 mg) and topetecan (1 mg) (n = 4) or melphalan (3 mg/5 mg/7.5 mg) alone (n = 2) between December 2013 and June 2014. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seeds control and globe salvage rates.Results:IAC was employed as primary (n = 1) or secondary (n = 5) modality of treatment. Each eye received mean 3 IAC sessions (median: 3; range: 1-4 sessions). Eyes were classified according to international classification of RB as Group B (n = 1), C (n = 1), D (n = 2) and E (n = 2). Following IAC, complete regression of the main tumor was seen in 3 cases (50%), partial regression in 2 (33%), while 1 case (15%) showed no response. Of 4 eyes with subretinal seeds, 1 (25%) eye had complete regression while 3 (75%) eyes had partial regression. Of 5 eyes with vitreous seeds, 2 (40%) eyes had complete regression while 3 (60%) eyes had a partial response. Globe salvage was achieved in 5 of 6 eyes (83%). Diffuse choroidal atrophy and vitreous hemorrhage were observed in 1 (17%) eye, each. No hematologic toxicity or cerebro-vascular events were observed. Mean follow-up period was 5.5 months (median: 6 months, range: 1-6 months).Conclusion:IAC is an effective therapy for globe preservation in eyes with RB. Larger studies with longer follow-up are required to validate these results.

Aim: The aim of this study is to describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC) for intraocular retinoblastoma (RB). Materials and Methods: A retrospective, interventional series of 10 eyes with RB which underwent IAC using melphalan (5 mg/7.5 mg) and topotecan (1 mg), or melphalan (5 mg/7.5 mg) alone. Treatment outcomes were evaluated in terms of tumor control, vitreous seeds (VS) and subretinal seeds (SRS) control, and globe salvage rates. Results: Ten eyes of 10 patients underwent 38 IAC sessions (mean = 3.8; median = 4; range = 3–5 sessions). Following IAC, complete regression of main tumor was seen in 9 eyes (90%) and partial regression in 1 (10%). All four eyes with SRS showed complete regression (100%). Of 5 eyes with VS, 3 eyes (60%) showed complete regression, 1 eye (20%) showed relapse, while 1 eye (20%) showed no response. Globe salvage was achieved in 8 of 10 eyes (80%). Complications included transient ophthalmic artery narrowing (n = 2), branched retinal vein occlusion (n = 1), forehead skin pigmentation (n = 1), and vitreous hemorrhage (n = 2). There was no case of stroke, hemiplegia, metastasis, or death. Transient hematological changes included relative pancytopenia (n = 4), relative leukopenia (n = 5), and relative thrombocytopenia (n = 4). Mean follow-up was 26 months (median = 28, range = 13–36) from the initiation of first IAC. Conclusions: IAC is an effective therapy for globe preservation in eyes with intraocular RB, in the setting of a developing country like India. Larger studies with longer follow-up are required to validate these results.

Aim:The aim of this study is to describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC) for intraocular retinoblastoma (RB).Materials and Methods:A retrospective, interventional series of 10 eyes with RB which underwent IAC using melphalan (5 mg/7.5 mg) and topotecan (1 mg), or melphalan (5 mg/7.5 mg) alone. Treatment outcomes were evaluated in terms of tumor control, vitreous seeds (VS) and subretinal seeds (SRS) control, and globe salvage rates.Results:Ten eyes of 10 patients underwent 38 IAC sessions (mean = 3.8; median = 4; range = 3–5 sessions). Following IAC, complete regression of main tumor was seen in 9 eyes (90%) and partial regression in 1 (10%). All four eyes with SRS showed complete regression (100%). Of 5 eyes with VS, 3 eyes (60%) showed complete regression, 1 eye (20%) showed relapse, while 1 eye (20%) showed no response. Globe salvage was achieved in 8 of 10 eyes (80%). Complications included transient ophthalmic artery narrowing (n = 2), branched retinal vein occlusion (n = 1), forehead skin pigmentation (n = 1), and vitreous hemorrhage (n = 2). There was no case of stroke, hemiplegia, metastasis, or death. Transient hematological changes included relative pancytopenia (n = 4), relative leukopenia (n = 5), and relative thrombocytopenia (n = 4). Mean follow-up was 26 months (median = 28, range = 13–36) from the initiation of first IAC.Conclusions:IAC is an effective therapy for globe preservation in eyes with intraocular RB, in the setting of a developing country like India. Larger studies with longer follow-up are required to validate these results.

Intra-arterial Chemotherapy for Retinoblastoma in 70 Eyes: Outcomes Based on the International Classification of Retinoblastoma

Intravenous versus super-selected intra-arterial chemotherapy in children with advanced unilateral retinoblastoma: an open-label, multicentre, randomised trial.

AimTo report our first three-and-a-half years’ experience with intra-arterial chemotherapy (IAC) in managing retinoblastoma (RB).MethodsSingle institution, retrospective, interventional case series of 14 retinoblastoma patients managed with IAC from December 2014 to June 2018. Demographics were described. Outcomes measures were tumor response, treatment complications and globe salvage.ResultsSubjects’ mean age at the first administration of IAC was 31.4 months. 57.1% of the eyes were Group D and E retinoblastoma, while 79% were bilateral disease. 93% of the eyes were as secondary treatment. Of 32 IAC cannulations performed, 23 (71.8%) were successful and received chemotherapy drug melphalan. Each eye received a mean of 1.8 (range 1–4) IAC injections. 53% of the eyes showed regression post treatment. After a mean follow up period of 19 months, globe salvage rate was 38%. Most of the adverse effects experienced were localized and transient.ConclusionIAC has provided an added recourse in the armamentarium of retinoblastoma treatment in our center. IAC treatment is a viable alternative in the treatment of retinoblastoma to salvage globe, for eyes that would conventionally require enucleation especially in bilateral disease.

10062 Background: Retinoblastoma (RB) is the most common childhood eye tumor. Intraocular RB cure rates approach 100%. Therefore, treatment now focuses on globe salvage and preserving functional vision. The Research into Visual Endpoints and RB Health Outcomes After Treatment (RIVERBOAT) consortium was established to examine patient outcomes in the transitional era from systemic to intraocular therapy. Methods: Patients with RB treated at 13 North American centers from 2008-2022 were identified. Medical record abstraction was performed for disease presentation, visual acuity, treatment, globe salvage and functional outcome. Enrollment on the study included submission of retrospective data and prospective data on newly diagnosed patients as well as retrospective data from chart reviews. Results: 830 patients (68% white race, 77% non-Hispanic ethnicity) were enrolled. In 420 of these, data was limited to chart review. Median age at diagnosis of the 830 patients (1165 eyes) was 1 year (0 - 16.3) and at enrollment was 7.8 years (0 - 28.6). 60% had unilateral disease and the eye group distribution (International Intraocular Retinoblastoma Classification) was 10% A, 16% B, 12% C, 31% D, 27% E, and 4% unknown (UK). Of the 1165 affected eyes, major treatment modalities included primary enucleation (15%), systemic chemotherapy (SC) (36%), intraarterial chemotherapy (IAC) (10%), SC followed by IAC in 9%, and intravitreal chemotherapy in combination in 6%. SC only was used in 55-59% of those with A-C eyes compared to 29% of D eyes. IAC only was used in 20% of D eyes and 16% of C eyes. Secondary enucleation occurred in 151 eyes (14%): 63/416 (15%) of SC; 34/120 (28%) of IAC; 25/106 (24%) of SC followed by IAC; 29/523 (6%) other treatments. The overall globe salvage rate was 86%. Second malignancies occurred in 5, metastatic disease in 8 and pineoblastoma in 3 patients. Eleven patients died of RB (1%). Visual acuity after treatment was reported in 229 eyes: 106 (eye group 24 A, 37 B, 22 C, 19 D, 3 E, 1 UK) had normal vision (20/20-20/40). 38 eyes, (6 A, 11 B, 4 C, 10 D, 5 E, 2 UK) had moderate vision loss ( &gt; 20/40 – 20/70). Twenty-five eyes (5 B, 2 C, 16 D, 2 E) had low vision ( &gt; 20/70 &lt; 20/200), and 60 eyes (12 B, 7 C, 32 D, 8 E, 1 UK) were legally blind (&gt;20/200). In those treated with IAC only, normal vision was found in 30% of eyes, moderate vision loss in 22%, low vision in 13%, and legal blindness in 35%. In those treated with SC only, normal vision was noted in 53% of eyes, moderate vision loss in 11%, low vision in 11%, and legal blindness in 25%. In those treated with SC followed by IAC, normal vision was reported in 32%, moderate vision in 26%, low vision in 5% and legal blindness in 37%. Conclusions: We demonstrate the significant benefits witnessed by the evolution of RB therapy. Cure rates remain high, with a very low incidence of second malignancies, metastatic disease or trilateral RB. Eye salvage rate was excellent, avoiding low vision or legal blindness in two-thirds of the patients.

Intra-arterial Chemotherapy for Retinoblastoma: Experience Matters but Risks Remain

Simple SummaryIntravenous chemoreduction (IVCRD) has been the standard of care for treatment of retinoblastoma (RB). Since survival rates exceed 95–98%, the goals of treatment have now shifted to emphasize eye salvage and vision preservation in addition to patient survival. Consequently, there has been a shift towards combining standard IVCRD with intravitreal chemotherapy or altogether replacing IVCRD with intra-arterial chemotherapy. As more data from intravitreal chemotherapy and intra-arterial chemotherapy are being published, there are claims of improved globe salvage rates resulting in more widespread use of these newer treatment modalities. However, there are no published randomized controlled trials comparing these to IVCRD head-to-head. To evaluate the relative efficacy of these new therapies, it is critical to determine the true success rates of IVCRD regimens alone. Therefore, it is both timely and essential to determine the baseline IVCRD success rates so that an evidence-based assessment of new and emerging therapies can be determined.To evaluate the relative efficacy of novel retinoblastoma treatments, eye classification-specific success rates for current standard-of-care intravenous chemotherapy regimens must be known. This meta-analysis included studies if: (1) patients received intravenous chemotherapy for retinoblastoma, (2) globe salvage data was reported, (3) only intravenous chemoreduction (with/without local consolidation) was used. The outcome measure was globe salvage success without need for salvage radiotherapy, subdivided by disease classification and chemotherapy regimen. Data from 27 studies (1483 eyes) were pooled. By Reese–Ellsworth classification, globe salvage rates were 85% (95%CI:73–92%) for Group I, 78% (95%CI:70–85%) for Group II, 68% (95%CI:56–78%) for Group III, 47% (95%CI:34–60%) for Group IV, and 35% (95%CI:26–45%) for Group V (Va: 35% [95%CI:21–54%]; Vb: 42% [95%CI:29–56%]; those without sub-classification: 31% [95%CI:19–47%]). By International Classification, globe salvage rates were 93% (95%CI:80–97%) for Group A, 83% (95%CI:73–89%) for Group B, 73% (95%CI:54–86%) for Group C, 40% (95%CI:31–51%) for Group D, and 19% (95%CI:5–50%) for Group E. Standard carboplatin-etoposide-vincristine out-performed two-drug regimens (odds ratio (OR) = 1.9 (95%CI:1.3–3.0) for Groups I-IV and OR = 2.1 (95%CI:1.3–3.4) for Group V; p = 0.002 for each). For eyes with diffuse vitreous seeds (Vb), an enhanced regimen out-performed standard chemotherapy (OR = 2.4 [95%CI:1.3–4.7]; p = 0.004). In conclusion, two-drug regimens were less effective for all eyes, whereas enhanced regimens were more effective for eyes with vitreous seeds. Novel therapies can now be compared to these baseline globe salvage rates.