Correlation of Technical and Adjunctive Factors with Quantitative Tumor Reduction in Children Undergoing Selective Ophthalmic Artery Infusion Chemotherapy for Retinoblastoma

Abstract

BACKGROUND AND PURPOSE: Selective ophthalmic artery infusion chemotherapy has improved ocular outcomes in children with retinoblastoma. Our aim was to correlate quantitative tumor reduction and dichotomous therapeutic response with technical and adjunctive factors during selective ophthalmic artery infusion chemotherapy for retinoblastoma. An understanding of such factors may improve therapeutic efficacy. MATERIALS AND METHODS:All patients with retinoblastoma treated by selective ophthalmic artery infusion chemotherapy at a single center during a 9-year period were reviewed. Only first-cycle treatments for previously untreated eyes were studied. Adjunctive factors (intra-arterial verapamil, intranasal oxymetazoline external carotid balloon occlusion) and technical factors (chemotherapy infusion time, fluoroscopy time) were documented by medical record review. Quantitative tumor reduction was determined by blinded comparison of retinal imaging acquired during examination under anesthesia before and 3-4 weeks after treatment. The dichotomous therapeutic response was classified according to quantitative tumor reduction as satisfactory ($ 50%) or poor (,50%).RESULTS: Twenty-one eyes met the inclusion criteria. Patients ranged from 2 to 59 months of age. Adjuncts included intra-arterial verapamil in 15, intranasal oxymetazoline in 14, and external carotid balloon occlusion in 14. Quantitative tumor reduction ranged from 15% to 95%. Six showed poor dichotomous therapeutic response. A satisfactory dichotomous therapeutic response was correlated with intra-arterial verapamil (P = .03) in the aggregate cohort and in a subgroup undergoing treatment with single-agent melphalan at a dose of ,5 mg (P ¼ .02). In the latter, higher average quantitative tumor reduction correlated with intra-arterial verapamil (P , .01).CONCLUSIONS: Intra-arterial verapamil during selective ophthalmic artery infusion chemotherapy is correlated with an improved therapeutic response, particularly when treating with lower doses of single-agent melphalan.ABBREVIATIONS: CIT ¼ chemotherapeutic infusion time; DTR ¼ dichotomous therapeutic response; ECBO ¼ external carotid artery balloon occlusion; FT ¼ fluoroscopy time; IAV ¼ intra-arterial verapamil; INA ¼ intra-nasal Afrin; OA ¼ ophthalmic artery; SOAIC ¼ selective ophthalmic artery infusion chemotherapy; QTR ¼ quantitative tumor reduction

Ocular survival after intra‐arterial chemotherapy for retinoblastoma improves with accrual of experience and programmatic evolution

“…40,41 Moreover, the nebulous effect of operator experience and collaboration among the multidisciplinary team, in addition to a relative lack of literature concerning technical factors promoting efficacy, lead to global disparities in management approach and knowledge. 37 The greatest Rb burden falls on lower and lower middle-income countries where realistic goals in improving survival and eye preservation typically focus on increasing screening of children with familial Rb, retaining families in the healthcare system, and promoting treatment adherence. 42 In some middle-and high-income countries (representing approximately 53% of new cases annually), 43 eye-preserving strategies have been increasingly used, though related adverse effects, comorbidities, and historically lower ocular salvage for more advanced eyes (groups D and E) leave room for improvement.…”

“…56,57 We have previously reported that TBO of the ECA is a safe and effective method for optimizing ocular hemodynamics with the intended effect of increasing treatment response. 31,37 Others have reported successful application of the bIAC technique. 58 Alternately, reports have described the use of cyanoacrylate-based embolization of ECA collaterals, 59 or selective occlusion of the middle meningeal artery to modulate ocular circulation.…”

“…Endotracheal albuterol was administered to mitigate procedure-related bronchospasm as previously reported. 31,[35][36][37] Most patients received intranasal oxymetazoline to prevent chemotherapy delivery to ethmoidal anastomoses between the sphenopalatine artery and ophthalmic artery. 17 After 2012, all patients undergoing IAC received intraarterial verapamil administered to the ipsilateral internal carotid artery and ophthalmic arteries to reduce arterial vasospasm and promote anterograde blood flow.…”

“…17 After 2012, all patients undergoing IAC received intraarterial verapamil administered to the ipsilateral internal carotid artery and ophthalmic arteries to reduce arterial vasospasm and promote anterograde blood flow. 37 To optimize hemodynamics within the ophthalmic artery, nearly all procedures after 2013 utilized a technical variation termed balloonassisted intra-arterial chemotherapy (bIAC), 31 which utilizes a balloon occlusion catheter introduced at the contralateral femoral artery and advanced to the ipsilateral ECA. Once positioned proximal to the origin of the facial artery, the catheter-mounted balloon is inflated, and flow cessation of the ECA is confirmed by digital subtraction angiography or fluoroscopic monitoring of contrast media injected into the common carotid artery.…”

“…Lower pressure within the ECA after occlusion predictably improves anterograde flow through the ophthalmic artery and promotes more complete delivery of the chemotherapy dose to the choroidal and retinal circulation. 31,37 IAC technical success was defined as complete delivery of the chemotherapy dose to the ophthalmic artery with angiographic evidence of sustained and robust anterograde flow.…”