Delayed Enucleation With Neoadjuvant Chemotherapy in Advanced Intraocular Unilateral Retinoblastoma: AHOPCA II, a Prospective, Multi-Institutional Protocol in Central America

Abstract

PURPOSE Treatment abandonment because of enucleation refusal is a limitation of improving outcomes for children with retinoblastoma in countries with limited resources. Furthermore, many children present with buphthalmos and a high risk of globe rupture during enucleation. To address these unique circumstances, the AHOPCA II protocol introduced neoadjuvant chemotherapy with delayed enucleation. PATIENTS AND METHODS Patients with advanced unilateral intraocular disease (International Retinoblastoma Staging System [IRSS] stage I) were considered for upfront enucleation. Those with diffuse invasion of the choroid, postlaminar optic nerve, and/or anterior chamber invasion received six cycles of adjuvant chemotherapy (vincristine, carboplatin, and etoposide). Patients with buphthalmos and those with a perceived risk for enucleation refusal and/or abandonment were given two to three cycles of chemotherapy before scheduled enucleation followed by adjuvant chemotherapy to complete six cycles, regardless of pathology. RESULTS A total of 161 patients had unilateral IRSS stage I disease; 102 underwent upfront enucleation, and 59 had delayed enucleation. The estimated 5-year abandonment-sensitive event-free and overall survival rates for the group were 0.81 ± 0.03 and 0.86 ± 0.03, respectively. The 5-year estimated abandonment-sensitive event-free survival rates for patients undergoing upfront and delayed enucleation were 0.89 ± 0.03 and 0.68 ± 0.06, respectively ( P = .001). Compared with AHOPCA I, abandonment for patients with IRSS stage I retinoblastoma decreased from 16% to 4%. CONCLUSION AHOPCA describes the results of advanced intraocular retinoblastoma treated with neoadjuvant chemotherapy. In eyes with buphthalmos and patients with risk of abandonment, neoadjuvant chemotherapy can be effective when followed by enucleation and adjuvant chemotherapy. Our study suggests that this approach can save patients with buphthalmos from ocular rupture and might reduce refusal of enucleation and abandonment.

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

“…Chemotherapy-related toxicity is one of the major concerns in the treatment of pediatric cancers. Even if common and relatively easily managed in centers of high-income countries, chemotherapy-related adverse effects may sometimes result in fatal toxicities in less developed countries (Luna-Fineman et al, 2019).…”

The COVID‐19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP‐E, SIOP‐PODC, IPSO, PROS, CCI, and St Jude Global

“…When diagnosed early and treated in a well‐resourced setting, retinoblastoma is nearly always cured, so the paramount considerations are the preservation of vision, the preservation of the globe, and the determination of a genetic predisposition 6,33‐36 . However, in many LMIC settings, retinoblastoma presents with advanced disease, with extraocular extension and local or distant metastasis, which carry a poor prognosis 37,38 . A pandemic‐adapted approach to the diagnosis and management of intra‐ and extraocular retinoblastoma in various resource settings is discussed in Supplement I and listed in Supporting Information Table S4.…”

“…In resource‐limited settings, most patients with advanced intraocular disease and no salvageable vison will require immediate enucleation to control disease followed by systemic chemotherapy 33,36 . We recommend standard post‐enucleation chemotherapy without dose modification as an outpatient 37 . Guidance is provided in Supplement I and Supporting Information Table S4a and b, for posttreatment surveillance with a modified frequency of examination and follow‐up.…”

“…33,36 We recommend standard post-enucleation chemotherapy without dose modification as an outpatient. 37 Guidance is provided in Supplement I and Supporting…”

Global Retinoblastoma Treatment Outcomes

“…Poor-outcomes for the world's children affected by RB is primarily related to delay in diagnosis and abandonment of treatment. 38 Because of religious beliefs and social stigma, some families refuse to accept enucleation even for cases of unilateral RB. Unrealistic hope for eye salvage, particularly in advanced cases, can result in multiple treatments, and delay of local cure and metastatic disease.…”