Role of PET/CT in Staging and Evaluation of Treatment Response After 3 Cycles of Chemotherapy in Locally Advanced Retinoblastoma: A Prospective Study

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Abstract
The present study prospectively evaluated the role of 18F-FDG PET/CT for staging, neoadjuvant chemotherapy response evaluation, and final outcome assessment in International Retinoblastoma Staging System (IRSS) stage III retinoblastoma. Methods: Twenty-five consecutive IRSS stage III patients, with a median age of 3 y, were prospectively enrolled after ethics approval. All patients received neoadjuvant chemotherapy followed by enucleation, radiotherapy, and adjuvant chemotherapy. PET/CT was performed at baseline (PET/CT-1) and after 3 cycles of neoadjuvant chemotherapy (PET/CT-2). All 25 patients underwent PET/CT-1, and 21 of 25 patients underwent PET/CT-2. PET/CT-1 was compared with routine staging, and response on PET/CT-2 was assessed by criteria from the European Organization for Research and Treatment of Cancer response. Event-free survival (EFS) and overall survival (OS) were calculated using Kaplan–Meier survival analysis, and differences between the groups were compared using log-rank test. A P value of 0.05 or less was considered significant. Results: Increased 18F-FDG uptake was noted in primary extraocular tumor in all patients, except 5 with bilateral retinoblastoma (one eye with advanced and the other eye with intraocular disease) in whom the intraocular tumor did not show 18F-FDG uptake. Five of 22 IRSS stage IIIA patients with clinically negative cervical lymph node involvement were found to have uptake in cervical lymph nodes on PET/CT-1, and 2 of 3 IRSS stage IIIB patients with pathologically confirmed cervical lymph node involvement did not show any uptake in the involved lymph nodes. No significant difference in EFS and OS was seen between IRSS stage IIIA and IIIB patients using routine staging or PET/CT staging (P ≥ 0.05); however, there was a trend toward better OS in patients with IRSS stage IIIB disease on PET/CT (P = 0.065). There was no significant discordance between routine staging and PET/CT staging (P = 0.256). The 8 patients with optic nerve uptake had lower EFS (P = 0.0001) and OS (P = 0.0009) than did 17 patients without optic nerve uptake on PET/CT-1. The 17 patients with complete response or partial response had better EFS (P = 0.042) and OS (P = 0.026) than did the 4 patients with progressive disease on PET/CT-2. Conclusion: Optic nerve uptake at baseline on PET/CT and response after neoadjuvant chemotherapy according to criteria from the European Organization for Research and Treatment of Cancer are strong predictors of EFS and OS in IRSS stage III retinoblastoma.