Adjuvant Chemotherapy in Retinoblastoma with Postlaminar Optic Nerve Invasion

  • Michelle Lin
  • , Sarah B. Pike
  • , Mark W. Reid
  • , Douglas Chigane
  • , Brianne Brown
  • , Swathi Kaliki
  • , Jesse L. Berry*
  • , Alia Ahmad
  • , Rosdali Diaz-Coronado
  • , Maya Eiger-Moscovich
  • , James E. Elder
  • , Ido Didi Fabian
  • , Shahar Frenkel
  • , Hans E. Grossniklaus
  • , G. Baker Hubbard
  • , Mona Mohammad
  • , John D. McKenzie
  • , Anu A. Mathew
  • , Roderick O’Day
  • , Jacob Pe’er
  • M. Ashwin Reddy, Olivia Rolfe, Soma Rani Roy, Mandeep S. Sagoo, Carol L. Shields, Sandra E. Staffieri, Mika Tanabe, Tatiana Ushakova, Vicktoria Vishnevskia-Dai, Vladimir Polyakov, Yacoub A. Yousef
*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose To evaluate outcomes of patients with retinoblastoma (RB) who underwent primary enucleation with histopathologic evidence of postlaminar optic nerve invasion (PLONI), comparing those who received adjuvant chemotherapy to those who did not. Design Multicenter retrospective cohort study. Participants A total of 292 patients across 9 countries with RB and histopathologic evidence of PLONI after primary enucleation. Methods Patients who received adjuvant chemotherapy ( n = 276) were compared with those who did not ( n = 16) using Fisher exact tests, Welch t tests, and proportional hazard models (Cox and competing risks). Subanalyses were performed for PLONI and massive choroidal invasion and isolated PLONI. Main Outcome Measures Orbital tumor recurrence, metastasis, and death. Results Patients who did not receive adjuvant chemotherapy had higher rates of orbital tumor recurrence (31% vs 2%, P < 0.001), metastasis (31% vs 6%, P = 0.001), and death (38% vs 9%, P = 0.007). In time-to-event analyses, patients who did not receive adjuvant chemotherapy experienced greater hazard of orbital tumor recurrence (subhazard ratio [SHR] = 19.31, 95% confidence interval [CI]: 5.56–67.05), metastasis (SHR = 5.39, 95% CI: 1.75–16.60), and death (hazard ratio = 4.74, 95% CI: 1.75–12.81). Outcomes were similar among patients with PLONI and massive choroidal invasion. Among patients with isolated PLONI, those who did not receive adjuvant chemotherapy showed significantly greater hazard of metastasis over time than those who received adjuvant chemotherapy (SHR = 40.68, 95% CI: 9.65–171.55, P < 0.001). All patients with metastasis or orbital tumor recurrence eventually died during follow-up (mean duration: 75.3 months). Conclusions In patients with RB and PLONI with additional high-risk histopathologic features, initiating adjuvant chemotherapy after primary enucleation significantly reduced rates of orbital tumor recurrence, metastasis, and death. Although patients with isolated PLONI experienced fewer events and had a lower metastatic risk compared with those with multiple histopathologic features, adjuvant chemotherapy still reduced metastatic risk over time. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Original languageEnglish
JournalOphthalmology Retina
DOIs
StateAccepted/In press - 2026
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2025 American Academy of Ophthalmology.

Keywords

  • Adjuvant chemotherapy
  • Postlaminar optic nerve invasion
  • Primary enucleation
  • Retinoblastoma

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