Improvements in Overall Survival in Trilateral Retinoblastoma Due to Improved Chemotherapy and Earlier Detection


Key Points

  • 5-year survival has increased dramatically since 1995, reflecting increased use of standard chemotherapy and high-dose chemotherapy with stem cell rescue.
  • Smaller tumor size, representing earlier tumor detection, is characteristic of long-term pineal trilateral retinoblastoma survivors.

In a systematic review and meta-analysis reported in The Lancet Oncology, de Jong et al found a dramatic improvement in overall survival among children with trilateral retinoblastoma since 1995, reflecting increased use of conventional and high-dose chemotherapy with stem cell rescue in pineal and nonpineal disease and earlier diagnosis in pineal disease.

Approximately 5% of children with retinoblastoma from germline mutations in RB1 are at risk of developing trilateral retinoblastoma consisting of intraocular retinoblastoma and a histologically similar brain tumor that occurs most commonly in the pineal gland.

In the study, a search for scientific literature assessing trilateral retinoblastoma cases published between January 1966 and April 2014 identified 90 studies including 174 patients. Outcomes before 1995 were compared with those since 1995.

Changes in Treatment and Diagnosis

The study found a decreasing use of radiotherapy, increasing use of chemotherapy and high-dose chemotherapy with stem cell rescue, and an increased proportion of actively treated patients since 1995. No clear trend for use of surgery was identified.

Pineal trilateral retinoblastomas diagnosed after 1995 were significantly smaller than those diagnosed earlier (median, 17.5 vs 30 mm, P = .0075). No marked difference in size was observed for nonpineal trilateral retinoblastomas (median, 33 vs 30 mm, P = .75).

Improved Survival

For patients diagnosed before vs after 1995, 5-year survival among those with pineal trilateral retinoblastoma increased from 6% to 44% (P < .0001) and 5-year survival among those with nonpineal trilateral retinoblastoma improved from 0% to 57% (P = .035). Analysis adjusting for presence of leptomeningeal metastases and trilateral retinoblastoma location indicated that both conventional (hazard ratio [HR] = 0.059, P < .0001) and high-dose chemotherapy with stem cell rescue (HR = 0.013, P < .0001) strongly contributed to the observed survival improvement. Although nonpineal trilateral retinoblastomas were larger than pineal tumors, survival outcomes were similar for both since 1995.

Long-Term Survivors

Many of the 22 long-term survivors with follow-up of ≥ 5 years did not receive radiotherapy or surgery, but all but one received chemotherapy, with at least 10 receiving chemotherapy alone. Of 15 long-term survivors of pineal trilateral retinoblastoma, 11 (73%) presented without symptoms; of seven with nonpineal tumors, three presented with no symptoms. The importance of early detection of pineal trilateral retinoblastoma to better outcome is indicted by the small tumor size (median, 14.5 mm) in long-term survivors.

The investigators concluded, “Our results suggest that improvements in overall survival are attributable to improved chemotherapy regimens and early detection of pineal trilateral retinoblastoma. As such, successful treatment of trilateral retinoblastoma should include screening at least at the time of retinoblastoma diagnosis and chemotherapy, which would preferably be a high-dose regimen with autologous stem-cell rescue.”

Marcus C. de Jong, MD, of VU University Medical Center, Amsterdam, is the corresponding author for the Lancet Oncology article.

The study authors reported no potential conflicts of interest.

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