Subsequent malignant neoplasms in the pediatric age in retinoblastoma survivors in Argentina

Abstract

Background Retinoblastoma survivors in low‐ and middle‐income countries are exposed to high‐intensity treatments that potentially place them at higher risk of early subsequent malignant neoplasms (SMNs). Methods We followed 714 (403 [56.4%] nonhereditary and 311 [43.5%] hereditary) retinoblastoma survivors diagnosed from August 1987 to December 2016, up to the age of 16 years. We quantified risk of SMNs with cumulative incidence (CI) and standardized incidence ratios (SIR) analysis. Multivariate regression Cox model was used to determine the association of treatments and risk of SMNs. Results Median follow‐up was of 9 years (range: 0.18–16.9) and 24 survivors (3.36%) developed 25 SMNs (n = 22 hereditary, n = 2 nonhereditary). SMNs included sarcomas (osteosarcomas, Ewing sarcomas, rhabdomyosarcomas; n = 12), leukemias (n = 5), and central nervous system tumors (CNS; n = 3). All cases of acute myeloid leukemia (AML) and most of Ewing sarcomas occurred within 5 years of retinoblastoma diagnosis. The type of SMN was the main indicator of mortality (five of five patients with leukemias, six of 12 with sarcomas, and zero of three with CNS tumors died). Compared to the general population, radiation increased the risk of Ewing sarcoma in hereditary survivors by 700‐fold (95% CI = 252–2422.6) and chemotherapy increased the risk of AML by 140‐fold (95% CI = 45.3–436). The CI of SMNs for hereditary survivors was 13.7% (95% CI = 8.4–22.1) at 15 years. Conclusion Retinoblastoma survivors from Argentina are at higher risk of developing SMNs early in life compared to the general Argentinean population, especially those treated with radiation plus chemotherapy. AML and Ewing sarcoma presented within 5 years of retinoblastoma diagnosis are associated with chemotherapy and radiation exposure.

Immunohistochemical expression of TFF1 is a marker of poor prognosis in retinoblastoma

“…This is in line with the reported observation that subtype 1 tumors show a stable genome with very few genomic events besides RB1 alterations 9 . Since subtype 1 is more common in patients with germline RB1 mutations, the avoidance of adjuvant therapy in these patients is critical to prevent long‐term chemo and radiotherapy side effects that including potentially fatal treatment‐related secondary malignancies 22 …”

How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP)

“…Although a study showed that two drugs (vincristine and carboplatin) are inferior to combinations with three drugs in the conservative treatment of retinoblastoma with systemic chemotherapy, our group decided to use the two‐drug combination, without the use of etoposide for patients receiving systemic chemoreduction 44 . The group agreed that the use of etoposide is not justified in centers that have OAC, as it has been associated with a higher risk of secondary leukemia in hereditary cases, even at doses considered safe in other neoplasms 45,46 …”

“…44 The group agreed that the use of etoposide is not justified in centers that have OAC, as it has been associated with a higher risk of secondary leukemia in hereditary cases, even at doses considered safe in other neoplasms. 45,46 In patients with bilateral disease presenting with one group B or C eye and the fellow eye of group D (the most common presentation in our continent), the use of tandem OAC is also preferred as this would provide better chances of success in the treatment of the D eye. In cases of limited access to OAC or in groups with less experience in the use of tandem therapy, the use of systemic chemotherapy followed by OAC (± intravitreous chemotherapy) only for consolidation of the D eye may be an option.…”

How We Approach Conservative Treatment of Retinoblastoma in South America in the Era of Local Ocular Treatments. A Consensus of the Grupo America Latina De Oncologia Pediatrica (Galop)

“…Although a study showed that two drugs (Vincristine and Carboplatin) are inferior to combinations with three drugs in the conservative treatment of retinoblastoma, our group decided to use the two-drug combination, without the use of Etoposide for patients receiving systemic chemoreduction 38 . The group agreed that the use of Etoposide is not justified in centers that have OAC since it has been associated with higher risk of secondary leukemias, even at doses considered safe in other neoplasms 39 .…”