Targeted Retinoblastoma Management
Targeted Retinoblastoma Management
IVC generally involves a 2, 3, or 4 drug regimen delivered through intravenous catheter on a monthly basis for 6–9 consecutive months. In our practice, we use 6 monthly IVC with standard-dose vincristine, etoposide, and carboplatin on the basis of patient weight for patients less than 3 years of age. Higher dose is employed if there are bilateral groups D and/or E. Following IVC delivery, there is a reduction in tumor size; hence, the term 'chemoreduction' is often used to describe this method. Following reduction, tumor consolidation with thermotherapy or cryotherapy adds to tumor control. IVC is effective for intraocular retinoblastoma control as well as prevention of metastasis, reduction of pineoblastoma development, and reduction of long-term second cancers.
The initial reports on IVC for retinoblastoma led the way to a new era for retinoblastoma management. Since then, there have been numerous publications on the efficacy of IVC for retinoblastoma from around the world. The indications for various chemotherapy protocols can vary in different retinoblastoma centers. In general, we employ IVC for patients with the following:
According to the International Classification of Retinoblastoma in 249 consecutive eyes, globe salvage was achieved in 100% of group A eyes, 93% of group B, 90% of group C, 47% of Group D, and 25% of Group E eyes (Fig. 1) (Table 3). Group D eyes can show improved control with additional periocular sub-Tenon's carboplatin (20 mg/2cc) injection, and groups D and E eyes can show improved control with the addition of low dose radiotherapy. Shields et al. showed that combined IVC followed by IAC for eyes with far-advanced groups D and/or E resulted in globe salvage in 57% of the groups.
(Enlarge Image)
Figure 1.
Intravenous chemotherapy (chemoreduction) for bilateral retinoblastoma and total retinal detachment both eyes in a child with nystagmus. Right eye (a) before and (b) after. Left eye (c) before and (d) after.
Systemic toxicity from IVC is minimal (Table 4). Transient pancytopenia and fever can be seen, as with most systemic chemotherapy. Long-term hearing and renal toxicity are rare, particularly if medications are prescribed accurately. There is no published evidence that IVC leads to infertility, despite inaccurate and unproven statements in the literature.
In addition to control of malignancy, IVC offers remarkable visual results with visual acuity at 20/20–20/40 in 37–50% of patients. Furthermore, protection from pineoblastoma was initially recognized in 2000 by Shields et al. when they noted a dramatic drop in the incidence of this malignancy in children treated with IVC. Ramasubramanian et al. confirmed the reduction as a trend continuing 13 years later.
There is a concern that etoposide, an agent used in the IVC protocol, could lead to induction of secondary leukemia within 5 years after exposure. Gombos et al. identified several cases worldwide, but there is a concern that high and prolonged dosing could have been an underlying factor in those cases. In our experience with over 500 patients treated with IVC and in the Surveillance, Epidemiology, and End Results database, there has been no leukemia in any child treated with chemotherapy alone. Turaka et al. explored long-term risks for second malignancies and found that children with germline mutation retinoblastoma who received six cycles of IVC had lower than expected second cancers with only 4% at mean 11-year follow-up. The authors stated that IVC does not likely cause additional risk for second cancer.
When to Use Intravenous Chemotherapy
IVC generally involves a 2, 3, or 4 drug regimen delivered through intravenous catheter on a monthly basis for 6–9 consecutive months. In our practice, we use 6 monthly IVC with standard-dose vincristine, etoposide, and carboplatin on the basis of patient weight for patients less than 3 years of age. Higher dose is employed if there are bilateral groups D and/or E. Following IVC delivery, there is a reduction in tumor size; hence, the term 'chemoreduction' is often used to describe this method. Following reduction, tumor consolidation with thermotherapy or cryotherapy adds to tumor control. IVC is effective for intraocular retinoblastoma control as well as prevention of metastasis, reduction of pineoblastoma development, and reduction of long-term second cancers.
The initial reports on IVC for retinoblastoma led the way to a new era for retinoblastoma management. Since then, there have been numerous publications on the efficacy of IVC for retinoblastoma from around the world. The indications for various chemotherapy protocols can vary in different retinoblastoma centers. In general, we employ IVC for patients with the following:
germline mutation retinoblastoma,
bilateral retinoblastoma,
familial retinoblastoma,
age of 4 months or younger,
suspicious evidence of early optic nerve or choroidal invasion.
According to the International Classification of Retinoblastoma in 249 consecutive eyes, globe salvage was achieved in 100% of group A eyes, 93% of group B, 90% of group C, 47% of Group D, and 25% of Group E eyes (Fig. 1) (Table 3). Group D eyes can show improved control with additional periocular sub-Tenon's carboplatin (20 mg/2cc) injection, and groups D and E eyes can show improved control with the addition of low dose radiotherapy. Shields et al. showed that combined IVC followed by IAC for eyes with far-advanced groups D and/or E resulted in globe salvage in 57% of the groups.
(Enlarge Image)
Figure 1.
Intravenous chemotherapy (chemoreduction) for bilateral retinoblastoma and total retinal detachment both eyes in a child with nystagmus. Right eye (a) before and (b) after. Left eye (c) before and (d) after.
Systemic toxicity from IVC is minimal (Table 4). Transient pancytopenia and fever can be seen, as with most systemic chemotherapy. Long-term hearing and renal toxicity are rare, particularly if medications are prescribed accurately. There is no published evidence that IVC leads to infertility, despite inaccurate and unproven statements in the literature.
In addition to control of malignancy, IVC offers remarkable visual results with visual acuity at 20/20–20/40 in 37–50% of patients. Furthermore, protection from pineoblastoma was initially recognized in 2000 by Shields et al. when they noted a dramatic drop in the incidence of this malignancy in children treated with IVC. Ramasubramanian et al. confirmed the reduction as a trend continuing 13 years later.
There is a concern that etoposide, an agent used in the IVC protocol, could lead to induction of secondary leukemia within 5 years after exposure. Gombos et al. identified several cases worldwide, but there is a concern that high and prolonged dosing could have been an underlying factor in those cases. In our experience with over 500 patients treated with IVC and in the Surveillance, Epidemiology, and End Results database, there has been no leukemia in any child treated with chemotherapy alone. Turaka et al. explored long-term risks for second malignancies and found that children with germline mutation retinoblastoma who received six cycles of IVC had lower than expected second cancers with only 4% at mean 11-year follow-up. The authors stated that IVC does not likely cause additional risk for second cancer.
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