Treatment-specific effects

The CCSS reported the increased risk of developing vision late effects in survivors who were 5 or more years from diagnosis. These late effects included cataracts (RR, 10.8), glaucoma (RR, 2.5), legal blindness (RR, 2.6), double vision (RR, 4.1), and dry eye (RR, 1.9), compared with siblings.[56] In a separate report, the authors provided additional data on the interval from radiation therapy and the radiation dose associated with cataract development.[57] Among 13,902 study participants, 3.5% developed cataracts (41% within 5 years of radiation therapy), with a median time to onset of 9.6 years and a maximum time of 37 years. Lens radiation doses were associated with an increased prevalence: 1.3% if less than 0.5 Gy, 6.1% after 2.5 to 3.49 Gy, and 40.6% after 20 to 60 Gy.

The CCSS reported the increased risk of developing vision late effects in survivors who were 5 or more years from diagnosis. These late effects included cataracts (RR, 10.8), glaucoma (RR, 2.5), legal blindness (RR, 2.6), double vision (RR, 4.1), and dry eye (RR, 1.9), compared with siblings.[56] In a separate report, the authors provided additional data on the interval from radiation therapy and the radiation dose associated with cataract development.[57] Among 13,902 study participants, 3.5% developed cataracts (41% within 5 years of radiation therapy), with a median time to onset of 9.6 years and a maximum time of 37 years. Lens radiation doses were associated with an increased prevalence: 1.3% if less than 0.5 Gy, 6.1% after 2.5 to 3.49 Gy, and 40.6% after 20 to 60 Gy.

Higher doses were associated with a shorter time interval to diagnosis. Of the group with cataracts, 31% reported having cataract surgery, supporting the clinical consequences.

The CCSS reported the increased risk of developing vision late effects in survivors who were 5 or more years from diagnosis. These late effects included cataracts (RR, 10.8), glaucoma (RR, 2.5), legal blindness (RR, 2.6), double vision (RR, 4.1), and dry eye (RR, 1.9), compared with siblings.[56] In a separate report, the authors provided additional data on the interval from radiation therapy and the radiation dose associated with cataract development.[57] Among 13,902 study participants, 3.5% developed cataracts (41% within 5 years of radiation therapy), with a median time to onset of 9.6 years and a maximum time of 37 years. Lens radiation doses were associated with an increased prevalence: 1.3% if less than 0.5 Gy, 6.1% after 2.5 to 3.49 Gy, and 40.6% after 20 to 60 Gy.

Cytosine arabinoside (OR, 1.5) and doxorubicin (OR, 1.5) were independently associated with cataract development, methotrexate was inversely associated (OR, 0.6), and no positive interaction between the use of corticosteroids and radiation therapy was observed.

In a cohort of 517 survivors of childhood acute lymphoblastic leukemia (median time from diagnosis, 10.9 years) who were all evaluated by slit lamp examination, the 15-year cumulative incidence of cataract was 4.5%. CNS radiation therapy was the only treatment-related risk factor identified for cataract development, which occurred in 11.1% of irradiated survivors, compared with 2.8% of those who were not irradiated.[58]

A retrospective study of 458 children (875 at-risk eyes) treated with proton therapy for intracranial malignancy assessed radiation therapy–related visual decline. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received 30 GyRBE or higher to 0.1 cm3.[59]

A retrospective study of 458 children (875 at-risk eyes) treated with proton therapy for intracranial malignancy assessed radiation therapy–related visual decline. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received 30 GyRBE or higher to 0.1 cm3.[59]

No patients experienced complete vision loss.

A retrospective study of 458 children (875 at-risk eyes) treated with proton therapy for intracranial malignancy assessed radiation therapy–related visual decline. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received 30 GyRBE or higher to 0.1 cm3.[59]

The actuarial 5-year rate of visual acuity decline was 2.6%.

A retrospective study of 458 children (875 at-risk eyes) treated with proton therapy for intracranial malignancy assessed radiation therapy–related visual decline. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received 30 GyRBE or higher to 0.1 cm3.[59]

Tumor location significantly correlated with risk. Investigators found that children with tumors of the suprasellar or the optic pathway region are at greatest risk. The reported risk was about 5% decline in visual acuity with a dose of 56 GyRBE to the optic nerve or optic pathway.

A retrospective study of 458 children (875 at-risk eyes) treated with proton therapy for intracranial malignancy assessed radiation therapy–related visual decline. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received 30 GyRBE or higher to 0.1 cm3.[59]

For children with tumors arising elsewhere in the brain, no toxicity was observed.

A St. Jude Children's Research Hospital investigation evaluated ocular complications in school-aged children and adolescents who survived at least 1 year following allogeneic HSCT. Among 162 patients (mean age at transplant, 13.4 years; mean follow-up, 4 years), the following was reported:[60]

A St. Jude Children's Research Hospital investigation evaluated ocular complications in school-aged children and adolescents who survived at least 1 year following allogeneic HSCT. Among 162 patients (mean age at transplant, 13.4 years; mean follow-up, 4 years), the following was reported:[60]

Cataract formation was noted in 57 patients (35%) and dry eye was noted in 51 patients (31%).

A St. Jude Children's Research Hospital investigation evaluated ocular complications in school-aged children and adolescents who survived at least 1 year following allogeneic HSCT. Among 162 patients (mean age at transplant, 13.4 years; mean follow-up, 4 years), the following was reported:[60]

Multivariate analysis of significant variables showed that TBI was a risk factor for cataract formation, and chronic graft-versus-host disease (GVHD) was a significant risk factor for dry eye syndrome.

Compared with patients treated with busulfan or other chemotherapy, patients treated with single-dose or fractionated TBI are at increased risk of cataracts.[61-64]

Compared with patients treated with busulfan or other chemotherapy, patients treated with single-dose or fractionated TBI are at increased risk of cataracts.[61-64]

The risk ranges from approximately 10% to 60% at 10 years posttreatment, depending on the total dose and fractionation, with a shorter latency period and more severe cataracts noted after single fraction and higher dose or dose-rate TBI.

One series evaluated 48 patients with high-risk neuroblastoma (median years since diagnosis, 14.1 years) who were all treated with multimodal therapy, including high-dose chemotherapy, HSCT (with or without TBI), radiation therapy, and immunotherapy.[10]

One series evaluated 48 patients with high-risk neuroblastoma (median years since diagnosis, 14.1 years) who were all treated with multimodal therapy, including high-dose chemotherapy, HSCT (with or without TBI), radiation therapy, and immunotherapy.[10]

Twenty-five of the survivors (52%) developed cataracts.

One series evaluated 48 patients with high-risk neuroblastoma (median years since diagnosis, 14.1 years) who were all treated with multimodal therapy, including high-dose chemotherapy, HSCT (with or without TBI), radiation therapy, and immunotherapy.[10]

All patients with cataracts had received TBI (P < .0001).

Patients receiving TBI doses of less than 40 Gy have a less than 10% chance of developing severe cataracts.[64]

Corticosteroids and GVHD may further increase risk.[61,65]

The prevalence of cataracts, evaluated by serial slit lamp testing, among 271 participants (mean follow-up, 10.3 years) in the Leucémie de l'Enfant et de l'Adolescent (LEA) program was 41.7%, with 8.1% requiring surgical intervention.[66]

The prevalence of cataracts, evaluated by serial slit lamp testing, among 271 participants (mean follow-up, 10.3 years) in the Leucémie de l'Enfant et de l'Adolescent (LEA) program was 41.7%, with 8.1% requiring surgical intervention.[66]

The cumulative incidence of cataracts among those treated with TBI increased over time from 30% at 5 years to 70.8% at 15 years and 78% at 20 years.

The prevalence of cataracts, evaluated by serial slit lamp testing, among 271 participants (mean follow-up, 10.3 years) in the Leucémie de l'Enfant et de l'Adolescent (LEA) program was 41.7%, with 8.1% requiring surgical intervention.[66]

The lack of a plateau in cataract incidence suggests that nearly all patients treated with TBI will develop cataracts as follow-up increases.

The prevalence of cataracts, evaluated by serial slit lamp testing, among 271 participants (mean follow-up, 10.3 years) in the Leucémie de l'Enfant et de l'Adolescent (LEA) program was 41.7%, with 8.1% requiring surgical intervention.[66]

In contrast, the 15-year cumulative incidence of cataracts was 12.5% among those conditioned with busulfan.

The prevalence of cataracts, evaluated by serial slit lamp testing, among 271 participants (mean follow-up, 10.3 years) in the Leucémie de l'Enfant et de l'Adolescent (LEA) program was 41.7%, with 8.1% requiring surgical intervention.[66]

Multivariable analysis identified high cumulative steroid dose as a potential cofactor with TBI for cataract risk.

Dry eye syndrome is the most common manifestation of chronic ocular GVHD, but it may occur as an isolated phenomenon in the absence of GVHD.

Dry eye syndrome is the most common manifestation of chronic ocular GVHD, but it may occur as an isolated phenomenon in the absence of GVHD.

A single-center study evaluated 484 consecutive children receiving HSCT who had ophthalmological examinations performed before HSCT and then annually until 5 years after HSCT.[67]

Dry eye syndrome is the most common manifestation of chronic ocular GVHD, but it may occur as an isolated phenomenon in the absence of GVHD. › A single-center study evaluated 484 consecutive children receiving HSCT who had ophthalmological examinations performed before HSCT and then annually until 5 years after HSCT.[67]

The cumulate incidence of chronic ocular GVHD was 6.0%.

Dry eye syndrome is the most common manifestation of chronic ocular GVHD, but it may occur as an isolated phenomenon in the absence of GVHD. › A single-center study evaluated 484 consecutive children receiving HSCT who had ophthalmological examinations performed before HSCT and then annually until 5 years after HSCT.[67]

The cumulative incidence of new-onset dry eye disease was 8.7%.

Dry eye syndrome is the most common manifestation of chronic ocular GVHD, but it may occur as an isolated phenomenon in the absence of GVHD. › A single-center study evaluated 484 consecutive children receiving HSCT who had ophthalmological examinations performed before HSCT and then annually until 5 years after HSCT.[67]

Younger age (0–4 years vs. age 10–16 years) was associated with reduced risk of dry eye disease.