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Late Effects of Treatment for Childhood Cancer (PDQ®)

Health Professional Version
Last Modified: 08/18/2014

Late Effects of the Special Senses

Orbital and Optic


Children treated for malignancies may be at risk for early- or delayed-onset hearing loss that can affect learning, communication, school performance, social interaction, and overall quality of life. Hearing loss as a late effect of therapy can occur after exposure to platinum compounds (cisplatin and carboplatin) and cranial irradiation. Children are more susceptible to ototoxicity from platinum agents than adults.[1,2] Risk factors associated with hearing loss with platinum agents include the following:

  • Younger age.
  • Higher cumulative dose of chemotherapy.
  • Central nervous system (CNS) tumors.
  • Concomitant CNS radiation.

For cisplatin, the risk of significant hearing loss involving the speech frequencies (500–2000 Hz) usually occurs with cumulative doses that exceed 400 mg/m2 in pediatric patients.[1,3] Ototoxicity after platinum chemotherapy can present or worsen years after completion of therapy. In 59 patients who had received cisplatin, 51% of them developed late-onset hearing loss (occurring at least 6 months after the last dose of cisplatin). Radiation to the posterior fossa and the use of hearing aids were associated with late-onset hearing loss.[4,5] Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[6] A single study observed ototoxicity after the use of non-stem cell transplant dosing of carboplatin for retinoblastoma, in that 8 children out of 175 developed hearing loss. For seven of the eight children, the onset of the ototoxicity was delayed a median of 3.7 years.[7] Another study evaluating audiological outcomes among 60 retinoblastoma survivors treated with nonmyeloablative systemic carboplatin and vincristine estimated a cumulative incidence of hearing loss of 20.3% at 10 years. Among the ten (17%) patients who developed sustained grade 3 or 4 hearing loss, nine were younger than 6 months at the start of chemotherapy. Younger age at the start of treatment was the only significant predictor of hearing loss; the cumulative incidence of hearing loss was 39% for patients younger than 6 months versus only 8.3% for patients aged 6 months and older (P = .004).[8] With myeloablative dosing, carboplatin may cause significant ototoxicity. For carboplatin, ototoxicity has been reported to occur at cumulative doses exceeding 400 mg/m2.[9]

Cranial radiation therapy, when used as a single modality, results in ototoxicity when cochlear dosage exceeds 32 Gy. Young patient age and presence of a brain tumor and/or hydrocephalus can increase susceptibility to hearing loss. The onset of radiation-associated hearing loss may be gradual, manifesting months to years after exposure. When used concomitantly with cisplatin, radiation therapy can substantially exacerbate the hearing loss associated with platinum chemotherapy.[10-13] In a report from the Childhood Cancer Survivor Study (CCSS), 5-year survivors were at increased risk of problems with hearing sounds (relative risk [RR], 2.3), tinnitus (RR, 1.7), hearing loss requiring an aid (RR, 4.4), and hearing loss in one or both ears not corrected by a hearing aid (RR, 5.2), compared with siblings. Temporal lobe (>30 Gy) and posterior fossa radiation (>50 Gy but also 30–49.9 Gy) was associated with these outcomes. Exposure to platinum was associated with an increased risk of problems with hearing sounds (RR, 2.1), tinnitus (RR, 2.8), and hearing loss requiring an aid (RR, 4.1).[14]

Table 15. Auditory Late Effects
Predisposing Therapy Potential Auditory Effects Health Screening/Interventions 
FM = frequency modulated.
Platinum agents (cisplatin, carboplatin); radiation impacting the earOtotoxicity; sensorineural hearing loss; tinnitus; vertigo; dehydrated ceruminosis; conductive hearing lossHistory: hearing difficulties, tinnitus, vertigo
Otoscopic exam
Audiology evaluation
Amplification in patients with progressive hearing loss
Speech and language therapy for children with hearing loss
Otolaryngology consultation in patients with chronic infection, cerumen impaction, or other anatomical problems exacerbating or contributing to hearing loss
Educational accommodations (e.g., preferential classroom seating, FM amplification system, etc.)

Orbital and Optic

Orbital complications are common after radiation therapy for retinoblastoma, childhood head and neck sarcomas, and CNS tumors, and as part of total-body irradiation (TBI).

For survivors of retinoblastoma, a small orbital volume may result from either enucleation or radiation therapy. Age younger than 1 year may increase risk, but this is not consistent across studies.[15,16] Progress has been made in the management of retinoblastoma with better enucleation implants, intravenous chemoreduction, and intra-arterial chemotherapy in addition to thermotherapy, cryotherapy, and plaque radiation. Longer follow-up is needed to assess the impact on vision in patients undergoing these treatment modalities.[15,17-19] Previously, tumors located near the macula and fovea were associated with an increased risk of complications leading to visual loss, although treatment of these tumors with foveal laser ablation has shown promise in preserving vision.[19-25] (Refer to the PDQ summary on Retinoblastoma Treatment for more information on the treatment of retinoblastoma.)

Survivors of orbital rhabdomyosarcoma are at risk of dry eye, cataract, orbital hypoplasia, ptosis, retinopathy, keratoconjunctivitis, optic neuropathy, lid epithelioma, and impairment of vision after radiation therapy doses of 30 Gy to 65 Gy. The higher dose ranges (>50 Gy) are associated with lid epitheliomas, keratoconjunctivitis, lacrimal duct atrophy, and severe dry eye. Retinitis and optic neuropathy may also result from doses of 50 Gy to 65 Gy and even at lower total doses if the individual fraction size is greater than 2 Gy.[26] Cataracts are reported after lower doses of 10 Gy to 18 Gy.[27-32] (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information on the treatment of rhabdomyosarcoma in children.)

Survivors of childhood cancer are at increased risk for ocular late effects related to both glucocorticoid and radiation exposure to the eye. The Childhood Cancer Survivor Study (CCSS) reported that survivors 5 or more years from diagnosis are at increased risk for cataracts, glaucoma, legal blindness, double vision, and dry eye, compared with siblings. The dose of radiation to the eye is significantly associated with risk of cataracts, legal blindness, double vision, and dry eye, in a dose-dependent manner. Risk of cataracts was associated with a radiation dose of 3,000 cGy or more to the posterior fossa, temporal lobe and exposure to prednisone. The cumulative incidence of cataracts, double vision, dry eye, and legal blindness continued to increase up to 20 years after diagnosis for those who received more than 500 cGy to the eye.[33]

Ocular complications such as cataracts and dry-eye syndrome are common after stem cell transplant in childhood. Compared with patients treated with busulfan or other chemotherapy, patients treated with single-dose or fractionated TBI are at increased risk of cataracts. 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.[34-37] Patients receiving TBI with biologically effective doses of less than 40 Gy have a less than 10% chance of developing severe cataracts.[37] Corticosteroids and graft-versus-host disease (GVHD) may further increase risk.[34,38] Epithelial superficial keratopathy has been shown to be more common if the patient was exposed to repeated high trough levels of cyclosporine A.[39]

Table 16. Ocular Late Effects
Predisposing Therapy Ocular/Vision Effects Health Screening/Interventions 
Busulfan; corticosteroids; radiation impacting the eyeCataractsHistory: decreased acuity, halos, diplopia
Eye exam: visual acuity, funduscopy
Ophthalmology consultation
Radiation impacting the eye including radioiodine (I-131)Ocular toxicity (orbital hypoplasia, lacrimal duct atrophy, xerophthalmia [keratoconjunctivitis sicca], keratitis, telangiectasias, retinopathy, optic chiasm neuropathy, enophthalmos, chronic painful eye, maculopathy, papillopathy, glaucoma)History: visual changes (decreased acuity, halos, diplopia), dry eye, persistent eye irritation, excessive tearing, light sensitivity, poor night vision, painful eye
Eye exam: visual acuity, funduscopy
Ophthalmology consultation
Hematopoietic cell transplantation with any history of chronic GVHDXerophthalmia (keratoconjunctivitis sicca)History: dry eye (burning, itching, foreign body sensation, inflammation)
Eye exam: visual acuity, funduscopy
EnucleationImpaired cosmesis; poor prosthetic fit; orbital hypoplasiaOcular prosthetic evaluation

GVHD = graft-versus-host disease.

Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for information on the late effects of special senses including risk factors, evaluation, and health counseling.

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  3. Kushner BH, Budnick A, Kramer K, et al.: Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma. Cancer 107 (2): 417-22, 2006.  [PUBMED Abstract]

  4. Kolinsky DC, Hayashi SS, Karzon R, et al.: Late onset hearing loss: a significant complication of cancer survivors treated with Cisplatin containing chemotherapy regimens. J Pediatr Hematol Oncol 32 (2): 119-23, 2010.  [PUBMED Abstract]

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