Late Effects of the Special Senses
Hearing loss and platinum-based therapy
Hearing loss and cranial radiation therapy
Orbital and Optic
Optic pathway glioma and craniopharyngioma
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), cranial radiation, or both. These therapeutic exposures are most common in the treatment of central nervous system (CNS) and non-CNS solid tumors. Children are more susceptible to otologic toxic effects from platinum agents than are adults.[1,2]
Risk factors associated with hearing loss include the following:
- Younger age at treatment.
- Higher cumulative dose of platinum-based chemotherapy.
- Exposure to cisplatin combined with myeloablative carboplatin.
- CNS tumors.
- Concomitant cranial radiation therapy.
Cisplatin-induced hearing loss involving the speech frequencies (500–2000 Hz) usually occurs with cumulative doses that exceed 400 mg/m2 in pediatric patients.[3,4] Otologic toxic effects after platinum chemotherapy can present or worsen years after completion of therapy.
Studies of hearing loss after platinum-based therapy in childhood cancer survivors have reported the following:
- In a study of 59 patients who received cisplatin, 51% of survivors developed late-onset hearing loss (occurring at least 6 months after the last dose of cisplatin). Radiation to the posterior fossa inclusive of the eighth cranial nerve and the use of hearing aids (suggestive of damage to the cochlea at the end of therapy) were associated with late-onset hearing loss.
- Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic. However, delayed-onset hearing loss has been reported in specific populations. A single study of otologic toxic effects after non–stem cell transplant dosing of carboplatin for retinoblastoma reported that 8 of 175 children developed hearing loss. For seven of the eight children, the onset of the otologic toxic effects was delayed a median of 3.7 years. Another study that evaluated 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 patients (17%) who developed sustained grade 3 or grade 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.
Cranial radiation therapy, when used as a single modality, may result in otologic toxic effects 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.[9-12] 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 radiation (>30 Gy) and posterior fossa radiation (>50 Gy but also 30–49.9 Gy) were associated with these adverse 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).Table 15. Auditory Late Effects
|Predisposing Therapy||Potential Auditory Effects||Health Screening/Interventions|
|FM = frequency modulated.|
|Platinum agents (cisplatin, carboplatin); radiation impacting the ear||Otologic toxic effects; sensorineural hearing loss; tinnitus; vertigo; dehydrated ceruminosis; conductive hearing loss||History: hearing difficulties, tinnitus, vertigo|
|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 and after total-body irradiation (TBI) and in children with head and neck sarcomas and CNS tumors.Retinoblastoma
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 finding is not consistent across studies.[14,15] 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 more contemporary treatment modalities.[14,16,17] Previously, tumors located near the macula and fovea were associated with an increased risk of complications leading to vision loss, although treatment of these tumors with foveal laser ablation has shown promise in preserving vision.[18-21]
(Refer to the PDQ summary on Retinoblastoma Treatment for more information on the treatment of retinoblastoma.)Rhabdomyosarcoma
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 higher than 2 Gy. Cataracts are reported after lower doses of 10 Gy to 18 Gy.[23-25]
(Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information on the treatment of rhabdomyosarcoma in children.)Optic pathway glioma and craniopharyngioma
Survivors of optic pathway glioma and craniopharyngioma are also at risk of visual complications, resulting in part from tumor proximity to the optic nerve.
Longitudinal follow-up (mean, 9 years) of 21 patients with optic pathway gliomas indicated that before treatment, 81% of patients had reduced visual acuity, 81% had optic nerve pallor, and all had reduced visual evoked potentials in one or both eyes. Treatment arrested acuity loss for 4 to 5 years. Visual acuity was stable or improved in 33% of patients at last follow-up; however, it declined on average. Visual acuity at follow-up was related to tumor volume at initial presentation.
In a study of 25 patients diagnosed with craniopharyngioma, 67% had visual complications at a mean follow-up of 11 years. A retrospective review of 30 children with craniopharyngioma revealed that 19 patients had vision loss before surgery; 21 patients had postsurgical vision loss. Preoperative vision loss was predicative of postoperative vision loss.Treatment-specific effects
Survivors of childhood cancer are at increased risk for ocular late effects related to both glucocorticoid and radiation exposure to the eye. The CCSS reported that survivorswho were 5 or more years from diagnosis were at increased risk for 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. 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 30 Gy or more to the posterior fossa and temporal lobe and treatment with 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 5 Gy to the eye.
Ocular complications, such as cataracts and dry-eye syndrome, are common after stem cell transplantation 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.[30-33] Patients receiving TBI doses of less than 40 Gy have a less than 10% chance of developing severe cataracts. Corticosteroids and graft-versus-host disease (GVHD) may further increase risk.[30,34] Epithelial superficial keratopathy has been shown to be more common if the patient was exposed to repeated high trough levels of cyclosporine A.Table 16. Ocular Late Effects
|Predisposing Therapy||Ocular/Vision Effects||Health Screening/Interventions|
|GVHD = graft-versus-host disease.|
|Busulfan; corticosteroids; radiation impacting the eye||Cataracts||History: decreased acuity, halos, diplopia|
|Eye exam: visual acuity, funduscopy|
|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|
|Hematopoietic cell transplantation with any history of chronic GVHD||Xerophthalmia (keratoconjunctivitis sicca)||History: dry eye (burning, itching, foreign body sensation, inflammation)|
|Eye exam: visual acuity, funduscopy|
|Enucleation||Impaired cosmesis; poor prosthetic fit; orbital hypoplasia||Ocular prosthetic evaluation|
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.References
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