Hearing loss and cranial radiation therapy

Cranial radiation therapy, when used as a single modality, may result in otologic toxic effects that may be gradual in onset, manifesting months to years after exposure. The threshold dose for auditory toxicity after radiation therapy alone is in the range of 35 Gy to 45 Gy for children.[23]

High-frequency sensorineural hearing loss is uncommon at cumulative radiation doses below 35 Gy, and is rarely severe below doses of 45 Gy.[24] The exception is for patients with supratentorial tumors and ventriculoperitoneal shunts, in whom doses below 30 Gy may be associated with intermediate frequency (1,000–2,000 Hz) hearing loss.[23,25]

To reduce the risk of hearing loss, the average cochlear dose should not exceed 30 Gy to 35 Gy, delivered over 6 weeks.

Sensorineural hearing loss after cranial radiation therapy can progress over time.

Sensorineural hearing loss after cranial radiation therapy can progress over time.

A study included 235 pediatric patients with brain tumors who were treated with conformal or intensity-modulated radiation therapy (without cisplatin or preexisting hearing loss) and monitored for a median of 9 years. Sensorineural hearing loss was prevalent in 14% of patients, with a median time to onset of 3.6 years from radiation therapy.[26]

Sensorineural hearing loss after cranial radiation therapy can progress over time. › A study included 235 pediatric patients with brain tumors who were treated with conformal or intensity-modulated radiation therapy (without cisplatin or preexisting hearing loss) and monitored for a median of 9 years. Sensorineural hearing loss was prevalent in 14% of patients, with a median time to onset of 3.6 years from radiation therapy.[26]

Follow-up evaluations among 29 patients identified continued decline in hearing sensitivity.

Sensorineural hearing loss after cranial radiation therapy can progress over time. › A study included 235 pediatric patients with brain tumors who were treated with conformal or intensity-modulated radiation therapy (without cisplatin or preexisting hearing loss) and monitored for a median of 9 years. Sensorineural hearing loss was prevalent in 14% of patients, with a median time to onset of 3.6 years from radiation therapy.[26]

Risk factors for cranial radiation–associated sensorineural hearing loss included younger age at initiation of radiation, higher cochlear radiation dose, and cerebrospinal fluid shunting.

When used concomitantly with cisplatin, radiation therapy can substantially exacerbate the hearing loss associated with platinum chemotherapy.[23,27-29]

In two reports from the CCSS, the following clinical and genetic factors were reported in 5-year cancer survivors:

In two reports from the CCSS, the following clinical and genetic factors were reported in 5-year cancer survivors:

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 irradiation (>30 Gy) and posterior fossa irradiation (>50 Gy but also 30–49.9 Gy) were associated with these adverse outcomes.[6]

In two reports from the CCSS, the following clinical and genetic factors were reported in 5-year cancer survivors:

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).[6]

In two reports from the CCSS, the following clinical and genetic factors were reported in 5-year cancer survivors:

Males were more likely than females to report cranial radiation therapy–related tinnitus (9.4% vs. 5.4%) and hearing loss (14.0% vs. 10.7%).[30]

In two reports from the CCSS, the following clinical and genetic factors were reported in 5-year cancer survivors:

Survivors with tinnitus or hearing loss were more likely than controls to experience persistent dizziness or vertigo, take antidepressants, and report poorer overall health.[30]

In two reports from the CCSS, the following clinical and genetic factors were reported in 5-year cancer survivors:

A genome-wide association study identified a single-nucleotide polymorphism on chromosome 6 as nearly genome-wide significant for association with cranial radiation therapy–related hearing loss. A replication analysis in the St. Jude Life (SJLIFE) cohort study supported its significant association with cranial radiation therapy–related and de novo hearing loss.[30]

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) investigation included 457 cochleas at risk in patients treated with radiation therapy without chemotherapy, and 398 cochleas in patients treated with chemotherapy.[31]

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) investigation included 457 cochleas at risk in patients treated with radiation therapy without chemotherapy, and 398 cochleas in patients treated with chemotherapy.[31]

The incidence and severity of cochlear hearing loss from radiation therapy exposure alone is related to dose and age. Risk of hearing loss was less than 5% in cochlea receiving a mean dose 35 Gy or lower but increased to 30% at a dose of 50 Gy.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) investigation included 457 cochleas at risk in patients treated with radiation therapy without chemotherapy, and 398 cochleas in patients treated with chemotherapy.[31]

Hearing loss risk ranged from 25% to 40% in children younger than 5 years at diagnosis, declining to 10% in older children for any radiation dose.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) investigation included 457 cochleas at risk in patients treated with radiation therapy without chemotherapy, and 398 cochleas in patients treated with chemotherapy.[31]

Probability of similar severe hearing loss occurred at doses 18.3 Gy higher for children younger than 3 years than those older than 3 years.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) investigation included 457 cochleas at risk in patients treated with radiation therapy without chemotherapy, and 398 cochleas in patients treated with chemotherapy.[31]

High-frequency hearing loss was most common, with average onset occurring 3.6 years (range, 0.4–13.2 years) after radiation therapy.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) investigation included 457 cochleas at risk in patients treated with radiation therapy without chemotherapy, and 398 cochleas in patients treated with chemotherapy.[31]

Low-frequency hearing loss was also seen after radiation therapy (in contrast with chemotherapy that primarily affects high frequency).

Chronic comorbidities were assessed in a cohort of 6,778 2-year survivors of adolescent and young adult cancer (defined as diagnosed with cancer between the ages of 15–39 years), with a median follow-up of 5.1 years after cancer diagnosis. The risk of developing chronic comorbidities was compared with matched individuals without a history of cancer. The crude incidence rate ratio (IRR) was 3.0 for hearing loss associated with radiation exposure higher than 30 Gy to the head. In multivariate analyses, a combined exposure to platinum (>450 mg/m2) and radiation to the head (30 Gy) was associated with increased risk of hearing loss (IRR,14.9).[32]