The relevance of ototoxicity induced by radiotherapy.

BACKGROUND: The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have undergone head-neck or brain radiation, or a combination of the two. To provide optimal care for these cancer survivors and minimize subsequent complications, it is crucial to comprehend the relationship between radiotherapy and ototoxicity. METHODS: A comprehensive search of databases, including the Cochrane Library, PubMed, Embase, and Web of Science, was conducted from the inception of the knowledge base up until January 2023. The metafor-package was employed to compare ototoxicity rates in individuals receiving radiotherapy. Two independent assessors extracted data and analyzed targets using a random-effects model. RESULTS: Out of the 28 randomized controlled trials (RCTs) included in the analysis, 25 were prospective RCTs. Subgroup analysis revealed that mean cochlear radiation dose, primary tumor location, radiotherapy modality, and patient age significantly influenced total hearing impairment. Intensity-modulated radiotherapy was associated with less ototoxicity than 2D conventional radiotherapy (OR, 0.53; 95% CI, 0.47-0.60; P = 0.73; I2 = 0%). Stereotactic radiotherapy appeared to be a superior option for hearing preservation compared to radiosurgery (OR, 1.44; 95% CI, 1.00-2.07; P = 0.69; I2 = 0%). Children demonstrated a higher risk of hearing impairment than adults. More than 50% of patients with vestibular neuroadenoma experienced hearing impairment following radiation therapy. A strong association was observed between the average cochlear radiation dose and hearing impairment. Increased cochlear radiation doses may result in a heightened risk of hearing impairment. CONCLUSION: Several risk factors for radiation-induced hearing impairment were identified in this study. High cochlear radiation doses were found to exacerbate the risk of hearing impairment resulting from radiation therapy.

Radiation for Sporadic Vestibular Schwannoma: An Update on Modalities, Emphasizing Hearing Loss, Side Effects, and Tumor Control.

Stereotactic radiosurgery (SRS) is a valid option for most patients undergoing treatment of small- and medium-sized vestibular schwannoma. Predictors of hearing preservation are the same for observation or surgery: when pretreatment hearing is normal, the tumor is smaller, and when a cerebrospinal fluid fundal cap exists. Hearing outcomes are poor when hearing loss exists pre-treatment. Rates of facial and trigeminal neuropathy are higher post-treatment after fractionated plans than single-fraction SRS. Subtotal resection and adjuvant radiation appears to offer patients with large tumors optimal outcomes for hearing, tumor control, and cranial nerve function versus gross total resection.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a multi-institutional study.

OBJECTIVE: Though stereotactic radiosurgery (SRS) is an established safe treatment for small- and medium-sized vestibular schwannomas (VSs), its role in the management of Koos grade IV VS is still unclear. In this retrospective multicenter study, the authors evaluated tumor control and the patient outcomes of primary, single-session SRS treatment for Koos grade IV VS. METHODS: This study included patients treated with primary, single-session SRS for Koos grade IV VS at 10 participating centers. Only those patients presenting with non-life-threatening or incapacitating symptoms and at least 12 months of clinical and neuroimaging follow-up were eligible for inclusion. Relevant data were collected, and the Kaplan-Meier method was used to perform time-dependent analysis for post-SRS tumor control, hearing preservation, and facial nerve function preservation. Univariate and multivariate analyses were performed for outcome measures using Cox regression analysis. RESULTS: Six hundred twenty-seven patients (344 females, median patient age 54 [IQR 22] years) treated with primary SRS were included in this study. The median tumor volume was 8.7 (IQR 5) cm3. Before SRS, serviceable hearing, facial nerve weakness (House-Brackmann grade > I), and trigeminal neuropathy were present in 205 (33%), 48 (7.7%), and 203 (32.4%) patients, respectively. The median prescription dose was 12 (IQR 1) Gy. At a median radiological follow-up of 38 (IQR 54) months, tumor control was achieved in 94.1% of patients. Early tumor expansion occurred in 67 (10.7%) patients and was associated with a loss of tumor control at the last follow-up (p = 0.001). Serviceable hearing preservation rates at the 5- and 10-year follow-ups were 65% and 44.6%, respectively. Gardner-Robertson class > 1 (p = 0.003) and cochlear dose ≥ 4 Gy (p = 0.02) were risk factors for hearing loss. Facial nerve function deterioration occurred in 19 (3.0%) patients at the last follow-up and was associated with margin doses ≥ 13 Gy (p = 0.03) and early tumor expansion (p = 0.04). Post-SRS, 33 patients developed hydrocephalus requiring shunting. Adverse radiation effects occurred in 92 patients and were managed medically or surgically in 34 and 18 cases, respectively. CONCLUSIONS: SRS is a safe and effective method of obtaining tumor control in patients with Koos grade IV VS presenting with non-life-threatening or debilitating symptoms, especially those with surgical comorbidities that contraindicate resection. To decrease the incidence of post-SRS facial palsy, a prescription dose < 13 Gy is recommended.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in young patients: a multi-institutional study.

PURPOSE: Surgery is the treatment of choice for large vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has been suggested as an alternative to resection in selected patients. However, the safety and efficacy of SRS in Koos grade IV patients ≤ 45 years old has not been evaluated. The aim of this study is to describe the clinical and radiological outcomes of Koos grade IV in young patient managed with a single-session SRS. METHODS: This retrospective, multicenter analysis included SRS-treated patients, ≤ 45 years old presenting with non-life threatening or incapacitating symptoms due to a Koos Grade IV VS and with follow-up ≥ 12 months. Tumor control and neurological outcomes were evaluated. RESULTS: 176 patients [median age of 36.0 (IQR 9) and median tumor volume of 9.3 cm3 (IQR 4.7)] were included. The median prescription dose was 12 Gy (IQR 0.5). Median follow-up period was 37.5 (IQR 53.5) months. The 5- and 10-year progression-free survival was 90.9% and 86.7%. Early tumor enlargement occurred in 10.9% of cases and was associated with tumor progression at the last follow-up. The probability of serviceable hearing preservation at 5- and 10-years was 56.8% and 45.2%, respectively. The probability of improvement or preservation of facial nerve function was 95.7% at 5 and 10-years. Adverse radiation effects were noted in 19.9%. New-onset hydrocephalus occurred in 4.0%. CONCLUSION: Single-session SRS is a safe and effective alternative to surgical resection in selected patients ≤ 45 years old particularly those with medical co-morbidities and those who decline resection. Longer term follow up is warranted.

Outcome and toxicity analysis of single dose stereotactic radiosurgery in vestibular schwannoma based on the Koos grading system.

Stereotactic radiosurgery (SRS) has evolved as widely accepted treatment option for small-sized (Koos I up to II) vestibular schwannoma (VS). For larger tumors (prevalent Koos VI), microsurgery or combined treatment strategies are mostly recommended. However, in patients not suited for microsurgery, SRS might also be an alternative to balance tumor control, hearing preservation and adverse effects. The purpose of this analysis was to evaluate the efficacy and toxicity of SRS for VS with regard to different Koos grades. All patients with untreated VS who received SRS at our center were included. Outcome analysis included tumor control, preservation of serviceable hearing based on median pure tone averages (PTA), and procedure-related adverse events rated by the Common Terminology Criteria for Adverse Events (CTCAE; v4.03) classification. In total, 258 patients (median age 58 years, range 21-84) were identified with a mean follow-up of 52 months (range 3-228 months). Mean tumor volume was 1.8 ml (range 0.1-18.5). The mean marginal dose was 12.3 Gy ± 0.6 (range 11-13.5). The cohort was divided into two groups: A (Koos grades I and II, n = 186) and B (Koos grades III and IV, n = 72). The actuarial tumor control rate was 98% after 2 years and 90% after 5 and 10 years. Koos grading did not show a significant impact on tumor control (p = 0.632) or hearing preservation (p = 0.231). After SRS, 18 patients (7%) had new transient or permanent symptoms classified by the CTCAE. The actuarial rate of CTCAE-free survival was not related to Koos grading (p = 0.093). Based on this selected population of Koos grade III and IV VS without or with only mild symptoms from brainstem compression, SRS can be recommended as the primary therapy with the advantage of low morbidity and satisfactory tumor control. The overall hearing preservation rate and toxicity of SRS was influenced by age and cannot be predicted by tumor volume or Koos grading alone.

Twelve-year results of LINAC-based radiosurgery for vestibular schwannomas.

PURPOSE: To report long-term outcomes of 53 patients with vestibular schwannomas (VS) submitted to a single high-dose LINAC-based radiosurgery (SRS) in our institution. METHODS: 48 (92%) patients were evaluable for clinical and MRI response as well as late toxicity. At a median follow-up of 12 years (range 2-16 years), local control (LC), hearing capacity, trigeminal and facial nerve function, and toxicity were assessed. Hearing capacity was classified according to the Gardner-Robertson scale, where class I-II patients had "serviceable hearing." RESULTS: Median dose of SRS was 16.5 Gy (range 13-20 Gy) and median tumor volume 1.7 cm3 (range 0.09-7.4 cm3). 35 (73%) patients were treated with SRS alone, in the remaining 13 (27%) patients, SRS was performed as salvage therapy for recurrent or progressive tumors after previous microsurgery. Before SRS, 44 patients (92%) had hearing loss and 25 (52%) had "non-serviceable" hearing. Tumor extension, classified with Koos categories, was grade I-II in 27 (56%) and grade III-IV in 21 (44%) cases. LC was 100% and hearing preservation in "serviceable hearing" patients was 91%. 4 (11%) patients developed incomplete and intermittent ipsilateral facial nerve palsy which regressed in a median time of 6 months. Trigeminal toxicity was registered in 11 (23%) patients, reversible in 6 (13%) and permanent in 5 (10%). Only Koos tumor grade III-IV significantly influenced late toxicity (p = 0.01). CONCLUSION: LC and hearing preservation after SRS were excellent. Toxicity proved acceptable. Although the median administered dose (16.5 Gy) was rather high, the only factor which significantly influenced late toxicity was Koos tumor grade III-IV.

Cardiac pacing using transmural multi-LED probes in channelrhodopsin-expressing mouse hearts.

Optogenetics enables cell-type specific monitoring and actuation via light-activated proteins. In cardiac research, expressing light-activated depolarising ion channels in cardiomyocytes allows optical pacing and defibrillation. Previous studies largely relied on epicardial illumination. Light penetration through the myocardium is however problematic when moving to larger animals and humans. To overcome this limitation, we assessed the utility of an implantable multi light-emitting diode (LED) optical probe (IMLOP) for intramural pacing of mouse hearts expressing cardiac-specific channelrhodopsin-2 (ChR2). Here we demonstrated that IMLOP insertion needs approximately 20 mN of force, limiting possible damage from excessive loads applied during implantation. Histological sections confirmed the confined nature of tissue damage during acute use. The temperature change of the surrounding tissue was below 1 K during LED operation, rendering the probe safe for use in situ. This was confirmed in control experiments where no effect on cardiac action potential conduction was observed even when using stimulation parameters twenty-fold greater than required for pacing. In situ experiments on ChR2-expressing mouse hearts demonstrated that optical stimulation is possible with light intensities as low as 700 µW/mm2; although stable pacing requires higher intensities. When pacing with a single LED, rheobase and chronaxie values were 13.3 mW/mm2 ± 0.9 mW/mm2 and 3 ms ± 0.6 ms, respectively. When doubling the stimulated volume the rheobase decreased significantly (6.5 mW/mm2 ± 0.9 mW/mm2). We have demonstrated IMLOP-based intramural optical pacing of the heart. Probes cause locally constrained tissue damage in the acute setting and require low light intensities for pacing. Further development is necessary to assess effects of chronic implantation.

Treatment Outcomes and Dose Rate Effects Following Gamma Knife Stereotactic Radiosurgery for Vestibular Schwannomas.

BACKGROUND: Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored. OBJECTIVE: To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas. METHODS: We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression. RESULTS: The study cohort included 227 patients with available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rates were 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044). CONCLUSION: Whereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effects may impact post-treatment functional outcomes. Further research remains warranted.

Photobiomodulation using low-level 808 nm diode laser rescues cochlear synaptopathy after acoustic overexposure in rat.

A certain degree of noise can cause hearing problems without a permanent change in the hearing threshold, which is called hidden hearing loss and results from partial loss of auditory synapses. Photobiomodulation (PBM) enhances neural growth and connections in the peripheral nervous systems. In this study, we assessed whether PBM could rescue cochlear synaptopathy after acoustic overexposure in rat. PBM was performed for 7 days after noise exposure. The auditory brainstem responses (ABRs) were acquired before and after noise exposure using a tone and a paired-click stimulus. Auditory response to paired click sound with short time interval was performed to evaluate auditory temporal processing ability. In the result, hearing threshold recovered 2 weeks after noise exposure in both groups. Peak wave 1 amplitude of the ABR and ABR recovery threshold did not recover in the noise only group, whereas it fully recovered in the noise + PBM group. The number of synaptic ribbons was significantly different in the control and noise only groups, while there was no difference between the control and noise + PBM group. These results indicate that PBM rescued peak wave 1 amplitude and maintained the auditory temporal processing ability resulting from a loss of synaptic ribbons after acoustic overexposure.

A Retrospective Cohort Study of Longitudinal Audiologic Assessment in Single and Fractionated Stereotactic Radiosurgery for Vestibular Schwannoma.

BACKGROUND: Fractionated stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) has been theorized to allow for tumor control with higher rates of hearing preservation in selected patients with useful hearing. However, there is a paucity of literature with formal audiologic measures of hearing preservation to support the standard use of fractionated SRS in VS. We hypothesized that fractionation would diminish the amount of hearing damage. OBJECTIVE: To evaluate the relationship between audiologic performance and SRS fractionation scheme. METHODS: We performed an IRB-approved retrospective review of patients treated with 1, 3, or 5 fraction SRS for VS at our institution from 1998 to 2016. Pre- and post-SRS audiograms with speech awareness threshold (SAT) in treated and contralateral ears were obtained. Contralateral ear measurements were used for hearing normalization to account for presbycusis. RESULTS: Fifty-six patients with median audiologic follow-up 2.0 yr (mean 2.66 yr, min-max 0.50-9.45 yr) were included. Patients treated with single fractionation had a significantly worsened SAT (dB) compared to patients treated with 5 fractions (P = .008) and compared to all multifraction patients (P = .009) at 12 to 24 mo follow-up. CONCLUSION: This retrospective analysis supports the use of fractionated SRS to preserve hearing in patients with VS. SAT can be used as an objective metric of hearing response to radiosurgery.

Clinical results of proton therapy reirradiation for recurrent nasopharyngeal carcinoma.

Background and purpose: Recurrent nasopharyngeal carcinoma (NPC) has limited curative treatment options. Reirradiation is the only potential definitive treatment in advanced stages at a cost of substantial severe and often life-threatening toxicity. Proton therapy (PT) reduces irradiated volume compared with X-ray radiotherapy and could be advantageous in terms of safety and efficacy in a population of heavily pretreated patients. We report the retrospective results of PT reirradiation in recurrent NPC patients treated at our Institution Methods: All recurrent NPC patients treated since the beginning of clinical activity entered the present analysis. Clinical target volume consisted of Gross Tumor volume plus a patient-specific margin depending on disease behavior, tumor location, proximity of organs at risk, previous radiation dose. No elective nodal irradiation was performed. Active scanning technique with the use of Single Field Optimization (SFO) or Multifield Optimization (MFO) was adopted. Cumulative X-ray -PT doses were calculated for all patients using a dose accumulation tool since 2016. Treatment toxicity was retrospectively collected. Results: Between February 2015, and October 2018, 17 recurrent NPC patients were treated. Median follow-up (FUP) was 10 months (range 2-41). Median PT reirradiation dose was 60 Gy RBE (range 30.6-66). The majority of patients (53%) underwent concomitant chemotherapy. Acute toxicity was low with no ≥ G3 adverse events. Late events ≥ G3 occurred in 23.5% of patients. Most frequent late toxicity was hearing impairment (17,6%). G2 soft tissue necrosis occurred in two patients. Fatal bleeding of uncertain cause (either tumor recurrence or G5 carotid blowout) occurred in one patient. Kaplan-Meier 18 months Overall Survival (OS) and Local control (LC) rates were 54.4% and 66.6%, respectively. Conclusions: Our initial results with the use of modern PT for reirradiation of recurrent NPC patients are encouraging. Favorable LC and OS rates were obtained at the cost of acceptable severe late toxicity.

Is intensity-modulated radiotherapy superior to conventional techniques to prevent late ear complications of nasopharyngeal cancer?

PURPOSE: This study analyzed the late ear complications of radiotherapy for nasopharyngeal cancer (NPC) and compared the conventional and intensity-modulated radiotherapy (2D-RT and IMRT, respectively). METHODS: At 2-21 years after the end of NPC treatment, 104 ears of 52 patients were evaluated with the otoscopic examination, pure tone audiometry test, tympanometry, and subjective complaints by being blinded to the radiotherapy technique. RESULTS: There were no differences in terms of the pathology of the external, middle or inner ear, air and bone-conduction hearing thresholds, and the air-bone (A-B) gap at 500, 1000, 2000, and 4000 Hz, and tympanometry types between 2D-RT and IMRT groups (p > 0.05). There were positive correlations between the values of A500 and A1000 thresholds; gap 500, 4000, and mean cochlear RT dose (p < 0.05). There were positive correlations between the values of A500, A1000, and A4000 thresholds; gap 500, 1000, 2000, 4000, and maximum cochlear RT dose (p < 0.05). CONCLUSION: IMRT was not found to be superior to 2D-RT to prevent RT-induced ear complications. The solution of the middle ear problems must be the goal of the strategies for complications treatment.

Progression of hearing loss after LINAC-based stereotactic radiotherapy for vestibular schwannoma is associated with cochlear dose, not with pre-treatment hearing level.

BACKGROUND: Although stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore wished to assess the change in hearing loss after SRT and to determine which patient, tumor and treatment-related factors influence deterioration. METHODS: We retrospectively analyzed progression of hearing loss in patients with vestibular schwannoma who had received stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) as a primary treatment between 2000 and 2014. SRS had been delivered as a single fraction of 12 Gy, and patients treated with FSRT had received 30 fractions of 1.8 Gy. To compare the effects of SRS and FSRT, we converted cochlear doses into EQD2. Primary outcomes were loss of functional hearing, Gardner Robertson (GR) classes I and II, and loss of baseline hearing class. These events were used in Kaplan Meier plots and Cox regression. We also calculated the rate of change in Pure Tone Average (PTA) in dB per month elapsed after radiation-a measure we use in linear regression-to assess the associations between the rate of change in PTA and age, pre-treatment hearing level, tumor size, dose scheme, cochlear dose, and time elapsed after treatment (time-to-first-audiogram). RESULTS: The median follow-up was 36 months for 67 SRS patients and 63 months for 27 FSRT patients. Multivariate Cox regression and in linear regression both showed that the cochlear V90 was significantly associated with the progression of hearing loss. But although pre-treatment PTA correlated with rate of change in Cox regression, it did not correlate in linear regression. The time-to-first-audiogram was also significantly associated, indicating time dependency of the rate of change. None of the analysis showed a significant difference between dose schemes. CONCLUSIONS: We found no significant difference between SRS and FSRT. As the deterioration in hearing after radiotherapy for vestibular schwannoma was associated with the cochlea V90, restricting the V90 may reduce progression of hearing loss. The association between loss of functional hearing and baseline PTA seems to be biased by the use of a categorized variable for hearing loss.

Radiosurgery of vestibular schwannoma: prognostic factors for hearing outcome using 3D-constructive interference in steady state (3D-CISS).

PURPOSE: Stereotactic radiosurgery (SRS) is an effective treatment for vestibular schwannoma (VS). Three-dimensional (3D) constructive interference in steady state (CISS) is the preferred magnetic resonance imaging (MRI) sequence for evaluating signal changes in the inner ear endolymph. Previous studies demonstrated a correlation between pretreatment cochlear signal intensity in 3D-CISS and posttherapeutic hearing outcomes. The purpose of our study was to compare 3D-CISS sequences before and after primary SRS of unilateral VSs to evaluate the effect of radiosurgery on the 3D-CISS signal intensities of cochlea and sacculus/utriculus. METHODS: We retrospectively reviewed 47 patients with unilateral VS treated with SRS. The neuroradiological MRI datasets were analysed to evaluate the signal intensity of the inner ear structure, tumour size, Koos grade, tumour volume, and infiltration of the cochlear aperture before therapy and at follow-up. The differences in these signal intensities before SRS and at follow-up were correlated with clinical symptoms, cochlear radiation dose, tumour volume and infiltration of the cochlear aperture. RESULTS: No differences were found between signal intensities in cochlea and utriculus/sacculus before and after SRS and no correlation with clinical symptoms, cochlear radiation dose, tumour volume, Koos grade or infiltration of the cochlear aperture (all p > 0.05). CONCLUSION: Our study supports the theory of a complex interaction causing alteration of the endolymph protein concentration and not a direct dependency on the SRS. Use of modern dosing schemes will have a positive impact on clinical outcome with preservation of hearing in patients with VS.

Prospective evaluation of the early effects of radiation on the auditory system frequencies of patients with head and neck cancers and brain tumors after radiotherapy.

Patients with head and neck cancer after radiotherapy often suffer disability such as hearing disorders. In this study, the effect of radiotherapy (RT) on hearing function of patients with head and neck cancer after RT was determined according to the total dose delivered to specific parts of the auditory system. A total of 66 patients treated with primary or postoperative radiation therapy for various cancers in the head and neck region were selected. All patients had audiologic evaluation with pure tone audiometry for the frequencies of 250, 500, 1,000, 2,000, 3,000, 4,000, 6,000, and 8,000 Hz before and immediately after completion of treatment and again 3 months later. The cochlea dose volume histograms of the patients were derived from their computed-tomography-based treatment plans. At study's end, RT-induced auditory complications developed in 33% of patients. The greatest hearing loss (changes >15 dB) occurred immediately after RT at frequencies of 3,000 (14.5%), 4,000 (12.9%), 6,000 (13.6%), and 8,000 Hz (10.6%), and after 3 months of follow-up, at 3,000 (6.8%), 4,000 (7.7%), 6,000 (10.7%), and 8,000 Hz (12.1%). Univariate and multivariate analyses indicated a positive relationship between dose delivered to the cochlea and hearing loss (p < 0.001, r = 0.484). An increased risk of hearing loss was present for patients receiving ≥40 Gy as their mean dose compared with those receiving <30 Gy. We conclude that radiation dose has negative effects on the auditory system. This effect occurs more in high-frequency hearing. The received dose to the cochlea was the main cause of damage to hearing.

Ototoxicity and cochlear sparing in children with medulloblastoma: Proton vs. photon radiotherapy.

PURPOSE: To compare ototoxicity rates between medulloblastoma patients treated with protons vs. photons. MATERIALS AND METHODS: The study included 84 children diagnosed with medulloblastoma treated with either passively scattered protons (n = 38) or photons (n = 46). Patients underwent maximal safe resection followed by craniospinal irradiation, posterior fossa and/or tumor bed boost and chemotherapy according to one of 3 multi-institutional trials. Median audiogram follow-up was 56 months for protons and 66 months for photons. RESULTS: Mean cochlear dose (Dmc) was lower in patients treated with protons for both standard (p < 0.0001) and high-risk disease (p < 0.001). Grade 3 and 4 ototoxicity was seen in 7 of 75 (9.3%) and 9 of 91 (9.9%) ears (Brock, p = 0.91), 13 of 75 (17.3%) and 19 of 91 (20.9%) ears (POG, p = 0.56), and 15 of 75 (20.0%) and 21 of 91 (23.1%) ears (SIOP Boston, p = 0.63) with protons and photons respectively. CONCLUSIONS: While cochlear doses were lower in the proton group, patients treated with either protons or photons had similar Grade 3 and 4 ototoxicity rates.

Chemoradiation-induced hearing loss remains a major concern for head and neck cancer patients.

OBJECTIVE: Review of the literature regarding hearing loss in patients with head and neck cancer treated with chemoradiation. DESIGN: Studies in the literature are reviewed that pertain to hearing loss sustained in head and neck cancer patients receiving cisplatin-based chemoradiation. Personal observations noted while treating these patients are also detailed. STUDY SAMPLE: PubMed was searched for pertinent articles regarding hearing loss in head and neck cancer patients receiving cisplatin chemotherapy and/or radiation. RESULTS: Studies on the incidence and severity of hearing loss in head and neck cancer patients are limited, but those studies suggest that the risk of hearing loss is greater with higher-dose regimens. CONCLUSIONS: Newer cisplatin chemotherapy regimens using lower, weekly doses may be associated with a lower incidence and severity of hearing loss; however, large prospective studies are needed. Such information will be paramount to effective pre-treatment counselling of head and neck cancer patients.

Population-Based Study of Stereotactic Radiosurgery or Fractionated Stereotactic Radiation Therapy for Vestibular Schwannoma: Long-Term Outcomes and Toxicities.

PURPOSE: To examine long-term local control of vestibular schwannoma and side effects in patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (SRT) in British Columbia. METHODS AND MATERIALS: From August 1998 to May 2009, 207 patients were treated with radiation therapy (RT) at British Columbia Cancer Agency. 136 (66%) received SRS, and 71 (34%) received SRT. Dose prescriptions were 50 Gy/25 fractions for SRT and 12 Gy/1 fraction for SRS. Our multidisciplinary provincial neuro-stereotactic conference recommended SRT for tumors >3 cm and for patients with serviceable hearing (Gardner-Robertson classes I and II). RESULTS: Median follow-up was 7.7 years to the last MRI and 6.4 years to the last clinical assessment. Local control for SRS versus SRT was 94% versus 87% at 5 years and 90% versus 85% at 10 years (P=.2). Five- and 10-year actuarial rates of RT-induced trigeminal nerve dysfunction were 25% and 25% after SRS, compared with 7% and 12% after SRT (P=.01). Five- and 10-year actuarial rates of RT-induced facial nerve dysfunction were 15% and 15% after SRS, versus 13% and 15% after SRT (P=.93). In the 49 patients with serviceable hearing at baseline who were treated with SRT, hearing preservation was 55% at 3 years, 37% at 5 years, and 29% at 7 years. In multivariable analysis, better pretreatment ipsilateral pure tone average was significantly associated with hearing preservation (hazard ratio 1.03; 95% confidence interval 1.00-1.07; P=.04). CONCLUSIONS: Both SRS and SRT provided excellent long-term local control of vestibular schwannoma. Stereotactic radiosurgery was associated with higher rates of trigeminal nerve dysfunction. Even with a fractionated course, hearing preservation declined steadily with long-term audiometric follow-up.

Effects of exposure to 2100 MHz GSM-like radiofrequency electromagnetic field on auditory system of rats / Efeitos da exposição a um campo eletromagnético na radiofrequência de 2100 MHz, similar ao sistema GSM, no sistema auditivo de ratos

Abstract Introduction: The use of mobile phones has become widespread in recent years. Although beneficial from the communication viewpoint, the electromagnetic fields generated by mobile phones may cause unwanted biological changes in the human body. Objective: In this study, we aimed to evaluate the effects of 2100 MHz Global System for Mobile communication (GSM-like) electromagnetic field, generated by an electromagnetic fields generator, on the auditory system of rats by using electrophysiological, histopathologic and immunohistochemical methods. Methods: Fourteen adult Wistar albino rats were included in the study. The rats were divided randomly into two groups of seven rats each. The study group was exposed continuously for 30 days to a 2100 MHz electromagnetic fields with a signal level (power) of 5.4 dBm (3.47 mW) to simulate the talk mode on a mobile phone. The control group was not exposed to the aforementioned electromagnetic fields. After 30 days, the Auditory Brainstem Responses of both groups were recorded and the rats were sacrificed. The cochlear nuclei were evaluated by histopathologic and immunohistochemical methods. Results: The Auditory Brainstem Responses records of the two groups did not differ significantly. The histopathologic analysis showed increased degeneration signs in the study group (p = 0.007). In addition, immunohistochemical analysis revealed increased apoptotic index in the study group compared to that in the control group (p = 0.002). Conclusion: The results support that long-term exposure to a GSM-like 2100 MHz electromagnetic fields causes an increase in neuronal degeneration and apoptosis in the auditory system.

Resumo Introdução: O uso de telefones celulares tornou-se generalizado nos últimos anos. Embora benéfico do ponto de vista da comunicação, os campos eletromagnéticos gerados por celulares pode causar alterações biológicas indesejáveis no corpo humano. Objetivo: Nesse estudo, o objetivo foi avaliar os efeitos do campo eletromagnético na frequência de 2.100 MHz, similar à modulação do Sistema Global para Comunicações Móveis, produzido por um gerador de campo eletromagnético, sobre o sistema auditivo de ratos usando os métodos eletrofisiológico, histopatológico e imunohistoquímico. Método: Foram incluídos no estudo catorze adultos ratos albinos Wistar. Os ratos foram divididos aleatoriamente em dois grupos de sete animais cada. O grupo de estudo foi exposto continuamente por 30 dias a um campo eletromagnético em 2100 MHz com um nível de sinal (potência) de 5,4 dBm (3,47 miliwatts) para simular o modo de conversação em um celular. O grupo controle não foi exposto ao campo eletromagnético acima mencionado. Após 30 dias, o potencial evocado auditivo de tronco encefálico de ambos os grupos foi gravado e os ratos foram sacrificados. Os núcleos cocleares foram avaliados pelos métodos histopatológico e imunohistoquímico. Resultados: Os registros do potencial evocado auditivo de tronco encefálico dos dois grupos não diferiram significativamente. A análise histopatológica mostrou aumento dos sinais de degeneração no grupo de estudo (p = 0,007). Além disso, a análise imuno-histoquímica revelou aumento do índice de apoptose no grupo de estudo em comparação com o grupo controle (p = 0,002). Conclusão: Os resultados confirmam que a exposição a longo prazo a um campo eletromagnético em 2100 MHz similar à modulação do sistema global para comunicações móveis causa um aumento na degeneração neuronal e apoptose no sistema auditivo.