Effect of shock wave power spectrum on the inner ear pathophysiology in blast-induced hearing loss.

Blast exposure can induce various types of hearing impairment, including permanent hearing loss, tinnitus, and hyperacusis. Herein, we conducted a detailed investigation of the cochlear pathophysiology in blast-induced hearing loss in mice using two blasts with different characteristics: a low-frequency dominant blast generated by a shock tube and a high-frequency dominant shock wave generated by laser irradiation (laser-induced shock wave). The pattern of sensorineural hearing loss (SNHL) was low-frequency- and high-frequency-dominant in response to the low- and high-frequency blasts, respectively. Pathological examination revealed that cochlear synaptopathy was the most frequent cochlear pathology after blast exposure, which involved synapse loss in the inner hair cells without hair cell loss, depending on the power spectrum of the blast. This pathological change completely reflected the physiological analysis of wave I amplitude using auditory brainstem responses. Stereociliary bundle disruption in the outer hair cells was also dependent on the blast's power spectrum. Therefore, we demonstrated that the dominant frequency of the blast power spectrum was the principal factor determining the region of cochlear damage. We believe that the presenting models would be valuable both in blast research and the investigation of various types of hearing loss whose pathogenesis involves cochlear synaptopathy.

Melatonin reduces radiation damage in inner ear.

The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P < 0.05). DPOAEs showed radiotherapy-induced hearing loss at 8-12 kHz, and hearing loss was greater on day 7 than day 3. However, hearing loss was less in the melatonin groups (P < 0.05). Histopathological examination showed irradiation resulted in breaks and distortion of the cochlear basement membrane, disruption of the stria vascularis, and swelling of outer hair cells. Melatonin reduced these changes. Radiotherapy upregulated prestin mRNA expression. Radiotherapy-induced upregulation of prestin was decreased in the melatonin groups (P < 0.05), and the decrease was greater in the 50 mg/kg melatonin group (P < 0.05). Melatonin protects against radiation-induced cochlear damage by reducing damage to outer hair cells.

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response.

BACKGROUND: In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 (RvE1) has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of RvE1 using mouse models. METHODS: A dose of RvE1 was delivered by intraperitoneal injection to mice before irradiation. Changes in the auditory brainstem response (ABR), relative balance ability, inner ear morphology and the expression levels of inflammatory factors in the inner ear were analyzed on days 7 and 14 after irradiation and compared among different experimental groups. RESULTS: Changes of ABR and relative balance ability showed the inner functions of experimental mice presented severe damage after irradiation, but the damage was significantly alleviated after RvE1 pretreatment compared to irradiation alone. Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the RvE1-pretreated group compared to that in the irradiation alone group. Along with these functional and morphological changes, the mRNA expression level of anti-inflammatory factors interleukin-2 was significantly increased, while those of proinflammatory factors interleukin-6 and tumor necrosis factor-α were significantly decreased in the inner ear of mice after RvE1 pretreatment compared to irradiation alone. CONCLUSIONS: We believe that inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that RvE1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.

Dosimetric evaluation of four whole brain radiation therapy approaches with hippocampus and inner ear avoidance and simultaneous integrated boost for limited brain metastases.

AIMS: To perform a dosimetric evaluation of four different simultaneous integrated boost whole brain radiotherapy modalities with hippocampus and inner ear avoidance in the treatment of limited brain metastases. METHODS: Computed tomography/magnetic resonance imaging data of 10 patients with limited (1-5) brain metastases were used to replan step-and-shoot intensity-modulated radiotherapy (sIMRT), dynamic intensity-modulated radiation therapy (dIMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (Tomo). The prescribed doses of 40-50 Gy in 10 fractions and 30 Gy in 10 fractions were simultaneously delivered to the metastatic lesions and the whole-brain volume, respectively. The hippocampal dose met the RTOG 0933 criteria for hippocampal avoidance (Dmax ≤17 Gy, D100% ≤10 Gy). The inner ear dose was restrained to Dmean ≤15 Gy. Target coverage (TC), homogeneity index (HI), conformity index (CI), maximum dose (Dmax), minimum dose (Dmin) and dose to organs at risk (OARs) were compared. RESULTS: All plans met the indicated dose restrictions. The mean percentage of planning target volume of metastases (PTVmets) coverage ranged from 97.1 to 99.4%. For planning target volume of brain (PTVbrain), Tomo provided the lowest average D2% (37.5 ± 2.8 Gy), the highest average D98% (25.2 ± 2.0 Gy), and the best TC (92.6% ± 2.1%) and CI (0.79 ± 0.06). The two fixed gantry IMRT modalities (step and shot, dynamic) provided similar PTVbrain dose homogeneity (both 0.76). Significant differences across the four approaches were observed for the maximum and minimum doses to the hippocampus and the maximum doses to the eyes, lens and optic nerves. CONCLUSION: All four radiotherapy modalities produced acceptable treatment plans with good avoidance of the hippocampus and inner ear. Tomo obtained satisfactory PTVbrain coverage and the best homogeneity index. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03414944 . Registered 29 January 2018.

[Effect of melatonin on expression of Prestin protein in the inner ear of mice following radiotherapy].

Objective: To investigate the effect of melatonin on the expression of prestin protein in the inner ear of mice following a single dose radiation therapy, so as to provide the basis for the mechanism study of radiation induced inner ear injury and its prevention. Methods: Sixty 4-week-old male mice were randomly divided into six groups, including the control group (A group), 50 mg/kg MLT group (B group), 5 mg/kg MLT group (C group), 50 mg/kg MLT + radiotherapy group (D group), 5 mg/kg MLT+ radiotherapy group (E group), and 16 Gy radiotherapy group (F group). Each experimental group was randomly subdivided into two subgroups, which were killed to harvest the cochlea on the 3rd and 7th days following 16 Gy radiation. The specimens were used for immunostaining and Western blot to detect the expression of prestin protein. SPSS 19.0 software was used for statistical analysis. Results: Prestin protein mainly distributed in the lateral membrane above the outer hair cell nucleus. When compared with A, B and C group, the expression of prestin protein in the inner ear was significantly up-regulated in F group (P<0.05). However, D and E group reduced the abnormal expression of prestin following radiotherapy when compared with F group, the difference was statistically significant (P<0.05), and the effect of D group was more significant than E group (P<0.05). Conclusions: The prestin protein of cochlea is mainly distributed in the lateral membrane above the outer hair cell nucleus. Following the high-dose radiotherapy, the prestin expression is upregulated, and melatonin can control the abnormal expression of prestin protein induced by radiotherapy with dose dependent.

Vestibular function disorders and potential mechanisms in irradiation nasopharyngeal carcinoma patients.

CONCLUSIONS: Vestibular function disorders were widespread among nasopharyngeal carcinoma (NPC) patients. The radiation doses to the inner ears were associated with the incidence of vestibular function disorders, but the correlations were mild. The inflammatory responses and possible resolution obstacles of inflammation participated in persistent vestibular function disorders after irradiation. OBJECTIVES: To investigate the incidence of vestibular function disorders in NPC patients after irradiation and potential mechanisms. METHODS: Patients who received radical intensity-modulated radiotherapy for their NPC were recruited. The serum levels of IL-6 and IL-17 were detected by ELISA method. Vestibular evoked myogenic potential (VEMP) tests were used to evaluate vestibular function and correlation analyses were used to analyze the potential mechanisms of vestibular function disorders. RESULTS: Thirty-eight patients were included. The incidences of abnormal ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were 65.79% and 80.26% at the time of completion of radiotherapy, and 61.84% and 71.05% at 3 months after radiotherapy. The mean and maximum radiation doses to the inner ears were both significantly associated with abnormal oVEMP and cVEMP (p < 0.05, all), but the correlations were all mild. The serum levels of IL-6 and IL-17 were both significantly associated with abnormal oVEMP and cVEMP after irradiation (p < 0.05, all).

Cancer treatment in determination of hearing loss / Tratamento oncológico na determinação das alterações auditivas

ABSTRACT INTRODUCTION: Chemotherapy and radiotherapy in oncology have repercussions in hearing health, and can damage structures of the inner ear. These repercussions usually, result in a bilateral and irreversible hearing loss. OBJECTIVE: To identify sensorineural hearing loss cases with complaints of tinnitus and difficulty in speech understanding and investigate their relationship with the types of chemotherapy and radiotherapy the patients received. METHODS: Cross-sectional, clinical, observational, analytical, historical cohort study of 58 subjects treated in a public hospital in the state of Sergipe, diagnosed with neoplasia. The subjects were submitted to anamnesis, conventional pure tone audiometry, and speech recognition threshold. RESULTS: Of the 116 ears, 25.9% presented sensorioneural hearing loss characterized by changes in high frequencies. There was a positive correlation between hearing loss and the association of chemotherapy and radiotherapy ( p = 0.035; R = 0.196). The auditory complaint analysis shows that most of the subjects had tinnitus and speech understanding difficulty, even with a normal auditory threshold. CONCLUSIONS: Cancer treatment causes hearing loss, associated with the administration of chemotherapy and radiotherapy. Cyclophosphamide increased the risk of causing hearing loss. Complaints of tinnitus and speech understanding difficulty were observed.

RESUMO INTRODUÇÃO: O tratamento quimioterápico e radioterápico na oncologia tem repercussão na saúde auditiva e pode lesar estruturas da orelha interna. Ocasiona perda auditiva, geralmente bilateral e irreversível. OBJETIVO: Identificar casos de perda auditiva sensorioneural e sua relação com a média de sessões de quimioterapia e radioterapia, com queixas de zumbido e dificuldade de entendimento da fala, bem como sua relação com medicamentos quimioterápicos. MÉTODO: Estudo de coorte histórica com corte transversal, clínico, observacional, analítico e retrospectivo em 58 sujeitos de um hospital público de Sergipe diagnosticados com neoplasia. Realizou-se anamnese, avaliação audiológica tonal convencional e pesquisa do limiar de reconhecimento de fala. RESULTADOS: Das 116 orelhas; 25,9% apresentaram perda auditiva sensorioneural caracterizada por alterações nas frequências agudas. Observou-se correlação significativa entre perda auditiva e associação da quimioterapia e radioterapia (p = 0,035; R = 0,196). Na análise das queixas auditivas, verificou-se que a maioria apresentou zumbido e dificuldade de entendimento de fala, mesmo com limiares auditivos normais. CONCLUSÕES: O tratamento oncológico gera perda auditiva, que foi determinada pela associação da quimioterapia e radioterapia. Ciclofosfamida aumentou as chances de gerar perda auditiva. Verificou-se presença de queixas de zumbido e dificuldade de entendimento da fala.

Cancer treatment in determination of hearing loss.

INTRODUCTION: Chemotherapy and radiotherapy in oncology have repercussions in hearing health, and can damage structures of the inner ear. These repercussions usually, result in a bilateral and irreversible hearing loss. OBJECTIVE: To identify sensorineural hearing loss cases with complaints of tinnitus and difficulty in speech understanding and investigate their relationship with the types of chemotherapy and radiotherapy the patients received. METHODS: Cross-sectional, clinical, observational, analytical, historical cohort study of 58 subjects treated in a public hospital in the state of Sergipe, diagnosed with neoplasia. The subjects were submitted to anamnesis, conventional pure tone audiometry, and speech recognition threshold. RESULTS: Of the 116 ears, 25.9% presented sensorioneural hearing loss characterized by changes in high frequencies. There was a positive correlation between hearing loss and the association of chemotherapy and radiotherapy (p=0.035; R=0.196). The auditory complaint analysis shows that most of the subjects had tinnitus and speech understanding difficulty, even with a normal auditory threshold. CONCLUSIONS: Cancer treatment causes hearing loss, associated with the administration of chemotherapy and radiotherapy. Cyclophosphamide increased the risk of causing hearing loss. Complaints of tinnitus and speech understanding difficulty were observed.

Radioprotective Effect of Aminothiol PrC-210 on Irradiated Inner Ear of Guinea Pig.

Radiotherapy of individuals suffering with head & neck or brain tumors subserve the risk of sensorineural hearing loss. Here, we evaluated the protective effect of Aminothiol PrC-210 (3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol) on the irradiated inner ear of guinea pigs. An intra-peritoneal or intra-tympanic dose of PrC-210 was administered prior to receiving a dose of gamma radiation (3000 cGy) to each ear. Auditory Brainstem Responses (ABRs) were recorded one week and two weeks after the radiation and compared with the sham animal group. ABR thresholds of guinea pigs that received an intra-peritoneal dose of PrC-210 were significantly better compared to the non-treated, control animals at one week post-radiation. Morphologic analysis of the inner ear revealed significant inflammation and degeneration of the spiral ganglion in the irradiated animals not treated with PrC-210. In contrast, when treated with PrC-210 the radiation effect and injury to the spiral ganglion was significantly alleviated. PrC-210 had no apparent cytotoxic effect in vivo and did not affect the morphology or count of cochlear hair cells. These findings suggest that aminothiol PrC-210 attenuated radiation-induced cochlea damage for at least one week and protected hearing.

Inner ear deficits in irradiated nasopharyngeal carcinoma survivors.

OBJECTIVES/HYPOTHESIS: Despite the advancement of concurrent chemoradiotherapy, inner ear symptoms such as hearing loss, tinnitus, or vertigo/dizziness are still experienced in irradiated nasopharyngeal carcinoma (NPC) survivors. This study utilized an inner ear test battery to assess the causes and sequence of inner ear deficits in irradiated NPC survivors with a mean interval of 10 years after radiotherapy. STUDY DESIGN: Retrospective study. METHODS: Thirty-six irradiated NPC survivors were enrolled. Otoscopy and an inner ear test battery comprising audiometry were performed, as well as ocular vestibular-evoked myogenic potential (oVEMP), cervical VEMP (cVEMP), and caloric tests. RESULTS: Otoscopic examination revealed middle ear complications in 37 ears (51%), including radiation-induced otitis media in 32 ears and otitis media with effusion in five ears. Percentages of abnormal cVEMP test, oVEMP test, bone-conducted mean hearing level, and caloric test were 91%, 75%, 67%, and 39%, respectively, exhibiting a significantly declining sequence in inner ear deficits. Most (67%) NPC survivors had inner ear deficit originated from peripheral vestibular lesion, mainly due to sequela of otitis media. In contrast, 33% of them had inner ear deficit caused by central vestibular disorder. CONCLUSIONS: A significant sequential decline in inner ear function of irradiated NPC survivors was observed from the saccule to the utricle, cochlea, and semicircular canals. Most of them were due to sequela of otitis media, followed by central vestibular disorder. LEVEL OF EVIDENCE: 4.

Melatonin protects inner ear against radiation damage in rats.

OBJECTIVES/HYPOTHESIS: To examine the effects of N-acetyl-5-methoxytryptamine (melatonin) on radiation-induced inner ear damage. STUDY DESIGN: An experimental animal model. METHODS: Forty rats were randomized into five groups, as follows: 1) melatonin and then radiotherapy group (n = 8), which received intraperitoneal (i.p.) melatonin (5 mg/kg) followed by irradiation 30 minutes later; 2) radiotherapy and then melatonin group (n = 8), which received irradiation with i.p. melatonin (5 mg/kg) 30 minutes later; 3) melatonin group (n = 8), which received i.p. melatonin (5 mg/kg); 4) radiotherapy group (n = 8), which underwent only irradiation; 5) and the control group (n = 8), which received i.p. 0.9% NaCl. The medications and irradiation were administered for 5 days. All rats underwent the distortion product otoacoustic emission (DPOAE) test before and 10 days after the experiment. The middle ears of the rats were excised, and assessment of tissue alterations in the organs of Corti, spiral ganglions, and stria vascularis were compared among the groups. RESULTS: In the radiotherapy group, the DPOAE amplitudes at frequencies of 4000 to 6000 Hz were significantly decreased when compared with the controls. The DPOAE amplitudes both in the melatonin and then radiotherapy group and the radiotherapy and then melatonin group exhibited better values than they did in the radiotherapy group. Histopathological evidence of damage to the organs of Corti, spiral ganglions, and stria vascularis damage was markedly reduced in both these two groups when compared to the radiotherapy group. CONCLUSION: These results indicate that melatonin may have significant ameliorative effects on cochlear damage secondary to ionizing radiation.

Effects of chronic exposure to electromagnetic waves on the auditory system.

CONCLUSION: The results support that chronic electromagnetic field exposure may cause damage by leading to neuronal degeneration of the auditory system. OBJECTIVES: Numerous researches have been done about the risks of exposure to the electromagnetic fields that occur during the use of these devices, especially the effects on hearing. The aim of this study is to evaluate the effects of the electromagnetic waves emitted by the mobile phones through the electrophysiological and histological methods. METHODS: Twelve adult Wistar albino rats were included in the study. The rats were divided into two groups of six rats. The study group was exposed to the electromagnetic waves over a period of 30 days. The control group was not given any exposure to the electromagnetic fields. After the completion of the electromagnetic wave application, the auditory brainstem responses of both groups were recorded under anesthesia. The degeneration of cochlear nuclei was graded by two different histologists, both of whom were blinded to group information. RESULTS: The histopathologic and immunohistochemical analysis showed neuronal degeneration signs, such as increased vacuolization in the cochlear nucleus, pyknotic cell appearance, and edema in the group exposed to the electromagnetic fields compared to the control group. The average latency of wave in the ABR was similar in both groups (p > 0.05).

Characteristics of laser-induced shock wave injury to the inner ear of rats.

Recently, the number of blast injuries of the inner ear has increased in the general population. In blast-induced inner ear injury, a shock wave (SW) component in the blast wave is considered to play an important role in sensorineural hearing loss. However, the mechanisms by which an SW affects inner ear tissue remain largely unknown. We aimed to establish a new animal model for SW-induced inner ear injury by using laser-induced SWs (LISWs) on rats. The LISWs were generated by irradiating an elastic laser target with 694-nm nanosecond pulses of a ruby laser. After LISW application to the cochlea through bone conduction, auditory measurements revealed the presence of inner ear dysfunction, the extent of which depended on LISW overpressure. A significantly lower survival rate of hair cells and spiral ganglion neurons, as well as severe oxidative damage, were observed in the inner ear exposed to an LISW. Although considerable differences in the pressure characteristics exist between LISWs and SWs in real blast waves, the functional and morphological changes shown by the present LISW-based model were similar to those observed in real blast-induced injury. Thus, our animal model is expected to be useful for laboratory-based research of blast-induced inner ear injury.

Volumetric modulated arc-based hypofractionated stereotactic radiotherapy for the treatment of selected intracranial arteriovenous malformations: dosimetric report and early clinical experience.

PURPOSE: To evaluate, with a dosimetric and clinical feasibility study, RapidArc (a volumetric modulated arc technique) for hypofractionated stereotactic radiotherapy treatment of large arteriovenous malformations (AVMs). METHODS AND MATERIALS: Nine patients were subject to multimodality imaging (magnetic resonance, computed tomography, and digital subtraction angiography) to determine nidus and target volumes, as well as involved organs at risk (optical structures, inner ear, brain stem). Plans for multiple intensity-modulated arcs with a single isocenter were optimized for a fractionation of 25 Gy in 5 fractions. All plans were optimized for 6-MV photon beams. Dose-volume histograms were analyzed to assess plan quality. Delivery parameters were reported to appraise technical features of RapidArc, and pretreatment quality assurance measurements were carried out to report on quality of delivery. RESULTS: Average size of AVM nidus was 26.2 cm(3), and RapidArc plans provided complete target coverage with minimal overdosage (V(100%) = 100% and V(110%) < 1%) and excellent homogeneity (<6%). Organs at risk were highly spared. The D(1%) to chiasm, eyes, lenses, optic nerves, and brainstem (mean ± SD) was 6.4 ± 8.3, 1.9 ± 3.8, 2.3 ± 2.2, 0.7 ± 0.9, 4.4 ± 7.2, 12.2 ± 9.6 Gy, respectively. Conformity index (CI(95%)) was 2.2 ± 0.1. The number of monitor units per gray was 277 ± 45, total beam-on time was 2.5 ± 0.3 min. Planning vs. delivery γ pass rate was 98.3% ± 0.9%. None of the patients developed acute toxicity. With a median follow-up of 9 months, 3 patients presented with deterioration of symptoms and were found to have postradiation changes but responded symptomatically to steroids. These patients continue to do well on follow-up. One patient developed headache and seizures, which was attributed to intracranial bleed, confirmed on imaging. CONCLUSION: Hypofractionated stereotactic radiotherapy can be successfully delivered using the RapidArc form of volumetric arc technology for intracranial AVMs. The quality of delivery and calculated parameters are in agreement with each other and are in line with published reports for other sites.

Neurophysiology: vertigo in MRI machines.

Subjects of brain-imaging studies often report experiencing vertigo while in MRI machines; a new study shows that the magnetic field stimulates the vestibular sensors in the inner ear by a Lorentz force.

MRI magnetic field stimulates rotational sensors of the brain.

Vertigo in and around magnetic resonance imaging (MRI) machines has been noted for years [1, 2]. Several mechanisms have been suggested to explain these sensations [3, 4], yet without direct, objective measures, the cause is unknown. We found that all of our healthy human subjects developed a robust nystagmus while simply lying in the static magnetic field of an MRI machine. Patients lacking labyrinthine function did not. We use the pattern of eye movements as a measure of vestibular stimulation to show that the stimulation is static (continuous, proportional to static magnetic field strength, requiring neither head movement nor dynamic change in magnetic field strength) and directional (sensitive to magnetic field polarity and head orientation). Our calculations and geometric model suggest that magnetic vestibular stimulation (MVS) derives from a Lorentz force resulting from interaction between the magnetic field and naturally occurring ionic currents in the labyrinthine endolymph fluid. This force pushes on the semicircular canal cupula, leading to nystagmus. We emphasize that the unique, dual role of endolymph in the delivery of both ionic current and fluid pressure, coupled with the cupula's function as a pressure sensor, makes magnetic-field-induced nystagmus and vertigo possible. Such effects could confound functional MRI studies of brain behavior, including resting-state brain activity.

Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients.

BACKGROUND: Sensorineural hearing loss (SNHL) is one of the major long term side effects from radiation therapy (RT) in nasopharyngeal cancer (NPC) patients. This study aims to review the incidences of SNHL when treating with different radiation techniques. The additional objective is to determine the relationship of the SNHL with the radiation doses delivered to the inner ear. METHODS: A retrospective cohort study of 134 individual ears from 68 NPC patients, treated with conventional RT and IMRT in combination with chemotherapy from 2004-2008 was performed. Dosimetric data of the cochlea were analyzed. Significant SNHL was defined as >15 dB increase in bone conduction threshold at 4 kHz and PTA (pure tone average of 0.5, 1, 2 kHz). Relative risk (RR) was used to determine the associated factors with the hearing threshold changes at 4 kHz and PTA. RESULTS: Median audiological follow up time was 14 months. The incidence of high frequency (4 kHz) SNHL was 44% for the whole group (48.75% in the conventional RT, 37% with IMRT). Internal auditory canal mean dose of >50 Gy had shown a trend to increase the risk of high frequency SNHL (RR 2.02 with 95% CI 1.01-4.03, p=0.047). CONCLUSION: IMRT and radiation dose limitation to the inner ear appeared to decrease SNHL.

Improved dosimetric and clinical outcomes with intensity-modulated radiotherapy for head-and-neck cancer of unknown primary origin.

PURPOSE: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. METHODS AND MATERIALS: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. RESULTS: The 2-year estimates of overall survival, local-regional control, and disease-specific survival for the entire patient population were 86%, 89%, and 84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p>0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p<0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p<0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p<0.001). CONCLUSIONS: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.

Low-frequency therapeutic ultrasound with varied duty cycle: effects on the ischemic brain and the inner ear.

Sonothrombolysis is a promising modality for acute stroke treatment. In vitro data suggest a duty cycle dependence of sonothrombolytic efficacy of low-frequency applications. The aim of our study was to examine its impact on safety issues in a rat model of middle cerebral artery occlusion. Rats were exposed to transcranial 60-kHz ultrasound with varied duty cycles. To determine effects on the inner ear, the acoustic threshold was determined in additional healthy animals (acoustic evoked potentials). A short duty cycle (20%) resulted in significant adverse effects (ischemic volume, hemorrhage, functional outcome), which was not observed in longer duty cycle (80%). Continuous-wave insonation produced high rates of mortality and subarachnoid hemorrhage. Hearing was impaired independent of duty cycle. In conclusion, cerebral side effects may be efficiently reduced by modulation of pulsed parameters, which is in line with data on an improved efficacy with longer duty cycle. However, side effects on the auditory system were found to be independent of parameter settings.

Generalized model of the microwave auditory effect.

A generalized theoretical model for evaluating the amplitudes of the sound waves generated in a spherical head model, which is irradiated by microwave pulses, is developed. The thermoelastic equation of motion is solved for a spherically symmetric heating pattern of arbitrary form. For previously treated heating patterns that are peaked at the sphere centre, the results reduce to those presented before. The generalized model is applied to the case in which the microwave absorption is concentrated near the sphere surface. It is found that, for equal average specific absorption rates, the sound intensity generated by a surface localized heating pattern is comparable to that generated by a heating pattern that is peaked at the centre. The dependence of the induced sound pressure on the shape of the microwave pulse is explored. Another theoretical extension, to the case of repeated pulses, is developed and applied to the interpretation of existing experimental data on the dependence of the human hearing effect threshold on the pulse repetition frequency.