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Postirradiation sensorineural hearing loss: A common but ignored late radiation complication
... Although in radiation therapy the concentration of the dose is on the tumor area, the normal tissue around the tumor may be affected by the radiotherapy (4,5). Radiotherapy also may cause a variety of side effects, such as oral problems, redness or skin irritation, swelling, salivary gland damages, etc. Hearing problems are also common side effects of radiotherapy in these patients (6)(7)(8)(9)(10). Anteunis et al. reported that more than 50% of patients treated by the radiation suffered from some hearing problems (11). ...
... Many studies reported that hearing problems is one of the most prevalent adverse events of radiotherapy in head and neck cancers (6)(7)(8)(9)(10)18). Pan et al. reported that hearing system was damaged between 0% to 50% (14). ...
... In this study, patients with variety of HNCs were included (Brain tumor, tongue, nasopharynx, parathyroid, face, jaw, tonsil, and orbital). Although in some studies the effect of radiation on threshold of hearing in patients with different HN tumors were evaluated (14,22,23), in most of the studies, only patients with nasopharynx carcinoma were investigated (8,10,(24)(25)(26)(27)(28). ...
Background: Radiotherapy is one of the important components of head and neck cancer (HNC) treatment. This treatment method may cause a variety of side effects like oral problems, swelling, and hearing loss. Objectives: In this study, the effect of radiotherapy on hearing loss in patients with HNC was investigated. Methods: In this prospective cohort research, patients with head and neck cancer referring to the Shohadaye Tajrish Hospital during 2014 to 2015 were investigated. All of these patients were candidate for radiotherapy as the main treatment. The radiotherapy of patients was done by 3D-computer based treatment planning system, using their CT scan. In order to oncologic assessment, pre-and post-radiotherapy audiologic evaluations were done. The common toxicity criteria for the adverse events (CTCAE V4.02) of the National Cancer Institute (NCI) were used for ototoxicity. A bivariate latent variable model was used to assess the effect of received dose on the severity of hearing loss. Results: In this study, 66 patients with HNC were investigated. Among them, 46 patients (70%) were male. The mean (SD) age of patients was 45.33 (15.11). The incidence rate of hearing loss in these patients was about 18%. The result of statistical modeling showed a positive relationship between severity of HL and received dose of radiation (P < 0.001). Conclusions: In general, the findings of this study showed a direct relationship between radiation dose received by the ears and severity of hearing loss in patients with HNC. In this context, paying more attention to dose-prescription limits and standards for assessing radiation therapy associated ototoxicity are strictly recommended. © 2018, Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences.
... As a result, radiation-induced hearing loss is a well-known complication after RT for head and neck cancers. [1][2][3][4] RT-related auditory complication may be acute or delayed, and its severity varies from moderate to severe. 5 Depending on the location of damage, the underlying 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 physiologic processes causing hearing loss may differ. ...
... That primary radiation induces hearing functional changes is well known. 2,4,5,6,24 The etiology of RT-induced hearing injury, as suggested by some investigators, is represented by a reduction in the inner and outer hair cells and cells of spiral ganglion, and atrophic changes in the facial vessel. 25 The present study includes patients with various head and neck primaries and brain tumors for which the inner ear was in the field of irradiation (primary brain tumors 57.59%, lymphoma 6.08%, nasopharynx 10.62%, facial tumors [jaw, tongue, orbital] 16.62%, parotid 9.09%). ...
... Most published studies on RT-induced hearing loss were conducted in patients with nasopharyngeal carcinoma. 2,8,14,16,24,26 Pan et al, 10 Zuur et al, 27 and Hermann et al 28 had the same distribution of cases in their studies, which were not confined to the nasopharynx. ...
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.
... The onset of SNHL following radiotherapy was noted for higher frequencies and at longer periods during follow up. 10,12,14 Monica Patel PS et al. in their study observed that there was significant hearing loss in both groups RT and CRT after one month of chemoradiation. 1 Bhandare et al. reported the median interval between RT and the development of persistent SNHL at 1.8 years (range, 0.5 -5.9 years). 10 Grau et al. and Chan et al. reported that most of SNHL was first noted 12 months after the RT completion. ...
... 10 Grau et al. and Chan et al. reported that most of SNHL was first noted 12 months after the RT completion. 14,12 Pan et al. did not find any time association between hearing loss and RT. 11 The present study with 6 months follow up period may be less and require longer follow up after chemoradiation to conclude SNHL. ...
BACKGROUND Radiotherapy is a very well-known treatment modality for head and neck cancers besides surgery. The cochlea and its neuroepithelium are sensitive to ionizing radiation and resultant damage as it remains in the field of irradiation, the chemotherapy also has a similar effect leading to sensorineural hearing loss (SNHL). To minimize the adverse effects of hearing the advent of technology like intensitymodulated radiotherapy (IMRT) using smaller doses of radiation is now available with good control of the disease. The intended concomitant uses of chemotherapeutic agent cisplatin for increasing the sensitivity of radiation may induce ototoxicity. Both of these modalities result in a pronounced effect on highfrequency sensorineural hearing loss. We wanted to determine and compare sensorineural hearing loss amongst cases of head and neck cancer treated by radiotherapy, chemotherapy either alone or in a combination of both. METHODS All clinically diagnosed patients of head and neck cancer requiring treatment using radiotherapy or chemotherapy alone or in combination having a normal hearing on pure tone audiometry (PTA) were enrolled in the study. All enrolled cases were divided into three groups namely A, B and C based on treatment received like radiotherapy, chemotherapy and combination respectively and their effect on hearing was compared. Hearing acuity was assessed by doing PTA before and after completion of treatment and at 6 months follow up in every case. RESULTS In groups A, B and C SNHL was noted at higher frequencies of 4 kHz and 8 kHz during 1st as well as final follow up. Hearing loss was found maximum in group C receiving combination treatment compared to the other two groups receiving in isolation. Hearing loss was the least in Group - A cases that received radiotherapy using the IMRT technique. CONCLUSIONS The possibility of SNHL is increased in cases receiving a combination of radio and chemotherapy (94 %). Extra care of shielding the cochlea is essentially required during treatment with high doses (> 60Gy) using conformal radiotherapy to limit the resultant radiotherapy-induced SNHL. Radiation-induced SNHL in the IMRT technique was the least (28 %) in the group - A cases and hence should be employed in every case. Future searches for cases of head and neck malignancy the newer effective combination of chemotherapeutic drug and radiation obviating the ototoxicity needs to be continued. KEY WORDS Cisplatin, Radiotherapy, Intensity - Modulated, Audiometry, Pure - Tone, Ototoxicity, Hearing Loss, Sensorineural
... The causes of CHL include damage to the outer (external) ear, tympanic membrane or middle ear, which can impair the conduction of sound waves from the middle to the inner ear. SNHL is caused by damage to the inner ear, which can adversely affect nerve conduction from the cochlea [3][4][5][6][7][8][9]. ...
... The observed incidences of hearing loss in the different sound frequency ranges were as follows: 14 at the high frequency range (4)(5)(6)(7)(8), five at the medium range (1-2 kHz) and two at the low range (0.25-0.5 kHz). Five ears suffered hearing loss at both high and medium frequency ranges. ...
Purpose
Head-and-neck (H&N) radiotherapy may cause hearing loss. Despite its negative effects on patients’ quality of life, little has been published on the dose–response relationship and normal tissue complication probability (NTCP) of the conductive subtype of hearing loss. The goals of this study were: (i) to observe the incidence of hearing loss in patients undergoing non-intensity-modulated H&N radiotherapy, (ii) to obtain the relationship between dose and conductive hearing loss, (iii) to test the current parameters of the Lyman-Kutcher-Burman (LKB) radiobiological model for estimating its NTCP, and (iv) to assess the need for considering the dose to middle and external ear as organ-at-risk when optimizing treatment plans.
Methods
In this prospective study, the dose–response relationship in the auditory system of 35 patients (70 ears) undergoing 3D conformal H&N radiotherapy was studied using the physical parameter of mean dose as well as the LKB NTCP model (with parameters TD50 = 40 Gy, M = 0.15, n = 0.10) calculated by BioSuite software. In order to include a wider dose range, the study was conducted at a clinic where, at the time, more advanced treatment delivery techniques were unavailable. The patients underwent routine external-beam megavoltage X-ray treatments following 3D treatment planning involving dose calculation using collapsed-cone convolution superposition. Prescribed doses were in the range 30–72 Gy, delivered 1.8–2.0 Gy per fraction. Hearing status was evaluated by pure tone audiometry one day before the start and one and three months after the end of the radiotherapy course.
Results
Nineteen ears (27%) suffered hearing loss. Sixteen ears (23%) had conductive hearing loss and 3 ears (4%) the sensorineural subtype (p<0.05). An approximately 40 Gy mean dose to the middle-ear planning organ-at-risk volume was predicted by the LKB NTCP model to cause a 50% risk of conductive hearing loss, which was also observed in the studied patients.
Conclusions
Incidence of conductive hearing loss in typical 3D conformal H&N radiotherapy can be significant. This suggests that the auditory system should also be considered in treatment plan optimization. The LKB model parameters provided a reasonably accurate NTCP. However, a study is underway to optimize its parameters.
... Sensorineural hearing loss (SNHL) has been recognized as an important adverse effect of treatment for patient with NPC [2][3][4][5][6]. SNHL can occur immediately or in months to years after RT, and plateaus after 18 to 24 months [7,8]. Radiation damage to hearing apparatus is believed to result in SNHL. ...
... Apart from RT and cisplatin, patient-related factors such as age [3,4,33,38,39] and SOM [3,7,36] have been reported to affect SNHL. The current study also revealed that patients with age N 40 or SOM experienced greater SNHL. ...
Purpose:
The incidence of sensorineural hearing loss (SNHL) after treatment with combination of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy in nasopharyngeal carcinoma (NPC) patients was evaluated, and relationships of SNHL with host factors, treatment-related factors, and radiation dosimetric parameters were investigated.
Methods:
Fifty-one NPC patients treated with IMRT from 2004 to 2009 were analyzed. All patients received neoadjuvant, concurrent, or adjuvant use of cisplatin. Pure tone audiometry was performed during the follow-up period with a median time of 60months, ranging from 28 to 84months. Correlation of SNHL at low frequencies (pure tone average, 0.5-2kHz) with a series of factors was analyzed.
Results:
Among 102 ears, 12.7% had low-frequency SNHL and 42.2% had high-frequency (4kHz) SNHL. The incidence of low-frequency SNHL was greater in patients with age>40, with T-stage 4, or who received cumulative cisplatin dose (CCD)>200mg/m(2) (P=.034, .011, and .003, respectively) and in ears with secretory otitis media (SOM) (P=.002). Several dosimetric parameters were found to be correlated with SNHL. Univariate analysis showed that the minimum radiation dose to 0.1ml highest dose volume (D0.1ml) of the cochlea was the best radiation-related predictive parameter. Multivariate analysis indicated that CCD, SOM, and D0.1ml of cochlea (P=.035, .012, and .022, respectively) were the factors associated with SNHL.
Conclusion:
For NPC patients treated with IMRT and chemotherapy, the incidence of treatment-related SNHL was associated with CCD, D0.1ml of cochlea, and SOM.
... The review of the literature shows that SNHL usually has features of late injury [17]. The cumulative risk of a significant persistent SNHL (> 15 dB) seems to stabilize within 2 years [10,21], whereas for severe SNHL (> 30 dB) the cumulative risk also continues to increase through the third and fourth year [10]. In a series with long follow-up (median of 13 years), stable rather than progressive character of SNHL was observed [18]. ...
... The review of the literature shows that SNHL usually has features of late injury [17]. The cumulative risk of a significant persistent SNHL (> 15 dB) seems to stabilize within 2 years [10,21], whereas for severe SNHL (> 30 dB) the cumulative risk also continues to increase through the third and fourth year [10]. In a series with long follow-up (median of 13 years), stable rather than progressive character of SNHL was observed [18]. ...
To analyze dose distribution in the hearing organ and to evaluate the dose effect on the hearing thresholds in patients treated with post-parotidectomy 3-dimensional conformal radiotherapy (3D-CRT).
A total of 17 patients received post-parotidectomy 3D-CRT (median dose: 63 Gy). The audiometric evaluation comprised pure tone audiometry and tympanometry performed before radiotherapy (RT) and 3, 6, and 24 months after RT. The ear structures were delineated on planning computer tomography scans. Mean and maximum doses were calculated and dose-volume histograms were plotted.
Before RT, the median baseline audiometric thresholds were normal. At 3 months post-RT, 3 patients were diagnosed as having middle ear underpressure and/or effusion that resolved completely by 6 months. During 2-year follow-up, none of the ears showed perceptive hearing loss at speech frequencies. The mean doses at ipsilateral external auditory canal, mastoids cells, tympanic case, Eustachian tube, semicircular canals, and cochlea were 44.8 Gy, 39.0 Gy, 30.9 Gy, 33.0 Gy, 19.6 Gy, and 19.2 Gy, respectively. The doses to the contralateral ear were negligible, except for the Eustachian tube (up to 28.2 Gy).
Post-parotidectomy 3D-CRT is associated with relatively low doses to the ear and the surrounding structures. Post-RT audiometry did not show any permanent (neither conductive nor perceptive) hearing impairment. Only in 3 patients were there signs of transient unilateral dysfunction of the Eustachian tube observed during the first few months after RT. Longer follow-up and larger patient series are warranted to confirm these preliminary findings.
... 4 Post-irradiation sensorineural hearing loss is common but often ignored. 5 The reported incidence varies from no sensorineural hearing loss to 54% after radiotherapy. [6][7][8][9] This is commoner in older patients, with a 37% incidence in those over 50 years old. ...
... Post-irradiation sensorineural hearing loss occurs 0.5 to 1 year after treatment and is probably progressive. 5 High-frequency sound is more susceptible to the harmful effects of radiotherapy. 13 At all intervals of follow-up, the mean deterioration expressed in decibels was always higher at 4 kHz than at pure tone average. ...
Introduction: We report a case of successful rehabilitation of hearing with a cochlear implant in a patient with nasopharyngeal carcinoma who developed post-irradiation hearing loss following treatment. Clinical Picture: A 55-year-old Chinese lady suffered from radiation-induced sensorineural hearing loss due to treatment for nasopharyngeal carcinoma. Audiological tests and imaging studies showed an intact retrocochlear pathway. Treatment: Cochlear implantation. Outcome: Cochlear implant was done with successful rehabilitation of hearing until the time of this report. Conclusions: If functionally active auditory fibres survive with no recurrent tumour, successful rehabilitation of post-irradiation induced sensorineural hearing loss is possible with a cochlear implant in a patient with nasopharyngeal carcinoma.
... Despite numerous reports on radiation-induced hearing loss, data on the dose-response relationship for inner ear morbidity are sparse." (97) Radiation induced vascular insufficiency (small vessel endothelial reactions) has been proposed as the etiology of SNHL (98,99). ...
... 7 It is typically chronic, progressive, and irreversible. 8 This could escape the radiotherapist's knowledge as the patient may have completed follow-up before expressing this complication. Ho et al reported that SNHL after radiation was found between 1.5 and 2 years and 40% of the ears recovered by 2 years. ...
Introduction The aim of the study is to assess the hearing loss in patients who receive chemoradiation (chemoradiotherapy or CTRT) for head and neck malignancies.
Materials and Methods Prospective study was conducted in the Department of ENT of a tertiary care center from September 2013 to August 2014. Forty patients suffering from head and neck malignancies (histologically proven) were included in the study. Patients with pre-existing hearing loss were excluded. All patients received radiotherapy dose of 66 to 70 Gy given as 2 Gy/d, 5 d/wk and chemotherapy dose of cisplatin 35 mg/m2 once a week for 6 weeks. Hearing was assessed by pure tone audiometry (PTA) and impedance audiometry conducted at regular intervals. Mcnemars chi-square test was used to compare the impedance and paired t-test and Pearson’s correlation were used to compare PTA at various stages.
Results Predominantly male patients (28) falling in the age group of 40 to 60 years, suffered from various head and neck cancer, most common being oropharynx (14). Twenty patients developed sensorineural hearing loss (SNHL)—11(55%) had mild, seven (35%) had moderate, and two (10%) had severe grade of SNHL. Majority of these patients, 12 (60%) started developing SNHL mid-therapy, five (25%) at the completion of therapy and three (15%) 3 months post-therapy. Hearing loss was found to be more with two-dimensional radiotherapy (2DRT) and three-dimensional radiotherapy (3DRT) than with intensity-modulated radiotherapy (IMRT) as assessed by serial PTA. The average dose of radiation to right and left ears, respectively were 27.10 and 24.66 Gy. The incidence of otitis media with effusion increased during the treatment accounting for the conductive hearing loss irrespective of the modality of radiation used.
Conclusion CTRT causes significant hearing loss in patients suffering from head and neck malignancies leading to further increase in the morbidity. Screening audiological assessment would be helpful to know the pretherapy status of the ear. Using newer modalities like IMRT can reduce hearing loss. Regular audiological screening can catch it at its onset and help in early use of hearing aids.
... The most serious complication is sensorineural hearing loss (SNHL) in the inner ear. SNHL can typically appear immediately or several months to years after RT (7,8) , and also it is characterized by degeneration and atrophy of the inner ear sensory structures, fibrosis and even ossification of the inner ear fluid spaces (9)(10)(11) . With advent of modern RT techniques such as three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT), the incidence of radiation-induced hearing loss is expected to decrease, due to a better radiation dose sparing of auditory system, in particular cochlea (6,12,13) . ...
Background: Hearing loss is a major concern in the patient with head and neck cancer (HNC) undergoing radiotherapy (RT) and/or chemotherapy (CHT). The present study aimed to assess the incidence of sensorineural hearing loss (SNHL) at 6 months follow-up after RT and/or concurrent Cisplatin-based CHT. Materials and Methods: In this prospective study, 60 patients with histopathologically proven HNC underwent three-dimensional conformal radiotherapy (3DCRT) (35 patients) and concurrent Cisplatin-based CHT and RT (25 patients). The status of the hearing was assessed pre-treatment (baseline), one day, 1, 3 and 6 months after treatment by pure tone audiometry (PTA) and other audiometric tests such as tympanometry (TM), acoustic reflex (AR), and speech audiometry (SA). Results: In the RT group, SNHL was observed in 18 patients and hearing loss occurred in 47 % (33 of 70 ears) of ears. In the chemo-radiotherapy (CRT) group, SNHL was discerned in 20 patients and hearing loss appeared in 88 % (44 of 50 ears) of ears. Perforation of the tympanic membrane occurred in 2/35 patients in the RT group and 1/25 patients in the CRT group. The AR threshold (ART) of patients with CRT significantly increased compared to the RT group at the end of 6 months after treatment (P <0.05). Meanwhile, there was a significant difference in the speech discrimination score (SDS) and speech recognition threshold (SRT) between the CRT group and RT group at the 6 months after treatment (P <0.05). Conclusion: The incidence of hearing loss in patients that underwent CRT was higher. The auditory system should be considered as a critical organ at risk (OAR) in treatment planning.
... Severe SNHL described as ≥20 dB difference between the irradiated and unirradiated ears by some authors (30,31); while some others accept ≥10-15 dB loss as the critical cut-off for severe loss (32,33). Though the clinical stage may settle in 2 years for permanent SNHL (>15 dB), yet, this interval may lengthen to 3 to 4 years for more severe (>30dB) SNHL (34). Nevertheless, in studies with longer follow-up periods, such as 13 years or more, SNHL is specified to have a stable characteristic rather than being progressive (35). ...
Radiation-induced sensorineural hearing loss (RI-SNHL) is a progressive and irreversible complication of radiotherapy (RT) or chemoradiotherapy (CRT) of brain or head and neck tumors. Onset and progression times of RI-SNHL may broadly vary depending on the RT technique, dose, and concurrent or adjuvant usage of ototoxic medications, such as cisplatin. Characteristically the high frequencies (≥4 kHz) form the first affected range on a typical audiogram, which may be trailed by impairements in the lower hearing frequencies. RI-SNHL may adversely impact both the academic and social advancement in pediatric age and may deteriorate quality of life measures in all affected patients regardless of their age. Even if not eliminate all, in absence of a unequivocally proven medical treatment to avoid or alleviate the RI-SNHL, utilization of more advanced RT techniques, such as the intensity-modulated RT, and limiting the cochlea doses to ≤40-45 Gy for RT alone,<10 Gy for concurrent RT and cisplatin, and <10-12 Gy for stereotactic radiosurgery applications may demonstrate valuable in minimizing the risk of SNHL development. Furthermore, as reactive oxygen species (ROS) are the essential introductory causatives in RT-induced damage via activating the apoptotic cascade in cochlear hair cells, hopefully the development of novel radioprotective agents with the ability to lessen ROS production may prove beneficial in reducing the cochlear damage, and therefore, RI-SNHL, in near future.
... These may include hearing loss, cardiac disease, hypothyroidism, neurocognitive deficits, and reduction in the patient's learning and mental skills at the learning age; [3][4][5][6][7] in addition, there is a risk of inducing secondary cancers. [8] When radiotherapy and chemotherapy are combined, the total dose to the craniospinal axis is reduced successfully from 35-36 Gy to 23. 4 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. ...
Aims:
In central nervous system (CNS) tumors, surgery combined with radiotherapy may cure many tumors. The basic technique in conventional radiotherapy is craniospinal radiotherapy; in this technique, spinal cord can be treated with electron or photon beams. This study was aimed to compare two radiotherapy techniques in craniospinal radiotherapy, (a) treatment of spine with a single photon beam and (b) with a combination of photon and electron beams.
Materials and methods:
The two techniques were planned. In the first technique, both brain and spine were irradiated with 6 MV photon beams. In the second technique, brain was irradiated with 6 MV photon and spine with 18 MeV electron beams. To compensate the dose deficiency in lumbar area, an anterior field of 15 MV photon beam was also applied in the second technique. The dose to target volume and organ at risks (OARs) were measured by thermoluminescent dosimeter and compared with the corresponding values calculated by Isogray treatment planning system.
Results:
OARs including heart, mandible, thyroid, and lungs received lower dose from technique 2 compared with technique 1; kidneys were exceptions which received higher dose in the technique 2.
Conclusions:
The dose to thyroid, mandible, heart, and lungs were lower in technique 2, while kidneys received higher dose in technique 2. This was caused by using the anterior 15 MV photon beam. Based on these results, for children, instead of photon beam for treatment of spinal cord, it is wiser to use electron beam.
... Because germinomas are slow growing tumors, long-term follow-up is mandatory for more than 10 years. The optimal treatment of CNS germinomas remains controversial and serves to focus the debate on the balance between progression-free survival and quality of life (QOL), particularly in relation to late sequelae of CNS irradiation [4,8,9,23,24]. To avoid long-term sequelae of CNS irradiation such as growth retardation, endocrine dysfunction and cognitive impairment, reduction or elimination of radiation dose has been advocated in the management of intracranial germinoma in association with long-term survival. ...
... There are many studies in the literature describing the pathological changes in irradiated animal ears, which include haemorrhage, lymphatic oedema with compression of the endolymph disruption of the organ of Corti in the cochlea and inflammation. [16][17][18] These are mostly acute processes that were observed in experimental animals sacrificed soon after irradiation and there are few studies that describe the pathological alterations responsible for delayed sensorineural hearing loss. In one such study, Bohne et al 19 found degeneration of sensory and supporting cells and loss of the VIII nerve fibres in the organ of Corti, 2 years after the experimental animals had been irradiated. ...
We report the case of a 42-year-old man who presented with fluctuating bilateral sensorineural hearing loss that subsequently progressed to a complete hearing loss, and we describe the correlation between the clinical and radiologic features of this case. To the best of our knowledge, this is the first report to demonstrate imaging evidence of progression from autoimmune inner ear disease to labyrinthitis ossificans. This is also the first reported case of a reversal of a loss of labyrinthine CISS (constructive interference in a steady state) signal, suggesting that T2-weighted hyposignal may be attributable to an alteration in labyrinthine fluid content and not to fibrosis only.
... [6] Whereas; many have focused on the individual toxicities of radiation and cisplatin on the auditory apparatus, few clinical studies have evaluated the synergistic ototoxic effects of radiation and cisplatin chemotherapy. Some have demonstrated that combined modality protocols with cochleotoxic compounds such as cisplatin may increase the detrimental effects of radiation on the inner ear, [7][8][9][10][11][12] with SNHL both immediate and delayed. [13,14] In examining the results, it is thus important to differentiate between radiationand cisplatin-induced ototoxicity. ...
Aims and Objectives: The objective of this study was to assess the prevalence and patterns of hearing loss after concomitant radiochemotherapy in patients enrolled in a larynx preservation protocol. Materials and Methods: The study comprised of audiological evaluation of 30 patients prior to and at 1, 3, and 6 months after treatment using pure tone audiometry and impedance audiometry. Results: At the end of 6 months, 43.33% suffered sensorineural hearing loss (SNHL), 8.33% conductive hearing loss, 16.67% mixed hearing loss, and 6.67% showed improvement in hearing. Discussion: The possible mechanism for hearing loss are discussed and compared with the result of such studies in literature. Conclusion: There exist a small but definite potential risk of hearing loss after concomitant radiotherapy and chemotherapy in patients with head and neck cancer.
... Although our data demonstrated that hearing loss stabilized at 9 months following initiation of protocol treatment, continued decline in hearing sensitivity years after therapy has been documented in patients treated with cisplatin 27,28 and cranial radiation. 29,30 The strengths of this research include the prospective and comprehensive audiological evaluations conducted and the standardized protocol used throughout the study period for administration of cisplatin, for effective supportive care for amifostine, and for administration of amifostine. In addition, the results of our published pharmacokinetic study of amifostine and WR1065 in this patient population further lead credence to the selection of the amifostine dosage and schedule for this patient population. ...
Background
The purpose of this study was to evaluate amifostine for protection from cisplatin-induced serious hearing loss in patients with average-risk medulloblastoma by extending a previous analysis to a much larger sample size. In addition, this study aimed to assess amifostine with serious hearing loss in patients with high-risk medulloblastoma treated with cisplatin.Methods
Newly diagnosed medulloblastoma patients (n = 379; ages 3-21 years), enrolled on one of 2 sequential St. Jude clinical protocols that included 4 courses of 75 mg/m(2) cisplatin, were compared for hearing loss by whether or not they received 600 mg/m(2) of amifostine immediately before and 3 hours into each cisplatin infusion. Amifostine administration was not randomized. The last audiological evaluation between 5.5 and 24.5 months following protocol treatment initiation was graded using the Chang Ototoxicity Scale. A grade of ≥2b (loss requiring a hearing aid or deafness) was considered a serious event.ResultsAmong average-risk patients (n = 263), amifostine was associated with protection from serious hearing loss (adjusted OR, 0.30; 95% CI, 0.14-0.64). For high-risk patients (n = 116), however, there was not sufficient evidence to conclude that amifostine prevented serious hearing loss (OR, 0.89; 95% CI, 0.31-2.54).Conclusions
Although patients in this study were not randomly assigned to amifostine treatment, we found evidence in favor of amifostine administration for protection against cisplatin-induced serious hearing loss in average-risk but not in high-risk, medulloblastoma patients.
... Because of the high survival rate, the fact that patients require radiotherapy, and the fact that children and adolescents are more likely to develop radiation-related late effects than adults, late (>5 years after treatment) effects from radiation are a major concern for medulloblastoma patients10111213. The late effects associated with CSI are well-documented and may include (but are not limited to) impaired growth [14], endocrine abnormalities151617, hearing loss [17,18], diminished fertility [17] , neuropsychological dysfunction [17,19], cardiac diseases [17,2021222324, and second cancers [17,22232425262728. For many decades, the standard of care radiotherapy regimen for CSI has been photon (megavoltave x-rays) therapy that included opposed lateral cranial fields and either single or multiple posterior spinal fields [29]. ...
For many decades, the standard of care radiotherapy regimen for medulloblastoma has been photon (megavoltage x-rays) craniospinal irradiation (CSI). The late effects associated with CSI are well-documented in the literature and are in-part attributed to unwanted dose to healthy tissue. Recently, there is growing interest in using proton therapy for CSI in pediatric and adolescent patients to reduce this undesirable dose. Previous comparisons of dose to target and non-target organs from conventional photon CSI and passively scattered proton CSI have been limited to small populations (n ≤ 3) and have not considered the use of age-dependent target volumes in proton CSI.
Standard of care treatment plans were developed for both photon and proton CSI for 18 patients. This cohort included both male and female medulloblastoma patients whose ages, heights, and weights spanned a clinically relevant and representative spectrum (age 2-16, BMI 16.4-37.9 kg/m2). Differences in plans were evaluated using Wilcoxon signed rank tests for various dosimetric parameters for the target volumes and normal tissue.
Proton CSI improved normal tissue sparing while also providing more homogeneous target coverage than photon CSI for patients across a wide age and BMI spectrum. Of the 24 parameters (V5, V10, V15, and V20 in the esophagus, heart, liver, thyroid, kidneys, and lungs) Wilcoxon signed rank test results indicated 20 were significantly higher for photon CSI compared to proton CSI (p ≤ 0.05) . Specifically, V15 and V20 in all six organs and V5, V10 in the esophagus, heart, liver, and thyroid were significantly higher with photon CSI.
Our patient cohort is the largest, to date, in which CSI with proton and photon therapies have been compared. This work adds to the body of literature that proton CSI reduces dose to normal tissue compared to photon CSI for pediatric patients who are at substantial risk for developing radiogenic late effects. Although the present study focused on medulloblastoma, our findings are generally applicable to other tumors that are treated with CSI.
... The rate of post-RT SNHL appears to increase with age (>50) (4,5,7,10,11,27). Grau (28) found a significant relationship between higher patient age and increased risk of hearing loss, but, when corrected for dose, the correlation disappeared. ...
A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associated ototoxicity as well as a detailed approach for scoring toxicity is presented.
Purpose:
To estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) from a clinical trial focused on reducing the target volume of intensity-modulated radiotherapy (IMRT).
Methods and materials:
This prospective, randomized clinical trial was conducted across six Chinese hospitals and included 212 patients with stage III-IVB NPC, who were randomly allocated a pre-IC or post-IC group. Eligible patients were treated with two cycles of IC+CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively.
Results:
After a median follow-up of 98.4 months, 32/97 (32.9%) and 33/115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1-2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rate in the pre-IC and post-IC groups were 78.2% vs. 83.3%, 72.0% vs. 78.1%, 90.2% vs. 93.5%, and 78.1% vs. 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared to the pre-IC group, the post-IC group showed significant improvement in cognitive function (p=0.045) and symptoms including dry mouth (p=0.004), sticky saliva (p=0.047), and feeling ill (p=0.041).
Conclusion:
After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.
Purpose:
To study effects of chemoradiation therapy on hearing in patients with malignancy of head and neck.
Methods and materials:
Patients receiving drugs other than cisplatin as well as those with any otology-related pathology or abnormalities were excluded from the study. Patients with primary biopsy-proven malignancy of the Nasopharynx, Oropharynx, Paranasal Sinuses, Oral Cavity, and Parotid with chemoradiation by cisplatin and different radiation modalities were all eligible. Areas of interest and OARs are indicated on CT images. All patients' hearing was assessed using pure tone audiometry at the beginning of treatment, at its conclusion, and six months later. Variations in pure tone thresholds from baseline and CTCAE - Common Terminology Criteria for Adverse Events grading are related to cochlear dose.
Results:
The study involves 75 patients. At cochlear dosage levels of more than 40 Gy, significant SNHL (>10 dB loss) is seen. Absolute PTA threshold values do not statistically differ from baseline to completion at any frequency. For 4000 and 8000 Hz, the absolute PTA threshold values differed from baseline to follow-up, but only for 8000 Hz was the difference statistically significant after six months of follow-up. Following treatment, 64% of patients had grade I CTCAE scoring and 16% and 12%, respectively, had otitis media with effusion and Eustachian tube dysfunction.
Conclusion:
The inner ear may be harmed in patients receiving radiation to the head and neck. Radiation-induced SNHL typically goes unreported in routine clinical practise because of its long-term nature. In the group of head and neck tumours with high-risk locations, nearly 90% of patients with SNHL were affected. Therefore, it's critical to reduce cochlear dosage in these patient populations. More investigation is needed to distinguish between cochlear and retro-cochlear types of sensorineural hearing loss.
Introduction: Head and neck cancer is among the most common malignancies in developing countries like India. The treatment modality for head and neck cancers is usually radiotherapy which can be used either after surgery or combined with chemotherapy. However, radiation therapy can damage the ear from pharyngotympanic tube to the auditory pathway upto brain-stem, causing hearing loss due to ultrastructural changes in organ of corti. Long term survivors can experience Sensorineural Hearing Loss (SNHL) due to the combined ototoxic effects of radiotherapy and cisplatin.
Aim: To study the effects of Intensity-Modulated Radiation Therapy (IMRT) along with chemotherapy on hearing, in head and neck cancer patients.
Materials and Methods: Twenty three patients were treated on Linear Accelerator- Varian Unique Performance with 6 MV photon and received dose 70 Gy in 35 fractions over 6.5 weeks; either by sequential IMRT (SEQ) or by Simultaneous Integrated Boost IMRT (SIB). They also received cisplatin 35 mg/m2 once weekly concurrently with radiotherapy for 6-8 weeks. Pre and post-radiotherapy Pure Tone Audiometry (PTA) were done to assess the hearing loss.
Results: Most of our patients developed either conductive hearing loss or mixed hearing loss. Only two patients developed sensorineural hearing loss.
Conclusion: Most of the patients developed mild hearing loss before and after chemoradiotherapy, indicating that both the arms of IMRT (radiotherapy) did not have any major influence on the inner ear.
Purpose:
Head-and-neck (H&N) and cranial radiotherapy may cause hearing loss. Little has been published on the dose-response relationship and normal-tissue complication probability (NTCP) of the conductive subtype of hearing loss. The aims were to observe the incidence of hearing loss in patients undergoing non-intensity-modulated H&N or cranial radiotherapy, obtain the relationship between dose and conductive hearing loss (CHL) and test the current Lyman-Kutcher-Burman (LKB) NTCP model parameters.
Methods:
The dose-response in the peripheral auditory system (PAS) of 35 patients (70 ears) was prospectively studied using mean dose and the current LKB model parameters. A wide dose range was obtained by conducting the study at a clinic without advanced treatment techniques. The patients underwent routine external-beam treatments following 3D treatment planning. Hearing status was evaluated by pure-tone audiometry one day before the start and one day and 30 days after the end of radiotherapy.
Results:
Nineteen ears (27%) experienced hearing loss. Sixteen (23%) had CHL and three (4%) the sensorineural subtype. On average, mean doses of the PAS structures and V95%, V40Gy and V30Gy volumes of the middle-ear planning-organ-at-risk volume (PRV) were significantly greater in ears that suffered CHL. The modelled 50% NTCP of CHL occurred at approximately 30-40 Gy mean dose to middle ear planning organ-at-risk volume.
Conclusions:
Incidence of conductive hearing loss in non-intensity-modulated radiotherapy of H&N and brain can be significant. CHL exhibits a dose-effect. This suggests that the PAS should be considered in treatment plan optimization. The LKB NTCP model was reasonably accurate but modifications are indicated.
Introduction
Radiotherapy either primary or adjuvant, is a commonly used modality of treatment in head and neck malignancies. The audiovestibular apparatus is often within the fields of radiation treatment, and hearing loss is a possible complication. This study was undertaken to assess the audiovestibular functions in patients undergoing radiation therapy for head and neck malignancies to determine the type and severity of hearing loss and vestibular dysfunction following radiation therapy.
Materials and methods
Fifty patients with head and neck malignancies reported to the malignant disease treatment center of INHS Asvini and received radiotherapy as a primary modality of treatment or in combination with surgery during the period May 2003 to Sep 2004 were included in this study. None of these patients had prior treatment by chemotherapy.
Conclusion
A significant number of patients who were subjected to radiation therapy for head and neck malignancies develop conductive hearing loss is predominant in the immediate postradiation period. Conductive hearing loss is reversible and improves with the conservative line of treatment. Sensorineural hearing loss more commonly affects the higher frequencies and is more common in older patients. Sensorineural hearing loss is more common when radiation doses exceed 60 Gy. There is no conclusive evidence of vestibular dysfunction in patients undergoing radiotherapy for head and neck cancers.
Recent developments in radiation therapy have largely centered on the improvement in delivering radiation to a highly conformal target with high precision. The increased use of stereotactic body radiotherapy (SBRT) has also introduced another dimension of treatment, potentially replacing surgery in select situations to aggressive treatment of oligometastatic disease to invoking a systemic response using immunomodulators. Simultaneously, advances in systemic therapy ranging from traditional chemotherapy regimens to targeted biologics, and more recently immune modulators, are rapidly affecting the field of radiation oncology. These advances rely on a synergy between significant improvements in radiation delivery, driven by image guidances and more conformal delivery or radiation, and a greater understanding of tumor biology. This chapter will focus on an understanding of advances in these areas and future directions for pediatric brain tumors levering these innovations.
Hearing loss as a side effect in patients with head and neck malignancies with chemoradiation is frequently ignored. Its effects on auditory functions are less studied and there are studies done on animals which are less reliable. The present study was undertaken to identify the type of hearing loss and also to quantify the degree of hearing loss in these patients. A prospective, descriptive study was undertaken in histologically proven head and neck cancer patients treated with cobalt 60 teletherapy who received a dose of 60–66 Grays (Gy) over a period of 6–7 weeks with concurrent Cisplatin 30 mg/m2 once weekly for 6 weeks. The study included 40 patients (80 ears) undergoing chemoradiation. A baseline pure tone audiometry and impedance audiometry was performed in all the cases prior to the therapy and the same was repeated immediately after the completion of treatment, at 8 and 16 weeks. The changes in pure tone level thresholds and impedance from baseline were correlated with the dose of radiation and chemotherapy. Sensori neural hearing loss (SNHL) and conductive hearing loss was observed in 82.5 and 17.5 % respectively. At the end of 16 weeks, SNHL was found in 27.5, 72.5 and 82.5 % at 2, 4 and 8 kHz respectively. In addition, Eustachian tube dysfunction and Otitis media with effusion was observed in 10 and 7.5 % of patients respectively which lead to conductive hearing loss. Further, it was noted that SNHL in patients with high risk site malignancy (81.8 %) was alarmingly higher compared with low risk site malignancy (18.1 %). The hearing loss at 62, 64 and 66 Gy in comparison to 60 Gy was statistically significant. Hearing loss, specially SNHL was the predominant finding in our study with >80 % of patients showing the inner ear damage due to irradiation of head and neck malignancies. Although, all the frequencies like 2, 4 and 8 kHz were significantly affected, SNHL was more marked in the latter two frequencies. Nearly, 90 % of the patients who had SNHL belonged to high risk site category of head and neck malignancies. Increasing the radiation dosage was directly proportional to the degree of hearing loss with the dose more than 60 Gy causing significant injury to the middle and inner ear.
Despite the known effects of ionizing radiation on the nervous system, most children with brain tumors have to undergo radiation therapy at some point during their treatment. As advances in neurosurgery, chemotherapy, and radiotherapy enter clinical practice, multimodality therapy has become the norm. For any tumor, the incorporation of radiation therapy into such treatment must consider the timing, dose, and treatment volume of radiation, the most appropriate radiation modality, short- and long-term toxicities, both for radiation alone and for radiation in conjunction with chemotherapy, and, finally, the integration of novel antineoplastic agents with radiation.
Despite the known effects of ionizing radiation on the nervous system, most children with brain tumors will receive radiation therapy at some point during treatment. As advances in neurosurgery, chemotherapy, and radiotherapy enter clinical practice, multimodality therapy has become the norm. For any given tumor, the incorporation of radiation therapy into such treatment must consider the timing of radiation, the most appropriate radiation modality, short-and long-term toxicities both for radiation alone and for radiation in conjunction with chemotherapy, and, finally, the integration of novel antineoplastic agents with radiation.
Sensori-neural hearing loss is a frequent complication of radiotherapy of head and neck tumours, when the auditory pathways have been included in the radiation field. This chapter focuses on the review of three aspects of radiation-induced SNHL that have a significant impact on modern day medicine: 1) effect of radiation on retro-cochlear nervous pathways, 2) cellular and molecular processes involved in radiation-induced ototoxicity, 3) combined ototoxic effects of radiation and cisplatin. A model of radiation-induced damage of the sensor-neural auditory system has been proposed, which is based on the concept of dose-dependent, reactive oxygen species related cochlear cell apoptosis without significant damage to the retro-cochlear pathway. This model supports the feasibility of cochlear implantation, should one be clinically indicated in such patients. It can explain clinical observations such as radiation-induced sensori-neural hearing loss being dose-dependent and affects the high frequencies more than the lower frequencies. It also opens up the possibility of preventive strategies targeted at different stages of the apoptotic process. The use of anti-oxidants which target upstream pathways, appear promising. In particular, it may have a major role in chemo-radiation where combined ototoxic effects lead to significant sensori-neural hearing loss.
To compare the incidence of sensorineural hearing loss between those treated with docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by carboplatin concurrent chemoradiotherapy and those treated with conventional concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma.
Serial pure tone audiometry was conducted in 36 nasopharyngeal carcinoma patients who were randomised into 2 groups. The first group received docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by carboplatin concurrent chemoradiotherapy. The second group received conventional concurrent chemoradiotherapy.
The incidence of sensorineural hearing loss at speech frequency in the first group was 10 per cent and in the second group was 50 per cent (p = 0.0027). Bone conduction thresholds were significantly increased after completion of the treatment at 2-4 kHz in the first group and at all frequencies in the second group.
The docetaxel, cisplatin and 5-fluorouracil induction chemotherapy regimen followed by concurrent chemoradiotherapy was associated with a lower incidence of sensorineural hearing loss than conventional concurrent chemoradiotherapy. This regimen may be the preferred choice of treatment for hearing preservation.
Background:
Improvement in radiotherapy during the past decades has made the risk of developing a radiation-induced secondary cancer as a result of dose to normal tissue a highly relevant survivorship issue. Important factors expected to influence secondary cancer risk include dose level and dose heterogeneity, as well as gender and type of tissue irradiated. The elevated radio-sensitivity in children calls for models particularly tailored to paediatric cancer patients.
Material and methods:
Treatment plans of six paediatric medulloblastoma patients were analysed with respect to secondary cancer risk following cranio-spinal irradiation (CSI), using either: 1) electrons and photons combined; 2) conformal photons; 3) double-scattering (DS) protons; or 4) intensity-modulated proton therapy (IMPT). The relative organ equivalent dose (OED) concept was applied in three dose-risk scenarios: a linear response model, a plateau response and an organ specific linear-exponential response. Life attributable risk (LAR) was calculated based on the BEIR VII committee's preferred models for estimating age- and site-specific solid cancer incidence. Uncertainties in the model input parameters were evaluated by error propagation using a Monte Carlo sampling procedure.
Results:
Both DS protons and IMPT achieved a significantly better dose conformity compared to the photon and electron irradiation techniques resulting in a six times lower overall risk of radiation-induced cancer. Secondary cancer risk in the thyroid and lungs contributed most to the overall risk in all compared modalities, while no significant difference was observed for the bones. Variations between DS protons and IMPT were small, as were differences between electrons and photons.
Conclusion:
Regardless of technique, using protons decreases the estimated risk of secondary cancer following paediatric CSI compared to conventional photon and electron techniques. Substantial uncertainties in the LAR estimates support relative risk comparisons by OED.
Tumor of the temporal bone is a rare disease with a very poor prognosis. Surgery and postoperative radiotherapy are usually the recommended treatments for squamous cell carcinoma (SCC) of the external and middle ear, which may cause conductive hearing loss. The purpose of this study was to evaluate the audiologic results and compliance of active middle ear implant (AMEI) and establish the feasibility of the procedure in a patient treated for middle ear cancer.
A 73-year-old patient treated with lateral petrosectomy, neck dissection, reconstruction/obliteration by pedicled pectoralis major myocutaneous flap, and postoperative full dose radiotherapy for external and middle ear SCC was selected for AMEI. Preoperative audiometric and speech audiometry tests were performed on both ears before and after the activation.
Pure tone free field audiometry. Binaural free field speech audiogram.
Aided pure tone free field audiometry AMEI results show an increase in air conduction. Speech audiogram showed better discrimination scores in AMEI-aided situations. No complications were observed.
AMEI after surgery followed by radiotherapy for middle ear cancer is feasible. Acoustic results in obliterated ear are satisfactory.
The main objective of this work was to describe, based on a literature survey, the radiation-induced toxicity of the ear and to try to establish the limiting dose. The limiting toxicity was the sensorineural hearing loss. A dose–effect relationship has been described by several authors. Thirty to 40% of patients who are irradiated for head and neck cancer are concerned, but the intensity of the hearing loss tends to depend on the exact localisation of the primary tumour: nasopharyngeal irradiations, paranasal sinusal and parotid irradiation are at greater risk of complication. High frequencies are more vulnerable than the lower ones. Age of patients, as well as baseline hearing abilities, deeply influence the issue. As far as possible, the dose to the inner ear – the cochlea more precisely – should be kept under 40Gy. In case of association with other causes of toxicity (such as age, low baseline value, association to cisplatin), this dose should be as low as possible. Should carcinologic constraints lead to toxic doses, then patients should be properly informed.
BACKGROUND
Combined modality therapy has become the standard of care for nasopharyngeal carcinoma, yet the combined ototoxic effects of radiation and cisplatin are poorly understood. The incidence and severity of sensorineural hearing loss (SNHL) with combined modality therapy was evaluated and the dose–response relation between radiation and hearing loss was investigated.METHODS
Patients with newly diagnosed AJCC Stage II–IVB nasopharynx carcinoma treated from 1994–2003 were identified. The records of 44 ears in 22 patients who received a preirradiation pure tone audiogram and followup audiograms 12+ months postirradiation were included in the analysis. All patients were treated with conformal radiotherapy to 70 Gy and received platinum-based chemotherapy similar to the Intergroup 0099 trial. Composite cochlear dose distributions were calculated. Ototoxicity was measured using intrasubject audiogram comparisons and SNHL was defined as per the American Speech and Hearing Association guidelines, with standard range of speech between 2000–4000 Hz. SNHL was analyzed using Fisher exact test and linear and logistic regression models.RESULTSPatient characteristics: median age, 45; 27% Asian; 68% male; 64% WHO III. Median audiologic followup was 29 months (range, 12–76 mos). Mean cochlear dose (Dmean) ranged from 28.4–70.0 Gy (median, 48.5 Gy). SNHL was detected in 25 of the 44 ears (57%) studied. There was an increased risk of SNHL for ears receiving Dmean > 48 Gy compared with those receiving ≤ 48 Gy at all frequencies within the range of speech (P = 0.04). Using univariate logistic regression analysis, Dmean to the cochlea, cycles of cisplatin, and time postradiotherapy were independently significant factors in determining the incidence of SNHL (P = 0.02, P = 0.03, and P = 0.04, respectively). In univariate and multivariate linear regression analysis, Dmean was statistically significant at all frequencies in affecting degree of SNHL, whereas the significance of cisplatin and time was variable.CONCLUSIONS
There was a significant increase in risk of SNHL among patients receiving > 48 Gy, suggesting a threshold in cochlear radiation dose–response in the setting of combined modality therapy. This dose should serve as a Dmean constraint maximum for intensity-modulated radiotherapy treatment of nasopharynx carcinoma. Cancer 2006. © 2006 American Cancer Society.
The purpose of this retrospective study was to determine the long-term effects of radiotherapy on hearing function in patients who underwent parotidectomy and postoperative radiotherapy for unilateral tumors of the parotid gland.
An extensive set of tests was used to measure hearing loss. The mean dose on middle ear, cochlea, and Eustachian tube was estimated with a CT-planning system.
A hearing loss of ≥ 15 dB in 3 frequencies was found in 32% of the 52 patients included in the study. Patients with an asymmetrical hearing loss received a higher mean dose on the hearing structures (p < .002). The threshold dose for clinically relevant hearing loss was found at 50 Gy on the cochlea and Eustachian tube.
Radiation-induced hearing loss is a common complication. A mean dose of > 50 Gy on the cochlea should be avoided. © 2006 Wiley Periodicals, Inc. Head Neck, 2006
The prognosis of malignant glioma and metastatic brain tumours is still extremely poor, despite recent advances in therapeutic strategies with molecular-targeted agents. Poly(ADP-ribose) polymerase (PARP) inhibitors are a promising, novel class of anticancer drugs to be used either as single agents or in combination with chemotherapy and radiotherapy. PARP-1 and PARP-2 are the only PARP proteins that bind to DNA single strand breaks (SSBs), facilitating the repair process by the base excision repair. For this reason, PARPs have been extensively investigated as targets of novel drugs that may be used to enhance the antitumour activity of SSBs inducing agents, such as the methylating compound temozolomide, which is the drug of choice for glioblastoma, or ionizing radiations. Moreover, PARP inhibitors exert cytotoxic effects in monotherapy in BRCA mutated tumours, which are defective in the homologous recombination (HR) repair. Finally, recent studies have shown that inhibition of PARP function might also induce anti-angiogenic effects which might contribute to impair tumour growth. Many clinical trials with PARP inhibitors are ongoing for the treatment of a variety of advanced solid tumours, including primary or secondary brain tumours. This review discusses the implications of targeting PARP on the design of new treatment regimens.
To compare tumor control and changes in audiometric parameters of acoustic neuroma patients treated with either linac-based stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) at Allegheny General Hospital.
Twenty-three patients with acoustic neuroma were treated between February 2003 and April 2009 with either SRS (n = 13) or SRT (n = 10). The median age for all patients was 69 years and the median size of lesions was 1.2 cm (range 0.5-2.2 cm). The prescribed dose was a single dose of 1250 cGy for all SRS patients compared to 2500 cGy in 5 daily fractions for SRT patients. All patients had pre- and post-procedure audiometry including hearing acuity assessed using pure tone average (PTA), speech discrimination score (SDS), and speech reception threshold (SR). The results of treatment type and tumor variables resulting in hearing degradation were evaluated and compared.
At a median follow-up of 13 months (range 3-36 months), only 1 of 13 patients treated with SRS and 2 of 10 patients treated with SRT develped progression of disease. However; all patients developed deterioration in PTA, SDS, or SR on the treated side. There were no statistically significant audiometric differences between patients treated with SRT or SRS and tumor response was similar regardless of irradiation technique.
Both SRS and SRT provide excellent local control rates for the treatment of acoustic neuroma. While SRS demonstrated a trend toward worsening of SDS and the treatment of lesions >1.2 cm demonstrated a trend toward worsening of PTA, neither reached statistical significance. Our data suggest that single dose irradiation using the SRS technique should be considered primarily for patient convenience. All patients treated with radiotherapy for acoustic neuromas should undergo formal hearing testing before and after treatment.
Definitive or postoperative radiation therapy (RT) is commonly used for the management of intracranial and extracranial head and neck tumors. Because of the variability of tumor location and dimensions, sparing of nontarget normal tissue and organs may not be possible. Treatment modalities that deliver the highest doses of radiation to the auditory system include stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for the treatment of vestibular schwannomas (VS), and fractionated radiotherapy (FRT) or intensity-modulated radiation therapy (IMRT) for the treatment of head and neck malignancies. Radiation therapy for VS is unique because of its involvement of the inner ear and preexisting auditory and vestibular dysfunction. Auditory and vestibular dysfunction following RT for VS may be limited by limiting the total dose of cranial nerve VIII irradiation and by fractionation.
Pediatric CNS tumors are the most common solid tumors of childhood and the second most common cancer after hematological malignancies accounting for approximate 20 to 25% of all primary pediatric tumors. With over 3,000 new cases per year in the United States, childhood CNS tumors are the leading cause of death related to cancer in this population. The prognosis for these patients has improved over the last few decades, but current therapies continue to carry a high risk of significant side effects, especially for the very young. Currently a combination of surgery, radiation, and chemotherapy is often used in children greater than 3 years of age. This article will outline current and future therapeutic strategies for the most common pediatric CNS tumors, including primitive neuroectodermal tumors such as medulloblastoma, as well as astrocytomas and ependymomas.
This is a retrospective study to evaluate the outcomes and complications of combined treatment, surgery with or without adjunctive intraoperative radiotherapy, of locally advanced temporal bone squamous cell carcinoma. A series of 17 patients with locally advanced squamous cell carcinoma of the temporal bone were treated between September 2002 and February 2007. Eleven patients had primary tumors, and 6 patients had recurrences. According to the University of Pittsburgh staging system, 5 patients were stage II (T2 N0), 6 patients were stage III (5, T3 N0 and 1, T1 N1), and 6 patients were stage IV (5, T3 N2b and 1, T4 N0). All patients underwent lateral temporal bone resection and pedicle flap reconstruction. Eight patients received intraoperative and postoperative radiotherapies, 4 patients underwent postoperative radiation alone, whereas 5 patients did not receive any adjunctive treatment. Median follow-up was 29.5 months. No major complications were observed. No patients were found to have residual gross tumor. Disease-free survival was 73.3%, and overall survival was 75.6%. Radical external auditory canal and/or middle ear canal resection is of utmost importance to obtain a good surgical outcome. Postoperative radiotherapy is necessary to obtain good local control; no major adverse effects were observed in the intraoperative radiotherapy patients. The incidence of major complication is minimal after pedicle flap reconstruction.
Radiotherapy (RT) is a common treatment of head-and-neck carcinoma. The objective of this study was to perform a prospective multivariate assessment of the dose-effect relationship between intensity-modulated RT and hearing loss.
Pure tone audiometry at 0.250-16 kHz was obtained before and after treatment in 101 patients (202 ears). All patients received full-course intensity-modulated RT (range, 56-70 Gy), with a median cochlear dose of 11.4 Gy (range, 0.2-69.7).
Audiometry was performed 1 week before and a median of 9 weeks (range, 1-112) after treatment. The mean hearing deterioration at pure tone average air-conduction 1-2-4 kHz was small (from 28.6 dB HL to 30.1 dB HL). However, individual patients showed clinically significant hearing loss, with 10-dB threshold shift incidences of 13% and 18% at pure tone averages air-conduction 1-2-4 kHz and 8-10-12.5 kHz, respectively. Post-treatment hearing capability was unfavorable in the case of greater inner ear radiation doses (p <0.0001), unfavorable baseline hearing capability (p <0.0001), green-eyed patients (p <0.0001), and older age (p <0.0001). Using multivariate analysis, a prediction of individual hearing capabiltity after treatment was made.
RT-induced hearing loss in the mean population is modest. However, clinically significant hearing loss was observed in older patients with green eyes and unfavorable pretreatment hearing. In these patients, the intended radiation dose may be adjusted according to the proposed predictive model, aiming to decrease the risk of ototoxicity.
Cis-platinum and radiation in combination are current organ preservation treatment strategies for head and neck cancer. Their individual ototoxicity has been investigated, with recent demonstration of ototoxicity in clinical studies. Currently, no ototoxicity studies have been performed in animals receiving similar schedules of radiation or cis-platinum to those patients with head and neck cancer.
In the present study, an animal model was developed to investigate the effects of combined modality therapy on hearing. Albino guinea pigs were given equivalent protocol dosages of cis-platinum (3 parenteral courses), fractionated radiation (25 fractions over 5 weeks), or both. Click and tone burst auditory brainstem response (ABR) measurements were performed before and 6 weeks after the completion of treatment.
Animals receiving radiation or cis-platinum and radiation experienced permanent significant ABR shifts at all frequencies, with 33% of the animals experiencing complete unilateral sensorineural hearing loss at 2 or more frequencies in the ear receiving the full radiation dose (7075 cGy over 25 fractions) (P < .05, paired t test analysis). The animals receiving 3 doses of cis-platinum had no significant ABR threshold shifts at 6 weeks. These data suggest that cis-platinum and radiation cause greater ototoxicity than cis-platinum alone. These findings correlate closely with sensorineural hearing loss in combined modality patients at our institution and in recent studies.
We conclude that the current animal results parallel those seen clinically and serve as a model for ototoxicity from combined modality therapies in future protocols.
Conventional radiation therapy for pediatric posterior fossa tumors can cause sequelae such as hearing loss and impairments in language and learning. Modern three-dimensional (3D) treatment techniques have improved dose conformity to the posterior fossa. This report compares the normal tissue dose-sparing capabilities of proton radiation therapy (PRT) with 3D conformal photon plans.
Nine children underwent previous PRT for primary CNS malignancies. Using original planning CT scans, the posterior fossa, inner and middle ear, and temporal lobes were delineated. Three-dimensional treatment plans were generated for protons and photons. Normal tissue exposures were calculated by averaging mean doses received and by analysis of dose-volume histogram.
The 95% isodose encompassed the posterior fossa in all plans. Normal structures received markedly less radiation from PRT plans than from 3D photon plans. The cochlea received an average mean of 25 +/- 4% of the prescribed dose from PRT, and 75 +/- 6% from photons. Forty percent of temporal lobe volume was completely excluded using protons; with photons 90% of the temporal lobe received 31% of the dose.
PRT resulted in increased dose sparing of normal structures analyzed. Posterior fossa conformity of 3D photons came at the expense of increasing amounts of normal tissue receiving low to moderate doses.
Hearing loss due to irradiation of the head-and-neck region is a rarely reported complication of such a treatment. Although experimental work had been performed in laboratory animals as early as at the turn of the century, substantiated clinical data in large series are lacking. The few reports published are somewhat contradictory as to the incidence, time of onset, type and severity of the hearing loss. Although infrequently encountered, the possibility of radiation-induced hearing loss should be kept in mind. The pertinent literature is reviewed. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7–84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy.
A retrospective study was done to ascertain the risks of cochlear damage from radiotherapy of the nasopharynx. Audiometric evaluation, pre and post-radiotherapy, revealed that 7 out of 13 patients had sustained sensori-neural deafness. Contrary to what is generally believed of the resistance of the cochlea to radiotherapeutic damage, eventual loss of hearing can occasionally be expected in patients undergoing radiation therapy for head and neck tumors.
The question of damage to the ear from exposure to ionizing radiation was addressed by exposing groups of chinchillas to fractioned doses of radiation (2 Gy per day) for total doses ranging from 40 to 90 Gy. In order to allow any delayed effects of radiation to become manifest, the animals were sacrificed two years after completion of treatment and their temporal bones were prepared for microscopic examination. The most pronounced effect of treatment was degeneration of sensory and supporting cells and loss of eighth nerve fibers in the organ of Corti. Damage increased with increasing dose of radiation. The degree of damage found in many of these ears was of sufficient magnitude to produce a permanent sensorineural hearing loss.
The effect of radiotherapy on hearing was studied in 30 patients who were treated by surgery and radiotherapy for a parotid neoplasm. Functions of the irradiated ear were compared with those of the non-irradiated ear in the same patient. Tympanometry showed a small but significant reduction of static compliance on the irradiated side when compared with the non-irradiated side. Audiometry showed a significant increase in hearing loss in the 1-2, 4-8 and 10-20 kHz ranges that increased with frequency. This hearing loss was mainly sensorineural in contrast to hearing loss at 250-500 Hz, where it was more of a conductive type. There appeared to be a significant dose-effect relation in sound perception at 4-8 kHz. Doses to the cochlea of less than 55 Gy seldom caused a hearing loss, in contrast to doses exceeding 65 Gy. Overall, radiotherapy was found to cause significant, mainly sensorineural hearing losses, which were partly dose-dependent.
The study evaluated the incidence and severity of brain stem myelopathy occurring after radiation exposure in a cohort of patients who received external radiation exposure for nasopharyngeal carcinoma (NPC).
Brain stem function was investigated by auditory brain stem responses (ABR).
Four of 21 patients who could be examined had aberrations in ABR. Three patients showed highly abnormal ABR, with no distinctive patterns or peaks. Two of these patients also showed clinical symptoms of brain stem dysfunction, including multiple palsies in cranial and peripheral nerves, whereas the third patient had no clinical signs of brain stem disorders. The fourth patient had minor conduction delays in ABR. The remaining group of 17 patients who could be examined had ABR latency and transmission times similar to those of the control group. None of these patients had neurologic symptoms. Dose-response analysis showed that patients who received radiation doses of 59 Gy or less to the brain stem had normal ABR, whereas four of six patients who received a dose of 68 Gy had manifest or subclinical brain stem dysfunction.
The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure.
The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy.
In this centre, platinum chemotherapy precedes radiotherapy in several primary malignancies arising in structures adjacent to the mastoid bone. The augmented ototoxicity of platinum and radiotherapy to fields encompassing the inner ear is exemplified by a case report. The order of administration may not be critical. This important toxicity, particularly for young patients, may be reduced by careful shielding considerations during planning of radiation portals, as exemplified in two further cases, and by carboplatin chemotherapy.
Hearing loss due to irradiation of the head-and-neck region is a rarely reported complication of such a treatment. Although experimental work had been performed in laboratory animals as early as at the turn of the century, substantiated clinical data in large series are lacking. The few reports published are somewhat contradictory as to the incidence, time of onset, type and severity of the hearing loss. Although infrequently encountered, the possibility of radiation-induced hearing loss should be kept in mind. The pertinent literature is reviewed.
We report on four children who received cis-platinum simultaneously with, or in one case 10 months after, cranial irradiation and experienced exaggerated ototoxicity affecting all audible frequencies. The hearing loss was severe, affecting the critical areas for speech perception, and necessitated the provision of bilateral hearing aids. The audiograms of these patients are shown and compared to those of four children who had received cis-platinum as part of their treatment for neuroblastoma but without cranial irradiation. The precipitation of the exaggerated hearing loss with the administration of cis-platinum in one patient 10 months after finishing cranial irradiation suggests that care should be taken in the timing of cis-platinum administration in relation to concurrent or previous cranial irradiation.
Assessment of the effect of chemotherapy and radiotherapy on the auditory function of children with cancer
Forty children with malignant disease underwent full audiological assessment with pure tone audiometry, tympanometry and measurement of brain stem auditory evoked potentials in an attempt to detect auditory dysfunction resulting from treatment. Significant auditory dysfunction was observed in 8 children. Three children with evidence of a conductive or sensorineural deafness on pure tone audiometry had normal brain stem evoked potentials. One child with a high tone hearing loss and 4 children with no detectable hearing loss on audiometry showed significant differences in the interaural interpeak latencies of selected brain stem auditory evoked potentials. In 2 children these abnormalities had resolved on subsequent testing, 2 had evidence of persistent retrocochlear dysfunction and the remaining child died prior to further evaluation. Routine measurement of brain stem auditory evoked potentials is probably not necessary for the majority of children undergoing treatment for cancer, although such measurements are of value when differentiation between cochlear and retrocochlear damage is required.
The question of damage to the ear from exposure to ionizing radiation was addressed by exposing groups of chinchillas to fractioned doses of radiation (2 Gy per day) for total doses ranging from 40 to 90 Gy. In order to allow any delayed effects of radiation to become manifest, the animals were sacrificed two years after completion of treatment and their temporal bones were prepared for microscopic examination. The most pronounced effect of treatment was degeneration of sensory and supporting cells and loss of eighth nerve fibers in the organ of Corti. Damage increased with increasing dose of radiation. The degree of damage found in many of these ears was of sufficient magnitude to produce a permanent sensorineural hearing loss.
The pattern of sensorineural hearing loss (SNHL) after primary treatment for nasopharyngeal carcinoma (NPC) was studied, and the effect of cisplatin, radiotherapy does, and fractionation were evaluated.
One hundred thirty-two patients, 227 ears, and 1100 audiogram reports were analyzed. Radiotherapy dose ranged from 59.5 to 76.5 Gy. Fifty-two patients received preirradiation cisplatin, total dose 100-185 mg/m(2). Serial postirradiation bone conduction thresholds at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz were compared with pretreatment thresholds at respective frequencies. Increase of at least 15 dB was considered as significant and was further grouped as transient or persistent SNHL. Univariate and multivariate analyses were performed to identify predicting factors for persistent SNHL.
At median follow-up of 30 months, 24.2% of ears developed persistent SNHL. High frequency was more affected than low frequencies, 22 vs. 5.3%. Males were more affected than females, 29.4 vs. 15.5%, p = 0.0132. Incidence of persistent SNHL increased with age, with 0, 17.2, and 37.4% of patients aged under 30, between 30-50 and over 50 affected, respectively, p = 0.0001. High incidence was found in patient with postirradiation serous otitis media (SOM), 46.9%. Chemotherapy with cisplatin and radiation dose or fractionation had no significant effect. Multivariate analysis confirmed age, sex, and postirradiation SOM as significant prognostic factors for persistent SNHL.
Transient and persistent SNHL occurred after radiotherapy, more commonly affecting high frequency. A low dose of preirradiation cisplatin did not increase the risk. A dose fractionation effect of radiotherapy was not confirmed in this study.
Keir, E. Enhanced radiation portals
- D A Walker
- J Pillow
- K D Waters
Walker, D. A.: Pillow, J.; Waters, K. D.: Keir, E. Enhanced radiation portals. Br. J. Radio1 62:457-462; 1989. cis-platinum ototoxicity in children with brain tumors who
have received simultaneous or prior cranial irradiation
- D L W Kwong
- W I Wei
- J S T Sham
- W K Ho
Kwong, D. L. W.; Wei, W. I.; Sham, J. S. T.; Ho, W. K.; have received simultaneous or prior cranial irradiation. Med.
5-1 year after treatment and is probably progressive. Postirradiation sensorineural hearing loss 0 C. C~KALI AXLJ .I. OVEKGAARI~ REFERENCES I Delayed effects of ionizing radiation on the ear
- G P Glasgow
Occurs with a latency of 0.5-1 year after treatment and is probably progressive. Postirradiation sensorineural hearing loss 0 C. C~KALI AXLJ.I. OVEKGAARI~ REFERENCES I. Bohne. B. A.; Marks, J. E.; Glasgow, G. P. Delayed effects of ionizing radiation on the ear. Laryngoscope 95:818-828; 1985.