Roland Laszig

Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial

BACKGROUND Anaemia is associated with poor cancer control, particularly in patients undergoing radiotherapy. We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer. METHODS We did a multicentre, double-blind, randomised, placebo-controlled trial in 351 patients (haemoglobin <120 g/L in women or <130 g/L in men) with carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received curative radiotherapy at 60 Gy for completely (R0) and histologically incomplete (R1) resected disease, or 70 Gy for macroscopically incompletely resected (R2) advanced disease (T3, T4, or nodal involvement) or for primary definitive treatment. All patients were assigned to subcutaneous placebo (n=171) or epoetin beta 300 IU/kg (n=180) three times weekly, from 10-14 days before and continuing throughout radiotherapy. The primary endpoint was locoregional progression-free survival. We assessed also time to locoregional progression and survival. Analysis was by intention to treat. FINDINGS 148 (82%) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L (women) or 150 g/L (men) compared with 26 (15%) given placebo. However, locoregional progression-free survival was poorer with epoetin beta than with placebo (adjusted relative risk 1.62 [95% CI 1.22-2.14]; p=0.0008). For locoregional progression the relative risk was 1.69 (1.16-2.47, p=0.007) and for survival was 1.39 (1.05-1.84, p=0.02). INTERPRETATION Epoetin beta corrects anaemia but does not improve cancer control or survival. Disease control might even be impaired. Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials.

Preservation of residual hearing with cochlear implantation: how and why.

Conclusions Hearing may be conserved in adults after implantation with the Nucleus Contour Advance perimodiolar electrode array. The degree of hearing preservation and the maximum insertion depth of the electrode array can vary considerably despite a defined surgical protocol. Residual hearing combined with electrical stimulation in the same ear can provide additional benefits even for conventional candidates for cochlear implantation. Objectives We present preliminary results from a prospective multicentre study investigating the conservation of residual hearing after implantation with a standard-length Nucleus Contour Advance perimodiolar electrode array and the benefits of combined electrical and acoustic stimulation. Material and methods The subjects were 12 adult candidates for cochlear implantation recruited according to national selection criteria. A “soft” surgery protocol was defined, as follows: 1–1.2-mm cochleostomy hole anterior and inferior to the round window; Nucleus Contour Advance electrode array inserted using the “Advance-off-stylet” technique; and insertion depth controlled by means of three square marker ribs left outside the cochleostomy hole. These procedures had been shown to reduce insertion forces in temporal bone preparations. Variations in surgical techniques were monitored using a questionnaire. Pure-tone thresholds were measured pre- and postoperatively. Patients who still retained thresholds <90 dB HL for frequencies up to 500 Hz were re-fitted with an in-the-ear (ITE) hearing aid. Word recognition was tested in quiet and sentence perception in noise for the cochlear implant alone and in combination with an ipsilateral hearing aid. Results Hearing threshold level data were available for 12 patients recruited from 6 of the centres. Median increases in hearing threshold levels were 23, 27 and 33 dB for the frequencies 125, 250 and 500 Hz, respectively. These median increases include the data for two patients who had total loss of residual hearing due to difficulties encountered during surgery. “Cochlear view” X-ray images indicated that the depth of insertion varied between 300 and 430°, despite modest variations in the length of the electrode inserted (17–19 mm). The insertion angle had some influence on the preservation of residual hearing at frequencies of 250–500 Hz. Six of the 12 patients retained sufficient hearing for effective use of an ipsilateral ITE hearing aid (≤80 dB HL at 125 and 250 Hz; ≤90 dB HL at 500 Hz). Word recognition scores in quiet were improved from 10% to 30% with the cochlear implant plus ipsilateral hearing aid in 3 patients who had at least 3 months postoperative experience. Signal:noise ratio thresholds for sentence recognition were improved by up to 3 dB. Patients reported that they experienced greatly improved sound quality and preferred to use the two devices together.

Comparison of pseudobinaural hearing to real binaural hearing rehabilitation after cochlear implantation in patients with unilateral deafness and tinnitus.

Objective: Up to now, treatment modalities of unilateral deafness consist of no treatment, conventional contralateral routing of signal (CROS), or Bone-Anchored Hearing Aid (BAHA) hearing aid. Cochlear implantation makes a new treatment modality available for patients with single-sided deafness. The aim of this study is to evaluate the use of unilateral electrical stimulation with normal hearing on the contralateral side after a period of 6 months compared with the preoperative unaided situation, conventional CROS, or BAHA hearing aids. Study Design: Prospective design. Setting: Tertiary referral center; cochlear implant (CI) program. Patients: Eleven adult subjects with unilateral deafness of various causes were enrolled in the study. Only those patients were included in whom therapy with CROS hearing aid or BAHA was not successful and in whom the auditory nerve was found to be intact and the cochlea patent for cochlear implantation. Intervention: All subjects were fitted in random order with a BAHA Intenso mounted on the softband/tension clamp or with a CROS hearing aid. After test periods with both devices, the subjects received a CI. Main Outcome Measures: The Hochmair-Schulz-Moser sentence test and the Oldenburg sentence test were used to test speech comprehension in 3 presentation configurations in the unaided situation, with conventional CROS and BAHA hearing aids before cochlear implantation as well as after 6 months with CI. Localization was assessed using an array of 7 speakers at head level in a frontal semicircle. Subjective improvement in daily life was evaluated using the Speech, Spatial and Qualities of Hearing Scale, the Health Utilities Index 3 and the International Outcome Inventory for Hearing Aids questionnaires. Tinnitus distress was measured with a tinnitus scale before and after CI implantation. Results: The results show significant improvement in localization ability as well as in speech comprehension in most presentation configurations with the CI. Especially, there is no negative effect on speech comprehension if the noise is presented to the CI ear and speech to the normal hearing ear. With the CI, the summation and squelch effects are not significant, but a significant combined head shadow effect is seen. Speech, Spatial and Qualities of Hearing results show an overall benefit of wearing the CI compared with the other treatment options. The tinnitus scale revealed a positive effect of CI stimulation in cases of preoperative tinnitus. Conclusion: The results in these patients suggest that cochlear implantation improves hearing abilities in people with single-sided deafness and is superior to the alternative treatment options. The use of the CI does not interfere with speech understanding in the normal hearing ear. Our data suggest that the binaural integration of electric and acoustic stimulation is possible even with unilateral normal hearing.

Quality control after insertion of the nucleus contour and contour advance electrode in adults.

Objective: To evaluate the quality of insertion of the Nucleus Contour and the newly developed Contour Advance electrode in adult cochlear implant recipients and to compare results of speech performance tests with regard to electrode position. Design: A total of 43 adult patients with a history of progressive hearing loss having received a Nucleus cochlear implant, 21 of which had received a Contour electrode and 22 a Contour Advance electrode, were evaluated by rotational tomography after surgery. Electrode position was determined to be in scala tympani, scala vestibuli, or with a dislocation from one scala to the other. Speech test results were collected for Freiburg numbers, Freiburg monosyllables, and Oldenburg sentence tests 1 yr after surgery. Results: The Contour array presented with a high rate of scala vestibuli insertions and a high rate of dislocations from scala tympani to scala vestibuli, whereas the Contour Advance array showed a high rate of scala tympani insertions with very few dislocations and few scala vestibuli insertions. Speech tests results varied with respect to the location of the intracochlear electrode position, with insertions into the scala tympani being significantly superior to the scala vestibuli. Conclusions: Results of studying the Contour array influenced the surgical procedure that improved surgical ability to perform insertions into the scala tympani by using the Contour Advance array. In addition, a comparison between Contour and Contour Advance electrode demonstrated an improved mechanical behavior of the Contour Advance electrode with a decrease of dislocation rate. The use of the Contour Advance electrode allows a more atraumatic electrode insertion, which is of interest with extending indications and the use of further advanced coding strategies. The intracochlear electrode position with regard to speech performance results demonstrated advantages of scala tympani insertions.

Benefits of bilateral electrical stimulation with the nucleus cochlear implant in adults: 6-month postoperative results.

Objective: To evaluate the benefits of bilateral electrical stimulation for hearing-impaired adult subjects using the Nucleus 24 cochlear implant in a multicenter study, and to compare and quantify performance on speech perception measures in quiet and in noise and localization ability for unilateral and bilateral cochlear implant use. Design: Repeated single subject measures were carried out for each subject, with each subject serving as their own control. Assessment of unilateral and bilateral listening conditions for performance on tests of speech comprehension and sound localization were performed. Speech comprehension measures were performed in quiet at 0 degree azimuth and in the presence of background noise simultaneously presented from the same speaker and spatially separated by 90 degrees, at S+45°N45° and at S−45°N+45°. Test materials included Freiburger monosyllabic words, Oldenburger sentences, and the Hochmair-Schulz-Moser sentences. Tests of localization were performed in the horizontal plane with 12 speaker locations 30 degrees apart using a shortened sentence stimulus from the Hochmair-Schulz-Moser sentences at two possible presentation levels of 55 and 70 dB sound pressure level for assessment of directionality. The binaural advantage provided by bilateral stimulation was calculated with respect to each ear separately, classified as either the better or poorer performing ear for each speech material in quiet and in noise test conditions. For localization of sound, the binaural advantage was compared with left and right ears separately. Paired comparisons for performance data in all conditions were carried out by considering measurements for each subject in different conditions as paired observations and applying the Student’s t test to determine the statistical difference between the data sets. Setting: Tertiary referral centers with a cochlear implant program. Patients: Thirty-seven profoundly hearing-impaired adults were enrolled in the study, 22 simultaneously and 15 sequentially bilaterally implanted. All patients received the Nucleus 24 cochlear implant and used the Nucleus SPrint or ESPrit 3G speech processor, with the vast majority using the ACE speech coding strategy. Results: For spatially separated speech in noise conditions, an interaural performance advantage for the ear closest to the speech source (i.e., with a superior signal to noise ratio) compared with that for the ear closest to the noise source (i.e., with an inferior signal to noise ratio) is consistently demonstrated regardless of whether it is the better or poorer performing ear closest to the speech signal. This is referred to as a significant binaural head-shadow benefit, resulting in a mean improvement between −10 dB and −11.4 dB in the critical signal to noise ratio required for 50% speech comprehension for the Olden-burger sentences and a mean improvement in the maximum score of 42% to 55% for the ear closest to the speech signal over the ear farthest away for the Hochmair-Schulz-Moser sentences. Bilateral stimulation is always observed to provide a performance advantage over the unilateral listening condition for either ear when ipsilateral to the noise source. In addition, as demonstrated by approximately half the subjects tested in noise with the Hochmair-Schulz-Moser sentences, a performance advantage of bilateral stimulation may be observed over the better ear alone when positioned ipsilateral to the speech signal, which is referred to as a binaural squelch effect. On average, for the group, this resulted in a statistically significant improvement in speech comprehension scores of 8% in the bilateral listening condition compared with the scores for the better ear alone. Through assessment of comprehension of coincidental speech in noise and speech in quiet, a significant benefit of binaural redundancy was noted for the group for Oldenburger sentence scores in noise and in quiet compared with unilateral scores for either ear and for the Freiburger monosyllabic words in quiet in comparison with the better ear alone scores. Binaural stimulation also led to a significant improvement in localization ability over either monaural condition, with the root mean square degrees of error reduced by 38 degrees compared with that observed for unilateral stimulation. Conclusion: Similar to what has been observed for bilateral acoustic stimulation in the past, bilateral electrical stimulation provides the foundation for the potential advantages of the head-shadow effect, providing a binaural head-shadow benefit and binaural auditory processing such as binaural redundancy and binaural squelch effects, all of which combine to lead to improved speech comprehension over unilateral listening conditions. The combination of improved speech comprehension and improved localization ability made available through bilateral electrical stimulation provides the necessary foundation to further assist the hearing-impaired listener to better cope with communication in the everyday listening situation both in noise and in quiet.

Surgical Complications with the Cochlear Multiple-Channel Intracochlear Implant: Experience at Hannover and Melbourne

The surgical complications for the first 153 multiple-channel cochlear implant operations carried out at the Medizinische Hochschule in Hannover and the first 100 operations at the University of Melbourne Clinic, The Royal Victorian Eye and Ear Hospital, are presented. In the Hannover experience the major complications were wound breakdown, wound infection, electrode tie erosion through the external auditory canal, electrode slippage, a persistent increase in tinnitus, and facial nerve stimulation. The incidence of wound breakdown requiring removal of the package was 0.6% in Hannover and 1.0% in Melbourne. The complications for the operation at both clinics were at acceptable levels. It was considered that wound breakdown requiring implant removal could be kept to a minimum by making a generous incision and suturing the flap without tension.

Results from a European clinical investigation of the Nucleus multichannel auditory brainstem implant.

Objective This study was designed to investigate the perceptual benefits and potential risks of implanting the Nucleus® multichannel auditory brainstem implant. Design Between September 1992 and October 1997 a total of 27 subjects received a Nucleus 20- or 21-channel Auditory Brainstem Implant (ABI). All subjects involved in the trial had bilateral acoustic tumour as a result of neurofibromatosis type 2 (NF2) resulting in complete dysfunction of the VIIIth nerve. The study used each subject as their own control without a preoperative baseline because residual hearing, if existing, was destroyed at surgery by tumour removal. A battery of speech tests was conducted to evaluate each patient’s performance and communication abilities. Tests were conducted, where possible, in the auditory-only, visual-only, and auditory-visual conditions at 3 days postoperatively (baseline), at 3-mo intervals for the first year and every 12 mo thereafter. A subjective performance questionnaire was administered together with an extensive neurological examination at each test interval. Results 27 subjects involved in this trial were successfully implanted with a Nucleus ABI. One subject died 2 days postoperatively due to a lung embolism unrelated to the device. Twenty-six subjects underwent device activation and all but one patient received auditory sensation at initial stimulation (96.2%). On average 8.6 (±4.2) of the available 21 electrodes were used in the patients’ MAPs. Performance evaluation measures showed that the majority of users had access to auditory information such as environmental sound awareness together with stress and rhythm cues in speech that assist with lipreading. Although most subjects did not achieve any functional auditory-alone, open-set speech understanding, two subjects from this series (7.4%) did receive sufficient benefit to be able to use the ABI in conversation without lipreading. Conclusions Although the medical risks and surgical complexity associated with ABI device implantation are far greater than those for a cochlear implant, the clinical results from this trial show that the Nucleus multichannel ABI is capable of providing a significant patient benefit over risk ratio for subjects suffering loss of hearing due to bilateral retrocochlear lesions.

Threshold, comfortable level and impedance changes as a function of electrode-modiolar distance.

Objective The study investigated the hypothesis that threshold and comfortable levels recorded from cochlear implant patients would reduce, and dynamic range increase, as distance of the electrode from the modiolar wall (radial distance) decreases. Two groups of cochlear implant patients participated; one group using the Nucleus® 24 Contour™ electrode array, and one group using the Nucleus standard straight (banded) array. The Nucleus 24 Contour array has been shown in temporal bone studies to lie closer to the modiolus than the banded array. The relationship of electrode impedance and radial distance is also investigated. Design The study, conducted at three centers, evaluated 21 patients using the Contour array, and 36 patients using the banded array. For each patient, threshold, comfortable levels and dynamic range were measured at four time points. Common ground electrode impedance was recorded clinically from each patient, at time intervals up to 12 wk. An estimate of the radial distance of the electrode from the modiolus was made by analysis of Cochlear view x-rays. Results Threshold and comfortable levels were significantly lower for the Nucleus 24 Contour array than for the banded array. However, dynamic range measurements did not show the predicted increase. In a majority of subjects, a significant correlation was found between the estimated radial distance of the electrode from the modiolus and the measured threshold and comfortable levels. This trend was not observed for dynamic range. The analysis indicates that other factors than radial distance are involved in the resultant psychophysical levels. Clinical impedance measures (common ground) were found to be significantly higher for the Contour array. However, the electrodes on the Contour array are half-rings, which are approximately only half the geometric size of the full rings as electrodes of the standard array. When the geometric electrode area in the two array designs are normalized, the trends in the electrode impedance behavior are similar. Conclusions The results support the hypothesis that the relationship between the radial distance of the electrode and the psychophysical measures are influenced by patterns of fibrous tissue growth and individual patient differences, such as etiology and neural survival. Impedance measures for the Nucleus 24 Contour electrode array were higher than the banded electrode array, but this is primarily due to the reduction in electrode surface area. The different outcomes in impedance over time suggest differences in the relative contributions of the components of impedance with the two arrays.

Quality control after cochlear implant surgery by means of rotational tomography.

Objective: To investigate the intracochlear electrode position in using rotational tomography in adult cochlear implant patients. Study Design: Retrospective. Setting: Tertiary referral center. Patients: Eighteen adult patients being implanted either with a Nucleus straight electrode array or a Contour electrode with a total of 22 implanted ears. Preoperative computed tomography had been without evidence for obliteration, ossification, or malformation of the cochlea. Intervention: Rotational tomography. Main Outcome Measures: The intracochlear electrode position was evaluated with regard to scala tympani, scala vestibuli, and a dislocation from one scala to the other. The intraoperative procedure was compared with the electrode position by analyzing the operating reports. Results: Preliminary results indicate, respectively, that there is a higher incidence of intracochlear trauma in using the Contour electrode array than expected with a more frequent dislocation of electrode arrays from scala tympani to scala vestibuli and that there is a higher rate of scala vestibuli insertions. Conclusions: The impact of these findings may influence further developments of electrode arrays as well as surgical techniques for implantation.

European multi-centre study of the Nucleus Hybrid L24 cochlear implant

Abstract Objectives: To investigate the preservation of residual hearing in subjects who received the Nucleus Hybrid L24 cochlear implant. To investigate the performance benefits up to one year post-implantation in terms of speech recognition, sound quality, and quality of life. Design: Prospective, with sequential enrolment and within-subject comparisons. Post-operative performance using a Freedom Hybrid sound processor was compared with that of pre-operative hearing aids. Study sample: Sixty-six adult hearing-impaired subjects with bilateral severe-to-profound high frequency hearing loss. Results: Group median increase in air-conduction thresholds in the implanted ear for test frequencies 125–1000 Hz was < 15 dB across the population; both immediately and one year post-operatively. Eighty-eight percent of subjects used the Hybrid processor at one year post-op. Sixty-five percent of subjects had significant gain in speech recognition in quiet, and 73% in noise (≥ 20 percentage points/2 dB SNR). Mean SSQ subscale scores were significantly improved (+ 1.2, + 1.3, + 1.8 points, p < 0.001), as was mean HUI3 score (+ 0.117, p < 0.01). Combining residual hearing with CI gave 22−26 %age points mean benefit in speech recognition scores over CI alone (p < 0.01). Conclusions: Useful residual hearing was conserved in 88% of subjects. Speech perception was significantly improved over preoperative hearing aids, as was sound quality and quality of life.