Treatment of inoperable or metastatic paragangliomas and pheochromocytomas with peptide receptor radionuclide therapy using 177Lu-DOTATATE.

OBJECTIVES: Inoperable or metastatic paragangliomas (PGLs) and malignant pheochromocytomas (PCCs) are rare tumours with limited options for systemic treatment. Aim of this study was to assess the safety and efficacy of the radiolabelled somatostatin analogue (177LutetiumDOTA0-Tyr3)octreotate (177Lu-DOTATATE) for the treatment of PGLs and PCCs. METHODS: Patients with histologically proven inoperable or malignant PGLs and PCCs treated with 177Lu-DOTATATE at our centre were retrospectively analysed. Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gb per cycle. Response was assessed with use of RECIST 1.1. RESULTS: Thirty patients were included: 17 with parasympathetic, 10 with sympathetic PGLs and 3 with PCCs. Grade 3/4 subacute haematotoxicity occurred in 6 (20%) of patients. A reversible subacute adverse event due to cardiac failure following possible catecholamine release occurred in two patients. Best tumour response was partial response in 7 (23%) and stable disease in 20 (67%), whereas 3 (10%) patients had progressive disease. In 20 patients with baseline disease progression, tumour control was observed in 17 (85%); the median progression-free survival was 91 months in patients with parasympathetic PGLs, 13 months in patients with sympathetic PGLs and 10 months in patients with metastatic PCCs. CONCLUSION: This study suggests that PRRT with 177Lu-DOTATATE is a safe and effective treatment option for patients with inoperable or malignant PGL and PCC.

Self-Adjustment of Upper Electrical Stimulation Levels in CI Programming and the Effect on Auditory Functioning.

OBJECTIVES: With current cochlear implants (CIs), CI recipients achieve good speech perception in quiet surroundings. However, in acoustically complex, real-life environments, speech comprehension remains difficult and sound quality often remains poor. It is, therefore, a challenge to program CIs for such environments in a clinic. The CI manufacturer Cochlear Ltd. recently introduced a remote control that enables CI recipients to alter the upper stimulation levels of their user programs themselves. In this concept, called remote assistant fitting (RAF), bass and treble controls can be adjusted by applying a tilt to emphasize either the low- or high-frequency C-levels, respectively. This concept of self-programming may be able to overcome limitations associated with fine-tuning the CI sound processor in a clinic. The aim of this study was to investigate to what extent CI recipients already accustomed to their clinically fitted program would adjust the settings in daily life if able to do so. Additionally, we studied the effects of these changes on auditory functioning in terms of speech intelligibility (in quiet and in noise), noise tolerance, and subjectively perceived speech perception and sound quality. DESIGN: Twenty-two experienced adult CI recipients (implant use >12 months) participated in this prospective clinical study, which used a within-subject repeated measures design. All participants had phoneme scores of ≥70% at 65 dB SPL in quiet conditions, and all used a Cochlear Nucleus CP810 sound processor. Auditory performance was tested by a speech-in-quiet test, a speech-in-noise test, an acceptable noise level test, and a questionnaire about perceived auditory functioning, that is, a speech and sound quality (SSQ-C) questionnaire. The first session consisted of a baseline test in which the participants used their own CI program and were instructed on how to use RAF. After the first session, participants used RAF for 3 weeks at home. After these 3 weeks, the participants returned to the clinic for auditory functioning tests with their self-adjusted programs and completed the SSQ-C. RESULTS: Fifteen participants (68%) adjusted their C-level frequency profile by more than 5 clinical levels for at least one electrode. Seven participants preferred a higher contribution of the high frequencies relative to the low frequencies, while five participants preferred more low-frequency stimulation. One-third of the participants adjusted the high and low frequencies equally, while some participants mainly used the overall volume to change their settings. Several parts of the SSQ-C questionnaire scores showed an improvement in perceived auditory functioning after the subjects used RAF. No significant change was found on the auditory functioning tests for speech-in-quiet, speech-in-noise, or acceptable noise level. CONCLUSIONS: In conclusion, the majority of experienced CI users made modest changes in the settings of their programs in various ways and were able to do so with the RAF. After altering the programs, the participants experienced an improvement in speech perception in quiet environments and improved perceived sound quality without compromising auditory performance. Therefore, it can be concluded that self-adjustment of CI settings is a useful and clinically applicable tool that may help CI recipients to improve perceived sound quality in their daily lives.

Prevalence of age-related hearing loss, including sex differences, in older adults in a large cohort study.

OBJECTIVES/HYPOTHESIS: To obtain actual status of age-related hearing loss in a general unscreened population of older Dutch adults and to investigate whether the prevalence or degree has changed over time. STUDY DESIGN: To investigate the prevalence and degree of hearing loss, we conducted a large prospective cohort study of older adults between February 2011 and July 2015. METHODS: Pure-tone air- and bone-conduction thresholds were measured for 4,743 participants. Results were compared to previous cohort studies. RESULTS: As expected, hearing loss increased with age. We found a correlation of R2 = 0.317 for men and R2 = 0.354 for women (right ears). A prevalence of hearing loss greater than 35 dB hearing level the average of 0.5/1/2/4 kHz in the better ear, was found in 33% of the male and almost 29% of the female participants aged 65 years and older. Compared with previous studies, men had less hearing loss at the frequencies of 2 kHz and above. Hearing thresholds in women were significantly higher at 4 and 8 kHz. The difference in hearing loss between men and women is significantly less than in earlier studies. CONCLUSIONS: Our study confirms that hearing loss is highly prevalent in the general unscreened population of older adults. However, the difference in hearing between sexes was considerably less than previously reported. This is probably due to changing lifestyle and environmental circumstances, LEVEL OF EVIDENCE: 2b Laryngoscope, 127:725-730, 2017.