Voice and speech outcomes of chemoradiation for advanced head and neck cancer: a systematic review

Purpose of this review is to systematically assess the effects on voice and speech of advanced head and neck cancer and its treatment by means of chemoradiotherapy (CRT). The databases Medline, Embase and Cochrane were searched (1991–2009) for terms head and neck cancer, chemoradiation, voice and speech rehabilitation. Twenty articles met the inclusion criteria, whereof 14 reported on voice outcomes and 10 on speech. Within the selected 20 studies, 18 different tools were used for speech or voice evaluation. Most studies assessed their data by means of patient questionnaires. Four studies presented outcome measures in more than one dimension. Most studies summarised the outcomes of posttreatment data that were assessed at various points in time after treatment. Except for four studies, pre-treatment measurements were lacking. This and the fact that most studies combined the outcomes of patients with radiated laryngeal cancers with outcome data of non-laryngeal cancer patients impedes an interpretation in terms of the effects of radiation versus the effects of the disease itself on voice or speech. Overall, the studies indicated that voice and speech degenerated during CRT, improved again 1–2 months after treatment and exceeded pre-treatment levels after 1 year or longer. However, voice and speech measures do not show normal values before or after treatment. Given the large-ranged posttreatment data, missing baseline assessment and the lacking separation of tumour/radiation sites, there is an urgent need for structured standardised multi-dimensional speech and voice assessment protocols in patients with advanced head and neck cancer treated with CRT

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

Purpose: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods: Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results: PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion: PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.National Institutes of Health (U.S.) (NIH grant R01AI050875

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations

Purpose: There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. Methods: This study is a narrative non-systematic review. Results: We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Conclusion: Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.National Institutes of Health (U.S.) (grant R01AI050875

Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved

Age Dependence of Thresholds for Speech in Noise in Normal-Hearing Adolescents

Previously found effects of age on thresholds for speech reception thresholds in noise in adolescents as measured by an online screening survey require further study in a well-controlled teenage sample. Speech reception thresholds (SRT) of 72 normal-hearing adolescent students were analyzed by means of the online speech-in-noise screening tool Earcheck (In Dutch: Oorcheck). Screening was performed at school and included pure-tone audiometry to ensure normal-hearing thresholds. The students’ ages ranged from 12 to 17 years. A group of young adults was included as a control group. Data were controlled for effects of gender and level of education. SRT scores within the controlled teenage sample revealed an effect of age on the order of an improvement of −0.2 dB per year. Effects of level of education and gender were not significant. Hearing screening tools that are based on SRT for speech in noise should control for an effect of age when assessing adolescents. Based on the present data, a correction factor of −0.2 dB per year between the ages of 12 and 17 is proposed. The proposed age-corrected SRT cut-off scores need to be evaluated in a larger sample including hearing-impaired adolescents

A new accurate 3D measurement tool to assess the range of motion of the tongue in oral cancer patients: a standardized model

In oral cancer treatment, function loss such as speech and swallowing deterioration can be severe, mostly due to reduced lingual mobility. Until now, there is no standardized measurement tool for tongue mobility and pre-operative prediction of function loss is based on expert opinion instead of evidence based insight. The purpose of this study was to assess the reliability of a triple-camera setup for the measurement of tongue range of motion (ROM) in healthy adults and its feasibility in patients with partial glossectomy. A triple-camera setup was used, and 3D coordinates of the tongue in five standardized tongue positions were achieved in 15 healthy volunteers. Maximum distances between the tip of the tongue and the maxillary midline were calculated. Each participant was recorded twice, and each movie was analysed three times by two separate raters. Intrarater, interrater and test–retest reliability were the main outcome measures. Secondly, feasibility of the method was tested in ten patients treated for oral tongue carcinoma. Intrarater, interrater and test–retest reliability all showed high correlation coefficients of >0.9 in both study groups. All healthy subjects showed perfect symmetrical tongue ROM. In patients, significant differences in lateral tongue movements were found, due to restricted tongue mobility after surgery. This triple-camera setup is a reliable measurement tool to assess three-dimensional information of tongue ROM. It constitutes an accurate tool for objective grading of reduced tongue mobility after partial glossectomy

Acoustic analysis of changes in articulation proficiency in patients with advanced head and neck cancer treated with chemoradiotherapy

Our aim was to characterize articulation proficiency and differences between tumor sites before and after chemoradiotherapy for advanced head and neck cancer with the help of acoustic measures. Our further goal was to improve objective speech measures and gain insight into muscle functioning before and after treatment. In 34 patients with laryngeal or hypopharyngeal, nasal or nasopharyngeal, or oral or oropharyngeal cancer, we acoustically analyzed nasality, vowel space, precision, and strength of articulation in 12 speech sounds (/a/, /i/, /u/, /p/, /s/, /z/, /1/, /t/, /tj/, /k/, /x/, /r/) before treatment and 10 weeks and 1 year after treatment. Outcomes were compared between assessment points and between tumor sites. Nasality in nonlaryngeal sites was significantly reduced by treatment. Most affected in articulation were the oral or oropharyngeal cancer sites, followed by the nasal or nasopharyngeal sites. One year after treatment, vowel space had not recovered and consonant articulation had weakened. Laryngeal sites were less affected in articulation by tumor or treatment. Analyses of articulatory-acoustic features are a useful instrument for assessing articulation and speech quality objectively. Assessment of a number of sounds representing various articulation manners, places, and tongue shapes revealed patterns of speech deterioration after chemoradiotherapy. The results suggest that patients' speech could benefit from articulation exercises to address changes in muscle coordination and/or sensitivity and to counteract side effects and "underexercise" atroph

Prospective Clinical Phase II Study of Two New Indwelling Voice Prostheses (Provox Vega 22.5 and 20 Fr) and a Novel Anterograde Insertion Device (Provox Smart Inserter)

Objectives/Hypothesis: To assess device life of the new Provox Vega 22.5 and 20 Fr prostheses, to establish whether the optimized airflow characteristics of these devices materialize in better voice characteristics in comparison to Provox2, and to assess the feasibility of voice prosthesis replacement with the new Smart Inserter. Study Design: Prospective clinical phase II study. Methods: Prospective clinical phase II study including two patient cohorts (Provox Vega 22.5 Fr: N = 33; Provox Vega 20 Fr: N = 26). Device-life assessment, subjective data collection with study-specific structured questionnaires, perceptual analysis (Comparative Mean Opinion Score), and objective voice analysis (standard Dutch text, maximum phonation time, and dynamic range). Results: Device life of both prostheses appears comparable to Provox2. Several voice characteristics were better in Vega 22.5, which coincides well with patients' preference. Voicing with Vega 20 appears comparable to Provox2. Use of Smart Inserter showed a short learning curve, and was considered an improvement by the clinicians. Conclusions: The new Provox Vega 22.5 and 20 Fr prostheses have a device life comparable to Provox2, whereas voicing is better than (with the 22.5Fr version) or comparable (with the 20 Fr version) to Provox2. The Smart Inserter, after a short learning curve, turns out to be a further improvement of the anterograde replacement of these indwelling device