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.

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/cm(2)), and no more than 6 J/cm(2) 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.

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.

Radiation dose to the tongue and velopharynx predicts acoustic-articulatory changes after chemo-IMRT treatment for advanced head and neck cancer.

The aim of this study was to investigate to what extent changes in speech after C-IMRT treatment are related to mean doses to the tongue and velopharynx (VP). In 34 patients with advanced hypopharyngeal, nasopharyngeal, or oropharyngeal cancer, changes in speech from pretreatment to 10 weeks and 1 year posttreatment were correlated with mean doses to the base of tongue (BOT), oral cavity (OC) and tonsillar fossa/soft palate (VP). Differences in anteroposterior tongue position, dorsoventral degree of tongue to palate or pharynx constriction, grooving, strength, nasality, and laryngeal rise, were assessed by acoustic changes in three speech sounds that depend on a (post-) alveolar closure or narrowing (/t/, /s/, /z/), three with a tongue to palate/pharyngeal narrowing (/l/, /r/, /u/), and in vowel /a/ at comfortable and highest pitch. Acoustically assessed changes in tongue positioning, shape, velopharyngeal constriction, and laryngeal elevation were significantly related to mean doses to the tongue and velopharynx. The mean dose to BOT predicted changes in anteroposterior tongue positioning from pre- to 10-weeks posttreatment. From pretreatment to 1-year, mean doses to BOT, OC, and VP were related to changes in grooving, strength, laryngeal height, nasality, palatalization, and degree of pharyngeal constriction. Changes in speech are related to mean doses to the base of tongue and velopharynx. The outcome indicates that strength, motility, and the balance between agonist and antagonist muscle forces change significantly after radiotherapy.

Prospective clinical study on long-term swallowing function and voice quality in advanced head and neck cancer patients treated with concurrent chemoradiotherapy and preventive swallowing exercises.

Concurrent chemoradiotherapy (CCRT) for advanced head and neck cancer (HNC) is associated with substantial early and late side effects, most notably regarding swallowing function, but also regarding voice quality and quality of life (QoL). Despite increased awareness/knowledge on acute dysphagia in HNC survivors, long-term (i.e., beyond 5 years) prospectively collected data on objective and subjective treatment-induced functional outcomes (and their impact on QoL) still are scarce. The objective of this study was the assessment of long-term CCRT-induced results on swallowing function and voice quality in advanced HNC patients. The study was conducted as a randomized controlled trial on preventive swallowing rehabilitation (2006-2008) in a tertiary comprehensive HNC center with twenty-two disease-free and evaluable HNC patients as participants. Multidimensional assessment of functional sequels was performed with videofluoroscopy, mouth opening measurements, Functional Oral Intake Scale, acoustic voice parameters, and (study specific, SWAL-QoL, and VHI) questionnaires. Outcome measures at 6 years post-treatment were compared with results at baseline and at 2 years post-treatment. At a mean follow-up of 6.1 years most initial tumor-, and treatment-related problems remained similarly low to those observed after 2 years follow-up, except increased xerostomia (68%) and increased (mild) pain (32%). Acoustic voice analysis showed less voicedness, increased fundamental frequency, and more vocal effort for the tumors located below the hyoid bone (n = 12), without recovery to baseline values. Patients' subjective vocal function (VHI score) was good. Functional swallowing and voice problems at 6 years post-treatment are minimal in this patient cohort, originating from preventive and continued post-treatment rehabilitation programs.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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" atrophy.

A new heat and moisture exchanger for laryngectomized patients: endotracheal temperature and humidity.

OBJECTIVE: To assess the endotracheal temperature and humidity and clinical effects of 2 models of a new heat and moisture exchanger (HME): Rplus, which has regular breathing resistance, and Lplus, which has lower breathing resistance. METHODS: We measured endotracheal temperature and humidity in 10 laryngectomized patients, for 10 min each, with and without the HMEs. We sequentially tested 4 HME models (all Atos Medical, Hörby, Sweden), in randomized order: Rplus, Lplus, Provox Normal (the HME we regularly use and which we considered the reference HME), and Stomvent (an older HME model). We also assessed the short-term clinical and practical effects of the Rplus and Lplus in a prospective 3-week trial with 13 laryngectomized patients. RESULTS: Rplus and Lplus had better humidification than Provox Normal (6.8 mg H(2)O/L, 4.3 mg H(2)O/L, and 3.7 mg H(2)O/L, respectively, P < .001), and no significant temperature difference. During the 3-week study period, 7 of the 13 patients reported noticeably lower mucus production with Rplus and Lplus. CONCLUSIONS: Rplus and Lplus had better heating and humidification than Provox Normal. Although Stomvent also performed well, its design is less convenient for laryngectomized patients. Further HME improvement is still warranted and should focus on improving the HME's heating capacity.

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.

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 multicenter, prospective, clinical trial evaluating a novel adhesive baseplate (Provox StabiliBase) for peristomal attachment of postlaryngectomy pulmonary and voice rehabilitation devices.

OBJECTIVES/HYPOTHESIS: Assessment of a novel adhesive baseplate (Provox StabiliBase) for heat and moisture exchanger (HME) and/or automatic speaking valve (ASV) application. STUDY DESIGN: Prospective, clinical, multicenter trial. METHODS: This was a trial in laryngectomized patients comparing their usual adhesive with the trial adhesive. Primary outcome measure was overall patient preference; additional outcome parameters possibly explaining patients' preferences were 1) patient tolerance and preference with respect to daily handling of the adhesive; 2) adhesive lifespan, and 3) voice and speech with the adhesives. Study specific questionnaires, visual analog scales, patients' diaries, and stoma assessments were used for data collection. RESULTS: In total, 58 of the 65 laryngectomized individuals entered in the study completed the trial. Patients' overall preference for the new device was high (76%; P < .001). Significantly better performance was found for the trial adhesive with respect to ease of application (P = .034), fit (P < .001), and air leakage through the adhesive (P < .001). Comfort and stoma depth correlated weakly (r = 0.297; P = .024; deeper stoma-more comfort with StabiliBase). The adhesive lifespan with HME is significantly increased (1.7 times and 15.7 hours-plus airtight use; P < .001). This longer lifespan coincided with somewhat increased dirtying of the adhesive (P = .02). There were no serious adverse events. CONCLUSIONS: The StabiliBase adhesive for peristomal attachment of HMEs and/or ASVs was preferred by 76% of study participants and showed a promising prolonged lifespan. This new device further increases the options for stoma attachment in laryngectomized individuals, and subsequently the availability of optimal voice and pulmonary rehabilitation for a larger proportion of patients.

Pre- and posttreatment voice and speech outcomes in patients with advanced head and neck cancer treated with chemoradiotherapy: expert listeners' and patient's perception.

OBJECTIVES: Perceptual judgments and patients' perception of voice and speech after concurrent chemoradiotherapy (CCRT) for advanced head and neck cancer. STUDY DESIGN: Prospective clinical trial. METHODS: A standard Dutch text and a diadochokinetic task were recorded. Expert listeners rated voice and speech quality (based on Grade, Roughness, Breathiness, Asthenia, and Strain), articulation (overall, [p], [t], [k]), and comparative mean opinion scores of voice and speech at three assessment points calculated. A structured study-specific questionnaire evaluated patients' perception pretreatment (N=55), at 10-week (N=49) and 1-year posttreatment (N=37). RESULTS: At 10 weeks, perceptual voice quality is significantly affected. The parameters overall voice quality (mean, -0.24; P=0.008), strain (mean, -0.12; P=0.012), nasality (mean, -0.08; P=0.009), roughness (mean, -0.22; P=0.001), and pitch (mean, -0.03; P=0.041) improved over time but not beyond baseline levels, except for asthenia at 1-year posttreatment (voice is less asthenic than at baseline; mean, +0.20; P=0.03). Perceptual analyses of articulation showed no significant differences. Patients judge their voice quality as good (score, 18/20) at all assessment points, but at 1-year posttreatment, most of them (70%) judge their "voice not as it used to be." In the 1-year versus 10-week posttreatment comparison, the larynx-hypopharynx tumor group was more strained, whereas nonlarynx tumor voices were judged less strained (mean, -0.33 and +0.07, respectively; P=0.031). Patients' perceived changes in voice and speech quality at 10-week post- versus pretreatment correlate weakly with expert judgments. CONCLUSION: Overall, perceptual CCRT effects on voice and speech seem to peak at 10-week posttreatment but level off at 1-year posttreatment. However, at that assessment point, most patients still perceive their voice as different from baseline.

Short-term endotracheal climate changes and clinical effects of a heat and moisture exchanger with an integrated electrostatic virus and bacterial filter developed for laryngectomized individuals.

CONCLUSION: Both the regularly used heat and moisture exchanger (R-HME) and the HME with both an antimicrobial and hygroscopic element (F-HME) are effective moisture exchangers. The antimicrobial filter of the F-HME acts as a heat exchanger. The external features of the F-HME were experienced as inconvenient, but decreased sputum production was reported as well. OBJECTIVES: Recently an HME with an integrated antimicrobial filter has become available for use in laryngectomized patients. The purpose of this study was to assess its short-term endotracheal climate changes and feasibility in daily practice. METHODS: Endotracheal temperature and humidity were successfully measured in 13 laryngectomized patients (2652 analysed full breaths), during 10 min rest-breathing with the R-HME, with an F-HME and without HME in a randomized sequence. Additionally, a 3 week prospective clinical feasibility trial was conducted in 17 laryngectomized patients. RESULTS: Both R-HME and F-HME increase endotracheal minimum humidity values (5.8 and 4.7 mgH(2)O/L, respectively; p < 0.0001). Compared with open stoma breathing, in contrast to the R-HME, the F-HME increases both end-inspiratory and end-expiratory temperature values (1.1 degrees C, and 0.6 degrees C, respectively). After the 3-week clinical feasibility trial, one patient dropped out; 11 patients (11/16 = 69%) disliked the larger design of the F-HME and all patients reported less optimal airtight occlusion. Five patients (5/16 = 31%) reported remarkably decreased sputum production.

Clinical phase I/feasibility study of the next generation indwelling Provox voice prosthesis (Provox Vega).

CONCLUSIONS: Provox Vega prostheses demonstrate good short-term feasibility, and their optimized airflow-resistance design offers laryngectomy patients indwelling voice prostheses with more choices in outer diameters without sacrificing (too) much in voice quality. OBJECTIVES: Technological progress enables improvement of in vitro airflow characteristics of voice prostheses and design of voice prostheses with smaller outer diameters. This could potentially improve voice quality in users of Provox2, and avoid diminished voice quality in users of prostheses with smaller outer diameters. METHODS: This was a prospective clinical phase I/feasibility study of three newly designed indwelling voice prostheses (Provox Vega 22.5 (Provox2 successor), 20, and 17Fr). Assessments consisted of patients' self-reported voice and speech, perceptual evaluation, acoustic analysis, maximum phonation time, loudness, speech rate, pull-out force and adaptation of the tracheoesophageal (TE) puncture to smaller diameter voice prostheses. Vega 22.5 was assessed in 15 patients (all Provox ActiValve users, observation period 3 weeks), and 16 patients with Vega 20/17 (2 weeks each). RESULTS: No voice prostheses problems were encountered. Half of the patients with Vega 22.5 preferred that for its better voice quality. Voice and speech were considered equal to Provox2 for Vega 20, but slightly less for Vega 17. Most TE punctures adapted well to the smaller diameter voice prostheses.

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 22.5 Fr 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 devices.