Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BACKGROUND: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. METHODS: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. DISCUSSION: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

Analysis of Potassium Titanyl Phosphate Laser Settings and Voice Outcomes in the Treatment of Reinke's Edema.

OBJECTIVE: Despite increased clinical utility of the 532-nm potassium titanyl phosphate (KTP) laser, no studies have examined outcomes for Reinke's edema (RE) as a function of laser parameters and initial treatment effects. Variability in delivery parameters, fiber-to-tissue distance, and immediate end-tissue effects limits universal application of existing study outcomes. We examine voice outcomes using standardized treatment classification, providing justification for laser parameter selection and immediate tissue effect in clinical use. METHODS: Retrospective review of 9 patients who underwent KTP laser treatment for RE. Demographics, RE severity, laser settings, total laser energy, and immediate tissue effects were correlated with quantified voice outcomes. RESULTS: An average of 157 joules (6-640 J) was delivered over a 0.369-second exposure time (0.1-0.9 seconds). Immediate tissue effects varied from nonablative treatment (type I and type II) to ablation without tissue removal (type III). Overall, Voice Handicap Index-10 (VHI-10) decreased by 8.23; improvement was most pronounced with type II treatments (delta VHI-10=12). No complications were encountered. CONCLUSION: Potassium titanyl phosphate laser can be safely and effectively used to improve voice in RE patients regardless of severity. This is the first study to provide detailed information on laser settings, energy delivery, and treatment effect in RE management; these results may guide clinical use of this modality, especially for novice laser surgeons.

[Chemoradiotherapy in the combined treatment for laryngopharyngeal cancer].

The study included 62 patients with morphologically verified squamous cell carcinoma of laryngopharynx, stages T2-4N0-2M0. As a result of the treatment complete regression was recorded in 28.1 ± 7.9% of cases, partial regression--in 50.0 ± 8.8% of patients, and stabilization--in 21.9 ± 7.3% of cases. The total efficiency of therapy made up 78.1 ± 7.3%. Chemotherapy complications and radiation injuries did not exceed I-II grade by CTC-NCIC criteria and PTOG/EORTC scale, were easily stopped, did not affect the time periods of further treatment and had no considerable influence on the postoperative period. Conservative surgery was performed in 26% of cases. The total 5-year survival rate made up 65.4 ± 8.4%, relapse-free 5-year survival rate--60.6 ± 8.9%. The efficiency of the vocal function rehabilitation made up 73.9 ± 9.1%. Rehabilitation time was 21 ± 8.2 days.

Cost-minimisation and cost-effectiveness analysis comparing transoral CO2 laser cordectomy, laryngofissure cordectomy and radiotherapy for the treatment of T1-2, N0, M0 glottic carcinoma.

The financial costs of laryngeal cancer treatment are a notable burden on healthcare budgets. In this study, we assess whether CO2 laser surgery is cheaper than radiotherapy or laryngofissure and cordectomy in the treatment of T1-2, N0, M0 glottic squamous cell carcinoma. 56 patients with a mean age of 65.88 years (SD = 10.04), 53 men and 3 women, with T1-2, N0, M0 glottic squamous cell carcinoma were retrospectively analysed. We conducted a comparative analysis of costs associated with three treatments: carbon dioxide laser cordectomy (n = 21), radiotherapy (n = 20), and laryngofissure cordectomy (n = 15). Complications of the radiotherapy and surgical treatments, need for tracheotomy and its permanence, length of hospital stay, occupation and ability to work and economic costs of treatments were recorded. Cost-minimisation and cost-effectiveness analysis were obtained. The cost of transoral laser cordectomy (2,289.79 euro) is statistically significantly lower than that of radiotherapy (4,804.72 euro) or laryngofissure cordectomy (13,229.75 euro) (p < 0.001). Transoral carbon dioxide laser surgery is the best option in terms of cost-effectiveness for the treatment of T1-2, N0, M0 glottic cancer.

[Management of T1a vocal fold carcinoma]. / Management des T1a Stimmlippenkarzinoms.

About 2/3 of the larynx carcinomas affect the vocal chords. The main risk factor is smoking. Carcinomas in this localisation often arise from leukoplakias with dysplasia. A typical symptom is dysphonia. Arrest of vibration in microlaryngostroboscopy is a hint that a carcinoma could be present. Transoral laser cordectomy or radiotherapy show equivalent oncological results and results in quality of voice in the treatment of vocal fold carcinoma (T1a). As lymph node and distant metastasis are very rare, follow-up can concentrate on microlaryngoscopy. In case of a suspicious area on the vocal fold, biopsy of the affected tissue is needed to plan correct treatment. The prognosis of the T1 vocal chord carcinoma is quite good with a 5-year survival rate of almost 100%.

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial.

BACKGROUND: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.

Concurrent Chemoradiotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil for T3 N0 Glottic Carcinoma Without Vocal Cord Fixation.

BACKGROUND/AIM: We retrospectively evaluated the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin, and 5-fluorouracil (TPF) for T3 N0 glottic carcinoma without vocal cord fixation. PATIENTS AND METHODS: Twenty-five patients underwent TPF-CCRT without elective nodal irradiaion (ENI). After the RT of 40 Gy, five patients (20%) without tumor regression underwent surgery. Others underwent RT with a median total dose of 66 Gy. RESULTS: Of the five patients who underwent surgery after the RT of 40 Gy, two showed residual carcinoma pathologically and the other three were confirmed to have complete pathological response to the treatment. The 5-year local control rate was 87%. No patients exhibited regional failure. No acute toxicities of grade 5 or late toxicities ≥grade 3 were observed. CONCLUSION: TPF-CCRT provides excellent tumor control with acceptable toxicities. CCRT while omitting ENI is a reasonable approach for T3 N0 glottic carcinoma without vocal cord fixation.

Pathologic effects of external-beam irradiation on human vocal folds.

OBJECTIVES: We sought to better characterize pathologic changes that occur in the human vocal fold after radiotherapy for head and neck cancer. METHODS: In a blinded, controlled study of archived tissue, we evaluated postirradiation salvage laryngectomy vocal fold tissue without evidence of malignant disease. Clinical and demographic patient data were collected. In a blinded fashion, irradiated tissue was compared to nonirradiated, benign control tissue. Histomorphometric analysis was used to assess muscle and collagen organization, superficial lamina propria (SLP) and vocal ligament thickness, vocalis muscle fiber area, collagen content, and hyaluronic acid content. Immunohistochemical analysis was used to assess the content of type I collagen, type IV collagen, vimentin, fibronectin, alpha-smooth muscle actin, matrix metalloproteinase 9, and laminin. RESULTS: Twenty irradiated vocal folds were evaluated and compared to control specimens. Collagen and muscle disorganization was noted in the irradiated specimens. The SLP and vocal ligament thicknesses and the mean muscle fiber diameters did not differ significantly. The SLP fibronectin and the vocalis muscle and SLP collagen content were significantly increased in the irradiated vocal folds, and the SLP collagen content increased significantly with time between irradiation and resection. The laminin content of irradiated vocalis muscles was significantly decreased. CONCLUSIONS: Radiotherapy results in significant vocal fold tissue changes. Having more precisely defined these changes, we plan continued investigation seeking targeted preventive and therapeutic interventions for improved vocal quality following radiotherapy.

Blue Light Laser Results in Less Vocal Fold Scarring Compared to KTP Laser in Normal Rat Vocal Folds.

OBJECTIVES: Preliminary investigations suggest that a novel blue light (BL) laser with a wavelength of 445 nm is comparable to the commonly utilized potassium titanyl phosphate (KTP) laser (532 nm) for treatment of various laryngeal pathologies. The objective of the current study is to make a direct histological comparison of the degree of vocal fold scarring after either BL or KTP laser treatment in an animal model. STUDY DESIGN: This was a randomized controlled study using rats. METHODS: Twenty-four Sprague-Dawley rats were randomized to BL or KTP laser treatment. Laser was delivered in non-overlapping pulses to normal rat vocal folds. Larynges in each group were harvested at three time points: post-operative day 1, 30, and 90. Three animals served as negative controls. The excised whole larynges were sectioned transversely and stained with hematoxylin/eosin and trichrome. Presence of subepithelial inflammation and protein deposition/fibrosis indicative of scarring were scored semi-quantitatively (from grade 1-3) by two pathologists blinded to treatment groups. RESULTS: Between-group comparison showed that both laser treatments resulted in significantly elevated subepithelial protein deposition/fibrosis 90 days after treatment compared to negative controls (BL: 2 ± 0; KTP: 2.67 ± 0.29; control: 1.17 ± 0.29; P < .05). However, the degree of protein deposition/fibrosis was significantly higher in the KTP group compared to the BL group (P = .016). Within-group comparison showed that the KTP group showed evidence of fibrosis as early as 30 days after treatment, which was not observed in the BL group. CONCLUSIONS: The current study suggests that the degree of scarring is significantly less after BL laser treatment compared to KTP in normal rat vocal fold tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 131:853-858, 2021.

Laser Microsurgery Versus Radiotherapy Versus Open Partial Laryngectomy for T2 Laryngeal Carcinoma: A Systematic Review of Oncological Outcomes.

INTRODUCTION: The aim of the current systematic review is to update the pooled survival outcome of patients with T2 glottic carcinoma treated with either laser surgery (CO2 transoral laser microsurgery [CO2 TOLMS]), radiotherapy (RT), or open partial laryngectomy (OPL). METHODS: A systematic search was performed using the MEDLINE database, Scopus, and Google scholar. The inclusion criteria were studies of patients with T2N0 glottic tumor, treated with either primary CO2 TOLMS, definitive curative RT, or primary OPL, and with reported oncological outcome at 5 years calculated with a Kaplan-Meier or Cox regression method. RESULTS: The results of the current review show that local control (LC) is higher with OPL 94.4%, while there are no differences in LC at 5-year posttreatment for patients treated with RT, compared to those treated with CO2 TOLMS (respectively, 75.6% and 75.4%). Primary treatment with OPL and CO2 TOLMS results in higher laryngeal preservation than primary treatment with RT (respectively 95.8%, 86.9%, and 82.4%). CONCLUSION: First-line treatment with OPL and CO2 TOLMS should be encouraged in selected T2 patients, because it results in higher laryngeal preservation and similar LC compared to primary treatment with RT. The involvement of the anterior commissure in the craniocaudal plane and T2b impaired vocal cord mobility have a poorer prognosis and LC compared to patients with T2a tumors for both CO2 TOLMS and RT.

Pulsed dye laser-induced inflammatory response and extracellular matrix turnover in rat vocal folds and vocal fold fibroblasts.

BACKGROUND AND OBJECTIVES: Disruption of the vocal fold extracellular matrix (ECM) can induce a profound and refractory dysphonia. Pulsed dye laser (PDL) irradiation has shown early promise as a treatment modality for disordered ECM in patients with chronic vocal fold scar; however, there are limited data addressing the mechanism by which this laser energy might induce cellular and extracellular changes in vocal fold tissues. In this study, we examined the inflammatory and ECM modulating effects of PDL irradiation on normal vocal fold tissues and cultured vocal fold fibroblasts (VFFs). STUDY DESIGN/MATERIALS AND METHODS: We evaluated the effects of 585 nm PDL irradiation on inflammatory cytokine and collagen/collagenase gene transcription in normal rat vocal folds in vivo (3-168 hours following delivery of approximately 39.46 J/cm(2) fluence) and VFFs in vitro (3-72 hours following delivery of 4.82 or 9.64 J/cm(2) fluence). We also examined morphological vocal fold tissue changes 3 hours, 1 week, and 1 month post-irradiation. RESULTS: PDL irradiation altered inflammatory cytokine and procollagen/collagenase expression at the transcript level, both in vitro and in vivo. Additionally, PDL irradiation induced an inflammatory repair process in vivo that was completed by 1 month with preservation of normal tissue morphology. CONCLUSIONS: PDL irradiation can modulate ECM turnover in phenotypically normal vocal folds. Additional work is required to determine if these findings extend to disordered ECM, such as is seen in vocal fold scar. Lasers Surg. Med. 41:585-594, 2009. (c) 2009 Wiley-Liss, Inc.

The Effects of Photobiomodulation on Vocal Fold Wound Healing: In Vivo and In Vitro Studies.

Background: Photobiomodulation (PBM) is increasingly used in dermatology and dentistry due to its benefit of promoting wound healing and relieving pain; however, there is no corresponding research report on the application of PBM to vocal fold wound healing. Objective: To assess the potential wound-healing effects of PBM on the vocal folds via in vivo and in vitro experiments. Materials and methods: In in vitro study, vocal fold fibroblasts (VFFs) were irradiated under a diode laser with wavelength of 635 nm at energy density of 8 J/cm2. The Cell Counting Kit-8 (CCK-8) assay was used to study the viability of VFFs, and the gene expressions of COL1A2, COL3A1, IL-6, HAS2, and COX-2 were investigated by real-time polymerase chain reaction (RT-PCR). In in vivo study, 15 rabbits were used. Lamina propria of the left vocal folds of 12 rabbits was unilaterally stripped, and 6 of them were treated with PBM. The remaining three rabbits served as normal controls. After 3 months, all animals were sacrificed to obtain histological results. We used laryngoscope to record images of the healing phase. Results: Irradiation with energy density of 8 J/cm2 resulted in a 2.8% increase in cell proliferation (p < 0.05). However, the difference between the experimental and the control group became larger after 48 and 72 h of subsequent irradiation. RT-PCR results showed that the expression of COL1A2, COL3A1, and HAS2 was higher, and the expression of IL-6 and COX-2 was lower. Histological examination showed that, compared with the injury group, hyaluronic acid (HA) increased significantly, collagen deposition decreased, and the configuration of collagen was more organized after PBM treatment. Conclusions: PBM can inhibit inflammatory reaction and promote the secretion of HA to decrease the deposition of collagen and regenerate vocal fold tissue without scar.

Irradiated macula flava in the human vocal fold mucosa.

PURPOSE: There have been no investigations regarding radiation-induced damage on human maculae flavae (MFs) in the vocal fold mucosa (VFM) and on stellate cells (SC) in the MF. The VFM, especially MF, after irradiation was investigated histologically. MATERIALS AND METHODS: The lamina propria of the irradiated VFM was investigated in 5 human adult vocal folds by light and electron microscopy. RESULTS: Fibroblasts in the irradiated Reinke's space (RS) showed no morphological changes. Irradiated RS was composed of fibrous tissue with increased collagenous fibers. Most of the SC in the irradiated MF had dark cytoplasm. The nucleus-cytoplasm ratio was relatively small, but there were few intracellular organelles in the cytoplasm. Some SC showed degeneration. Fewer vesicles were present at the periphery of the cytoplasm. The MF was rather deficient in fibrous components. Elastic and collagenous fibers immediately surrounding SC in the irradiated MF were lower in number than usual, but elastic fibers and collagenous fibers composed of irregular collagen fibrils could be detected at a distance from SC. It was suggested that precursors of collagenous and elastic fibers synthesized by SC were damaged by irradiation. Radiation sensitivity of SC was higher than that of conventional fibroblasts in RS, and SC appeared to decrease their level of activity. CONCLUSIONS: Radiation sensitivity of SC was different from that of conventional fibroblasts. Radiation induced not only changes in the lamina propria of the VFM but also dysfunction of the SC in the MF, and is one of the causes of voice disorders after irradiation.

Voice of postradiotherapy nasopharyngeal carcinoma patients: evidence of vocal tract effect.

This study was aimed at identifying acoustic and physiological measures useful for monitoring voice changes in postnasopharyngeal patients with nonlaryngeal malignancies, and providing evidences of vocal tract effect on voice through comparisons between individuals with and without intact vocal tract. Simultaneous acoustic-electroglottographic signals recorded during phonation of vowels /i/ and /a/ sustained at habitual, high, and low pitch levels were compared among 10 postradiotherapy patients with nasopharyngeal carcinoma (NPC), 10 voice patients (VPs) with intact vocal tract, and 10 healthy individuals with normal voice (NORM). Results from a series of discriminant analyses revealed that the NPC group generally exhibited lower signal-to-noise (SNR) and open quotient (OQ) and higher Formant 1 frequency (F(1)) and speed quotient (SQ) than the NORM group. Unlike both VP and NORM groups, the NPC group failed to show a pitch effect on all voice measures, including OQ, SQ, percent jitter, percent shimmer, and SNR, suggesting an effect of radiotherapy and/or vocal tract on laryngeal behaviors. For the vowel /i/, on the other hand, only the NPC and NORM groups showed a pattern of pitch-dependent F(1) raising, a reflection of increased pharyngeal narrowing. These findings suggested that the pitch effect on laryngeal behaviors differed not only between individuals with intact vocal tract and those without but also between those with structural and dynamic changes of vocal tract.

Acoustic voice analysis in different phonetic contexts after larynx radiotherapy for T1 vocal cord carcinoma.

INTRODUCTION: Radiotherapy for early vocal cord carcinoma affects quality of voice. Nevertheless, most patients refer to having a high satisfaction level with their voice. The few acoustic studies on quality of voice have been performed only in prolonged vowel production, which is not a usual speech situation. The present study has been done with the aim of establishing which phonetic situations reflect a greater alteration in voice production related to irradiation. MATERIAL AND METHODS: Eighteen male patients irradiated for Tis-T1 vocal cord carcinoma and a control group of 31 non-irradiated subjects were included in a study of acoustic voice analysis. This analysis was performed one year after radiotherapy. Patients and control group voices were tape recorded in extended vowel production, oral reading of a standard paragraph, spontaneous speech and in a song. Acoustic analysis was performed by a Kay Elemetric's Computerized Speech Lab (model CSL #4300). Fundamental frequency, jitter, shimmer and harmonics-to-noise ratio were obtained in both groups. Statistical test: Lin concordance coefficient and Pearson's correlation coefficient, Student's t-test and ROC curves. RESULTS: Concordance and correlation studies did not allow selection of any subgroup in acoustic parameters and different acoustic situations. Acoustic parameters had higher median values in irradiated patients. Student's t-test showed significant differences for fundamental frequency in sustained vowel production and spontaneous speech; for jitter there was statistical significance in all the acoustic situations and for shimmer in oral reading and song. Jitter showed a cut-off of 2.02% with a sensitivity of 89% and specificity of 97% in classifying irradiated and non-irradiated groups. The ROC curve for jitter correctly classified 94% of subjects into irradiated or non-irradiated groups. CONCLUSIONS: The present study showed that jitter obtained from spontaneous speech was the most relevant parameter in discriminating voice in irradiated patients by acoustic analysis. Jitter in spontaneous speech is in need of more analysis in bigger series and in more advanced stages of larynx cancer as its relevance has been demonstrated.

A Multidimensional Study of Vocal Function Following Radiation Therapy for Laryngeal Cancers.

BACKGROUND: Radiation therapy (XRT) has proven to be an effective curative modality in the treatment of laryngeal cancers. However, XRT also has deleterious effects on vocal function. AIM: To demonstrate the multidimensional nature of deficits in vocal function as a result of radiation therapy for laryngeal cancer. STUDY DESIGN: Cohort study. METHODOLOGY: Vocal function parameters were chosen from the 5 domains of voice assessment to complete a multidimensional assessment battery. Adults irradiated (XRT group) for laryngeal cancers were compared to a control group of individuals with no history of head and neck cancers or radiation therapy. The control group was matched in age, sex, and pack years of smoking. RESULTS: Eighteen participants were recruited for the study. The XRT group demonstrated significantly worse clinical values as compared to the control group across select parameters in the each of the 5 domains of voice assessment. DISCUSSION: Radiation therapy for laryngeal cancers results in multidimensional deficits in vocal function. Notably, these deficits persist long term. In the present study sample, multidimensional deficits were persistent 2 to 7 years following completion of XRT. The observed multidimensional persistent vocal difficulties highlight the importance of vocal rehabilitation in the irradiated larynx cancer population.

Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post chemoradiotherapy.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) used for definitive management of locally advanced head and neck squamous cell carcinoma (HNSCC) allows organ preservation at the cost of preservation of function. Vocal cords, being within the field of irradiation, undergo acute and chronic changes which adversely impacts the patients' voice. AIMS: To assess the acute changes in the acoustic characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC. MATERIALS AND METHODS: Thirty patients with HNSCC treated with CCRT, a total dose of 66-70 Gy/33-35 fractions at five fractions/week, with weekly cisplatin. Acoustic analysis (AA) and laryngoscopic examination performed at baseline, 6 weeks, and 3 months post-CCRT. Statistical analysis of the parameters using ANOVA and Student's t-test was performed. RESULTS: Of the thirty patients, 26 patients completed CCRT. At 6 weeks post-CCRT, among 14/26 patients, most (11/14 [78.57%]) developed Grade III toxicity. On AA, both increase and decrease in mean F0 from baseline was observed. An increase (P < 0.05) in each, i.e., jitter, shimmer, and noise to harmonics ratio (NHR) were recorded. At 3 months post-CCRT, among 8/14 available, most (6/8 [75%]) showed Grade II toxicity. The mean F0 reduced for both genders; jitter and shimmer, and NHR values maintained an increase (P > 0.05). CONCLUSIONS: Periodic AA allows quantification of voice changes and mapping of vocal toxicity induced by CCRT.

Retrospective analysis: concurrent chemoradiotherapy using protracted continuous infusion of low-dose cisplatin and 5-fluorouracil for T2N0 glottic cancer.

PURPOSE: Treatment with conventional radiotherapy alone for local control of T2 glottic cancer (T2GC) is insufficient. To improve local control of T2GC, we have simultaneously administered continuous intravenous infusions of low-dose cisplatin and 5-fluorouracil (5-FU) in combination with irradiation. MATERIALS AND METHODS: We performed this combination therapy in a total of 11 consecutive patients with previously untreated invasive squamous cell carcinoma (T2GC). Cisplatin was administered at 4 mg/m2/day and 5-FU at 200 mg/m2/day for 120 h, except during weekends, beginning on the day irradiation with a once-daily fraction at 2 Gy was started. RESULTS: An initial local control rate of the primary tumor was achieved in 10 of the 11 patients (91%), and ultimate laryngeal preservation by cordectomy was achieved in all cases. Regarding adverse reactions, grade 3 or 4 hemotoxicity did not develop in any of the patients. Grade 3 laryngitis was observed in four patients (36%), but none of these patients required interruption of treatment owing to acute laryngeal reactions. CONCLUSION: Instead of radiotherapy alone, this combination chemoradiotherapy is suggested with the possibility of improving local control of T2GCs.

Determination of scattering properties and damage thresholds in tissue using ultrafast laser ablation.

Ultrafast laser surgery of tissue requires precise knowledge of the tissue's optical properties to control the extent of subsurface ablation. Here, we present a method to determine the scattering lengths, ?s, and fluence thresholds, Fth, in multilayered and turbid tissue by finding the input energies required to initiate ablation at various depths in each tissue layer. We validated the method using tissue-mimicking phantoms and applied it to porcine vocal folds, which consist of an epithelial (ep) layer and a superficial lamina propia (SLP) layer. Across five vocal fold samples, we found ?s,ep=51.0±3.9???m, Fth,ep=1.78±0.08??J/cm2, ?s,SLP=26.5±1.6???m, and Fth,SLP=1.14±0.12??J/cm2. Our method can enable personalized determination of tissue optical properties in a clinical setting, leading to less patient-to-patient variability and more favorable outcomes in operations, such as femto-LASIK surgery.

Early Cellular Response to Radiation in Human Vocal Fold Fibroblasts.

OBJECTIVES: Radiation therapy is a common treatment strategy for laryngeal carcinoma. However, radiation is not without adverse side effects, especially toward healthy vocal fold tissue, which can lead to long-term impairments in vocal function. The objective of this preliminary study was to investigate early responses of healthy human vocal fold fibroblasts (VFF) to radiation. METHODS: VFF were exposed to a single or fractionated dose radiation scheme. Nonradiated VFF served as controls. Morphology of radiated and control VFF was subjectively examined. Quantitative polymerase chain reaction was used to evaluate the effect of radiation on extracellular matrix and inflammatory-related genes. VFF viability was investigated using a LIVE/DEAD and clonogenic assay. RESULTS: Single or fractioned dose radiated VFF were morphologically indistinguishable from control VFF. No significant differences in gene expression were observed following either radiation scheme and as compared to controls. Clonogenic assay revealed reduced VFF viability following the fractionated but not single dose scheme. No changes in viability were detected using the LIVE/DEAD assay. CONCLUSIONS: We present one of the first investigations to evaluate early responses of healthy VFF to radiation. Findings will contribute to a growing body of literature seeking to elucidate the biological mechanisms underlying voice changes following radiation therapy for laryngeal carcinoma.