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Purpose: The purpose of this study was to evaluate the short-term outcomes in terms of oncological outcomes, toxicities, and impact of quality of voice on livability of early glottic cancer (EGC) (T1) patients after hypofractionated radiotherapy., Material and Methods: 30 patients of early glottic carcinoma, staged cT1a-T1bN0M0 with Eastern Cooperative Oncology Performance Status (ECOG PS ≤ 2). Exclusion criteria included ECOG PS > 2, T2-T4 disease, and any other head and neck malignancy. Voice Handicap Index-10 (VHI-10) was used to score voice outcomes of patient's pre- and post-radiation., Results: All the subjects were predominantly smokers (80%) having hoarseness of voice as the most common presenting complaint (76.7%) followed by dry cough (13.3%) and foreign body sensation (10%). On posttreatment response assessment, there has been a significant reduction in VHI-10 scores from pre-radiotherapy (RT) to 6, 12, and 24 weeks post-radiation completion in all three domains (functional, emotional, and physical), as well as total scores, with a significant P value (<0.05) being observed., Conclusion: The use of modest hypofractionated regimen (63 Gy in 28 fractions) in patients of early glottic disease (T1a and T1b) posttreatment completion provides good oncological outcomes with better quality of voice being observed., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Objective: Glottic cancer has an excellent probability of cure. The early glottic cancer is usually treated by radiotherapy with different fractionation schedules. The aim of this study was to compare conventional versus hypofractionated radiotherapy with respect to overall survival and disease-free survival., Materials and Methods: A total of fifty patients with T1-2N0M0 glottic cancer with no previous treatment history were prospectively randomized into two arms. In Arm A (Study), patients received a total of 55 Gy in 20# at 2.75 Gy/#, 5 days a week. In Arm B (Control), patients received a total of 66 Gy in 33# at 2 Gy/#, 5 days a week. Disease response was evaluated by the WHO criteria at the end of treatment, then at 1, 2, and 3 months to complete their 6-month follow-up. Overall survival and disease-free survival were evaluated at 1, 2, and 3 years., Results: Overall, 100% of patients in the study arm and 96% of patients in the control arm had complete response after 6 months. Overall survival rates at 1, 2, and 3 years were 96%, 96%, and 88%, respectively, in the study arm, while in the control arm, these values were 92%, 84%, and 80%, respectively, and the difference was not statistically significant (P > 0.05). Disease-free survival at 3 years was 88% in the study arm and 80% in the control arm., Conclusion: The study suggests that hypofractionated regimen may be better in local control and symptomatic relief with the added advantage of shorter treatment time, which offers better patient compliance and advantageous in busy setups where there is heavy patient load., Competing Interests: None

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 (CO 2 transoral laser microsurgery [CO 2 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 CO 2 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 CO 2 TOLMS (respectively, 75.6% and 75.4%). Primary treatment with OPL and CO 2 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 CO 2 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 CO 2 TOLMS and RT.

Purpose: In this study, it is aimed to compare three different radiotherapy treatment planning techniques in terms of critical organ scoring index (COSI), two different conformity index (CI), tumor control probability (TCP), and normal tissue complication probability (NTCP) calculations in early (T1) glottic larynx carcinoma (T1GL). Furthermore, it is aimed to investigate these parameters compliance with dose-volume histograms (DVH) parameters., Materials and Methods: Ten T1GL patients were immobilized in a supine position with a head and neck thermoplastic mask. Treatment plans were created with opposed lateral fields (OLAFs) and intensity-modulated radiation therapy (IMRT) techniques with a total dose of 66 Gy in 33 fraction with 2 Gy/day. IMRT fields were selected as five fields (5IMRT) and seven fields (7IMRT). Dosimetric evaluation of three different treatment plans for T1GL carcinoma was performed in two consequential steps. First step was the assessment of planning target volume (PTV), all organs at risks (OARs), and normal tissue (NT) dose calculations according to given dose constraint directions and comparing the plans via DVH. In the second step, for PTV, the compatibility of DVH data with CIs-TCP was investigated where COSI-NTCP was compared with DVH for OARs. The DVH data were considered as reference in all evaluations., Results: The CI RTOG mean values were significantly closer to 1 with IMRT plans when compared to OLAF plans (P = 0.005). The CI PADDICK mean values revealed that OLAF plans were significantly worse than IMRT plans (P = 0.005). No statistically significant difference was found between all three plans in terms of homogeneity index mean values (P = 0.076). The calculated mean TCP values were significantly better for 7IMRT plans when compared to OLAF and 5IMRT plans (P = 0.007 and P = 0.017, respectively). Both NTCP and COSI evaluations, which is compatible with DVH, significantly favored OLAF plan for spinal cord and 7IMRT for thyroid gland. The COSI evaluations, which are compatible with DVH, significantly favored 7IMRT plan for carotid arteries and 5IMRT plan for NT., Conclusion: Our results demonstrated that CI PADDICK -TCP calculations for PTV and COSI-NTCP calculations for OARs were compatible with DVH in T1 GL plans. Therefore, we suggest such parameters as valuable tools for choosing the feasible one among multiple plans and even with different treatment machines., Competing Interests: None

Background: Definitive radiotherapy is an effective single-modality in T1 glottic cancer. Hypofractionated schemes could offer excellent results in a shorter treatment period. We aimed to evaluate the clinical outcomes and toxicity comparing conventional vs. hypofractionated radiotherapy treatment in T1N0M0-glottic cancer., Patients and Methods: Between Jan-1st, 2005 and August-1st, 2017, in a prospective cohort study, with 10-year follow-up, 138 patients were treated with conventional schedule 2 Gy/day, total dose 70 Gy/7 weeks (N = 71) or hypofractionated schedule 2, 2-2, 25 Gy/day, total dose 63, 8-63 Gy/5, 5 weeks (N = 67). Endpoints were clinical-response rate, local relapse-free survival (LRFS), laryngectomy-free survival (LFS), toxicity rates, relapse-free survival (RFS), metastasis-free survival (MFS), second tumour-free survival (2TFS), and overall survival (OS)., Results: All patients showed a complete clinical response. No differences were found for LRFS (p = 0.869), LFS (p = 0.975), RFS (p = 0.767), MFS (p = 0.601), 2TFS (p = 0.293), or OS (p = 0.685). Acute toxicity for skin and mucosae was similar (p = 0.550 and p = 0.698). Acute laryngeal toxicity was higher in the hypofractionation group (p = 0.004), due to an increase in slight moderate grade. No differences in late laryngeal edema were found (p = 0.989)., Conclusion: Radiotherapy offers high rate survival, local control, and larynx preservation after 5-10-year follow-up. A hypofractionation could be preferable, since it offers the same results as conventional with fewer treatment sessions.

Background Radiotherapy (RT) is a successful mode of treatment for early glottic cancer. The aim of the study was to assess voice quality both before and 3 months after successful RT using multimodal methods while also identifying the factors affecting it. Patients and methods In 50 patients with T1 glottic carcinoma, the subjective (patients' assessment of voice quality [VAS], Voice Handicap Index [VHI] questionnaire, phoniatricians' assessment using the grade/roughness/ breathiness [GRB] scale), and objective assessments (fundamental laryngeal frequency [F0], jitter, shimmer, maximum phonation time [MPT]) of voice quality were performed before RT and 3 months post-RT. The data on gender, age, extent of the tumors, biopsy types, smoking, local findings, and RT were obtained from the medical documentation. Results Three months after the treatment, VAS, VHI, G and R scores, F0, and MPT significantly improved in comparison with their assessment prior to treatment. Before the treatment, the involvement of the anterior commissure significantly deteriorated jitter (p = 0.044) and the involvement of both vocal folds deteriorated jitter (p = 0.003) and shimmer (p = 0.007). After the RT, F0 was significantly higher in the patients with repeated biopsy than in the others (p = 0.047). In patients with post-RT changes, the B score was significantly higher than in those without post-RT changes (p = 0.029). Conclusions Voice quality already significantly improved three months after the treatment of glottic cancer. The main reason for the decreased voice quality prior to treatment is the tumor's extent. Post-RT laryngeal changes and repeated biopsies caused more scarring on vocal folds adversely influencing voice quality after the treatment.

Purpose: Presentation of long-term results of radiation treatment in patients with T1 glottic cancer and evaluation of prognostic factors., Methods: We performed a retrospective analysis in a group of 569 patients with T1 squamous cell glottic carcinoma treated with radiotherapy at the Center of Oncology in Cracow between 1977 and 2007. In all, 503 (88%) patients presented with T1a stage disease and 66 (12%) with T1b. Anterior commissure infiltration was present in 179 (31%) patients. Average hemoglobin level prior to therapy was 13.9 g/dl. Using the body mass index (BMI), 114 (20%) patients were underweight, and 91 (16%) were overweight. Median time between collecting tumor specimen and beginning of radiotherapy was 56 days (range 14-145 days). Treatment regimen was normofractionated with single fraction ≤2 Gy in 102 (18%) and hypofractionated in 467 (82%) patients., Results: The 5‑ and 10-year overall survival (OS), disease-specific survival (DSS) and local control (LC) rates were 85 and 68%, 88 and 86%, 89 and 87%, respectively. Multivariate analysis showed that tobacco smoking, low hemoglobin level (<13 g/dl), anterior commissure infiltration, fraction dose ≤2 Gy and time from collecting specimen to beginning of therapy longer than 30 days had negative impact on LC and DSS. Patients' age over 60 years, worse performance status and malnutrition (BMI <18.5) had negative impacts on OS., Conclusions: Radiotherapy is a highly effective treatment method in patients with T1N0M0 glottic cancer. LC and DSS may be improved following hypofractionation, smoking cessation, and shortening of waiting-time until start of treatment. OS was mainly influenced by nutritional and performance status.

Laser surgery and radiotherapy are the two most common ways to treat glottic carcinomas, which is more efficacious and remains controversial. PubMed, Embase, and Cochrane Library were searched to identify relevant studies of laser surgery versus radiotherapy in patients with glottic carcinomas through April 2017. Sensitivity analysis and subgroup analysis were performed to evaluate heterogeneity. Eighteen studies were selected, which included 2480 patients. Patients who had laser surgery had higher rates of laryngeal preservation (OR 3.852; 95% CI 1.922-7.721) and overall survival (OR 1.388; 95% CI 1.063-1.811) versus who had radiotherapy. No significant differences were observed between laser surgery and radiotherapy on local control (OR 1.186; 95% CI 0.759-1.854), recurrence (OR 0.758; 95% CI 0.445-1.289), or disease-specific survival (OR 1.597; 95% CI 0.887-2.876). There were clinical benefits for patients with glottic carcinoma after laser surgery compared with radiotherapy with respect to survival and laryngeal preservation.

Objectives: Long-term voice outcome (LTVO) after radiation (XRT) or trans-oral laser microsurgery (TLM) is unclear. This study is a multi-modality analysis of LTVO following XRT or TLM in patients with early glottic cancer. We hypothesize that as compared with TLM, LTVO is worse in the XRT group because of progressive fibrosis in the glottic tissue MATERIAL AND METHODS: One hundred and two patients with early glottic carcinoma (carcinoma in situ, T1, T2) were included. Multi-modality voice analyses were performed with self-perception using Voice Handicap Index-10, objective analysis using Analysis of Dysphonia in Speech and Voice Software (Cepstral Spectral Index of Dysphonia score for Consensus Auditory-Perceptual Evaluation of Voice sentences), and perceptual rating by two blinded speech language pathologists (GRBAS scale)., Results: Fifty-five patients received TLM (mean follow-up = 52 months) and 47 patients had XRT (mean follow-up = 65 months). There is no difference between the two groups in sex, age, stage, and follow-up time. Intraclass correlation coefficient between raters was high at 0.94. Controlling for age and stage, XRT increases total GRBAS score by 1.38 points (P = 0.006) and increases Cepstral Spectral Index of Dysphonia score by 13.7 points (P < 0.001) when compared with the TLM group. No significant differences were found in the Voice Handicap Index score between the XRT and the TLM groups., Conclusions: This is the first multi-modality voice analysis to suggest TLM results in better LTVO than XRT in GRBAS score and objective voice analysis but not in self-perception. These differences may reflect the progressive effects of XRT on glottic tissue. A randomized controlled study is required to confirm our findings., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to perform a comparison between robust optimization and planning target volume (PTV)-based optimization plans using volumetric modulated arc-therapy (VMAT) by evaluating perturbed doses induced by localization offsets for setup uncertainties in larynx cancer radiation therapy., Methods: Ten patients with early-stage (T1-2N0) glottis carcinoma were selected. The clinical target volume (CTV), carotid arteries, and spinal cord were contoured by a radiation oncologist. PTV-based and robust optimization plans were normalized at D 50% to the PTV and D 98% to the CTV, respectively. Both optimization plans were evaluated using perturbed doses by specifying user defined shifted values from the isocenter. CTV dose (D 98% , D 50% , and D 2% ), homogeneity index (HI) and conformity index (CI 95% , CI 80% , and CI 50% ), as well as doses to the carotid arteries and spinal cord were compared between PTV-based and robust optimization plans., Results: The robust optimization plans exhibited superior CTV coverage and a reduced dose to the carotid arteries compared to the PTV-based optimization plans (p < 0.05). HI, CI 95% and the dose to the spinal cord did not significantly differ between the PTV-based and robust optimization plans (p > 0.05). The robust optimization plans showed better CI 80% and CI 50% compared to the PTV-based optimization plans (p < 0.05). Plan perturbed evaluations showed that the robust optimization plan has small variations in the doses to the CTV, carotid arteries, and spinal cord compared to the PTV-based optimization plan., Conclusions: The robust optimization plan may be a suitable treatment method in radiotherapy for larynx cancer patient., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Over the course of the last several decades, the treatment options for early laryngeal cancers (T1 and T2) have evolved; however, simultaneously the mortality rate has increased. As larynx preservation approaches have become the standard of care, the selection of the proper treatment modality has become paramount. Radiation therapy or transoral laser microsurgery are the most common options for treatment of these early lesions. Oncologic and functional outcomes are considered equivalent between the two modalities for early glottic cancers; however, no direct comparisons exist for robust analysis. In terms of larynx preservation, there also is not compelling data favoring one treatment option or another. For early stage lesions, the goal for any larynx-sparing technique, either radiation or surgery, should be the intent to cure with single modality treatment and minimal short- and long-term toxicity. This article is designed to create a frame of reference for managing early stage disease with respect to lesions of the glottis and supraglottis while weighing treatment implications from an oncologic, functional, and cost perspective., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Laser cordectomy (LC) or radiotherapy (RT) is often recommended in the early stage of laryngeal cancer. We conducted perceptual and acoustic analysis to compare sustained vowel and stop consonants since there is no article evaluating both the sustained vowel and stop consonants. Eventually, we might determine which management is superior in terms of speech production., Subjects and Methods: A total of 28 patients who underwent LC and RT for early T1 glottic cancer were selected. The sustained vowel /a/ and bilabial stop consonants were used to assess the perceptual scores. The fundamental frequency (F o ), jitter, shimmer and noise-to-harmonic ratio (NHR) levels for sustained vowels were evaluated. Voice onset time (VOT), vowel duration (VD) and closure duration of the bilabial plosives were analyzed. A receiver operating characteristic curve analysis was used to evaluate significant results statistically., Results: The GRBAS and discrimination scores were not significantly different between two groups. F o and jitter were significantly higher in the LC than RT. The cut-off value was statistically higher in the LC group and statistically lower in the RT group. The VOT was significantly longer in the LC than RT. The cut-off value of the /pipida/ VOT was statistically longer in the LC group and statistically shorter in the RT group., Conclusions: The differences may have been due to muscular fibrosis after RT. Movements of vocal cords with fibrosis were sluggish, when impulsion developed to pronounce the initial /p/ sound, so the VOT was shortened and the VD was longer after RT.

Objectives: The aim of this study was to investigate long-term voice outcomes and voice-related quality of life (QOL) for early glottic cancer treated with radiotherapy., Study Design: Long-term exploratory follow-up study of a prospective patient cohort comparing outcomes at a mean of 11 years postradiotherapy with the original 1-year posttreatment results., Method: Eight patients completed voice tasks for auditory perception and acoustic and aerodynamic measures. Patient-reported voice-related QOL (VR-QOL) and voice quality were measured. Changes in outcomes over time were analysed using repeated-measures linear mixed models., Results: Acoustic and aerodynamic outcomes remained stable from 1 year postradiotherapy to long-term follow-up, with only jitter mildly increasing from 1.9% at 1 year posttreatment to 2.8% (difference = 1.0%, 95% confidence interval [CI] = 0.1-1.9). Perceptually, voice remained relatively stable with only phonation breaks slightly increasing within the normal range, from 1.1 to 1.7 (difference = 0.6, 95% CI = 0.3-0.9) and breathy quality increasing from normal to slight impairment, with scores increasing from 1.8 to 2.4 (difference = 0.6, 95% CI = 0.3-1.1). QOL scores indicate a good level of VR-QOL that were unchanged at long-term follow-up when compared with 1 year posttreatment., Conclusions: Improvement in voice outcomes found at 1 year postradiotherapy were largely maintained long term, with only minor changes observed. QOL scores indicate that a high level of VR-QOL was maintained many years after curative radiotherapy., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

A therapeutic decision in the treatment of Tis/T1a glottic carcinoma with radiotherapy (RT) or transoral laser surgery (TOS) is still an open issue. Oncologic outcome and voice quality may support the choice for the latter To conduct a systematic review and meta-analysis to compare oncologic and functional outcomes of TOS and RT as treatment options for Tis/T1a glottic cancer. Literature research on online databases was carried out. Potentially eligible articles were reviewed. Relevant articles were selected and evaluated. There was statistical significance favoring patients initially treated with TOS when it comes to overall survival, disease-specific survival and larynx preservation. No difference in local control was found. TMF, Jitter and Shimmmer measurements presented statistically significant results in favor of RT. Self-assessment of voice quality (VHI) and f0 showed no statistically significant differences. Maximum Phonation Time (MPT) had a better response to RT. There is a trend in favor of RT. Tis/T1a glottic cancer patients submitted to TOS had significant overall and disease specific survival and had fewer risks of having a total laryngectomy, when compared to the radiotherapy group. The self-assessment of voice quality and f0 did not show any difference; however, Jitter, Shimmer and MPT measurements favored radiotherapy.

Purpose of Review: To give an overview of the laryngeal preservation and functional outcomes of patients treated with transoral CO2 laser microsurgery (TLM) or radiotherapy for T2 glottic carcinoma. This information supports physicians and patients in treatment counselling and choices., Recent Findings: A recent systematic review showed that local control rates at 5-year did not differ between radiotherapy and TLM for T2 glottic tumours. However, there is a lack of comparative data on laryngeal preservation as well as functional outcomes in T2 glottic carcinoma., Summary: Laryngeal preservation for T2 tumours in this review is higher for patients treated primarily with TLM (88.8 vs. 79.0%). It is important to differentiate between tumours with normal and impaired mobility (T2a and T2b) because the latter showed poorer prognosis for both TLM and radiotherapy. Involvement of the anterior commissure does not result in significantly lower oncological results, if adequately staged and treated. More studies are needed to support these data and to compare the functional outcomes between TLM and radiotherapy for T2 glottic carcinoma.

Objectives: For early stage supraglottic squamous cell carcinoma (SCC), single modality treatment either in the form of primary organ preservation surgery alone or radiation alone is recommended. Thus, a definite treatment strategy for early stage supraglottic SCC remains undefined. The primary objective of this study was to conduct a systematic review and meta-analysis comparing the oncologic outcomes of surgery and radiotherapy in early stage (Stage I and II) T1 N0 and T2 N0 supraglottic SCC., Methods: Systematic methods were used to identify published and unpublished data. Two reviewers independently screened all titles, abstracts and articles for relevance using predefined criteria. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated., Results: Five studies met the inclusion criteria for disease specific mortality with a total of 2864 pooled patients. 5-year disease specific mortality was lower in the surgery group (ORs 0.43, 95% CI 0.31-0.60). Four studies met the inclusion criteria for 5-year overall mortality with a total of 2790 pooled patients. Five-year overall mortality was lower in surgery group (ORs 0.40, 95% CI 0.29-0.55)., Conclusions: This is the first study to examine the management of early stage supraglottic SCC using meta-analytic methodology. Our results suggest that primary surgery may result in decreased disease specific and overall mortality compared to primary radiotherapy.

Background: The optimal treatment strategy for stage I-II glottic squamous cell carcinoma (SCC) is not well-defined. This study analyzed treatment results and prognostic factors., Patients and Methods: This is a single-institution retrospective analysis of 244 patients with T1-2 glottic SCC who underwent normofractionated radiotherapy (RT) and/or surgery between 1990 and 2013. The primary endpoint was relapse-free survival (RFS)., Results: Median age was 65 years (range: 36-92 years), the majority (82%) having stage I disease. Definitive RT was used in 82% (median dose: 68 Gy, 2 Gy per fraction). Median follow-up was 59 months. The 5‑year RFS rates were 83 and 75% (p = 0.05) for stage I and 62 and 50% (p = 0.47) for stage II in the RT and surgery groups, respectively. Multivariate analyses indicate T1 vs. T2 and RT vs. surgery as independent prognostic factors for RFS, with hazard ratios of 0.38 (95% confidence interval, CI: 0.21-0.72) and 0.53 (95% CI: 0.30-0.99), respectively (p < 0.05). The 5‑year overall and cause-specific survival rates in the whole cohort were 92 and 96%, respectively, with no significant differences between treatment groups. Anterior commissure involvement was neither a prognostic nor a predictive factor. The incidence of secondary malignancies was not significantly different between patients treated with and without RT (22 vs. 9% at 10 years, respectively, p = 0.18)., Conclusion: Despite a possible selection bias, our series demonstrates improved RFS with RT over surgery in stage I glottic SCC.

Background: The aim of this study was to report outcomes and late toxicity following hypofractionated accelerated radiotherapy for T2 glottic cancers. We highlight the importance of hypofractionated treatments with shorter overall treatment times, in improving outcomes for T2 glottic cancers. We also compare the biologically effective dose of hypofractionated regimes, with conventional fractionation., Methods: One hundred twelve patients with T2 glottic cancer were treated between January 1999 and December 2005. All patients were prescribed a hypofractionated accelerated radiotherapy dose of 52.5 Gray in 3.28 Gray per fraction, delivered over 22 days. Radiobiological calculations were used to assess the relationship of fraction size and overall treatment time on local control outcomes and late toxicity., Results: The 5-year overall survival was 67%, the 5-year local control was 82%, and the 5-year disease-specific survival was 90%. The respective 5-year local control for T2a and T2b disease was 88.8 and 70.8% (p = 0.032). Severe late toxicity occurred in two patients (1.8%). Radiobiological calculations showed an increase in local control of nearly 12%, with a 10 Gray increase in biologically effective dose., Conclusion: This study has demonstrated that accelerated hypofractionated regimes have improved local control and similar late toxicity compared with conventional fractionation schedules. This supports the use of hypofractionated regimes as the standard of care for early glottic laryngeal cancers.

Background: Radiotherapy alone is often used to treat early-stage glottic cancer (ESGC); however, the optimal radiation treatment schedule remains unknown. The National Comprehensive Cancer Network (NCCN) guidelines recommend both hypofractionated radiotherapy (HFX) and conventionally fractionated radiotherapy (CFX). We compared overall survival (OS) and treatment patterns among patients treated with HFX vs CFX for ESGC using a large national database., Methods: We identified patients diagnosed with stage I-II (cT1-2N0M0) glottic cancer from 2004 to 2013 within the National Cancer Data Base who were treated with either HFX (2.25 Gy/fraction to 63-65.25 Gy) or CFX (2.0 Gy/fraction to 66-70 Gy). The overall survival of patients receiving HFX vs CFX was compared using the log-rank test, multivariable Cox proportional hazards regression, and propensity score matching. All statistical tests were two-sided., Results: Among 10 212 included patients, 4030 patients (39.5%) received HFX and 6182 patients (60.5%) received CFX. Predictors for receipt of HFX included clinical T1 disease, recent year of diagnosis, and treatment at academic and higher-volume centers (all P < .001). Patients treated with HFX increased from 22.1% in 2004 to 58.0% in 2013. HFX was associated with improved OS compared with CFX on univariate (five-year OS = 77.1%, 95% CI = 75.2% to 78.8%, vs 73.5%, 95% CI = 72.1% to 74.8%, respectively, log-rank P < .001) and multivariable analysis (HR = 0.89, 95% CI = 0.81 to 0.98, P = .02), a finding confirmed on propensity score matching., Conclusions: HFX is associated with improved survival compared with CFX among patients treated with definitive radiotherapy for ESGC, particularly among patients with cT2 disease. HFX utilization increased over the study period; however, 40% of patients in our cohort did not receive HFX in the most recent year of our analysis., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53β, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53β revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53β as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.

Purpose: To confirm safety and feasibility of hypofractionated SBRT for early-stage glottic laryngeal cancer., Methods: Twenty consecutive patients with cTis-T2N0M0 carcinoma of glottic larynx were enrolled. Patients entered dose-fractionation cohorts of incrementally shorter bio-equivalent schedules starting with 50 Gy in 15 fractions (fx), followed by 45 Gy/10 fx and, finally, 42.5 Gy/5 fx. Maximum combined CTV-PTV expansion was limited to 5 mm. Patients were treated on a Model G5 Cyberknife (Accuray, Sunnyvale, CA)., Results: Median follow-up is 13.4 months (range: 5.6-24.6 months), with 12 patients followed for at least one year. Maximum acute toxicity consisted of grade 2 hoarseness and dysphagia. Maximum chronic toxicity was seen in one patient treated with 45 Gy/10 fx who continued to smoke >1 pack/day and ultimately required protective tracheostomy. At 1-year follow-up, estimated local disease free survival for the full cohort was 82%. Overall survival is 100% at last follow-up., Conclusions: We were able to reduce equipotent total fractions of SBRT from 15 to 5 without exceeding protocol-defined acute/subacute toxicity limits. With limited follow-up, disease control appears comparable to standard treatment. We continue to enroll to the 42.5 Gy/5 fx cohort and follow patients for late toxicity., Trial Registration: ClinicalTrials.gov NCT01984502.

Transoral laser microsurgery (TLM) and radiotherapy (RT) are both accepted treatment modalities for glottic cancer. The objective of the study was to assess the oncologic outcomes and life quality of TLM in comparison with RT for T1 glottic carcinoma. We searched Medline/PubMed, Web of knowledge, EMBASE, the Cochrane Library, the Wiley online library, Springer, Google, China National Knowledge Infrastructure (CNKI), etc. We screened the literature, assessed the quality of the studies, and extracted the relevant data through the establishment of inclusion and exclusion criteria. Meta-analysis was done using the Cochrane collaboration' s RevMan 5.0 for data analysis. A total of 11 studies were included in this meta-analysis. The laryngeal preservation for patients undergoing TLM was significantly better than that for RT (P < 0.00). The laser surgery significantly improved the overall survival of patients with T1 glottic carcinoma (P = 0.04). No statistically significant differences were found between TLM and RT regarding the local control (P = 0.91). The funnel plot demonstrates no apparent publication bias in the overall survival and laryngeal preservation comparison. Our meta-analysis suggested that laser surgery was a preferred method than radiotherapy with respect to significantly better overall survival and laryngeal preservation. But the local control was not significant different. Further prospective randomized controlled studies will be needed.

Aims: Recently, carotid-sparing intensity-modulated radiotherapy (IMRT) for early laryngeal glottis (T1/T2N0M0) cancer has generated interest in the hope of avoiding long-term carotid toxicity, as well as concerns relating to geographical misses and long-term normal tissue toxicity. The aim of this review was to summarise the current literature on carotid-sparing IMRT for early glottis cancer, with particular focus on definitions of target volumes and the carotid arteries as organs at risk. In addition, we make suggestions for standardisation of these structures, dose constraints and dose reporting., Materials and Methods: From 73 references, 16 articles met the criteria for inclusion in this systematic review. These papers described two case reports, 11 planning studies and three prospective studies., Results: There was variation in all target volume definitions with no clear consensus. The greatest variability was in clinical target volume definition. Carotid artery and spinal cord delineation were not always defined and most studies did not use a carotid artery constraint. Of the eight studies that reported carotid artery delineation, no two studies delineated the same length of carotid artery, yet most studies reported mean doses. Most studies used IMRT with three to seven fields. Five studies used arc therapy and two studies used tomotherapy., Conclusion: This review highlights a lack of consensus in target volume definitions in carotid-sparing IMRT. Ultimately, long-term prospective data are required to show the benefit of carotid-sparing IMRT. Pooled data will prove useful as most studies will report on small numbers of patients. Therefore, adopting a consensus now on target volume definition, dose constraints and dose reporting will be crucial., (Copyright © 2016. Published by Elsevier Ltd.)

Purpose: To describe the pattern of failure in a national consecutive cohort of patients with glottic squamous cell carcinomas (SCC) treated with primary radiotherapy (RT) with curative intent over a 41-year period., Materials and Methods: All patients undergoing curative treatment for a glottic SCC diagnosed in Denmark between 1971 and 2011 were included and followed from the first contact with the oncology center to death or February 15, 2015., Results: 5001 patients were identified of whom 98% had primary RT. The median follow-up was 9.1 years/5.7 years (patients alive/patients who died). Ten patients were lost to follow-up. In total 1511 failures were observed; of these 93%, 11% and 5% included T site, N site, and M site, respectively. For patients diagnosed in the 70s and the 00s, respectively, the five-year incidences were: local failure (32% vs 19%), loco-regional failure (34% vs 21%), laryngectomy (26% vs 10%), laryngectomy-free survival (48% vs 62%), disease-free survival (62% vs 68%), and overall survival (62% vs 68%). The five-year incidence of ultimate failure (13-16%) remained statistically unchanged., Conclusion: From the 70s to the 00s a continually improving primary disease-control was observed with a concurrent decrease in the incidence of laryngectomy. The survival rate was significantly higher in the 00s compared to the previous three decades., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: This study evaluates the long-term results of definitive radiotherapy (RT) for early glottic cancer. Clinical and treatment factors related to local control and patterns of failure are analyzed., Materials and Methods: We retrospectively reviewed 222 patients with T1-2N0 squamous cell carcinoma of the glottic larynx treated with definitive RT from 1981 to 2010. None of the patients received elective nodal RT or combined chemotherapy. The median total RT dose was 66 Gy. The daily fraction size was < 2.5 Gy in 69% and 2.5 Gy in 31% of patients. The RT field extended from the hyoid bone to the cricoid cartilage., Results: The median age was 60 years, and 155 patients (70%) had T1 disease. The 5-year rates of local recurrence-free survival (LRFS) and ultimate LRFS with voice preservation were 87.8% and 90.3%, respectively. T2 (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.08 to 4.94) and anterior commissural involvement (HR, 3.37; 95% CI, 1.62 to 7.02) were significant prognostic factors for LRFS. In 34 patients with local recurrence, tumors recurred in the ipsilateral vocal cord in 28 patients. There were no contralateral vocal cord recurrences. Most acute complications included grade 1-2 dysphagia and/or hoarseness. There was no grade 3 or greater chronic toxicity., Conclusion: Definitive RT achieved a high cure rate, voice preservation, and tolerable toxicity in early glottic cancer. T2 stage and anterior commissural involvement were prognostic factors for local control. Further optimization of the RT method is needed to reduce the risk of ipsilateral tumor recurrence.

Aim: To report on clinical outcomes of patients with early-stage glottic cancer treated with exclusive radiotherapy with specific analysis of voice quality., Patients and Methods: A consecutive cohort of 55 patients with early glottic cancer was retrospectively analyzed. Patients were treated with exclusive radiation up to a conventionally fractionated total dose of 66-70 Gy with a 3-dimensional conformal technique. Oncological outcomes and toxicity profiles were investigated. A sub-sample of this cohort was also analyzed in terms of voice quality employing subjective and objective tools such as the Voice Handicap Index-10 (VHI-10) and the Multidimensional Voice Program (MDVP™) software and was compared to a group of similar patients treated with CO2 laser cordectomy., Results: after a median observation time of 74.5 months, 5- and 10-year local control was 89% [95% confidence interval (CI)=70.7-93.1%] and 86% (95% CI=68.7-89.6%), respectively. Larynx-preservation rate was 91.8% (95% CI=82.4%-94.9%) at 10 years. Five- and 10-year actuarial overall survival was 72% (95% CI=50.4-79.2%) and 56% (95% CI=48.7-64.3%). Maximum detected acute toxicity included G3 dermatitis (5.4%) and G4 dyspnea (1.8%). Late toxicity profile was mild. VHI-10 scores showed a mild voice disability in both groups, with no statistically significant difference (p=0.12), even when investigating different domains. Patients treated with radiation had a lower deterioration rate in all parameters excluding low voice, interruptions of sound and diplophony., Conclusion: Exclusive radiation proved an effective treatment for patients with early glottic cancer in terms of both oncological outcome and voice quality., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To improve the outcomes of radiotherapy alone for T2 glottic carcinoma (GC), we initiated a prospective study of concurrent chemoradiotherapy with S-1 for patients with early GC, primarily T2 cases. We report the efficacy and safety of this protocol., Patients and Methods: Eligible patients had T1b or T2 glottic squamous cell carcinomas. Patients received S-1 (55.3 mg/m(2)/day, once daily) and radiotherapy (2 Gy/day, five days/week, to a total of 30 fractions)., Results: Thirteen patients were eligible. Complete responses were observed in all 13 patients (100%). At a median follow-up duration of 53 months (range=23-68 months), the 3-year local control and overall survival rates were both 100%. Grade 3 dermatitis occurred in only one patient., Conclusion: This chemoradiotherapy protocol is well -tolerated and effective in patients with early glottic carcinoma. Furthermore, due to its once-daily administration, this protocol is considered to be easier than usual chemoradiotherapy, and makes outpatient-treatment possible., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: This study aims to compare dosimetrically and radiobiologically 3D conformal, intensity modulated radiation therapy (IMRT), RapidArc (RA) volumetric modulated arc therapy and proton therapy techniques for early-stage glottic cancer., Methods: Ten patients were retrospectively selected. Photon treatment planning was performed using Eclipse External Beam Planning, and proton planning was performed using CMS Xio. The minimum, mean and maximum dose values for planning target volume (PTV), mean and maximum dose values for organ at risk, % of volume of PTV receiving at least 95% of the prescription dose, and D20, D50 and D90 of carotid arteries were compared. Biological response models of tumour control probabilities and normal tissue complication probabilities were calculated., Results: IMRT, RA and proton plans versus three-dimensional conformal radiotherapy (3D-CRT) plans consistently provided superior PTV coverage and decreased mean dose to the thyroid and carotid arteries., Conclusion: All these three modalities showed superiority with less variation among themselves compared with 3D-CRT plans. Clinical investigation is warranted to determine if these treatment approaches will translate into a reduction in radiation therapy-induced toxicities., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Background: The purpose of this study was to assess the quality of life (QOL) and voice handicap in a sample of disease-free patients who had been treated at our center with radiotherapy (RT) or surgery for early glottic cancer., Methods: QOL and voice handicap were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires Quality of Life Questionnaire-Core 30-questions (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35-questions (QLQ-H&N35) and the Voice Handicap Index (VHI)., Results: Ninety-one patients completed the questionnaires. Fifty-nine patients (65%) were treated with RT and 32 (35%) with surgery. QOL scores for the sample recorded, moderate limitations in 6 areas, and more than moderate limitations (>30 of 100) in 2 areas. Significant differences were found in emotional functioning (88.5 vs 76.6) and social contact (4.6 vs 12.1) on the EORTC questionnaires and on the VHI (6.1 vs 12.8), which favored the RT group., Conclusion: In this cross-sectional study, voice quality, emotional functioning, and social contact were better in the RT group., (© 2014 Wiley Periodicals, Inc.)

Background: To provide further information about short-term effects on voice quality and health-related quality of life (HRQL) following radiotherapy for laryngeal cancer, comparing glottic and supraglottic tumours., Material and Methods: Sixty-seven male patients who received radiotherapy for glottic and supraglottic tumours were included. Voice recordings were performed and patient reported outcome questionnaires filled in before radiotherapy and one-month post-completion. Acoustic and temporal measures were produced from the recordings and compared to an age-matched, vocally healthy control group (n = 23)., Results: Deterioration of HRQL post-radiotherapy was noted for both the glottic and supraglottic cohort. Pre- radiotherapy the glottic cohort demonstrated acoustic and temporal measures that were statistically different from healthy controls, with improvements post-radiotherapy where several measures showed no statistically significant differences compared to healthy controls. The supraglottic cohort revealed voice measures comparable to the healthy controls but demonstrated statistically significant impairments in HRQL compared to the glottic cohort following radiotherapy., Conclusion: Patients with supraglottic tumours may experience more eating and swallowing related problems prior to radiotherapy compared to glottic tumours and demonstrate a more significant reduction in HRQL following treatment. However, in terms of voice measurements, subjective measures correlate poorly with objective acoustic parameters, thereby emphasising the importance of patient-reported outcomes as part of treatment evaluation.

Purpose: To describe voice and speech quality changes and their predictors in patients with locally advanced oropharyngeal cancer treated on prospective clinical studies of organ-preserving chemotherapy-intensity modulated radiation therapy (chemo-IMRT)., Methods and Materials: Ninety-one patients with stage III/IV oropharyngeal cancer were treated on 2 consecutive prospective studies of definitive chemoradiation using whole-field IMRT from 2003 to 2011. Patient-reported voice and speech quality were longitudinally assessed from before treatment through 24 months using the Communication Domain of the Head and Neck Quality of Life (HNQOL-C) instrument and the Speech question of the University of Washington Quality of Life (UWQOL-S) instrument, respectively. Factors associated with patient-reported voice quality worsening from baseline and speech impairment were assessed., Results: Voice quality decreased maximally at 1 month, with 68% and 41% of patients reporting worse HNQOL-C and UWQOL-S scores compared with before treatment, and improved thereafter, recovering to baseline by 12-18 months on average. In contrast, observer-rated larynx toxicity was rare (7% at 3 months; 5% at 6 months). Among patients with mean glottic larynx (GL) dose ≤20 Gy, >20-30 Gy, >30-40 Gy, >40-50 Gy, and >50 Gy, 10%, 32%, 25%, 30%, and 63%, respectively, reported worse voice quality at 12 months compared with before treatment (P=.011). Results for speech impairment were similar. Glottic larynx dose, N stage, neck dissection, oral cavity dose, and time since chemo-IMRT were univariately associated with either voice worsening or speech impairment. On multivariate analysis, mean GL dose remained independently predictive for both voice quality worsening (8.1%/Gy) and speech impairment (4.3%/Gy)., Conclusions: Voice quality worsening and speech impairment after chemo-IMRT for locally advanced oropharyngeal cancer were frequently reported by patients, underrecognized by clinicians, and independently associated with GL dose. These findings support reducing mean GL dose to as low as reasonably achievable, aiming at ≤20 Gy when the larynx is not a target., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a rare location described to carry a poor prognosis. The aim of this study was to analyze outcomes and feasibility of larynx preservation in sSCC patients., Patients and Methods: Between 1996 and 2012, 197 patients with sSCC were treated at our institution and included in the analysis. Stage III-IV tumors accounted for 76%. Patients received surgery (62%), radiotherapy (RT) (18%), or induction chemotherapy (CT) (20%) as front-line therapy., Results: The 5-year actuarial overall survival (OS), locoregional control (LRC), and distant control rate were 59% (95% CI 51-68), 83% (95% CI 77-89), and 88% (95% CI 83-93), respectively, with a median follow-up of 54.4 months. There was no difference in OS and LRC according to front-line treatments or between primary subglottic cancer and glottosupraglottic cancers with subglottic extension. In the multivariate analysis, age > 60 years and positive N stage were the only predictors for OS (HR 2, 95% CI 1.2-3.6; HR1.9, 95% CI 1-3.5, respectively). A lower LRC was observed for T3 patients receiving a larynx preservation protocol as compared with those receiving a front-line surgery (HR 14.1, 95% CI 2.5-136.7; p = 0.02); however, no difference of ultimate LRC was observed according to the first therapy when including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients receiving a larynx preservation protocol, the 5-year larynx-preservation rate was 55% (95% CI 43-68), with 36% in T3 patients. The 5-year larynx preservation rate was 81% (95% CI 65-96) and 35% (95% CI 20-51) for patients who received RT or induction CT as a front-line treatment, respectively., Conclusion: Outcomes of sSCC are comparable with other laryngeal cancers when managed with modern therapeutic options. Larynx-preservation protocols could be a suitable option in T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT).

Background: To evaluate outcome in patients with glottic cancer treated with intensity-modulated radiotherapy (IMRT) and to show effectiveness of partial laryngeal- and/or carotid artery sparing in low to intermediate risk tumors., Study Design: Retrospective analysis., Material and Methods: From 01/2004 to 03/2013 77 consecutive patients presenting with glottic cancer were treated in our department with IMRT as definitive treatment. T-stages distributed as follows: T1: n = 17, T2: n = 24, T3: n = 15, T4: n = 13 and recurrences: 8 patients. Concomitant systemic therapy was applied in 39 patients consisting of either cisplatin or cetuximab., Results: Mean/median follow-up (FU) time was 32.2/28 months (range: 4-98.7). Three year local control (LC), ultimate LRC and laryngectomy free survival rate was 77%, 92% and 80%, respectively. Three year overall survival of the entire cohort was 81%. Three year local control for T1/T2, T3/T4, and recurred tumors was 95%, 65%, and 38%, respectively. Three year overall survival was 86% for T1-4 stages, 55% for recurred disease, respectively. Partial laryngeal/carotid artery sparing was performed in all T1 patients (n = 17) and 17/22 T2N0 patients. Rate of late sequels was low., Conclusion: IMRT for glottic cancer shows high control rates. In low to intermediate risk tumors an individualized treatment volume with partial larynx +/- carotid artery sparing is effective and holds the potential to reduce long term toxicity. The therapeutic outcome was not compromised.

Objective: Radiotherapy for T1 glottic cancer is commonly delivered using a lateral parallel opposed pair of megavoltage photon fields. There is increasing reported evidence of cerebrovascular events due to radiation-induced carotid stenosis. An alternative field arrangement is to use an anterior oblique technique. This study compares the carotid dosimetry between the two techniques and reviews the evidence for the risk of radiation-induced vascular events., Methods: The radiotherapy plans of 10 patients with T1 glottic cancer treated with an anterior oblique technique were examined for carotid dose. Alternative plans were then created using a parallel opposed pair of fields and the dose to the carotids compared. All patients received 50 Gy in 16 fractions treating once daily, for 5 days in a week., Results: The average of the mean dose to the carotids with the anterior oblique technique was 21 Gy compared with 37 Gy using the lateral parallel opposed pair arrangement (p < 0.0001)., Conclusion: An anterior oblique field arrangement for the treatment of T1 glottic cancer results in a significantly lower radiation dose to the carotid arteries, which may be clinically important in terms of reducing the risk of cerebrovascular events in long-term survivors., Advances in Knowledge: Although the anterior oblique technique for treating early glottic cancers is well described, and it is predictable that the dose received by the carotid arteries should be lower with this technique, to our knowledge this is the first study to quantify that reduction in dose with a series of patients.

Objectives/hypothesis: To compare voice handicap and quality of life after radiotherapy (RT) versus transoral laser surgery (LS) for T1a glottic carcinoma., Study Design: Retrospective study (1996-2011) of patients treated with RT or LS for T1a glottic squamous cell carcinoma with curative intent., Methods: Disease-free patients were assessed using Voice Handicap Index (VHI 30) and European Organization for Research and Treatment of Cancer Head and Neck Quality of Life (EORTC QLQ-HN35) questionnaires., Results: Of 147 patients, 95 (65%) completed the questionnaires: fifty-one patients an average of 8 years after RT and 44 patients an average of 4 years after LS (no difference in age or sex ratio). The average total VHI 30 was 13.1 for RT and 29.2 for LS (P < .0001), with average emotional, physical and functional subscores significantly different. The average total EORTC QLQ-HN35 was 37.7 for RT versus 40.7 for LS (P = .7), with a difference only in the speaking subscore (P = .04)., Conclusions: Long-term subjective voice-related quality of life was worse after LS, with no difference in other domains. These results should be interpreted in light of the biases inherent in retrospective studies., Level of Evidence: 4., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To evaluate the treatment outcomes for T1 N0 glottic carcinoma after definitive radiotherapy., Methods: One hundred and seventeen patients treated with radical radiotherapy from 1990 to 2006 were retrospectively reviewed. The median follow-up duration for the entire group was 92 months (range 4-227). A median dose of 70 Gy (range 63-70 Gy) was administered. We determined the rates of local control (LC), regional control, overall survival (OS) and cause-specific survival (CSS) at 5, 10 and 15 years by Kaplan-Meier product-limit method. The Cox regression analysis was performed to identify significant prognostic factors for LC and survival. The incidence of secondary malignancies is also reported., Results: The 5-, 10- and 15-year LC rates for the whole group were 84, 80.2 and 80.2 %, respectively. There were 20 local recurrences, of which 19 were salvaged with laryngectomy, giving an ultimate control rate of 90.6 %. The 5-/10-/15-year OS and CSS rates were 81.2 %/66.1 %/48.3 % and 90.6 %/90.6 %/90.6 %, respectively. None of the parameters analyzed exhibited a statistically significant relationship with LC. The age ≥65 years had a statistically significant effect on OS (but not in CSS), with a hazard ratio of 2.45 (95 % confidence interval 1.29-4.66; p = 0.006). During follow-up, 26 patients (22 %) developed a secondary malignancy. Only two patients (1.7 %) presented with severe toxicity (edema and mucositis)., Conclusions: Radiotherapy alone offers a high likelihood of LC and an excellent CSS rate. In addition, the surgical approach for the salvage is a successful option.

Aims: To determine the influence of dose and fractionation on tumour characteristics, toxicity, disease control and survival outcomes in T1 glottic carcinoma., Materials and Methods: Between 1975 and 2000, treatment charts of 652 patients with T1 glottic carcinoma who received curative radiation with four hypofractionated schedules (50 Gy/15 fractions [3.3 Gy/fraction] or 55 Gy/16 fractions [3.43 Gy/fraction] or 60 Gy/24 fractions or 62.5 Gy/25 fractions [2.5 Gy/fraction]) were analysed. The patients were divided into two groups based on fraction size <3 Gy and >3 Gy. Local control and overall survival were calculated. Patient- and tumour-related factors affecting local control were analysed using univariate and multivariate analysis. Factors affecting late toxicity were also analysed., Results: The local control and overall survival at 10 years were 84 and 86.1%, respectively, for T1 glottic carcinoma. The response to radiation had a significant effect on local control with univariate analysis (P = 0.001). Other factors, such as beam energy, anterior commissure involvement and fractionation, did not affect local control. Persistent radiation oedema was seen in 123 patients (23.4%) and was significantly worse in patients who received radiation with a larger field size (>36 cm(2)) on a telecobalt machine (P < 0.001)., Conclusions: Radical radiotherapy schedules incorporating a higher dose per fraction yield acceptable local control rates and late toxicity. Telecobalt therapy for early glottic cancer is a safe alternative to treatment with 6 MV photons on a linear accelerator in terms of local control and late toxicity as long as field sizes smaller than 36 cm(2) are used., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the variability of organ at risk (OAR) delineation and the resulting impact on intensity modulated radiation therapy (IMRT) treatment plan optimization in head-and-neck cancer., Methods and Materials: An expert panel of 3 radiation oncologists jointly delineated OARs, including the parotid and submandibular glands (SM), pharyngeal constrictors (PC), larynx, and glottis (GL), in 10 patients with advanced oropharynx cancer in 3 contouring sessions, spaced at least 1 week apart. Contour variability and uncertainty, as well as their dosimetric impact on IMRT planning for each case, were assessed., Results: The mean difference in total volume for each OAR was 1 cm(3) (σ 0.5 cm(3)). Mean fractional overlap was 0.7 (σ 0.1) and was highest (0.8) for the larynx and bilateral SMs and parotids and lowest (0.5) for PC. There were considerable spatial differences in contours, with the ipsilateral parotid and PC displaying the most variability (0.9 cm), which was most prominent in cases in which tumors obliterated fat planes. Both SMs and GL had the smallest differences (0.5 cm). The mean difference in OAR dose was 0.9 Gy (range 0.6-1.1 Gy, σ 0.1 Gy), with the smallest difference for GL and largest for both SMs and the larynx., Conclusions: Despite substantial difference in OAR contours, optimization was barely affected, with a 0.9-Gy mean difference between optimizations, suggesting relative insensitivity of dose distributions for IMRT of oropharynx cancer to the extent of OARs., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To evaluate the long-term voice characteristics and quality of life of early glottic cancer patients after definitive treatment., Study Design: Case series with chart review in a tertiary care medical center in Taiwan., Methods: Forty-two consecutive patients who received radiation therapy (RT) or transoral laser microsurgery (TLM) for early glottic cancer over 12 months were evaluated for voice laboratory data and quality-of-life measurements., Results: Twenty-four patients received RT, and 18 underwent TLM. There was no difference between the two groups on acoustic and aerodynamic voice measures except for modal fundamental frequency in males. In the Functional Assessment of Cancer Therapy-Head and Neck survey, the TLM group had better communication than the RT group, but there were no differences in voice quality and strength. There was also no significant difference in the Voice Handicap Index 10 evaluation., Conclusions: Male patients who received TLM have higher modal fundamental frequency than male patients who received RT and norms. Voice-related life quality is similar in patients regardless of RT or TLM treatment for early glottic cancer, but those who receive TLM have better communication abilities than those who receive RT., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Objective: The purpose of the present pilot study is to investigate whether the beneficial short-term effects of voice therapy in patients with voice problems after treatment of early glottic cancer as reported in our earlier study remain present on the long term., Study Design: In this prospective study, 12 patients, selected based on a screening questionnaire about voice problems and randomly assigned for treatment with voice therapy (vs no treatment), were evaluated with a mean of 13 months after finishing voice therapy to evaluate the long-term voice effects., Methods: Voice assessment consisted of the Voice Handicap Index (VHI) and acoustic analyses (percent jitter, percent shimmer, and noise-to-harmonics ratio)., Results: Statistical analysis showed that the beneficial short-term effect on the mean VHI, percent jitter, and shimmer remained stable after more than a year of follow-up., Conclusions: The present study provides initial evidence that the beneficial effect of voice therapy is not just a short-lived voice improvement but may result in a better voice for a period of at least 1 year. Future long-term randomized controlled trials are needed to confirm our findings., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Aims and Background: We compared conformal, intensity-modulated radiotherapy (IMRT) and intensity-modulated arc therapy (IMAT) in early stage glottic cancer in terms of dosimetric features as target coverage, dose to the organs at risk and total treatment time., Methods and Materials: Five consecutive T1 glottic squamous cell carcinoma patients were selected for the study. Three-dimensional conformal radiotherapy (3D-CRT), 3-field or 5-field intensity-modulated radiotherapy (3F-IMRT and 5F-IMRT), or IMAT, which was in 2 different forms--a regular IMAT (R-IMAT) and an alternative IMAT (A-IMAT) with an unirradiated section, was planned for each patient. The prescribed dose was 63 Gy in 28 fractions. The minimum dose for 95% of the clinical target volume (D95), maximum dose point at clinical target volume (Dmax), total monitor units, left and right carotid artery doses (V35 and V50 - percentage of volume receiving 35 Gy and 50 Gy), and total treatment time were calculated for each plan., Results: Median D95 values in the 5 plans studied with each technique ranged between 63 and 63.3 Gy (P = NS). Median Dmax values for each technique ranged between 65.4 and 70.8 Gy. The number of hot spots with IMRT and IMAT was significantly higher than with 3D-CRT plans. Conformal radiotherapy plans median V35 (93.6%) and V50 (76.6-83.3%) values for carotid arteries were significantly higher than with IMRT and IMAT (2.9%-11.4% and 0.0%). Average treatment times for 3D-CRT, 3F-IMRT, 5F-IMRT, R-IMAT and A-IMAT techniques were calculated as 64, 119, 147, 39 and 32 seconds, respectively., Conclusions: IMAT has significantly decreased the treatment time compared to IMRT and 3D-CRT with acceptable homogeneous clinical target volume coverage and low carotid dose.

Objectives: Increasing incidence of laryngeal carcinoma and advancement in diagnostics and therapy methods, have led to constant exploration in that field. Early glottic carcinoma can be treated successfully with several procedures: cordectomy through laryngofissure, laser cordectomy, and radiotherapy. Our objective was to assess the voice quality after these different modalities of treatment., Study Design: Prospective controlled study with 69 patients, treated in a 1-year period for glottic Tis and T1a carcinoma at the tertiary medical centre., Methods: Nineteen of our patients were treated endoscopically with CO(2) laser (types III-IV cordectomy according to recommended European Laryngological Society classification of endoscopic cordectomies). Thirty-five patients underwent cordectomy through laryngofissure, 15 patients had radiotherapy. Multidimensional computer analysis of voice and speech was conducted 1, 6, and 12 months after the treatment. Three programs included 14 parameters, which were observed., Results: While comparing the parameters between the groups, there were significant differences in the values of fundamental frequency (Hz), jitter (%), normalized noise energy (dB), standard deviation of fundamental frequency (Hz), percent silent time (%), and sound-pressure level in the different follow-up periods (P<0.05)., Conclusion: In the long run, patients treated with radiotherapy show better voice quality in comparison with other two groups., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Background: Early-stage laryngeal squamous cell carcinoma is managed with radiotherapy or endoscopic surgery. Although cure rates are high, radiation failures often require total laryngectomy for salvage. Biomarkers that can predict tumour radioresistance may be useful in modifying the treatment approach for individual patients., Methods: Retrospective patient chart review yielded 75 patients with T1-T2 glottic squamous cell carcinoma treated with radiation therapy at the London Health Sciences Centre. Pretreatment tumour biopsies were immunostained for B-cell lymphoma 2 (Bcl-2), Ki-67, and epidermal growth factor receptor (EGFR) to correlate biomarker expression with disease-free survival (DFS)., Results: Ki-67 expression was strongly associated with recurrence following radiation and independently predicted poor DFS (hazard ratio 4.86, 95% CI 1.58-15.00; p  =  .006). EGFR and Bcl-2 were not associated with a risk of recurrence., Conclusions: Ki-67 expression identified a subset of patients with increased risk of local recurrence after radiation therapy. Ki-67 expression can potentially guide improved personalized treatments for patients with early-stage glottic squamous cell carcinomas.

Background: The objective of this study was to conduct a systematic review and meta-analysis to compare the oncologic and functional outcomes between transoral laser surgery (TLS) and radiotherapy (RT)., Methods: An electronic library search of the relevant English- and Chinese-language literature was conducted. Potentially eligible articles were reviewed. Qualified articles were selected and evaluated., Results: No significant differences were identified between TLS and RT with respect to local control, overall survival, disease-specific survival, and posttreatment voice quality. However, larynx preservation was significantly higher in patients initially treated with TLS than those initially treated with RT., Conclusions: The approach for optimal treatment of T1a glottic cancer remains unanswered. This results from the relatively inconclusive evidence obtained from the current literature. Properly designed, prospective, randomized, or well-controlled studies will be required. Similar methodologies for treatment and reporting need to be established to make a valid and meaningful comparison between studies., (Copyright © 2011 Wiley Periodicals, Inc.)

Altered fractionated radiotherapy and concurrent chemoradiation could improve local control and survival for patients with locally advanced head and neck cancer. However, intensified treatment seems to increase late toxicity. Late swallowing dysfunction is common and has a large impact on quality of life and can get life-threatening character. Recent studies could show interrelations between the radiation dose to certain anatomical structures involved in the swallowing process and the risk of swallowing dysfunction. Important structures seem to be the pharyngeal constrictors and the supraglottic and glottic larynx. Further prospective clinical validations using standardized diagnostic protocols for dysphagia are necessary to establish dose constraints to anatomical structures involved in swallowing., (© Georg Thieme Verlag KG Stuttgart · New York.)

Unlabelled: Early glottic cancer can be effectively treated with radiation or surgery, but recurrence is a possibility when using any of the treatment modalities., Aim: To assess the outcome of radiotherapy as initial treatment in the control of squamous cell carcinoma of vocal cord (T1) and the effectiveness of salvage surgery (endoscopic or open) after treatment failure., Materials and Methods: A retrospective study was based on the analysis of medical records from 43 patients with T1 squamous cell carcinoma of the glottis, radiotherapy as initial treatment and follow-up period of five years., Results: The rate of recurrence after radiotherapy was 30.2% of the cases, mean diagnosis interval was 29.5 months. As an option for salvage treatment, patients underwent open partial laryngectomy or endoscopic surgery with control rates of 77.7% and 25% respectively., Conclusion: Our cases showed high rates of recurrence after radiotherapy and open partial laryngectomy was more effective for the salvage surgery.

Background: To evaluate prognostic factors that may influence local control (LC) of T1N0 glottic cancer treated by primary radiotherapy (RT) with 6 MV photons., Methods: We retrospectively reviewed the medical records of 433 consecutive patients with T1N0 glottic cancer treated between 1983 and 2005 by RT in our institution. All patients were treated with 6 MV photons. One hundred and seventy seven (41%) patients received 52.5 Gy in 23 fractions with 2.5 Gy/fraction, and 256 (59%) patients received 66 Gy in 33 fractions with 2 Gy/fraction., Results: The median follow-up time was 10.5 years. The 10-year LC rates were 91% and 87% for T1a and T1b respectively. Multivariate analysis showed LC rate was adversely affected by poorly differentiated histology (Hazard Ratio [HR]: 7.5, p = 0.035); involvement of anterior commissure (HR: 2.34, p = 0.011); fraction size of 2.0 Gy (HR: 2.17, p = 0.035) and tumor biologically effective dose (BED) < 65 Gy15 (HR: 3.38, p = 0.017)., Conclusions: The negative impact of anterior commissure involvement could be overcome by delivering a higher tumor BED through using fraction size of > 2.0 Gy. We recommend that fraction size > 2.0 Gy should be utilized, for radiation schedules with five daily fractions each week.

Introduction: We indicate the exclusive radiation therapy as initial approach for T1a glottic tumors, and the frontolateral laryngectomy for the tumors staged as T1b and selected T2 glottic tumors. The videolaryngostroboscopy is a useful tool to analyze the laryngeal structural changes and compensatory motion after the therapeutic approach., Objectives: To evaluate the endolaryngeal structures of patients who participate in the vibratory sound source after the early glottic cancer treatment through the videolaryngostroboscopy., Methods: It was a retrospective transversal study in which 20 patients who underwent exclusive radiation therapy and 25 patients who underwent frontolateral laryngectomy were analyzed by means of videolaryngostroboscopy. The radiation doses ranged from 5000 to 7020 cGy in the radiation therapy group. The mucosal wave and the vibratory source components were evaluated., Results: All of the irradiated patients presented vibratory behavior, and hyperfunction was occasionally observed in four cases. The mucosal wave source was glottic in 18 cases and mixed in two cases. In the laryngectomy group, 10 supraglottic sources, 10 glottic sources, and five mixed sources were identified. Among the 10 cases of supraglottic source, eight patients presented global constriction and two patients presented medial constriction. Among the five cases of mixed source, two patients presented global constriction, one patient presented medial constriction, and one patient presented anteroposterior constriction. Regarding the number of anatomical structures presenting vibratory pattern, five patients had two structures, four patients had three structures, and one patient had four structures., Conclusion: Patients who underwent radiation therapy recruit less supraglottic structures as vibratory source than the patients undergoing vertical laryngectomy., (Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Purpose: The purpose of this study was to retrospectively analyze patients with T1-T2N0 squamous cell carcinomas of the glottic larynx treated at a private institution, to review the pertinent literature, and to compare our outcomes to those of academic institutions., Methods and Materials: A total of 118 patients were treated with radiation therapy between May 1987 and August 2006 at a private institution and followed up for ≥2 years. Three patients were lost to follow-up between 18 and 19 months., Results: The 5-year local control rates were: T1a, 91%; T1b, 95%; T2a, 96%; and T2b, 100%. The 5-year ultimate local control rates after irradiation and including patients who were successfully salvaged with surgery after a local recurrence were: T1a, 94%; T1b, 100%; T2a, 96%; and T2b, 100%. Eight (7%) of the 118 patients developed a local recurrence. There were no isolated regional or distant recurrences. The 5-year overall survival rates were: T1a, 73%; T1b, 78%; T2a, 62%; and T2b, 69%. The 5-year cause-specific survival rates were: T1a, 96%; T1b, 100%; T2a, 100%; and T2b, 100%. Two patients experienced severe complications., Conclusion: Patients with limited T1aN0 cancers may be treated with either transoral laser excision or RT. Those with more advanced T1-T2N0 cancers are treated with definitive RT. We do not advocate elective nodal irradiation, even for those with bulky T2B malignancies. The addition of concomitant weekly cisplatin 30 mg/M² is considered for patients with T2B cancers. Open parotid laryngectomy is reserved for salvage of suitable patients with a local recurrence.