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Simple Summary: Anterior commissure involvement (ACI) is an important factor in the local control of early-stage glottic squamous cell carcinoma (EGSCC). We initiated a radiotherapeutic treatment regimen focusing on ACI, which has included hyperfractionated radiotherapy since 2008. One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. Hyperfractionated radiotherapy (74.4 Gy in 62 fractions) was used for EGSCC with ACI. The 10-year overall survival and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. In conclusion, hyperfractionated radiotherapy was effective for T1 disease with ACI but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation. Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation. [ABSTRACT FROM AUTHOR]

Surgical resection is recommended for advanced-stage, resectable glottic cancer. However, total laryngectomy results in the loss of vocal function and reduces patients’ quality of life. At our institution, patients with cT3N0M0 stage III resectable glottic cancer who wish to preserve their larynx are treated with super-selective cisplatin infusion with concomitant radiotherapy (RADPLAT) to improve local control over systemic chemotherapy. Herein, we present 4 patients with glottic cancer who underwent biweekly intra-arterial infusion chemotherapy combined with radiation therapy 3 times. For intra-arterial infusion chemotherapy, 100 mg cis-diaminodichloroplatinum was infused into the superior thyroid artery, including the superior laryngeal artery branch. Thereafter, intensity-modulated radiation therapy was administered at doses of 70 Gy in 35 fractions for 3 patients and 66 Gy in 33 fractions for 1 patient. These patients showed complete response after chemoradiotherapy with no recurrence or metastases during the follow-up period to date (mean follow-up period: 56 months, range: 39-76 months).

The aim of this study was to compare the dosimetry of carotid arteries (CAs) using three radiation therapy (RT) techniques, three-dimensional conformal RT (3D-CRT), helical tomotherapy-intensity-modulated RT (HT-IMRT), and volumetric modulated arc therapy (VMAT), in patients with early-stage glottic cancer.

Abstract Objectives Glottic tumors with infiltration of the anterior/posterior commissure, and lesions with subglottic, cricoid, or cricoarytenoid joint infiltration have been highly controversial in the past, from the perspective of oncological safety. Although conservation laryngeal resection options exist, most are limited by the extent of resection proscribed by the technique and the postoperative functional results. Oncologically speaking, extended vertical hemilaryngectomy is often the optimal solution. However, limited reconstruction methods often compel total laryngectomy. Methods Eight patients with vocal fold malignancy, which infiltrated the anterior and sometimes the posterior commissure and with subglottic extension and resultant uni/bilateral vocal fold motion impairment, were treated by single stage extended vertical partial laryngectomy with rotational crico‐thyrotracheopexy as a functional reconstruction of the laryngeal framework. Patients were evaluated with objective and subjective function tests. Results Histologic examination demonstrated tumor‐free margins in every case. Definitive decannulation was successful in all cases within 2 weeks. All patients had a stable and adequate airway during follow‐up and reported socially acceptable voice. Oral feeding was possible in seven patients. Conclusion Rotational crico‐thyrotracheopexy, as a single stage reconstruction technique, is based on well‐vascularized, readily available, appropriately shaped local tissues, without significant donor site morbidity or need for long‐term stenting to reconstruct large laryngeal defects after extended vertical hemilaryngectomy for advanced unilateral glottic tumors and is applicable even with supra/subglottic invasion or infiltration of the contralateral vocal fold. An adequate airway can be achieved with socially acceptable voice and safe swallowing without compromising oncologic reliability. Level of Evidence 4 (retrospective case series review).

Objectives: Glottic tumors with infiltration of the anterior/posterior commissure, and lesions with subglottic, cricoid, or cricoarytenoid joint infiltration have been highly controversial in the past, from the perspective of oncological safety. Although conservation laryngeal resection options exist, most are limited by the extent of resection proscribed by the technique and the postoperative functional results. Oncologically speaking, extended vertical hemilaryngectomy is often the optimal solution. However, limited reconstruction methods often compel total laryngectomy. Methods: Eight patients with vocal fold malignancy, which infiltrated the anterior and sometimes the posterior commissure and with subglottic extension and resultant uni/bilateral vocal fold motion impairment, were treated by single stage extended vertical partial laryngectomy with rotational crico‐thyrotracheopexy as a functional reconstruction of the laryngeal framework. Patients were evaluated with objective and subjective function tests. Results: Histologic examination demonstrated tumor‐free margins in every case. Definitive decannulation was successful in all cases within 2 weeks. All patients had a stable and adequate airway during follow‐up and reported socially acceptable voice. Oral feeding was possible in seven patients. Conclusion: Rotational crico‐thyrotracheopexy, as a single stage reconstruction technique, is based on well‐vascularized, readily available, appropriately shaped local tissues, without significant donor site morbidity or need for long‐term stenting to reconstruct large laryngeal defects after extended vertical hemilaryngectomy for advanced unilateral glottic tumors and is applicable even with supra/subglottic invasion or infiltration of the contralateral vocal fold. An adequate airway can be achieved with socially acceptable voice and safe swallowing without compromising oncologic reliability. Level of Evidence: 4 (retrospective case series review). [ABSTRACT FROM AUTHOR]

Background: Cancer is a leading health problem in India with approximately 1.1 million cases occurring each year. Cancer of the Larynx represents about 1% of the total cancer burden and accounts for 0.3% of all cancer deaths. Glottic tumors typically metastasize after they have directly invaded adjacent structures with better drainage. Glottic cancer has a high rate of cure and regardless of the modality used. Radiotherapy is generally the favoured treatment in most centers despite comparable cure rates for selected T1 and T2 glottis tumors. The present study was conducted to compare radiation induced acute and late treatment related toxicities of hypo-fractionated radiotherapy and conventional radiotherapy in early glottic cancer T1-2N0M0". Material and Methods: The study was conducted in Acharya Tulsi Regional Cancer Treatment and Research Institute, Sardar Patel Medical College, Bikaner. It was done on 50 histologically proven new cases of early glottic cancer with age <70 years. Patients were treated by radiotherapy and randomized into either of the two arms Arm A (Study) and Arm B (Control). On ARM A Hypo-fractionated radiotherapy 55Gy/20# in 2.75Gy/# in 4 weeks and on ARM B Conventional radiotherapy 66Gy/33# in 2Gy/#6.5 weeks was given. Voice quality and toxicities were graded at the end of treatment, after 1, 2, 3 and 6 months. Data was analyzed using percentage, mean, chi square test and p-value. Results: Majority of the patients were in their 6th decade of life and all patients were male. Majority of the population had ECOG Performance Score of 1. 46 (92%) of patients presented with hoarseness alone while 4 (8%) of them presented with hoarseness and dysphagia, which were comparable in both the groups. Histologically, patients had Squamous Cell carcinoma (SCC). In study vs control arm where 11 (44%) vs 5 (20%) patients were T1A, 9 (36%) vs 5 (20%) in T1B, 4 (20%) vs 10 (40%) in T2A and 1 (4%) vs 5 (20%) in T2B respectively. In the study arm 25 (100%) patients received 58.4 Gy (2GyEq) whereas in control population 15 (60%) received 66 Gy and the rest 10 (40%) received 64 Gy. All 25 (100%) patients in both arms completed treatment. At the end of treatment, only 3 (12%) patients in study arm and 5 (20%) in control arm had normal voice. At 1st month of follow up, 7 (28%) vs 9 (36%) patients, at 3rd month of follow up, 13 (52%) vs 15 (60%) patients and at 6th month follow up, 21 (84%) vs 22 (88%) patients in study and control arm respectively had normal voice. (X² = 1.026, p value = 0.599). As compared, at the end of the treatment, at 1st, 3rd and 6th months follow up, grades of skin reactions, mucositis and dysphagia reduced from 2 to 1 and later 1 to 0. Conclusions: Hypo-fractionated radiotherapy is a safe modality of treatment with high local control rates, acceptable long term toxicities, favorable voice outcomes and symptomatic relief with added advantage of shorter treatment time which offers better patient compliance. [ABSTRACT FROM AUTHOR]

Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.

Abstract Background For recurrent laryngeal cancer, the feasibility of salvage transoral laser microsurgery (TLM) remains controversial. This study compared the efficacy of TLM and open partial laryngectomy (OPL) for treatment of early local recurrence of glottic squamous cell cancer (GSCC) and confirm the effectiveness of salvage TLM as a treatment option. Methods This retrospective study involved 55 patients with early local recurrent GSCC treated with TLM, and the oncologic outcomes, functional outcomes, hospitalization time and complications were compared with a group of 40 recurrent GSCC patients matched for clinical variables of TLM group, treated by OPL by the same team of surgeons. Results The 5-year overall survival and disease-specific survival rates were 65.8% and 91.5%, respectively, for 55 patients with rTis–rT2 stage treated by TLM and 77.1% and 94.7%, respectively, for 40 patients with rTis–rT2 stage treated by OPL (OPL group). In the TLM and OPL groups, the local control rates after 5 years were 77.5% and 79.3%, respectively, and the laryngeal preservation rates were 94.4% and 83.6%, respectively (p > 0.05). Compared with the OPL group, the complication rate (1.82%) and hospitalization duration (5.42 ± 2.26 days) were significantly lower in the TLM group (p

Simple Summary: The standard protocol for distinguishing between benign and malignant lesions remains clinical judgment and histopathological confirmation by an experienced otolaryngologist. An additional tool is high-speed videoendoscopy (HSV), an accurate method for an objective assessment of vocal fold oscillations. The aim of the study was to utilize a quantitative assessment of the vibratory characteristics of vocal folds in diagnosing benign and malignant lesions of the glottis using HSV. The machine learning model identifying malignancy among organic lesions reached an AUC equal to 0.85 and presented with 80.6% accuracy, 100% sensitivity, and 71.1% specificity on the training set. Important predictive factors were frequency perturbation measures. The results suggested that advanced machine learning models based on HSV analysis could potentially indicate a heightened risk of cancerous mass. Therefore, this technology could, in future, aid in early cancer detection; however, further investigation and validation is needed. The aim of the study was to utilize a quantitative assessment of the vibratory characteristics of vocal folds in diagnosing benign and malignant lesions of the glottis using high-speed videolaryngoscopy (HSV). Methods: Case-control study including 100 patients with unilateral vocal fold lesions in comparison to 38 normophonic subjects. Quantitative assessment with the determination of vocal fold oscillation parameters was performed based on HSV kymography. Machine-learning predictive models were developed and validated. Results: All calculated parameters differed significantly between healthy subjects and patients with organic lesions. The first predictive model distinguishing any organic lesion patients from healthy subjects reached an area under the curve (AUC) equal to 0.983 and presented with 89.3% accuracy, 97.0% sensitivity, and 71.4% specificity on the testing set. The second model identifying malignancy among organic lesions reached an AUC equal to 0.85 and presented with 80.6% accuracy, 100% sensitivity, and 71.1% specificity on the training set. Important predictive factors for the models were frequency perturbation measures. Conclusions: The standard protocol for distinguishing between benign and malignant lesions continues to be clinical evaluation by an experienced ENT specialist and confirmed by histopathological examination. Our findings did suggest that advanced machine learning models, which consider the complex interactions present in HSV data, could potentially indicate a heightened risk of malignancy. Therefore, this technology could prove pivotal in aiding in early cancer detection, thereby emphasizing the need for further investigation and validation. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) is an appropriate treatment option for early-stage glottic cancer (ESGC) that achieves high local control and preserves voice quality. However, the optimal radiation treatment schedule remains unknown. We present our institution’s 14-year experience in treating ESGC with definitive radiotherapy between 2005 and 2019 inclusively. Materials and methods: We reviewed the medical records of 104 patients; 63 (60.5%) were treated with conventional fractionation (CF), and 41 (39.5%) were treated with hypofractionated radiotherapy (HF). The clinical T-stage was T1a in 50 patients (48%), T1b in 27 (26%), and T2 in 27 (26%). Age, gender, anterior commissure involvement, stage, radiotherapy technique, radiation fraction size, and overall treatment time (OTT) were analyzed as prognostic factors. The survival outcomes, local regional control (LRC), and laryngeal preservation rate were evaluated. Results: The 5-year overall survival (OS) and LCR were 83.3% and 78%, respectively. On univariate analysis, treatment with CF (p = 0.02), prolonged OTT > 49 days in CF and > 40 days in HF (p = 0.04), and RT total dose < 66 Gy (p = 0.03) were associated with poor LRC. Multivariate analysis showed a non-significant association with LRC (all p > 0.05). The 5-year OS rate in the CF and HF-treated patients was 84.9% and 72.1%, respectively (p = 0.99), and in patients who had T1a, T1b, and T2 disease, were 78.2%, 96.0%, and 82.1%, respectively (p = 0.43). All patients and tumor variables showed no statistically significant association with OS. Only low-grade acute toxicity was observed. Conclusion: Non-inferiority results supported the HF schedule to ESGC, including high local disease control and decreased overall treatment time. Our study supports its efficacy in the primary care of ESGC with manageable side effects. [ABSTRACT FROM AUTHOR]

Abstract Background The treatment of glottic cancer remains challenging, especially with regard to morbidity reduction and larynx preservation rates. The National Comprehensive Cancer Network (NCCN) has published guidelines to aid decision‐making about this treatment according to the tumor site, clinical stage, and patient medical status. Aim The present review was conducted to identify changes in the NCCN guidelines for glottic cancer treatment made between 2011 and 2022 and to describe the published evidence concerning glottic cancer treatment and oncological outcomes in the same time period. Methods and Results Clinical practice guidelines for head and neck cancer published from 2011 up to 2022 were obtained from the NCCN website (www.NCCN.org). Data on glottic cancer treatment recommendations were extracted, and descriptive analysis was performed. In addition, a review of literature registered in the PubMed database was performed to obtain data on glottic cancer management protocols and treatment outcomes from randomized controlled trials, systematic reviews, and meta‐analyses published from 2011 to 2022. In total, 24 NCCN guidelines and updates and 68 relevant studies included in the PubMed database were identified. The main guideline changes made pertained to surgical and systemic therapies, the consideration of adverse features, and new options for the treatment of metastatic disease at initial presentation. Early‐stage glottic cancer received the most research attention, with transoral endoscopic laser surgery and radiotherapy assessed and compared as the main treatment modalities. Reported associations between treatment types and survival rates for this stage of glottic cancer appear to be similar, but functional outcomes can be highly compromised. Conclusion NCCN panel members provide updated recommendations based on currently accepted treatment approaches for glottic cancer, constantly reviewing new surgical and non‐surgical techniques. The guidelines support decision‐making about glottic cancer treatment that should be individualized and prioritize patients' quality of life, functionality, and preferences.

Abstract Background Due to the increasing expertise in transoral laser surgery and image-guided radiation therapy, treatment outcomes have recently improved in patients with early-stage glottic cancer. The objective of the current study was to evaluate intensity-modulated proton therapy (IMPT) as novel treatment option. Methods A total of 15 patients with T1-2N0 glottic squamous cell carcinoma, treated between 2017 and 2020, were evaluated. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Results The majority were T1a/b tumors (66.7%) and no patient had lymph node or distant metastases. The median total dose was 70 Gy relative biological effectiveness (RBE) (range 66–70 Gy RBE). The one- and two-year OS and metastases-free survival were 100%. One patient developed local failure and received salvage laryngectomy. No higher-grade acute or late toxicity was reported. The mean number of CTCAE grade I and II overall toxicity events per patient was 4.1 (95%-[confidence interval] CI 3.1–5.3) and 1.0 (95%-CI 0.5–1.5). Conclusion High-precision proton therapy of T1-2N0 glottic cancer resulted in exceptional treatment tolerability with high rates of laryngeal function preservation and promising oncological outcome. IMPT has the potential to become a standard treatment option for patients with early-stage laryngeal cancer.

Abstract 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

Simple Summary: Compared with other head and neck cancer types, the prognosis of recurrent early glottic cancer (rEGC) may be less dependent on the presence of regional (N) and/or distant metastases (M). The latter two are clinically infrequent due to rEGC's peculiar biology, but the currently available staging systems still rely upon these parameters. Thus, we developed a new staging system (SUD) centered on the comparison between the T stages of the recurrence and the primary tumor. Then, in our cohort of 258 patients with rEGC treated at our Institution in Florence, Italy, we verified how the SUD system performs in the prediction of the overall and disease-specific survival, compared to the other classifications already in use. (1) Background: The treatment of recurrent early glottic cancer (rEGC) remains challenging. We wanted to investigate how the oncological outcomes are affected by the initial and recurrent stages, in order to propose our newly developed Same–Up–Down (SUD) staging system. (2) Methods: In our cohort of 258 rEGC patients, we retrospectively assessed the prognostic performances of the rTNM (the TNM staging system for recurrence), CLRSS, CLRSS-2, and SUD staging systems by univariate and multivariate Cox analysis, comparing their predictive capability using Harrell's C-index. (3) Results: The SUD classification satisfactorily predicted both overall survival (p = 0.022) and second-recurrence-free survival (p = 0.024, as same + down vs. upstage) in our cohort. It also outperformed the other three systems in terms of prediction of survival, with an improvement of 1.52%, 1.18%, and 3.96% in the predictive capacity of overall survival, disease-specific survival, and second-recurrence-free survival, respectively. (4) Conclusions: The SUD staging system can efficiently predict survival in rEGC patients, whose prognosis heavily depends on both the initial and recurrent locoregional extension. [ABSTRACT FROM AUTHOR]

Introduction: In many regions, laryngeal carcinoma is a common upper respiratory tract cancer, most commonly involving the glottic region. The treatment of early glottic cancer includes radiotherapy, open surgery and laryngeal laser microsurgery. However, the preferred treatment for early glottic cancer is still controversial. Objectives: To study the factors affecting the 5-year survival rate of Tis-2N0M0 early glottis cancer and to demonstrate the oncological safety of different treatments. Methods: 144 patients with early glottic cancer were analyzed retrospectively. All patients were clinically node negative. 53 patients underwent open surgery, transoral CO2 laser microsurgery in 46 cases and radiotherapy in 45 cases. The patients were followed up for 26 − 84 months, with an average follow-up period of 62.9 months. Results: The 5-year overall survival was 82.6%. The 5 year survival rates of open surgery, laser microsurgery and radiotherapy were 83.0%, 82.6% and 82.2%, respectively. There was no significant difference in 5-year survival rate among the three treatments (p = 0.987). In multivariate analysis, age, T-stage, pathological grading, and anterior commissure involvement were important prognostic factors for early glottic cancer. Conclusion: There was no significant difference in 5 year survival rate among patients treated by either radiotherapy, laser microsurgery or open surgery for early glottic cancer. We urge more attention to the age, T-stage, pathological grade, and anterior commissure involvement of the patients.

The aim of this study was to compare the dosimetry of carotid arteries (CAs) using three radiation therapy (RT) techniques, three-dimensional conformal RT (3D-CRT), helical tomotherapy-intensity-modulated RT (HT-IMRT), and volumetric modulated arc therapy (VMAT), in patients with early-stage glottic cancer. A retrospective analysis of 28 patients was performed, and the right and left CAs were delineated. Mean and maximum dose (Dmax) values were compared across the three treatment techniques. The results indicate that 3D-CRT plans had the highest mean and maximum doses to CAs, while VMAT plans had the lowest doses. Our study demonstrates the feasibility of sparing CAs with newer RT modalities. Further clinical studies are needed to determine if these techniques can reduce carotid stenosis-related events. [ABSTRACT FROM AUTHOR]

Background: Due to the increasing expertise in transoral laser surgery and image-guided radiation therapy, treatment outcomes have recently improved in patients with early-stage glottic cancer. The objective of the current study was to evaluate intensity-modulated proton therapy (IMPT) as novel treatment option.Methods: A total of 15 patients with T1-2N0 glottic squamous cell carcinoma, treated between 2017 and 2020, were evaluated. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.Results: The majority were T1a/b tumors (66.7%) and no patient had lymph node or distant metastases. The median total dose was 70 Gy relative biological effectiveness (RBE) (range 66-70 Gy RBE). The one- and two-year OS and metastases-free survival were 100%. One patient developed local failure and received salvage laryngectomy. No higher-grade acute or late toxicity was reported. The mean number of CTCAE grade I and II overall toxicity events per patient was 4.1 (95%-[confidence interval] CI 3.1-5.3) and 1.0 (95%-CI 0.5-1.5).Conclusion: High-precision proton therapy of T1-2N0 glottic cancer resulted in exceptional treatment tolerability with high rates of laryngeal function preservation and promising oncological outcome. IMPT has the potential to become a standard treatment option for patients with early-stage laryngeal cancer. [ABSTRACT FROM AUTHOR]

(1) Background: Early-stage glottic cancer is easily missed on magnetic resonance imaging (MRI). Diffusion-weighted imaging (DWI) may improve diagnostic accuracy. Therefore, our aim was to assess the value of adding diffusion-weighted imaging with background body signal suppression (DWIBS) to pre-therapeutic MRI staging. (2) Methods: Two radiologists with 8 and 13 years of experience, blinded to each other's findings, initially interpreted only standard MRI, later DWIBS alone, and afterward, standard MRI + DWIBS in 41 patients with histopathologically proven pT1a laryngeal cancer of the glottis. (3) Results: Detectability rates with standard MRI, DWIBS only, and standard MRI + DWIBS were 68–71%, 63–66%, and 73–76%, respectively. Moreover, interobserver reliability was calculated as good (κ = 0.712), very good (κ = 0.84), and good (κ = 0.69) for standard MRI, DWIBS only, and standard MRI + DWIBS, respectively. (4) Conclusions: Standard MRI, DWIBS alone, and standard MRI + DWIBS showed an encouraging detection rate, as well as distinct interobserver reliability in the diagnosis of early-stage laryngeal cancer when compared to the definitive histopathologic report. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The study was performed with 50 patients, 24 patients in Arm A and 26 patients in Arm B. Arm A—Conventional Telecobalt RT 66 Gy/33 fraction in stage T1N0M0 and stage T2N0M0 and Arm B—3D-CRT 66 Gy/33 fraction in T1N0M0 and T2N0M0 used. At the end of RT, 6 weeks, 3 months acute and late toxicities were noted by RTOG/EORTC morbidity scoring criteria for skin reaction, dysphagia and laryngeal toxicity. Fiber optic Laryngoscopy clinical assessment criteria were used to assess response after 6 weeks, 3 months of treatment completion. At 6 weeks of follow-up—Both Arm A and B complete response rate were 83.3% and 88.5% respectively and at 3 months rate were 85.0% and 95.7% respectively. There was no superiority of results with 3D-CRT over 2DRT. At the end of RT dysphagia grade 3 toxicity seen 1 patient (4.2%) but in Arm B (total 26 patients) no grade 3 toxicity found. At the end of 6 week and 3 month, one patient (4.3%) had grade 3 toxicity on Arm B only at 3 month. All these results are comparable. At the end of RT, one patient (3.8%) had incidentally dermatitis grade 3 toxicity in Arm B only. But all the results are comparable. On follow up, 6 week and 3 months, no grade 3 toxicity noted. At the end of RT, grade 3 laryngeal toxicity noted in 3 (12.5%) in Arm A and 2 (7.7%) in Arm B, not statistically significant. At 6 week, grade 3 toxicity found in 3/24 (12.5%) in Arm A and 2/26 (7.7%) in Arm B, at 3 months, 1/26 (4.3%) patient had incidental grade 3 toxicity only in Arm B. As conformal radiotherapy is more time consuming, less available in India and more costly than 2DRT, we can consider Conventional 2D planning for patients in India where most of people belong to low economic profile. Due to limitation in sample size and long-term follow-up further randomized studies are needed to validate the results. [ABSTRACT FROM AUTHOR]

Abstract Background Laryngeal cancers of glottic origin comprise a large proportion of head and neck malignancies. Transoral laser microsurgery (TLM) and radiation therapy are mainstays in the treatment of early stage glottic cancer, but debate persists as to which modality is functionally superior. Furthermore, there is a paucity of North American data related to functional and oncological outcomes in T1a glottic cancer. Here, we assessed oncological and functional outcomes of T1a glottic squamous cell carcinoma (SCC) with TLM to supplement evidence from jurisdictions outside North America. Methods This study is a retrospective cohort study performed from a prospectively collected tertiary center institutional TLM database. Patients who were diagnosed with T1a glottic SCC and underwent TLM as their primary treatment were included. Functional outcomes were analyzed using the Voice Handicap Index-10 (VHI-10) questionnaire. Ultimate control with TLM only was considered to be those patients with locoregional control with repeat TLM procedures, but without addition of other modalities. Student’s t-test was used to test significance and Kaplan–Meier survival analysis was used to assess oncological outcomes. Results 48 patients met study criteria. The mean follow-up time was 74 months. The 5-year locoregional, ultimate control with TLM only and laryngeal preservation rates were 83.2%, 90.4% and 100%, respectively. The overall survival and disease-specific survival were 87.2% and 100%, respectively. VHI-10 scores were available for 13/48 patients and mean scores improved non-significantly from pre-op (mean: 11.23; range: 2 to 30; median: 10) and post op (mean: 7.92; range: 0 to 18; median: 8) scoring (p-value = 0.15). Sub-stratification of voice data revealed a significant improvement between pre and post-operative scores (mean difference − 10.6, 95% CI: − 0.99 to − 20.21, p-value = 0.035) for patients with abnormal pre-operative scores (VHI > 11). Conclusion To our knowledge, the current work represents one of the first North American studies to report both functional and oncologic outcomes for TLM treatment of T1a glottic SCC. The oncologic and functional outcomes presented here add to existing evidence in favor of TLM as a safe and effective primary treatment option for early staged T1a glottic cancer. Graphical abstract

The aim of the study was to utilize a quantitative assessment of the vibratory characteristics of vocal folds in diagnosing benign and malignant lesions of the glottis using high-speed videolaryngoscopy (HSV). Methods: Case-control study including 100 patients with unilateral vocal fold lesions in comparison to 38 normophonic subjects. Quantitative assessment with the determination of vocal fold oscillation parameters was performed based on HSV kymography. Machine-learning predictive models were developed and validated. Results: All calculated parameters differed significantly between healthy subjects and patients with organic lesions. The first predictive model distinguishing any organic lesion patients from healthy subjects reached an area under the curve (AUC) equal to 0.983 and presented with 89.3% accuracy, 97.0% sensitivity, and 71.4% specificity on the testing set. The second model identifying malignancy among organic lesions reached an AUC equal to 0.85 and presented with 80.6% accuracy, 100% sensitivity, and 71.1% specificity on the training set. Important predictive factors for the models were frequency perturbation measures. Conclusions: The standard protocol for distinguishing between benign and malignant lesions continues to be clinical evaluation by an experienced ENT specialist and confirmed by histopathological examination. Our findings did suggest that advanced machine learning models, which consider the complex interactions present in HSV data, could potentially indicate a heightened risk of malignancy. Therefore, this technology could prove pivotal in aiding in early cancer detection, thereby emphasizing the need for further investigation and validation.

BackgroundThe surgical treatment of glottic, or vocal cord, cancer has seen considerable progression over the past several decades. Specifically, there has been a stark transition from open partial laryngectomy surgery to endoscopic laser microsurgical techniques which have been inspired in large part by two landmark studies: Professor Wolfgang Steiner's original case series describing transoral laser microsurgery for glottic cancer (1993) and the European Laryngological Society's (ELS) classification scheme (2000). We performed a comprehensive review of published literature to characterize the pattern of this novel modality as compared with two landmark studies over the past four decades.MethodsAn English literature search was conducted on PubMed for available original investigations on surgical treatment of glottic laryngeal cancer published over the past 40 years. Our Boolean criteria included the following terms: cancer, glottic, laryngeal, surgery, endoscopic, and laser. The publication rates were calculated as annual compound growth as well as corrected growth rates as defined by the Fisher equation for inflation effects.ResultsOur review identified 13,372 studies covering larynx cancer and 3,557 studies covering glottic cancer original studies. Among these, we analyzed the compound annual growth rates and correct growth rates for three distinct publication periods or epochs, prior to 1993, 1993-1999, and 2000-2017. For all but two of the search term groups covering both glottic cancer as well as larynx cancer, there was a substantial growth improvement in the time period following the ELS classification scheme as compared with the growth rate of the time period following Steiner's case series.ConclusionThe progress toward minimally invasive treatment of glottic cancer has progressed steadily over the past several decades. Analysis of publication show increased growth during the time period following the ELS classification scheme over the time period following Steiner's landmark study. A mistake would be concluding any diminished importance of Professor Steiner's work, instead, our analysis demonstrates the wide-spread adoption of the endoscopic laser cordectomy procedure following the ELS classification system. Complex surgical techniques such as transoral laser microsurgery are optimally disseminated within well-defined classification schemes, though further validation is warranted.

Abstract Background We report the case of a patient with smoking‐induced radiation laryngeal necrosis (RLN) after undergoing definitive radiotherapy (RT) alone for T1a glottic squamous cell carcinoma. Case The patient was a 63‐year‐old man who had a history of heavy smoking. He quit smoking when he was diagnosed with glottic squamous cell carcinoma. The RT dose was 63 Gy, delivered in 28 fractions with the three‐dimensional conventional RT technique for the larynx. After RT completion, the initial treatment response was complete response. He then underwent follow‐up examinations. At 13 months after RT, the patient resumed smoking. At 2 months after resuming smoking, he had severe sore throat and hoarseness. Laryngoscopy revealed a large tumor in the glottis. Surgical excision was performed, and the patient was histologically diagnosed with RLN, as late toxicity without cancer recurrence. At 3 weeks postoperatively, the patient had dyspnea, and laryngoscopy revealed total laryngeal paralysis. Thus, he underwent an emergent tracheostomy. The administration of steroids affected RLN, and laryngeal paralysis gradually improved. Conclusions This case suggests that smoking may have the potential to induce RLN after RT. Moreover, continuing smoking cessation is significantly important for patients with glottic cancer who receive RT. Rather than leaving smoking cessation up to the patient, it would be necessary for clinicians to actively intervene to help patients continue their effort to quit smoking.

Abstract Purpose The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. Methods and materials Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. Results For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). Conclusions In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.

Abstract 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

Introduction: This retrospective study aimed at analyzing the recurrence rates in early glottic cancers (tumor, node, metastasis Stages I and II) treated at Gujarat Cancer and Research Institute (GCRI) from 2014 to 2018 by radiotherapy alone. Materials and Methods: The present study included 170 patients treated at GCRI from January 2014 to December 2018. One hundred and twenty-six patients were of stage T1N0, and rest 44 were of T2N0. Total radiotherapy dose received by them were 60 Gray in 30 fractions on linear accelerator with 6 MV photons without elective neck irradiation. Results: The mean duration of follow-up was 60 months. The local control (LC) rate was 93.65% in stage T1N0 stage and 84.1% in stage T2N0 glottic cancer. Out of the total 170 patients included in this study, 15 patients developed local recurrence which was biopsy proven, leading to overall local failure rate of 8.82%, and the mean time to recurrence as noted in our study was 9.1 months. Ultimate LC rate by radiotherapy alone was 91.2%. Conclusion: Radiotherapy provides better LC along with the advantage of organ preservation in T1N0 and T2N0 glottic cancer, and the local failure can be salvaged by surgery.

(1) Background: The treatment of recurrent early glottic cancer (rEGC) remains challenging. We wanted to investigate how the oncological outcomes are affected by the initial and recurrent stages, in order to propose our newly developed Same–Up–Down (SUD) staging system. (2) Methods: In our cohort of 258 rEGC patients, we retrospectively assessed the prognostic performances of the rTNM (the TNM staging system for recurrence), CLRSS, CLRSS-2, and SUD staging systems by univariate and multivariate Cox analysis, comparing their predictive capability using Harrell’s C-index. (3) Results: The SUD classification satisfactorily predicted both overall survival (p = 0.022) and second-recurrence-free survival (p = 0.024, as same + down vs. upstage) in our cohort. It also outperformed the other three systems in terms of prediction of survival, with an improvement of 1.52%, 1.18%, and 3.96% in the predictive capacity of overall survival, disease-specific survival, and second-recurrence-free survival, respectively. (4) Conclusions: The SUD staging system can efficiently predict survival in rEGC patients, whose prognosis heavily depends on both the initial and recurrent locoregional extension.

Background/Aim: The purpose of this study was to determine whether a semi-cylindrical beam spoiler (sCBS) developed herein effectively increases the skin dose in patients with early-stage glottic cancer. Patients and Methods: We measured the surface doses for 26 patients who used the sCBS during treatment of early-stage glottic cancer through a parallel-opposed lateral two-field 6 MV photon beam. Measurements were performed by attaching optically stimulated luminescent dosimeters to the left, right, anterior (in-field), inferior, and superior (out-field) sides of the patient. Results: The measured results were 81.8±2.1% (left), 81.0±1.7% (right), and 76.8±2.7% (anterior) in the in-field region compared to prescription doses, with 5.7±1.7% (superior) and 2.7±0.7% (inferior) in the out-field region. Conclusion: sCBS can deliver a suitably ideal surface dose for treatment of early-stage glottic cancer. [ABSTRACT FROM AUTHOR]

Background/Aim: To assess the dosimetric influence of a semi-cylindrical beam spoiler (sCBS) for the treatment of early glottic cancer using a 6 MV photon beam. Patients and Methods: The 2D dose distributions were also calculated and measured with and without the sCBS and with a 0.5 cm thick bolus. A retrospective study of 8 patients treated between 2012 and 2018 was performed. Results: The 2D dose distributions obtained from the treatment planning system (TPS) and film measurements were in good agreement. In the planning study, the V95%, V100%, conformal index (CI), and homogeneity index (HI) of all pPTVs for the sCBS plans were better than those for the open field plans (p<0.01). Especially, sCBS plans had better skin sparing effect than bolus plans (p<0.05). Conclusion: The sCBS of the 6 MV photon beam could be a useful tool for the treatment of early glottic cancers. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the dose distribution characteristics for early-stage glottic cancer by comparing the dose distribution between intensity-modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT) and to examine the usefulness of PSPT for early-stage glottic cancer. Materials and Methods: Computed tomography datasets of 8 patients with T1-2 glottic cancer who had been treated by PSPT were used to create an IMRT plan in Eclipse with 7 fields and a PSPT plan in XiO-M with 2 fields. Organs at risk (OARs) included the carotid arteries, arytenoids, inferior constrictor muscles, strap muscles, thyroid cartilage, cricoid cartilage, and spinal cord. The prescription dose was 66 GyRBE in 33 fractions to the planning target volume (PTV). All plans were optimized such that 95% of the PTV received 90% of the prescription dose considering that the skin was slightly spared. Results: The superiority of the PSPT was confirmed in all OARs. In the PSPT, the dose to the contralateral carotid artery and the spinal cord, which is slightly distant from the PTV, was dramatically reduced while maintaining the dose distribution uniformity of the PTV by comparison with IMRT. Conclusion: PSPT for early-stage glottic cancer resulted in good target dose homogeneity and significantly spared the OARs as compared with the IMRT. PSPT is expected to be effective in reducing late effects and particularly useful for young people.

Introduction: Discerning the preoperative nature of vocal fold leukoplakia (VFL) with a substantial degree of certainty is fundamental, seeing that the histological diagnosis of VFL includes a wide spectrum of pathology and there is no consensus on an appropriate treatment strategy or frequency of surveillance. The goal of our study was to establish a clear schedule of the diagnostics and decision-making in which the timing and necessity of surgical intervention are crucial to not miss this cancer hidden underneath the white plaque. Material and Methods: We define a schedule as a combination of procedures (white light and Narrow Band Imaging diagnostic tools), methods of evaluating the results (a combination of multiple image classifications in white light and Narrow Band Imaging), and taking into account patient-related risk factors, precise lesion location, and morphology. A total number of 259 patients with 296 vocal folds affected by leukoplakia were enrolled in the study. All patients were assessed for three classifications, in detail according to Ni 2019 and ELS 2015 for Narrow Band Imaging and according to Chen 2019 for white light. In 41 of the 296 folds (13.9%), the VFL specimens in the final histology revealed invasive cancer. We compared the results from the classifications to the final histology results. Results: The results showed that the classifications and evaluations of the involvement of anterior commissure improve the clinical utility of these classifications and showed improved diagnostic performance. The AUC of this model was the highest (0.973) with the highest sensitivity, specificity, PPV, and NPV (90.2%, 89%, 56.9%, and 98.3%, respectively). Conclusion: The schedule that combines white light and Narrow Band Imaging, with a combination of the two classifications, improves the specificity and predictive value, especially of anterior commissure involvement. [ABSTRACT FROM AUTHOR]

Abstract Introduction Narrowband imaging (NBI) is a special endoscopic optical enhancement setting allowing better visualization of mucosal microvasculature compared to white light endoscopy. This study evaluates the validity of NBI using the Ni classification in the detection and differentiation of severe dysplasia (SD) and glottic squamous cell carcinoma (SCC). Methods Patients with suspicious vocal cord lesions underwent conventional white light endoscopy followed by clinically indicated biopsy. At the same time, NBI images were obtained and graded independently. Lesions were graded from I to V according to the Ni classification and compared to histopathological findings. Results Fifty‐two patients were included in this study (40 SCC and 12 SD). The sensitivity and specificity of NBI in diagnosing laryngeal cancer was 95.0% (CI, 83.9%‐99.4%) and 83.3% (CI, 51.6%‐97.9%), respectively. The negative likelihood ratio was 0.06. Higher Ni grades correlated very strongly with more advanced disease. Conclusions NBI using the Ni classification is a sensitive diagnostic tool for the detection and differentiation of early neoplastic and preneoplastic glottic lesions. As higher Ni classification correlates strongly with advanced disease, it serves as a useful adjunct to white light endoscopy in the diagnosis of laryngeal cancer. Level of Evidence: Level IV.

Introduction: Glottic carcinomas represent approximately one third of the laryngeal cancers. True glottis includes both true vocal cords including anterior and posterior commissures. True vocal cord are as such devoid of lymphatics, so the chances of lymph node metastasis as such is very low. The chances of distant metastasis is also very rare. Herein we report a case of glottic cancer metastasising to parotid gland. Case report: A sixty eight year old male non smoker reported to our department with complaint of change of voice since three months. On computed tomography scan of head and neck, soft tissue thickness of about seven millimeter was seen over right true and false vocal cord and 2.3 * 1.9 cm lesion was seen involving the left lobe of the parotid gland. MRI of neck and paranasal sinuses was performed immediately following tomography which showed 2.6*1.9*3.1 cm lesion was seen involving deep lobe of left parotid gland which appeared isointense on T1w, hyperintense on T2w, not suppressed on STIR. There was no any evidence of capsular breach. Seven millimeter thickness was seen over right true and false vocal cord. These findings were further confirmed by direct laryngoscopic examination which showed mucosal irregularity over right true and false vocal cord with normal mobility of both vocal cords and punch biopsy was taken from it which came out to be well differentiated squamous cell carcinoma. Ultrasonography guided biopsy was taken from the deep lobe of the left parotid gland which came out to be metastatic squamous cell carcinoma. Patient was offered curative radiotherapy to a dose of 55 Gy in 20 fractions and the parotid lesion was addressed by parotidectomy, which showed no evidence of malignancy which might be considered to be an abscopal effect. Conclusion: The involvement of the parotid gland in case of glottic cancer is a very rare occurrence.

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.

IntroductionDiscerning the preoperative nature of vocal fold leukoplakia (VFL) with a substantial degree of certainty is fundamental, seeing that the histological diagnosis of VFL includes a wide spectrum of pathology and there is no consensus on an appropriate treatment strategy or frequency of surveillance. The goal of our study was to establish a clear schedule of the diagnostics and decision-making in which the timing and necessity of surgical intervention are crucial to not miss this cancer hidden underneath the white plaque.Material and MethodsWe define a schedule as a combination of procedures (white light and Narrow Band Imaging diagnostic tools), methods of evaluating the results (a combination of multiple image classifications in white light and Narrow Band Imaging), and taking into account patient-related risk factors, precise lesion location, and morphology. A total number of 259 patients with 296 vocal folds affected by leukoplakia were enrolled in the study. All patients were assessed for three classifications, in detail according to Ni 2019 and ELS 2015 for Narrow Band Imaging and according to Chen 2019 for white light. In 41 of the 296 folds (13.9%), the VFL specimens in the final histology revealed invasive cancer. We compared the results from the classifications to the final histology results.ResultsThe results showed that the classifications and evaluations of the involvement of anterior commissure improve the clinical utility of these classifications and showed improved diagnostic performance. The AUC of this model was the highest (0.973) with the highest sensitivity, specificity, PPV, and NPV (90.2%, 89%, 56.9%, and 98.3%, respectively).ConclusionThe schedule that combines white light and Narrow Band Imaging, with a combination of the two classifications, improves the specificity and predictive value, especially of anterior commissure involvement.

(1) Background: Early-stage glottic cancer is easily missed on magnetic resonance imaging (MRI). Diffusion-weighted imaging (DWI) may improve diagnostic accuracy. Therefore, our aim was to assess the value of adding diffusion-weighted imaging with background body signal suppression (DWIBS) to pre-therapeutic MRI staging. (2) Methods: Two radiologists with 8 and 13 years of experience, blinded to each other’s findings, initially interpreted only standard MRI, later DWIBS alone, and afterward, standard MRI + DWIBS in 41 patients with histopathologically proven pT1a laryngeal cancer of the glottis. (3) Results: Detectability rates with standard MRI, DWIBS only, and standard MRI + DWIBS were 68–71%, 63–66%, and 73–76%, respectively. Moreover, interobserver reliability was calculated as good (κ = 0.712), very good (κ = 0.84), and good (κ = 0.69) for standard MRI, DWIBS only, and standard MRI + DWIBS, respectively. (4) Conclusions: Standard MRI, DWIBS alone, and standard MRI + DWIBS showed an encouraging detection rate, as well as distinct interobserver reliability in the diagnosis of early-stage laryngeal cancer when compared to the definitive histopathologic report.

BackgroundAlthough intensity-modulated radiotherapy (IMRT) is a standard of care for many head and neck cancers, its use for carotid-sparing (CS) therapy in early-stage laryngeal carcinoma is controversial.Methods330 consecutive patients with early-stage laryngeal carcinoma were treated from 1/1989 to 5/2011, including 282 conventional radiotherapy (CRT) and 48 CS-IMRT patients. The median follow-up was 43 (CS-IMRT) and 66 (CRT) months.ResultsThere was no difference in local failure rates comparing patients undergoing CS-IMRT with CRT, with 3-year local control rates of 88% vs. 89%, respectively (p=0.938). Using a 1cm circumferential margin, the average dose to the left and right carotid arteries was 48.3 and 47.9 Gy, respectively. 88% of locoregional recurrences involved the ipsilateral true vocal cord, including all local recurrences in the IMRT group.ConclusionsThese results warrant further prospective evaluation of CS-IMRT for early-stage glottic larynx cancer.

Background/PurposeThe value of margin status after TLM for glottic cancer is debatable, due to difficulties in specimen orientation and margin analysis. To reduce these difficulties, we recently introduced a standardized protocol of oriented fixation of TLM specimens. This proved feasible and resulted in high margin evaluability rates and a decreased rate of false positive deep margins, when compared to a historical TLM cohort. For the patients whose specimens were processed according to this protocol, we prospectively analyzed oncological outcomes, identified prognostic factors and assessed the influence of the protocol introduction on outcomes compared with a historical TLM cohort.MethodsNinety-six patients with glottic malignancies treated with TLM were included. Resection specimens were processed according to the new protocol. Descriptive statistics and survival analyses were used to determine oncological outcomes. To assess the effect of the protocol introduction on outcomes, a matched-case-control analysis was performed, using a historical TLM-cohort as controls. The Cox proportional hazards model was used to analyze prognostic effects of patient and treatment characteristics, including the pathology protocol introduction, on overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and local recurrence-free survival (LRFS).ResultsTwo-year outcomes were favorable: 88.5% OS, 97.0% DSS, and 87.6% LRFS. At multivariable analysis, the presence of multiple positive superficial margins was a negative prognosticator for OS (HR 4.102) and increasing cT classification proved a negative prognosticator for DFS (HR 2.828) and LRFS (HR 2.676). Matched case-control analysis did not reveal a significant difference in oncological outcomes between cohorts. Deep margin status had a strong differential effect for DFS (p-value for interaction = 0.0205) and for LRFS (p-value for interaction = 0.0176) between cohorts, indicating a prognostic effect of deep margin status on both outcomes in the current cohort, but not in the historical cohort.Discussion/ConclusionThe introduction of a new standardized technique of oriented fixation of TLM specimens did not affect oncological outcomes when compared to a historical TLM cohort, but assigned a significant prognostic effect to deep margin status for DFS and LRFS, facilitating the decision making process with regards to planning of second-look procedures, administration of adjuvant radiotherapy or determination of follow-up intensity.

Abstract Introduction Transoral laser microsurgery (TLM) is the treatment of choice for Tis-T2 squamous cell glottic carcinomas due to its advantages compared with open surgery and radiotherapy. However, the CO2 laser beam causes changes and damage on the specimens, making the histological assessment of resection margins, the gold standard for confirming radical tumor resection, sometimes difficult. Objective To assess the different ways to manage patients depending on the status of the histopathological margin according to recent studies to detect the most commonly shared therapeutic strategy. Data Synthesis We analyzed the literature available on the PubMed and Web of Science databases, including only articles published since 2005, using specific keywords to retrieve articles whose titles and abstracts were read and analyzed independently by two authors to detect relevant studies. Therefore, we focused on disease-free survival, overall survival, local control, laryngeal preservation, and disease-specific survival. Thus, 17 studies were included in the present review; they were grouped according to the status of the histological margin, and we analyzed the different management policies described in them. This analysis showed that there is not a shared strategy, though in most studies the authors performed a second-look surgery in the cases of positive margins and a close follow-up in cases of negative ones. The main disagreement is regarding the management of close or non-valuable resection margins, since some some authors performed a second-look surgery, and others, a close follow-up. Conclusions Definitely, the most shared policy is the second-look surgery in case of positive surgical margins, and a close follow-up in case of close or non-valuable resection margins. Key Points To date, TLM is the treatment of choice for Tis-T2 squamous cell glottic carcinomas. The CO2 laser beam could impair the histological assessment of the resection margins, which is the gold standard to confirm radical tumor resection. Second-look TLM is the most performed strategy in case of positive surgical margins. Close follow-up is the most shared policy in case of close or non-valuable resection margins. In cases of negative resection margins, follow-up represents the best approach.

Purpose: The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer.Methods and Materials: Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated.Results: For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively).Conclusions: In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins. [ABSTRACT FROM AUTHOR]

Background/Purpose: The value of margin status after TLM for glottic cancer is debatable, due to difficulties in specimen orientation and margin analysis. To reduce these difficulties, we recently introduced a standardized protocol of oriented fixation of TLM specimens. This proved feasible and resulted in high margin evaluability rates and a decreased rate of false positive deep margins, when compared to a historical TLM cohort. For the patients whose specimens were processed according to this protocol, we prospectively analyzed oncological outcomes, identified prognostic factors and assessed the influence of the protocol introduction on outcomes compared with a historical TLM cohort. Methods: Ninety-six patients with glottic malignancies treated with TLM were included. Resection specimens were processed according to the new protocol. Descriptive statistics and survival analyses were used to determine oncological outcomes. To assess the effect of the protocol introduction on outcomes, a matched-case-control analysis was performed, using a historical TLM-cohort as controls. The Cox proportional hazards model was used to analyze prognostic effects of patient and treatment characteristics, including the pathology protocol introduction, on overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and local recurrence-free survival (LRFS). Results: Two-year outcomes were favorable: 88.5% OS, 97.0% DSS, and 87.6% LRFS. At multivariable analysis, the presence of multiple positive superficial margins was a negative prognosticator for OS (HR 4.102) and increasing cT classification proved a negative prognosticator for DFS (HR 2.828) and LRFS (HR 2.676). Matched case-control analysis did not reveal a significant difference in oncological outcomes between cohorts. Deep margin status had a strong differential effect for DFS (p-value for interaction = 0.0205) and for LRFS (p-value for interaction = 0.0176) between cohorts, indicating a prognostic effect of deep margin status on both outcomes in the current cohort, but not in the historical cohort. Discussion/Conclusion: The introduction of a new standardized technique of oriented fixation of TLM specimens did not affect oncological outcomes when compared to a historical TLM cohort, but assigned a significant prognostic effect to deep margin status for DFS and LRFS, facilitating the decision making process with regards to planning of second-look procedures, administration of adjuvant radiotherapy or determination of follow-up intensity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction Transoral laser microsurgery (TLM) is the treatment of choice for Tis-T2 squamous cell glottic carcinomas due to its advantages compared with open surgery and radiotherapy. However, the CO2 laser beamcauses changes and damage on the specimens, making the histological assessment of resection margins, the gold standard for confirming radical tumor resection, sometimes difficult. Objective To assess the different ways to manage patients depending on the status of the histopathological margin according to recent studies to detect themost commonly shared therapeutic strategy. Data Synthesis We analyzed the literature available on the PubMed andWeb of Science databases, including only articles published since 2005, using specific keywords to retrieve articles whose titles and abstractswere read and analyzed independently by two authors to detect relevant studies. Therefore, we focused on disease-free survival, overall survival, local control, laryngeal preservation, and disease-specific survival. Thus, 17 studies were included in the present review; they were grouped according to the status of the histological margin, and we analyzed the different management policies described in them. This analysis showed that there is not a shared strategy, though inmost studies the authors performeda second-look surgery in the cases of positive margins anda close followup in cases of negative ones. The main disagreement is regarding themanagement of close or non-valuable resection margins, since some some authors performed a second-look surgery, and others, a close follow-up. Conclusions Definitely, the most shared policy is the second-look surgery in case of positive surgical margins, and a close follow-up in case of close or non-valuable resection margins. [ABSTRACT FROM AUTHOR]

Abstract Background There is a paucity of evidence comparing oncological and voice outcomes between T2a and T2b glottic squamous cell carcinoma (SCC) patients treated with transoral laser microsurgery (TLM). This study identified functional and oncological outcomes in this cohort. Methods Retrospective review of prospectively collected data of patients treated with TLM for T2 glottic SCC from 2003 to 2017. Results In total, 75 patients were included. Five-year local control rates were significantly different between T2a and T2b patients (75.2% vs 57.0%, p = 0.022). There was no difference in five-year survival between patients with T2a disease and T2b disease (69.5% vs 73.4%, p = 0.627). There was no significant difference in mean VHI-10 scores in the pre-operative period (18.3 vs 21.4, p = 0.409). However, patients with T2b disease had significantly worse perceived voice outcomes post-operatively (6.6 vs 21.3 p = 0.001). Patients with T2a disease saw significant improvements in mean VHI-10 scores following surgery (18.3 vs 6.6, p = 0.000), while T2b patients did not (21.4 vs 21.3, p = 0.979). The overall laryngeal preservation rate was 94.7%, with 11.5% of T2b patients requiring salvage organ sacrifice. Conclusions This study highlights positive functional outcomes for T2a glottic SCC. Patients with T2b disease appear to have significantly worse oncological and functional outcomes, including worse voice quality following surgery and higher rates of salvage laryngectomy.

The aim of this study was to compare the outcomes, patterns of failure and laryngeal preservation rates in patients with T1N0 glottic cancer treated with surgery or radiotherapy. Retrospective study of T1N0 glottic cancer patients treated in our institution between January 2007 and December 2017. Histologically proven squamous cell carcinoma patients, treated with upfront cordectomy/partial laryngectomy (S group) or radiotherapy (RT group) were included. Elective treatment of the neck was not permitted. Local failure (LF), disease-free survival (DFS), ultimate disease-free survival (UDFS), laryngectomy-free survival (LFS), disease-specific mortality (DSM) and overall survival (OS) were evaluated. Two hundred and one patients were eligible (172 S group, 29 RT group), with a median follow-up of 38.8 months. Overall, 33 (16%) patients had a recurrence, 30 (17%) in the S group and 3 (10%) in the RT group. Local failure was the predominant site of failure (28 S, 2 RT). Overall, of all those that were salvaged, 17 (8%) underwent total laryngectomy (15 S, 2 RT). There was no significant difference in the 5-year cumulative incidence of LF (20.8% S, 8.1% RT, p = 0.138), 5-y LFS (85.0% vs. 91.7%, p = 0.809), 5-y DFS (67.5% vs. 82.1%, p = 0.343), 5-y UDFS (82.5% vs. 90.3%, p = 0.647) and 5-y OS (84.5% vs. 90.3%, p = 0.892). Multivariate analysis showed no correlation between initial treatment and the analyzed outcomes. Primary surgery or radiotherapy were similar first line options, since they do not differ in all outcomes. Patients' and physician's preferences must be considered when choosing first treatment. [ABSTRACT FROM AUTHOR]

Purpose and Objective: To evaluate the disease-free survival, overall survival, dosimetric, and voice handicap index (VHI) results of T1a glottic invasive squamous cell carcinoma (SCC) patients who underwent hypofractionated single vocal cord irradiation (HSVCI).Materials and Methods: The data of 18 patients with stage T1a glottic SCC were collected prospectively and analyzed retrospectively between July 2016 and July 2019. Patients were immobilized using a custom-fitted thermoplastic face and shoulder mask in hyperextension position. The CT scan was performed with 1-mm-thick slices. A planned target volume (PTV) margin of 3 mm was given to clinical target volume (CTV) in all directions, and 13 organs at risk were identified. Patients were prescribed a total of 5760–5808 cGy in 15–16 fractions. Patients had daily cone-beam computed tomography (CBCT), and the treatment was carried out with the physician. VHI test was applied to patients before and at the end of radiotherapy (RT) and 1, 2, 3, 4, and 6 months after the completion of RT.Results: Local control and overall survival rate is 100% for a median of 18 months (6–44 months) of follow-up. A patient was diagnosed with 2nd primary lung cancer and active treatment still continues. All patients completed the treatment within the scheduled time. Grade 1–2 dysphagia and dermatitis occurred in all patients, and no grade 3 and above side effects were observed. The mean values of VHI were 37.00, 39.83, 38.28, 17.17, 12.22, 8.56, and 6.06 at the beginning of RT, at the end of RT, and 1, 2, 3, 4, and 6 months after RT, respectively.Conclusion: Compared to surgery and conventional laryngeal radiotherapy, HSVCI is an alternative treatment method for T1a glottic cancer by reducing the treatment time to 3 weeks, facilitating recurrence treatment, and providing effective sound quality without compromising local control. Considering that ~80% of recurrences in glottic cancer occur within the first 2 years, 100% local control in a median of 18 months is extremely successful, but long-term follow-up is essential to observe possible late side effects.