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.

OBJECTIVE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI).
METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV.
RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing.
CONCLUSIONS: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.

OBJECTIVE: The study aimed to assess the relevance of objective vibratory parameters derived from high-speed videolaryngoscopy (HSV) as a supporting tool, to assist clinicians in establishing the initial diagnosis of benign and malignant glottal organic lesions.
METHODS: The HSV examinations were conducted in 175 subjects: 50 normophonic, 85 subjects with benign vocal fold lesions, and 40 with early glottic cancer; organic lesions were confirmed by histopathologic examination. The parameters, derived from HSV kymography: amplitude, symmetry, and glottal dynamic characteristics, were compared statistically between the groups with the following ROC analysis.
RESULTS: Among 14 calculated parameters, 10 differed significantly between the groups. Four of them, the average resultant amplitude of the involved vocal fold (AmpInvolvedAvg), average amplitude asymmetry for the whole glottis and its middle third part (AmplAsymAvg; AmplAsymAvg_2/3), and absolute average phase difference (AbsPhaseDiffAvg), showed significant differences between benign and malignant lesions. Amplitude values were decreasing, while asymmetry and phase difference values were increasing with the risk of malignancy. In ROC analysis, the highest AUC was observed for AmpAsymAvg (0.719; p < 0.0001), and next in order was AmpInvolvedAvg (0.70; p = 0.0002).
CONCLUSIONS: The golden standard in the diagnosis of organic lesions of glottis remains clinical examination with videolaryngoscopy, confirmed by histopathological examination. Our results showed that measurements of amplitude, asymmetry, and phase of vibrations in malignant vocal fold masses deteriorate significantly in comparison to benign vocal lesions. High-speed videolaryngoscopy could aid their preliminary differentiation noninvasively before histopathological examination; however, further research on larger groups is needed.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 4 (retrospective case series review).

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).

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Submucosal laryngeal lesions have proven themselves to be a diagnostic challenge in the field of medicine, often presenting inconsistently between endoscopic visualization, various imaging modalities, and biopsy. The conflicting clinical picture can lead to a delay in definitive diagnosis and treatment. A variety of laryngeal imaging modalities exist that give a unique perspective of the tumor being evaluated and can be used in combination to clarify discrepancies in presentation.  This report describes the clinical course of an undiagnosed laryngeal squamous cell carcinoma (SCC) presenting with persistent dysphonia, dysphagia, and unilateral vocal fold immobility. A negative head and neck computerized tomography (CT) scan reduced the concern for cancer, so symptomatic treatment with vocal fold augmentation was performed. Augmentation curiously worsened the dysphonia and also may have delayed the process of definitive diagnosis. Upon presenting to the laryngology clinic, stroboscopy demonstrated no vibration of the affected vocal fold. Submucosal vascular irregularity was noted with narrow band imaging with a very subtle keratotic mucosal change raising suspicion for underlying malignancy. Despite two CT scans that failed to visualize the lesion initially, a biopsy revealed keratinizing SCC, which was subsequently staged as T3N0M0. The patient elected to receive radiation therapy alone given his medical comorbidities. This case showcases the elusive ability submucosal laryngeal cancers have in diagnostic workups. Heavy reliance on any single diagnostic modality may be misleading, resulting in delayed diagnosis and treatment. An early, thorough, and multimodal approach that analyzes the cumulative results of a variety of diagnostic tools is essential in identifying and treating these elusive cancers in a timely manner.

OBJECTIVE: Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.4 Gy.
METHODS: A total of 102 patients with stage 1 GC underwent RT alone between 2007 and 2021, with 43 in the AHF group and 59 in the ODF group. A p-value less than 0.05 was considered to indicate a significant difference.
RESULTS: The 5-year LC rate was 98% in the AHF group and 91% in the ODF group (p=0.19). During RT, significantly more patients in the AHF group required opioids due to mucositis than in the ODF group (74% vs. 25%, p<0.001), and the rate of aspiration pneumonia tended to be higher in the AHF group than in the ODF group (7% vs. 0%, p=0.072).
CONCLUSIONS: There was no difference in the LC rate between AHF and ODF for stage 1 GC. Moreover, the AHF group required opioids at a higher rate and tended to have a higher risk of developing aspiration pneumonia.

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.

Paraneoplastic IgA nephropathy (IgAN) is an underrecognized condition in which malignancy manifests as symptoms of IgAN, and it remains controversial regarding their mechanistic relation between IgAN and malignancy. Herein, we report a case of a 68-year-old Japanese man with glottic cancer who developed nephrotic syndrome as a clinical manifestation of IgAN. Renal biopsy revealed diffuse proliferative glomerulonephritis with glomerular capillary IgA deposition that is a rare subtype of IgAN. After complete remission of the glottic cancer by irradiation, proteinuria and hematuria disappeared. Based on his clinical course, we diagnosed paraneoplastic IgAN. Therefore, we should consider the possibility that IgAN with glomerular capillary IgA deposition might be paraneoplastic glomerulopathy especially before initiating immunosuppressive therapy. The patient thereafter developed prostate cancer and hepatocellular cancer, but IgAN did not recur. The association of IgAN specifically with the glottic cancer in this triple-cancer patient may suggest a potential link between IgAN and mucosal cancer. Because galactose-deficient IgA1 (Gd-IgA1) was observed in the similar pattern as IgA, Gd-IgA1 also may play an important role in the pathogenesis of paraneoplastic IgAN.