Factors Impacting Provider Treatment Decision-Making in Early Glottic Cancer.

OBJECTIVES: Transoral laser microsurgery (TLMS) and radiotherapy (XRT) are mainstays of treatment for early glottic carcinoma (EGC). Here, we investigated case-dependent provider treatment preferences and identify factors which impact decision-making in EGC. METHODS: This cross-sectional survey of laryngologists, head-and-neck surgeons, and radiation oncologists presented five diagrammatic cases of progressively advanced EGC (T1/2, N0). Respondents indicated preference for TLMS or XRT and ranked factors which influenced their recommendation for each case. Analysis utilized descriptive statistics, Fischer's exact tests, and Kruskal-Wallis tests for nonparametric data. RESULTS: A total of 141 complete responses (69.5% laryngologists) were received. Most respondents practiced in academic settings (93.5%) and within multidisciplinary teams (94.0%). Anterior commissure involvement was the most important a priori tumor factor for case-independent treatment recommendation (Likert Scale: 4.22/5), followed by Laterality (Likert Scale: 4.02/5). Across all specialties, TLMS was recommended for unilateral T1a lesions. Laryngologists continued recommending TLMS in T2 lesions (41.0%) more than head-and-neck surgeons (5.0%) and radiation oncologists (0.0%). Across all cases, survival and voice outcomes were the most important clinical factors impacting treatment decisions. Radiation oncologists weighed voice more heavily than laryngologists in more complex presentations of EGC (rank: 1.6 vs. 2.7, Kruskall-Wallis: p < 0.05). CONCLUSIONS: In more complex clinical presentations of EGC, preference for TLMS compared to XRT differed across specialists, despite similar rankings of factors driving these treatment recommendations. This may be driven by differing experiences and viewpoints on case-dependent voice outcomes following TLMS versus XRT, suggesting a need for increased understanding of how tumor location and depth impact voice outcomes. LEVEL OF EVIDENCE: V Laryngoscope, 2024.

Targeting Anterior Commissure Involvement with Hyperfractionated Radiotherapy for T1-T2 Squamous Cell Carcinoma of the Glottic Larynx.

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.

Dosimetric impact of VMAT delivery angles for early glottic cancer treatment.

This study investigates the dosimetric effects of different gantry rotation angles used in volumetric modulated arc therapy (VMAT) for early glottic carcinoma. VMAT treatment plans using full-arc, half-arc, and partial-arc gantry rotation angles were generated from 22 computed tomography datasets of early-stage (T1-2N0) glottic laryngeal cancer. Dosimetric parameters associated with the planning target volume (PTV) and organs at risk (OARs), specifically the carotid arteries and thyroid, were compared. To assess the robustness of the VMAT plans, dose variations were analyzed by introducing positional shifts of 1, 3, and 5 mm from the isocenter of each plan along the superior-inferior, left-right, and anterior-posterior axes. Furthermore, we examined the size of the PTV, the air cavity volume within the PTV, and the variability of the beam path length through the gantry angles to investigate their correlations with PTV dose variations in the presence of positioning errors. Compared to full-arc and half-arc plans, the dosimetric parameters of partial-arc plans were found to be higher in PTV (D2%, D5%, D50%, and Dmean) and lower in OARs, while their dose variations of OAR parameters were greater for positioning errors. In addition, a correlation was observed between PTV size and PTV dose variations. Air cavity volume and depth variability were also correlated with some PTV parameters, depending on the arc plan. The results presented in this study suggest that the partial-arc gantry angles can allow higher PTV doses while minimizing OAR doses in VMAT treatment planning for early glottic cancer. However, the small delivery angles may lead to greater dose variations in the OARs when positioning errors occur.

Assessment and validation of glottic motion using cone-beam CT and real-time cine MRI.

PURPOSE: 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. CONCLUSION: 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.

Patterns of Care for T1 Glottic Squamous Cell Carcinomas from 2004-2020.

OBJECTIVE(S): Describe recent national trends in overall treatment modalities for T1 glottic squamous cell carcinomas (SCC), and identify factors associated with treatment regimens. METHODS: National Cancer Database from 2004-2020 was queried for all patients with glottic cT1N0M0 SCC. Treatment patterns over time were analyzed using the Cochran-Armitage test for trend. Multivariable logistic regressions were used to determine the factors associated with treatment regimens. RESULTS: Of the 22,414 patients identified, most patients received RT only (57%), 21% received surgery only, and 22% received dual-modality treatment ("over-treatment"). Over the time period, there was a decreasing trend in rates of over-treatment for T1 glottic SCC (p < 0.001) and an increasing trend in surgery only (p < 0.001). Treatment in 2016-2018 (OR: 1.168 [1.004 to 1.359]), 2013-2015 (OR: 1.419 [1.221 to 1.648]), 2010-2012 (OR: 1.611 [1.388 to 1.871]), 2007-2009 (OR: 1.682 [1.450 to 1.951]), or 2004-2006 (OR: 1.795 [1.548 to 2.081]) versus 2019-2020 was associated with greater likelihood of over-treatment. T1b tumors were less likely to be over-treated (OR: 0.795 [0.707 to 0.894]) versus T1a tumors, and less likely to receive surgery first (OR: 0.536 [0.485 to 0.592]) versus T1a tumors. CONCLUSION: Over-treatment for T1 glottic SCC has been declining, with increasing rates of surgery only. Year of treatment was significantly associated with the receipt of dual-modality treatment. Finally, patients with T1b disease were more likely to receive RT as the first and only treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Transoral laser microsurgery for T1 glottic cancer with anterior commissure: Identifying clinical and radiological variables that predict oncological outcome.

PURPOSE: The involvement of the anterior commissure (AC) is regarded to be a risk factor for poor results after transoral laser microsurgery (TLM) for early glottic cancer. The objective of this study was to determine how AC-related clinical and radiological factors affected oncological outcomes in a cohort of patients with T1 stage early glottic carcinoma involving the anterior commissure who were treated with TLM with negative surgical margins. METHODS: Retrospective analysis was performed on clinical, radiological, and follow-up data of patients consecutively treated with TLM at a tertiary academic center between November 2011 and August 2021 for T1 glottic squamous cell carcinoma involving the anterior commissure. Recurrence-free survival (RFS), local control with laser alone (LCL), laryngeal preservation (LP), and overall survival (OS) rates (Kaplan-Meier) were the primary outcome metrics. RESULTS: In our series, 5-year OS probability was 75.1%, RFS was 64.8%, LCL was 73.8%, and LP was 83.4%. OS and RFS were higher in patients with early stages of AC pattern than in patients with advanced stage (p = 0.004, p = 0.034, respectively). Vertical extension ratio was found to be associated with OS and RFS (p = 0.023, p = 0.001, respectively), and thyroid cartilage interlaminar angle with LCL by multiple Cox regression analysis (p = 0.041). CONCLUSION: TLM remains a valuable treatment option for AC involvement. AC3 type involvement and elevated vertical extension ratio were associated with negative prognosis. There have been signs that thyroid cartilage with a narrow angle increases recurrence. Alternative modalities should be kept in mind in the treatment decision of these cases.

Value of high-speed videoendoscopy as an auxiliary tool in differentiation of benign and malignant unilateral vocal lesions.

PURPOSE: 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). CONCLUSION: 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.

Prognostic value of preoperative inflammatory ratios in early glottic cancer treated with transoral laser surgery.

BACKGROUND: There is growing evidence regarding the prognostic utility of ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII) in head and neck squamous cell carcinoma (HNSCC). However, most studies to date include heterogeneous series with different treatments or tumor subsites. METHODS: We collected data from 201 patients with stage I-II glottic squamous cell carcinoma treated with transoral laser surgery. NLR, PLR, and SIII were calculated from preoperative cell blood count, cut-off points were obtained by ROC curve analysis, and survival rates were calculated. RESULTS: High NLR (p = 0.012) and SIII (p = 0.037), but not PLR (p = 0.48), were associated with worse disease-specific survival (DSS). A similar trend was observed with overall survival (OS), although it did not reach statistical significance. On multivariable analyses, both high NLR (HR = 3.8, 95% CI = 1.5-9.9, p = 0.006) and high SIII (HR = 2.77, 95% CI = 1.1-6.9, p = 0.03) were significantly associated with shortened DSS. CONCLUSIONS: Preoperative NLR and SIII emerge as independent prognostic biomarkers for early-stage surgically treated glottic tumors and could guide individualized follow-up.

Visual Gaze Patterns in the Analysis of Glottic Lesions: Does Experience Increase Diagnostic Accuracy?

OBJECTIVES: The purpose of this study was to evaluate visual gaze patterns and the ability to correctly identify cancer among participants of different experience levels when viewing benign and malignant vocal cord lesions. METHODS: Thirty-one participants were divided into groups based on level of experience. These included novice (medical students, PGY1-2 otolaryngology residents), intermediate (PGY3-5 otolaryngology residents, gastroenterology fellow), advanced practice providers (physician assistants, nurse practitioners, and speech language pathologists), and experts (board-certified otolaryngologists). Each participant was shown 7 images of vocal cord pathology including glottic cancer, infectious laryngitis, and granuloma and asked to determine the likelihood of cancer on a scale of certain, probable, possible, and unlikely. Eye tracking data were collected and used to identify the area of interest (AOI) that each participant fixated on first, fixated on the longest, and had the greatest number of fixations. RESULTS: No significant differences were seen among groups when comparing AOI with first fixation, AOI with longest fixation, or AOI with most fixations. Novices were significantly more likely to rate a low likelihood of cancer when viewing infectious laryngitis compared to more experienced groups (P < .001). There was no difference in likelihood of cancer rating among groups for the remaining images. CONCLUSIONS: There was no significant difference in gaze targets among participants of different experience levels evaluating vocal cord pathology. Symmetric appearance of vocal cord lesions may explain differences seen in likelihood of cancer rating among groups. Future studies with larger sample sizes will better elucidate gaze targets that lead to accurate diagnosis of vocal cord pathology.

Value and role of surgical margins in transoral laser microsurgery of the larynx, literature review and clinical considerations.

PURPOSE: There is no agreement on the most appropriate post-operative pathway for the management of positive margins after laser cordectomy for early stage glottic tumours (T1-2N0M0). This literature review and meta-analysis aim to evaluate the post-operative treatment with the best oncological results among follow-up, radiotherapy (RT) and surgical second look. The parameters utilized were incidence of recurrence, overall (OS), disease-specific (DSS) and disease-free (DFS) survival and larynx preservation (LP). METHODS: The articles were found through a string typed into PubMed from 2007 to 2022. The studies with detailed oncological results were selected according to inclusion criteria, and then the meta-analysis was carried out. RESULTS: Sixteen studies met the inclusion criteria for 2808 patients. The positive margin was found in 748 patients (26.6%), of which 416 were referred to follow-up, 89 to RT and 242 to a surgical second look. A false positive margin was found in 58/104 patients (56%). The recurrence rate in patients with positive margins was significantly higher (p = 0.003). In OS, DSS, DFS and LP, the odds ratio (OR) value was always greater than 1, assessing the role of the positive margin as a risk factor. CONCLUSIONS: Prospective studies will be necessary to establish the role of positive margin as a prognostic factor. A surgical second look in case of positive margin seems to be the best option for the patient in terms of lower risk of recurrence and better oncological results. Better collaboration between surgeon and pathologist would be desirable to limit the real and false positive margins.

A case of paraneoplastic IgA nephropathy with glomerular capillary IgA and galactose-deficient IgA1 deposition.

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.

Sobrevida del cáncer glótico en estadio inicial en 4 centros hospitalarios de Uruguay / Survival of glottic cancer in the initial stage in 4 hospital centers in Uruguay / Sobrevivência de câncer glótico em estágio inicial em 4 hospitais uruguaios

Introducción: El cáncer de laringe es el tumor maligno de mayor prevalencia en la Otorrinolaringología. La topografía glótica es la más frecuente en Uruguay y suele detectarse en estadios tempranos dada la manifestación precoz y sostenida de disfonía. El objetivo de este estudio es describir la sobrevida libre de enfermedad (SLE) y la sobrevida global (SG) de los pacientes con cáncer de laringe glótico en estadio T1N0M0 en 4 instituciones de Montevideo. Metodología: Se analizó de forma retrospectiva la SG y SLE de 55 pacientes diagnosticados con cáncer de glotis T1 entre los años 2009 y 2019. Para el cálculo de la sobrevida se utilizó el método de Kaplan-Meier. Se estudió además el efecto de variables pronósticas de interés sobre la SG mediante análisis univariado y multivariado. Resultados: En la muestra analizada la SG de los pacientes con cáncer glótico T1N0M0 fue como media de 7.706 años (IC 95% 6.63 - 8.78). A los 5 años, la SG fue de 77.5% (± 7%) y de 62% (± 9.8%) a los 10 años. La SLE para todos los pacientes correspondió al 74.6% (± 7.5%) y 63.1% (± 9.8%), a 5 y 10 años respectivamente. No se alcanzaron las medianas de SG ni de SLE para los grupos. Conclusiones: Los valores de SG y SLE medios obtenidos en nuestro medio son comparables a los valores reportados en la bibliografía internacional. No se alcanzó la mediana de SG ni de SLE, por lo que se puede afirmar que ésta enfermedad tiene, cuando se realiza el tratamiento adecuado, un buen pronóstico vital a los 10 años. Se requiere un seguimiento más largo para determinar las medianas de SG y SLE de los grupos en estudio.

Introduction: Laryngeal cancer is the most prevalent malignant tumor in Otorhinolaryngology. Glottic topography is the most frequent in Uruguay and is usually detected in early stages given the early and sustained manifestation of dysphonia. The objective of this study is to analyze disease-free survival (DFS) and overall survival (OS) of patients with stage T1N0M0 glottic laryngeal cancer at 4 institutions in Montevideo. Methodology: The mean OS and DFS of 55 patients diagnosed with T1 glottic cancer between 2009 and 2019 were retrospectively analyzed. Kaplan-Meier method was used to calculate survival. The prognostic effect of certain variables of interest on OS was also studied using univariate and multivariate analysis. Results: In this study, mean odds survival (OS) for T1N0M0 glottic cancer was 7.706 years (CI 95% 6.63 - 8.78). At 5 years, OS was 77.5% (± 7%) and at 10 years was 62% (± 9.8%). Disease free survival (DFS) was 74.6% ± (7.5%) at 5 years and 63.1% (± 9.8%), at 10 years. Median OS and DFS for the groups were not reached. Conclusions: OS and DFS in our medium is comparable to that reported in the international literature. The median OS and DFS were not reached, so it can be stated that this disease has, when appropriate treatment is performed, a good vital prognosis at 10 years. Longer follow-up is required to determine the median OS and DFS of the study groups.

Introdução: O câncer de laringe é o tumor maligno mais prevalente na Otorrinolaringologia. A topografia glótica é a mais frequente no Uruguai e geralmente é detectada em estágios iniciais devido à manifestação precoce e sustentada da disfonia. O objetivo deste estudo é analisar a sobrevida livre de doença (DFS) e a sobrevida global (OS) de pacientes com câncer de laringe glótico estágio T1N0M0 em 4 instituições em Montevidéu. Metodologia: Foram analisados retrospectivamente o OS e DFS de 55 pacientes diagnosticados com câncer glótico T1 entre 2009 e 2019. O método de Kaplan-Meier foi usado para calcular a sobrevida. Resultados: Na amostra, a sobrevida global (OS) do câncer glótico T1N0M0 foi em média de 7.706 anos (IC 95% 6,63 - 8,78). Aos 5 anos, a OS foi de 77,5% (± 7%) e 62% (± 9,8%) aos 10 anos. A DFS para todos os pacientes correspondeu a 74,6% (± 7,5%) e 63,1% (± 9,8%), aos 5 e 10 anos, respectivamente. As medianas de OS e DFS para os grupos não foram alcançadas. Conclusões: OS e DFS em nosso ambiente é comparável ao relatado na literatura internacional. As medianas de SG e SLD não foram alcançadas, pelo que se pode afirmar que esta doença apresenta, quando realizado tratamento adequado, um bom prognóstico vital aos 10 anos. É necessário um acompanhamento mais longo para determinar a mediana da SG e da SLD dos grupos de estudo.

Oncological outcomes and failure patterns of laser cordectomy in recurrent glottic cancer.

PURPOSE: Laser cordectomy is a widely accepted treatment modality for selected cases of early glottic cancers, but its role as a salvage treatment remains unclear. We aimed to investigate the oncological outcomes and failure patterns of salvage cordectomy. MATERIALS AND METHODS: This was a retrospective cohort study of patients who underwent cordectomy for early glottic cancer between 2013 and 2022 at a tertiary referral center. The main outcome measures were overall survival, larynx-preservation rate, tracheostomy dependency rate, and disease-free survival. RESULTS: A total of 142 patients (mean age: 63 years, interquartile range [IQR]: 45-72, 123[86.9 %] males) were analyzed. There were 38 (26.8 %) recurrences after a mean of 22 months (IQR: 17-26). Among them, 25 (17.6 %) underwent salvage cordectomy, while 13 (9.1 %) received other salvage treatments (11[7.7 %] (chemo)radiotherapy and 2[1.4 %] total laryngectomy). In comparison to the other salvage treatments, salvage cordectomy demonstrated lower tracheostomy rates (0 vs. 31 %, p = 0.05), comparable 5-year disease-free survival (62 % vs. 54 %, p = 0.4), higher 5-year larynx preservation rate (92 % vs. 54 %, p = 0.02), and improved 5-year overall survival rate (84 % vs. 62 %, p = 0.01). Factors associated with salvage cordectomy failure were age >60 years (odds ratio [OR]: 1.3, 95 % confidence interval [CI]: 1.15-1.53), smoking continuation (OR: 3.73, 95 % CI: 3.5-4.4), heavy smoking (OR: 1.24, 95 % CI:1.07-2.15), and pT1b + (OR: 2.26, 95 % CI: 2.1-2.9). CONCLUSIONS: Salvage cordectomy offers favorable larynx preservation rates and oncological outcomes for recurrent disease amenable to conservative surgery. Smoking, advanced age, and advanced tumor stages are associated with salvage cordectomy failure.

Management of positive resection margins following transoral laser microsurgery for glottic cancer.

Objectives: The current literature provides limited guidance on the management of positive margins (PMs) following transoral laser microsurgery (TLM) for glottic squamous cell carcinoma (SCC). Long-term data exploring the treatment of PMs with both initial observation and re-resection are limited. Our objective was to determine the optimal treatment for PM patients following TLM for glottic SCC. Methods: Clinical information on glottic SCC patients with PMs following treatment with TLM was prospectively collected at our institution from 2007 to 2018. We use a laryngeal template during the initial TLM where the area of resection is outlined for future reference. Data were compared with univariate analysis and survival plots were generated using the Kaplan-Meier method. Results: A total of 29 patients with PMs were treated with either re-resection (19 patients), close observation (6 patients), or adjuvant radiation alone (4 patients). Re-resection patients had SCC or severe dysplasia on initial margin pathology and 23% with early-stage disease had recurrence (T1-T2). Five (83%) patients who underwent close observation required re-resection based on clinical suspicion of recurrence (confirmed on final pathology), which was significantly different from the re-resection patients (p < .05). Close observation was therefore discontinued as a management of PMs. Four patients (21%) had no residual malignancy on re-resection specimens. Deep margins only accounted for 17% of all PMs. Disease-specific survival for all PM patients at 5 years was 82.4% (SE 9.6%, CI 53.4%-91.6%). Conclusions: Our long-term experience with treating early-stage glottic SCC with TLM supports re-resection as an appropriate management for cases of PMs. Level of Evidence: 4.

Extended partial laryngectomy with functional preservation using the rotational crico-thyrotracheopexy.

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).

Complete response of glottic cancer to intra-arterial infusion chemotherapy combined with radiotherapy: A report of 4 cases.

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 Multimodal Diagnostic Approach Necessary in Detecting Elusive Submucosal Laryngeal Cancer.

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.

The outcome of early-stage glottic carcinoma patients treated with radiotherapy: Egyptian National Cancer Institute (NCI-Egypt) experience.

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.

Is CO2 laser microsurgery better than radiotherapy in early glottic cancer: a meta-analysis.

The choice between radiotherapy (RT) and CO2 laser surgery (CO2-LS) for early glottic cancer remains controversial. We systematically examined electronic databases in order to identify prospective trials comparing patients who had undergone CO2-LS or RT to treat early glottic cancer. Eleven studies involving 1053 patients were included. In the selected literature, the parameter setting of CO2 laser equipment can be summarized as wavelength 10.6 µm, superpulsed mode, continuous setting, power tailored on target structures (1-3 W for subtle resections and 4-15 W for cutting a larger tumor), and approximately 2080-3900 W/cm2 of laser energy. Using RevMan 5.3, we estimated pooled odds ratios (ORs) for dichotomous variables and pooled mean differences (MDs) for continuous variables, along with associated 95% confidence intervals (CIs). The heterogeneity in the treatment variables was measured using Higgins' inconsistency test and expressed as I2 values. The continuous variables were then depicted as histograms developed using PlotDigitizer 2.6.8. Compared to patients treated with CO2-LS, those treated with RT had better jitter (MD 1.27%, 95% CI 1.21 ~ 1.32, P < 0.001), and high scores on the "Grade (MD 6.54, 95% CI 5.31 ~ 7.76, P < 0.001), Breathiness (MD 9.08, 95% CI 4.02 ~ 14.13, P < 0.001), Asthenia (MD 2.13, 95% CI 0.29 ~ 3.98, P = 0.02), and Strain (MD 3.32, 95% CI 0.57 ~ 6.07, P = 0.02)" scale. Patients treated with CO2-LS had worse local control rates (OR 3.14, 95% CI 1.52 ~ 6.48, P = 0.002) while lower incidence of second primary tumor (OR 0.30, 95% CI 0.15 ~ 0.61, P < 0.001). It is hoped that retrospective analysis can provide suggestions for early glottis patients to choose personalized treatment.

Transcriptional subtypes of glottic cancer characterized by differential activation of canonical oncogenic programming.

BACKGROUND: There is a paucity of data concerning molecular heterogeneity among glottic squamous cell carcinoma, and the clinical implications thereof. METHODS: Data corresponding to glottic squamous cell carcinoma were derived from The Cancer Genome Atlas. The Onco-GPS computational methodology was levied to derive four patterns of transcriptional activity and three functional subtypes of glottic cancer. RESULTS: Thirty glottic cancer samples stratified to three distinct oncogenic states (S0-S2) based on a Onco-GPS model containing four transcriptional components (F0-F3). Membership in S2 and association with transcriptional component F0 conveyed an invasive phenotype, with transcriptional activity strongly reflecting EMT programming (including TGF-B and NF-KB signaling). S2 membership also correlated with inferior disease-specific survival (HR 9.027, 95% CI 1.021-79.767), and higher incidences of extracapsular spread and perineural invasion. CONCLUSIONS: We present a functional taxonomy of glottic cancer, with subtypes demonstrating differential upregulation of canonical oncogenic networks and survival implications.