The effect of surgery plus intensity-modulated radiotherapy on treatment in laryngeal cancer: A clinical retrospective study.

PURPOSE: As a common head and neck tumor, laryngeal cancer has attracted heightened attention for its treatment and prognosis. Surgery and radiotherapy were mainly therapeutic approaches in laryngeal cancer, and intensity-modulated radiotherapy (IMRT) was a precision treatment way in radiotherapy. However, the therapeutic effect of surgery plus IMRT in laryngeal cancer was rarely reported. This study aims to determine the effect of IMRT on the treatment of patients with laryngeal cancer. METHODS: A total of 125 patients with laryngeal cancer were collected and retrospectively analyzed based on their clinical data and follow-up results. These patients had a clear treatment plan for surgery and intensity-modulated radiotherapy. RESULTS: Smoking, lymph node metastasis, TNM staging and therapeutic approaches could affect the survival of patients with laryngeal cancer. It was shown that the laryngeal function retention rate in the simple IMRT group was significantly higher than the simple surgery group and surgery plus IMRT group. The 5-year survival rate of surgery plus IMRT, simple surgery and simple IMRT were 82.86%, 53.85% and 43.33%, respectively. The locoregional recurrences rate of surgery plus IMRT, simple surgery and simple IMRT were 14.29%, 34.62% and 43.33%. CONCLUSION: Surgery plus IMRT was a feasible and efficacious treatment technique for patients with laryngeal cancer, which effectively prolong the survival time of patients.

Infiltration of CD1a-positive dendritic cells in advanced laryngeal cancer correlates with unfavorable outcomes post-laryngectomy.

BACKGROUND: The prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established. METHODS: We retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters. RESULTS: Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013). CONCLUSIONS: Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment.

Twenty-year experience with salvage total laryngectomy: lessons learned.

OBJECTIVE: The purpose of this study was to evaluate the outcome of salvage total laryngectomy and identify areas for further improvement. METHOD: A retrospective analysis of all patients who underwent salvage total laryngectomy between January 1999 and December 2018 was performed. RESULTS: Thirty-one patients were identified. The most common primary tumour site was the glottis (83.8 per cent). Early stage (T1-T2) disease was identified in 83.9 per cent of cases. Overall survival at 2 and 5 years post-salvage total laryngectomy was 71 per cent and 45 per cent, respectively. Disease-free survival at 2 and 5 years post-salvage total laryngectomy was 65 per cent and 42 per cent, respectively. The rate of post-salvage total laryngectomy pharyngocutaneous fistula was 29 per cent. CONCLUSION: More than half of patients will not survive beyond five years after salvage total laryngectomy. Regional recurrence was the most common form of failure and death. From this study, elective lateral and central neck dissection is advocated in patients with early laryngeal cancer who present with an advanced recurrence.

Survival and function following pharyngo-laryngo-oesophagectomy in Wales: a twelve-year case series.

OBJECTIVE: Treatment of locally advanced hypopharyngeal cancer can cause significant morbidity and late toxicity. Pharyngo-laryngo-oesophagectomy can achieve adequate surgical margins, but data on survival and functional outcome are limited, especially in Wales. This study aimed to describe mortality, morbidity and functional outcome following pharyngo-laryngo-oesophagectomy in a Welsh population. METHOD: This study was a retrospective case note review of pharyngo-laryngo-oesophagectomy cases in Wales over 12 years. RESULTS: Fifteen patients underwent pharyngo-laryngo-oesophagectomy; all but one underwent gastric pull-up. Median survival and disease-free survival were 17 months (range, 2-53 months) and 14 months. Censored 3-month, 1-year and 3-year survival was 93, 71 and 50 per cent, respectively. Common Terminology Criteria for Adverse Events grading of long-term dysphagia was 1 in 58 per cent, 2 in 33 per cent and 3 in 8 per cent, and 87.5 per cent achieved a 'moderate' or 'good' voice rehabilitation. CONCLUSION: These results demonstrate favourable survival and reasonable functional outcome following pharyngo-laryngo-oesophagectomy, suggesting pharyngo-laryngo-oesophagectomy should be considered in all appropriate surgical candidates.

Oncological and Functional Outcomes of Primary and Salvage Total Laryngectomy.

OBJECTIVES: To evaluate and compare the oncological and functional outcomes of total laryngectomies (TL) performed as first line treatment or for salvage after failure of conservative approaches for treating advanced laryngeal carcinoma (LSCC). STUDY DESIGN: A retrospective cohort study. METHODS: A cohort of 217 patients who underwent TL was divided according to whether the procedure was for primary treatment of their LSCC (101 patients) or for recurrences after conservative surgery or chemo-radiotherapy (116 patients). RESULTS: The overall survival rate and disease-specific survival rate were significantly higher in the primary TL group than in the salvage TL group (P = .04 and P = .01, respectively). The recurrence rate was significantly higher and the disease-free survival (in months) was shorter for patients who had salvage TL than for those who had primary TL (P = .00 and P = .01, respectively). The salvage TL group also included significantly more cases of postoperative pharyngo-cutaneous fistula needing salivary stent positioning, and experienced significantly longer hospital stays than the primary TL group (P = .04 and P = .03, respectively). CONCLUSION: Oncological and functional outcomes of primary TL were significantly better than after salvage TL. If salvage TL was performed after conservative surgery had failed, the oncological and functional results were better than after the failure of organ-preserving protocols. This could justify a first attempt at conservative surgery for intermediate-advanced LSCC in selected cases, reserving chemo-radiotherapy only for patients unsuitable for surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E569-E575, 2021.

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

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

Laryngeal Synovial Sarcoma: A Systematic Review of the Last 40 Years of Reported Cases.

Primary laryngeal synovial sarcoma is an extremely rare tumor predominantly affecting young adults. There are currently no well-defined guidelines to direct investigation and management, and treatment is largely based on what is known for synovial sarcoma of the upper and lower limbs. This PROSPERO-registered study aims to review the diagnostic methods, treatment regimens, and survival outcomes for patients with synovial sarcoma of the larynx. A systematic search of databases Medline, Embase, SCOPUS, and Web of Science was undertaken in December 2017. The literature search identified 1031 potentially relevant studies, and after the deletion of duplicates and excluded papers, 98 full-text articles were screened. A total of 39 cases were reviewed from 32 studies in the data extraction. The average age at the time of laryngeal synovial sarcoma diagnosis was 32 years (range, 11-79 years). In all cases (n = 39), patients underwent wide surgical excision, with 20 patients requiring a partial or total laryngectomy. A total of 18 patients received adjuvant and 3 received neoadjuvant radiotherapy. Chemotherapy was used in 10 cases, with ifosfamide the most frequently used agent. There was considerable variability in the order and combinations of the abovementioned treatments. No clinicopathologic factors or treatment regimens were associated with improved overall survival or lower rate of recurrence. There is a paucity of literature and heterogeneity in clinical approaches to this highly aggressive sarcoma. Reporting of cases must be standardized and formal guidelines must be established to guide clinical management.

Oncologic and functional outcomes following laryngectomy for locally advanced thyroid cancer.

BACKGROUND AND OBJECTIVES: Total laryngectomy in thyroid cancer is controversial. Functional and oncologic outcomes are needed to inform surgical indications in this population. METHODS: A retrospective cohort study was performed at a tertiary referral center from 1997 to 2018 to identify patients with a diagnosis of thyroid carcinoma who underwent total laryngectomy. Complications, survival outcomes, and functional outcomes were analyzed. RESULTS: Thirty patients met the inclusion criteria. The mean age was 62 years (range, 30-88 years) and the male-to-female ratio was 1:2.75. The most common diagnosis was well-differentiated thyroid cancer (53.3%), followed by poorly differentiated (30%) and anaplastic (16.7%). Total laryngectomy was performed with a 10% rate of Clavien-Dindo Grade III-V complications. The median overall survival was 40 months (range, 1-237). Five-year overall survival was 39.5% and disease-specific survival was 51.1%. Locoregional control was achieved in 80.0% of patients. Twelve months postoperatively, 100% of surviving patients were taking oral intake and 86.4% had a self-reported functional voice. CONCLUSION: Total laryngectomy for locally advanced thyroid cancer is safe and provides acceptable rates of locoregional control. While the risk of distant metastases remains high, advances in systemic therapy may justify aggressive local control strategies to improve the quality of life.

Prognostic implications of Fibroblast growth factor receptor 1 (FGFR1) gene amplification and protein overexpression in hypopharyngeal and laryngeal squamous cell carcinoma.

BACKGROUND: The gene encoding fibroblast growth factor receptor 1 (FGFR1) is emerging as a therapeutic and prognostic biomarker in various cancer types, including head and neck squamous cell carcinoma (SCC). Here, we investigated the clinicopathologic implication of FGFR1 gene amplification and protein overexpression in hypopharyngeal and laryngeal SCC. METHODS: Fluorescence in situ hybridization and immunohistochemistry were performed to determine FGFR1 gene amplification and protein overexpression in 209 surgically resected cases. RESULTS: FGFR1 amplification observed in 8 (8/66, 12.1%; 6 hypopharynx and 2 larynx) patients and high FGFR1 expression in 21 (21/199, 10.6%) patients significantly correlated with lymph node metastasis and advanced pathological stages. FGFR1 amplification was also associated with worse disease-free survival in multivariate analysis (hazard ratio = 4.527, P = 0.032). High FGFR1 expression was more frequently observed, consistent with the worsening of the degree of histologic differentiation. CONCLUSIONS: FGFR1 amplification may serve as an independent prognostic factor for disease-free survival in hypopharyngeal and laryngeal SCC. Aberrant FGFR signaling caused by FGFR1 gene amplification or protein overexpression may play a crucial role in the malignant evolution and progression of hypopharyngeal and laryngeal SCC, and offer novel therapeutic opportunities in patients with hypopharyngeal and laryngeal SCC that usually lack specific therapeutic targets.

Tumor radiomic features complement clinico-radiological factors in predicting long-term local control and laryngectomy free survival in locally advanced laryngo-pharyngeal cancers.

OBJECTIVE: To study if pre-treatment CT texture features in locally advanced squamous cell carcinoma of laryngo-pharynx can predict long-term local control and laryngectomy free survival (LFS). METHODS: Image texture features of 60 patients treated with chemoradiation (CTRT) within an ethically approved study were studied on contrast-enhanced images using a texture analysis research software (TexRad, UK). A filtration-histogram technique was used where the filtration step extracted and enhanced features of different sizes and intensity variations corresponding to a particular spatial scale filter (SSF): SSF = 0 (without filtration), SSF = 2 mm (fine texture), SSF = 3-5 mm (medium texture) and SSF = 6 mm (coarse texture). Quantification by statistical and histogram technique comprised mean intensity, standard-deviation, entropy, mean positive pixels, skewness and kurtosis. The ability of texture analysis to predict LFS or local control was determined using Kaplan-Meier analysis and multivariate cox model. RESULTS: Median follow-up of patients was 24 months (95% CI:20-28). 39 (65%) patients were locally controlled at last follow-up. 10 (16%) had undergone salvage laryngectomy after CTRT. For both local control & LFS, threshold optimal cut-off values of texture features were analyzed. Medium filtered-texture feature that were associated with poorer laryngectomy free survival were entropy ≥4.54, (p = 0.006), kurtosis ≥4.18; p = 0.019, skewness ≤-0.59, p = 0.001, and standard deviation ≥43.18; p = 0.009). Inferior local control was associated with medium filtered features entropy ≥4.54; p 0.01 and skewness ≤ - 0.12; p = 0.02. Using fine filters, entropy ≥4.29 and kurtosis ≥-0.27 were also associated with inferior local control (p = 0.01 for both parameters). Multivariate analysis showed medium filter entropy as an independent predictor for LFS and local control (p < 0.001 & p = 0.001). CONCLUSION: Medium texture entropy is a predictor for inferior local control and laryngectomy free survival in locally advanced laryngo-pharyngeal cancer and this can complement clinico-radiological factors in predicting prognosticating these tumors. ADVANCES IN KNOWLEDGE: Texture features play an important role as a surrogate imaging biomarker for predicting local control and laryngectomy free survival in locally advanced laryngo-pharyngeal tumors treated with definitive chemoradiation.

Prognostic Analysis of Preoperative Inflammatory Biomarkers in Patients With Laryngeal Squamous Cell Carcinoma.

OBJECTIVE: The purpose of this study was to demonstrate the prognostic role of inflammatory biomarkers in patients with laryngeal squamous cell carcinoma. METHODS: For this study, we enrolled 151 patients who had undergone surgery for laryngeal squamous cell carcinoma. We assessed the preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume, red cell distribution width, and alkaline phosphatase. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were conducted on overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival of patients with laryngeal squamous cell carcinoma. RESULTS: Both Kaplan-Meier analysis and univariate analysis showed significant prognostic differences with age, laryngectomy methods, Tumor Node Metastasis (TNM) staging, tumor location, NLR, PLR, MLR, and mean platelet volume. Multivariate analysis indicated that NLR (overall survival: hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 1.28-7.10, P = .011), PLR (overall survival: HR = 0.33, 95% CI: 0.14-0.78, P = .011; progression-free survival: HR = 0.016,95% CI: 0.10-0.79, P = .016), and MLR (overall survival: HR = 0.29, 95% CI: 0.11-0.76, P = .012) were independent prognostic factors for 5-year survival. However, red cell distribution width and alkaline phosphatase had no significant difference in overall survival and progression-free survival. CONCLUSIONS: Preoperative high NLR, PLR, and MLR were associated with poor prognosis. They were found to be effective and reliable inflammatory biomarkers for patients with laryngeal squamous cell carcinoma.

Oncological results of salvage laryngectomy in patients with laryngeal carcinoma. / Resultados oncológicos de la laringectomía de rescate en pacientes con carcinomas escamosos de laringe.

OBJECTIVE: To analyse the oncological results of a salvage total laryngectomy in patients with a laryngeal carcinoma. MATERIAL AND METHODS: Retrospective review of a cohort of 241 patients treated with a salvage laryngectomy after a local recurrence. The initial treatment received by these patients was radiotherapy (n=201, 83.4%), chemoradiotherapy (n=19, 7.9%), and partial surgery (n=21, 8.7%), RESULTS: Total laryngectomy as salvage treatment achieved local control of the disease in 81.3% of cases, with a 5-year specific survival of 65.3%. The variables related with specific survival in a univariate analysis were the location of the primary tumour, the local extension of the initial tumour and of the recurrence, the resection margins, and the pathological status of the neck dissections. According to the results of a multivariate analysis, the variables related to specific survival were the status of the resection margins, the presence of simultaneous regional recurrence, and the local extension of the recurrence. CONCLUSION: The 5-year specific survival of patients treated with a salvage laryngectomy was 65.3%. The variables related with the control of the disease were the status of the resection margins, the presence of simultaneous regional recurrence and the local extension of the recurrence.

The Effect of Extranodal Extension on Survival in Laryngeal Carcinoma.

It is known that lymph node metastasis lowers the survival rates in laryngeal carcinoma. This study aimed to investigate the effect of extranodal extension in lymph node metastasis on survival. The demographic characteristics and histopathologic results of 81 patients who underwent total laryngectomy and neck dissection due to advanced larynx squamous cell carcinoma between 2011 and 2018 were reviewed retrospectively. The patients were divided into 3 groups by lymph node metastasis status as reactive lymph node (group 1), lymph node metastasis without detected extranodal extension (group 2), and lymph node metastasis with detected extranodal extension (group 3). Survival analysis was performed between these 3 groups. In the patient population with a mean age of 61.56 years consisting of 6 females and 75 males, demographic characteristics between groups were comparable. Overall survival (OS) rates were detected to be 81% in group 1, 69.2% in group 2, and 61.5% in group 3. Two-year OS rates were detected to be 66.7% in group 1, 46.2% in group 2, and 38.5% in group 3. Statistical difference was detected between group 1 and group 3 both for OS and 2-year OS (P = .014, P = .008, respectively). No statistical difference was detected between group 2 and group 1, and between group 2 and group 3. In this study, we found a negative effect of detecting neck lymphadenopathy metastasis and extranodal extension on survival in patients who underwent total laryngectomy and neck dissection due to advanced laryngeal carcinoma.

Primary Laryngectomy Versus Salvage Laryngectomy: A Comparison of Outcomes in the Chemoradiation Era.

OBJECTIVE: To compare primary total laryngectomy (TL) versus salvage TL and analyze the functional outcomes, complications, recurrence rates, and survival. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: Fifteen-year retrospective analysis of 208 patients with laryngeal squamous cell carcinoma treated by TL was completed. Outcome measures included survival, swallowing rehabilitation, speech rehabilitation, complications, and assessment of comorbidity. Survival estimates were analyzed with Kaplan-Meier method, and regression analysis utilized the Cox proportional hazards model. RESULTS: Alaryngeal speech was not significantly different between primary TL and salvage TL, 68% versus 82% (P = 0.14). Comparing primary and salvage TL, the perioperative complication rate was 33% versus 48% (P = 0.036). Thirty-six percent of primary TL patients had recurrence compared to 26% of salvage patients. Five-year overall survival rates between primary TL and salvage TL were not significantly different (P = 0.68). Comorbidity was an independent predictor of survival. CONCLUSIONS: Development of a functional voice was not significantly different between salvage and primary TL patients, with a majority achieving alaryngeal speech. Perioperative complications were more prevalent in the salvage TL group. Recurrence and survival are significantly associated with comorbidity status. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2179-2185, 2020.

Long-term functional outcome after laryngeal cancer treatment.

BACKGROUND: The functional outcome after the treatment of laryngeal cancer is tightly related to the quality of life of affected patients. The aim of this study is to describe the long-term morbidity and functional outcomes associated with the different treatment modalities for laryngeal cancer. METHODS: Retrospective chart review of 477 patients undergoing curatively intended treatment for laryngeal cancer at our tertiary referral center from 2001 to 2014: Details on patient and disease characteristics, diagnostics and treatment related functional outcomes were analyzed. RESULTS: With a median follow-up of 51 months, the crude rate of functional larynx preservation was 74.6%. Radiotherapy +/- chemotherapy was the dominant treatment modality (n = 359-75.3%), whereas 24.7% (n = 118) underwent primary surgery, with 58.5% (69) receiving adjuvant treatment. The 5-year laryngectomy-free survival was 57% (95% CI, 48-66%) after surgery vs. 69% (95% CI, 64-75%) after chemoradiotherapy (p < 0.01). In stage III-IVB, these rates were 26% (95% CI, 16-39%) vs. 47% (95% CI, 36-59%), respectively (p < 0.01). Aspiration occurred in 7%, tracheostomy was necessary in 19.8% and feeding tube placement in 25.4%. Feeding tube and tracheostomy necessity was higher in the initially surgically treated group. Primary surgery (HR: 1.67, 95% CI: 1.19-2.32; p < 0.01), stage III-IVB (HR: 4.07, 95% CI: 2.97-5.60; p < 0.01) and tumor recurrence (HR: 3.83, 95% CI: 2.79-5.28; p < 0.01) remained as adverse factors for laryngectomy-free survival. CONCLUSIONS: Preserving the laryngeal function after cancer treatment is challenging. Advanced tumor stages, primary surgery and recurrence are related to a poor functional outcome. Therefore, the criteria for initial decision-making needs to be further refined.

Total laryngopharyngectomy with circumferential reconstruction: Helsinki institutional study.

PURPOSE: Surgical complications after total laryngopharyngectomy (TLP) are common, reconstruction is challenging, and patients often lose their ability to swallow and speak. To evaluate these aspects, we analysed outcome after TLP. METHODS: We reviewed all patients who underwent TLP and subsequent circumferential pharyngeal reconstruction through 2004-2017 at the Helsinki University Hospital. RESULTS: For the 26 eligible patients, TLP was the primary treatment for 11 and salvage surgery for 15, followed by reconstruction with free flaps in 22 patients and pedicled flaps in 4. An early (≤ 30 days) pharyngocutaneous fistula developed in seven patients (27%; median time 13 days; range 6-26), and a late (> 30 days) fistula in five patients (19%; median time 370 days; range 46-785). In addition, ten patients (39%) developed an oesophageal stricture. Four patients (15%) resumed full oral feeding. A speech prosthesis was inserted for 15 patients (58%) and most of them could produce intelligible speech. We found acceptable survival figures for patients undergoing TLP both as a primary treatment and as salvage procedure: the overall survival at 1 year was 82% and 67%, and at 5 years 33% and 27%, respectively. Disease-specific survival at 1 year was 90% and 70%, and that at 5 years was 45% and 43%, respectively. CONCLUSIONS: Despite fair survival, TLP carries a high risk for postoperative complications with limited functional outcome, thus necessitating cautious patient selection and surgical experience.

Failed larynx preservation and survival in patients with advanced larynx cancer.

PURPOSE: To evaluate the survival benefit of total laryngectomy (TL) after induction chemotherapy in locally advanced laryngeal cancer patients. MATERIALS AND METHODS: This is a retrospective study utilizing the National Cancer Database, which captures >80% of newly diagnosed head and neck squamous cell carcinoma cases in the United States. We included patients diagnosed with advanced stage laryngeal squamous cell carcinoma between 2004 and 2013 (n = 5649) who received either TL (n = 4113; 72.8%) or induction chemotherapy followed by either radiation therapy (n = 1431) or TL (n = 105). Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate overall survival. A Cox regression model was computed to examine how the prognostic impact of treatment differed by clinical stage. RESULTS: In multivariable analysis, when compared to patients receiving TL alone, those receiving induction chemotherapy followed by TL experienced no significant difference in survival (HR 0.85, 95% CI 0.63-1.13), while those receiving induction chemotherapy followed by radiation experienced poorer survival (HR 1.15, 95% CI 1.06-1.26). Induction chemotherapy followed by TL was associated with improved survival compared to induction chemotherapy and radiation (P = .042). Among patients with T4a tumors, TL (P < .001) and induction chemotherapy followed by TL (P = .002) were both associated with improved survival compared to induction chemotherapy and radiation. There were no survival differences between TL and induction chemotherapy followed by TL (HR 0.76, 95% CI 0.52-1.10). CONCLUSIONS: Larynx preservation may be attempted without compromising survival in patients with locally advanced larynx cancer who fail induction chemotherapy and undergo TL.

Elective Paratracheal Lymph Node Dissection in Salvage Laryngectomy.

BACKGROUND: Indications for and efficacy of paratracheal nodal dissection (PTND) in patients undergoing laryngectomy (salvage) for persistent or recurrent laryngeal squamous cell carcinoma are not well-defined. METHODS: A retrospective cohort study was performed for patients undergoing salvage laryngectomy with clinically and radiographically negative neck disease between 1998 and 2015 (n = 210). Univariate and multivariate Cox regression analyses were performed. RESULTS: PTND was performed on 77/210 patients (36%). The PTND cohort had a greater proportion of advanced T classification (rT3/rT4) tumors (78%) than subjects without PTND (55%; p = 0.001). There was a 14% rate of occult nodal metastases in the paratracheal basin; of these, 55% did not have pathologic lateral neck disease. Multivariate analysis controlling for tumor site, tumor stage, and pathologic lateral neck disease demonstrated that PTND was associated with improved overall survival [OS] (p = 0.03; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.38-0.96), disease-free survival [DFS] (p = 0.03; HR 0.55, 95% CI 0.31-0.96), and distant DFS survival (p = 0.01; HR 0.29, 95% CI 0.11-0.77). The rate of hypocalcemia did not differ between subjects who underwent bilateral PTND, unilateral PTND, or no PTND (p = 0.19 at discharge, p = 0.17 at last follow-up). CONCLUSIONS: PTND at the time of salvage laryngectomy was more common in patients with rT3/rT4 tumors and was associated with improved OS and DFS, with no effect on hypocalcemia. In patients undergoing PTND, the finding of occult paratracheal metastases was often independent of lateral neck metastases.

Nonsquamous cell laryngeal cancers: Incidence, demographics, care patterns, and effect of surgery.

OBJECTIVES: To analyze the incidence and clinical profile of nonsquamous cell (non-SCC) laryngeal carcinomas and to analyze the effect of surgery on survival. STUDY DESIGN: A retrospective analysis of the National Cancer Database (2004-2014). METHODS: Adult patients with non-SCC laryngeal cancers were divided into six major histological subtypes. A descriptive clinical profile was obtained for non-SCC patients, and multivariate regressions were performed to analyze the effect of surgery on survival within the non-SCC cohort. RESULTS: We identified 878 cases of non-SCC laryngeal cancers, representing 1.02% of all malignant laryngeal cancers. Neuroendocrine tumors and bone/cartilage sarcomas made up the largest groups (37.02% and 32.35%, respectively). Metastasis (M) was higher in neuroendocrine tumors, representing 19.1% of those with known clinical M stages. Of those treated, the majority of patients with bone/cartilage sarcomas (80.9%) and minor salivary gland tumors (82.6%) received surgery as part of their treatment. Survival varied significantly based upon histology, with bone/cartilage sarcomas having the highest 5-year survival at 90.4%, and neuroendocrine tumors exhibiting the poorest 5-year survival at 25.7%. Multivariate analyses found surgery to be significantly associated with improved survival (hazard ratio: 0.679; 95% confidence interval: 0.472-0.976; P = 0.036). The specific surgical method (i.e., local excision vs. partial vs. total laryngectomy) did not have any effect on survival. CONCLUSION: Approximately 1% of all malignant laryngeal cancers are non-SCC in origin. At presentation, neuroendocrine tumors have the highest rate of distant metastasis and have the worst prognosis of the non-SCC cancers. Most non-SCC patients received surgery as part of their treatment regimen. LEVEL OF EVIDENCE: NA. Laryngoscope, 129:2496-2505, 2019.

Supraglottic Squamous Cell Carcinoma: A Population-Based Study of 22,675 Cases.

OBJECTIVES/HYPOTHESIS: The authors used the Surveillance, Epidemiology, and End Results (SEER) database to analyze epidemiological features of patients presenting with supraglottic squamous cell carcinoma (SCCa) and to evaluate treatment trends and outcomes. METHODS: The SEER database was queried for patients with supraglottic SCCa from 1973 to 2013. Information on demographics; tumor size; histologic grade; American Joint Committee on Cancer (AJCC) stage; SEER local, regional, distant stage; and treatment modality were analyzed. RESULTS: There were 22,675 cases of primary supraglottic SCCa identified. The mean age at diagnosis was 62.3 years, with males accounting for 70.3% of all cases. A high percentage of patients presented with stage IV disease (44.9%). The most common treatment modality was radiotherapy (46.6%), followed by combination of surgery and radiotherapy (29.2%) and surgery alone (15.0%). Overall 5-year disease-specific survival (DSS) for all cases was 54.0%. When stratified by treatment modality, 5-year DSS was best for patients receiving surgery alone (64.2%). However, for patients with AJCC stage IV disease, survival was significantly better with combined surgery and radiotherapy (52.5%). CONCLUSION: In general, supraglottic SCCa is treated most commonly with radiotherapy, followed by surgery and radiotherapy. Patients managed surgically had better 5-year DSS when compared to patients treated by other modalities. However, when stratified by stage, patients with AJCC stage IV disease had significantly better survival with combined surgery and radiotherapy. Of patients receiving surgery, supraglottic laryngectomy was found to have a significantly better 5-year DSS when compared to both total laryngectomy and laryngectomy, not otherwise specified. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1822-1827, 2019.