Advanced Laryngeal Carcinoma Research Articles

Diagnostic impact of 18F-FDG PET/CT imaging on the detection of immune-related adverse events in patients treated with immunotherapy.

Immunotherapy is an effective treatment method for cancer cells with humoral and cellular immune mechanisms of action but triggers an inflammatory response and disrupts standard protective immune tolerance. Early detection of immune-related adverse events (irAEs) on PET/CT is crucial for patient management and subsequent therapy decisions. In this study, we aimed to evaluate the impact of 18F-FDG PET/CT on detecting of irAEs in patients receiving immunotherapy. Forty-six patients with advanced RCC (n: 32), malign melanoma (n: 9), lung cancer (n: 4), and laryngeal carcinoma (n: 1), who underwent 18F-FDG PET/CT imaging for response assessment after immunotherapy, were enrolled in the study. Newly detected findings associated with irAEs on posttreatment PET/CT images were compared with the pretreatment PET/CT, both qualitatively and semi-quantitatively. Twenty-eight (61%) patients developed irAEs as observed on PET/CT. Enteritis/colitis was the most frequent irAE visualized on PET/CT with 13 patients (28.2%), followed by gastritis (17.3%), thyroiditis (13%), and myositis/arthritis (13%). Hepatitis (6.5%), pneumonitis (6.5%), sarcoid-like reaction (4.3%), and hypophysitis (4.3%) were observed to a lesser extent. The median time between the appearance of irAEs on PET/CT and the initiation of immunotherapy was 4.3months. There were no significant differences in age, sex, and treatment response status of patients with and without irAEs. 18F-FDG PET/CT plays a fundamental role in cancer immunotherapy with the potential to show significant irAEs both in the diagnosis and in follow-up of irAEs. IrAEs were present on PET/CT images of more than half of the patients who received immunotherapy in our study.

Predictors of Thyroid Gland Invasion in Total Laryngectomy for Advanced Laryngeal Squamous Cell Carcinoma.

Objectives: Thyroidectomy for advanced laryngeal squamous cell carcinoma (LSCC) is controversial. This study aimed to identify predictors of thyroid gland invasion in patients with LSCC and management of the thyroid gland during total laryngectomy. Patients and Methods: Clinical data and pathological characteristics of 113 patients, who underwent laryngectomy with thyroidectomy for advanced LSCC in Guangdong Provincial People's Hospital between 2009 and 2019, were retrospectively analyzed. The incidence and predictors of thyroid gland invasion were analyzed, and a new predictor was proposed using a parallel test. Results: Of 113 patients, 25.7% exhibited thyroid invasion. A new predictor that combined the lower third of thyroid cartilage invasion and thyroid gland invasion on computed tomography/magnetic resonance imaging (CT/MRI) was associated with pathological thyroid gland invasion (P = 0.001; sensitivity, 88.2%; negative predictive value, 95%). Conclusion: Thyroidectomy may be required during total laryngectomy in those with invasion of the lower third of thyroid cartilage and/or thyroid gland invasion revealed on CT/MRI instead of being performed routinely.

Circular RNA MTCL1 promotes advanced laryngeal squamous cell carcinoma progression by inhibiting C1QBP ubiquitin degradation and mediating beta-catenin activation

BackgroundCircular RNAs (circRNAs) are involved in regulatory processes of ubiquitination and deubiquitination in various tumors at post-transcriptional epigenetic modification level. However, the underlying mechanism and its biological functions of circRNAs in the advanced laryngeal squamous cell carcinoma (LSCC) remain obscure.MethodsRNA sequencing and quantitative real-time PCR (qRT-PCR) assays were applied to screen for circRNAs differentially expressed in LSCC tissues and cell lines. The candidate RNA-binding proteins and target signalling pathway were detected by RNA pull-down and mass spectrometry, in situ hybridization (ISH), immunohistochemistry (IHC), qRT-PCR assays, and bioinformatics analysis. The functional roles of these molecules were investigated using in vitro and in vivo experiments including EdU, transwell, wound healing, western blot assays, and the xenograft mice models. The molecular mechanisms were identified using RNA pull-down assays, RNA immunoprecipitation (RIP), Co-IP, ISH, Ubiquitination assay, bioinformatics analysis, and the rescue experiments.ResultsHere, we unveil that microtubule cross-linking factor 1 circRNA (circMTCL1, circ0000825) exerts its critical oncogenic functions by promoting complement C1q-binding protein (C1QBP)-dependent ubiquitin degradation and subsequently activating Wnt/β-catenin signalling in laryngeal carcinoma initiation and development. Specifically, circMTCL1 was remarkably up-regulated in the paired tissues of patients with LSCC (n = 67), which predicted a worse clinical outcome. Functionally, circMTCL1 exerted oncogenic biological charactersistics by promoting cell proliferative capability and invasive and migrative abilities. Ectopic circMTCL1 augumented cell proliferation, migration, and invasion of LSCC cells, and this effect could be reversed by C1QBP knocking down in vitro and in vivo. Mechanistically, circMTCL1 directly recruited C1QBP protein by harboring the specific recognized sequence (+ 159 − + 210), thereby accelerating the translation of C1QBP expression by inhibiting its ubiquitin–proteasome-mediated degradation. Importantly, the direct interaction of C1QBP with β-catenin protein was enhanced via suppressing the β-catenin phosphorylation and accelerating its accumulation in cytoplasm and nucleus.ConclusionOur findings manifested a novel circMTCL1-C1QBP-β-catenin signaling axis involving in LSCC tumorigenesis and progression, which shed new light on circRNAs-ubiquitous acidic glycoprotein mediated ubiquitin degradation and provided strategies and targets in the therapeutic intervention of LSCC.

The importance of weight loss during definitive radiotherapy in patients with laryngeal carcinoma.

The aim of this study is to determine the prognostic significance of weight loss (WL) on overall survival (OS) and progression-free survival (PFS) in patients with locally advanced unresectable laryngeal carcinoma undergoing definitive radiotherapy (RT) or chemo-RT (CRT) in a single institution. One hundred and thirty-two patients with newly diagnosed locally advanced laryngeal carcinoma were included in this study retrospectively. All patients were treated with definitive RT or CRT. The tumor and metastatic lymph nodes received 70 Gy. Subclinical disease (low-risk and high-risk area) was irradiated 50-60 Gy prophylactically. Unintentional WL ≥5% was defined as the "critical level." Bodyweight was evaluated on the 1st day of RT and once a week during RT. Caloric needs were calculated as 25-30 kcal/kg/day. Median follow-up was 17.8 months (range: 2.35-85 months). During treatment, there was a statistically significant WL in patients (P = 0.004). WL was ≥5% in 62 (47%) of the patients. There was a statistically significant relationship between WL and tumor differentiation (P = 0.004), completion of treatment (P = 0.004), WHO performance status (P < 0.0001), T stage (P = 0.003), N stage (P = 0.049), and supraglottic tumor location (P = 0.005). In the univariate analysis, WL, WHO performance status, T stage, N stage, tumor localization, and tumor differentiation, were seen to affect OS. Additionally, WL, WHO performance status, N stage, and tumor differentiation were prognostic factors for PFS. In the multivariate analysis, it was observed that only WL and WHO performance status were significant factors for both OS (P = 0.001, and P < 0.01) and PFS (P < 0.001, and P < 0.001), respectively. Three-year OS and PFS was 50.3% and 19.5% for patients with WL versus 77.8% and 49.0% for patients without WL. It is clear that WL has prognostic significance in patients who have undergone definitive RT or CRT due to locally advanced laryngeal carcinoma. In particular, it should be taken into consideration that patients with supraglottic tumor, lymph node involvement, and poor performance status are at greater risk for WL.

Analysis of the pathological characteristics of locally advanced laryngeal carcinoma in Egyptian females: 7-year review

BackgroundStudy the pathological features, extent of treatment, and epidemiological distribution of laryngeal carcinoma among Egyptian female patients.ResultsThe study population consisted of 34 female patients treated for laryngeal cancer at the Otolaryngology Department, Faculty of Medicine, Cairo University, between 2011 and 2017. The data were collected in a retrospective manner, based on the analysis of patients’ medical records. The mean age of the total cohort is 56.5 years. Twenty-six patients (76.5%) had supraglottic carcinoma, 7 patients (20.5%) had glottic carcinoma, and only 1 patient (3%) had subglottic tumor. The regional disease of the neck affected 18% of the patients. Ninety-one percent of the patients showed a moderate degree of tumor differentiation.ConclusionThere may be important gender differences in laryngeal sub-site incidence for patients with laryngeal carcinoma.

Role of CSE1L expression in determining recurrence and survival of laryngeal tumors.

The correlation of CSE1L (human chromosomal segregation 1-like) staining intensity with disease-free survival, disease recurrence and development of distant metastases in Advanced Laryngeal Tumors. Specimens of patients with advanced glottic larynx cancer (T3, T4) were evaluated for nuclear CSE1L staining intensity. According to mild, moderate and severe CSE1L staining, patients were compared in terms of disease-free survival, disease recurrence and development of distant metastases. 17 of the 57 patients died within 5years, distant metastases developed in 5 patients, and recurrence in 5 patients. Of the 17 patients who died within 5years, 10(%59) showed severe staining with CSE1L, 6 (%35) showed moderate staining, and only 1 (%6) patient showed mild staining. 4 (%80) out of 5 patients who developed distant metastases were those with moderate staining with CSE1L. Metastases did not develop in any patient who stained poorly with CSE1L. 2 (%40) of the 5 patients who developed relapse were patients with severe staining with CSE1L, while 3 (%60) were patients with moderate staining with CSE1L. No recurrence was observed in any patient with mild staining with CSE1L. CSE1L will help in demonstrating the increased risk of distant metastasis, increased recurrence probability and shortened life expectancy of advanced laryngeal carcinoma.

Routine thyroidectomy with total laryngectomy: Is it really indicated? A randomized controlled trial

BackgroundWe investigated the incidence of thyroid gland invasion in patients with advanced laryngeal carcinoma who were treated with total laryngectomy, also the impact of different preoperative and intraoperative predictors on thyroid gland invasion. Moreover, the impact of thyroid gland preservation on the locoregional tumor control and the recurrence rates after surgery were investigated. Materials and methodsThis study was conducted over 5 years on 100 patients with advanced laryngeal carcinoma who underwent total laryngectomy. The adopted protocol in our hospital is to perform an ipsilateral thyroid lobectomy if there is subglottic extension, thyroid or cricoid cartilage invasion or true invasion of the thyroid gland. The patients of the study were divided into thyroid sparing and thyroid sacrificing groups. The two groups were compared in terms of demographic data, tumor characteristics, incidence of postoperative hypothyroidism and tumor recurrence. ResultsThere was no significant difference between groups regarding the tumor profile. Regarding local tumor spread, the only two subsites that showed significant difference is anterior commissure and thyroid cartilage invasion. In the thyroid sacrificing group, invasion of the thyroid gland was proved histopathologically in only one patient. Postoperatively, the incidence of hypothyroidism was significantly higher in the thyroid sacrificing group. However, there was no statistically significant difference between the two groups regarding the incidence of tumor recurrence. ConclusionThe incidence of thyroid gland invasion by an advanced laryngeal carcinoma is low. Preservation of the thyroid gland during laryngectomy to reduce the risk of thyroid dysfunction does not affect the oncological control.

Dexmedetomidine and emergency front of neck access for acute stridor in advanced laryngeal carcinoma: Anesthetic challenges

Supraglottic airway obstruction due to airway malignancy resulting in respiratory distress is a medical emergency requiring urgent re-establishment of airway patency, with tracheostomy to alleviate the stridor and threat to life. We report a 61-year-old male patient who presented with acute stridor, dyspnea, and a left-sided metastatic neck mass to the emergency room. The patient was rushed to the operation theater for emergency tracheostomy under monitored anesthesia care. We hereby discuss a successful surgical cricothyroidotomy, post failed emergency tracheostomy under dexmedetomidine infusion.

Relationship of E-cadherin, Beta-catenin, N-cadherin, ZEB1 and αSMA as Epithelial Mesenchymal Transition markers with prognostic factors in early and advanced stage laryngeal squamous cell carcinomas.

To investigate the relationship between E-cadherin, beta-catenin, N-cadherin, ZEB1, and αSMA as epithelial-mesenchymal transformation markers with tumor stage, lymph node metastasis (LNM), and overall survival (OS) in laryngeal squamous cell carcinomas (LSCC). A total of 100 cases diagnosed with LSCC were included in the study. Data about the lymphovascular invasion (LVI), perineural invasion (PNI), necrosis, and LNM were recorded by evaluating hematoxylin-eosin-stained slides. Markers of E-cadherin, beta-catenin, N-cadherin, ZEB1, and αSMA were applied to the sections prepared from paraffin blocks of tumor samples. Ninety-five male and five female patients were included in the study, and 38 of them exited. A significant relationship was observed between OS with advanced tumor stage, presence of LNM and PNI. A significant relationship was found between increased tumor Zeb1 expression and advanced tumor stage. In univariate and multivariate analyses, a significant negative relationship with OS, and increased Zeb1 expression in tumor and tumor stroma was seen. Any relationship was not observed between E-cadherin, beta-catenin, N-cadherin, and αSMA and OS. Among the EMT markers, we evaluated in our study, it was seen that Zeb1, which is an EMT transcription factor, is associated with tumor stage, LNM, and OS. Remarkably, Zeb1 expression observed in tumor stroma was also significant for OS. Any similar data reported for LSCCs have not been encountered in the literature, and it was thought that it would be appropriate to support our findings with further studies to be performed on this subject.

A Pilot Study on Immunohistochemical Expressions of NF-ĸB, Cyclin-D1, VEGF, and Cox-2 in Advanced Stage Laryngeal Carcinoma

BACKGROUND: Progression of laryngeal carcinoma can be classified with the clinical staging, however there are different patterns of progressions observed in the patient with the same clinical stage which also affects their prognoses. Therefore biomarkers should be used. Nuclear factor (NF)-ĸB, Cyclin-D1, vascular endothelial growth factor (VEGF), cyclooxygenase (Cox)-2 have been reported for laryngeal carcinoma. However, it is still unclear how these markers are expressed and correlated in advanced stage laryngeal carcinoma. Therefore current study was conducted to investigate the expressions of NF-ĸB, Cyclin-D1, VEGF and Cox-2 and their correlations in advanced stage laryngeal carcinoma.METHODS: Subjects were recruited and laryngeal biopsies were collected, fixed in formalin and prepared for immunohistochemistry. The immunohistochemistry was performed using mouse monoclonal anti-NF-kB p65, anti-Cyclin-D12 anti-VEGF, and anti-Cox-2 antibodies. The immunohistochemistry results were documented and measured using ImmunoRatio. Pearson or Spearman correlation test was used based on the results of Shapiro-Wilk test of normality. A p-value of less than 0.05 is considered statistically significant.RESULTS: Twelve male subjects were included in this study. Expressions of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 were clearly observed. Mean of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 IHC expression levels measured with ImmunoRatio were 57.50±20.06%, 45.00±24.31%, 43.33±17.23% and 40.42±16.98%, respectively. There was significant correlation between the expressions of VEGF dan Cox-2 (p=0.031, r=0.622).CONCLUSION: Since correlation between the VEGF and Cox-2 expressions was statistically significant, VEGF and Cox-2 might have important roles in the growth, invasion and metastasis of laryngeal carcinoma.KEYWORDS: advanced stage laryngeal carcinoma, immunohistochemistry, NF-ĸB, Cyclin-D1, VEGF, Cox-2

Virtual Laryngectomy Club: A Reality.

Total laryngectomy remains an essential treatment for locally advanced laryngeal carcinoma. However, it involves lifestyle changes for the patient, such as the inability to communicate verbally, breathing or aesthetic changes, which affect their quality of life and require comprehensive rehabilitation. Speech rehabilitation is of utmost importance for these patients. Hence to provide comprehensive rehabilitation after total laryngectomy we have been running a successful laryngectomee club at our institute for the benefit of our patients. But when the World Health Organization on March 11, 2020, declared the novel coronavirus (COVID-19) outbreak a global pandemic, many of our patients couldn't make their regular followup visits. We have successfully conducted the first ever online virtual meeting for our laryngectomee club members via video conferencing service.

Comparison of Patients With Total and Salvage Laryngectomy

Introduction and objectivesTotal laryngectomy (TL) is one of the treatments available in locally advanced laryngeal carcinomas or as a salvage therapy when organ preservation fails, achieving high survival rates and few complications. The aim of this study was to analyse the oncological outcomes, comparing the data obtained with the current literature and analysing complications and survival. MethodsThe study included 62 patients with primary carcinoma of the larynx treated by primary or salvage TL between 2003 and 2019. We analysed the demographic, clinical and pathological characteristics, tumour stage, complementary treatments, postoperative complications, locoregional recurrences, metastases, and causes of death. ResultsThe mean age was 64 years, 90.3% were men, 96.8% were smokers, 43.5% had multiple pathologies and 82.3% had a locally advanced stage. Of all TL 71% were primary and 29% salvage. Neck dissection was performed in 59.6%. Lymphovascular invasion was present in 30.6%, perineural invasion in 30.6% and margin involvement in 14.5%. During the follow-up, 17.7% presented locoregional recurrence and 11.3% distant metastases. Regarding complementary treatments, 56.4% of the patients received adjuvant therapy. The incidence of haemorrhage was 11.3%, infection 14.5%, and pharyngocutaneous fistula 21%. There was a statistically significant correlation between fistula and haemorrhage (P = .000) and between fistula and infection (P = .000). No statistically significant differences were found between the studied factors of primary and salvage TL. The 3-year overall survival was 92% and 5-year overall survival was 88%, finding statistical significance with the locally advanced stage (P = .038), T4 (P = .026), lymphovascular invasion (P = .019) and the involvement of more than 3 lymph nodes in the pathological anatomy (P = .005). On the multivariate analysis, the only variable that showed a significant relationship with survival was lymphovascular invasion (P = .026). ConclusionsAlthough organ preservation is a primary objective, TL remains a leading treatment in locally advanced carcinomas and as salvage in case of failure of medical therapy or partial surgery.

Concurrent Immunotherapy With Chemoradiation for Definitive Management of Locally Advanced Laryngeal Cancer: A Prospective Trial

<h3>Purpose/Objective(s)</h3> Cisplatin-based chemoradiation is an established organ-preserving strategy for locally advanced laryngeal squamous cell carcinoma, but long-term survival remains suboptimal, warranting an improved approach. Immunotherapy has been studied in the metastatic and unresectable recurrent setting, but additional data are needed to assess its role in definitive therapy. The study hypothesis was that the use of immunotherapy in conjunction with chemoradiation would be safe and result in improved laryngectomy-free survival (LFS) compared to standard of care chemoradiation. <h3>Materials/Methods</h3> This trial was an open-label, single-arm, prospective, multi-institutional study. The study included a Phase I run-in portion to assess safety in the first 6 enrolled patients and a planned subsequent Phase II component. Due to slow accrual, the study was closed after enrollment of 9 patients and the data were allowed to mature. The primary endpoint of the Phase II portion was LFS at 18 months. Study patients had Stage III or IV (T1-3; N0-3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given as a 200 mg flat dose 3 weeks prior to the start of chemoradiation and was then given q21 days until the completion of chemoradiation. Cisplatin was given at a dose of 100 mg/m² q21 days during radiation with allowed dose modifications for toxicities. Radiation was prescribed to a total dose of 70 Gy in 35 daily fractions using IMRT with an elective nodal dose of 56-63 Gy. <h3>Results</h3> A total of 9 patients with a median age of 54 were enrolled from 2017 to 2019. The median follow-up time was 30.1 months. None of the enrolled patients required laryngectomy, resulting in 100% LFS at 18 months for evaluable patients. The 18-month overall survival (OS) rate was 66.7%; of the 3 patient deaths, 2 were due to co-morbid conditions (diabetes, peripheral arterial disease) rather than malignancy. The remaining 6 patients were alive at the time of last follow-up and the median duration of OS was not reached. There were 27 Grade 3 toxicities, with 2 attributable to pembrolizumab. Nearly all Grade 4 (n = 4) and Grade 5 (n = 1) toxicities occurred in a single patient with poorly-controlled diabetes; the Grade 5 toxicity was due to diabetic ketoacidosis. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation; the edema has since resolved and the tracheostomy was reversed. <h3>Conclusion</h3> The use of concurrent pembrolizumab with chemoradiation for locally advanced larynx cancer resulted in high LFS. Most toxicities were attributable to chemoradiation and the majority of Grade 4 and 5 toxicities occurred in a patient with poorly-controlled diabetes. A case of late Grade 4 laryngeal edema could have been related to immunotherapy. Future studies with concurrent immunotherapy with chemoradiation should account for this possibility.

Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma

BackgroundCompared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear.MethodsWe performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan–Meier and Cox’s proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination.ResultsImmunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively.ConclusionsNuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.

MCM-2, Ki-67, and EGFR downregulated expression levels in advanced stage laryngeal squamous cell carcinoma

We present the conceptual study investigated the capacity of minichromosome maintenance-2 (MCM-2), Ki-67, and epidermal growth factor receptor (EGFR) to assess the severity and progression of laryngeal squamous cell carcinoma (LSCC) disease and to study the correlations among these markers. A total of 30 patients with LSCC with immunohistochemistry (IHC) staining for MCM-2, Ki-67 and EGFR were examined. Mean expression levels of the three markers were evaluated for comparing between early and advanced stages of LSCC. The mean MCM-2, Ki-67, and EGFR expression levels were significantly decreased in advanced-stage compared with early-stage LSCC. Pearson correlation analysis showed a statistically significant correlation between the MCM-2 and Ki-67. Regarding subgroup analyses, MCM-2, Ki-67, and EGFR showed significant differences between early- and advanced-stage LSCC with non-recurrence, while for the recurrent subgroup LSCC, only MCM-2 revealed a significant difference between early- and advanced-stage LSCC. Altogether, these results support the role for downregulation of MCM-2, Ki-67 and EGFR in advanced-stage LSCC and correlation of MCM-2 and Ki-67 expressions that would be a promising strategy to predict prognosis of LSCC including severity and progression. We contextualize our findings and advocate the position of the biological markers, especially MCM-2, as an emerging evaluation tool for LSCC disease.

Tracheoesophageal Voice Rehabilitation after Total laryngectomy: Primary Versus Secondary Tracheoesophageal Puncture

Background: Voice prosthesis is the current standard for post laryngectomy rehabilitation. Several clinical factors can affect the functional outcomes of voice prosthesis. Various complications are recorded with voice prosthesis. Objective: This study aimed to compare the results of primary and secondary provox insertion in patients with advanced laryngeal carcinoma undergoing total laryngectomy. Patients and Methods: Randomized-controlled clinical study included 24 patients with provox voice prosthesis rehabilitation 12 had primary tracheoesophageal puncture and 12 had secondary tracheoesophageal puncture. All patients were evaluated for successful voice restoration and complications rates. Results: Short-term success rate was 92% in the primary group and 83% in the secondary group. Long-term success rate was 83% in the primary group and 75% in the secondary group. Success rates were higher in the primary group but without statistically significant difference. Complications rate in the primary group was 58.3% and in the secondary group 66.6%. Complications rate was higher in the secondary group but without statistically significant difference. Conclusion: Provox voice prosthesis provides consistent and good voice results, which improve with time. Primary provox insertion had better success rates and fewer complications. Periprosthetic leak is the most common complication.

A pilot study reveals the potential of miR-31-3p and miR-196a-5p as non-invasive biomarkers in advanced laryngeal cancer

Recently, miRNAs have become popular molecules used as non-invasive biomarkers in cancer diseases. The aim of the study was to explore the expression of four miRNAs isoforms: miR-31-3p, miR-196a-5p, miR-210-3p and miR-424-5p in plasma and tissue samples from patients with advanced laryngeal squamous cell carcinoma (LSCC) and healthy controls. Fresh-frozen tumour and normal laryngeal tissue as well as plasma samples were obtained from 22 patients diagnosed with advanced LSCC. The control group included plasma samples from 21 cancer-free volunteers. Total RNA (including miRNAs) extraction, reverse transcription and real time qPCR were the laboratory techniques used in the study. The obtained results were analyzed using SPSS software v. 23. We found that miR-31-3p, miR-196a-5p, and miR-210-3p levels were significantly elevated in laryngeal tumour tissue, but only the levels of miR-31-3p and miR-196a-5p were significantly upregulated in the plasma LSCC target group. Positive correlation was obtained for miR-31-3p (rs=0.443, p=0.039) and miR-196a-5p (rs=0.548; p=0.008) between plasma and adjacent tumour tissue LSCC samples. ROC analyses were used to evaluate the discriminative power of both miRNAs alone and in combination. The combination of miR-31-3p and miR-196a-5p showed best results with AUC=0.978 (95% CI: 0.945-1.000, p.

Organ Preservation in Patients With Advanced Laryngeal Tumours. Results of Induction Chemotherapy Versus Chemoradiotherapy in Actual Clinical Practice

Introduction and objectivesA high percentage of patients with locally advanced laryngeal carcinoma are candidates for inclusion in organ preservation protocols. The aim of this study was to compare in actual clinical practice the results of two preservation schemes, induction chemotherapy versus chemoradiotherapy, in patients with locally advanced laryngeal carcinoma. MethodsRetrospective study conducted in 157 patients with locally advanced laryngeal tumours (T3-T4) treated with induction chemotherapy (n=121) or chemoradiotherapy (n=36). ResultsOf the 121 patients who started treatment with induction chemotherapy, 6 died as a result of toxicity, 37 were treated with surgery, and 78 completed the preservation scheme; 36 patients were treated with chemoradiotherapy. There was no significant difference in specific survival at 5 years according to whether the patients had started treatment with either induction chemotherapy or chemoradiotherapy (68.9% versus 75.7%, P=.259). A total of 45.9% of the patients achieved preservation of laryngeal function. There was a tendency for patients treated with chemotherapy to achieve laryngeal dysfunction-free survival at 5 years, which was higher than the patients treated with induction chemotherapy (55.6% versus 44.8%, P=.079). ConclusionThe patients included in a preservation protocol achieved 45.9% laryngeal dysfunction-free survival at 5 years. No significant difference in specific survival was observed between patients treated with induction chemotherapy or chemoradiotherapy.

Comparison of treatment modalities for selected advanced laryngeal squamous cell carcinoma.

The authors aimed to clarify the optimal treatment strategy and the indication of different treatments in managing advanced laryngeal squamous cell carcinoma (LSCC). A total of 9700 patients with advanced (T3-4aN0-3M0) LSCC who treated with (1) surgery alone, (2) surgery plus adjuvant radiation with or without chemotherapy (aCRT/RT), or (3) definitive CRT/RT was retrieved from the SEER database. The propensity score matching (PSM) was applied to balance confounding factors. Kaplan-Meier method and Cox proportional hazards regression were used to comparing the overall survival (OS) of patients. After optimal matching, 907 patients were screened from each treatment cohort. Kaplan-Meier and multivariate analyses presented that patients treated with surgery plus aCRT/CT had significantly longer OS than those treated with either surgery alone or CRT/RT, even after PSM. However, significant interactions were tested in treatment effects in stratified analyses of the primary subsite, T stage, N stage, and insurance status (PInteraction < 0.05 for all). Specifically, surgery plus aCRT/CT significantly improved the OS of patients with supraglottic, T4a, and N + tumors (P < 0.001 for all), while three treatment modalities achieved equal OS rates for patients with glottic, T3, and N0 tumors (P > 0.05 for all). Besides, supraglottic tumors presented a poorer prognosis than glottic subsite. Current study suggests that surgery with aCRT/RT is the preferred initial therapy for patients with T4a tumors, whereas patients with T3 tumors could be treated with either surgery (followed by aCRT/RT if it presents N +) or definitive CRT/RT for achieving laryngeal preservation. More-intense treatment should be emphasized for advanced supraglottic cancer.

Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy.

Simple SummaryThere are no randomized studies comparing organ-preservation protocols with chemo-selection to the classical total laryngectomy plus (chemo)radiotherapy. Thus, we performed a matched-pair analysis to compare these two treatments with respect to locoregional control, disease-specific survival (DSS), and overall survival (OS) in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx. The results did not show differences between the two treatments for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control, and metastasis-free survival.Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48–1.18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57–1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67–7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51–2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.