Recurrent Laryngeal Cancer Research Articles

Survival Outcomes of Total Laryngectomy: Evaluating the Intersection of Race and Social Determinants.

Analyze joint effects of race and social determinants on survival outcomes for patients undergoing total laryngectomy for advanced or recurrent laryngeal cancer at a tertiary care institute. Retrospective chart review of adult patients undergoing total laryngectomy for laryngeal cancer at a tertiary care center from 2013 to 2020. Extracted data included demographics, pathological staging and features, treatment modalities, and outcomes such as recurrence, fistula formation, and 2- and 5-year disease-free survival (DFS) and overall survival (OS). Area Deprivation Index (ADI) was calculated for each patient. Among 185 patients identified, 113 were Black (61.1%) and 69 were White (37.3%). No significant differences were observed between racial groups regarding age, gender, ADI, or cancer stage. There was no significant difference in 2-year DFS/OS between groups. ADI was comparable between racial groups, with the majority in the highest deprivation quintile (63.8% of Whites vs. 62.5% of Blacks). No significant differences were observed in gender, race, cancer stage, positive margins, extracapsular extension, or smoking status among ADI quintiles. We observed a significant difference in 2-year DFS stratified by ADI (p = 0.025). Stratifying by ADI and race revealed improved survival of White patients in lower quintiles but higher survival of Black patients in the highest disparity quintile (p = 0.013). Overall, survival outcomes by race were comparable among laryngectomy patients, but there was a significant difference in 2-year DFS when stratified by ADI. Further research into survival outcomes related to social determinants is needed to better delineate their effects on head and neck cancer outcomes. 3 Laryngoscope, 2024.

The role of human papillomavirus in laryngeal cancer and recurrent respiratory papillomatosis: epidemiological and clinical aspects

In the recent decade, the number of laryngeal cancer cases increased worldwide by 23 %. Currently, laryngeal cancer morbidity and associated mortality do not show statistically significant trends toward a decrease. The main risk factors for laryngeal carcinoma are smoking, alcohol consumption, human papilloma virus (HPV) infection, recurrent respiratory papillomatosis, and genetic predisposition.Aim. To evaluate the incidence and role of HPV in etiology and clinical course of laryngeal cancer and recurrent respiratory papillomatosis.Analysis of the available literature sources published in the Medline, Pubmed, and eLibrary databases was performed. The review is based on 59 of 584 identified scientific studies. Frequency of HPV detection in laryngeal cancer tumor tissue varies and is associated with the studied country’s geographical location. The incidence of these viruses in tumor tissue varies between 2.7 and 62.6 %. Genotype 16 human papilloma virus is more common in women between the ages of 31 and 40 years and is mostly located near the glottic aperture. Genotype 6 and 11 human papilloma viruses promote development of recurrent respiratory papillomatosis of the larynx and are detected in 0–87.5 % of cases. It is noted that in patients with HPV-positive neoplasms of the larynx, better response to radiation therapy and higher survival rates are observed compared to patients without the virus. In countries where national programs of vaccination against HPV infection have been implemented, a significant decrease in the incidence of recurrent respiratory papillomatosis is observed.The incidence of HPV in laryngeal cancer and recurrent respiratory papillomatosis varies. The role of these viruses in carcinogenesis has not yet been fully understood. Clinical course of HPV-associated laryngeal carcinoma is more favorable than HPV-free laryngeal carcinoma, however, this statement requires further confirmation. Evaluation of the results of programs of vaccination against HPV and their effect on recurrent respiratory papillomatosis and laryngeal cancer morbidity is important.

The Value of Computed Tomography in Recurrent Laryngeal Cancer Following Organ Preservation Therapy.

This study aims to assess the accuracy of computed tomography (CT) in detecting recurrent laryngeal tumors after failed chemoradiation therapy (CRT). Local recurrence of laryngeal tumors following CRT has been reported in approximately 25%, yet it is often difficult to detect. Ten patients with laryngeal cancer who failed CRT and subsequently underwent salvage total laryngectomy were included. The laryngeal subsites involved in the tumor were identified based on postoperative pathology. The corresponding preoperative CT scans were selected for review by seven experts (head-and-neck surgeons or radiologists) who scored the extent of tumor spread on each scan on a 5-point scale, from no tumor detected to clearly visible tumor. The rates of high tumor detectability (scores 4-5) varied according to laryngeal subsite, from 75% in the glottic region, to 45% in the subglottic region, and to 19% in the supraglottic region (P=0.01). The detectability rates were higher on scans performed 2 years or more after CRT. The CT evaluation of laryngeal cancer after CRT has limited value, particularly in the epiglottis and subglottis.

Elevated Tumor Cell-Intrinsic STING Expression in Advanced Laryngeal Cancer

Laryngeal cancer is the second most common malignancy of the head and neck, worldwide. Immunotherapy targeting checkpoint inhibitors has been approved for the treatment of patients with recurrent or metastatic laryngeal cancer but has a relatively low response rate and outcomes that leave many patients underserved. Targeting the cGAS–STING signaling pathway can potentially improve the activation of immune effector cells, although its role in the development and progression of laryngeal cancer has not yet been investigated in depth. Fifty-nine tumor samples from patients with pathologically confirmed squamous cell carcinoma of the larynx, stage I–IV non-metastatic disease, who were treated at the University Hospital of Split, were immunohistochemically stained for the expression of STING, cGAS, CD8, CD68, and CD163. Elevated tumor cell-intrinsic STING expression was positively associated with stage IV (p = 0.0031), pT3, and pT4 laryngeal cancers (p = 0.0336) as well as with higher histological grades (G2 and G3) (p = 0.0204) and lymph node-positive tumors (p = 0.0371). After adjusting for age, sex, location, and cGAS expression, elevated STING expression was significantly associated with stage IV cancer in a multiple logistic regression model (β = 1.849, SE = ±0.8643, p = 0.0324). Elevated STING expression represents a potentially favorable predictive biomarker for new therapeutic approaches involving STING agonists combined with immunotherapy and DNA-damaging agents (radiotherapy, cisplatin, and PARP inhibitors) in laryngeal cancer.

Reirradiation for local recurrence of oral, pharyngeal, and laryngeal cancers: a multi-institutional study

This study aimed to examine the efficacy and toxicity of reirradiation in patients with locally recurrent oral, pharyngeal, and laryngeal cancers. We conducted a retrospective, multi-institutional analysis of 129 patients with previously irradiated cancer. The most frequent primary sites were the nasopharynx (43.4%), oral cavity (24.8%), and oropharynx (18.6%). With a median follow-up duration of 10.6 months, the median overall survival was 14.4 months and the 2-year overall survival rate was 40.6%. For each primary site, the 2-year overall survival rates were 32.1%, 34.6%, 30%, 60.8%, and 5.7% for the hypopharynx, oral cavity, larynx, nasopharynx, and oropharynx, respectively. Prognostic factors for overall survival were primary site (nasopharynx versus other sites) and gross tumor volume (GTV) (≤ 25 cm3 versus > 25 cm3). The 2-year local control rate was 41.2%. Twenty-four patients (18.6%) presented with grade ≥ 3 toxicities, including nine with hemorrhages that led to grade 5 toxicities in seven patients. All nine tumors that caused hemorrhage showed tumor encasement of the carotid ≥ 180 degrees and eight of nine tumors had larger GTV > 25 cm3. Reirradiation is a feasible treatment option for small local recurrence of oral, pharyngeal, and laryngeal cancers, with the requirement of a strict eligibility assessment for large tumors with carotid encasement.

Identification of immunocell infiltrates and effective diagnostic biomarkers in laryngeal carcinoma.

Laryngeal cancer (LC) is a malignant tumor that occurs in the head and neck. Laryngeal cancer is one of the most common cancers of the neck and head, and its prognosis has always been poor. The incidence of LC increased gradually and showed an early rising trend. Laryngeal cancer is rarely studied in relation to immunity, Malignant tumors will change the state of the human body in various ways to adapt to their own survival and avoid the immune system. This study aims to explore the immune molecular mechanism of laryngeal cancer through bioinformatics analysis. The gene expression data was downloaded for 3 microarray datasets: GSE27020, GSE59102, and GSE51985. CIBERSORT algorithm was performed to evaluate immune cell infiltration in tissues between LC and healthy control (HC). Differentially expressed genes (DEGs) were screened. Functional correlation of DEGs were analyzed by Gene Ontology, Gene Set Enrichment Analysis and Kyoto encyclopedia of genes and genomes. Candidate biomarkers were identified by cytoHubba of Cytoscape. Spearman correlations between the above biomarkers and infiltrating immune cells were explored using R software analysis. The immune cell types of LC and HC were significantly different. Twenty-one DEGs were obtained by cross-screening. The function of DEGs is closely related to the number of immune cells. Five central genes (TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4) were screened. The HUB gene was demonstrated to have the ability to diagnose LC and HC with good specificity and sensitivity. The correlation between immune cells and biomarkers showed that hub gene was positively correlated with macrophages and dendritic cells, and negatively correlated with CD4 + T cell. TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4 can be used as diagnostic biomarker for LC. Macrophages, dendritic cells and CD4 + T cell may participate in the occurrence and development of LC.

Narrow Band Imaging Technology: Role in the Detection of Recurrent Laryngeal and Hypopharyngeal Cancers Post-radiotherapy.

To assess the diagnostic accuracy of NBI endoscopy for the diagnosis of early recurrent laryngeal and hypopharyngeal cancers after radiotherapy. The study was conducted over a period of two and a half years from June 2019 to February 2022 and included 123 post-RT patients with laryngeal and hypopharyngeal cancers. The patients were planned for endoscopy with white light and narrow-band imaging. The biopsy was carried out in NBI suspected lesions and sent for histopathological examination. The pathologist was blinded to the outcome of NBI and WLE results to eliminate observer bias. The age group most commonly affected in our study was 40-50 years. Out of the 123 patients, 106 were males and 17 were females. The overall Sensitivity, Specificity, Positive predictive value and Negative predictive value of NBI for malignant lesions were 90.6%, 99%, 95.2% and 98% respectively. NBI Technology is a first-rate diagnostic tool that can help in diagnosing early recurrent cancer lesions, especially after RT, in which the recurrence is otherwise difficult to differentiate from post-radiotherapy oedema. This technology can significantly reduce the rates of failure to detect cancers in early stages.

Perineural Invasion Predicts Local Recurrence and Poor Survival in Laryngeal Cancer.

(1) Background: Perineural invasion (PNI) in head and neck cancer is associated with a poor prognosis; however, the effect of PNI on the prognosis of laryngeal cancer remains under debate. This retrospective study aimed to investigate the effect of PNI in fresh or salvaged larynges on survival in patients who had undergone laryngectomy for squamous cell carcinoma. (2) Methods: This study enrolled 240 patients diagnosed with laryngeal cancer who had undergone open surgery at Seoul St. Mary's Hospital, Korea. The effects of PNI, other histopathologic factors, and treatment history on survival and recurrence patterns were assessed. (3) Results: PNI was observed in 30 of 240 patients (12.5%). PNI (HR: 3.05; 95% CI: 1.90-4.88; p = 0.01) was a significant predictor of poor 5-year disease-free survival. In fresh cases, preepiglottic invasion (HR: 2.37; 95% CI: 1.45-3.88; p = 0.01) and PNI (HR: 2.96; 95% CI: 1.62-2.96; p = 0.01) were negative prognostic factors for 5-year disease-free survival. In the salvage group, however, only PNI (HR: 2.74; 95% CI: 1.26-5.92; p = 0.01) was a significant predictor of disease-free survival. Further, PNI significantly influenced high local recurrence (HR: 5.02, 95% CI: 1.28-9.66; p = 0.02). (4) Conclusions: Independent of treatment history, PNI is a prognostic factor for poor survival and local recurrence in laryngeal cancer.

Salvage transoral laser microsurgery for early local recurrence of glottic squamous cell cancer

BackgroundFor recurrent laryngeal cancer, the feasibility of salvage transoral laser microsurgery (TLM) remains controversial. This study compared the efficacy of TLM and open partial laryngectomy (OPL) for treatment of early local recurrence of glottic squamous cell cancer (GSCC) and confirm the effectiveness of salvage TLM as a treatment option.MethodsThis retrospective study involved 55 patients with early local recurrent GSCC treated with TLM, and the oncologic outcomes, functional outcomes, hospitalization time and complications were compared with a group of 40 recurrent GSCC patients matched for clinical variables of TLM group, treated by OPL by the same team of surgeons.ResultsThe 5-year overall survival and disease-specific survival rates were 65.8% and 91.5%, respectively, for 55 patients with rTis–rT2 stage treated by TLM and 77.1% and 94.7%, respectively, for 40 patients with rTis–rT2 stage treated by OPL (OPL group). In the TLM and OPL groups, the local control rates after 5 years were 77.5% and 79.3%, respectively, and the laryngeal preservation rates were 94.4% and 83.6%, respectively (p > 0.05). Compared with the OPL group, the complication rate (1.82%) and hospitalization duration (5.42 ± 2.26 days) were significantly lower in the TLM group (p < 0.05). Compared with the OPL group, postsurgical health-related quality of life and quality of voice were significantly better in the TLM group (p < 0.001).ConclusionSalvage TLM can be used as an effective treatment option for suitable patients after a full, comprehensive, and careful assessment of the characteristics of early locally recurrent glottic carcinoma.Graphical

Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20–23 % (p = 0.0058–0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-ɣ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-ɣ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs.

Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis.

To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects. Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7-88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7-89.4), 53.9% (38.5-75.3), and 39.1% (25.2-60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0-95.3), 67.8% (50.9-90.3), and 58.9% (42.7-81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9-104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7-80.6), 53.2% (42.2-66.9), and 40.4% (29.6-55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5-99.1), 77.0% (64.4-92.0), and 67.1% (51.6-87.3). TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. NA Laryngoscope, 133:1425-1433, 2023.

Patterns of neck metastasis and occult neck disease during recurrent laryngeal cancer.

Numerous factors are considered to impact on the rate of complications during salvage total laryngectomy procedures. Neck dissection could be one of these factors. This study analysed the pattern of lymph node metastasis and rate of occult neck disease during salvage total laryngectomy as well as the impact of neck dissection on survival and complication rates. This was a retrospective analysis of a prospectively maintained laryngectomy database in two large tertiary teaching hospitals. The rate of occult neck disease was 11.1 per cent. Most cases with occult neck disease had rT4 disease. Patients with complications, advanced tumour stage and positive margins had a significant decrease in overall survival. Patients receiving elective neck dissection did not have any survival benefit. Positron emission tomography-computed tomography showed a very high specificity and negative predictive value. According to the low risk of occult neck disease when using contemporary imaging techniques as well as the lack of impact on survival, conservative management of the neck should be considered for crT1-T3 recurrence.

NOTCH1 mutation associates with impaired immune response and decreased relapse-free survival in patients with resected T1-2N0 laryngeal cancer.

BackgroundPatients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear.MethodsA total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively.ResultsTo the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (>10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients.ConclusionsGenomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.

Role of elective neck dissection with salvage laryngectomy

BackgroundElective neck dissection with salvage laryngectomy was associated with decreased quality of life, increased operative time, and increased incidence of complications; some surgeons prefer wait-and-see observation policy. However, lymph nodes recurrence after salvage total laryngectomy during follow-up period carry very poor quality of life and very poor survival rate.The aim of this study is to investigate the risk of nodal metastases in patients undergoing salvage laryngectomy and to search for predictors of occult metastases in this group of patients. Our study included 30 patients presented with recurrent laryngeal cancer after failure of organ preservation protocol. All selected patients were without detected lymph nodes both clinically and radiologically, classified as N0 according to The TNM classification.All patients were candidate for salvage total laryngectomy and had elective neck dissection performed during surgery to detect the possible occult cervical lymph node metastasis.ResultsThe positive nodal metastasis incidence was 14% in glottic, 29% in supraglottic, and 57% in trans-glottic tumors of all positive patients. The previously indicated results showed statistically significantly increased incidence of positive LN in the supraglottic tumor site and increased incidence of negative LN in the glottic site.Regarding the recurrence T stage in our study, lymph nodes were negative for metastasis in one patient with rT1 representing 4%, 6 patients with rT2 representing 26%, and for rT3 and rT4 were 65% and 4%, respectively. The nodal metastasis was positive in 3 patients with rT3 representing 43% and 4 patients with rT4 representing 57%. No patients with rT1 or rT2 showed nodal metastasis.ConclusionsOur findings demonstrated that patients with advanced local disease at recurrence undergoing salvage total laryngectomy may benefit from an elective neck dissection.

Elective Neck Dissection during Salvage Total Laryngectomy: Personal Experience.

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate.

Vertical resections for larynx cancer with preservation of the thyroid cartridge plates

To increase the functional safety of the larynx and improve the quality of life of patients with laryngeal cancer by using the developed method of organ-preserving surgical intervention in combined treatment. The study included 197 patients who were operated on by the same method for a primary tumor or in connection with a relapse of the disease. At the first stage, all primary patients underwent a course of radiation or chemoradiation therapy 40-50 Gy. In 78 patients with recurrent laryngeal cancer who underwent resection of the larynx, the previous treatment was carried out in the form of a full course of radiation or chemoradiation therapy with a above 60 Gy. Wound healing by primary intention in patients with preoperative irradiation was observed in 92.4% of cases. With resections for a primary tumor, restoration of functions was observed in 115 (96.6%) patients, and with resections of recurrent tumors - in 71 (91%) patients. Three-year disease-free survival in these patients was 74.4%. The presented data showed the high efficiency of the method. This is evidenced by the course of the postoperative period, functional and oncological results are comparable, and in some cases exceed those of other researchers.

Hub Genes of Recurrent Laryngeal Cancer Identified by Weighted Gene Co-Expression Network Analysis

Objective in order to discover correlated gene modules and hub genes for recurrent laryngeal squamous cell carcinoma through weighted gene co-expression network analysis method. The microarray dataset of recurrent laryngeal cancer, namely GSE27020, were obtained from the gene expression Omnibus database. Weighted gene co-expression network analysis was introduced to establish a gene co-expression network, mining key clinical trait correlated hub genes. Gene ontology enrichment analyses were performed for the genes in modules related to recurrent laryngeal squamous cell carcinoma. Then, we build up a proteinprotein interaction network with the genes in interest gene module and identified hub genes through analyze such protein-protein interaction network. The hub genes were mined using cytohubba plus-in. Finally, we analyzed these hub genes overall survival using gene expression profiling interactive analysis database. Forty four gene co-expression gene modules were achieved via weighted gene co-expression network analysis analysis. We found that the orangered4 module was the most correlated module with recurrence in laryngeal squamous cell carcinoma patients. Genes in the orangered4 module were related to organelle organization, response to chemical, regulation of catalytic activity and regulation of cell differentiation. Two genes were discovered as hub genes which were related to poor prognosis, namely annexin A2 and S100 calcium binding protein A10. Here, we found several hub genes that played important roles in recurrent laryngeal squamous cell carcinoma, which may improve our understanding of the mechanisms underlying recurrence laryngeal squamous cell carcinoma.

Surgical and oncological outcomes of transoral robotic total laryngectomy: A case series

ObjectiveTo evaluate the oncological, functional and voice rehabilitation outcomes of transoral robotic surgery for total laryngectomy (TORS-TL). MethodsA retrospective chart review of patients treated by TORS-TL was conducted at a single academic medical center. The following outcomes were studied: indication; average robotic set-up and operative times; mean estimated blood loss; postoperative complications; re-feeding features; mean hospital stay; need of adjuvant therapy and voice rehabilitation type. ResultsTORS-TL was performed in 10 patients for the following indications: nonfunctional larynx (N = 2); low-grade cricoid chondrosarcoma (N = 3) and recurrent laryngeal cancer after (chemo) radiation (N = 5). Two patients were excluded because the larynx was not exposable. Average robotic set-up and operative times were 20 and 278 min, respectively. The mean estimated blood loss was 50 mL. The mean hospital stay was 13.9 days (8–28 days). There was no local recurrence in patients operated for cancer recurrence (N = 5) 5 years after the surgery. Distant metastases occurred in one patient. A patient with laryngeal chondrosarcoma experienced local failure 3 years after TORS-TL. The voice rehabilitation consisted of esophageal voice (N = 2) and tracheoesophageal prosthesis (Provox®, N = 8). The main reasons for prosthesis replacement were transprosthetic (79%) and periprosthetic leaks (21%). The median lifespan of prostheses was 81 days. ConclusionTORS-TL may be a safe and effective surgical approach for selected surgical indications. Future controlled studies are needed to determine additional indications and limitations of this procedure.

Role of Thyroidectomy in Recurrent Laryngeal Carcinoma.

Management of recurrent laryngeal cancer presents a major challenge, and salvage laryngectomy is complicated by previous oncologic treatments. Thyroidectomy as part of salvage laryngectomy adds a nonnegligible degree of morbidity. The purpose of this study is to assess the rate of thyroid gland invasion in patients undergoing salvage laryngectomy to determine relevant predictive factors. Case series with chart review. Department of Otorhinolaryngology, Head and Neck Surgery, Guy's Hospital, London, United Kingdom. A retrospective review of patients undergoing salvage laryngectomy between 2009 and 2019 was undertaken. Preoperative cross-sectional imaging and histopathological analysis were performed to define evidence and predictors of thyroid gland invasion (TGI). Fifty-one patients had salvage laryngectomy. Histological evidence of TGI was found in 4 patients (7.8%). No significant relationship was found between histological TGI and subsite of primary carcinoma, degree of differentiation, T staging, or radiological TGI. Preoperative computed tomography had a high negative predictive value for TGI. Thyroidectomy should be carefully considered in patients undergoing salvage laryngectomy, and its extent should be defined on an individual basis. Total thyroidectomy should not routinely be performed in salvage laryngectomy or pharyngolaryngectomy in patients with no preoperative radiological evidence of TGI on cross-sectional imaging, unless there is intraoperative evidence of TGI.

Association of Pharyngocutaneous Fistula With Cancer Outcomes in Patients After Laryngectomy

Pharyngocutaneous fistula (PCF) results in an inflammatory reaction, but its association with the rate of locoregional and distant control, disease-free survival, and overall survival in laryngeal cancer remains uncertain. To determine if pharyngocutaneous fistula after salvage laryngectomy is associated with locoregional and distant control, disease-free survival, and/or overall survival. A multicenter collaborative retrospective cohort study conducted at 5 centers in Canada and the US of 550 patients who underwent salvage laryngectomy for recurrent laryngeal cancer from January 1, 2000, to December 31, 2014. The median follow-up time was 5.7 years (range, 0-18 years). Outcomes examined included locoregional and distant control, disease-free survival, and overall survival. Fine and Gray competing risk regression and Cox-proportional hazard regression models were used for outcomes. Competing risks and the Kaplan-Meier methods were used to estimate outcomes at 3 years and 5 years. In all, 550 patients (mean [SD] age, 64 [10.4] years; men, 465 [85%]) met inclusion criteria. Pharyngocutaneous fistula occurred in 127 patients (23%). The difference in locoregional control between the group of patients with PCF (75%) and the non-PCF (72%) group was 3% (95% CI, -6% to 12%). The difference in overall survival between the group with PCF (44%) and the non-PCF group (52%) was 8% (95% CI, -2% to 20%). The difference in disease-free survival between PCF and non-PCF groups was 6% (95% CI, -4% to 16%). In the multivariable model, patients with PCF were at a 2-fold higher rate of distant metastases (hazard ratio, 2.00; 95% CI, 1.22 to 3.27). Distant control was reduced in those with PCF, a 13% (95% CI, 3% to 21%) difference in 5-year distant control. This multicenter retrospective cohort study found that development of PCF after salvage laryngectomy is associated with an increased risk for the development of distant metastases.