An update on the immune landscape in lung and head and neck cancers.

Immunotherapy has dramatically changed the treatment landscape for patients with cancer. Programmed death-ligand 1/programmed death-1 checkpoint inhibitors have been in the forefront of this clinical revolution. Currently, there are 6 US Food and Drug Administration-approved checkpoint inhibitors for approximately 18 different histologic types of cancer. Lung cancer and head and neck squamous cell carcinoma (HNSCC) are 2 diseases that have led the way in the development of immunotherapy. Atezolizumab, durvalumab, nivolumab, and pembrolizumab are all currently used as part of standard-of-care treatment for different stages of lung cancer. Similarly, nivolumab and pembrolizumab have US regulatory approval as treatment for advanced metastatic HNSCC. This is significant because lung cancer represents the most common and most fatal cancer globally, and HNSCC is the sixth most common. Currently, most of the approvals for the use of immunotherapy agents are for patients diagnosed in the metastatic setting. However, research is ongoing to evaluate these drugs in earlier stage disease. There is plausible biological rationale to expect that pharmacologic activation of the immune system will be effective for early-stage and smaller tumors. In addition, selecting patients who are more likely to respond to immunotherapy and understanding why resistance develops are crucial areas of ongoing research. The objective of this review was to provide an overview of the current immune landscape and future directions in lung cancer and HNSCC.

Prognostic analysis of surgical treatment for T3 glottic laryngeal cancer based on different tumor extension patterns.

BACKGROUND AND OBJECTIVES: To investigate the prognostic impact of different tumor invasion patterns in the surgical treatment of T3 glottic laryngeal cancer. METHODS: We conducted a retrospective analysis of clinical data of 91 patients with T3 glottic laryngeal cancer. RESULTS: We found that the posterior invasion being significantly associated with involvement of the lamina of cricoid cartilage (P < 0.001), arytenoid cartilage (P = 0.001), and subglottic (P = 0.001). There was no statistical difference in survival outcomes between the total laryngectomy (TL) group and the partial laryngectomy (PL) group, but in the PL group, tumors with anterior invasion were associated with a better 5-year DFS than tumors with posterior invasion (HR: 4.681, 95% CI: 1.337-16.393, P = 0.016), and subglottic involvement was associated with worse LRRFS (HR: 3.931, 95% CI: 1.054-14.658, P = 0.041). At the same time, we found that involvement of the lamina of cricoid cartilage was an independent risk factor for postoperative laryngeal stenosis in PL patients (HR: 11.67, 95% CI: 1.89-71.98, P = 0.008). CONCLUSION: Selectively performed PL can also achieve favorable oncological outcomes comparable to those of TL. Posterior invasion and subglottic involvement are independent prognostic factors for recurrence after PL in T3 glottic laryngeal cancer, and involvement of the lamina of cricoid cartilage is associated with postoperative laryngeal stenosis. The tumor invasion pattern of patients with laryngeal cancer should be further subdivided to allow for selection of a more individualized treatment plan.

[Occupational diseases related to otorhinolaryngology]. / Berufskrankheiten mit Bezug zur HNO-Heilkunde.

In the German Ordinance on Occupational Diseases (BKV), there are currently 82 occupational diseases listed, of which 18 partially or completely fall within the field of ENT medicine due to the associated health disorders. Noise-induced hearing loss is usually the focus of attention for the ENT specialist, but it has long since ceased to be the only occupational disease. In order to help uncover possible causalities between occupational noxious substances and diseases, it is important that physicians report their own observations and new scientific findings regarding suspected cases to the German Social Accident Insurance, especially in situations where cancer may be linked to occupational influences.

Ultrasound-guided core needle biopsy for accessing laryngeal masses with unsatisfactory laryngoscopy and biopsy results.

BACKGROUND: Laryngoscopy and biopsy is the standard techniques to sample and diagnose laryngeal neoplasms, but not all patients with laryngeal neoplasm are eligible for biopsy via laryngoscopy (e.g., submucosal neoplasms). PURPOSE: This study was conducted to evaluate the feasibility and diagnostic yield of ultrasound-guided core needle biopsy (US-CNB) for submucosal laryngeal neoplasms with unsatisfactory laryngoscopy and biopsy results. METHODS: We retrospectively reviewed the medical records of 24 patients with unsatisfactory laryngoscopy and biopsy results who were referred to our center for US-CNB from January 2017 to November 2021. For all enrolled patients, we assessed consistency between the laryngoscopic biopsy, US-CNB, and final results. The final results were determined from the surgical biopsy results or clinical follow-up information (at least 3 month). Differences between biopsy techniques were compared using the Fisher's exact test. A P value less than 0.05 indicated statistical significance. RESULTS: Twenty-four patients (median [range] age: 60.6 [41-76] years, 20 men) were included in our study. Among the 24 patients, 12 were eligible for laryngoscopic biopsy. In total, 24 patients underwent 26 US-CNB. Two patients underwent a repeat US-CNB for conformation of a benign histological result or due to inadequate specimen collection. The results of laryngoscopic biopsy and US-CNB were compared with the final result. The overall accuracy of US-CNB for differentiating benign from malignant lesions was 95.8 % (23/24), and this procedure had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.2 %, 100 %, 100 %, and 75 %, respectively. The results of US-CNB are significantly better than those of laryngoscopic biopsy. CONCLUSIONS: US-CNB is a safe, effective, and feasible technique for investigating suspicious submucosal laryngeal neoplasms and can serve as a complementary method for early and timely diagnosis of those neoplasms.

[Laryngeal-preservation surgery in laryngeal cancer]. / Kehlkopferhaltende Operationen bei Larynxkarzinomen.

After oral cavity and pharyngeal cancer, laryngeal cancer is the third most common malignant tumor in the head and neck region. According to the current German S3 guideline on the diagnosis, treatment, and follow-up of laryngeal cancer, larynx-preserving surgical interventions are part of the standard treatment of this disease, even in advanced tumor stages. However, in order to achieve the desired function-preserving effect, an exact indication is of crucial importance. In this article, the most important larynx-preserving interventions and their indications but also the respective contraindications are presented, with the aim of illuminating the surgical treatment options up to just before total laryngectomy.

The Prognostic Utilities of Various Risk Factors for Laryngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Objective: To assess the prognostic utilities of various risk factors for laryngeal squamous cell carcinoma. Methods: Six databases were searched to January 2022. Hazard ratios for overall survival and disease-free survival were collected and study characteristics were recorded. The risk of bias was evaluated using the Newcastle-Ottawa scale. Results: Twenty-eight studies involving 32,128 patients were finally included. In terms of overall survival, older age, a history of alcohol consumption, a high Charlson comorbidity index score, a high TNM stage (III and IV), a high tumor stage (III and IV), nodal involvement, poor pathological differentiation, primary chemoradiotherapy and radiotherapy were associated with increased risks of death. In terms of disease-free survival, older age (≥60 years), TNM stages III and IV, tumor stages III and IV, supraglottic tumors, and nodal involvement all increased the risk of death. Conclusions: The TNM stage importantly predicts overall survival, and tumor location predicts the disease-free survival of patients with laryngeal squamous cell carcinoma. Of patients with risk factors, the Charlson comorbidity index usefully predicts overall survival.

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

BACKGROUND: Circular 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. METHODS: RNA 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. RESULTS: Here, 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/ß-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 ß-catenin protein was enhanced via suppressing the ß-catenin phosphorylation and accelerating its accumulation in cytoplasm and nucleus. CONCLUSION: Our findings manifested a novel circMTCL1-C1QBP-ß-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.

Association of histological features with laryngeal squamous cell carcinoma recurrences: a population-based study of 1502 patients in the Netherlands.

BACKGROUND: Recurrences remain an important problem in laryngeal squamous cell carcinoma. Little has been described about histological characteristics of the primary laryngeal tumor that may be associated with recurrences. Identifying risk factors for recurrences might help in adapting treatment or follow-up. Using real-life population-based data, we aimed to identify histological features of the primary tumor associated with recurrences and overall survival. MATERIAL AND METHODS: Demographic, clinical and treatment information on all first primary invasive laryngeal tumors diagnosed in 2010-2014 (N = 3705) were extracted from the population-based nationwide Netherlands cancer registry (NCR) and linked to PALGA, the nationwide Dutch pathology registry, to obtain data on histological factors and recurrences. For a random 1502 patients histological information i.e., keratinization, perineural invasion (PNI+), vascular invasion (VI+), growth pattern, degree of differentiation, extracapsular spread (ECS+), cartilage- and bone invasion and extralaryngeal extension, was manually extracted from narrative pathology reports and analyzed for locoregional recurrence and overall survival using cox regression analysis. RESULTS: In total, 299 patients developed a locoregional recurrence and 555 patients died. Keratinization (HR = 0.96 (95%CI: 0.68-1.34) p = 0.79), two or three adverse characteristics (PNI+, VI+, non-cohesive growth) (HR = 1.38 (95% CI: 0.63-3.01) p = 0.42), and ECS+ (HR = 1.38 (95% CI: 0.48-4.02) p = 0.55) were not associated to recurrence. For death, also no significant association was found. CONCLUSION: In this population-based real-life dataset on laryngeal carcinoma in the Netherlands, histological factors were not associated with locoregional recurrences or overall survival, but future studies should investigate the role of these features in treatment decisions.

Dual-energy CT may predict post-operative recurrence in early-stage glottic laryngeal cancer: a novel nomogram and risk stratification system.

OBJECTIVES: To establish and validate a predictive model integrating with clinical and dual-energy CT (DECT) variables for individual recurrence-free survival (RFS) prediction in early-stage glottic laryngeal cancer (EGLC) after larynx-preserving surgery. METHODS: This retrospective study included 212 consecutive patients with EGLC who underwent DECT before larynx-preserving surgery between January 2015 and December 2018. Using Cox proportional hazard regression model to determine independent predictors for RFS and presented on a nomogram. The model's performance was assessed using Harrell's concordance index (C-index), time-dependent area under curve (TD-AUC) plot, and calibration curve. A risk stratification system was established using the nomogram with median scores of all cases to divide all patients into two prognostic groups. RESULTS: Recurrence occurred in 39/212 (18.4%) cases. Normalized iodine concentration in arterial (NICAP) and venous phases (NICVP) were verified as significant predictors of RFS in multivariate Cox regression (hazard ratio [HR], 4.2; 95% confidence interval [CI]: 2.3, 7.7, p < .001 and HR, 3.0; 95% CI: 1.5, 5.9, p = .002, respectively). Nomogram based on clinical and DECT variables was better than did only clinical variables. The prediction model proved well-calibrated and had good discriminative ability in the training and validation samples. A risk stratification system was built that could effectively classify EGLC patients into two risk groups. CONCLUSIONS: DECT could provide independent RFS indicators in patients with EGLC, and the nomogram based on DECT and clinical variables was useful in predicting RFS at several time points. KEY POINTS: • Dual-energy CT(DECT) variables can predict recurrence-free survival (RFS) after larynx-preserving surgery in patients with early-stage glottic laryngeal cancer (EGLC). • The model that integrates clinical and DECT variables predicted RFS better than did only clinical variables. • A risk stratification system based on the nomogram could effectively classify EGLC patients into two risk groups.

Effect of voice rehabilitation following radiotherapy for laryngeal cancer - a 3-year follow-up of a randomised controlled trial.

OBJECTIVES: This study aims to report on the effectiveness of voice rehabilitation following radiotherapy for laryngeal cancer in a long-term perspective, i.e., up to three years after completion of radiotherapy. METHODS: The study included a total of 74 patients that were randomised into an intervention group (n = 37) or a control group (n = 37). Voice recordings with blinded assessment of voice quality with the GRBAS protocol (Grade, Roughness, Breathiness, Asthenia, Strain) and acoustic analysis was performed at baseline, 12 and 36 months following radiotherapy. Voice rehabilitation was performed in 10 sessions immediately following completion of radiotherapy. Patients also filled out the Swedish Self-Evaluation of Communication Experiences after Laryngeal cancer. RESULTS: The S-SECEL demonstrated statistically significant improvements in the intervention group when comparing baseline and 36 months, and no changes in the control group. Acoustic measures did not reveal any significant changes. The perceptual analysis demonstrated that when comparing the changes within the groups between baseline and 36 months there were statistically significant differences between the intervention and control group regarding the voice qualities Roughness, Breathiness and Strain. In the control group, 50% demonstrated deterioration in roughness, while in the intervention group only 7% deteriorated during this time. In Breathiness and Strain, 57 and 50%, respectively, improved in the intervention group, while only 32% and 23% improved, respectively, in the control group. CONCLUSION: Voice rehabilitation following radiotherapy for laryngeal cancer demonstrate positive effects in patient reported outcomes and perceptual measures of voice quality, and the effects remain up to three years following radiotherapy.

Notch1 signaling modulates hypoxia-induced multidrug resistance in human laryngeal cancer cells.

BACKGROUND: Laryngeal carcinoma is one of the common malignant tumors of the head and neck. Multidrug resistance (MDR) remains a critical problem in the chemotherapy of patients with laryngeal cancer. This study aims to clarify the role and mechanisms of Notch1 signaling in MDR induced by hypoxia in laryngeal cancer cells. METHODS AND RESULTS: Laryngeal carcinoma cells were cultured under normoxia or hypoxia. Notch1 expression was inhibited by small interfering RNA (siRNA). The mRNA expression of Notch1, Hes1, Hey1, MDR1 and survivin was analyzed by real-time PCR. The protein expression of Notch1, the Notch1 intracellular domain (N1ICD), MDR1/P-gp and survivin was analyzed by Western blotting. Current research has shown that hypoxia can upregulate Notch1 expression and Notch1 signaling activity. Furthermore, suppression of Notch1 expression effectively downregulated Notch1 signaling activity and the expression of the MDR and survivin genes in laryngeal cancer cells under hypoxic conditions (P < 0.05). The Cell Counting Kit-8 (CCK-8) assay results confirmed that the sensitivity of hypoxic laryngeal cancer cells to a variety of drugs could be upregulated by suppressing Notch1 expression (P < 0.05). Additionally, flow cytometry (FCM) showed that suppression of Notch1 expression significantly increased drug-induced apoptosis and intracellular rhodamine 123 (Rh123) accumulation in hypoxic laryngeal carcinoma cells (P < 0.05). CONCLUSIONS: Notch1 signalling could be regarded as a pivotal regulator of hypoxia-induced MDR in laryngeal cancer cells through the regulation of survivin-mediated apoptosis resistance and MDR1/P-gp-mediated drug transport.

Deregulation of purinergic ectoenzyme activity in head and neck cancer promotes immunosuppression.

BACKGROUND: Head and neck cancer (HNC) comprises a spectrum of neoplasms that affect the upper aerodigestive tract and are the sixth most common cancers worldwide. Individuals with HNC exhibit various symptoms and metabolic changes, including immune alterations and alterations of the purinergic pathway, which may signal worse outcomes. Therefore, the purpose of this research was to measure the activity of purinergic ectoenzymes and interleukins in patients with HNC, oral cavity cancer, and larynx cancer. METHODS AND RESULTS: We recruited 32 patients and 33 healthy control subjects and performed the laboratory analyses. We identified dysregulation in the purinergic signaling pathway characterized by an increase in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and a decrease in the deamination of adenosine to inosine in these cancers (p < 0.05). These alterations were likely caused by increased activity of the ectoenzymes E-NTPDase and ecto-5'-nucleotidase and reduced adenosine deaminase activity. This dysregulation was associated with immune alterations, increased levels of IL-10, and decreased myeloperoxidase activity (p < 0.05), suggesting immunosuppression in these patients and suggesting possible accumulation of adenosine in the extracellular environment. CONCLUSIONS: Adenosine is a potent immunosuppressive molecule associated with tumor progression and immune evasion. Our findings suggest a relationship between extracellular purines and the development and progression of the tumor microenvironment and poor outcomes. These findings increase the understanding of biological mechanisms related to HNC and demonstrate that these components are potential diagnostic markers and therapeutic targets for future management strategies and improvement in the quality of life.

Effect of Notch1 signaling on cellular proliferation and apoptosis in human laryngeal carcinoma.

BACKGROUND: The occurrence and development of malignancies include excessive proliferation and apoptosis resistance in tumor cells. This study aimed to identify the effects of Notch1 signaling on proliferation and apoptosis of laryngeal cancer cells in a hypoxic microenvironment. METHODS: Notch1 and Ki-67 expression in laryngeal squamous cell carcinoma (LSCC) tissues was detected by immunohistochemistry. The apoptotic index (AI) of LSCC was evaluated by the TUNEL method. Small interfering RNA (siRNA) was used to inhibit Notch1 expression in laryngeal cancer cells. Real-time PCR was used to measure Notch1, Hes1, and Hey1 mRNA expression, and Western blotting was used to measure Notch1 and Notch1 intracellular domain (N1ICD) protein expression. Annexin V-FITC/propidium iodide staining and Cell Counting Kit-8 assays were used to measure cell apoptosis and proliferation, respectively. RESULTS: Notch1 expression was significantly related to the proliferation index (PI) and AI in LSCC tissues. Hypoxia could induce proliferation and inhibit apoptosis in cancer cells. Notch1 expression and Notch1 signaling activity could be upregulated by hypoxia. Suppressing Notch1 signaling activity in hypoxic cells could decrease proliferation and increase apoptosis. CONCLUSIONS: Our study has demonstrated that hypoxia may promote proliferation and inhibit apoptosis of laryngeal cancer cells. Notch1 signaling may play a pivotal role in regulating the proliferation and apoptosis resistance of laryngeal cancer cells under hypoxic conditions.

Association between pathological differentiation and survival outcomes of patients with laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic value of histopathological differentiation for the survival of patients with laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: Retrospective clinical and histopathological differentiation data on consecutive cases of LSCC from a single institution over a 10-years period were collected and analyzed in this study. Oncological outcomes were assessed based on disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) using the Kaplan-Meier method and Cox proportional hazards regression analysis. Propensity score matching (PSM) was performed to reduce or eliminate the bias due to confounding variables. RESULTS: A total of 998 LSCC cases were identified in this study. As compared to well to moderately differentiated LSCC, poorly differentiated tumors had adjusted hazard ratios (aHRs) of 1.78 (95% confidence interval [CI] 1.31-2.43), 2.00 (95% CI 1.51-2.65), and 1.72 (95% CI 1.28-2.31) for DSS, DFS, and OS, respectively. The new patient cohort consisted of 138 patients with well to moderately differentiated LSCC and 138 patients with poorly differentiated LSCC after PSM. The survival outcomes of patients with well to moderately differentiated LSCCs were significantly better than those of patients with poorly differentiated tumors in DSS (aHR 1.91; 95% CI 1.24-2.95), DFS (aHR 2.07; 95% CI 1.37-3.12), and OS (aHR 2.14; 95% CI 1.39-3.28). CONCLUSION: This study showed that survival outcomes of patients with poorly differentiated LSCC were significantly worse than those of patients with well to moderately differentiated LSCC. In addition, histopathological differentiation is an important prognostic factor for LSCC survival. Therefore, further treatment plans should focus on poorly differentiated LSCC to improve the survival outcomes.

Surgical management and oncological outcome of non-squamous cell carcinoma of the larynx: a bicentric study.

PURPOSE: Non-squamous cell carcinoma (non-SCC) accounts for about 5% of laryngeal malignancies. Survival data are limited, and consensus on management principles is lacking. The present study reviews our experience in the surgical treatment of non-metastatic non-SCC of the larynx and compares oncological and functional outcomes in a cohort of patients affected by traditional SCC. METHODS: We collected data on 592 patients affected by laryngeal neoplasms. Univariate and multivariable survival analyses were performed using Cox proportional-hazards models; survival estimates were reported by hazard ratios (HR) with 95% confidence intervals (CI), and survival curves were established with the Kaplan-Meier method. RESULTS: We identified 326 patients affected by untreated SCC, while 21 had non-SCC histotypes. The non-SCC cohort was composed of 5 soft tissue sarcomas, 8 chondrosarcomas, 2 adenoid cystic carcinomas, 2 neuroendocrine carcinomas, 2 solitary fibrous tumors, 1 Kaposi's sarcoma, and 1 malignant peripheral nerve sheath tumor. Overall survival and disease-specific survival were not significantly different according to histology (p = 0.6 and p = 0.349, respectively). The non-SCC group showed an increased risk of recurrence (HR 5.87; CI95 2.15-16.06; p < 0.001). Nonetheless, no significant difference (p = 0.31) was found at multivariable analysis between the two groups in total laryngectomy-free survival with an organ preservation rate over 5 years of 81% for the non-SCC histologies. CONCLUSION: Non-SCC is a broad spectrum pathology, but generalized laryngeal surgical management principles are still feasible and it is possible to identify patients amenable to conservative surgical treatment without affecting survival.

Quality of life following treatment for T1a glottic cancer with surgery or radiotherapy: outcomes from the Head and Neck 5000 cohort.

OBJECTIVES: To investigate the quality of life in patients treated with either RT or surgery alone for T1a glottic carcinoma. DESIGN: This prospective cohort study aims to assess generic- and disease-specific patient-reported QoL in patients treated with either surgery or RT for T1a glottic carcinoma. SETTINGS: Multicentre, secondary care specialist head and neck units in the UK. PARTICIPANTS: Participants were recruited as part of the multicentre, prospective Head and Neck 5000 cohort between 2011 and 2014. MAIN OUTCOME MEASURES: Baseline demographic data were collected. All participants completed the EORTC QLQ C30 and EORTC QLQ H&N35 questionnaires at baseline, 4 months, 12 months and after 36 months. RESULTS: One hundred and twenty three participants received radiotherapy only (n = 68) or surgery only (n = 55). Overall QoL scores were similar between both groups. The median (IQR) EORTC QLQ C30 summary scores at 12 months were 89.3 (79.1, 95.7) and 92.6 (74.4, 97.9) for the radiotherapy and surgery groups respectively. The equivalent summary scores for the EORTC QLQ H&N35 were 91.9 (83.8, 94.9) and 90.4 (85.5, 94.9). There was a modest difference in some QoL subscales between the groups, but no differences existed beyond 4 months. CONCLUSIONS: Patient-reported QoL is similar following either radiotherapy or surgery for T1a glottic carcinoma. These data support current guidance recommended TLM for this disease.

[Salvage laryngectomy after primary radio- and radiochemotherapy : A retrospective study. German version]. / Salvage-Laryngektomie nach primärer Radio- und Radiochemotherapie : Eine retrospektive Fallzusammenfassung.

BACKGROUND: Recurrent and residual laryngeal cancer after organ-preserving radio- or radiochemotherapy is associated with a poor prognosis. Salvage surgery is the most important therapeutic option in these cases. OBJECTIVE: The study assessed rates of recurrence and residual tumor as well as survival and complication rates after salvage laryngectomy at the authors' academic cancer center. MATERIALS AND METHODS: A retrospective examination of all patients receiving laryngectomy between 2001 and 2019 due to tumor residuals or recurrence after primary radio- and radiochemotherapy was conducted. RESULTS: A total of 33 salvage procedures were performed. Defect reconstruction was performed by free flap surgery in 30.3% (n = 10) and regional flap surgery in 15.2% (n = 5) . One patient received regional flap surgery and free flap surgery simultaneously. Overall survival after 1, 2, and 5 years was 68.7, 47.9, and 24.2%, and disease-free survival was 81.6, 47.8, and 24.2%, respectively, with 48.5% (n = 16) postoperative tumor recurrences overall. Disease-free survival was significantly shorter for tumor extension into or onto the hypopharynx (p = 0.041). Postoperatively, 72.7% of patients developed a pharyngocutaneous fistula, of which 24.2% required surgical treatment. The hospital stay was 28.0 ± 16.1 days. CONCLUSION: Salvage laryngectomy is associated with a high rate of treatable complications and high morbidity. Nevertheless, considering the advanced tumor stages treated, it allows for respectable oncological results.

Prognostic risk factors for initially diagnosed T2N0M0 glottic cancer: competing risk analysis and propensity-score matched cohort analysis.

BACKGROUND: Prognostic risk factors of patients with initially diagnosed T2N0M0 glottic cancer remain unclear. This study was aimed to conduct a comprehensive analysis to identify valuable prognostic risk factors for initially diagnosed T2N0M0 glottic cancer. METHODS: Data of patients with initially diagnosed T2N0M0 glottic cancer were extracted from the Surveillance, Epidemiology, and End Results database. Survival analyses and Cox regression analyses were conducted to evaluate overall survival (OS) and cancer-specific survival (CSS). In consideration of competing events, the competing risk (CR) analysis was applied. Furthermore, propensity-score matching (PSM) was applied to mimic randomized-controlled trials and reduce selection bias. RESULTS: A total of 923 eligible patients met the inclusion criteria. Survival analyses showed that age, marital status, primary site surgery, and radiation were independent predictors of OS. Besides, age, marital status, primary site surgery, radiation, and chemotherapy were independent predictors of CSS. Cox regression analyses and the CR analysis were basically consistent with this result. In addition, an internal validation and PSM were performed to explore the role of chemotherapy. CONCLUSION: We conducted a comprehensive analysis to prove that age, marital status, primary site surgery, radiation, and chemotherapy may be valuable prognostic risk factors for initially diagnosed T2N0M0 glottic cancer. Primary site surgery and radiation should be recommended, whereas chemotherapy was likely not suitable so far. Furthermore, we constructed a CR nomogram to predict survival rates.

Tumor volume as a prognostic factor of locally advanced laryngeal cancer.

PURPOSE: The TNM tumor staging system is the most widely used for laryngeal cancer. However, in the same T stage, lesions with different primary tumor volumes (TV) can be found, impacting treatment outcomes. METHODS: 145 patients with T3 and T4a laryngeal cancer, according to Union for International Cancer Control, who underwent surgical treatment from 2008 to 2017, were analyzed. TV measurements were collected and compared to different outcomes. RESULTS: The mean TV was 23.0 ± 16.4 cm3. A cutoff point for TV of 14.2 cm3 was established. Cumulative sample 5-year overall survival (OS) was 62.1%, while 5-years disease-free survival (DFS) was 65.5%. In univariate analysis, TV ≥ 14.2 cm3 was associated with a higher risk of distant metastases (p = 0.045), and worse rates of OS (p = 0.009) and DFS (p = 0.035). In multivariate analysis, TV was not an independent risk factor of worse DFS (p = 0.569) or OS (p = 0.094). CONCLUSION: Primary lesion TV showed significant association, in univariate analysis, with worse rates of recurrence and survival in advanced laryngeal cancer undergoing surgical treatment and can be a promising prognostic for these patients.

Biomarkers of laryngeal squamous cell carcinoma: a review.

Laryngeal carcinoma is the second common malignancy of the upper aerodigestive tract after lung cancer; in most cases is a squamous cell carcinoma, whose risk factors include tobacco smoking and alcohol consumption. Despite therapeutic progress, the five-year overall survival rate for this malignancy has remained nearly 50% and many patients already present metastasis at the time of diagnosis. To date, there are no tools that predict the evolution of laryngeal carcinoma: in this light, during the last years, many studies were planned with the aim to investigate the role played by different biomarkers expressed by larynx cancer, which can help make an early diagnosis, predict disease evolution and direct therapeutic choice. This review aims to summarize these markers and correlating them with disease evolution.