Radiation-Induced Oropharyngeal Squamous Cell Carcinoma: Case Report and Review of the Literature.

BACKGROUND: Radiation therapy (RT) is a mainstay for the treatment of head and neck (HN) cancers, with 80% of patients receiving such treatment. Radiation-induced malignancies represent a life-threatening long-term effect of RT, with an incidence of 0.5% to 15%. CASE DESCRIPTION: After 13 years, a 33-year-old woman treated with chemo-radiotherapy for nasopharyngeal carcinoma developed a locally advanced, radiation-induced, p16-negative oropharyngeal squamous cell carcinoma (SCC) at the base of the tongue. Chemo/immunotherapy was administered as a first-line treatment. Given the optimal response and the feasibility of surgery, after three cycles, the patient underwent a total glossectomy, bilateral neck dissection, and reconstruction with a thoraco-dorsal free flap. A histological examination found SCC with a residual cancer burden of 70% and free margins. DISCUSSION: The mechanisms responsible for carcinogenesis after RT are still not completely clear. Diagnosis may be challenging due to the previous treatment; growth patterns are unusual, and lymphotropism is lower. Prognosis is usually poor since surgical resectability is often not achievable. CONCLUSIONS: Radiation-induced malignancies are difficult to treat. Patient management should always be discussed at a multidisciplinary level. Future research is needed to assess whether the promising results of clinical studies with pre-operative immunotherapy in locally advanced HN SCC patients may be translated into radiation-induced cancers.

Treatment of primary epiglottis collapse in OSA in adults with glossoepiglottopexy: a 5-year experience.

Objective: To review our 5-year experience with a modified version of glossoepiglottopexy for treatment of obstructive sleep apnoea syndrome (OSA) in two hospitals. Methods: A retrospective analysis was carried out on a cohort of adult patients affected by OSA suffering from primary collapse of the epiglottis who underwent a modified glossoepiglottopexy. All patients underwent drug-induced sleep endoscopy, polysomnographic and swallowing evaluation, and assessment with the Epworth Sleepiness Scale (ESS). Results: Forty-nine patients were retrospectively evaluated. Both the apnoea-hypopnoea index (AHI) (median AHIpost-AHIpre = -22.4 events/h; p < 0.001) and oxygen desaturation index (ODI) showed a significant postoperative decrease (median ODIpost-ODIpre = -18 events/h; p < 0.001), as did hypoxaemia index (median T90% post-T90% pre = -5%; p < 0.001). The ESS questionnaire revealed a significant decrease in postoperative scores (median ESSpost-ESSpre =- 9; p < 0.001). None of the patients developed postoperative dysphagia. Conclusions: Our 5-year experience demonstrates that modified glossoepiglottopexy is a safe and reliable surgical technique for treatment of primary epiglottic collapse in OSA patients.

Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28- T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28- T cells, and CD8+CD28-CD127-CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28- T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28-CD127-CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition.

Management of loco-regionally advanced squamous laryngeal cancer in elderly patients.

PURPOSE: To describe the management and outcomes of loco-regionally advanced (stages III-IV) laryngeal cancer (LRALC) in elderly patients. METHODS: Clinical records of 88 LRALC patients treated at our Institution from 2002 to 2017 were retrospectively reviewed. Patients were divided in 2 subgroups: age > 65 years (elderly) and age ≤ 65 years (controls). Survivals were estimated with Kaplan-Meier method and compared with log-rank test, multivariate analysis were performed with Cox proportional hazard methods. RESULTS: Eighty-eight LRALC patients were included: 45 elderly and 43 controls. Median follow-up was 55.3 months. Median age was 66 years (range 41-84) in the overall population, 72 years (range 66-84) in the elderly cohort. The majority (98%) of elderly patients had at least one comorbidity (ACE27 1-3), while ACE27 was 0 in 37% of controls (p = 0.0001). ECOG PS was 0 in 42% of elderly vs 79% of controls (p = 0.0029). Clinical stage (TNM eighth edition) was III in 67%, IVA in 22% and IVB in 11%. Treatment consisted in total laryngectomy (TL) in 55%, chemo-radiation in 29%, exclusive radiotherapy in 9%, and conservative surgery in 7%. In elderly patients 2-year disease-free and overall survivals were 58% and 74%, respectively. Multivariate analysis performed on the overall group of 88 patients showed that age (HR 1.07, p = 0.0006) and TNM (for both 7th and 8th Editions HR 0.27 for stage III vs IV, p = 0.0005) maintained an independent statistical significant association with OS. CONCLUSIONS: In this monocentric cohort, age and TNM confirmed their independent prognostic role in LRALC patients. Organ-preservation is still an unmet need in a significant portion of elderly patients.

Comparison of Different Staging Systems Applied to a Cohort of Patients With Oral Tongue and Floor of the Mouth Cancer.

Purpose: The present work compares the effects produced by the application of the 7th edition of the tumor node metastasis (TNM) staging system (TNM7), 8th Edition (TNM8) with its two subsequent revisions, and pN-N+ classification on a cohort of patients with oral tongue and floor of the mouth cancer. Methods: A monocentric cohort of 148 patients was retrospectively analyzed. Patients were staged according to the TNM7, TNM8 and revisions, and pN-N+ classification. Stage migration was assessed and overall survival (OS) analyzed with the Kaplan-Meier method. The pT, pN, and stage stratification was evaluated with univariate and multivariate Cox regression and comparing adjacent categories with the log-rank method. Results: pT3-T4a categories showed significant differences in comparison to pT1-T2 for each staging metric employed in both uni- and multivariate analysis. When comparing adjacent pT categories, OS was significantly different only between pT2 and pT3 categories of the TNM8. Disproportionate patient distribution among pN categories was observed in the TNM8, and stratification was scarce. Conversely, in the pN-N+ classification the difference between pN2 and pN3a categories was significant. Only stage IVa reached statistical significance in TNM7, whereas stage III and above were significant in TNM8 and revisions in both uni- and multivariate analysis. However, no significant difference was noted comparing adjacent stages. Conclusion: The TNM8 pT classification differentiated low- from high-risk diseases. Nonetheless, it failed to separate pT1 from pT2 and pT3 from pT4a categories. Conversely, although TNM8 nodal staging was inaccurate, the number of metastatic lymph nodes was more valuable.

Head and neck adult-type soft tissues sarcomas: survival analysis and comparison between the last two editions of the TNM staging system.

PURPOSE: Head and neck soft tissues sarcomas (HNSTS) are a heterogeneous group of rare tumours. The 8th edition of the TNM staging system (8TNM) considered these lesions separately for the first time. The aim of this study is to assess its effectiveness and identify the most significant prognostic factors for HNSTS. METHODS: A retrospective survival analysis on 101 HNSTS operated between 1995 and 2015 at the National Cancer Institute of Milan was carried out. The variables considered were pathological stage (according to both the 7TNM and 8TNM), site, histotype, depth, grading, surgical radicality, (neo)adjuvant radiotherapy and/or chemotherapy. RESULTS: According to the 7TNM, the T category distribution was 35 T1a, 23 T1b, 11 T2a, and 32 T2b. Applying the 8TNM, the distribution changed to 19 T1, 18 T2, 35 T3, and 29 T4. Five-year overall and disease-specific survivals were 74.3 and 76.2%, respectively. Univariate analysis demonstrated an increased hazard ratio (HR) for deep lesions invading adjacent structures, high-grade, surgery with close/microscopically positive margins, and chemotherapy. Multivariate analysis confirmed an increased HR for deep location and size > 5 cm, G2-G3 tumours, and marginal surgery. No significant difference was found among T categories of the 8TNM. CONCLUSION: The present study underlines the negative prognostic impact of depth, size > 5 cm, high grade, and marginal treatment for HNSTS. Our results did not allow to validate the 8TNM staging system since, apparently, it was not associated with meaningful prognostic stratification. Further studies with wider multicentric cohorts should, however, be performed to obtain more powerful statistical data.

Transoral management of adult benign laryngeal stenosis.

PURPOSE: Management of benign laryngeal stenosis (BLS) remains challenging even though transoral treatments in selected cases have shown satisfactory results, at least comparable to open-neck approaches, with reduced invasiveness. To date, no overall consensus has been reached on many issues. The aim of this study is to assess the effectiveness of a purely transoral treatment in a cohort of patients affected by BLS. METHODS: We evaluated 40 patients affected by BLS, treated by transoral surgery between 2013 and 2017. The European Laryngological Society classification for laryngotracheal stenosis was applied for the staging. Improvement in airway patency and quality of life was assessed by decannulation rate, Airway-Dyspnea-Voice-Swallowing (ADVS) score, Voice handicap index (VHI)-30, and Eating assessment tool (EAT)-10 questionnaires. RESULTS: Mean age was 61 years and M:F ratio was 1.4:1. Previous laryngeal surgery was the most common cause of stenosis (50%), followed by radiotherapy (20%), idiopathic etiology (12%), granulomatosis with polyangiitis (10%), and prolonged intubation (8%). Transoral treatment entailed an improvement in quality of life with a significant decrease in the VHI score (p < 0.0001) and improvement in Airway (p = 0.008), Dyspnea (p < 0.0001), and Voice (p < 0.0001) scores. No major perioperative complications were observed. The decannulation rate among patients with a tracheostomy in place (N = 16) was 63%. CONCLUSIONS: Transoral treatment of selected BLS managed by a team with high-level expertise in surgery and anesthesiology is associated with significant improvement of quality of life, especially with regard to voice and breathing functions.

Fascio-cutaneous-free flaps as primary reconstruction in salvage total laryngectomy.

INTRODUCTION: Salvage total laryngectomy (STL) is the most common treatment for recurrent laryngeal cancer after (chemo)-radiotherapy [(C)RT]. In this scenario, a higher rate of local wound complications, such as pharyngo-cutaneous fistula (PCF) and pharyngo-esophageal stenosis (PES), is generally expected. The aim of the present study is to evaluate outcomes using a standardized reconstructive protocol. METHODS: Between 2009 and 2019, patients undergoing STL after (C)RT were collected at two referral hospitals with the objective of evaluating surgical outcomes using a standardized reconstructive policy based on the use of fascio-cutaneous free flaps as inlay patch grafts and a long-lasting salivary bypass stent. RESULTS: Fifty-five patients (mean age, 66 years; male-to-female ratio, 8:1) were included in the study. Previous treatments were RT in 22 (40%) patients, CRT in 21 (38.2%), and partial laryngeal surgery followed by adjuvant (C)RT in 12 (21.8%). Reconstruction was accomplished by radial forearm and anterolateral thigh free flaps in 16 (29.1%) and 39 (70.9%) patients, respectively. Flap success rate was 98.2%. Concerning postoperative complications, we encountered 3 PCFs (5.4%) and 1 PES (1.8%). CONCLUSION: The standardized reconstructive protocol analyzed herein granted significantly lower rates of PCF and PES after STL compared with data available in the literature.

Laryngeal Compartmentalization Does Not Affect the Prognosis of T3-T4 Laryngeal Cancer Treated by Upfront Total Laryngectomy.

A picture is emerging in which advanced laryngeal cancers (LCs) are potentially not homogeneous and may be characterized by subpopulations which, if identified, could allow selection of patients amenable to organ preservation treatments in contrast to those to be treated with total laryngectomy (TL). This work aims to analyze a multicentric cohort of T3-T4a LCs treated by upfront TL, investigating the clinical and pathological features that can best predict oncologic outcomes. A total of 149 previously untreated patients who underwent TL for T3-T4a LC at four institutions were analyzed. Survival and disease-control were considered as the main outcomes. A secondary end-point was the identification of covariates associated with nodal status, investigating also the tumor thickness. T and N categories were significantly associated with both overall and disease-specific survival. The number of positive nodes and tracheal involvement were associated with loco-regional failure; post-cricoid area invasion and extra-nodal extension with distant failure. Posterior laryngeal compartment involvement was not a significant prognostic feature, by either univariable and multivariable analyses. These results support the conclusion that laryngeal compartmentalization has no impact on survival in patients treated by upfront TL and the current TNM staging system remains a robust prognosticator in advanced LC.

Outcome predictors for non-resective pharyngoplasty alone or as a part of multilevel surgery, in obstructive sleep apnea-hypopnea syndrome.

PURPOSE: Non-resective pharyngoplasty techniques have been shown to be effective to treat oropharyngeal collapse in patients affected by obstructive sleep apnea-hypopnea syndrome (OSAHS). The aim of our study is to evaluate outcome predictors in a cohort of patients affected by OSAHS and treated with non-resective pharyngoplasty, including variation of pharyngeal measures at the end of the surgical procedure. METHODS: A cohort of patients affected by OSAHS, with palatal or lateral pharyngeal wall collapse, who underwent non-resective pharyngoplasty, were enrolled between 2014 and 2017. Surgical procedures encompassed non-resective pharyngoplasty by expansion sphincter pharyngoplasty (ESP) or barbed antero-lateral pharyngoplasty with barbed reposition pharyngoplasty (BRP) or barbed suspension pharyngoplasty (BSP) techniques, eventually associated with nasal surgery. Pharyngeal measures were recorded intraoperatively and their variation at the end of the procedure was considered. Surgical success was evaluated at least 6 months after surgery with respiratory polygraphy and ESS questionnaire. Outcome predictors were examined by multivariable logistic regression and ROC curve analysis. RESULTS: Seventy patients met the study inclusion criteria. ESP, BRP, and BSP in a uni-/multilevel setting led to significant improvement of all respiratory polygraphic parameters and daily sleepiness (p < 0.0001). Outcome analysis showed that greater variation of antero-posterior pharyngeal measure was associated with success (p = 0.01), with an optimal cutoff value of 8.5 mm; low AHIpre, high ESSpre, and antero-lateral pharyngoplasty with barbed sutures were associated with a higher rate of cure (p < 0.05). CONCLUSIONS: Non-resective pharyngoplasty is effective in treating OSAHS patients affected by palatal or lateral pharyngeal wall collapse, and intraoperative variation of antero-posterior width may be a useful tool to predict surgical success.

Prognostic Significance of Peripheral T-Cell Subsets in Laryngeal Squamous Cell Carcinoma.

OBJECTIVES: The role of the immune system in head and neck squamous cell carcinoma is controversial. The aim of our study was to analyze full blood counts and distribution of T cell subsets in patients affected by laryngeal squamous cell cancer (LSCC) and their association with clinical variables and survival. STUDY DESIGN: Retrospective study. METHODS: We analyzed the levels of platelets, lymphocytes, and neutrophils, as well as the CD4+, CD8+, and CD3+ T-cell subpopulations by cytofluorometry in LSCC patients. A cohort of healthy patients was used as control group. The disease-specific survival (DSS) was considered as survival outcome. RESULTS: Sixty-five LSCC patients and 48 controls were enrolled. In LSCC patients, neutrophils were higher than in the healthy group (P < .0001). The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) were both higher in LSCC patients (P < .0001). In patients treated for recurrent disease, the CD8+/CD3+ ratio was increased (P = .02), while the CD4+/CD8+ (P = .03) and CD4+/CD3+ (P = .04) ratios were lower. In patients with lymph node metastases, leukocytes (P = .03), CD3+ (P = .04), and CD4+ (P = .0098) were all higher. Among Stages III-IV patients, low lymphocyte and low leukocyte count were associated with worse DSS. CONCLUSION: Our data demonstrate that NLR and PLR are significantly increased in LSCC. Lower CD4+/CD8+ and CD3+/CD8+ ratios are related to recurrent disease and a higher level of CD3+ and CD4+ is associated with nodal metastasis. LEVEL OF EVIDENCE: 4.

Postoperative radiotherapy (PORT) for early oral cavity cancer (pT1-2,N0-1): A review.

Early stage (T1-2, N0-1) oral squamous cell carcinoma (OSCC) has a generally favorable prognostic outcome. However, locoregional recurrences can occur in up to 30-35% of patients, and 20% will eventually die of disease. National and international treatment guidelines do not recommend the use of postoperative radiotherapy (PORT) in a setting of early OSCC, and highlight surgery alone as the standard single modality treatment. Notwithstanding, the negative prognostic impact of some adverse pathological features, such as perineural and lymphovascular invasion, poor differentiation, depth of invasion >4 mm, and presence of nodal metastasis, is well known. The advantages of PORT in such scenarios are still debated. The aim of this study was to review the more recent literature to provide evidence on the benefits of PORT in the context of early stage OSCC.

A Multidisciplinary Team Guided Approach to the Management of cT3 Laryngeal Cancer: A Retrospective Analysis of 104 Cases.

The optimal treatment for T3 laryngeal carcinoma (LC) is still a matter of debate. Different therapeutic options are available: Transoral laser microsurgery (TLM), open partial horizontal laryngectomies (OPHLs), total laryngectomy (TL), and organ preservation protocols (radiation therapy (RT) or chemo-radiation (CRT)). This study aimed to retrospectively evaluate oncologic outcomes of 104 T3 LCs treated by surgery or non-surgical approaches from January 2011 to December 2016 at a single academic tertiary referral center. Each case was evaluated by a multidisciplinary team (MDT) devoted to the management of head and neck cancers. We divided the cohort into two subgroups: Group A, surgical treatment (TLM, OPHLs, TL) and Group B, non-surgical treatment (RT, CRT). For the entire cohort, two- and five-year overall survival (OS) rates were 83% and 56%, respectively. The two- and five-year disease-free survival (DFS) rates were 75% and 65%, and disease-specific survival rates were 93% and 70%, respectively. The N category was a significant independent prognosticator for OS (p = 0.02), whereas Group B was significantly and independently associated with DFS (HR 4.10, p = 0.006). Analyzing laryngo-esophageal dysfunction-free survival as an outcome, it was found that this was significantly lower in higher N categories (p = 0.04) and in cases that underwent non-surgical treatments (p = 0.002). Optimization of oncologic outcomes in T3 LCs may be obtained only by a comprehensive MDT approach, considering that different treatment options have heterogenous toxicity profiles and indications.

Barbed suspension pharyngoplasty for treatment of lateral pharyngeal wall and palatal collapse in patients affected by OSAHS.

PURPOSE: The aim of this study is to analyze the efficacy of a new modified pharyngoplasty technique with barbed sutures: barbed suspension pharyngoplasty (BSP). METHODS: We enrolled patients affected by obstructive sleep apnea-hypopnea syndrome (OSAHS), having the main site of obstruction at the palatal and lateral pharyngeal walls, who refused or failed to tolerate CPAP therapy and underwent non-resective pharyngoplasty with barbed sutures between January 2014 and October 2017. Two surgical techniques with barbed sutures were used: barbed reposition pharyngoplasty (BRP) and BSP; the main characteristics of the latter are a double passage of the needle, each side, through the soft palate. RESULTS: Forty-two patients met the study inclusion criteria and were included in the analysis. Twenty-two patients underwent BRP and 20 BSP. Patients treated with both BRP and BSP achieved significant improvement in polysomnographic parameters: AHI, ODI, t90%, and daily sleepiness tested by the ESS questionnaire (p < 0.001). There were no significant differences between groups considering gender, age, or severity of OSAHS (p > 0.05). Outcomes were also comparable (p = 0.10) in the two groups; patients who underwent BSP had successful treatment in 100% of cases, compared to 86% with BRP, with a cure rate of 40% vs. 18%. CONCLUSIONS: BSP is a novel surgical technique that is effective in treating oropharyngeal collapse and can be tailored for patients with high collapsibility of the soft palate who might benefit from the palatal stiffness given by multiple passages of the suture inside it.

Open Partial Horizontal Laryngectomies for T3⁻T4 Laryngeal Cancer: Prognostic Impact of Anterior vs. Posterior Laryngeal Compartmentalization.

Open partial horizontal laryngectomies (OPHLs) are well-established and oncologically safe procedures for intermediate⁻advanced laryngeal cancers (LC). T⁻N categories are well-known prognosticators: herein we tested if "anterior" vs. "posterior" tumor location (as defined in respect to the paraglottic space divided according to a plane passing through the arytenoid vocal process, perpendicular to the ipsilateral thyroid lamina) may represent an additional prognostic factor. We analyzed a retrospective cohort of 85 T3⁻4a glottic LCs, treated by Type II or III OPHL (according to the European Laryngological Society classification) from 2005 to 2017 at two academic institutions. Five-year overall survival (OS), disease-specific survivals (DSS), and recurrence-free survivals (RFS) were compared according to tumor location and pT category. Anterior and posterior tumors were 43.5% and 56.5%, respectively, 78.8% of lesions were T3 and 21.2% were T4a. Five-year OS, DSS, and RFS for T3 were 74.1%, 80.5%, and 63.4%, respectively, and for T4a 71.8%, 71.8%, and 43%, respectively (p not significant). In relation to tumor location, the survival outcomes were 91%, 94.1%, and 72.6%, respectively, for anterior tumors, and 60.3%, 66.3%, and 49.1%, respectively, for posterior lesions (statistically significant differences). These data provide evidence that laryngeal compartmentalization is a valid prognosticator, even more powerful than the pT category.

Unknown primary of the head and neck: a new entry in the TNM staging system with old dilemmas for everyday practice.

PURPOSE OF REVIEW: To summarize the most recent nuances in diagnosis, management, and prognostic stratification of carcinoma of unknown primary of the head and neck (CUPHN), in light of its recent re-assessment in the eighth edition of the TNM Classification Manual. RECENT FINDINGS: At least in Western Countries, most CUPHN are expected to be Human Papilloma Virus (HPV)-positive with an oropharyngeal origin. Their appropriate diagnosis starts with fine needle aspiration cytology and/or core biopsy of pathologic lymph node(s) with staining for p16 by immunohistochemistry and subsequent HPV detection by PCR. If these exams are negative (especially in Eastern Countries), in-situ hybridization for Epstein-Barr virus detection should be added. Thorough clinical examination should encompass white light videoendoscopy with the adjunction of bioendoscopic techniques (such as narrow band imaging). Radiologic workup (by CT, MR and/or PET) should be limited to cases that are persistently negative after comprehensive endoscopic evaluation. Invasive diagnostic procedures, such as unilateral or bilateral palatine tonsillectomy and base of tongue mucosectomy, may play a staging as well as a therapeutic role in CUPHN management. SUMMARY: Every effort should be made to identify and remove the primary site of a CUPHN: in doing so, possible subsequent de-intensification protocols by irradiation of the neck alone (with or without previous neck dissection according to the cN category, patient's risk profile, and general status) can be taken into consideration on a case-by-case basis.

Glottic exposure for transoral laser microsurgery: Proposal of a mini-version of the laryngoscore.

OBJECTIVES: Good laryngeal exposure (GLE) is typically regarded as an essential prerequisite for transoral laser microsurgery (TLM). The Laryngoscore is a preoperative scoring system aimed at predicting glottic visualization through the laryngoscope using easy patient-derived parameters. However, the presence of subjective variables may hamper its reliability and reproducibility. The aim of the present study was to provide a validation of the Laryngoscore and to develop a revised mini-version of the same, called mini-Laryngoscore (mLS), which could allow even quicker, yet sufficiently accurate, preoperative prediction of GLE. STUDY DESIGN: Prospective cohort study. METHODS: We prospectively evaluated 310 consecutive patients submitted to TLM between 2014 and 2017, grading each patient according to the variables considered in the Laryngoscore. RESULTS: Among the 11 variables of the previous Laryngoscore, three were confirmed as statistically significant at validation: interincisors gap, thyromental distance, and upper jaw dental status. We chose these three variables as part of the revised mLS (ranging from 0 to 4). In our cohort, 30% of the patients obtained a score of 0, 57% a score of 1, 11% a score of 2, and 2% a score of ≥3. GLE was achieved in 97%, 85%, 65%, and 20% of cases, respectively. CONCLUSION: Our validation confirmed the predictive ability of the Laryngoscore. Furthermore, although composed of only three clinical parameters, the mLS was still able to convey useful information regarding the possibility of obtaining GLE. LEVEL OF EVIDENCE: 2 Laryngoscope, 129:1617-1622, 2019.

Radiation-Induced Sarcoma of the Head and Neck: A Review of the Literature.

In the last decades, radiotherapy (RT) has become one of the cornerstones in the treatment of head and neck (HN) malignancies and has paralleled an increase in long-term patient survival. This lead to a concomitant increase in the incidence of radiation-induced sarcomas (RIS) of the irradiated field, with an annual rate up to 0.17%. The new techniques of irradiation do not seem to influence the risk of RIS of the HN (RISHN), which mainly develop within the middle-dose field. The median latency of RISHN after RT is 10-12 years and osteosarcoma is the most represented histotype, even though there is a high variability in time of occurrence and histological features observed. There is no clear evidence of predisposing factors for RISHN, and genetic findings so far have not revealed any common mutation. Early clinical diagnosis of RISHN is challenging, since it usually occurs within fibrotic and hardened tissues, while radiological findings are not pathognomonic and able to differentiate them from other neoplastic entities. Given the highly aggressive behavior of RISHN and its poor sensitivity to chemotherapy, radical surgery is the most important prognostic factor and the only curative option at present. Nevertheless, the anatomy of the HN district and the infiltrative nature of RIS do not always allow radical intervention. Therefore, a wise integration with systemic therapy and, when feasible, re-irradiation should be performed. Future findings in the genomic features of RISHN will be crucial to identify a possible sensitivity to specific drugs in order to optimize a multimodal treatment that will be ideally complementary to surgery and re-irradiation.

Three-Dimensional Map of Isoprognostic Zones in Glottic Cancer Treated by Transoral Laser Microsurgery as a Unimodal Treatment Strategy.

INTRODUCTION: The Union for International Cancer Control-American Joint Committee on Cancer TNM staging system for glottic squamous cell carcinoma (SCC) includes different types of lesions defined by the involvement of specific subsites in each T category. Our study aims to identify different subcategories according to tumor local extension and determine oncologic outcomes after treatment by transoral laser microsurgery (TLM) alone. METHODS: We retrospectively evaluated 410 patients affected by previously untreated pT1-pT3 glottic SCC treated by TLM alone from January 2005 to December 2015 at the Departments of Otorhinolaryngology-Head and Neck Surgery, Universities of Genoa and Brescia, Italy. All patients had at least 2 years of follow-up. Clinical, radiological, surgical, and histopathological data were reviewed and tumors divided into six subcategories: I, pT1a not involving the anterior commissure (AC); II, pT1b involving the AC; III, pT2 extending superficially to the supraglottis or the subglottis; IV, pT2 infiltrating the vocal muscle; V, pT3 involving the anterior paraglottic space; VI, pT2 or pT3 with vertical extension across the AC with/without involvement of the pre-epiglottic space. Recurrence-free survival (RFS), local control with laser alone (LCL), and organ preservation (OP) were defined as the primary oncologic outcomes. RESULTS: The 2, 5, and 10-year RFS for the entire series were 85.7, 80.3, and 73.8%, LCL rates 93.8, 92.1, and 89.6%, and OP rates 96.8, 95.9, and 93.5%, respectively. However, when comparing the rates of RFS, LCL, and OP for each subcategory, important differences emerged. In particular, subcategories V and VI showed a significantly increased risk of local recurrence [hazard ratio (HR) = 9.2 and 13.3, respectively]. These subcategories also had a significantly reduced probability to achieve LCL (HR: 73.6 and 93.5, respectively) and OP (HR: 6.4 and 8.1, respectively). CONCLUSION: The present classification in subcategories allows introducing the concept of a three-dimensional map of isoprognostic zones in glottic SCC treated by TLM alone as a useful tool in its management by a multidisciplinary tumor board.

Anatomical Cadaver Study of Endolaryngeal Vascularization: Focus on the Glottis, Supraglottis, and Subglottis From the Transoral Microsurgical Point of View.

INTRODUCTION: Carbon dioxide laser coagulation during transoral laser microsurgery (TLM) for laryngeal cancer allows control of bleeding from vessels smaller than 0.5 mm. Therefore, larger arteries and veins must be carefully managed by clipping and/or monopolar cautery. The aim of this paper is to detail endolaryngeal vascular anatomy and identify areas of possible bleeding during TLM. METHODS: We performed an anatomical study on a series of 11 fresh-frozen human cadavers. After injection of a bicomponent red silicone into the innominate, left common carotid, and left subclavian arteries, 22 hemilarynges were dissected, the course of the supraglottic, glottic, and subglottic vessels were traced after microdissection of the intervening structures, and their size measured at specific landmark points where such vessels are more frequently encountered during TLM. RESULTS: Three vessels arising from the superior laryngeal artery were identified after its entry point at the level of the thyro-hyoid membrane: (1) the epiglottic artery (EA), documented in 100% of cases, a common trunk dividing into two main vessels (2) the postero-inferior artery (PIA), present in 100% of the specimens, running downward and dividing in a posterior (pPIA), and anterior (aPIA) branches (3) the antero-inferior artery (AIA), present in 95% of our specimens, running downward to the anterior commissure (AC). Two transverse anastomotic networks (TANs) connected the AIA and PIA, both parallel to the vocal muscle, one lateral (present in 100% of cases), and another medial (91% of specimens). Finally, a fourth vessel supplying the glottic plane was found to be the endolaryngeal paracommissural branch of the crico-thyroid artery (PCA), arising from the inferior laryngeal artery and emerging just below the AC, through the crico-thyroid membrane (reported in 100% of the specimens). This vessel anastomosed in 91% of cases with the AIA, through one or both of the TANs. CONCLUSION: The course of the endolaryngeal arteries, their relationships with adjacent structures, and size at specific landmark points have been herein described in order to provide surgeons with a map to guide them during the steep learning curve of transoral surgery of the larynx, with special emphasis given to TLM.