Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, and Larynx: A Scoping Review of Treatment Guidelines Worldwide.

Head and neck cancer (HNC) treatments have been based on single or multimodal therapies with surgery, radiotherapy (RT), chemotherapy, and immunotherapy. However, treatment recommendations among countries may differ due to technological/human resources and usual local practices. This scoping review aims to identify, compare, and map the clinical practice guidelines (CPGs) for treating squamous cell carcinoma (SCC) of the oral cavity, oropharynx, and larynx worldwide. A search strategy on global CPGs for HNC was performed by using five electronic databases and grey literature. CPGs were selected for inclusion using EndNote-20 and Rayyan online software. No language or publication date restrictions were applied. The results were analyzed descriptively considering the most updated CPG version. In total, 25 CPGs covering the head and neck region (10), the larynx (7), the oral cavity (5), and the oropharynx (3), were found in 13 geographical regions, and 19 were developed by medical societies from 1996 to 2023. Surgery and RT remain the main modalities for early-stage HNC, with surgery preferred in low-resource countries, and RT in selected cases, especially in the larynx/oropharynx aiming to achieve a cure with organ preservation. Human papillomavirus infection for oropharyngeal SCC is not tested in some Asian countries and there is still no consensus to treat p16-positive cases differently from p16-negative. Recommendations for larynx preservation vary according to facilities in each country, however, individualized choice is emphasized. Inequality across countries/continents is evident, with a similar pattern of recommendations among developed as well as developing ones. No CPGs were found in Latin America as well as Oceania countries, where the incidence of HNC is high and limitations of access to treatment may be encountered.

Overview of glottic laryngeal cancer treatment recommendation changes in the NCCN guidelines from 2011 to 2022.

BACKGROUND: The treatment of glottic cancer remains challenging, especially with regard to morbidity reduction and larynx preservation rates. The National Comprehensive Cancer Network (NCCN) has published guidelines to aid decision-making about this treatment according to the tumor site, clinical stage, and patient medical status. AIM: The present review was conducted to identify changes in the NCCN guidelines for glottic cancer treatment made between 2011 and 2022 and to describe the published evidence concerning glottic cancer treatment and oncological outcomes in the same time period. METHODS AND RESULTS: Clinical practice guidelines for head and neck cancer published from 2011 up to 2022 were obtained from the NCCN website (www.NCCN.org). Data on glottic cancer treatment recommendations were extracted, and descriptive analysis was performed. In addition, a review of literature registered in the PubMed database was performed to obtain data on glottic cancer management protocols and treatment outcomes from randomized controlled trials, systematic reviews, and meta-analyses published from 2011 to 2022. In total, 24 NCCN guidelines and updates and 68 relevant studies included in the PubMed database were identified. The main guideline changes made pertained to surgical and systemic therapies, the consideration of adverse features, and new options for the treatment of metastatic disease at initial presentation. Early-stage glottic cancer received the most research attention, with transoral endoscopic laser surgery and radiotherapy assessed and compared as the main treatment modalities. Reported associations between treatment types and survival rates for this stage of glottic cancer appear to be similar, but functional outcomes can be highly compromised. CONCLUSION: NCCN panel members provide updated recommendations based on currently accepted treatment approaches for glottic cancer, constantly reviewing new surgical and non-surgical techniques. The guidelines support decision-making about glottic cancer treatment that should be individualized and prioritize patients' quality of life, functionality, and preferences.

Organ preservation and oncological outcomes in early laryngeal cancer: a propensity score-based study.

BACKGROUND: The rates of laryngeal preservation according to therapeutic modality in patients with initial laryngeal squamous cell carcinoma (LSCC) are still controversial. This study evaluated the rates of laryngeal preservation in patients who underwent treatment with surgery or radiotherapy. METHODS: This retrospective cohort study evaluated 151 patients with stage I or II LSCC. Ninety-six patients were matched using a propensity-score and outcomes were compared within this group. RESULTS: Regarding overall, cancer-specific survival and larynx preservation, no differences were observed according to the therapeutic modalities, but patients who underwent radiotherapy had a higher rate of local recurrence than those who underwent surgery. Patients classified as ASA 3 or 4 and treated with radiotherapy showed a tendency of higher risk of larynx loss. CONCLUSIONS: Patients with stage I or II laryngeal tumours can be submitted to surgery or radiotherapy with similar rates of laryngeal preservation.

Identification of secondary predictive factors for acute hypocalcemia following thyroidectomy in patients with low postoperative parathyroid hormone levels without overt calcium deficiency: A cohort study.

BACKGROUND: The transient acute hypocalcemia (HypoCa) is the most prevalent complication after total thyroidectomy, detected primarily by subnormal intact parathyroid hormone (iPTH) and calcium levels. However, the need for calcium supplementation is ambiguous in patients who exhibit low iPTH with normal calcium levels. The aim of this study was to evaluate complementary predictors of HypoCa in this scenario. METHODS: A retrospective cohort study with of 1597 consecutive patients undergoing total thyroidectomy, with or without neck dissection, from January 2014 to December 2018 at a single institution. Patients with an iPTH <12 pg/mL and a total calcium level ≥8 mg/dL in the first 8 h after surgery were included. RESULTS: 1597 patients identified with low postoperative iPTH without overt calcium deficiency was diagnosed. The transient HypoCa in that specific subgroup was 509 (31.9%). Multivariate analysis indicated that HYPOCA was associated with bilateral level VI neck dissection and pre- to postoperative calcium reduction >38 pg/mL. To better illustrate the model, we plotted a nomogram with the variables selected for the final model. CONCLUSION: Total thyroidectomy patients who exhibit low postoperative iPTH levels without overt calcium deficiency should be considered for calcium replacement therapy when they a marked drop in iPTH postoperatively and underwent bilateral level VI neck dissection.

Transoral thyroidectomy (TOETVA): Complications, surgical time and learning curve.

BACKGROUND: Since 2018, transoral endoscopic thyroidectomy vestibular approach (TOETVA) has emerged as a true scarless thyroid surgery. In this study, we explore early outcomes and learning curve of this new approach. METHODS: A retrospective cohort including conventional thyroidectomies and TOETVAs performed in a cancer center was designed. Learning curve and early surgical outcomes of TOETVA were assessed and compared to conventional thyroidectomy. RESULTS: A total of 56 TOETVAs and 745 conventional thyroid procedures were included. In the TOETVA group, we had a 14.4% total complication rate with no permanent vocal cord paresis or hypocalcemia. The mean surgical time dropped from 167 to 117 min (p = 0.0001) after the 15 first cases. Comparing to conventional procedures, we didn't find any significant difference in complications rate. Operative time was longer in the TOETVA group. CONCLUSIONS: In this study, TOETVA was safe and feasible, with a learning curve of 15 cases.

Impact of treatment modality on survival in patients with stage IV laryngeal cancer: A population-based propensity score analysis.

INTRODUCTION: The treatment of advanced stage laryngeal suffered a major shift away from surgery and towards larynx-preservation alternatives after the publication of major clinical trials. But its applicability in real-world situations is not consensual. MATERIALS AND METHODS: We reviewed a population-based database from Brazil regarding patients treated for laryngeal cancer and selected those with stage IV disease at presentation. Survival analysis was realized by the Cox proportional hazards method and propensity scores were used to compensate for non-random allocation to different treatment arms. RESULTS: A total of 5577 patients were included in the analyses, with 4243 staged as CS IVa, 1010 as CS IVb and 324 as CS IVc. In univariate and multivariate analysis, gender, cT stage, cN stage, cM stage and treatment modality were significant predictors of disease-specific survival. In patients with CS IVa, age, gender, payment modality, location within the larynx, cT and cN stages and treatment modality were significant. After propensity score adjustment, treatment modality remained significant, favoring primary surgery with disease-specific survival (HR: 0.5041, 95% CI: 0.4494-0.5644, p < 0.001) and overall survival (HR: 0.5485, 95% CI: 0.4955-0.6072, p < 0.001) as outcomes of interest. Patients staged as cT4a cN0 were selected and analyzed as a distinct subset. In multivariate analysis, treatment modality was the only variable with significant prognostic impact with improved outcome for surgery-based treatment (HR: 2.521, 95% CI: 1.897-3.350, p < 0.001). CONCLUSIONS: The extrapolation of clinical trials to the real-world facilities must be carefully weighted. The setting of trial conduction may influence its outcome and may not be reproducible. Our results show that patient selection and the facilities of clinical trials may play a significant role in the success of non-surgical approaches to non-metastatic stage IV laryngeal cancer.

Increased DSG2 plasmatic levels identified by transcriptomic-based secretome analysis is a potential prognostic biomarker in laryngeal carcinoma.

OBJECTIVES: The tumor secretome deconvolution is a promising strategy to identify diagnostic and prognostic biomarkers. Here, transcriptomic-based secretome analysis was performed aiming to discover laryngeal squamous cell carcinomas (LSCC) biomarkers from potentially secreted proteins (PSPs). MATERIAL AND METHODS: The tumor expression profile (35 LSCC biopsies compared with surrounding normal tissues - SN) revealed 589 overexpressed genes. This gene list was used for secretome analysis based on laryngeal tumors and related secretome databases. RESULTS: Forty-nine (Laryngeal tumor secretome database) and 50 (Human Protein Atlas and Cancer Secretome Database) PSPs presented an association with worse overall survival. Specifically, DSG2 overexpression was strongly correlated with poor survival and distant metastasis. DSG2 increased expression was confirmed in the LSCC dataset (LSCC = 111; SN = 12) from TCGA. A significant association between shorter survival and DSG2 overexpression was also detected. In an independent cohort of cases, we analyzed and confirmed high protein levels of DSG2 in plasma from LSCC patients. CONCLUSION: A set of PSPs including the circulating DSG2, were associated with shorter overall survival in LSCC. DSG2 overexpression was also correlated with distant metastasis. The high plasmatic protein levels of DSG2 suggest its potential to be tested in liquid biopsies and applied as prognostic biomarker of LSCC.

Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients.

OBJECTIVES: The current treatment of laryngeal squamous cell carcinoma (LSCC) is based on radical surgery and radiotherapy resulting in high morbidity. Chemoradiotherapy has been used as alternative to organ sparing; however, several advanced cases presented resistance to treatment, which contributes to a high risk of recurrence and mortality. Coding RNAs and miRNAs have potential to be used as biomarkers or targets for cancer therapy. MATERIALS AND METHODS: In this study, 36 LSCC and 5 non-neoplastic control samples were investigated using miRNA and mRNA large-scale expression analysis and a cross-validation was performed using the TCGA database (116 LSCC and 12 surrounding normal tissues). RESULTS: The large-scale profiling revealed the involvement of 28 miRNAs and 817 genes differentially expressed in LSCC. An integrative analysis comprising predicted and experimentally validated miRNA/mRNA interactions (negatively correlated), resulted in 28 miRNAs and 543 mRNAs. Decreased expression of miR-199b was significantly associated with shorter disease-free survival in LSCC (internal and TCGA datasets). The expression levels of selected miRNAs (miR-199b-5p, miR-29c-3p, miR-204-5p, miR-125b-5p and miR-92a-3p) and genes (COL3A1, COL10A1, ERBB4, HMGA2, HLF, TOP2A, MMP3, MMP13, MMP10 and PPP1R3) were confirmed as altered in LSCC by RT-qPCR. Additionally, a drug target prediction analysis revealed drug combinations based on miRNA and mRNA expression, pointing out novel alternatives to optimize the LSCC treatment. CONCLUSION: Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets.

Early metabolic 18F-FDG PET/CT response of locally advanced squamous-cell carcinoma of head and neck to induction chemotherapy: A prospective pilot study.

OBJECTIVE: The objective of this study was to assess the clinical value of 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) after the first cycle of induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LASCCHN). METHODS AND FINDINGS: A prospective, single-arm, single center study was performed, with patients enrolled between February 2010 and July 2013.Patients (n = 49) with stage III/IVA-B LASCCHN who underwent IC with taxanes, cisplatin, and fluorouracil were recruited. Staging procedures included loco-regional and chest imaging, endoscopic examination, and PET/CT scan. On day 14 of the first cycle, a second PET/CT scan was performed. Patients with no early increase in regional lymph node maximum 18F-FDG standard uptake value (SUV), detected using 18F-FDG PET/CT after first IC had better progression-free survival (hazard ratio (HR) = 0.18, 95%, confidence interval (CI) 0.056-0.585; p = 0.004) and overall survival (HR = 0.14, 95% CI 0.040-0.498; p = 0.002), and were considered responders. In this subgroup, patients who achieved a reduction of ≥ 45% maximum primary tumor SUV experienced improved progression-free (HR = 0.23, 95% CI 0.062-0.854; p = 0.028) and overall (HR = 0.11, 95% CI 0.013-0.96; p = 0.046) survival. CONCLUSIONS: These results suggest a potential role for early response evaluation with PET/CT examination in patients with LASCCHN undergoing IC. Increased regional lymph node maximum SUV and insufficient decrease in primary tumor uptake predict poorer outcomes.

Retroauricular endoscopic and robotic versus conventional neck dissection for oral cancer.

There has been a significant increase in concern towards improving aesthetic and functional outcomes without compromising the oncologic effectiveness in head and neck surgery. The aim of the current study is to assess the feasibility and oncological outcome of the retroauricular approach for endoscopic and robot-assisted selective neck dissection (SND) for oral cancer in comparison with the conventional SND. A retrospective single institute cohort study was designed. Patients undergoing an SND for oral cavity carcinoma were included and allocated into two groups: (1) retroauricular approach group for endoscopic-assisted or robot-assisted SND or (2) transcervical approach group for the conventional SND. Primary endpoint was the perioperative and postoperative treatment outcomes. Secondary endpoint was the early oncologic outcome. Sixty patients were included (17 retroauricular; 43 conventional). For the primary outcome, only a significant longer operative time in the retroauricular group was identified. No unintentional injury or conversion to the conventional surgery was recorded. There was no significant difference identified in the early oncologic outcome, including number of retrieved lymph nodes and disease-free survival. Postoperative aesthetic results were considered superior when subjectively compared to the conventional approaches. Endoscopic and robot-assisted SND via a retroauricular approach is feasible, safe, and oncologically efficient when compared with the conventional surgery in a short follow-up scenario. It can be used for selected cases with a clear cosmetic benefit. However, further research with longer follow-up and patient satisfaction analysis is mandatory.

Quality assessment in head and neck oncologic surgery in a Brazilian cancer center compared with MD Anderson Cancer Center benchmarks.

BACKGROUND: Quality assessment is a major tool for evaluation of health care delivery. In head and neck surgery, the University of Texas MD Anderson Cancer Center (MD Anderson) has defined quality standards by publishing benchmarks. METHODS: We conducted an analysis of 360 head and neck surgeries performed at the AC Camargo Cancer Center (AC Camargo). The procedures were stratified into low-acuity procedures (LAPs) or high-acuity procedures (HAPs) and outcome indicators where compared to MD Anderson benchmarks. RESULTS: In the 360 cases, there were 332 LAPs (92.2%) and 28 HAPs (7.8%). Patients with any comorbid condition had a higher incidence of negative outcome indicators (p = .005). In the LAPs, we achieved the MD Anderson benchmarks in all outcome indicators. In HAPs, the rate of surgical site infection and length of hospital stay were higher than what is established by the benchmarks. CONCLUSION: Quality assessment of head and neck surgery is possible and should be disseminated, improving effectiveness in health care delivery. © 2015 Wiley Periodicals, Inc. Head Neck 38: 1002-1007, 2016.

Swallowing, speech and quality of life in patients undergoing resection of soft palate.

The aim of this study was to evaluate swallowing, speech and quality of life in patients undergoing surgery for malignant tumors involving soft palate. We performed a cross sectional study of 23 patients (aged 32-80 years), submitted to soft palate resection, free of disease for at least 1 year. Primary closure of the surgical defect was performed in 5 patients (21.7 %), adaptation of a palatal obturator prosthesis in 2 (8.7 %), myocutaneous flap in 5 (21.7 %), local flap in 2 (8.7 %) and microsurgical free flap in 9 (39.1 %). All patients were submitted to fibreoptic endoscopic evaluation and completed functional and quality of life questionnaires. Functional evaluation of swallowing showed higher prevalence of pooling of food in the nasopharynx in patients submitted to regional flap reconstruction or primary closure (53.9 %). Swallowing difficulties were predominantly related to solid foods (54.5 %) and were associated with more extensive palatal resections. Most individuals submitted to reconstruction with microsurgical flaps had satisfactory velopharyngeal mobility (87 %). The presence of nasal air escape or velopharyngeal gap was minimal in most of the sample. Hypernasality contributed minimally to imprecisions in speech articulation or intelligibility. Vocal alteration did not impact patients' quality of life. Pharyngeal phase of swallowing was satisfactory in most patients. However, nasal reflux and penetration were present in a few patients. Most patients had minimal phono-articulatory alterations as a global outcome. Scores of swallowing and speech parameters regarding the questionnaires used were high, demonstrating minor impact on quality of life.