Discovery and Validation of a CT-Based Radiomic Signature for Preoperative Prediction of Early Recurrence in Hypopharyngeal Carcinoma.

PURPOSE: In the clinical management of hypopharyngeal squamous cell carcinoma (HSCC), preoperative identification of early recurrence (≤2 years) after curative resection is essential. Thus, we aimed to develop a CT-based radiomic signature to predict early recurrence in HSCC patients preoperatively. METHODS: In total, 167 HSCC patients who underwent partial surgery were enrolled in this retrospective study and divided into two groups, i.e., the training cohort (n = 133) and the validation cohort (n = 34). Each individual was followed up for at least for 2 years. Radiomic features were extracted from CT images, and the radiomic signature was built with the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model. The associations of preoperative clinical factors with early recurrence were evaluated. A radiomic signature-combined model was built, and the area under the curve (AUC) was used to explore their performance in discriminating early recurrence. RESULTS: Among the 1415 features, 335 of them were selected using the variance threshold method. Then, the SelectKBest method was further used for the selection of 31 candidate features. Finally, 11 out of 31 optimal features were identified with the LASSO algorithm. In the LR classifier, the AUCs of the training and validation sets in discriminating early recurrence were 0.83 (95% CI: 0.76-0.90) (sensitivity 0.8 and specificity 0.83) and 0.83 (95% CI: 0.67-0.99) (sensitivity 0.69 and specificity 0.71), respectively. CONCLUSIONS: Using the radiomic signature, we developed a radiomic signature to preoperatively predict early recurrence in patients with HSCC, which may serve as a potential noninvasive tool to guide personalized treatment.

An atypical lipomatous tumor mimicking a giant fibrovascular polyp of the hypopharynx: A case report.

RATIONALE: Giant fibrovascular polyps (GFVPs) found in the hypopharynx are exceedingly rare. These are benign tumors which are identified by CT or MRI and usually treated based on symptoms. Even more rarely, pathology may identify one of these masses as an atypical lipomatous tumor (ALT). This paper will present a case of an ALT of the hypopharynx that was originally classified as a GFVP, highlighting the difficulty in distinguishing between them and the importance of making the correct diagnosis. PATIENT CONCERNS: An 84-year-old man presented to the emergency department with a 6-month history of a pedunculated hypopharyngeal growth, dysphagia, and intermittent dyspnea. DIAGNOSES: The mass was characterized as a GFVP by barium swallow and MRI. INTERVENTIONS: The hypopharyngeal mass was resected for obstructive symptoms and to confirm the diagnosis. Final pathology found the mass to be more consistent with an atypical lipomatous tumor (ALT). OUTCOMES: The patient's dysphagia and dyspnea resolved. He was free of recurrence at 22 months postoperative. LESSONS: Both GFVPs and ALTs are very rarely found in the hypopharynx but can be easily misclassified as one another. Imaging is useful to initially characterize the mass, but to definitively differentiate between them, pathological analysis is necessary. Although they are rare, it is important to consider both possibilities on the differential for hypopharyngeal masses. Further, accurate analysis is essential to distinguish between them because their definitive management and follow-up is different.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space.

Chapter 3 "Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space" of the World Health Organization (WHO) Blue Book 2017 "Classification of Head and Neck Tumours" shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial-mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier classification, consisting of low- and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine carcinomas (NEC) represents a considerable improvement in terminology and classification. NEC are divided into well-, moderate- and poorly-differentiated neuroendocrine carcinoma. The latter is additionally divided into small cell NEC and large cell NEC (LCNEC). It is of extreme importance that LCNEC, which was associated in the WHO 2005 edition with atypical carcinoid/moderately differentiated neuroendocrine carcinoma, grade II, has now been transferred into the group of poorly differentiated NEC, grade III, displaying a specific morphology and poorer prognosis.

Modified Tumor Classification With Inclusion of Tumor Characteristics Improves Discrimination and Prediction Accuracy in Oral and Hypopharyngeal Cancer Patients Who Underwent Surgery.

Several histopathological characteristics have a significant prognostic impact on recurrence and survival rates in head and neck squamous cell carcinoma (HNSCC). We conducted a retrospective study on patients with HNSCC to compare traditional pathological T (pT) classification to a new T classification system that incorporates these histopathological characteristics.Newly diagnosed patients with HNSCC (n = 349) post major surgery were identified from the cancer registry database between 2004 and 2013. The pT and new T classification systems were compared with respect to recurrence-free survival (RFS), disease-specific survival (DSS), and survival rates using the Cox proportional hazards model with adjustments. The discriminatory ability of these 2 classification systems was evaluated using the adjusted hazard ratio (HR) and Akaike information criterion (AIC) in a multivariate regression model. The prediction accuracy was assessed using Harrell's C-statistic.The new T classification, which incorporated tumor size, extent, and location with histopathological features had better discriminatory ability and monotonicity of gradients than did pT classification. The new T4 classification yielded a higher adjusted HR in RFS (HR, 4.11; 95% confidence interval [CI], 7.75-9.65) and in DSS (HR, 4.39; 95% CI, 1.6-12.03), and a lower AIC in recurrence (927 vs 969) and survival rates (791 vs 833).The new T classification system had better discriminatory ability in RFS and DSS compared with the routinely used American Joint Committee on Cancer (AJCC) pT classification system. Therefore, this new T classification system, which includes tumor size, location, extent, and histopathological features, could be used as an alternative to AJCC pT classification for patients with HNSCC.

Novel laryngoscopic strategies to improve evaluation of the site and extent of primary hypopharyngeal tumours.

OBJECTIVE: To investigate different strategies for displaying the hypopharynx and oesophageal entrance during laryngoscopy for hypopharyngeal cancer. PATIENTS AND METHODS: A total of 113 patients with hypopharyngeal cancer underwent laryngoscopy prior to surgery. The hypopharynx was displayed by: (1) pulling the anterior cervical skin; (2) having the patient perform the Valsalva balloon-blowing manoeuvre; and (3) injecting oxygen through the biopsy channel to expose the oesophageal entrance. The effect of these methods on visualisation of primary tumour size and extent was assessed. RESULTS: During pronunciation of the letter 'e', the hypopharynx was displayed in only 33 patients (29.2 per cent); with anterior cervical skin traction plus the balloon-blowing manoeuvre, the hypopharynx was displayed in 106 patients (93.8 per cent; p < 0.001). The combined strategy was superior especially when judging the extent of posterior pharyngeal wall and postcricoid invasion. Oesophageal entrance involvement was visible in 33 patients upon injecting oxygen through the laryngoscopic biopsy channel, and in 25 patients during radiological examination; laryngoscopy was superior to radiological examination in determining the extent of oesophageal entrance invasion (p = 0.003). CONCLUSION: Adequate laryngoscopic display of the hypopharynx could increase the accuracy of pre-treatment hypopharyngeal cancer staging.

Towards further understanding of prognostic factors for head and neck cancer patients: the example of hypopharyngeal cancer.

OBJECTIVES: Knowledge of prognostic factors is essential for patient care and research. The objectives of this study were to demonstrate that prognostic factors and their impact can vary depending on study design and to examine the relationships between select prognostic factors. METHODS: Retrospective population-based study of patients with cancer of the hypopharynx in Ontario, Canada, from January 1990 to December 1999 identifying and comparing prognostic factors for different survival outcomes and different subpopulations using Kaplan Meier analysis and Cox Proportional Hazards models. RESULTS: The impact of prognostic factors varies within subgroups of a study population, varies with treatment decisions, and varies with the outcome of interest. CONCLUSIONS: N and T category were the dominant prognostic factors in hypopharyngeal cancer. Performance status was an independent predictor of survival.

TNM-based stage groupings in head and neck cancer: application in cancer of the hypopharynx.

BACKGROUND: The purpose of this study was to test the Union Internationale Contre le Cancer (UICC)/TNM category-based head and neck cancer stage grouping systems proposed in the literature for their ability to create clinically relevant prognostic groups of like-patients with cancer of the hypopharynx. METHODS: Population-based retrospective survival study of 595 patients with squamous cell carcinoma of the hypopharynx across Ontario, Canada, from January 1990 to January 2000. The grouping systems of UICC/TNM, T and N Integer Score (TANIS), Hart, Berg, Snyderman, Kiricuta, and Hall were tested and compared for prognostic ability using hazard consistency, hazard discrimination, percent variance explained, outcome prediction, and balance. RESULTS: All 8 systems predicted disease-specific survival. The system proposed by Snyderman performed the best, and UICC/TNM sixth edition did not perform as well as most. CONCLUSION: The UICC/TNM stage group classification, although successful in creating statistically distinct groups, did not perform as well as other stage grouping systems, continuing a theme that has been reported previously.

La nueva clasificación de la O.M.S. 2005. Lesiones precursoras y los tumores de la laringe, hipofaringe y tráquea / The updated WHO Head and Neck Tumours Classification (2005). Epithelial precursor lesions and tumours of the larynx, hypopharynx and trachea

Se revisa la última clasificación de los Tumores de la Cabeza y Cuello de la Organización Mundial de la Salud (OMS) 2005 de las áreas de laringe, hipofaringe y traquea, especialmente en lo relativo a las nuevas entidades. Se comentan los aspectos específicos tanto de los tumores de células escamosas y sus variedades, así como de algunos otros de partes blandas y óseas. Además se trata acerca de las recomendaciones que aporta para su inclusión en los informes de patología así como la evaluación de los factores predictivos y pronósticos para cada tipo histológico. Se hace hincapié en el valor añadido de la nueva clasificación al integrar la anatomía y la patología convencional y la inmunohistoquímica con la epidemiología, etiología, el diagnóstico por imagen, la genética y los factores pronósticos y predictivos, todo ello encaminado al adecuado manejo clínico de estos tumores

We revise the last WHO 2005 Head and Neck Tumour classification, focusing on Larynx, Hypopharynx and Trachea, and especially on new entities. Specifically, we discuss about different aspects related to squamous carcinoma and its variants, soft tissue and bone tumours. The classification includes a predictive factor evaluation for each histological type, as well as recommendations about the inclusion of these changes in a pathology report. We further stress the value added by this new classification, as it integrates Anatomy and Histopathology with Immunohistochemistry, Epidemiology, Radiology and Genetics, leading to a better clinic handling of these tumours

Comparison of the Radiation Therapy Oncology Group recursive partitioning classification and Union Internationale Contre le Cancer TNM classification for patients with head and neck carcinoma.

BACKGROUND: Prognostic models need to be tested in external validation studies to assess generalizability. Recursive partitioning analysis (RPA), a prognostic system based on the creation of a classification tree, has been proposed as a classification method in patients with head and neck carcinoma. The aim of this study was to compare the RPA and Union Internationale Contre le Cancer (UICC) TNM classification systems in patients with head and neck carcinoma treated consecutively in a single center. METHODS: A total of 2166 patients with carcinomas of the oral cavity, oropharynx, hypopharynx, and larynx was classified according to both the RPA and the TNM classification systems, and the results were compared. The endpoints considered were observed survival and survival free of locoregional tumor. The two methods of classification were evaluated objectively by use of measures of intrastage homogeneity (hazard consistency), interstage heterogeneity (hazard discrimination), predictive power (outcome prediction), and patient distribution between stages (balance). RESULTS: When the endpoint considered was observed survival, there were no clinically relevant differences between the two classifications. However, when the endpoint was locoregional control, the RPA system was sensitive to the type of treatment used, and it was not generalizable. CONCLUSIONS: To evaluate generalizability, new classification proposals need external validation studies that objectively measure the quality of the model. The performance of the RPA system was not reproducible in our cohort of patients when the endpoint evaluated was locoregional control.

Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation and susceptibility to metastasis. We report the first large-scale gene expression analysis of a unique HNSCC location, the hypopharynx. Four normal and 34 tumour samples were analysed with 12 600 gene microarrays. Clusters of differentially expressed genes were identified in the chromosomal regions 3q27.3, 17q21.2-q21.31, 7q11.22-q22.1 and 11q13.1-q13.3, which, interestingly, have already been identified by comparative genomic hybridization (CGH) as major regions of gene amplification. We showed that six overexpressed genes (EIF4G1, DVL3, EPHB4, MCM7, BRMS1 and SART1) located in these regions are indeed amplified. We report 119 genes that are highly differentially expressed between 'early' tumours and normal samples. Of these, we validated by quantitative PCR six novel poorly characterized genes. These genes are potential new markers of HNSCC. Comparing patients with relatively nonaggressive and aggressive tumours (without or with clinical evidence of metastasis 3 years after surgery), we identified 164 differentially expressed genes potentially involved in the acquisition of metastatic potential. This study contributes to the understanding of HNSCC, staging patients into prognostic groups and identifying high-risk patients who may benefit from more aggressive treatment.

Basaloid squamous cell carcinoma of the hypopharynx.

In a retrospective study, clinical, histopathological and immunohistochemical findings of basaloid squamous cell carcinoma (BSCC) of the hypopharynx are analyzed and compared with the literature. Among 196 patients treated for hypopharyngeal carcinoma between January 1993 and December 2000, 6 patients fulfilled the morphological and immunohistochemical criteria of a BSCC. Three primary tumors were initially classified as T(3) and 3 as T(1), 3 presented with lymph node metastases. In no case was the BSCC associated with another primary neoplasm. Two patients developed distant metastases during the follow-up and died from the disease at 26 and 35 months. Four patients are alive with no evidence of disease at 27, 29, 61 and 87 months. We observed a contrast in the clinical behavior between the cases reported in the literature and our cases, as our BSCC of the hypopharynx were not detected at a more advanced stage than were the SCC and were in no case associated with another second primary tumor. However, the number of our cases is too small to draw reliable conclusions.

[Epidemiologic analysis of patients with laryngeal and hypopharyngeal cancer treated in the Department of Otolaryngology in Bialystok from 1986-1999]. / Analiza epidemiologiczna chorych na raka krtani i gardla dolnego leczonych w Klinice Otolaryngologii AM w Bialymstoku w latach 1986-1999.

Epidemiological analysis of patients with the larynx cancer, who were treated in the Department of Otolaryngology in Bialystok from 1996 to 1999 was performed. The following aspects were assessed: a) number of patients, b) gender, c) age, d) place of living, e) primary site of the tumour. The results in years 1996-1999 were compared with the earlier published results in years 1986-1994. Altogether 1431 patients (1340-93.6% males and 91-6.4% females) in that period and there were similar numbers of hospitalizations every year. Among patients there were 28-33% farmers, 41-46% labourers, 5-9% white collar workers, the others were old age pensioners. 55-59% patients came from the rural areas and 41-45% patients from urban areas. The most common site of the primary tumour was the supraglottic region (831-58.1%), then glottis (421-29.4%) and rarely in the subglottic region (5-0.3%). Hypopharynx was the tumor primary site in 174 (12.2%) patients. The analysis showed that the numbers of patients with cancer of the larynx or hypopharynx are similar in each year. A constant increase in number of female patients; coming from the rural area, farmers or labourers was found. Increasing incidence rate of supraglottic tumours and little decrease in the number of glottic tumours were also found.

Cancers of the upper aerodigestive tract in Korea.

Cancers of the upper aerodigestive tract (UADT) constitute 3.5-4% of all malignancies. Since the majority of cases are squamous cell carcinomas which are related with epidemiologic factors, a different pattern of UADT cancer might be present between the Western and Asian populations. We performed a pathology based statistical study on UADT cancers in Korean patients. Cases from Korea Cancer Center Hospital, from January 1, 1988 through December 31, 1998, were subjected to the study. Among 2,842 cases, epithelial malignancies accounted for 87.8%, with squamous cell carcinoma as the major type (76.5%). The larynx was the most commonly affected site (26%), followed by the oral cavity (25.1%), oropharynx (13%), nasopharynx (9%), hypopharynx (8.4%), paranasal sinuses (6.4%), nasal cavity (6%) and salivary glands (6.1%). The percentage of squamous cell carcinoma was highest (98.7%) at the hypopharynx, and lowest at the nasal cavity (42.3%), which showed the most diverse tumor entities. Korean patients with UADT cancers presented with a higher incidence of non-epidermoid malignancy including sarcoma (1.5%) and malignant melanoma (1.4%), and a higher frequency of involvement of the sinonasal tract, compared with the Western patients.

Cancers of the Upper Aerodigestive Tract in Korea

Cancers of the upper aerodigestive tract (UADT) constitute 3.5-4% of all malignancies. Since the majority of cases are squamous cell carcinomas which are related with epidemiologic factors, a different pattern of UADT cancer might be present between the Western and Asian populations. We performed a pathology based statistical study on UADT cancers in Korean patients. Cases from Korea Cancer Center Hospital, from January 1, 1988 through December 31, 1998, were subjected to the study. Among 2,842 cases, epithelial malignancies accounted for 87.8%, with squamous cell carcinoma as the major type (76.5%). The larynx was the most commonly affected site (26%), followed by the oral cavity (25.1%), oropharynx (13%), nasopharynx (9%), hypopharynx (8.4%), paranasal sinuses (6.4%), nasal cavity (6%) and salivary glands (6.1%). The percentage of squamous cell carcinoma was highest (98.7%) at the hypopharynx, and lowest at the nasal cavity (42.3%), which showed the most diverse tumor entities. Korean patients with UADT cancers presented with a higher incidence of non-epidermoid malignancy including sarcoma (1.5%) and malignant melanoma (1.4%), and a higher frequency of involvement of the sinonasal tract, compared with the Western patients.

Submucosal tumor extension in hypopharyngeal cancer.

OBJECTIVES: To study the incidence and extent of submucosal tumor extension in hypopharyngeal cancer and to evaluate the impact on the tumor recurrence and overall survival rates. METHODS: Fifty-seven resected specimens of hypopharyngeal cancer were studied in detail from January 1986 to December 1989 by use of the whole-organ, step-serial sectioning technique. RESULTS: Three types of submucosal tumor extension could be identified. Type I extension was characterized by a tumor with a smooth round contour that extended submucosally. The mucosa was thereby elevated and was detectable on gross inspection at operation. In type II extension, tongues and islands of tumor infiltrated within the submucosa, and these were not noticeable on gross examination. Skip metastasis in the submucosa where the submucosal tumor was completely separated from the main tumor bulk was classified as type III extension. Thirty-three patients (58%) had submucosal tumor extension. The frequencies (and extents of submucosal tumor extension) in the superior, medial, lateral, and inferior directions were 16% (3-10 mm), 37% (2-37 mm), 26% (2-37 mm), and 28% (3-35 mm), respectively. Two thirds of the submucosal extension was type I (22 of 33), and only 1 patient had a true skip lesion submucosally (type III extension). Type II submucosal extension was found in one third of the patients (11 of 33). This occurred significantly more often in the patients who had received radiotherapy before surgery (82% [9/11]; P < .001; 95% confidence interval, 1.28-4.44). The presence of submucosal tumor extension had no effect on the tumor recurrence and overall survival rates. CONCLUSIONS: The incidence of submucosal tumor extensions in hypopharyngeal cancer is high (58%), but most (67%) of them can be detected grossly at operation. The presence of submucosal tumor extension does not adversely affect the survival and tumor recurrence rates.

[Value of the association of partial surgery and postoperative radiotherapy in the management of tumors of the hypopharynx. A study of 141 T1-T2 cases of hypopharyngeal cancer treated by partial surgery, radical surgery or radiotherapy alone]. / Intérêt de l'association chirurgie partielle-radiothérapie postopératoire pour le traitement des tumeurs de l'hypopharynx. Etude à propos de 142 T1-T2 traités par chirurgie partielle, chirurgie radicale ou radiothérapie exclusive.

A retrospective study of 142 T1-T2 hypopharyngeal cancers treated from 1977 to 1988 was carried out. Forty-seven patients were treated by local conservative surgery, curage and postoperative radiotherapy of the remaining pharyngolarynx and cervical node areas (group 1), 48 by radical surgery and postoperative radiotherapy (group 2) and 47 by radiotherapy alone (group 3). There were more T1 tumors in group 1 (64%), than in group 2 (33%), and group 3 (40%). Sixty two percent of the patients of group 1 had clinical nodes, 56% of group 2 and 49% of group 3. There were 70% N+ and 30% N+ with extracapsular invasion (N+ RC+) in group 1, 81% N+ and 35% N+ RC+ in group 2. A histologically non-satisfactory resection was observed in 21% of patients of group 1 and 6% in group 2. Patients more than seventy years old comprised 11% in group 1, 15% in group 2 and 26% in group 3. Indications for radiotherapy alone was for 75% an impossibility for surgery (surgical contraindications or refusal by the patients). Overall survival was 34% at 5 years and 18% at 10 years. Five-year survival for groups 1, 2 and 3 were 48%, 33.5% and 22%. Deaths by cancer evolution was as frequent in group 2 as in group 3 (43%) but deaths by metastatic evolutions were twice as frequent in group 2 and deaths by local regional evolution twice as frequent in group 1 (2%). Treatment of group 1 was recommended because of the good survival at 5 years, 48%, and the good voice conservation, 100% (despite non-satisfactory resections and N+ RC+). At present, some of these conservative surgeries would be replaced by radiotherapy alone in case of complete response after initial chemotherapy, which would be an advantage for cases with an indication for radical surgery, but not necessarily so for cases with an indication for partial surgery, taking into account the good results that we have achieved with an association of partial surgery and radiotherapy.