-
JAMA Network Open Nov 2020Postoperative chemoradiation is the standard of care for cancers with positive margins or extracapsular extension, but the benefit of chemotherapy is unclear for...
IMPORTANCE
Postoperative chemoradiation is the standard of care for cancers with positive margins or extracapsular extension, but the benefit of chemotherapy is unclear for patients with other intermediate risk features.
OBJECTIVE
To evaluate whether machine learning models could identify patients with intermediate-risk head and neck squamous cell carcinoma who would benefit from chemoradiation.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx from January 1, 2004, through December 31, 2016. Patients had resected disease and underwent adjuvant radiotherapy. Analysis was performed from October 1, 2019, through September 1, 2020. Patients were selected from the National Cancer Database, a hospital-based registry that captures data from more than 70% of newly diagnosed cancers in the United States. Three machine learning survival models were trained using 80% of the cohort, with the remaining 20% used to assess model performance.
EXPOSURES
Receipt of adjuvant chemoradiation or radiation alone.
MAIN OUTCOMES AND MEASURES
Patients who received treatment recommended by machine learning models were compared with those who did not. Overall survival for treatment according to model recommendations was the primary outcome. Secondary outcomes included frequency of recommendation for chemotherapy and chemotherapy benefit in patients recommended for chemoradiation vs radiation alone.
RESULTS
A total of 33 527 patients (24 189 [72%] men; 28 036 [84%] aged ≤70 years) met the inclusion criteria. Median follow-up in the validation data set was 43.2 (interquartile range, 19.8-65.5) months. DeepSurv, neural multitask logistic regression, and survival forest models recommended chemoradiation for 17 589 (52%), 15 917 (47%), and 14 912 patients (44%), respectively. Treatment according to model recommendations was associated with a survival benefit, with a hazard ratio of 0.79 (95% CI, 0.72-0.85; P < .001) for DeepSurv, 0.83 (95% CI, 0.77-0.90; P < .001) for neural multitask logistic regression, and 0.90 (95% CI, 0.83-0.98; P = .01) for random survival forest models. No survival benefit for chemotherapy was seen for patients recommended to receive radiotherapy alone.
CONCLUSIONS AND RELEVANCE
These findings suggest that machine learning models may identify patients with intermediate risk who could benefit from chemoradiation. These models predicted that approximately half of such patients have no added benefit from chemotherapy.
Topics: Aged; Chemoradiotherapy, Adjuvant; Cohort Studies; Deep Learning; Female; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Logistic Models; Lymph Nodes; Machine Learning; Male; Mouth Neoplasms; Neoplasm Grading; Neoplasm Staging; Neural Networks, Computer; Oropharyngeal Neoplasms; Otorhinolaryngologic Surgical Procedures; Patient Selection; Proportional Hazards Models; Radiotherapy, Adjuvant; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tumor Burden
PubMed: 33211108
DOI: 10.1001/jamanetworkopen.2020.25881 -
Oncology Reports Nov 2021Laryngopharyngeal reflux, a variant of gastroesophageal reflux disease, has been considered a risk factor in the development of hypopharyngeal cancer. Bile acids are... (Review)
Review
Laryngopharyngeal reflux, a variant of gastroesophageal reflux disease, has been considered a risk factor in the development of hypopharyngeal cancer. Bile acids are frequently present in the gastroesophageal refluxate and their effect has been associated with inflammatory and neoplastic changes in the upper aerodigestive tract. Recent and studies have provided direct evidence of the role of acidic bile refluxate in hypopharyngeal carcinogenesis and documented the crucial role of NF‑κB as a key mediator of early oncogenic molecular events in this process and also suggested a contribution of STAT3. Acidic bile can cause premalignant changes and invasive squamous cell cancer in the affected hypopharynx accompanied by DNA damage, elevated p53 expression and oncogenic mRNA and microRNA alterations, previously linked to head and neck cancer. Weakly acidic bile can also increase the risk for hypopharyngeal carcinogenesis by inducing DNA damage, exerting anti‑apoptotic effects and causing precancerous lesions. The most important findings that strongly support bile reflux as an independent risk factor for hypopharyngeal cancer are presented in the current review and the underlying mechanisms are provided.
Topics: Bile Acids and Salts; Bile Reflux; Carcinoma, Squamous Cell; DNA Damage; Humans; Hypopharyngeal Neoplasms; NF-kappa B; RNA, Messenger; Risk Factors; STAT3 Transcription Factor; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 34558652
DOI: 10.3892/or.2021.8195 -
Magnetic Resonance Imaging Clinics of... Feb 2022State-of-the-art MR imaging of the larynx and hypopharynx with high-resolution surface coils, parallel imaging techniques, and DWI has several advantages over CT for... (Review)
Review
State-of-the-art MR imaging of the larynx and hypopharynx with high-resolution surface coils, parallel imaging techniques, and DWI has several advantages over CT for assessing submucosal tumor spread, in particular neoplastic involvement of the paraglottic space, laryngeal cartilages, and extralaryngeal soft tissues. Current diagnostic MR imaging criteria based on a combination of distinct imaging features on morphologic sequences combined with DWI allow improved discrimination between tumor, peritumoral inflammation, and fibrosis and, ultimately, an increased precision for submucosal tumor delineation, which is a key prerequisite for tailored treatment options. Multiparametric MR imaging with DWI has a higher diagnostic performance than CT.
Topics: Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Larynx; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 34802581
DOI: 10.1016/j.mric.2021.08.002 -
Nature Communications Mar 2023The efficacy of the first-line treatment for hypopharyngeal carcinoma (HPC), a predominantly male cancer, at advanced stage is only about 50% without reliable molecular...
The efficacy of the first-line treatment for hypopharyngeal carcinoma (HPC), a predominantly male cancer, at advanced stage is only about 50% without reliable molecular indicators for its prognosis. In this study, HPC biopsy samples collected before and after the first-line treatment are classified into different groups according to treatment responses. We analyze the changes of HPC tumor microenvironment (TME) at the single-cell level in response to the treatment and identify three gene modules associated with advanced HPC prognosis. We estimate cell constitutions based on bulk RNA-seq of our HPC samples and build a binary classifier model based on non-malignant cell subtype abundance in TME, which can be used to accurately identify treatment-resistant advanced HPC patients in time and enlarge the possibility to preserve their laryngeal function. In summary, we provide a useful approach to identify gene modules and a classifier model as reliable indicators to predict treatment responses in HPC.
Topics: Humans; Male; Female; Carcinoma, Squamous Cell; Transcriptome; Tumor Microenvironment; Hypopharyngeal Neoplasms
PubMed: 36928331
DOI: 10.1038/s41467-023-37159-8 -
European Annals of Otorhinolaryngology,... Oct 2021Three types of reconstruction are possible following total laryngopharyngectomy (TLP) for advanced hypopharyngeal cancer: locoregional tubularized island flaps, gastric...
Three types of reconstruction are possible following total laryngopharyngectomy (TLP) for advanced hypopharyngeal cancer: locoregional tubularized island flaps, gastric pull-up and free flaps. Gastro-omental free flap (GOFF) is rarely used in this setting. However, because of its composite nature, this flap has the advantage of being able to restore digestive continuity and reconstruct part of the skin of the neck when it needs to be sacrificed because of tumour invasion or poor trophicity. The GOFF is a reliable and robust flap particularly indicated in hostile environments: repeated neck surgery, atrophic and devascularized skin after radiotherapy, sepsis in the context of fistula and/or pharyngostomy. It requires the collaboration of two or even three surgical teams. In this article, we describe the flap harvesting technique and the complications and functional outcome.
Topics: Free Tissue Flaps; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Pharyngectomy; Plastic Surgery Procedures
PubMed: 33431349
DOI: 10.1016/j.anorl.2020.12.013 -
Acta Otorhinolaryngologica Italica :... Jun 2015Our objective was to evaluate recurrence patterns of hypopharyngeal and laryngeal carcinoma after chemoradiation and options for salvage surgery, with special emphasis... (Review)
Review
Our objective was to evaluate recurrence patterns of hypopharyngeal and laryngeal carcinoma after chemoradiation and options for salvage surgery, with special emphasis on elderly patients. In a retrospective study all patients who underwent chemoradiation for hypopharyngeal and laryngeal carcinoma in a tertiary care academic center from 1990 through 2010 were evaluated. Primary outcome measures were the survival and complication rates of patients undergoing salvage surgery, especially in elderly patients. Secondary outcome measures were the predictors for salvage surgery for patients with locoregional recurrence after failed chemoradiotherapy. A review of the literature was performed. Of the 136 included patients, 60 patients had recurrent locoregional disease, of whom 22 underwent salvage surgery. Fifteen patients underwent a total laryngectomy with neck dissection(s) and 7 neck dissection without primary tumour surgery. Independent predictors for salvage surgery within the group of 60 patients with recurrent disease, were age under the median of 59 years (p = 0.036) and larynx vs. hypopharynx (p = 0.002) in multivariate analyses. The complication rate was 68% (14% major and 54% minor), with fistulas in 23% of the patients. Significantly more wound related complications occurred in patients with current excessive alcohol use (p = 0.04). Five-year disease free control rate of 35%, overall survival rate of 27% and disease specific survival rate of 35% were found. For the 38 patients who were not suitable for salvage surgery, median survival was 12 months. Patients in whom the tumour was controlled had a 5-year overall survival of 70%. In patients selected for salvage surgery age was not predictive for complications and survival. In conclusion, at two years follow-up after chemoradiation 40% of the patients were diagnosed with recurrent locoregional disease. One third underwent salvage surgery with 35% 5-year disease specific survival and 14% major complications. Older patients selected for salvage surgery had a similar complication rate and survival as younger patients.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Female; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Male; Middle Aged; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 26246660
DOI: No ID Found -
Computational Intelligence and... 2022Hypopharyngeal carcinoma is usually present at late stages, necessitating an aggressive line of management consisting of surgical procedures, chemotherapy, and radiation... (Review)
Review
Hypopharyngeal carcinoma is usually present at late stages, necessitating an aggressive line of management consisting of surgical procedures, chemotherapy, and radiation therapy, depending on the case. Practitioners tend to support total laryngectomies or total esophagostomies for most cases of hypopharyngeal carcinoma. The extensive procedures needed will most probably require, depending on the residual defect, a follow-up reconstructive procedure that might require utilizing flaps. Types of reconstructive methods and types of grafts or flaps used could be divided into a multitude of categories depending on the magnitude, shape, extension, and whether the underlying defect that is being reconstructed is circumferential or not. These reconstructive procedures are aimed at improving the quality of life, improving the aesthetic outcome, and restoring the functionality of the pharyngoesophageal segment. When it comes to hypopharyngeal cancer, the most common kind is squamous cell carcinoma (SCC), which has the worst prognosis of all the head and neck malignancies. Overall, the 5-year survival rate remains low, despite recent advancements in diagnostic imaging, radiation, and chemotherapy, as well as enhanced surgical methods and techniques. Hypopharyngeal malignancies are more probable than other tumors to present with advanced primary illness, with nodal metastasis a distinct possibility. The size and amount of local dissemination of the original carcinoma, as well as the extent of involvement of regional lymph nodes, are the most critical factors in predicting prognosis. Hypopharyngeal cancers are more likely than other head and neck cancers to manifest with distant metastases at the time of diagnosis. The appearance of second primary tumors, as well as the development of distant metastases, is a contributing factor to poor survival rate. Imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) with contrast remain the gold standard for evaluating hypopharyngeal carcinoma in the early stages. In most cases, imaging leads to an increase in the tumor stage at the time of presentation. . The main objectives are to review the research published about flaps, outline the optimum situations that will dictate the usage of a few of the most often used flaps for the rebuilding of the hypopharyngeal segment defects, and outline some of the complications associated with reconstruction. . The processing was carried out with the title-specific search of the PubMed database using the query terms "hypopharyngeal carcinoma" and "reconstruction" to identify the most relevant articles without restricting publication dates. Information about the types of defects and methods of reconstruction was extracted from the reviewed articles. Two books were also reviewed, which were Regional and Free Flaps for Head and Neck Reconstruction (second edition) and Head and Neck Reconstruction: A Defect-Oriented Approach. . Deciding the appropriate approach to a case should be individualized and should depend on the capabilities of the center, the defect's size and status, and lastly, the surgeon's training. The use of interpretation in the diagnosis of flaps can offer the best results in restoring functionality and vascularity and might also offer improved cosmesis.
Topics: Carcinoma, Squamous Cell; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Laryngectomy; Quality of Life; Retrospective Studies
PubMed: 35178078
DOI: 10.1155/2022/6132481 -
Thoracic Cancer May 2021G protein-coupled receptor 12 (GPR12) is an orphan receptor with no confirmed endogenous ligands. It plays important roles in both physiological and pathological...
BACKGROUND
G protein-coupled receptor 12 (GPR12) is an orphan receptor with no confirmed endogenous ligands. It plays important roles in both physiological and pathological conditions such as neurogenesis and neural inflammation. However, it remains unclear whether GPR12 regulates carcinogenesis and progression in head and neck squamous cell carcinoma (HNSCC), such as esophageal cancer (EC) and hypopharyngeal cancer (HC).
METHODS
The Cancer Genome Atlas (TCGA) database was applied to explore the expression of GPR12. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of GPR12 in cancer tissues. Wound healing and transwell assays were carried out to verify the effect of GPR12 on cell migration. Flow cytometric analysis and caspase-Glo 3/7 assay were carried out to verify the influence of GPR12 on cell apoptosis. Western blotting was used to measure the expression of proteins related to migration and apoptosis.
RESULT
The qRT-PCR analyses showed that the expression of GPR12 decreased in EC and HC than that in their paired adjacent normal tissues. Wound healing assay and transwell assay demonstrated that GPR12 inhibited tumor cell migration. Flow cytometry analysis and Caspase-Glo 3/7 Assay suggested that GPR12 promoted apoptosis. The mechanism of GPR12 may function via modulating caspase-7, E-cadherin, and α-catenin in EC and HC cells.
CONCLUSION
In conclusion, GPR12 induced apoptosis by activating caspase-7 and inhibited migration through epithelial-to-mesenchymal transition (EMT) in EC and HC. Our findings demonstrated that GPR12 as a potential tumor suppressor mediated cell migration and apoptosis in EC and HC.
Topics: Apoptosis; Cell Movement; Esophageal Neoplasms; Humans; Hypopharyngeal Neoplasms; Receptors, G-Protein-Coupled; Transfection
PubMed: 33742771
DOI: 10.1111/1759-7714.13933 -
Cell Communication and Signaling : CCS Oct 2023Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among all head-and-neck cancers, and treatment options are limited. Tumor microenvironment (TME)...
BACKGROUND
Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among all head-and-neck cancers, and treatment options are limited. Tumor microenvironment (TME) analysis can help identify new therapeutic targets and combined treatment strategies.
METHODS
Six primary HPSCC tissues and two adjacent normal mucosae from six treatment-naïve patients with HPSCC were analyzed using scRNA-seq. Cell types were curated in detail, ecosystemic landscapes were mapped, and cell-cell interactions were inferred. Key results were validated with The Cancer Genome Atlas and cell biology experiments.
RESULTS
Malignant HPSCC epithelial cells showed significant intratumor heterogeneity. Different subtypes exhibited distinct histological features, biological behaviors, and spatial localization, all affecting treatment selection and prognosis. Extracellular matrix cancer-associated fibroblasts (mCAFs) expressing fibroblast activation protein were the dominant CAFs in HPSCC tumors. mCAFs, constituting an aggressive CAF subset, promoted tumor cell invasion, activated endothelial cells to trigger angiogenesis, and synergized with SPP1 tumor associated macrophages to induce tumor progression, ultimately decreasing the overall survival of patients with HPSCC. Moreover, the LAMP3 dendritic cell subset was identified in HPSCC and formed an immunosuppressive TME by recruiting Tregs and suppressing CD8+ T cell function.
CONCLUSIONS
mCAFs, acting as the communication center of the HPSCC TME, enhance the invasion ability of HPSCC cells, mobilizing surrounding cells to construct a tumor-favorable microenvironment. Inhibiting mCAF activation offers a new anti-HPSCC therapeutic strategy. Video Abstract.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Cancer-Associated Fibroblasts; Endothelial Cells; Hypopharyngeal Neoplasms; Head and Neck Neoplasms; Sequence Analysis, RNA; Tumor Microenvironment
PubMed: 37853464
DOI: 10.1186/s12964-023-01312-z -
Tomography (Ann Arbor, Mich.) Mar 2021(1) Purpose: The objective was to evaluate CT perfusion and radiomic features for prediction of one year disease free survival in laryngeal and hypopharyngeal cancer....
(1) Purpose: The objective was to evaluate CT perfusion and radiomic features for prediction of one year disease free survival in laryngeal and hypopharyngeal cancer. (2) Method and Materials: This retrospective study included pre and post therapy CT neck studies in 36 patients with laryngeal/hypopharyngeal cancer. Tumor contouring was performed semi-autonomously by the computer and manually by two radiologists. Twenty-six radiomic features including morphological and gray-level features were extracted by an internally developed and validated computer-aided image analysis system. The five perfusion features analyzed included permeability surface area product (PS), blood flow (flow), blood volume (BV), mean transit time (MTT), and time-to-maximum (Tmax). One year persistent/recurrent disease data were obtained following the final treatment of definitive chemoradiation or after total laryngectomy. We performed a two-loop leave-one-out feature selection and linear discriminant analysis classifier with generation of receiver operating characteristic (ROC) curves and confidence intervals (CI). (3) Results: 10 patients (28%) had recurrence/persistent disease at 1 year. For prediction, the change in blood flow demonstrated a training AUC of 0.68 (CI 0.47-0.85) and testing AUC of 0.66 (CI 0.47-0.85). The best features selected were a combination of perfusion and radiomic features including training AUC of 0.68 (CI 0.5-0.85) and testing AUC of 0.69 (CI 0.5-0.85). The laryngoscopic percent change in volume was a poor predictor with a testing AUC of 0.4 (CI 0.16-0.57). (4) Conclusions: A combination of CT perfusion and radiomic features are potential predictors of one-year disease free survival in laryngeal and hypopharyngeal cancer patients.
Topics: Disease-Free Survival; Humans; Hypopharyngeal Neoplasms; Neoplasm Recurrence, Local; Perfusion; Pilot Projects; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 33681460
DOI: 10.3390/tomography7010002