Prognostic value of interim CT-based peritumoral and intratumoral radiomics in laryngeal and hypopharyngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND AND PURPOSE: We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC). MATERIALS AND METHODS: A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO-Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated. RESULTS: The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia. CONCLUSION: Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT.

Prevalence and risk factors for retropharyngeal and retro-styloid lymph node metastasis in hypopharyngeal carcinoma.

BACKGROUND: We evaluated the prevalence and identified the risk factors for retropharyngeal and retro-styloid lymph node metastasis (LNM) in patients with hypopharyngeal carcinoma (HPC). This was achieved using a combination of magnetic resonance (MR) and [18 F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) images. METHODS: Two board-certified radiation oncologists retrospectively reviewed pretreatment FDG-PET/CT images and contrast-enhanced thin-slice CT and MR images of 155 patients with HPC who underwent radiotherapy. Fisher's exact tests and logistic regression analyses were performed to assess the risk factors for LNM. RESULTS: Retropharyngeal LNM (RPLNM) was confirmed in 20 (13%) patients. Posterior wall (PW) tumors (odds ratio [OR]: 4.128, 95% confidence interval [CI]: 1.339-12.727; p = 0.014) and bilateral or contralateral cervical LNM (OR: 11.577, 95% CI: 2.135-62.789; p = 0.005) were significantly correlated with RPLNM. The RPLNM was found in 9 (32%) of the 28 patients with PW tumors. Of these 9 patients, 2 (7%) had ipsilateral RPLNM, 3 (11%) had contralateral RPLNM, and 4 (14%) had bilateral RPLNM. The PW tumors were significantly associated with contralateral RPLNM (p < 0.001). Retro-styloid LNM (RSLNM) was confirmed in two (1%) patients, both of whom had ipsilateral RSLNM with lymph nodes (LNs) of ≥ 15 mm in the upper limit of ipsilateral level II. A significant association was found between LNs of ≥ 15 mm in the upper limit of ipsilateral level II and ipsilateral RSLNM (p = 0.001). CONCLUSIONS: The RPLNM was identified in 13% of patients with HPC. The PW tumors and bilateral or contralateral cervical LNM were risk factors for RPLNM; particularly, PW tumors were a specific risk factor for contralateral RPLNM. Although the RSLNM was rare, LNs of ≥ 15 mm in the upper limit of ipsilateral level II were a risk factor for ipsilateral RSLNM.

Fibrinogen-to-lymphocyte Ratio Predicts the Outcomes of Hypopharyngeal Squamous Cell Carcinoma Treated With Definitive Radiotherapy.

BACKGROUND/AIM: Previous studies have identified several inflammatory biomarkers that are useful as prognostic biomarkers for various cancer types. However, the fibrinogen-to-lymphocyte ratio (FLR) has not been addressed in head and neck squamous cell carcinoma. Here, we aimed to examine the value of pretreatment FLR as a prognostic marker in patients who received definitive radiotherapy for hypopharyngeal squamous cell carcinoma (HpSCC). PATIENTS AND METHODS: This retrospective study included 95 patients treated with definitive radiotherapy for HpSCC between 2013 and 2020. The prognostic factors for progression-free (PFS) and overall (OS) survival were identified. RESULTS: The optimal cut-off value of pretreatment FLR for discriminating PFS was 2.46. Based on this value, 57 and 38 patients were classified into groups with high and low FLR, respectively. A high FLR was significantly associated with advanced local disease and overall stage, and with the development of synchronous second primary cancer compared with a low FLR. The high FLR group had significantly lower PFS and OS rates than the low FLR group. Multivariate analysis showed that having a high pretreatment FLR was an independent prognostic factor for poorer PFS and OS [PFS: hazard ratio (HR)=2.14, 95% confidence interval (CI)=1.09-4.19, p=0.026; OS: HR=2.86, 95% CI=1.14-7.20, p=0.024]. CONCLUSION: The FLR has a clinical effect on PFS and OS in patients with HpSCC, suggesting that it has potential application as a prognostic factor for patients with HpSCC.

The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma.

BACKGROUND: For patients with less chemosensitive neck nodes, poor prognosis after chemoradiotherapy (CRT) could be predicted and neck dissection is needed. METHODS: Ninety-two N2/3 hypopharyngeal carcinoma patients were retrospectively studied. According to response after induction chemotherapy (ICT), patients were treated with neck dissection followed by concurrent CRT (CCRT) (group 1), surgery plus postoperative CRT (group 2), or CCRT for primary and regional sites (group 3). RESULTS: Overall survival and disease-free survival rates of group 1 were significantly higher than group 2 (p = 0.038, p = 0.031) and group 3 (both p = 0.018). Regional control rate of group 1 was significantly higher than group 3 (p = 0.041). There were no significant differences between groups 1 and 2 regarding local and regional control (p = 0.746, p = 0.302). CONCLUSIONS: Neck dissection followed by CCRT is the best choice for patients with responsive primary but nonresponsive nodes.

Case Report: First-Line Immunotherapy for Esophageal Squamous Carcinoma Combined With Hypopharyngeal Squamous Carcinoma Yields Sustained Survival Benefit.

Esophageal cancer, as one of the most common malignant tumors in the upper gastrointestinal tract, is highly invasive, with poor prognosis and low 5-year survival rate. Hypopharyngeal cancer has a low incidence among head and neck malignant tumors, but its prognosis is poor and it is prone to recurrence, and because the upper respiratory tract has similar tissue types as the upper gastrointestinal tract, it is prone to the second primary tumor of the upper gastrointestinal tract, however, such patients with double primary carcinoma are uncommon in the clinic, and most of them are already advanced at the time of diagnosis, losing the chance of surgical resection, with poor results and poor prognosis after radiotherapy treatment, therefore, the choice of treatment strategy for such inoperable resectable patients is still a great challenge for clinicians.In this case, we report a patient with a double primary esophageal squamous carcinoma combined with hypopharyngeal squamous carcinoma without family history of tumor, who achieved complete remission after first-line chemotherapy combined with immunotherapy, with both lesions shrinking and the hypopharyngeal tumor disappearing. The survival benefit was ensured at the same time.

[Survival outcomes and prognostic factors of patients with salvage surgery for hypopharyngeal carcinoma after radiotherapy].

Objective: To investigate the survival outcomes and prognostic factors of patients with salvage surgery for hypopharyngeal carcinoma after radiotherapy. Methods: A retrospective analysis was performed, including 26 patients treated in Ningbo Medical Center Lihuili Hospital between January 2010 and December 2015. All patients were males, aged 48-83 years, of whom 8 cases were local residual after radiotherapy alone, 8 cases were local recurrence after postoperative radiotherapy, 2 cases were residual of cervical lymph nodes after radiotherapy alone, 2 cases were recurrence of cervical lymph nodes after radiotherapy alone, 2 cases were recurrence of cervical lymph nodes after postoperative radiotherapy and 4 cases were recurrence of tracheal stoma. The salvage operations included: local resection, local resection with neck dissection, simple neck dissection, tumor resection of tracheostomy, and additional repair according to the defect. Chi square test was used for recurrence and metastasis analysis, Kaplan-Meier method for survival analysis, Log-rank test for univariate analysis, and Cox regression model for multivariate analysis. Results: The complication rate of salvage surgery was 23.1% (6/26). The recurrence rate was 65.4% (17/26) and the distant metastasis rate was 42.3% (11/26) in the 5-year follow-up after salvage surgery. Patient's age and tumor invasion extent were correlated with recurrence. Initial treatment, tumor persistence or recurrence after radiotherapy, recurrence location and tumor invasion extent were correlated with distant metastasis (all P<0.05). Overall, 3 year and 5 year survival rates were 42.3% and 23.1% respectively. Age, recurrence location, surgical margin and tumor invasion extent were related to prognosis (χ²=6.56, 10.68, 9.32, and 7.90 respectively, all P<0.05). Multivariate analysis showed that surgical margin and tumor invasion extent were independent risk factors for prognosis (OR (95%CI) = 3.19 (1.03-9.84), 14.37 (2.46-84.08), both P<0.05). Conclusion: Salvage surgery is the first choice for patients with recurrence after radiotherapy for hypopharyngeal carcinoma. Safe surgical margin should be ensured, especially in tumors invading muscle, bone tissue or lymph node capsule.

Deep learning approach of diffusion-weighted imaging as an outcome predictor in laryngeal and hypopharyngeal cancer patients with radiotherapy-related curative treatment: a preliminary study.

OBJECTIVES: This preliminary study aimed to develop a deep learning (DL) model using diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps to predict local recurrence and 2-year progression-free survival (PFS) in laryngeal and hypopharyngeal cancer patients treated with various forms of radiotherapy-related curative therapy. METHODS: Seventy patients with laryngeal and hypopharyngeal cancers treated by radiotherapy, chemoradiotherapy, or induction-(chemo)radiotherapy were enrolled and divided into training (N = 49) and test (N = 21) groups based on presentation timeline. All patients underwent MR before and 4 weeks after the start of radiotherapy. The DL models that extracted imaging features on pre- and intra-treatment DWI and ADC maps were trained to predict the local recurrence within a 2-year follow-up. In the test group, each DL model was analyzed for recurrence prediction. Additionally, the Kaplan-Meier and multivariable Cox regression analyses were performed to evaluate the prognostic significance of the DL models and clinical variables. RESULTS: The highest area under the receiver operating characteristics curve and accuracy for predicting the local recurrence in the DL model were 0.767 and 81.0%, respectively, using intra-treatment DWI (DWIintra). The log-rank test showed that DWIintra was significantly associated with PFS (p = 0.013). DWIintra was an independent prognostic factor for PFS in multivariate analysis (p = 0.023). CONCLUSION: DL models using DWIintra may have prognostic value in patients with laryngeal and hypopharyngeal cancers treated by curative radiotherapy. The model-related findings may contribute to determining the therapeutic strategy in the early stage of the treatment. KEY POINTS: • Deep learning models using intra-treatment diffusion-weighted imaging have prognostic value in patients with laryngeal and hypopharyngeal cancers treated by curative radiotherapy. • The findings from these models may contribute to determining the therapeutic strategy at the early stage of the treatment.

Hypopharyngeal Reconstruction: Possibilities, Outcomes, and Updates for Improving the Human Health for Quality of Life.

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. Objectives. 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. Methods. 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. Conclusion. 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.

Oncological and Functional Outcomes of Larynx-preserving Surgery for Hypopharyngeal Cancer: A Comparison with Definitive Radiation-based Treatment.

PURPOSE: Larynx-preserving surgery (LPS) have recently gained popularity and achieved comparable oncologic outcomes to conventional radical surgery for localized hypopharyngeal cancer (HPC). In the current study, the role of LPS has been assessed thoroughly in comparison with upfront radiation therapy (RT). MATERIALS AND METHODS: We retrospectively reviewed 185 candidates for LPS with cT1-2 disease; 59 patients underwent upfront LPS while 126 patients received upfront RT, respectively. Oncological and functional outcomes were investigated and compared. RESULTS: Following LPS, safe margin (≥ 5 mm) was achieved in 37.3% of patients. Overall, better clinical outcomes at 5 years were achieved following upfront LPS than those following upfront RT: overall survival (OS) (72.7% vs. 59.0%, p=0.045), disease-free survival (DFS) (59.8% vs. 45.0%, p=0.039), and functional laryngeal preservation (100% vs. 89.7%, p=0.010). Although similar outcomes were observed in patients with cT1 disease, better 5-year DFS was achieved following upfront LPS in patients with cT2 disease (57.0% vs. 36.4%, p=0.023) by virtue of better local control. Despite frequent cN2-3 disease in upfront LPS group, comparable outcomes were observed between upfront RT and LPS group. However, multivariable analyses revealed that performance status and double primary cancer diagnosed within 6 months of HPC diagnosis affected OS significantly, while treatment modality per se did not. CONCLUSION: Although upfront LPS could provide better local control than upfront RT in patients with cT2 disease, overall outcomes were comparable following either modality. Treatment selection of larynx-preserving approach for HPC should be individualized based on tumor and patient factors.

Radiotherapy for hypopharynx cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy for hypopharynx. Intensity-modulated radiotherapy is the gold standard treatment for hypopharynx cancers. Early T1 and T2 tumors could be treated by exclusive radiotherapy or surgery followed by postoperative radiotherapy in case of high recurrence risk. For locally advanced tumours requiring total pharyngolaryngectomy (T2 or T3) or with significant lymph nodes involvement, induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy were possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on initial primary tumour treatment. In non-surgical procedure, for 35 fractions, curative dose is 70Gy (2Gy per fraction) and prophylactic dose are 50 to 56Gy (2Gy per fraction in case of sequential radiotherapy or 1.6Gy in case of integrated simultaneous boost) radiotherapy; for 33 fractions, curative dose is 69.96Gy (2.12Gy per fraction) and prophylactic dose is 52.8Gy (1.6Gy per fraction in integrated simultaneous boost radiotherapy or 54Gy in 1.64Gy per fraction); for 30 fractions, curative dose is 66Gy (2.2Gy per fraction) and prophylactic dose is 54Gy (1.8Gy per fraction in integrated simultaneous boost radiotherapy). Doses over 2Gy per fraction could be done when chemotherapy is not used regarding potential larynx toxicity. Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria, 60 to 66Gy for R1 resection and 54 to 60Gy for complete resection in bed tumour; 50 to 66Gy in lymph nodes areas regarding extracapsular spread. Volume delineation were based on guidelines cited in this article.

Association of neutrophil-to-lymphocyte ratio with severe radiation-induced mucositis in pharyngeal or laryngeal cancer patients: a retrospective study.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that informs clinical decisions regarding recurrence and overall survival in most epithelial cancers. Radiotherapy for head and neck cancer leads to mucositis in almost all patients and severe radiation-mucositis affects their quality of life (QOL). However, little is known about the NLR for severe mucositis. Therefore, this study aimed to show the association between the NLR and severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients. METHODS: In this retrospective study, we determined the incidence of grade 3 mucositis in 99 patients who were receiving definitive radiotherapy or chemoradiotherapy (CRT) for hypopharyngeal or laryngeal cancer. We performed univariate and multivariate logistic regression analyses to investigate the characteristics of grade 3 mucositis. Kaplan-Meier curves and log-rank tests were used to evaluate the occurrence of grade 3 mucositis between two groups with high (NLR > 5) or low (NLR < 5) systemic inflammation. RESULTS: The incidence of grade 3 mucositis was 39%. Univariate logistic regression analysis showed that the NLR (Odd ratio [OR] = 1.09; 95% confidence interval [CI] = 1.02-1.16; p = 0.016) and smoking (OR = 1.02; 95% CI = 1.00-1.03; p = 0.048) were significantly associated with grade 3 mucositis. Multivariate logistic regression analysis showed that the NLR was independently associated with grade 3 mucositis (OR = 1.09; 95% CI = 1.01-1.17; p = 0.021). Kaplan-Meier curves also showed that patients with higher NLR (NLR > 5) prior to radiotherapy developed grade 3 mucositis more frequently than those with lower NLR during radiotherapy (p = 0.045). CONCLUSION: This study suggests that a higher NLR is a risk factor and predictor of severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients.

Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial.

BACKGROUND: Radical (chemo)radiotherapy offers potentially curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated intensity-modulated radiotherapy (DE-IMRT) improved locoregional control. METHODS: We performed a phase III open-label randomised controlled trial in patients with laryngeal or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7). Patients were randomised (1:1) to DE-IMRT or standard dose IMRT (ST-IMRT) using a minimisation algorithm, balancing for centre, tumour site, nodal status and chemotherapy use. DE-IMRT was 67.2 gray (Gy) in 28 fractions (f) to the primary tumour and 56Gy/28f to at-risk nodes; ST-IMRT was 65Gy/30f to primary tumour and 54Gy/30f to at-risk nodes. Suitable patients received 2 cycles of concomitant cisplatin and up to 3 cycles of platinum-based induction chemotherapy. The primary end-point was time to locoregional failure analysed by intention-to-treat analysis using competing risk methodology. FINDINGS: Between February 2011 and October 2015, 276 patients (138 ST-IMRT; 138 DE-IMRT) were randomised. A preplanned interim futility analysis met the criterion for early closure. After a median follow-up of 47.9 months (interquartile range 37.5-60.5), there were locoregional failures in 38 of 138 (27.5%) ST-IMRT patients and 42 of 138 (30.4%) DE-IMRT patients; an adjusted subhazard ratio of 1.16 (95% confidence interval: 0.74-1.83, p = 0.519) indicated no evidence of benefit with DE-IMRT. Acute grade 2 pharyngeal mucositis was reported more frequently with DE-IMRT than with ST-IMRT (42% vs. 32%). No differences in grade ≥3 acute or late toxicity rates were seen. CONCLUSION: DE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer. The trial is registered: ISRCTN01483375.

Robotic surgery may improve overall survival for T1 and T2 tumors of the hypopharynx: An NCDB cohort study.

BACKGROUND: Hypopharyngeal cancer is associated with poor survival. Robotic surgery is emerging as a treatment for hypopharyngeal tumors, but no rigorous data are available to assess its effect on survival. METHODS: The National Cancer Database (NCDB) was used to identify patients with T1 and T2 hypopharyngeal tumors undergoing robotic surgery, laser surgery, and primary radiation with or without chemotherapy from 2010 to 2016. All adult patients with available staging and no distant metastasis were included. RESULTS: We compared 57 patients undergoing robotic surgery, 236 undergoing laser surgery, and 5,742 undergoing primary radiation. Compared to laser surgery, patients undergoing robotic surgery were significantly more likely to have negative margins, neck dissection, lower incomes, and care at an academic center. Rates of robotic surgery also significantly increased from 2010 to 2015. After multivariate regression, robotic surgery was associated with significantly improved overall survival compared to laser surgery and primary radiation. CONCLUSION: Robotic surgery improves overall survival for T1 and T2 hypopharyngeal tumors compared to laser surgery and primary radiation in this NCDB cohort. This effect may be mediated by decreased positive margin rates relative to laser surgery. Rates of hypopharyngeal robotic surgery are expected to increase with wider adoption of robotic platforms and may improve overall survival rates for hypopharyngeal cancer.

Quality assurance of radiotherapy in the ongoing EORTC 1420 "Best of" trial for early stage oropharyngeal, supraglottic and hypopharyngeal carcinoma: results of the benchmark case procedure.

INTRODUCTION: The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS). MATERIALS AND METHODS: Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV). RESULTS: 65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD). CONCLUSIONS: This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients' clinical outcome.

N6-methyladenosine modification of circCUX1 confers radioresistance of hypopharyngeal squamous cell carcinoma through caspase1 pathway.

Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most common malignant tumors in otolaryngology head and neck surgery and is one of the worst prognostic malignant tumors. Endogenous circular RNA (circRNA) is more stable than mRNA, microRNA (miRNA), and long non-coding RNA (LncRNA) in exosomes, plasma, and urine, and participates in gene expression regulation to perform different functions. Therefore, circRNA is expected to become a biomarker and therapy target for many tumors. However, the expression and function of circRNA regulated by N6-methyladenosine (m6A) are still unclear in HNSCC. In this study, we demonstrated that a specific circRNA, circCUX1, was upregulated in HPSCC patients who are resistant to radiotherapy and predicts poor survival outcome. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circCUX1 and stabilizes its expression. Knockdown circCUX1 promotes the sensitivity of hypopharyngeal cancer cells to radiotherapy. In addition, circCUX1 binds to Caspase1 and inhibits its expression, resulting in a decrease in the release of inflammatory factors, thereby developing tolerance to radiotherapy. Our findings indicate that circCUX1 is a potential therapeutic target for radiotherapy tolerance in HPSCC patients.

Improved Tumor Control Related to Radiotherapy Technological Development for Hypopharyngeal Cancer.

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. METHODS: Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. RESULTS: One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P < .001) beginning in the 2000s. The 24-month FFLR using two-dimensional RT (2D-RT), three-dimensional conformal RT (3D-CRT), and intensity-modulated RT (IMRT) was 52%, 55%, and 80%, respectively; 24-month PFS was 39%, 46%, and 73%, respectively; and 24-month OS was 27%, 40%, and 68%, respectively. OS (P = .01), PFS (P = .03), and FFLR (P = 0.02) were improved with IMRT over 2D-RT, and FFLR appeared to be improved over 3D-CRT (P = .06). Controlling for chemotherapy use and other major variables, IMRT produced a strong influence over FFLR (adjusted hazard ratio [HR] = 0.2, 95% confidence interval [CI]: 0.0-1.2, P = .08) and a benefit in OS (adjusted HR = 0.1, 95% CI: 0.0-0.4, P = .005). CONCLUSIONS: Across 6 decades, patient and tumor characteristics remained similar whereas use of chemoradiation increased and IMRT was adopted. The introduction of IMRT was associated with improved FFLR, PFS, and OS, and a reduction in acute toxicity as compared to earlier radiation technologies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E452-E458, 2021.

Vascular events from carotid artery atherosclerosis after radiation therapy for laryngeal and hypopharyngeal cancer: the incidence and risk factors.

In this retrospective cohort study, we evaluated the incidence of vascular events from carotid artery atherosclerosis after radiotherapy indication for laryngeal and hypopharyngeal cancer. From January 2007 to December 2016, we investigated 111 laryngeal/hypopharyngeal cancer patients who underwent curative radiotherapy and were followed up for ≥1 year (median follow-up duration, 60 months). We evaluated the incidence of vascular events from carotid artery atherosclerosis, defined as a transient ischemic attack or an atherothrombotic cerebral infarction, or from undergoing treatment such as carotid artery stenting for carotid artery stenosis. The median radiation dose was 66 Gy (range, 60-74); 48 patients (43.2%) received concurrent chemotherapy. The 5-year overall survival was 86.2%. Six patients required treatment for carotid artery disease. Carotid stenting was performed in three patients with carotid artery stenosis; three patients developed atherosclerotic cerebral infarction and received medical treatment, with a median of 51.7 months (range, 0.3-78.3) after radiotherapy initiation. The vascular event occurrence rate was 5.4% within 5 years and 10.7% within 8 years. In the univariate analysis, dyslipidemia, diabetes mellitus, and carotid calcification were significant factors for event occurrence. Because three out of six cases occurred out of the irradiated field, no carotid artery or carotid bulb dosimetric parameters showed significant correlation. As laryngeal/hypopharyngeal cancer patients, particularly with complications including dyslipidemia and diabetes mellitus, are at a high risk of carotid artery stenosis after radiotherapy, long-term carotid artery evaluation is necessary. Early intervention by stroke specialists can reduce the risk of fatal cerebral infarction.

5-Nitro-2,4-Dichloropyrimidine as an Universal Model for Low-Energy Electron Processes Relevant for Radiosensitization.

We report experimental results of low-energy electron interactions with.

Involvement of Differentially Expressed microRNAs in the PEGylated Liposome Encapsulated 188Rhenium-Mediated Suppression of Orthotopic Hypopharyngeal Tumor.

Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic 188Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of 188Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of 188Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by 188Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of 188Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by 188Re-liposome. 188Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. 188Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.