SSTR2 in Nasopharyngeal Carcinoma:Relationship with Latent EBV Infection and Potential as a Therapeutic Target

SIMPLE SUMMARY: Nasopharyngeal cancer (NPC) is a malignant epithelial tumor endemic to parts of Asia and associated with infection by the Epstein–Barr virus (EBV) in these regions. The cancer is often detected at a late stage which is associated with poor outcomes (63% 5-year survival). Advances for the management of this disease have remained largely stagnant and treatment relies primarily on radiotherapy and chemotherapy, as well as surgery when indicated. Nevertheless, our understanding of its underlying biology has grown rapidly in the past two decades, laying the foundation for the development of improved therapeutics which have the potential to improve outcomes. This review offers a comprehensive, up-to-date summary of this disease, with a focus on the role of somatostatin receptor 2 (SSTR2) in NPC and how this increased knowledge may lead to improved diagnosis and management of this disease. ABSTRACT: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor, most commonly located in the pharyngeal recess and endemic to parts of Asia. It is often detected at a late stage which is associated with poor prognosis (5-year survival rate of 63%). Treatment for this malignancy relies predominantly on radiotherapy and/or systemic chemotherapy, which can be associated with significant morbidity and impaired quality of life. In endemic regions NPC is associated with infection by Epstein–Barr virus (EBV) which was shown to upregulate the somatostatin receptor 2 (SSTR2) cell surface receptor. With recent advances in molecular techniques allowing for an improved understanding of the molecular aetiology of this disease and its relation to SSTR2 expression, we provide a comprehensive and up-to-date overview of this disease and highlight the emergence of SSTR2 as a key tumor biomarker and promising target for imaging and therapy

Functional Shoulder Outcome and Quality of Life Following Modified Muscle-Sparing Pectoralis Major Flap Surgery

Background: The pedicled pectoralis major muscle flap (PMMF) is a well established flap for fistula prophylaxis after salvage laryngectomy. To reduce donor site morbidity, we established a modified muscle-sparing harvesting technique. We herein investigate postoperative shoulder function and health-related quality of life (HRQOL). Methods: A chart review of patients receiving the modified muscle-sparing pectoralis major muscle flap between 2013–2020 was performed. Nineteen patients (male = 18, female = 1) were potentially eligible and six male patients were ultimately enrolled. Postoperative shoulder function was assessed on both sides (flap side versus non-flap side) using the Constant Murley Score and the Bak criteria. Health-related quality of life was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire in cancer patients (EORTC QLQ-C30) and head and neck cancer patients (EORTC H&N35). Results: No Constant Murley Score subscale was statistically significant (p ≥ 0.180). Bak criteria was overall rated “Good“. Solely upper extremity adduction force was significantly altered on the flap side (p = 0.039). Median EORTC QLQ-C30 score was 82.2 (IQR 11.1) on the functional scale and 10.3 (IQR 2.6) on the symptomatic scale. Median quality of life score was 75.0 (IQR 33.3) and median EORTC QLQ-H&N35 was 20.6 (IQR 9.8). Conclusions: Postoperative shoulder function after modified muscle-sparing pectoralis major muscle flap surgery is comparable to function of the healthy side with a significant deficiency in adduction force not compromising daily life in this small study cohort

Awareness of Human Papillomavirus (HPV) and HPV Vaccination amongst the General Population in Germany: Lack of Awareness and Need for Action

Introduction: The oncogenic human papillomaviruses (HPV) types 16 and 18 contribute to more than 73% cases of all HPV-related cancers and commonly affect the anogenital and head and neck region, with rapidly rising incidence rates of HPV-related oropharyngeal squamous cell carcinomas (OPSCC). HPV vaccination has the potential to decrease the burden of HPV-related disease, but vaccination rates remain low in many countries. We investigated the level of awareness of HPV, and HPV-OPSCC in particular, in a representative sample of the German population. Materials and Methods: As part of an online, population-based survey, an electronic questionnaire was administered to a representative sample of 1,095 adult individuals with a specific emphasis on awareness of HPV, transmission, and indicator symptoms of oropharyngeal cancer. Statistical analysis of levels of awareness and relation of these to age, gender, and socioeconomic background were conducted using the IBM SPSS Statistics Version 25.0. Results: 699/1,095 (63.8%) subjects had never heard of HPV. Of the subjects with awareness for HPV, 210 knew that HPV could be transmitted during sex (58.3%) and 138 recognized HPV as a risk factor for OPSCC (14.2%), unrelated to gender (p = 0.357), educational status (p = 0.581), or family status (p = 0.719). 416 subjects knew that a preventive vaccine against HPV existed (44.9%). Women were significantly more aware of HPV (34.2% vs. 22.8%, p < 0.001) and the vaccination (56.4% vs. 32.7%, p < 0.001) as were men. Younger individuals (age group 25-34) were significantly more aware of HPV (p < 0.001), likely as they were offered and/or had received the HPV vaccination. There was no regional variation of HPV awareness within the German state (p = 0.051). Conclusion: Here we demonstrate a significant lack of awareness of HPV and HPV vaccination in a representative sample of the German population. Levels of awareness of the link of HPV and oropharyngeal cancer are particularly low, bearing in mind that this cancer is commonly affecting men and incidence rates are rapidly rising in many European countries and the USA. Awareness programs and further education are required to tackle the low awareness rates and increase the uptake of the vaccination program not only in Germany, but also worldwide. (c) 2022 The Author(s). Published by S. Karger AG, Base

Additional file 1 of Analysis of cells of epithelial, connective tissue and immune differentiation in HPV-positive-, HPV-negative oropharyngeal carcinoma and normal oropharyngeal tissue by immunofluorescence multiplex image cytometry: a preliminary report

Supplementary Material

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System

OBJECTIVES: Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. METHODS: We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. RESULTS: One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57–0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25–1.00, p = 0.036). CONCLUSIONS: We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field

International multicenter study of clinical outcomes of sinonasal melanoma shows survival benefit for patients treated with immune checkpoint inhibitors and potential improvements to the current TNM staging system

Objectives: Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods: We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p &lt; 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions: We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma

Introduction: olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.Methods: we conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).Results: dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).Conclusions: this study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.</p