Long-term outcomes and prognosis of neuroendocrine neoplasms of the head and neck: a cohort from a single institution.

BACKGROUND: Neuroendocrine neoplasm is a rare cancer of head and neck. This study aimed to evaluate clinical features, treatment outcomes, and prognostic factors of neuroendocrine neoplasm of head and neck treated at a single institution. METHODS: Between Nov 2000 and Nov 2021, ninety-three patients diagnosed with neuroendocrine neoplasms of head and neck treated at our institution were reviewed retrospectively. The initial treatments included chemotherapy (induction, adjuvant, or concurrent) combined with radiotherapy in 40 patients (C + RT group), surgery followed by post-operative RT in 34 (S + RT group), and surgery plus salvage therapy in 19 patients (S + Sa group). RESULTS: The median follow-up time was 64.5 months. 5-year overall survival rate (OS), progression-free survival rate (PFS), loco-regional relapse-free survival free rate (LRRFS) and distant metastasis-free survival rate (DMFS) were 64.5%, 51.6%, 66.6%, and 62.1%, respectively. For stage I-II, the 5-year LRRFS for patients' treatment regimen with or without radiotherapy (C + RT and S + RT groups versus S + Sa group) was 75.0% versus 12.7% (p = 0.015) while for stage III-IV, the 5-year LRRFS was 77.8% versus 50.0% (p = 0.006). The 5-year DMFS values for patients with or without systemic therapy (C + RT group versus S + RT or S + Sa) were 71.2% and 51.5% (p = 0.075). 44 patients (47.3%) experienced treatment failure and distant metastasis was the main failure pattern. CONCLUSIONS: Radiotherapy improved local-regional control and played an important role in the management of HNNENs. The optimal treatment regimen for HNNENs remains the combination of local and systemic treatments.

Effectiveness of early palliative care in patients with head and neck cancer in Taiwan.

BACKGROUND: Early palliative care (EPC) benefits some cancers, but its clinical outcomes differ depending on patients' racial and ethnic disparities, and customs. To determine whether EPC improves symptoms, emotional distress, and quality of life among Taiwanese patients with early or advanced-stage head and neck cancer (HNC). METHODS: Based on participants' pathological stages, they were categorized as having early and advanced-stage HNC. Those willing and unwilling to undergo EPC were assigned to the EPC and standard groups, respectively. Their daily cancer-related symptoms were assessed using the Distress Thermometer (DT) and MD Anderson Symptom Inventory (MDASI), whose scores' concurrent validity was evaluated using the European Organization for Research and Treatment of Core Quality of Life (EORTC-QLQ-C30) and Head and Neck 35 (EORTC-QLQ-H&N35) questionnaires. RESULTS: Patients (n = 93) diagnosed with HNC at Taiwan's Chia-Yi Christian Hospital from November 2020 to October 2022 were recruited. The patients voluntarily split into two groups: EPC groups and standard groups (23 and 11 in early-stage; 46 and 13 in advanced-stage, respectively). DT assessment showed significant emotional distress improvements for all patients with HNC who received EPC. The EORTC-QLQ-C30 questionnaire indicated that, compared to standard interventions, EPC groups significantly improved the quality of life and some symptoms for both early and advanced-stage HNC patients. However, the EORTC-QLQ-H&N35 questionnaire found no significant difference between the two groups. Furthermore, advanced-stage patients' anticancer treatment completion rates with EPC and standard interventions were 95.35% and 75%, respectively. CONCLUSION: EPC improves symptoms, emotional distress, quality of life, and treatment completion rates in Taiwanese patients with early or advanced-stage HNC. Nonetheless, further extensive clinical studies are required for validation.

Exosome Therapy for a Nonhealing Scalp Wound Following Chemoradiation and Surgical Therapy.

This case report describes the safety and utility of a noninvasive therapy, Purified Exosome Product (PEP), for poorly healing scalp wounds in the setting of prior chemoradiation and surgery. A man in his 60s with a history of high-grade angiosarcoma of the right temporoparietal scalp reconstruction had a 1-year history of 2 nonhealing scalp wounds after neoadjuvant chemotherapy followed by concurrent chemoradiation therapy, wide local excision, and latissimus dorsi free flap and split-thickness skin graft. The patient underwent débridement followed by 4 collagen (Bellafill)-PEP and 4 fibrin (Tisseel)-PEP applications during 7 months in 2022. Photographs of the area of exposed bone of the temporoparietal wound were measured and standardized by ImageJ open-source software. The frontal wound was not routinely measured and therefore was qualitatively assessed by reviewing photographs over time. The frontal wound completely healed, and the temporoparietal wound showed a 96% decrease in overall size. The patient had no adverse effects of treatment and continues to demonstrate ongoing healing. This case exhibits the safety and utility of topical PEP therapy for noninvasive treatment of poorly healing scalp wounds and offers the potential for an alternative treatment of patients who are poor candidates for additional surgical intervention.

Preliminary outcomes of boron neutron capture therapy for head and neck cancers as a treatment covered by public health insurance system in Japan: Real-world experiences over a 2-year period.

PURPOSE: Since June 2020, boron neutron capture therapy (BNCT) has been a health care service covered by health insurance in Japan to treat locally advanced or recurrent unresectable head and neck cancers. Therefore, we aimed to assess the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers. MATERIALS AND METHODS: We retrospectively analyzed data from patients who were treated using BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. We assessed objective response rates based on the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events based on the Common Terminology Criteria for Adverse Events, version 5.0. Additionally, we conducted a survival analysis and explored the factors that contributed to the treatment results. RESULTS: Sixty-nine patients (72 treatments) were included in the study, with a median observation period of 15 months. The objective response rate was 80.5%, and the 1-year locoregional control, progression-free survival, and overall survival rates were 57.1% (95% confidence interval [CI]: 43.9%-68.3%), 42.2% (95% CI: 30.1%-53.8%), and 75.4% (95% CI: 62.5%-84.5%), respectively. Locoregional control was significantly longer in patients with earlier TNM staging and no history of chemotherapy. CONCLUSIONS: BNCT may be an effective treatment option for locally advanced or recurrent unresectable head and neck cancers with no other definitive therapies. If definitive surgery or radiation therapy are not feasible, BNCT should be considered at early disease stages.

Ethnic Disparities for Survival and Mortality in New Zealand Patients With Head and Neck Cancer.

Importance: It is essential to identify inequitable cancer care for ethnic minority groups, which may allow policy change associated with improved survival and decreased mortality and morbidity. Objective: To investigate ethnic disparities in survival and mortality among New Zealand (NZ) patients with head and neck cancer (HNC) and the association of other variables, including socioeconomic status, tumor stage, and age at diagnosis, with survival rates. Design, Setting, and Participants: This retrospective cohort study was conducted among NZ patients diagnosed with specific HNCs from 2010 to 2020. Anonymized data were obtained from the NZ Cancer Registry, including patients diagnosed from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes C00-C14 and C30-C32. Data were analyzed from July 2020 through January 2024. Main Outcomes and Measures: Censored Kaplan-Meier estimates were used to analyze survival distribution. Cox regression models were used to estimate the association of age, tumor stage at diagnosis, and socioeconomic status with survival rates. Age-standardized mortality rates were assessed. Results: Among 6593 patients with HNCs (4590 males [69.6%]; 4187 patients aged 51-75 years [63.5%]), there were 706 Maori individuals (10.7%) and 5887 individuals with other ethnicity (89.3%), including 4327 NZ European individuals (65.6%; defined as New Zealanders of European descent). Maori individuals had a decreased survival proportion at all years after diagnosis compared with individuals with other ethnicity (eg, 66.1% [95% CI, 62.6%% to 69.8%] vs 71.2% [95% CI, 70.0% to 72.4%] at 2 years). At 1 year after diagnosis, Maori individuals did not have a significantly increased mortality rate compared with 5795 individuals with other ethnicity with data (193 deaths [27.3%] vs 1400 deaths [24.2%]; P = .06), but the rate was significantly increased at 5 years after diagnosis (277 deaths [39.3%] vs 2034 deaths [35.1%]; P = .03); there was greater disparity compared with NZ European individuals (1 year: 969 deaths [22.4%]; P = .003; 5 years: 1441 deaths [33.3%]; P = .002). There were persistent age-adjusted mortality rate disparities: 40.1% (95% CI, -25.9% to 71.2%) for Maori individuals and 18.8% (95% CI, -15.4% to 24.4%) for individuals with other ethnicity. Maori individuals were diagnosed at a mean age of 58.0 years (95% CI, 57.1-59.1 years) vs 64.3 years. (95% CI, 64.0-64.7 years) for individuals with other ethnicity, or 5 to 7 years younger, and died at mean age of 63.5 years (95% CI, 62.0-64.9 years) compared with 72.3 years (95% CI, 71.8-72.9 years) for individuals with other ethnicity, or 7 to 10 years earlier. Maori individuals presented with proportionally more advanced disease (only localized disease, 102 patients [14.5%; 95% CI, 12.0%-17.4%] vs 1413 patients [24.0%; 95% CI, 22.9%-25.1%]; P < .001) and showed an increase in regional lymph nodes (276 patients [39.1%; 95% CI, 35.5%-42.9%] vs 1796 patients [30.5%; 95% CI, 29.3%-31.8%]; P < .001) at diagnosis compared with individuals with other ethnicity. Socioeconomic status was not associated with survival. Conclusions and Relevance: This study found that Maori individuals experienced worse survival outcomes and greater mortality rates from HNC in NZ and presented with more advanced disease at a younger age. These findings suggest the need for further research to alleviate these disparities, highlight the importance of research into minority populations with HNC globally, and may encourage equity research for all cancers.

[Cervical CUP Syndrome: Diagnosis and Therapy]. / Zervikales CUP-Syndrom: Diagnostik und Therapie.

In CUP syndrome (CUP = cancer of unknown primary) there are 1 or more metastases of a primary tumor that cannot be localized despite extensive diagnostics. CUP syndrome accounts for 5% of all human malignancies, making it one of the 10 most common forms of cancer. In addition to inflammatory lymph node enlargement and benign changes such as cervical cysts, lymph node metastases are among the most common cervical masses. Cervical CUP syndrome is a histologically confirmed cervical lymph node metastasis with an unknown primary tumor. In addition to anamnesis, clinical examination and histological confirmation, diagnostics include radiological imaging using PET-CT and panendoscopy with histological primary tumor search. Treatment options include surgical therapy with neck dissection and chemoradiotherapy.

Neoadjuvant immunotherapy for head and neck squamous cell carcinoma. / Neoadjuvante Immuntherapie bei Kopf-Hals- Plattenepithelkarzinomen.

The neoadjuvant immunotherapy approach marks a significant shift in the treatment paradigm of potentially curable HNSCC. Here, current therapies, despite being highly individualized and advanced, often fall short in achieving satisfactory long-term survival rates and are frequently associated with substantial morbidity.The primary advantage of this approach lies in its potential to intensify and enhance treatment regimens, offering a distinct modality that complements the existing triad of surgery, radiotherapy, and chemotherapy. Checkpoint inhibitors have been at the forefront of this evolution. Demonstrating moderate yet significant survival benefits in the recurrent-metastatic setting with a relatively better safety profile compared to conventional treatments, these agents hold promise when considered for earlier stages of HNSCC.On the other hand, a significant potential benefit of introducing immunotherapy in the neoadjuvant phase is the possibility of treatment de-escalation. By reducing the tumor burden before surgery, this strategy could lead to less invasive surgical interventions. The prospect of organ-sparing protocols becomes a realistic and highly valued goal in this context. Further, the early application of immunotherapy might catalyze a more effective and durable immune response. The induction of an immune memory may potentially lead to a more effective surveillance of residual disease, decreasing the rates of local, regional, and distant recurrences, thereby enhancing overall and recurrence-free survival.However, neoadjuvant immunotherapy is not without its challenges. One of the primary concerns is the safety and adverse events profile. While data suggest that adverse events are relatively rare and manageable, the long-term safety profile in the neoadjuvant setting, especially in the context of curative intent, remains a subject for ongoing research. Another unsolved issue lies in the accurate assessment of treatment response. The discrepancy between radiographic assessment using RECIST criteria and histological findings has been noted, indicating a gap in current imaging techniques' ability to accurately reflect the true efficacy of immunotherapy. This gap underscores the necessity for improved imaging methodologies and the development of new radiologic and pathologic criteria tailored to evaluate the response to immunotherapy accurately.Treatment combinations and timing represent another layer of complexity. There is a vast array of possibilities in combining immunotherapy agents with conventional chemotherapy, targeted therapy, radiation, and other experimental treatments. Determining the optimal treatment regimen for individual patients becomes an intricate task, especially when comparing small, single-arm, non-randomized trials with varying regimens and outcome measures.Moreover, one needs to consider the importance of pre- and intraoperative decision-making in the context of neoadjuvant immunotherapy. As experience with this treatment paradigm grows, there is potential for more tailored surgical approaches based on the patient's remaining disease post-neoadjuvant treatment. This consideration is particularly relevant in extensive surgeries, where organ-sparing protocols could be evaluated.In practical terms, the multi-modal nature of this treatment strategy introduces complexities, especially outside clinical trial settings. Patients face challenges in navigating the treatment landscape, which involves coordination across multiple medical disciplines, highlighting the necessity for streamlined care pathways at specialized centers to facilitate effective treatment management if the neoadjuvant approach is introduced to the real-world.These potential harms and open questions underscore the critical need for meticulously designed clinical trials and correlational studies to ensure patient safety and efficacy. Only these can ensure that this new treatment approach is introduced in a safe way and fulfils the promise it theoretically holds.

Interdisciplinary Management of Vascular Anomalies in the Head and Neck. / Interdisziplinäres Management vaskulärer Anomalien im Kopf-Hals-Bereich.

Vascular anomalies in the head and neck area are usually rare diseases and pose a particular diagnostic and therapeutic challenge. They are divided into vascular tumours and vascular malformations. A distinction is made between benign tumours, such as infantile haemangioma, and rare malignant tumours, such as angiosarcoma. Vascular malformations are categorised as simple malformations, mixed malformations, large vessel anomalies and those associated with other anomalies. Treatment is interdisciplinary and various modalities are available. These include clinical observation, sclerotherapy, embolisation, ablative and coagulating procedures, surgical resection and systemic drug therapy. Treatment is challenging, as vascular anomalies in the head and neck region practically always affect function and aesthetics. A better understanding of the genetic and molecular biological basis of vascular anomalies has recently led to clinical research into targeted drug therapies. This article provides an up-to-date overview of the diagnosis, clinic and treatment of vascular anomalies in the head and neck region.

Research progress of immunotherapy for advanced head and neck cancer.

Head and neck cancer accounts for about one-fifth of all malignant tumors, and the incidence is increasing year by year. The overall mortality rate was high and the 5-year survival rate was low. At present, the combination of surgery, radiotherapy, and chemotherapy is the main treatment in clinical practice, but the treatment of recurrent or metastatic advanced head and neck cancer is still a challenge. With the rise of immunotherapy, more and more studies on immune checkpoint inhibitors have been conducted. This review summarizes the mechanism, clinical application and safety of immunotherapy for advanced head and neck cancer.

Breaking Ground in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Novel Therapies Beyond PD-L1 Immunotherapy.

The treatment for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (anti-PD1) with or without chemotherapy has led to an improvement in survival. Yet, despite this therapeutic advancement, only 15%-19% of patients remain alive at four years, highlighting the poor survival and unmet need for improved therapies for this patient population. Some of the key evolving novel therapeutics beyond anti-PD1 in R/M HNSCC have included therapeutic vaccine therapies, bispecific antibodies/fusion proteins and multitargeted kinase inhibitors, and antibody-drug conjugates (ADCs). Multiple concurrent investigations of novel therapeutics for patients with R/M HNSCC beyond anti-PD(L)1 inhibition are currently underway with some promising early results. Beyond immune checkpoint inhibition, novel immunotherapeutic strategies including therapeutic vaccines ranging from targeting human papillomavirus-specific epitopes to personalized neoantigen vaccines are ongoing with some early efficacy signals and large, randomized trials. Other novel weapons including bispecific antibodies, fusion proteins, and multitargeted kinase inhibitors leverage multiple concurrent targets and modulation of the tumor microenvironment to harness antitumor immunity and inhibition of protumorigenic signaling pathways with emerging promising results. Finally, as with other solid tumors, ADCs remain a promising therapeutic intervention either alone or in combination with immunotherapy for patients with R/M HNSCC. With early enthusiasm across novel therapies in R/M HNSCC, results of larger randomized trials in R/M HNSCC are eagerly awaited.

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research.

With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.

[Help and support for smoking cessation : an integral part of the treatment of ENT cancer]. / Aide et accompagnement au sevrage tabagique : partie intégrante du traitement du cancer ORL.

Inform, prevent, educate and encourage are the key words must be the keywords of all stakeholders who take care of a patient with ENT cancer in order to potentiate the effectiveness of the different treatments but also to improve the quality of life of patients.

Les cancers ORL sont favorisés par le tabagisme. Beaucoup de nos patients ne connaissent pas les conséquences qui découlent de leur assuétude. Informer, prévenir, éduquer et encourager doivent être les mots clé de tous les intervenants qui prennent en charge un patient atteint d'un cancer ORL afin de potentialiser l'efficacité des différents traitements mais aussi d'améliorer la qualité de vie des patients.

Comprehensive analysis revealed P4Hs as new biomarkers for prognosis and immunotherapy in head and neck cancer.

Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.

m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling.

N1-methyladenosine (m1A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels. Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.

Advancements in neoadjuvant immune checkpoint inhibitor therapy for locally advanced head and neck squamous Carcinoma: A narrative review.

The prevalent treatment paradigm for locally advanced head and neck squamous carcinoma (HNSCC) typically entails surgery followed by adjuvant radiotherapy and chemotherapy. Despite this, a significant proportion of patients experience recurrence and metastasis. Immune checkpoint inhibitors (ICIs), notably pembrolizumab and nivolumab, have been established as the first and second lines of treatment for recurrent and metastatic HNSCC (R/M HNSCC). The application of ICIs as neoadjuvant immunotherapy in this context is currently under rigorous investigation. This review synthesizes data from clinical trials focusing on neoadjuvant ICIs, highlighting that the pathological responses elicited by these treatments are promising. Furthermore, it is noted that the safety profiles of both monotherapy and combination therapies with ICIs are manageable, with no new safety signals identified. The review concludes by contemplating the future direction and challenges associated with neoadjuvant ICI therapy, encompassing aspects such as the refinement of imaging and pathological response criteria, selection criteria for adjuvant therapies, evaluation of the efficacy and safety of various combination treatment modalities, and the identification of responsive patient cohorts.