Neoadjuvant chemotherapy followed by transoral robotic surgery versus upfront surgery for locoregionally advanced oropharyngeal carcinoma: A propensity score matched analysis.

BACKGROUND: Transoral robotic surgery (TORS) performed after neoadjuvant chemotherapy (NAC) is a promising treatment for advanced-stage oropharyngeal carcinoma (OPSCC) able to reduce the adjuvant therapy administration rate. METHODS: A retrospective bi-centric study was conducted to analyze NAC + TORS versus upfront TORS patients. A 1:1 propensity score matching was used to compare the two groups. RESULTS: Among the 300 patients with stage III-IV OPSCC, 204 patients were matched for comparing NAC + TORS versus upfront TORS. Between the two groups, no significant difference was observed in recurrences and in survival for RFS, OS, and DSS. In the NAC + TORS p16-positive population, adjuvant therapy could be spared in 51% versus 16% in the upfront surgery cohort (p < 0.001) due to the lower frequency of pathological risk factors after NAC. CONCLUSIONS: NAC followed by TORS for locoregionally advanced OPSCC demonstrated to achieve non-inferior survival outcomes to upfront surgery, while in the p16-positive population allowed to significantly spare adjuvant therapy.

Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer-Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of Stromal Cell-Based Pharmacological Strategies.

Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC.

Intraoperative surgical navigation as a precision medicine tool in sinonasal and craniofacial oncologic surgery.

INTRODUCTION: Recent evidence supports the efficacy of surgical navigation (SN) in improving outcomes of sinonasal and craniofacial oncologic surgery. This study aims to demonstrate the utility of SN as a tool for integrating surgical, radiologic, and pathologic information. Additionally, a system for recording and mapping biopsy samples has been devised to facilitate sharing of spatial information. MATERIALS AND METHODS: SN was utilized for biopsy mapping in 10 sinonasal/craniofacial oncologic procedures. Twenty-five raters with experience in anterior skull base oncology were interviewed to identify 15 anatomical structures in preoperative imaging, relying on topographical descriptions and surgical video clips. The difference in the localization of anatomical structures by raters was analyzed, using the SN-mapped coordinates as a reference (this difference was defined as spatial error). RESULTS: The analysis revealed an average spatial error of 9.0 mm (95 % confidence interval: 8.3-9.6 mm), with significant differences between surgeons and radiation oncologists (7.9 mm vs 12.5 mm, respectively, p < 0.0001). The proposed model for transferring SN-mapped coordinates can serve as a tool for consultation in multidisciplinary discussions and radiotherapy planning. CONCLUSIONS: The current standard method to evaluate disease extension and margin status is associated with a spatial error approaching 1 cm, which could affect treatment precision and outcomes. The study emphasizes the potential of SN in increasing spatial precision and information sharing. Further research is needed to incorporate this method into a multidisciplinary workflow and measure its impact on outcomes.

Neoadjuvant Hyperthermia Combined with Hybrid Nanoarchitectures Enhances Chemoradiotherapy Efficacy in Head and Neck Carcinoma.

Head and neck squamous cell carcinomas are characterized by a high incidence of recurrence, especially in patients with locally advanced disease. Standard treatment strategies can be associated with severe side effects to healthy tissues that can negatively impact the patient's quality of life. Hyperthermia (HT) is a noninvasive treatment modality that has improved the effectiveness of chemotherapy (CT) and/or radiotherapy (RT) for the management of some solid neoplasms. In this context, the association of this approach with rationally designed nanomaterials may further enhance the treatment outcome. In this study, we demonstrate the enhanced effect of neoadjuvant HT in combination with hybrid nanoarchitectures enclosing a cisplatin prodrug (NAs-CisPt) and RT. All the treatments and their combinations have been fully evaluated by employing standardized chorioallantoic membrane tumor models of HPV-negative head and neck carcinoma. An improved tumor-shrinking effect was observed by the administration of the trimodal treatment (HT/NAs-CisPt/RT), which also highlighted a significant increase in apoptosis. Our findings demonstrate that the combination of HT with nanotechnology-based CT and RT in a certain order enhances the in vivo treatment outcome. On a broader basis, this study paves the way for the next exploration of noninvasive treatment approaches for the clinical management of oral cancer based on innovative strategies.

Development and validation of the head and neck cancer psychosocial distress scale (HNCPDS) to identify patients at high risk for psychological problems : a multicenter study.

To develop the Head and Neck Cancer Psychosocial Distress Scale (HNCPDS) with the aim of identifying high-risk individuals for psychosocial distress among patients, and to assess its reliability, validity and applicability. Using the classical test theory, a total of 435 head and neck cancer patients from six tertiary hospitals in China were recruited for developing the HNCPDS. Delphi expert consultation and item analysis were used to improve the content validity of the preliminary HNCPDS. Factor analysis (FA) and Structural equation modeling (SEM) were used to test the structural validity of HNCPDS. Cronbach's alpha coefficient, Spearman-Brown coefficient and Intra-class correlation coefficient (ICC) were used to test the internal consistency and retest reliability of HNCPDS. Multiple stepped-linear regression was used to analyze the risk factors of psychological disorder, and Pearson correlation coefficient was used to analyze the correlation between psychosocial distress and quality of life (QOL). The HNCPDS consisted of 14 items, which were divided into 3 subscales: 3 items for cancer discrimination, 5 items for anxiety and depression, and 6 items for social phobia. The HNCPDS had good validity [KMO coefficient was 0.947, Bartlett's test was 5027.496 (P < 0.001), Cumulative variance contribution rate was 75.416%, and all factor loadings were greater than 0.55], reliability (Cronbach's alpha coefficient was 0.954, Spearman-Brown coefficient was 0.955, test-retest reliability was 0.845) and acceptability [average completion time (14.31 ± 2.354 min) and effective completion rate of 90.63%]. Financial burden, sex, age and personality were found to be independent risk factors for HNCPDS (P < 0.05), and patients with higher HNCPDS scores reported a lower QOL (P < 0.01). The HNCPDS is effective and reliable in early identification and assessment of the level of psychosocial distress in patients with head and neck cancer, which can provide an effective basis for health education, psychological counseling, and social support in the future.

Current aspects of the quality of head and neck cancer care - survey of the Scandinavian Society for Head and Neck Oncology.

BACKGROUND: All Nordic countries have national cancer registries collecting data on head and neck cancer (HNC) incidence and survival. However, there is a lack of consensus on how other quality aspects should be monitored. AIMS: We conducted a web-based survey to find opportunities for quality control and improvement. METHODS: A web-based survey was sent to one otorhinolaryngology - head and neck (ORL-HN) surgeon, and one oncologist at each Nordic university hospital treating HNC. In total, 42 responses from all 21 university hospitals were included. RESULTS: In over half of the university hospitals, an oncologist, an ORL-HN surgeon, a pathologist, a radiologist, and a specialized nurse was always present at the multidisciplinary tumor board (MTB) meeting. Of 42 respondents 35 (83%) agreed that treatment delays were systematically recorded for each patient. Eleven of 21 (52%) oncologists agreed that side-effects of (chemo)radiotherapy were systematically recorded. Less than half of the respondents agreed that complications of surgery, and post-treatment quality of life (QOL) were systematically recorded. CONCLUSIONS: In the Nordic countries, the importance of HNC treatment timelines is well acknowledged. There is a lack of consensus on the composition of MTB meeting, and how treatment-related morbidity should be monitored outside clinical trials.

Psychological Factors Related to Treatment Outcomes in Head and Neck Cancer.

BACKGROUND: Patients with head and neck cancer (HNC) often demonstrate stress, distress, anxiety, depression, and are at risk for suicide. These affect their quality of life (QoL) but less attention has been given to psychological variables that may impact response to treatment. OBJECTIVES: This study aims to systematically review publications during 2013-2023 to collate evidence on the effects of psychological variables on HNC treatment outcomes. METHODS: We searched Ovid Medline, PubMed, Scopus, and Web of Science for articles that examined psychological factors related to treatment outcomes in patients with HNC. RESULTS: There were 29 studies (5 before treatment, 2 during, 17 after, and 5 covering the whole management trajectory) including 362,766 patients. The psychological factors were either behavioral (adjustment and coping strategy, unrealistic ideas, self-blame), cognitive (elevated risk of psychiatric co-comorbidity), or emotional (distress, depression, anxiety, nervousness, and fear of disfigurement and complications). It was found that there was a relationship between depression and decreased survival in patients with HNC. Pretreatment pain was an independent predictor of decreased survival in a large sample of patients. The distress level was approximately  54%, emotional problems ranged between 10 and 44%, while financial difficulties were identified in 54% of the patients. Sixty-nine percent of patients were reported to have used at least one cost-coping strategy within 6 months after treatment initiation. During post-treatment period, depression increased from 15% at the baseline to 29%, while the fear of recurrence was found among at least 35% of patients. DISCUSSION AND CONCLUSION: Several psychological factors predict QoL and survival among HNC survivors. Distress encompasses depression and anxiety, and physical burden from HNC diagnosis and treatment. Routine screening and early interventions that target distress could improve HNC survivors' QoL. A systematic and standardized measurement approach for QoL is warranted to homogenize these findings and to understand the underlying relationships.

Study protocol for a single-site feasibility study evaluating the adoption and fidelity of Prep-4-RT: prehabilitation for head and neck cancer patients undergoing radiotherapy.

INTRODUCTION: Prep-4-RT is a co-designed stepped-care multimodal prehabilitation program for people scheduled to receive radiotherapy for head and neck cancer (HNC). Prehabilitation, which occurs between diagnosis and treatment commencement, aims to improve a patient's health to reduce the incidence and severity of current and future impairments. HNC treatment can be distressing and has detrimental impacts on function and quality of life. HNC patients have increased social vulnerabilities including higher rates of socio-economic disadvantage and engagement in lifestyle habits which increase cancer risk. High levels of physical and psychological impacts of HNC treatment and increased social vulnerabilities of this population warrant investigation of optimal pathways of care, such as prehabilitation. This paper describes a research protocol to evaluate the feasibility of Prep-4-RT, which was designed to prepare HNC patients for the physical and psychological impacts of radiotherapy. METHODS AND ANALYSIS: At least sixty adult HNC patients, scheduled to receive radiotherapy (with or without chemotherapy), will be recruited over a five-month period. All participants will receive access to Prep-4-RT self-management resources. Participants identified through screening as high-risk will also be offered individualised interventions with relevant allied health professionals prior to the commencement of radiotherapy (psychologists, dietitians, speech pathologists and physiotherapists). Participants will complete evaluation surveys assessing their experiences with Prep-4-RT resources and interventions. Clinicians will also complete program evaluation surveys. Primary feasibility outcomes include adoption (uptake and intention to try) and fidelity (adherence to the specialist prehabilitation pathway). Secondary feasibility outcomes include acceptability (patient and clinician) of and satisfaction (patient) with Prep-4-RT as well as operational costs. Feasibility outcome data will be analysed using exact binomial and one-sample t tests, as appropriate. ETHICS AND DISSEMINATION: Ethics approval has been obtained at the Peter MacCallum Cancer Centre in Melbourne, Australia. Results will be presented at national conferences and published in peer-reviewed journal(s) so that it can be accessed by clinicians involved in the care of HNC patients receiving radiotherapy. If the model of care is found to be feasible and acceptable, the transferability and scalability to other cancer centres, or for other cancer types, may be investigated. REGISTRATION DETAILS: ANZCTA (Australian New Zealand Clinical Trials Registry) ACTRN12623000770662.

Highlighting immune features of the tumor ecosystem and prognostic value of Tfh and Th17 cell infiltration in head and neck squamous cell carcinoma by single-cell RNA-seq.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) typically present with a complex anatomical distribution, often accompanied by insidious symptoms. This combination contributes to its high incidence and poor prognosis. It is now understood that the immune features of cellular components within the tumor ecosystem and their complex interactions are critical factors influencing both tumor progression and the effective immune response. METHODS: We obtained single-cell RNA sequencing data of 26,496 cells from three tumor tissues and five normal tissues and performed subsequent analyses. Immunohistochemical staining on tumor sections was used to validate the presence of malignant cells. Additionally, we included bulk RNA sequencing data from 502 HNSCC patients. Kaplan-Meier analysis and the log-rank test were employed to assess predictors of patient outcomes. RESULTS: We identified three epithelial subclusters exhibiting immune-related features. These subclusters promoted the infiltration of T cells, dendritic cells, and monocytes into the tumor microenvironment. Additionally, cancer-associated fibroblasts displayed tumor-promoting and angiogenesis characteristics, contrasting with the predominant antigen-presenting and inflammatory roles observed in fibroblasts from normal tissues. Furthermore, tumor endothelial subsets exhibited a double-sided effect, promoting tumor progression and enhancing the effectiveness of immune response. Finally, follicular helper T cells and T helper 17 cells were found to be significantly correlated with improved outcomes in HNSCC patients. These CD4+ T cell subpopulations could promote the anti-tumor immune response by recruiting and activating B and T cells. CONCLUSION: Our findings provide deeper insights into the immune features of the tumor ecosystem and reveal the prognostic significance of follicular helper T cells and T helper 17 cells. These findings may pave the way for the development of therapeutic approaches.

Vaccine a promising immunotherapy option for head and neck cancer patients.

Head and neck cancer (HNC) is a diversified group of tumors arising from the upper aerodigestive tract, encompassing the oral cavity, larynx, and pharynx. Globally, this particular cancer ranks sixth in prevalence, resulting in an annual mortality rate above 325,000 individuals. Surgery, radiation, and chemotherapy are the primary therapeutic options for HNC, which are frequently used in combination. Despite their extensive use, these treatments are typically unsuccessful and can significantly impair patient quality of life. Therapeutic vaccinations are administered to cancer patients instead of preventative immunizations administered to a healthy population. The efficacy of this modality has considerably transformed the application and success of cancer management by providing an additional and effective therapeutic option for patients. Cancer treatment has been revolutionized by introducing Immune Checkpoint receptors inhibitors (ICR), such as anti-CTLA4, anti-PD-1, and anti-PD-L1.3. ICR have also established immunity against self-generated cancerous cells. Cancer vaccines have shown extraordinary synergistic potential with checkpoint inhibitors to maximize tumor-specific CD8+ expansion and activity, which detects and destroys tumor cells. Personalized neoantigen vaccination therapies can potentially combat the heterogeneity of each patient's tumor. The findings of this review suggest that recent advances in cancer immunology and genetics imply that cancer vaccination can be a promising alternative treatment for head and neck cancer patients. This review conducted a comprehensive literature search to identify relevant studies on immunotherapy options for head and neck cancer patients. The search strategy was designed to capture a wide range of peer-reviewed articles, conference proceedings, and grey literature from 2013 to 2023. The databases searched to ensure comprehensive coverage of the literature included PubMed, Web of Science, and Google Scholar; to include grey literature and articles not indexed in traditional databases.

Decreased Rates of Radiation-induced Trismus and Lowered Mastication Structure Doses in Patients Treated for Head and Neck Cancer During the Last Two Decades.

AIMS: To investigate how absorbed doses to mastication structures in modern radiotherapy (RT) technique for head and neck cancer (HNC) compared with earlier RT techniques and with published trismus tolerance doses. To compare the incidence of radiation-induced trismus by earlier and newer RT techniques. MATERIALS AND METHODS: This study investigated two HNC patient cohorts treated with RT in 2007-2012 (three-dimensional conformal radiotherapy [3DCRT] and/or intensity-modulated radiotherapy [IMRT]; n =121 [Cohort 1]) and 2017-2020 (volumetric-modulated arc therapy [VMAT]; n =124 [Cohort 2]). All patients underwent RT without mastication structure-sparing intent, had normal mouth-opening ability before RT, and were prospectively assessed. Trismus was defined as the maximal interincisal opening ≤35 mm at any follow-up (3-, 6-, and 12-months post-RT). The temporomandibular joints (TMJs), masseter, and medial/lateral pterygoid muscles were delineated on the planning CT:s. Mean doses were compared between cohorts, and evaluated with respect to published trismus tolerance doses. P values ≤ 0.05 indicated statistical significance. RESULTS: Within 12 months post RT, 74/121 (61%) of patients in Cohort 1 had experienced trismus compared to 11/124 (9%) in Cohort 2. Averaged mean doses (±S.D.) for the masseter muscles were 35.2±8.3 Gy in Cohort 1 and 20.2±8.7 Gy in Cohort 2 (P <0.001). Corresponding numbers were 19.1±16.2 and 4.3±4.3 Gy for the TMJs, 53.7±10.1 and 40.2±16.8 Gy for the medial pterygoid muscles, and 29.2±18.7 and 9.2±8.4 Gy for the lateral pterygoid muscles (all P <0.001). Masseter muscle doses were below tolerance doses in 23% of patients in Cohort 1 compared with 90% in Cohort 2. The corresponding numbers were 52% and 96% for the TMJs, 8% and 36% for the medial pterygoid muscles and 72% and 100% for the lateral pterygoid muscles. CONCLUSION: Mastication structure mean doses by more recent RT techniques were generally below proposed tolerance doses, with dose reductions of 10-20 Gy compared with earlier techniques. Modern RT without mastication-structure-sparing intent resulted in below 10% of HNC patients experiencing trismus compared with 60% treated with earlier techniques.

The prognostic role of MRI-based radiomics in tongue carcinoma: a multicentric validation study.

PURPOSE: Radiomics is an emerging field that utilizes quantitative features extracted from medical images to predict clinically meaningful outcomes. Validating findings is crucial to assess radiomics applicability. We aimed to validate previously published magnetic resonance imaging (MRI) radiomics models to predict oncological outcomes in oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: Retrospective multicentric study on OTSCC surgically treated from 2010 to 2019. All patients performed preoperative MRI, including contrast-enhanced T1-weighted (CE-T1), diffusion-weighted sequences and apparent diffusion coefficient map. We evaluated overall survival (OS), locoregional recurrence-free survival (LRRFS), cause-specific mortality (CSM). We elaborated different models based on clinical and radiomic data. C-indexes assessed the prediction accuracy of the models. RESULTS: We collected 112 consecutive independent patients from three Italian Institutions to validate the previously published MRI radiomic models based on 79 different patients. The C-indexes for the hybrid clinical-radiomic models in the validation cohort were lower than those in the training cohort but remained > 0.5 in most cases. CE-T1 sequence provided the best fit to the models: the C-indexes obtained were 0.61, 0.59, 0.64 (pretreatment model) and 0.65, 0.69, 0.70 (posttreatment model) for OS, LRRFS and CSM, respectively. CONCLUSION: Our clinical-radiomic models retain a potential to predict OS, LRRFS and CSM in heterogeneous cohorts across different centers. These findings encourage further research, aimed at overcoming current limitations, due to the variability of imaging acquisition, processing and tumor volume delineation.

Analysis of the Ki-67 Proliferation Index in Relation to Tumor, Node, and Metastasis (TNM) Stage in Patients With Oral Cavity Squamous Cell Carcinoma.

Introduction Squamous cell carcinoma (SCC) comprises more than 90% of malignant tumors of the oral cavity, accounting for up to 40% of all malignancies in South Asia. Despite the progress made in cancer management, the five-year survival rate for SCC has remained around 50%. To improve this survival rate, it is essential to understand the tumor's biology at its core. In our study, the Ki-67 proliferation index of tumor cells was analyzed and correlated with the tumor stage, nodal stage, and tumor grade to determine the tumor's biological aggressiveness. Materials and methods The study was conducted in a tertiary care center in South Asia from 2018 to 2022. A total of 50 adult patients with biopsy-proven oral cavity SCC were taken for analysis. The Ki-67 index was assessed in tumor cells using immunohistochemistry. Results Ki-67 was classified into two subcategories: <20% and >20%. Patients with an advanced T stage (T3-T4) have a greater chance of having a higher Ki-67 index (>20%), with p = 0.047. However, there is no statistically significant association between nodal status and tumor grade. Conclusion The Ki-67 proliferation index predicts the behavior of SCC lesions regarding tumor size and invasiveness.

Head and neck cancer surveillance: The value of computed tomography and clinical exam.

PURPOSE: The recurrence of head and neck cancer (HNC) is most prevalent during the initial two years following curative treatment, underscoring the criticality of regular surveillance for HNC survivors. This study aims to evaluate the effectiveness of computed tomography (CT) imaging and clinical physical examination (CE) in HNC surveillance, assessing whether these imaging protocols meet the current treatment limitations confronting HNC specialists. METHODS: Retrospective chart review of a 9-year experience with head and neck cancer patients at a single, academic tertiary care center. Demographic data was collected along with data regarding whether the recurrences were detected primarily through CE, flexible endoscopic exam (scope exam), or CT or CT/PET scan. Subsets of the data were analyzed and compared by sensitivity, specificity, and negative predictive values. RESULTS: 264 HNC patients were identified. 72 total recurrences (27 %) were noted. The method of initial detection spurring further investigation was imaging in 42 (58.3 %) patients, CE (33.3 %) in 24 patients, scope exam in 6 (8.4 %) patients. Overall, 65 (90.3 %) patients had imaging that showed recurrence regardless of method of initial detection. Sensitivity, (87.1 % vs 70.5 %), and specificity (93.95 % vs 96.9 %) were noted for CT and CE respectively. Combined sensitivity and specificity for CT and CE was 96.2 % and 91.05 % respectively. CONCLUSION: The data suggests that imaging could provide sufficient methods of HNC surveillance despite limitations the COVID-19 pandemic presents.

Validity of a single-item indicator of treatment side effect bother in patients with head and neck cancer.

PURPOSE: Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burden currently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, "I am bothered by side effects of treatment") with overall side effects in HNSCC. METHODS: We performed a retrospective secondary analysis of development of the Functional Assessment of Cancer Therapy (FACT) Head/Neck Symptom Index (FHNSI-10), which included completing FACT-HN (including Head/Neck Cancer Subscale (HNCS) and Trial Outcome Index (TOI)) and the pain intensity numeric rating scale (NRS). We calculated Spearman's correlations between GP5 and these measures of patient-reported global health, head/neck side effects, and pain intensity NRS. A correlation of > 0.4 was considered sufficient evidence of association. RESULTS: Ninety-seven patients completed baseline and 85 completed 3-month follow-up surveys. GP5 was highly correlated with FACT-HN total score (baseline r = 0.66, 3 months r = 0.67) and FHNSI-10 (baseline r = 0.63, 3 months r = 0.65). GP5 correlated with multiple FACT-HN subscales including FACT-G, physical well-being, functional well-being, HNCS, and TOI (range baseline r = 0.53-0.77, range 3 months r = 0.49-0.77). Worsening GP5 score was associated with worsening overall HNCS (p = 0.002), worsening FHNSI-10 score (p < 0.001), and worsening mean pain intensity (p < 0.001). CONCLUSION: GP5 exhibited validity within HNSCC, exhibiting substantial correlations with a number of HNSCC-related PRO measures including FACT-HN and FHNSI-10. Worsening GP5 was associated with worsening HNCS, FHNSI summary score, and pain intensity. GP5 has promise as a summary indicator of symptom and side effect bother in HNSCC.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008.

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

A novel prognostic score (HAMP) for head and neck cancer patients with single and multiple SBRT-treated lung metastases derived from retrospective analyses of survival outcome.

BACKGROUND: We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). METHODS: In this retrospective study, we examined selected factors associated with progression-free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. RESULTS: Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut-off total score of ≤18 scoring points for patients in a high-risk (HR) subcohort, and of ≥19 scoring points for patients in a low-risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low-risk group compared to the high-risk group. CONCLUSION: The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow-up. The accuracy and reliability of the score requires further evaluation in prospective studies.

Adjuvant Therapy with Immune Checkpoint Inhibitors after Carbon Ion Radiotherapy for Mucosal Melanoma of the Head and Neck: A Case-Control Study.

The development of new treatment strategies to improve the prognosis of mucosal malignant melanoma of the head and neck (MMHN) after carbon ion radiotherapy (CIRT) is essential because of the risk of distant metastases. Therefore, our objective was to evaluate the outcomes of immune checkpoint inhibitor (ICI) treatment to justify its inclusion in the regimen after CIRT. Thirty-four patients who received CIRT as an initial treatment were included in the analysis and stratified into three groups: those who did not receive ICIs (Group A), those who received ICIs after recurrence or metastasis (Group B), and those who received ICIs as adjuvant therapy after CIRT (Group C). In total, 62% of the patients (n = 21) received ICIs. The 2-year local control and overall survival (OS) rates for all patients were 90.0% and 66.8%, respectively. The 2-year OS rates for patients in Groups A, B, and C were 50.8%, 66.7%, and 100%, respectively. No significant differences were observed between Groups A and B (p = 0.192) and Groups B and C (p = 0.112). However, a significant difference was confirmed between Groups A and C (p = 0.017). Adjuvant therapy following CIRT for MMHN may be a promising treatment modality that can extend patient survival.

Impact of Treatment on Quality of Life in Oropharyngeal Cancer Survivors: A 3-Year Prospective Study.

(1) Background: This prospective study aimed to assess the impact on quality of life (QoL) from pretreatment to 3 years after treatment in oropharyngeal carcinoma (OPC) survivors. (2) Methods: QoL was measured with the EORTC QLQ-C30 and EORTC QLQ-H&N35 scales before treatment and in the first and third years. (3) Results: Of 72 patients, 51 completed all questionnaires over 3 years. A variable deterioration of QoL scores was detected before treatment. Most items worsened significantly after treatment and during the first year and improved in the third year. Advanced-stage cancer and definitive chemoradiotherapy treatment showed the worst scores. At 3 years, patients who underwent surgery with adjuvant radiation therapy/chemotherapy had significantly better scores on global QoL and emotional functioning compared to those treated with definitive chemoradiotherapy, who also reported problems with sticky salivation and dry mouth. Patients treated with an open surgical approach showed significantly greater deterioration in physical and role functioning compared to transoral surgery. (4) Conclusions: This long-term prospective study is the first in Spain to use EORCT scales in a homogeneous group of OPC survivors. QoL was generally good, although patients needed a long period of time to recover from both cancer and side effects of treatment. Advanced-stage cancer and definitive chemoradiotherapy showed the worst scores.

Bufalin Suppresses Head and Neck Cancer Development by Modulating Immune Responses and Targeting the ß-Catenin Signaling Pathway.

Bufalin, a cardiotonic steroid derived from the Chinese toad (Bufo gargarizans), has demonstrated potent anticancer properties across various cancer types, positioning it as a promising therapeutic candidate. However, comprehensive mechanistic studies specific to head and neck cancers have been lacking. Our study aimed to bridge this gap by investigating bufalin's mechanisms of action in head and neck cancer cells. Using several methods, such as Western blotting, immunofluorescence, and flow cytometry, we observed bufalin's dose-dependent reduction in cell viability, disruption of cell membrane integrity, and inhibition of colony formation in both HPV-positive and HPV-negative cell lines. Bufalin induces apoptosis through the modulation of apoptosis-related proteins, mitochondrial function, and reactive oxygen species production. It also arrests the cell cycle at the G2/M phase and attenuates cell migration while affecting epithelial-mesenchymal transition markers and targeting pivotal signaling pathways, including Wnt/ß-catenin, EGFR, and NF-κB. Additionally, bufalin exerted immunomodulatory effects by polarizing macrophages toward the M1 phenotype, bolstering antitumor immune responses. These findings underscore bufalin's potential as a multifaceted therapeutic agent against head and neck cancers, targeting essential pathways involved in proliferation, apoptosis, cell cycle regulation, metastasis, and immune modulation. Further research is warranted to validate these mechanisms and optimize bufalin's clinical application.