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1.
Artigo em Inglês | MEDLINE | ID: mdl-39353158

RESUMO

OBJECTIVE: To characterize the concerns of head and neck cancer (HNC) patients and discern changes in quality-of-life (QoL) during long-term follow-up. STUDY DESIGN: Retrospective review. SETTING: Survivorship clinic at a tertiary academic center. METHODS: A retrospective review was conducted on HNC patients seen in our survivorship clinic between 1/2020 and 1/2024 using the University of Washington Quality of Life (UW-QOL) Questionnaire. RESULTS: Three hundred and forty-two patients were seen for 914 encounters. Patients were divided into 4 groups: pretreatment (n = 326), 0 to 12 months posttreatment (n = 247), 1 to 3 years posttreatment (n = 248), and more than 3 years posttreatment (n = 64). The average follow-up after treatment was 459 days (range: 0-5.2 years). Multivariable analysis revealed significant improvements in overall QoL, health-related QoL, social-emotional composite scores, activity, anxiety, appearance, chewing, mood, pain, speech, and recreation at more than 1-year posttreatment compared to less than 1-year posttreatment. However, declines were noted in saliva and taste scores. No differences in scores were observed between patients 1 to 3 years posttreatment and those >3 years posttreatment. At all timepoints before and after treatment, top concerns were pain, activity, and swallowing. Patients with oral cancer followed for more than 1-year posttreatment had worse scores in appearance, chewing, pain, and speech compared to those with oropharyngeal cancer. CONCLUSIONS: Understanding the evolving concerns of HNC patients is imperative for enhancing care. Most QoL domains improve at 1-year posttreatment except for saliva, taste, swallowing, and shoulder function. QoL scores stabilize after 1-year post-treatment. Pain, activity, and swallowing remain the top concerns at all time points.

2.
Cell Oncol (Dordr) ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361147

RESUMO

Head and neck cancer (HNC) remains a major global health burden, prompting the need for innovative therapeutic strategies. This review examines the role of the cystine/glutamate antiporter (xCT) in HNC, specifically focusing on how xCT contributes to cancer progression through mechanisms such as redox imbalance, ferroptosis, and treatment resistance. The central questions addressed include how xCT dysregulation affects tumor biology and the potential for targeting xCT to enhance treatment outcomes. We explore recent developments in xCT-targeted current and emerging therapies, including xCT inhibitors and novel treatment modalities, and their role in addressing therapeutic challenges. This review aims to provide a comprehensive analysis of xCT as a therapeutic target and to outline future directions for research and clinical application.

3.
Acta Endocrinol (Buchar) ; 20(1): 59-64, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372295

RESUMO

Introduction: Radiation-induced hypothyroidism is a well-recognized entity that occurs after an interval of 15-21 months. However, in the treatment of locally advanced Head and neck Squamous cell carcinoma (HNSCC), thyroid-sparing techniques are infrequently employed. Aims: To evaluate the dosimetric and early clinical outcomes of thyroid-sparing SIB-VMAT technique (Simultaneous Integrated Boost - Volumetric Modulated Arc Radiotherapy) in patients of locally advanced HNSCC. Methods: In this two-arm prospective pilot study, patients in the study group received radiotherapy by SIB-VMAT technique with a thyroid constraint to a dose of 70 Gy to the gross disease and 59.4 Gy to nodal and subclinical disease in 33 fractions over 6 ½ weeks with concurrent cisplatin. V50Gy<75% was the thyroid constraint used. The control group was treated with the same dose and technique but without using a thyroid gland constraint. The dose-volume parameters of the thyroid gland, PTV (Planning Target Volume) along with thyroid profile were analyzed. Results: Twenty-six patients were recruited. Thyroid V50Gy of the study group (65.33 ±6.63 %) was significantly lower than that of control group (80.35 ±13.40 %) (p=0.003). Tumor dose parameters of both groups were compared and revealed no significant difference. At 18 months follow-up, the incidence of any degree of hypothyroidism was 46.15% in the study group and 23.07% in the control group (p=0.216). Conclusion: In locally advanced HNSCC, it is feasible to spare the thyroid gland without compromising the tumour coverage. This has the potential to reduce the frequency of radiation-induced hypothyroidism.

5.
Pract Radiat Oncol ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39389420

RESUMO

PURPOSE: A digital visual communication tool was recently developed by MyCareGorithm which incorporates explanations of treatments and procedures for cancer patients. This study will evaluate if this novel tool can enhance both patient and provider satisfaction. METHODS: In an IRB approved, prospective, pilot study, patients and caregivers at a single institution receiving head and neck cancer radiation underwent an initial consult using this digital tool and completed a survey of 6 questions to evaluate their understanding of their disease. Providers completed a 7-question survey to rate their satisfaction. Patients and caregivers with 4 or more "Yes" answers and providers with 5 or more "Yes" answers were defined as "Satisfied". In order to obtain 90% power to detect that the proportion of "Satisfied" patients (assumed 75%) is greater than 50% with a significance level 5% using a one-sided Z test, we planned to enroll 30 patients. RESULTS: Thirty patients enrolled and completed all surveys. Most patients were male (66%), white (60%) and spoke English as a primary language (93%). Patients most commonly had oropharyngeal cancer (23%). Overall, 27 out of 30 of patients (90%; one sided 95%CI: 76.1%) were satisfied (z = 4.38, p < 0.05), 16 of the 17 caregivers (94%; one sided 95% CI: 74.8%) were satisfied and 100% of providers were satisfied with the digital tool. Most patients (90%) and caregivers (94%) felt that the tool improved their understanding of the disease. One male answered "No" for all 6 questions commenting that it was only marginally helpful. One female also answered "No" for all questions commenting that she did not find it helpful on its own without the provider explanation. Out of the 30 patients, 26 (87%) stayed at our institution to receive treatment. CONCLUSIONS: These findings showed high rates of patient, caregiver and provider satisfaction with their initial consult when incorporating a digital visual tool. Its routine use in clinical practice should be strongly considered.

6.
Med Dosim ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39389801

RESUMO

PURPOSE: Head and Neck (H&N) cancer accounts for 3% of cancer cases in the United States. Precise tumor segmentation in H&N is of utmost importance for treatment planning and administering personalized treatment dose. We aimed to develop an automatic tumor localization and segmentation method in enhancing the clinical efficiency and ultimately improving treatment outcomes. APPROACH: In this study, a hybrid neural network (HNN) was developed by integrating object localization and segmentation into a unified framework. It consists of 4 stages: preprocessing, HNN training, object localization and segmentation, and postprocessing. We utilized a dataset consisting of PET and CT images for 48 patients and designed a Hybrid Neural Network (HNN) which consists of YOLOv4 object detection model + U-Net model for image segmentation. YOLOv4 was used to identify regions of interests (ROI), while the U-Net was employed for the precise image segmentation. In our experiments we considered 2 object detection architectures to identify possible tumor regions, namely YOLOv4 and Faster-RCNN. The evaluation metrics for both were evaluated and compared. RESULTS: We evaluated the performance of 3 model combinations: YOLOv4 + U-Net, Faster-RCNN + U-Net, and U-Net alone. The models were evaluated based on Sensitivity, Specificity, F-Score, and Intersection over Union (IoU). YOLOv4 + U-Net achieved the best values with Sensitivity of 0.89, Specificity of 0.99, F-Score of 0.84, and IoU of 0.72. CONCLUSION: A new hybrid neural network (HNN) for fully automatic tumor localization and segmentation was developed and the experimental results. showcased the HNN's impressive performance, indicating its potential to be a valuable H&N tumor segmentation tool.

7.
Cancer Radiother ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39389843

RESUMO

The modalities of management by reirradiation for recurrence or a second localization of head and neck squamous cell carcinoma (HNSCC) in previously irradiated terrain is challenging due to the great heterogeneity of data in the literature, mainly retrospective data reporting non-negligible risks of serious late toxicity events. With the recent development of more precise and conformal radiotherapy techniques such as intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic radiotherapy (SBRT), the benefit-to-risk ratio of reirradiation has evolved in recent years with encouraging results, but patient selection is crucial. The aim of this review is to discuss the role of HNSCC reirradiation in terms of patient selection and external photon radiotherapy techniques for definitive tumor reirradiation and postoperative reirradiation.

8.
Ann Oncol ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39389887

RESUMO

BACKGROUND: Outcomes for patients with locally advanced head and neck cancer (HNC) treated with curative intent remain disappointing, with 5-year survival rates at 50%. Most recurrences occur within the first 2 years after treatment, providing a window of opportunity to identify patients with molecular residual disease (MRD). A tissue-agnostic test for MRD detection in patients with human papillomavirus (HPV) positive and negative HNC, where tissue is often scarce, is needed. PATIENTS AND METHODS: Patients with stage I-IVB HNC, including patients positive and negative for HPV, were enrolled and peripheral blood plasma was collected longitudinally at diagnosis and ∼3, 12, and 24 months after curative intent treatment. The full cohort includes 325 patients with 1155 samples. Samples were split into distinct sets to train and validate a classifier capable of identifying MRD using a tissue-agnostic genome-wide methylome enrichment platform. The primary endpoint was recurrence-free survival (RFS). RESULTS: With a median follow-up of 60 months, patients in the blinded validation set with MRD positivity experienced significantly worse RFS with a hazard ratio (HR) of 35.7 [95% confidence interval (CI) 10.8-117.8; P < 0.0001]. For patients with HPV negativity, HR was 42.3 (95% CI 9.8-182.3; P < 0.0001); for patients with HPV-positive oropharyngeal cancer, HR was 24.1 (95% CI 3.0-196.8; P < 0.0001). Moreover, the lead time between MRD positivity and clinical recurrence was up to 14.9 months, with a mean lead time of 4.1 months. Surveillance sensitivity was 91% (95% CI 77% to 97%) and specificity was 88% (95% CI 80% to 93%). CONCLUSIONS: Here we validate the clinical performance characteristics of a tissue-agnostic genome-wide methylome enrichment assay for MRD detection in patients with HNC. The MRD detection test showed high sensitivity for identifying recurrence at high specificity across different anatomical sites, HPV status, and treatment regimens, highlighting the broad applicability for MRD detection in patients with HNC.

9.
Sleep Breath ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390313

RESUMO

STUDY OBJECTIVES: Sleep-disordered breathing (SDB) is a very common and underdiagnosed condition in head and neck cancers (HNC) patients. If untreated, SDB can lead to negative health consequences. The identification of SDB in HNC patients is crucial to ensure appropriate treatment and to improve outcomes. The purpose of the study was to investigate the incidence of coexisting SDB in HNC patients and to evaluate methods of assessing SDB in the population. METHODS: A systematic search of PubMed, Embase, CINAHL, Cochrane Database, the Web of Science, and Scopus was performed for studies related to SDB in HNC patients. In total, 1713 articles were identified. 19 articles were selected for qualitative synthesis. The studies involved 584 subjects. RESULTS: The prevalence of SDB ranged from 57 to 90% before cancer treatment and from 12 to 96% after. When using an apnea-hypopnea index (AHI) cut-off ≥ 5/h to diagnosis SDB, the prevalence of SDB was 57-90% before cancer treatment and 12-94% after treatment. Sleep studies using polysomnography are the most commonly used assessment tools, but thresholds for diagnosis have been inconsistent. CONCLUSIONS: There is a high prevalence of SDB in HNC patients. However, the diagnostic and thresholds methods used for detecting SDB vary widely. To determine the accurate prevalence of SDB, prospective, systematic studies of SDB in unselected cohorts of HNC participants are required.

10.
West J Nurs Res ; : 1939459241287451, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390796

RESUMO

BACKGROUND: Patients with head and neck cancer (HNC) have to cope with a multitude of treatment-related adverse effects that impact their quality of life (QoL) post-treatment completion. The presence of family resilience could potentially foster individual resilience and might contribute to patients' QoL. However, this interconnection has not been confirmed. OBJECTIVE: To explore the relationships between family resilience, individual resilience, and QoL in patients with HNC and to determine whether individual resilience in HNC patients functions as a mediator between family resilience and QoL. METHODS: From September 2022 to June 2023, a cross-sectional survey was conducted among 185 patients with HNC recruited through convenience sampling from a tertiary care hospital in Jiangsu Province, China. Self-report measures of family resilience, individual resilience, and QoL were assessed. Relationships were examined by Pearson's correlations. Structural equation models were used to assess whether individual resilience played a mediating role between family resilience and QoL. RESULTS: There were significant positive correlations between QoL and both family resilience (r = 0.43, P < .01) and individual resilience (r = 0.59, P < .01). Moreover, family resilience had an indirect influence on QoL through its effect on individual resilience (ß = 0.319, 95% CI: 0.336-0.815). CONCLUSION: Family resilience emerges as a significant positive factor capable of enhancing QoL for patients with HNC by bolstering their resilience. To mitigate the detrimental effects of inadequate individual resilience on QoL of patients with HNC, it is advised to implement interventions focused on enhancing family resilience. CHINA CLINICAL TRIALS REGISTRY NUMBER: ChiCTR2300067612.

11.
Chin Clin Oncol ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39390921

RESUMO

BACKGROUND: The conventional method of drug development in oncology typically progresses through phase I, phase II and randomized phase III trials. Nevertheless, some recent drug approvals for head and neck cancer (HNC) relied on findings from single-arm phase II trials. This underscores the significance of disease-specific phase I trials as a crucial step in exploring new drugs for HNC patients. The purpose of this review is to present the currently available data of phase I clinical trials conducted in HNC and to provide an overview of ongoing therapeutic trends in HNC. METHODS: We performed a scoping review of phase I trials evaluating single-agent treatments specifically designed for HNC patients. The PubMed database was searched using "(phase I) AND (head and neck)". To ensure exhaustiveness, we also performed a search from the American Society of Clinical Oncology, European Society for Medical Oncology and American Association for Cancer Research websites. RESULTS: We screened 1,134 articles and selected 29 trials that met eligibility criteria, published between 1994 and 2023, for a total of 741 patients. Twenty-one trials comprised patients with different sites of HNSCC and only 8 trials (27%) focused on a specified subsite of head and neck. Most of trials investigated treatments in recurrent/metastatic (R/M) settings (86%). Immunotherapeutic agents were the most examined followed by targeted agents, cytotoxic drugs and "others" including a nanoparticle, a therapeutic gene, a fusion protein and a modulator of gene expression. Among trials reporting activity for R/M head and neck patients (n=23), the global median overall response rate (ORR) was 12% and four trials (17%) did not report any response. The incidence of grade 3/4 treatment-related adverse events (TRAEs) was low (7%). However, in seven trials safety results are not clearly assessable from the published data. CONCLUSIONS: Phase I trials of single agents designed for head and neck patients were generally safe but with a low ORR. Future development of new drugs dedicated for HNC patients that can more accurately reflect the heterogeneity of HNC and provide more detailed subgroup analyses is warranted.

12.
Pathol Res Pract ; 263: 155603, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39368364

RESUMO

The gut microbiome, a complex community of microorganisms residing in the gastrointestinal tract, plays a crucial role in maintaining human health and influencing disease outcomes. Recent advancements in sequencing technologies have revealed the intricate relationship between gut microbiota and various health conditions. This review explores the impact of gut microbiome dysbiosis on immune function, chronic inflammation, and cancer progression. Dysbiosis, characterized by an imbalance in microbial populations, can lead to immune dysfunction, creating a pro-inflammatory environment conducive to tumorigenesis. Gut microbiome metabolites, such as short-chain fatty acids and bile acids, also play a significant role in modulating these processes. The interplay between these factors contributes to the development and progression of HNC. Furthermore, this review highlights the potential of therapeutic interventions targeting the gut microbiome, including probiotics, prebiotics, and dietary modifications, to restore microbial balance and mitigate cancer risk. Understanding the mechanisms by which the gut microbiome influences HNC can provide valuable insights into novel preventive and therapeutic strategies. Future research should focus on elucidating the specific microbial taxa and metabolites involved in HNC, as well as the impact of lifestyle factors such as diet, alcohol consumption, and oral hygiene on the gut microbiome. By leveraging the growing knowledge of the gut microbiome, it may be possible to develop personalized approaches to cancer prevention and treatment, ultimately improving patient outcomes.

13.
Clin Neurol Neurosurg ; 246: 108584, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39368393

RESUMO

INTRODUCTION: Carotid blowout syndrome (CBS) is a potentially life-threatening complication of head and neck cancer and associated treatment. In this study, we assess the safety and efficacy of deconstructive and reconstructive procedures with a focus on CBS recurrence. METHODS: We conducted a multicenter retrospective analysis of a prospectively maintained database and identified 80 consecutive neurointerventions for CBS from 2016 to 2020. Patients were divided into 2 groups: deconstructive embolization (68 patients) and reconstructive stenting (12 patients). A comparative analysis was performed between the two groups. RESULTS: The CBS recurrence rate was 23.8 % with 84.2 % of recurrences occurring within 90 days of the primary event. The median time to rebleeding was 8.0 days (IQR: 2.0 - 28.5) with a mortality rate of 26.3 %. There was no significant difference in rates of peri-operative ischemic stroke (1.5 % vs. 0 %, p=0.672) or peri-operative mortality (1.5 % vs. 0 %, p=0.670). CBS recurrence was significantly higher in the reconstructive group (58.3 % vs. 17.6 %, p=0.002). On multivariate analysis, reconstructive stenting independently predicted rebleeding (adjusted hazard ratio 8.31, 95 % CI: 2.34-29.59, p=0.001). There was no significant association between CBS recurrence and pre-operative (p=0.600) or post-operative (p=0.275) anticoagulant/antiplatelet use. CONCLUSION: CBS remains a challenging and potentially catastrophic complication of head and neck cancers. Reconstructive procedures, including stenting, predicted CBS recurrence independent of bleeding site or tumor invasion. Postoperative surveillance based on time intervals to CBS recurrence and engineering advancements including improved vessel reconstruction devices have the potential to reduce rehemorrhage rates and improve patient outcomes. Further clinical investigations amongst larger cohorts are needed.

14.
Oral Dis ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39370774

RESUMO

BACKGROUND: Head and neck cancer (HNC) and its treatments can cause significant pain, which can profoundly impact patients' quality of life and treatment outcomes. Understanding the full scope of HNC pain is essential for effective management and improved patient care. OBJECTIVE: This review aims to comprehensively analyze the multifaceted nature of pain experienced by individuals with HNC, including its various etiologies and management strategies. RESULTS: HNC pain can arise from tumor extent, treatment-related toxicity, or comorbid conditions. The pathophysiology involves complex interactions between nociceptive, neuropathic, and inflammatory mechanisms. Optimal pain control requires a multimodal patient-tailored approach utilizing both pharmacological and non-pharmacological therapies. CONCLUSION: Enhancing our understanding of HNC pain and optimizing its management is imperative for improving the overall well-being and treatment outcomes of affected individuals. Future research should focus on understanding detailed pain mechanisms, with the goal of developing personalized pain management strategies and exploring novel therapeutic targets. By implementing comprehensive approaches to HNC pain management, healthcare providers can better support patients through their cancer treatment journey.

15.
Ann Med Surg (Lond) ; 86(10): 6149-6152, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39359846

RESUMO

Introduction: Most cases of squamous cell carcinoma (SCC) of the tongue occur on the lateral surface; however, SCC of the dorsum is extremely rare. Case presentation: The authors describe the case of a 79-year-old man with SCC involving the midline of the dorsum of the tongue. The lesion was surgically resected. The patient was followed up for 1 year and 6 months, and no recurrence was noted. Discussion: SCC of the dorsal midline is even rarer and accounts for less than 1% of tongue carcinomas. SCC involving the dorsum may have a worse prognosis than SCC of the lateral or ventral surface. This report is the first to use submental flap reconstruction to treat cancer of the midline dorsum of the tongue. Conclusion: The authors encountered a case of SCC involving the midline of the dorsum of the tongue, which has rarely been reported in the literature. The authors attained a favorable outcome through surgical intervention.

16.
Front Cell Infect Microbiol ; 14: 1477143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39359935

RESUMO

Oral mucositis is a common and debilitating oral complication in head and neck cancer patients undergoing radiotherapy, resulting in diminished quality of life and potential treatment disruptions. Oral microbiota has long been recognized as a contributing factor in the initiation and progression of radiation-induced oral mucositis (RIOM). Numerous studies have indicated that the radiation-induced oral microbial dysbiosis promotes the occurrence and severity of oral mucositis. Therefore, approaches that modulate oral microbial ecology are promising for the management of RIOM. Probiotics as a relatively predicable and safe measure that modulates microecology have garnered significant interest. In this review, we discussed the correlation between RIOM and oral microbiota, with a particular focus on the efficacy of probiotics in the control of RIOM, in order to provide novel paradigm for the management of this disease.


Assuntos
Disbiose , Probióticos , Lesões por Radiação , Estomatite , Probióticos/uso terapêutico , Humanos , Estomatite/etiologia , Estomatite/microbiologia , Estomatite/terapia , Estomatite/prevenção & controle , Lesões por Radiação/terapia , Microbiota , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia/efeitos adversos , Boca/microbiologia , Qualidade de Vida
17.
Phys Med ; 126: 104818, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39357299

RESUMO

The neutron beam in boron neutron capture therapy (BNCT) exhibits poor directionality and significantly decreasing neutron flux with increasing distance. Therefore, the treatment site must be close to the irradiation aperture. Some patients with head and neck cancer may benefit from a sitting-position setup. The study aim was to evaluate the treatment-positioning accuracy and dose error in sitting patients receiving BNCT. Thirty-two patients with head and neck cancer who underwent sitting-position BNCT at Southern Tohoku BNCT Research Center were included in the study. Horizontal (ΔX) and vertical (ΔY) errors were defined as the displacement between the treatment planning system (TPS) digital reconstructed radiograph and the pre-treatment X-ray image. Using in-house software, image matching was performed. The beam-axial directional (ΔZ) error was compared with the parameters entered into the TPS and the actual pre-treatment measured values. The translational-position error was reflected in the TPS's patient coordinate system with respect to the reference plan. Re-dose calculations were performed to evaluate the effect of positional error on tumor and normal-tissue doses. The [ΔX, ΔY, ΔZ] DRR-CR mean ± 1SD were - 0.40 ± 2.0, 0.30 ± 2.3, and - 1.4 ± 1.5 mm, respectively. The Dmean and D98% tumor-dose errors were 1.22 % ± 1.44 % and 0.99 % ± 1.63 %, respectively. The D2% pharyngeal and oral mucosal-dose errors were 0.98 % ± 1.91 % and 1.21 % ± 1.78 %, respectively. The tumor- and normal-tissue dose errors were typically < 5 %. High-precision treatment was feasible in sitting-positioned BNCT.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias de Cabeça e Pescoço , Posicionamento do Paciente , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Estudos Retrospectivos , Planejamento da Radioterapia Assistida por Computador/métodos , Postura Sentada , Masculino , Doses de Radiação , Feminino , Pessoa de Meia-Idade , Idoso
18.
J Immunother Cancer ; 12(10)2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39357981

RESUMO

BACKGROUND: Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity. METHODS: This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E. RESULTS: Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress. CONCLUSION: In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.


Assuntos
Anticorpos Biespecíficos , Antígenos B7 , Antígeno B7-H1 , Imunoconjugados , Humanos , Animais , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Camundongos , Antígeno B7-H1/antagonistas & inibidores , Antígenos B7/antagonistas & inibidores , Linhagem Celular Tumoral , Feminino
19.
Indian J Otolaryngol Head Neck Surg ; 76(5): 4153-4162, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39376339

RESUMO

OBJECTIVE: the study aimed to characterize the novel entity referred to as secretory carcinoma of the salivary glands. METHODS: we comprehensively evaluated 150 patients afflicted by malignant salivary gland tumors who had been under treatment at the University of Verona. Inclusion criteria primarily focused on the availability of paraffin block materials and adequate follow-up data. Subsequently, we conducted a comprehensive Fluorescent In Situ Hybridization (FISH) analysis, utilizing probes targeting NTRK-3, MALM-2, EWRS-1, HER-2, MDM-2, and NTRK1-2. RESULTS: out of the initial cohort, 37 patients met the eligibility criteria for our study. We identified NTRK3 gene rearrangements in four patients (11%), two of whom had mucoepidermoid carcinoma, and the remaining two had acinic cell carcinoma. Notably, none of these patients had initially received a secretory carcinoma diagnosis. The primary treatment approach for all patients entailed surgical parotid gland resection. The overall survival (OS) for patients with NTRK3 rearrangements amounted to 78 months, with a corresponding progression-free survival (PFS) of 73 months. CONCLUSION: in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes.

20.
Indian J Otolaryngol Head Neck Surg ; 76(5): 3845-3853, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39376350

RESUMO

Oral tongue squamous cell cancer (OTSCC) is one of the most prevalent cancers worldwide and incidence increases with age. An alarming increase in the incidence of OTSCC in the younger age group. This study aimed to explore clinical and histopathological characteristics, survival, and other post-surgical outcomes in patients with OTSCC treated with glossectomy through the Department of Otolaryngology-Head & Neck Surgery at the Ministry of National Guard Health Affairs (MNGHA) within our study period. This is a retrospective study carried out through the collection and analysis of data from medical charts of 56 patients with oral tongue cancer who were treated by glossectomy. Treatment was initiated from January 2010 to December 2021. Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were collected and analyzed. At diagnosis, 62.5% were tobacco smokers, 46.8% had poor dental hygiene, and 76.8% had ulcerative lesions. Furthermore, 33 cases presented with early-stage clinical disease and 23 cases with advanced stage. The median follow-up was 54 months, 28 patients (50%) were free for 3-5 years. Patients who were free on 5-year follow-up had a significantly higher percentage of negative lymphovascular and perineural invasion (p < 0.05). Additionally, 12 patients (21.4%) had developed recurrence. Mortality in all cases was 30.3, but mortality-related cancer was 19.6%. Locoregional failure remains the main cause of treatment failure in resectable OTSCC. Pathological T-stage, N-stage, LVI, PNI, ECE, and LNR are all considered strong prognostic factors.

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