Search Results (118)

Disease progression and treatment resistance in colorectal and other cancers are driven by a subset of cells within the tumor that have stem-cell-like properties and long-term tumorigenic potential. These stem-cell-like cells express the leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) and have characteristics similar to tissue-resident stem cells in normal adult tissues such as the colon. Organoid models of murine and human colorectal and other cancers contain LGR5-expressing (LGR5+) stem-cell-like cells and can be used to investigate the underlying mechanisms of cancer development, progression, therapy vulnerability, and resistance. A large biobank of organoids derived from colorectal cancer or adjacent normal tissue was developed. We performed a large-scale unbiased functional screen to identify bispecific antibodies (BsAbs) that preferentially inhibit the growth of colon tumor-derived, as compared to normal tissue-derived, organoids. We identified the most potent BsAb in the screen as petosemtamab, a Biclonics^® BsAb targeting both LGR5 and the epidermal growth factor receptor (EGFR). Petosemtamab employs three distinct mechanisms of action: EGFR ligand blocking, EGFR receptor internalization and degradation in LGR5+ cells, and Fc-mediated activation of the innate immune system by antibody-dependent cellular phagocytosis (ADCP) and enhanced antibody-dependent cellular cytotoxicity (ADCC) (see graphical abstract). Petosemtamab has demonstrated substantial clinical activity in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC). The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC. Full article

Despite significant progress in its prevention, diagnosis, and treatment, head and neck cancer (HNC) remains a major global health issue due to its multifactorial pathogenesis. Indeed, HNCs have been found to be associated with different environmental and lifestyle factors, as well as with infection with oncogenic viruses. To date, seven viruses are recognized for their tumorigenic properties and have been proposed as implicated in HNC development, including Merkel Cell Polyomavirus (MCPyV). MCPyV is well recognized as the major etiological agent of Merkel cell carcinoma (MCC), a rare but rapidly metastasizing skin neoplasm. Specifically, in almost 80% of MCC cases, viral genome integration occurs, and a truncated form of Large T Antigen (tLT) is expressed. Although MCC is a rare cancer, MCPyV is a ubiquitous virus, widely distributed among the human population. Therefore, a plausible role of the virus has been proposed, even for other tumors. The current review provides an overview of the available data describing the presence of MCPyV in non-MCC tumors, such as HNCs, with the aim of elucidating the potential contribution of MCPyV to oral cancer. Understanding the role of viral infections in the etiology of cancer opens up the opportunity for developing preventive measures and targeted therapies that effectively address HNC progression while reducing treatment-related side effects. Full article

Background: Skin lesions associated with head and neck carcinomas present a diagnostic challenge. Conventional imaging methods, such as dermoscopy and RGB imaging, often face limitations in providing detailed information about skin lesions and accurately differentiating tumor tissue from healthy skin. Methods: This study developed a novel approach utilizing tissue index images derived from hyperspectral imaging (HSI) in combination with machine learning (ML) classifiers to enhance lesion classification. The primary aim was to identify essential features for categorizing tumor, peritumor, and healthy skin regions using both RGB and hyperspectral data. Detailed skin lesion images of 16 patients, comprising 24 lesions, were acquired using HSI. The first- and second-order statistics radiomic features were extracted from both the tissue index images and RGB images, with the minimum redundancy–maximum relevance (mRMR) algorithm used to select the most relevant ones that played an important role in improving classification accuracy and offering insights into the complexities of skin lesion morphology. We assessed the classification accuracy across three scenarios: using only RGB images (Scenario I), only tissue index images (Scenario II), and their combination (Scenario III). Results: The results indicated an accuracy of 87.73% for RGB images alone, which improved to 91.75% for tissue index images. The area under the curve (AUC) for lesion classifications reached 0.85 with RGB images and over 0.94 with tissue index images. Conclusions: These findings underscore the potential of utilizing HSI-derived tissue index images as a method for the non-invasive characterization of tissues and tumor analysis. Full article

Ultrasound imaging has become an indispensable diagnostic tool across various medical fields. In recent years, there has been growing interest in the use of ultrasonography for the evaluation of skin lesions. However, scientific reports detailing the precise role of ultrasound in determining the morphology of malignant skin tumors still remain limited. Malignant skin lesions, particularly in the head and neck region—their most common location—pose significant challenges due to the complex anatomy of these areas. The primary treatment for non-melanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is surgical excision. Mohs micrographic surgery is considered the gold standard due to its tissue-sparing approach and high cure rates. However, it is a time-consuming and resource-intensive procedure that is not always widely accessible. In contrast, standard surgical excision, while more widely available, often results in incomplete tumor removal, necessitating subsequent surgical radicalization or the use of adjuvant therapies. Routine ultrasound evaluation of both benign and malignant skin lesions could enhance early detection and facilitate timely treatment. However, the current body of evidence for the usage of skin ultrasound in presurgical evaluation is poor and lacks standardization. Given these challenges, in this review, we aim to highlight the potential value of preoperative skin ultrasonography in accurately assessing benign and malignant skin lesion dimensions and morphology. Full article

Background/Objectives: Vitamin D is classically associated with calcium and phosphate homeostasis, but recent research has expanded its role to include several new roles such as immune regulation, inflammation, and potential anti-cancer properties. The vitamin D receptor (VDR) is expressed in over 400 tissues, including those of the head and neck, implying a potential link between vitamin D and head and neck cancers (HNCs). Given the need for newer and better therapeutic approaches, this systematic review aims to synthesize existing clinical evidence on the relationship between vitamin D status and clinical outcomes in HNC patients. Methods and Results: A comprehensive literature search, across multiple databases including PubMed, Google Scholar and Science Direct, identified 187,642 studies related to vitamin D and cancer, from which 16 studies met the inclusion criteria. The inclusion criteria were English-language, full-text original research (2015–2025) on vitamin D’s role in HNC progression and treatment, focusing on human studies. The findings indicate that vitamin D deficiency is highly prevalent among HNC patients, with rates ranging from 47% to 95%, particularly in advanced-stage cancers and those undergoing intensive treatment. Inverse association between vitamin D levels and HNC risk was reported, with higher serum 25(OH)D levels linked to a 30–32% reduction in cancer risk. Additionally, higher vitamin D levels correlated with improved survival rates and reduced recurrence, though some findings lacked statistical significance. Deficiencies were associated with higher rates of malnutrition and postoperative complications, reinforcing vitamin D’s role in nutritional stability and surgical recovery. Conclusions: This systematic review highlights how common and significant vitamin D deficiency is among head and neck cancer (HNC) patients, exploring its possible role in cancer risk, prognosis, survival, treatment-related side effects, malnutrition, and post-surgical complications. The evidence suggests that while higher vitamin D levels are linked to better survival and fewer treatment-related issues, the benefits seem to level off beyond a certain point, indicating a more complex relationship. Additionally, vitamin D supplementation appears to help reduce chemoradiation side effects like mucositis, skin toxicity, dysphagia, and pain, ultimately improving patients’ quality of life during treatment. Full article

Cutaneous squamous scell carcinoma (cSCC) is a frequent non-melanoma skin cancer that originates from keratinocytes with increased prevalence. cSCC can be either in situ, as in Bowen’s disease, or extended. Advanced age, accumulated sun exposure, light pigmentation, and prior skin cancer diagnosis are all significant risk factors for cSCC. Although most cSCCs can be treated surgically, some recur and metastasize, resulting in death. The role of immune status is not yet determined in the prognosis of these patients. Objective. Immunosuppressed patients are more likely to develop cSCC, which is often characterized by more aggressive, multifocal lesions. This study aimed to determine the risks of mortality in patients with cSCC and immunosuppression versus non immunosuppression and to compare variations in overall survival based on different clinical features. Method. We evaluated clinical cases of patients at “Sfantul Apostol Andrei” Emergency Hospital of Galati, Romania, from 1 March 2018 to 1 April 2024. Subjects in the trial had to be at least 18 years old and have a pathologically confirmed diagnosis of cutaneous head and neck squamous cell carcinoma (cHNSCC). We divided the patients into two different categories based on whether they had immunosuppression. Results. In this cohort of 68 subjects with cSCC, patients with immunosuppression had significantly lower overall survival, as well as lower three- and five-year survival rates compared with those without immunosuppression, even after adjustment for age, sex, stage, and previous surgical treatment. The median survival time for immunosuppressed individuals ranged from 11 to 21 months, varying based on their particular characteristics, and most critically, on the presence of other malignancies, while that of immunocompetent patients ranged from 18 to 51 months. In addition, immune-deficient patients with early-stage disease had a 21-month median survival rate that changed to11 months for advanced-stage cases. In a similar manner, immunocompetent patients with early-stage cancer had a significantly better median survival than those withadvancedstages,43 versus 18months. Our results indicate that immunosuppression is a distinct risk factors associated with a less favorable outcome in patients with cHNSCC. Full article

In exploring adjuvant therapies for head and neck cancer, hyperthermia (40–45 °C) has shown efficacy in enhancing chemotherapy and radiation, as well as the delivery of liposomal drugs. Current hyperthermia treatments, however, struggle to reach large deep tumors uniformly and non-invasively. This study investigates the feasibility of delivering targeted uniform hyperthermia deep into the tissue using a non-invasive ultrasound spherical random phased array transducer. Simulations in 3D patient-specific models for thyroid and oropharyngeal cancers assessed the transducer’s proficiency. The transducer consisting of 256 elements randomly positioned on a spherical shell, operated at a frequency of 1 MHz with various phasing schemes and power modulations to analyze 40, 41, and 43 °C isothermal volumes and the penetration depth of the heating volume, along with temperature uniformity within the target area using T10, T50, and T90 temperatures, across different tumor models. Intensity distributions and volumetric temperature contours were calculated to define moderate hyperthermia boundaries. The results indicated the array’s ability to produce controlled heating volumes from 1 to 48 cm³ at 40 °C, 0.35 to 27 cm³ at 41 °C, and 0.1 to 8 cm³ at 43 °C. The heating depths ranged from 7 to 39 mm minimum and 52 to 59 mm maximum, measured from the skin’s inner surface. The transducer, with optimal phasing and water-cooled bolus, confined the heating to the targeted regions effectively. Multifocal sonications also improved the heating homogeneity, reducing the length-to-diameter ratio by 38% when using eight foci versus a single one. This approach shows potential for treating a range of tumors, notably deep-seated and challenging oropharyngeal cancers. Full article

Skin cancer is one of the most prevalent malignancies in the world, with increasing incidence. In 2022, the World Health Organization estimated over 1.5 million new diagnoses of skin malignancies, primarily affecting the older population. Surgical excision, particularly in the head and neck area, can cause aesthetic deficits and significantly impair patients’ quality of life. There are limited therapeutic options for advanced skin malignancies, and the development of resistance to targeted therapy further restricts treatment choices. Cancer metabolism may offer a novel approach to overcome these challenges. The pentose phosphate pathway, along with its rate-limiting enzyme, glucose-6-phosphate dehydrogenase, is essential for both the antioxidative response and the synthesis of ribonucleotides and may play a critical role in the proliferation and growth of cancer cells. This review examines current knowledge on the correlation between altered glucose-6-phosphate dehydrogenase expression and activity and skin cancer progression, with the aim of identifying a potential therapeutic target for treating advanced skin cancer. Full article

Late-onset Alzheimer’s disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of sodium thiosulfate (STS) as a possible multi-targeting treatment option for LOAD. Sulfur is widely available in our environment and is responsible for forming organosulfur compounds that are known to be associated with a wide range of biological activities in the brain. STS is known to have (i) antioxidant and (ii) anti-inflammatory properties; (iii) chelation properties for calcium and the pro-oxidative cation metals such as iron and copper; (iv) donor properties for hydrogen sulfide production; (v) possible restorative properties for brain endothelial-cell-derived bioavailable nitric oxide. Thus, it becomes apparent that STS has the potential for neuroprotection and neuromodulation and may allow for an attenuation of the progressive nature of neurodegeneration and impaired cognition in LOAD. STS has been successfully used to prevent cisplatin oxidative-stress-induced ototoxicity in the treatment of head and neck and solid cancers, cyanide and arsenic poisoning, and fungal skin diseases. Most recently, intravenous STS has become part of the treatment plan for calciphylaxis globally due to vascular calcification and ischemia-induced skin necrosis and ulceration. Side effects have been minimal with reports of metabolic acidosis and increased anion gap; as with any drug treatment, there is also the possibility of allergic reactions, possible long-term osteoporosis from animal studies to date, and minor side-effects of nausea, headache, and rhinorrhea if infused too rapidly. While STS poorly penetrates the intact blood–brain barrier(s) (BBBs), it could readily penetrate BBBs that are dysfunctional and disrupted to deliver its neuroprotective and neuromodulating effects in addition to its ability to penetrate the blood–cerebrospinal fluid barrier of the choroid plexus. Novel strategies such as the future use of nano-technology may be helpful in allowing an increased entry of STS into the brain. Full article

Background: The incidence of melanoma is increasing globally. The estimated worldwide incidence is projected to increase from 324,635 cases in 2020 to 510,000 in 2040. In the UK, melanoma accounts for 4% of all new cases of cancer. Melanomas occurring in the skin of the head and neck represent 13% and 23% of cases in women and men, respectively. Prognostic indicators include presence of nodal or distant metastasis, ulceration, and Breslow thickness, where >4 mm thickness predicts poorest overall survival rates. Giant melanomas, a term generally applied to melanomas larger than 5–10 cm, are rare and often have a very poor prognosis. Clinical case: An 82-year-old female presented acutely with a 2–3-day history of delirium and urinary retention in February 2022. In addition, she was noted to have a large fungating growth on her forehead that obscured the bridge of the nose and had been slowly increasing in size for the past year prior to admission. She had initially presented in primary care with a small growth on her forehead but declined further investigations for fear of contracting COVID-19. She consented to having further assessment and management of the forehead mass. A shave biopsy revealed giant nodular melanoma, specifically, the largest melanoma of the face reported in the literature. Remarkably, our patient underwent a successful complete excision and skin grafting, with no evidence of recurrence or distal metastasis after 2 years of follow up. Conclusions: This case highlights the anxieties people felt about contracting COVID-19 when national guidelines recommended shielding that had resulted in further morbidity. Despite poor prognostic factors, clinically and histologically, our patient did not need any systemic anticancer therapy nor radiotherapy. She was well after 2 years follow up without any signs of recurrence. Full article

Introduction: Skin cancer impacts a significant proportion of the population. While surgical management is often the mainstay of treatment, advanced or metastatic cutaneous malignancies require additional local and/or systemic therapies. Methods: A review of the literature was performed studying the use of radiation therapy, chemotherapy, and immunotherapy for locally advanced or metastatic cutaneous malignancies. Results: A summary of the present literature on the management of locally advanced or metastatic cutaneous malignancies is presented across cutaneous head and neck basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The addition of multidisciplinary therapies to resection is often associated with improved outcomes. Conclusion: The management of cutaneous head and neck malignancies requires an approach integrating multiple specialties, to optimize outcomes and minimize toxicities. Full article

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with a lifetime risk of 14–20% that is rising every year. Although prognosis for cSCC is generally good, certain high-risk features of cSCC portend increased rates of nodal and distant metastasis, recurrence, and disease-specific mortality. One such high-risk factor is perineural invasion (PNI), which is broadly defined as the invasion of cancer into and around nerves. Compared to other high-risk factors, PNI presence is associated with the highest risk for locoregional and distant metastasis. Still, the mechanisms underlying the pathogenesis of PNI remain poorly understood. Recent studies suggest the migration and invasion of tumors into nerves is a result of complex molecular crosstalk within the tumor-nerve microenvironment, wherein the milieu of signaling molecules simultaneously promote neuronal growth and tumor cell invasion. Methods: Understanding the molecular and cellular mechanisms that promote PNI will lead to future developments of targeted therapies that may improve locoregional control and survival. Results/Conclusions: In our article, we aim to provide a comprehensive review of recent findings about the pathogenesis of PNI, clinical implications of PNI-positive disease in cSCC, available treatment modalities, and potential future therapeutic targets. Full article

Background/Objectives: Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are non-melanoma skin cancers (NMSCs) and the most prevalent cancers in the United States. Image-guided superficial radiotherapy (IGSRT) is a relatively new treatment option that uses high-resolution dermal ultrasound integrated with superficial radiotherapy to improve tumor visualization. IGSRT is a clinically equivalent non-surgical alternative to Mohs micrographic surgery at 2 years of follow-up in early-stage NMSC, but larger cohort studies with longer follow-up periods that allow for analysis of patient outcomes by demographic and disease characteristics are needed. Methods: This large, retrospective cohort study was conducted to determine the effect of risk factors (tumor location, tumor stage, and sex) on 2-, 4-, and 6-year freedom from recurrence rates in 19,988 NMSC lesions treated with IGSRT, including lesions with complete treatment courses. Results: Overall freedom from recurrence rates were 99.68% at 2 years, 99.54% at 4 years, and 99.54% at 6 years; rates did not differ significantly by tumor location (head/neck versus other locations, p = 0.9) or sex (male versus female, p = 0.4). In contrast, there was a significant difference in freedom from recurrence rates when analyzed by tumor stage (p = 0.004). Conclusions: There was no significant effect of tumor location or sex on freedom from recurrence in IGSRT-treated NMSC. Although there was a significant difference according to tumor stage, freedom from recurrence rates exceeded 99% at all stages. Full article

Background. Basal cell carcinomas (BCCs) are common human malignancies with a rising incidence in recent years. While BCCs have a low mortality rate, they are often associated with significant local skin damage characterized by erythema, skin ulceration, and persistent pigmentation. Surgery, radiotherapy, and systemic chemotherapy have traditionally been the principal treatments for these skin injuries. However, electrochemotherapy has recently been proposed as a novel local treatment with promising results for various skin cancers, including BCC, while avoiding the side effects of conventional therapies. ECT involves a local electrical stimulus that enhances cell membrane permeability, thereby enabling the targeted intracellular accumulation of the chemotherapeutic agent. Case Report: We report a case of a 68-year-old man with an ulcerated BCC, following his progress up to 14 months post-ECT treatment, with positive outcomes. Discussion and Conclusions: We achieved a complete clinical response and noted an improvement in the patient’s quality of life. This technique is fast, repeatable, requires minimal hospitalization, and reduces healthcare costs and adverse effects compared to major surgery. Therefore, it can be considered an alternative or complementary approach to traditional surgery for treating BCC of the head and neck. Full article

Background and Objectives: The radial forearm free flap (RFFF) is the most commonly used flap for head and neck reconstruction. However, complications at the donor site are its major drawbacks. We aimed to identify the patient comorbidities and factors that predict donor site complications after RFFF. Materials and Methods: A retrospective chart review of consecutive patients who underwent RFFF reconstruction for head and neck cancer between 2015 and 2022 was performed. Demographic variables, clinical processes, and postoperative complications were assessed. All variables were analyzed using univariate and multivariate analyses. Results: Sixty-seven patients underwent RFFF reconstruction, and all received a split-thickness skin graft at the donor site. Twenty-five patients experienced delayed skin graft healing, whereas nine experienced sensory changes at the donor site. Hypertension and age had statistically significant negative effects on wound healing. The incidence of hand swelling was related to graft size, and the occurrence of paresthesia was significantly higher in diabetic patients and significantly lower in those with acellular dermal matrix (ADM). Conclusions: Patients with hypertension had a higher risk of prolonged wound healing after RFFF than their normotensive patients. Clinicians should pay particular attention to wound healing strategies in patients with hypertension. Additionally, better neuropathy care is recommended to achieve sensory recovery after RFFF in patients with diabetes. Using a skin graft with ADM could be a method to alleviate neurological symptoms. Full article