Search Results (168)

Unc-51-like kinase 3 (ULK3) is a key member of the ULK serine/threonine kinase family. Aberrant ULK3 expression has been increasingly linked to tumorigenesis and malignant progression in multiple cancer types. However, the precise role of ULK3 in tumor initiation and progression remains incompletely understood. Leveraging integrated multi-omics data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we systematically characterized the expression of ULK3 at both the transcript and protein levels across 33 cancer types. We also evaluated genomic alterations, prognostic significance, alternative splicing, pathway enrichment, tumor stemness, immune infiltration, and immunotherapy-related biomarkers. In parallel, we investigated the function of ULK3 in prostate cancer PC-3 cells using cellular localization analysis, wound-healing assays, and MTT assays. We further applied Connectivity Map (CMap) screening and molecular docking to identify candidate ULK3 activators. ULK3 was significantly upregulated in 13 cancer types, including Bladder Urothelial Carcinoma, Breast Invasive Carcinoma, and Lung Adenocarcinoma. In contrast, ULK3 was downregulated in Cholangiocarcinoma and Head and Neck Squamous Cell Carcinoma. High ULK3 expression was associated with poor overall survival in Adrenocortical Carcinoma, Kidney Renal Clear Cell Carcinoma, and Skin Cutaneous Melanoma. Copy number amplification contributed to ULK3 overexpression. A recurrent A206V missense mutation was detected in the protein kinase (Pkinase) domain. Genes co-expressed with ULK3 were enriched in RNA splicing, methylation, oxidative phosphorylation, and energy metabolism. ULK3 expression showed positive correlations with tumor stemness indices and m1A/m5C/m6A RNA modification regulators. From an immunological perspective, high ULK3 expression was associated with lower Immune Score, increased M2 macrophage infiltration, and co-expression of PD-L1, CTLA4, and LAG3 in most cancers. ULK3 expression was also correlated with Tumor Mutational Burden in Kidney Renal Clear Cell Carcinoma and Rectum Adenocarcinoma. In addition, ULK3 expression was associated with Microsatellite Instability in Brain Lower Grade Glioma, Lung Adenocarcinoma, and Uterine Corpus Endometrial Carcinoma. ULK3 overexpression promoted proliferation and migration in PC-3 cells. Cephaeline was screened as a putative ULK3 activator. Overall, ULK3 expression and amplification were associated with poor clinical outcomes, tumor stemness, immunosuppression, and RNA dysregulation. These findings highlight the potential value of ULK3 as a pan-cancer diagnostic and prognostic biomarker and as a predictor of immunotherapy response, particularly in prostate cancer. Full article

Background: Non-melanoma skin cancers (NMSCs) of the head and neck represent a therapeutic challenge due to the region’s complex anatomy, functional considerations, and frequent involvement of high-risk anatomical zones. Local recurrence remains a clinically significant concern, however real-world data regarding recurrence patterns and associated risk factors in facial NMSCs are limited. Objectives: To evaluate the incidence of local recurrence of facial skin cancers after surgical treatment and to determine clinicopathological and anatomical actors associated with an increased risk of recurrence. Methods: In this single-center retrospective cohort study, consecutive patients undergoing surgical excision of facial NMSC were included. The treatment of choice was always surgical excision under general or local anesthesia, with an adequate margin of macroscopically unchanged tissue. Mohs surgery was not used, and none of the patients received immunosuppression. Clinical and pathological data were extracted from medical records. Histopathological examination constituted the basis for establishing the final clinical diagnosis and thus was not verified otherwise. The primary outcome was histologically confirmed local recurrence defined as the reappearance of a tumor of the same histopathological type at the same anatomical site as the previously excised lesion. Patients in the non-recurrence group were defined as those who did not experience any recurrence within a 5-year follow-up period after the initial surgical treatment. Fisher’s exact test and the Mann–Whitney U test were used for statistical analysis. Logistic regression was performed to explore factors associated with recurrence. Due to incomplete follow-up data for the non-recurrent group, we limited the timing analysis to recurrent cases only, as these limitations precluded the use of standard survival analysis. Results: A total of 302 lesions were analyzed, with recurrence status available for 291 tumors. The overall recurrence rate was 28.52%. Basal cell carcinoma (BCC) was the most common histopathological subtype. Recurrences occurred more frequently in anatomically high-risk areas, particularly the scalp, temple and nose. Infiltrative BCC subtypes demonstrated higher recurrence rates than nodular and superficial subtypes. Patients with recurrent tumors were younger than those without recurrence. A history of prior skin radiotherapy was associated with increased odds of recurrence. Tumor size and surgical margin width were not significantly associated with recurrence. Multivariate models showed limited discriminatory ability, suggesting that additional unmeasured factors contribute to recurrence risk. Conclusions: Local recurrence of non-melanoma skin cancers in the head and neck region remains a substantial clinical concern, particularly in high-risk anatomical sites and tumors with aggressive histopathological features. These findings highlight the importance of long-term follow-up and support further prospective studies to improve recurrence risk assessment and treatment strategies. Full article

Background: Lentigo maligna (LM) represents melanoma in situ and predominantly affects elderly individuals, typically arising on chronically sun-exposed skin of the head and neck. Although LM is characterized by slow horizontal growth and generally favourable prognosis, progression to invasive lentigo maligna melanoma may occur, making timely and effective treatment essential. Surgical excision remains the standard of care; however, advanced age, comorbidities, lesion size, and cosmetic or functional considerations may limit surgical feasibility. Case presentation: We report the case of a 93-year-old woman with no prior history of skin cancer who presented with a gradually enlarging pigmented lesion on the forehead. Clinical examination revealed an irregularly pigmented macule measuring 25 × 27 mm. Multiple mapping biopsies confirmed melanoma in situ of the lentigo maligna type, with adnexal extension and no evidence of dermal invasion. Given the patient’s advanced age and lesion location, a non-surgical approach was selected. Topical imiquimod 5% cream was applied five times per week for 12 weeks to the visible lesion and to a 20 mm margin around it. The patient was monitored closely throughout the treatment. Local inflammatory reactions were mild to moderate, consisting mainly of erythema, crusting, and superficial erosion, without systemic adverse effects. At treatment completion, marked clinical improvement with near-complete resolution of pigmentation was observed. Follow-up dermoscopic evaluation demonstrated only minimal residual granular pigmentation. Post-treatment mapping biopsies confirmed complete histological clearance of atypical melanocytic cells. Conclusions: This case illustrates that topical imiquimod may serve as a safe and effective alternative to surgery in carefully selected elderly patients with lentigo maligna. Close clinical follow-up and histological confirmation of clearance are essential to ensure treatment success and durable outcomes. Full article

Head and neck non-melanoma skin cancers (H&N NMSCs) account for most head and neck malignancies. While primary treatment comprises surgery, adjuvant radiation is recommended in advanced tumors. Radiation oncology practice patterns for resected locally advanced (rLA) and locoregional (rLR) H&N NMSCs have not been well characterized. Using data from the Institute for Clinical Evaluative Sciences (ICES) between 2003 and 2019, we conducted a longitudinal, population-based study characterizing disease incidence, survival outcomes, and radiation utilization patterns. Among 2962 rLA and 1055 rLR cases, rLA incidence rose more than tenfold compared to population growth; however rLR incidence remained stable. Radiation oncology consultations occurred in 29.6% of rLA and 50.7% of rLR patients. Increased age, multiple cancers at diagnosis, non-rural demographic, and higher SES were observed to be correlated to receipt of adjuvant radiation treatment. Only 19.4% of rLA and 37.95 of rLR disease received adjuvant RT, which is much lower than expected based on international guidelines. Five-year overall survival (OS) was 69% (95% confidence interval (CI): 67–71%) for rLA and 68% (95% CI: 65–71%) for rLR disease. These findings highlight the burden of advanced H&N NMSC, low rates of radiation utilization and the need for improving referral pathways and guideline adherence. Full article

Background/Objectives: The rapid expansion of targeted therapies has reshaped oncology by exploiting ligand-receptor interactions (LRI) to improve treatment specificity and patient outcomes. However, the data describing these ligands remain fragmented across multiple sources, limiting accessibility for researchers and clinicians. To address this gap, we developed the OncoSolidDB, the first curated and oncology-focused bioinformatics database dedicated to ligands associated with solid malignancies. Methods: OncoSolidDB integrates and harmonizes data from reliable repositories, including ChEMBL, DrugBank and the Anti-Cancer Fund, consolidating curated structural, chemical, pharmacological, and clinical annotations along with standardized identifiers. Results: The database currently encompasses 243 ligands across 15 major solid tumor types including breast, lung, colorectal, melanoma, prostate, gastric, ovarian, cervical, bladder, esophageal, head and neck, thyroid, pancreatic, renal and liver cancer (Hepatocellular Carcinoma, HCC). Each entry is annotated by standardized identifiers (DrugBank, ChEMBL), approval year, chemical structures (SMILES strings, 2D images), and downloadable protein structure files (PDB format). Temporal coverage spans 1953–2025, enabling exploration of historical trends in oncology drug approvals. The database content is suitable for bioinformatics analysis, molecular docking, virtual screening, ligand-based modeling, and drug repurposing studies. Outputs are available through a freely accessible web interface that supports search browsing by cancer type. Conclusions: By consolidating oncology-specific ligand data into a single, structured platform, OncoSolidDB offers a valuable resource for advancing drug discovery, repurposing strategies, and the rational design of next-generation targeted therapies for solid tumors. OncoSolidDB is accessible via our Bioinformatics Research PortalEinstein. Full article

Background: Artificial intelligence (AI) is reshaping oncology at every stage of the cancer care pathway, from population-level screening through molecular diagnosis, treatment planning, and post-treatment surveillance. Despite an exponential growth in AI oncology publications exceeding 5000 peer-reviewed studies annually, a critical and persistent gap separates demonstrated algorithmic performance from genuine patient benefit. Most published evidence derives from retrospective, single-institution studies conducted in curated dataset environments that systematically differ from real-world clinical deployment conditions. This comprehensive review examines the translational maturity of AI applications across 18 major malignancies, providing an evidence-stratified, cross-cancer assessment of where AI has fulfilled, approaches, or remains far from fulfilling its transformative potential in oncological care. Methods: A structured narrative review was conducted across PubMed/MEDLINE, Embase, IEEE Xplore, and the Cochrane Library, supplemented by regulatory grey literature including FDA 510(k) decision summaries, CE Technical Files, and ClinicalTrials.gov. Search terms combined cancer site-specific terminology with AI methodology terms and translational outcome descriptors. Studies were only included if they applied an AI or machine learning methodology to a defined clinical oncological task, reported a clearly specified performance evaluation, and involved human subjects or human-derived clinical data. Evidence quality was assessed using QUADAS-2, PROBAST, and Cochrane RoB 2. A five-tier translational readiness framework, grounded in the NIH T0–T4 translational spectrum and CONSORT-AI/SPIRIT-AI guidelines, was applied a priori to enable cross-cancer comparison. A rigorous distinction was maintained between diagnostic accuracy and clinical utility, defined as demonstrated impact on clinical decision-making or patient-centered outcomes. Results: Across all 18 malignancies, AI development varied profoundly by cancer type. Breast cancer and prostate cancer (Tier 1) represent the most mature AI ecosystems, with multiple FDA-cleared tools for mammographic screening and digital pathology achieving prospective multi-institutional validation; however, randomized evidence demonstrating reduced cancer-specific mortality remains absent. Lung, hepatocellular, and melanoma AI (Tier 2) have achieved regulatory milestones but face documented performance disparities across demographic subgroups, including DermaSensor’s 20.7% specificity in primary care settings and HCC model failures in non-viral disease etiologies. Colorectal, glioma, pancreatic, and ovarian cancers (Tier 3) exhibit technical maturity without clinical clarity: colorectal CADe systems increase adenoma detection but meta-analyses of 18,232 patients across 21 RCTs fail to demonstrate improvement in advanced neoplasia detection or cancer incidence reduction. A full study-level presentation of pooled estimates, confidence intervals, and heterogeneity statistics for each cited randomized evidence base across all cancer types would extend beyond the intended scope and format of this cross-cancer narrative review. Gastric, esophageal, cervical, bladder, head and neck, and endometrial cancers (Tier 4) demonstrate promising single-institutional or geographically restricted results without multi-institutional external validation, particularly notable for cervical cancer AI’s transformative potential in low- and middle-income countries constrained by absent regulatory frameworks. Hematologic malignancies, sarcoma, and pediatric solid tumors (Tier 5) face structural barriers, workflow incompatibility in hematopathology, extreme rarity in sarcoma (>70 subtypes, <15,000 US cases annually), and irreducible ethical constraints in pediatric data governance, that cannot be resolved through algorithmic refinement alone. Conclusions: Oncological AI has not yet fulfilled its clinical promise. Across all five translational tiers, a single finding is consistent: diagnostic accuracy is not a surrogate for patient benefit. AI tools with high sensitivity and specificity have repeatedly failed to demonstrate equivalent reductions in cancer-specific mortality, overdiagnosis, or procedural harm under real-world outcome scrutiny. Simultaneously, documented performance disparities across races, ethnicity, disease etiology, and geographic setting reveal that current AI systems risk amplifying the very health inequities they are positioned to resolve. Bridging this translational gap requires three coordinated systemic shifts: regulatory frameworks mandating post-market outcome surveillance as a condition of clinical clearance; prospective trial designs measuring patient-centered endpoints rather than diagnostic concordance alone; and sustained infrastructure investment in federated data governance, demographically inclusive training datasets, and LMIC-accessible regulatory pathways. AI holds genuine potential to reduce cancer mortality on a global scale—but only if held to the evidentiary and equity standards that the stakes of oncological care demand. Full article

Background/Objectives. Head and neck mucosal melanoma (HNMM) is a rare, aggressive malignancy with poor outcomes and limited evidence to guide prognostication and treatment. A detailed assessment of long-term survival and prognostic factors is needed to inform clinical management and staging. This work aimed to describe outcomes and prognostic factors in HNMM patients treated over 45 years. Methods. This was a retrospective observational cohort study of consecutive patients treated at a tertiary referral center in Italy from 1975 to 2020. Random-forest-based screening informed covariate selection for Cox models. Endpoints were overall survival (OS), disease-free survival (DFS), and post-recurrence DFS (prDFS). Associations with clinical and pathological variables were evaluated using Kaplan–Meier estimates, log-rank tests, and multivariable Cox regression. Results. Among 112 patients (median follow-up, 121.1 months), 3-/5-year OS was 42.8%/28.0%, DFS 20.5%/13.2%, and 1-/3-year prDFS 36.7%/10.9%. Ulceration was associated with worse OS (HR 2.12; 95% CI 1.05–4.26) and DFS (HR 2.23; 95% CI 1.16–4.28). Male sex showed a trend toward poorer OS and DFS. Regional lymph-node treatment correlated strongly with OS and prDFS (overall p < 0.001), with neck dissection indicating unfavorable risk (OS HR 5.22; 95% CI 2.39–11.40). Conclusions. HNMM remains a high-mortality disease with frequent recurrence. Ulceration and nodal involvement were key adverse prognostic factors, while surgery was associated with improved survival. The findings support incorporating ulceration into future staging and highlight the potential for durable control through salvage surgery. Further investigation of treatment intensification, biomarkers, and multimodal strategies is warranted. Full article

Head and neck mucosal melanoma (HNMM) arises in the nasal and oral cavities and has the propensity to metastasize to local and distant body sites. HNMM is also notable for its resistance to available therapeutics. The rarity of this disease makes it difficult to conduct large-scale clinical studies to develop standard treatment protocols. In contrast to cutaneous melanoma, c-Kit-dependent pathways are well studied in HNNMM and provide a potential therapeutic target. We identified and isolated genetically distinct subpopulations with stem cell characteristics in HNMM samples bearing Kit wild-type and mutations. Functional analysis of these subpopulations reveals that, in addition to expressing the stem cell marker proteins CD20, CD117, CD133, and CD166, these subpopulations are characterized by self-renewal potential, migratory capacity, and resistance to Kit inhibitors such as Imatinib. Immunofluorescence staining and inhibition experiments demonstrate that the maintenance and resistance of HHMM subpopulations to Kit inhibitors is mediated by the Kit signal to the PI3K signaling pathway. The KIT signal to the PI3K signaling pathway does not result exclusively from a KIT mutation localized to Exon 17, but can also be triggered by mutations localized to Exons 11 and 13. In the present study, we identify and characterize an HNMM subpopulation with stemness properties in patients with c-Kit wild-type and mutation, and demonstrate for the first time the mechanisms by which the CD117⁺/CD133⁺ HNMM subpopulations survive and confer resistance to the specific inhibitor of c-Kit mutation. Full article

Background: Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy often resected with postoperative irradiation, with some evidence supporting the use of immune checkpoint inhibitors (ICIs). This study explores the potential efficacy and safety of nivolumab in 16 patients with SNMM, and reviews the literature of ICI use in it. Methods: We retrospectively analyzed 16 patients who had pathologically confirmed SNMM treated at Gifu University Hospital over a 14-year period between 2010 and 2024, of whom 11 received nivolumab. Clinical characteristics, treatment modalities, immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS) were examined. Kaplan–Meier and log-rank tests were used for survival analysis. A comprehensive literature review was done regarding ICI in SNMM. Results: Among the 16 patients, 11 received nivolumab and five did not. The nivolumab group showed longer median survival (median OS 26 mo vs. 8 mo; p = 0.00056) and a median PFS of 13 mo vs. 3 mo, p = 0.00175. In recurrent cases, nivolumab was associated with longer median OS (23 mo vs. 9 mo, p = 0.015) and PFS (11 mo vs. 3 mo, p = 0.019). irAEs occurred in four out of eleven of these cases, leading to nivolumab discontinuation; however, three of these four patients maintained durable disease control. A literature review identified generally favorable outcomes for ICIs in SNMM, although results were varied due to small sample sizes and heterogeneous treatment settings. Conclusions: Nivolumab was associated with longer survival in this small cohort in patients with SNMM, including those who discontinued therapy due to irAEs. Our data supports recent meta-analyses demonstrating a benefit of ICIs in SNMM. Full article

Background/Objectives: Accurate target delineation is critical in radiotherapy for head and neck non-melanoma skin cancer (NMSC), where tumor depth and subclinical extension are often underestimated by clinical and dermoscopic assessment alone. While high frequency ultrasound has shown value in surface-based radiotherapy techniques, the role of ultra-high frequency ultrasound (UHFUS) within external beam radiotherapy (EBRT) workflows remains poorly defined. Methods: We conducted a single-institution observational feasibility study including all consecutive patients with head and neck NMSC treated with definitive or adjuvant radiotherapy between July 2022 and July 2023 using a structured multidisciplinary workflow integrating pre-treatment UHFUS. UHFUS was systematically performed prior to CT simulation and incorporated into radiotherapy planning. The primary endpoint was the impact of UHFUS on radiotherapy decision-making, predefined as modification of target delineation, treatment intent, or beam modality selection. Secondary endpoints included feasibility, early local control, and late toxicity (descriptive). Results: Thirty patients were included (median age 85 years; range 66–99). UHFUS influenced at least one decision endpoint in 13 patients (43.3%). In the definitive radiotherapy cohort (n = 18), UHFUS modified gross tumor volume delineation in eight patients (44.4%), with an increase in median GTV from 17.5 cm³ to 24.3 cm³. Among patients initially referred for adjuvant radiotherapy (n = 12), UHFUS identified macroscopic residual disease in two cases, leading to a change in treatment intent from adjuvant to definitive radiotherapy. UHFUS supported beam modality selection in three patients by enabling safe use of electron therapy for superficial lesions. After a median follow-up of 24 months (range 12–24), no local recurrences were observed. Late toxicity was limited to grade 1 cutaneous events. Conclusions: Integration of UHFUS into EBRT planning for head and neck NMSC is feasible and clinically informative. UHFUS acts as a decision-shaping tool, influencing target delineation, treatment intent, and modality selection within a multidisciplinary workflow. These findings support further prospective evaluation of UHFUS-guided radiotherapy planning to standardize decision algorithms and assess long-term clinical impact. Full article

Boron neutron capture therapy (BNCT) is experiencing a global resurgence driven by advances in boron pharmacology, accelerator-based neutron sources, and molecular imaging-guided theranostics. BNCT produces high linear energy transfer particles with micrometer-range energy deposition, enabling cell-selective irradiation confined to boron-enriched tumor cells in a geometrically targeted region by the neutron beam. This mechanism offers the potential for exceptionally high therapeutic ratios, provided two core requirements are met: sufficient differential tumor uptake of ¹⁰B and a neutron beam with appropriate energy and penetration. After early clinical attempts in the mid-20th century were hindered by inadequate boron agents and reactor-based neutron beams, recent technological breakthroughs have made BNCT clinically viable. The development of hospital-compatible accelerator neutron sources, next-generation boron delivery systems (such as receptor-targeted compounds and nanoparticles), advanced theranostic approaches (such as ¹⁸F-BPA positron emission tomography and boron-sensitive magnetic resonance imaging), and AI-driven biodistribution modeling now support personalized treatment planning and patient selection. These innovations have catalyzed modern clinical implementation, exemplified by Japan’s regulatory approval of BNCT for recurrent head and neck cancer and the rapid expansion of clinical programs across Asia, Europe, and South America. Building on these foundations, BNCT has transitioned from a predominantly academic experimental modality into an increasingly commercialized and industrially supported therapeutic platform. The emergence of dedicated BNCT companies, international collaborations between accelerator manufacturers and hospitals, and pharmaceutical development pipelines for next-generation boron carriers has accelerated clinical translation. Moreover, BNCT now occupies a unique position among radiation modalities due to its hybrid nature, namely combining the biological targeting of radiopharmaceutical therapy with the external-beam controllability of radiotherapy, thereby offering new therapeutic opportunities where competitive approaches fall short. Emerging evidence suggests therapeutic promise in glioblastoma, recurrent head and neck cancers, melanoma, meningioma, lung cancer, sarcomas, and other difficult-to-treat malignancies. Looking ahead, continued innovation in compact neutron source engineering, boron nanocarriers, multimodal theranostics, microdosimetry-guided treatment planning, and combination strategies with systemic therapies such as immunotherapy will be essential for optimizing outcomes. Together, these converging developments position BNCT as a biologically targeted and potentially transformative modality in the era of precision oncology. Full article

Background: Cutaneous squamous cell carcinoma (cSCC) represents the second most common form of non-melanoma skin malignancy, and, when not amenable to curative surgery or radiotherapy, it is a life-threatening disease. The anti-PD-1 monoclonal antibody cemiplimab has transformed the outcome of advanced or metastatic cSCC, with response rates approaching 50% and sustained benefit beyond three years in clinical trials. Cemiplimab is now the first-line standard of care treatment for advanced disease. Methods: This retrospective observational study included consecutive adult patients with locally advanced (lac) or metastatic (m) cSCC who received cemiplimab (350 mg every three weeks) at the Center for Immuno-Oncology, University Hospital of Siena, Italy, either through an Expanded Access Program or routine clinical practice. Clinical outcome and treatment related adverse events (TRAEs) are reported. Results: Between December 2019 and December 2023, 27 patients (24 male; median age 82 years [range 41–90]) diagnosed with lacSCC (n = 20 [74.0%]) or mcSCC (n = 7 [25.9%]) were treated with cemiplimab as first line therapy and were followed until June 2024. Head and neck were the primary tumor location for 88.8% of patients, followed by trunk (7.4%) and lower extremities (3.7%). All patients had comorbidities, including six patients (22.2%) with hematologic malignancies. With a median follow-up of 31 months (data cut-off June 2024), the ORR was 66.6% (complete response 22.2%) and the disease control rate (DCR) 77.7%. Median progression-free survival (mPFS) and overall survival (mOS) were not reached, while 2-year PFS and OS rates were 65.2% and 71%, respectively. Treatment was well-tolerated, with three (11.1%) patients experiencing grade ≥3 TRAEs, and three patients discontinuing treatment due to TRAEs. Conclusions: Our real-world experience confirms the high rate of durable objective responses, good tolerability and long treatment duration of cemiplimab in elderly and frail cSCC patients as well. Full article

Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients. Full article

Background: Head and neck (H&N) cutaneous melanomas have poorer outcomes than melanomas at other sites, yet sentinel lymph node biopsy (SLNB)—a key prognostic tool in clinically node-negative disease—is less frequently performed, particularly outside tertiary centers. We evaluated the feasibility and prognostic relevance of SLNB in a medium-volume regional institution. Methods: We retrospectively reviewed patients with primary H&N cutaneous melanoma who underwent SLNB at the Department of Oral and Maxillofacial Surgery, University of Szeged, between 2010 and 2022. Clinicopathological features, nodal outcomes, recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were analyzed using Kaplan–Meier methods and univariate Cox regression. Results: Thirty-eight patients underwent SLNB, with a 100% sentinel lymph node identification rate and no major complications. Positive sentinel lymph nodes were identified in 8 patients (21.1%). Two false-negative events occurred, resulting in a false-omission rate of 6.7% and a negative predictive value of 93.3%. SLN-negative patients demonstrated longer RFS and OS, although differences were not statistically significant. Among patients with intermediate-risk melanoma (pT1b–pT3a), 18.5% had a positive SLN. Conclusions: SLNB is a safe and clinically meaningful staging procedure for H&N melanoma in a medium-volume regional center. Sentinel node status provides important prognostic information and supports appropriate patient selection for contemporary adjuvant therapy. Full article

Mucosal melanoma (MM) is a rare, aggressive cancer whose incidence has increased continuously over the years. This subtype of melanoma arises from melanocytes on hairless surfaces, typically in the respiratory tract, gastrointestinal (GI) tract, and urogenital tract. The most common sites of occurrence include the head and neck, the anorectal region, and the vulvovaginal region, while the rare sites of MM are the urinary tract and the upper and lower GI tract, including the esophagus, duodenum and the gallbladder. MM arises in melanocytes of the ectodermal mucosa that originate from neural crest cells and migrate through embryonic mesenchyme to their destination. Although melanocytes are located mainly in the epidermis and dermis, their presence in various extracutaneous sites, such as the eyes, mucosal tissue, and leptomeninges, is known. Although both cutaneous melanoma (CM) and MM differ in their epidemiology, genetic profile, and clinical presentation, their treatment options are similar. In contrast to the higher treatment response of CM, MM is characterized by a lower response rate to available treatment options, resulting in a poorer survival rate. In this review, we provide an overview of the biology of MM and the mechanisms regulating its development, progression and treatment resistance. Full article