Search Results (142)

Background/Objectives: Metatypical basal cell carcinoma (MTBCC) is a rare and aggressive variant of non-melanoma skin cancer (NMSC) characterised by overlapping histological features of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Owing to its increased propensity for local invasion, recurrence, and metastasis, MTBCC poses diagnostic and therapeutic challenges. This study aimed to characterise the epidemiological, histopathological, and clinical features of MTBCC and to evaluate temporal changes in tumour characteristics and aggressiveness before, during, and after the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on 129 histologically confirmed MTBCC lesions diagnosed in the Pathology Department of the Mures Clinical County Hospital, Targu Mures, Romania, between January 2017 and December 2025. Demographic data, tumour location, histological subtypes, differentiation of the squamous component, aggressiveness parameters, and volumetric measurements of tumours and excision specimens were analysed. Volumetric analyses were restricted to cases with complete three-dimensional measurements. Statistical comparisons were performed across demographic variables and the following three time periods: pre-pandemic, pandemic, and post-pandemic. Results: The median age at diagnosis was 71 years, with a slight male predominance (p = 0.25) and a significant predominance of patients from urban areas (p < 0.001). Most tumours were located in the head and neck region. Mixed-type MTBCC was significantly associated with higher tumour aggressiveness (p = 0.0019) and with high-risk histological subtypes, particularly micronodular and adenoid–cystic variants. Tumour volume showed a significant inverse correlation with year of diagnosis (p = 0.0139; r = (−) 0.50), whereas excision specimen volume differed significantly according to year of diagnosis (p = 0.0425). Neither tumour volume nor excision specimen volume was associated with histopathological aggressiveness. Conclusions: Metatypical basal cell carcinoma is a rare skin malignancy in which biological behaviour appears to be determined primarily by histopathological architecture rather than tumour size. Mixed-type lesions were associated with significantly higher aggressiveness, underscoring the need for accurate histopathological assessment. These findings support a pathology-driven approach to management and emphasise the importance of adequate surgical treatment and long-term follow-up in patients with MTBCC. Full article

Salivary adenoid cystic carcinoma (SACC) is an immunologically cold malignancy with limited response to current immunotherapies. Integrated transcriptomic profiling of peripheral blood, primary tumors, lung metastases, and a two-donor single-cell dataset revealed compartment-specific expression signatures and, through computational inference, systemic immune dysregulation marked by hematopoietic suppression, T-cell exhaustion, compensatory myelopoiesis, and an immature B-cell expansion. To explore the transcriptional basis of this peripheral immune aberration, blood-derived RNA-seq was interrogated, identifying only 32 unique genes meeting |log2FC| > 1 and q < 0.05 among 34,999 transcripts; qPCR confirmed concordant upregulation of IL33 and CCL14, providing directional rather than confirmatory support, suggesting peripheral immune molecular aberrations that still require validation through broader differential gene expression validation. Complementing this transcriptomic signature, detection of MYB-NFIB fusion transcripts matching tumor tissue in one patient’s blood suggested that tumor-derived signals may access the circulation, although cohort validation remains necessary. Extending these peripheral observations to tissue compartments, we applied expression stratification, correlation networks, ligand-receptor mapping, and a virtual gain-loss model to computationally predict regulatory associations involving IL17RB/OLIG1/NOTCH1 in primary tumors and a CD24/IL17RB/MYB/MYBL2/CXCL13/CXCR5 module in lung metastases. At the single-cell level, cluster 10 emerged as a cell-cycle-high tumor population with transcriptional overlap with proliferating immune progenitors, providing a potential cellular basis for tumor cell entry into the circulation. Collectively, these computational inferences generate testable hypotheses for multicompartment immune dysregulation in SACC, positioning IL17RB as a candidate molecule that warrants prospective validation in SACC-specific preclinical models. Full article

Background/Objectives: Differences among scanners and reconstruction methods may limit the comparability of quantitative metrics derived from fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT). Although harmonization reduces inter-scanner variability in standardized uptake values (SUVs), its impact on the preservation of lesion-level ranking in real-world clinical datasets remains unclear. Here, we evaluated the robustness of PET quantitative metrics, particularly focusing on rank preservation after harmonization. Methods: Phantom and clinical data retrospectively acquired from three institutions using four PET/CT scanner types were analyzed. Harmonization parameters were derived from National Electrical Manufacturers Association IEC Body Phantom data, using the oldest scanner as the reference, and were directly applied to the clinical datasets. Clinical evaluation included head and neck malignant melanoma (HNMM; high FDG avidity) and adenoid cystic carcinoma (ACC; low FDG avidity). Rank preservation between pre- and post-harmonization values was assessed using Spearman’s rank correlation coefficient (ρ). Results: Phantom-based harmonization reduced inter-scanner differences and enabled consistent evaluation in clinical datasets (HNMM: 34 patients, 93 lesions; ACC: 18 patients, 38 lesions). SUVpeak demonstrated the highest rank preservation across tumor types and lesion sizes (ρ = 0.94–1.00). Metabolic tumor volume (MTV) showed a high rank correlation in HNMM with an absolute threshold (MTV2.5; ρ = 0.99), but robustness varied depending on threshold definition, tumor type, and lesion size. Tumor-to-liver ratios showed moderate rank preservation. Conclusions: Our results suggested that SUVpeak is the most robust preservation of lesion ranking across tumor types after harmonization, suggesting its suitability as a reliable imaging biomarker in multicenter studies. Meanwhile, careful standardization is needed when using MTV-based metrics for prognostic evaluation. Full article

Salivary gland cancers (SGCs) are rare and heterogeneous tumours, making the identification of reliable prognostic biomarkers challenging. MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may play important roles in tumour progression and treatment response. This systematic review aims to identify and summarize the current evidence on miRNA dysregulation in SGCs, with a particular focus on their prognostic relevance and therapeutic potential. A systematic search of PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library was conducted up to 3 December 2025, following PRISMA guidelines and a pre-registered protocol (CRD420251231827). Observational cohort and cross-sectional studies reporting microRNA dysregulation in human salivary gland tissues with prognostic assessment were included. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Due to considerable heterogeneity, a narrative synthesis was conducted. Twenty studies published between 2013 and 2025 that fulfilled the search criteria were further analyzed. Based on the currently available evidence, dysregulation of miRNAs associated with prognosis has been identified only in adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC). Most studies originated from Asia and used qRT-PCR for miRNA assessment. Most researchers focused on the evaluation of selected candidate miRNAs, rather than conducting comprehensive miRNA profiling approaches in relation to prognosis. Several distinct dysregulated miRNAs were identified across the studies. Among them, miR-9, miR-21, miR-24 miR-29, miR-34c-5p, miR-125a-5p, miR-143, miR-145 and miR-205 were reported in more than one study and linked to clinicopathological advancement and a more aggressive disease course, thus leading to a poorer outcome. MiRNAs appear to represent promising prognostic biomarkers, either as independent predictors or in combination with established clinicopathological features. However, current evidence remains limited to selected histological subtypes and relatively small patient cohorts. Further well-designed studies with long-term follow-up are required. Moreover, comprehensive miRNA profiling with prognosis assessment is necessary before specific miRNAs could be reliably established as biomarkers and utilized in daily clinical practice. Full article

Background/Objectives: Breast adenoid cystic carcinoma (ACC) is a rare tumor with limited data on imaging features and treatment response. This study investigated the clinical and radiological characteristics of ACC of the breast. Methods: Patients with ACC who underwent surgery at our institution between February 2010 and December 2023 were included. Clinical characteristics, biopsy and surgical pathology findings, and follow-up outcomes were reviewed. Preoperative mammography, ultrasound (US), and MRI findings were analyzed. Results: Twenty-eight women (mean age, 57 ± 8 years) were identified. Half presented with palpable masses, and the remainder were detected on screening. Percutaneous biopsy was performed in 27 patients, correctly diagnosing ACC in 18 (66.7%), whereas 9 (33.3%) were misdiagnosed as having invasive ductal carcinoma. The mean tumor size was 2.9 cm (range, 0.9–8 cm), with axillary metastasis in two women (7.1%). Most tumors were triple-negative (78.6%), while six showed low estrogen-receptor positivity (<10%). Ki-67 was <20% in 64.3%, with no high values (≥75%). Three patients received neoadjuvant chemotherapy, with two non-responders. No recurrences occurred during a median follow-up of 51 months. Imaging revealed masses on mammography (85.2%), US (92.9%), and MRI (92.3%), with calcifications in two cases. Most lesions were highly suspicious (BI-RADS 4C or 5) and showed increased vascularity in 92.3% on Doppler US. Conclusions: Breast ACC typically presents as a hypervascular, highly suspicious mass. Despite frequent triple-negative profiles, it shows low proliferation, poor response to chemotherapy, and favorable prognosis. Full article

Background/Objectives: Adenoid cystic carcinoma (ACC) is a heterogenous disease and defining aggressive subtypes to inform surveillance and treatment strategies remains clinically pertinent. NOTCH pathway-activated ACC is associated with worse outcomes. We describe the distribution of tumour mutational burden (TMB) and characterise its relationship with NOTCH gain-of-function (GoF) mutation and survival in locally advanced or recurrent/metastatic (LA-R/M) ACC. Methods: 124 tumours from the UK NHS (NHS group) and 139 tumours from cBioPortal; MSK metTropism (MSK group) were evaluated as independent cohorts. TMB (mut/Mb) was calculated either by F1CDx or its precursor FoundationOne NGS in the NHS group, or MSK-IMPACT NGS in the MSK group. NOTCH1/2 mutations were classed as GoF if predicted to disrupt the NRR/PEST domains. Overall survival (OS) was measured from diagnosis of unresectable LA-R/M ACC. Results: Median TMB was 1.26 mut/Mb (IQR 0–2.52) in the NHS group and 1.96 (IQR 0.87–3.46) in the MSK group. NOTCH1/2 GoF mutation was seen in 16/124 (13%) in the NHS group and 22/139 (16%) in the MSK group. Median TMB for tumours with NOTCH1/2 GoF mutation was 2.52 mut/Mb (IQR 1.82–3.84) in the NHS group and 4.38 mut/Mb (IQR 3.33–4.89) in the MSK group. For tumours with NOTCH1/2 GoF mutation, median OS reduced with TMB > median of 2.52 mut/Mb (0.7 yrs vs. 2.6 yrs, p = 0.02) in the NHS group. Conclusions: LA-R/M ACC has a low TMB profile overall. Median TMB was higher in NOTCH-activated ACC in both the NHS and MSK groups and TMB may have value in further stratifying patients with LA-R/M ACC. Full article

Background/Objectives: Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) has no standard systemic therapy. VEGFR-targeting tyrosine kinase inhibitors (TKIs) are commonly used first-line, though no international standard exists; cisplatin-based chemotherapy is an alternative. We retrospectively reviewed the cyclophosphamide–epirubicin–cisplatin (CEP) regimen to determine whether prior TKI exposure compromises subsequent chemotherapy efficacy. Methods: We studied 31 patients given CEP for progressive R/M ACC (2018–2023). Tumor response was assessed by RECIST 1.1. Molecular subtype was determined by c-MYC/p63 immunohistochemistry (ACC-I, c-MYC-positive/p63-negative; ACC-II, p63-positive/c-MYC-low or negative). Multivariable models used Firth’s penalized likelihood Cox regression. Next-generation sequencing (NGS) was available in 21 of 31 patients. Results: Thirty-one patients were enrolled (median age 48; 17 [54.8%] with prior TKI). At median follow-up of 22.6 months, the objective response rate (ORR) was 19.4%, disease control rate 71.0%, median progression-free survival (PFS) 5.3 months, and median overall survival (OS) 10.3 months. Prior TKI did not lower efficacy: ORR 17.6% vs. 21.4%, PFS hazard ratio 0.76 (p = 0.519). All six partial responses occurred in ACC-I tumors (35.3% vs. 0% in ACC-II, p = 0.021). In the NGS subset (5 PIK3CA-mutant), PIK3CA mutation (OS HR 6.19, p = 0.024) and bone metastasis (OS HR 5.84, p = 0.027) remained associated with shorter OS after adjustment. No treatment-related deaths occurred. Conclusions: CEP is active in R/M ACC, and prior TKI exposure did not appear to reduce efficacy. Higher response rates in ACC-I tumors and the apparent PIK3CA-related survival deficit are exploratory observations that need prospective testing before they can guide treatment. Full article

Background: Accurate differentiation between benign and malignant cervical lymphadenopathy remains clinically important for diagnostic stratification and treatment planning. This study evaluated the diagnostic performance of conventional morphological magnetic resonance imaging (MRI) features and apparent diffusion coefficient (ADC) values in a mixed cohort of cervical lymphadenopathies. Methods: This retrospective lesion-based diagnostic study included 88 cervical lymph nodes from 39 patients who underwent head-and-neck MRI between September 2023 and December 2025. The cohort had malignant entities such as squamous cell carcinoma metastases, thyroid carcinoma, non-Hodgkin lymphoma, adenoid cystic carcinoma, and medullary thyroid carcinoma, as well as benign/reactive, inflammatory, CMV-related, tuberculous, Warthin tumor-associated, and cystic lymphangioma-related lymphadenopathies. MRI examinations were performed for heterogeneous indications, including the initial assessment of palpable cervical lymphadenopathy, oncological staging, post-biopsy follow-up, suspected recurrence, and benign/inflammatory lesion characterization; therefore, not all patients underwent MRI for the same clinical indication. Most examinations were performed during the initial diagnostic work-up, while six cases represented post-biopsy follow-up. Morphological features and ADC values were analyzed using Mann–Whitney U tests, chi-square tests, ROC analysis, DeLong testing, Firth penalized logistic regression, generalized estimating equations (GEE), patient-level bootstrap resampling, and calibration analysis. Statistical analyses were performed using Python (Version 3.12), with exploratory verification in JASP. Statistical significance was set at p < 0.05. Results: The cohort included 39 patients with a mean age of 54 years (range: 18–74 years), with 20 males and 19 females. Of the 88 lymph nodes, 33 were malignant and 55 benign. Malignant nodes demonstrated significantly lower ADC values than benign nodes (0.87 ± 0.23 vs. 1.25 ± 0.22 × 10⁻³ mm²/s; U = 207, p < 0.001). ADC alone showed good diagnostic performance, with an AUC of 0.886 (95% CI: 0.803–0.960). The optimal ADC cutoff was 0.900 × 10⁻³ mm²/s, yielding 75.8% sensitivity and 89.1% specificity. The final GEE model, including the ADC, nodal shape, and margin characteristics while accounting for intra-patient clustering, achieved an apparent AUC of 0.956. Leave-one-patient-out cross-validation yielded an AUC of 0.929, and the bootstrap optimism-corrected AUC was 0.949. DeLong testing confirmed that the combined model significantly outperformed the ADC alone (AUC improvement = 0.070; p = 0.006), and the inter- and intra-observer reproducibility for ADC was excellent. Conclusions: ADC values, nodal shape, and margin characteristics provide complementary diagnostic information for differentiating benign from malignant cervical lymph nodes. A structured multiparametric MRI approach demonstrated high diagnostic performance, although the findings should be interpreted in the context of the retrospective single-center design and histopathological heterogeneity. Full article

Salivary adenoid cystic carcinoma (SACC) is a malignant salivary gland neoplasm characterized by aggressive local invasion and a marked propensity for metastasis. However, the role of MEOX1 in SACC progression remains poorly defined. In this study, we examined the effects of MEOX1 overexpression on the malignant behavior of SACC cells in vitro and in vivo. Human SACC-83 and SACC-LM cells were transduced with lentiviral vectors encoding MEOX1 or an empty vector control, and cell proliferation, migration, invasion, and cell cycle distribution were assessed using CCK-8, wound healing, Transwell, and flow cytometric assays, respectively. RNA sequencing was performed to characterize transcriptional changes associated with MEOX1 overexpression. In vivo, tumor growth was evaluated in BALB/c nude mice bearing subcutaneous xenografts, and pulmonary metastatic colonization was assessed using a tail vein injection model. MEOX1 overexpression reduced the proliferation, migration, and invasion of SACC cells in vitro and increased the G2/M phase fraction. In xenograft models, MEOX1-overexpressing cells formed smaller tumors and showed lower Ki67 staining than control cells. In the experimental lung metastasis model, mice injected with MEOX1-overexpressing cells developed fewer pulmonary metastatic nodules. RNA-seq identified 588 differentially expressed genes associated with MEOX1 overexpression, with enrichment in pathways including cytokine–cytokine receptor interaction, Toll-like receptor signaling, and G protein-coupled receptor signaling. Together, these findings indicate that enforced MEOX1 expression is associated with reduced malignant phenotypes in SACC models and with transcriptomic alterations in pathways related to immune response, G protein-coupled receptor signaling, and DNA damage response. Full article

Background: Adenoid cystic carcinoma (ACC) demonstrates marked clinical heterogeneity that is inadequately explained by conventional histopathologic and staging systems alone. Recent studies have identified two molecular subtypes based on transcriptomic profiling and MYC/TP63 expression (ACC I: MYC-high/TP63-low; ACC II: MYC-low/TP63-high) with potential prognostic significance. However, the magnitude and consistency of their survival impact remain uncertain. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Embase, and PubMed Central were searched through January 2026 for studies reporting overall survival in ACC stratified by MYC/TP63 molecular subtype. Hazard ratios (HRs) were pooled using random-effects models. Heterogeneity, subgroup analyses by classification method, sensitivity analyses, cumulative meta-analysis, influence diagnostics, and publication bias assessment were performed. Results: Five independent cohorts from two publications comprising 247 patients (90 ACC I, 157 ACC II) were included. ACC I was associated with significantly worse overall survival compared with ACC II, with a pooled HR of 3.88 (95% CI: 2.55–5.90; p < 0.001). No statistical heterogeneity was observed (I² = 0%). Prognostic separation was consistent across RNA sequencing and immunohistochemistry-based classification methods. Conclusions: Transcriptomic and MYC/TP63-based molecular subtyping provides strong and reproducible prognostic stratification in ACC. ACC I tumors confer an approximately four-fold higher mortality risk compared with ACC II tumors. Incorporation of molecular subtype into routine diagnostic and clinical decision-making may improve risk stratification, surveillance strategies, and future trial design in ACC. Full article

Salivary gland tumors have diverse biological behaviors, and the exact molecular factors underlying their pathogenesis remain unclear. The expression of Annexin V and its potential association with Ki-67 in these tumors has not been explored. Therefore, this study aimed to evaluate the immunohistochemical expression of Ki-67 and Annexin V and to assess their relationship in salivary gland tumors. This study included 45 formalin-fixed, paraffin-embedded blocks (5 normal salivary gland tissues, 10 pleomorphic adenomas, 10 Warthin tumors, 10 mucoepidermoid carcinomas, and 10 adenoid cystic carcinomas). Immunohistochemical staining for Ki-67 and Annexin V was performed and evaluated semi-quantitatively. Depending on the results of the normality test, one-way ANOVA or the Kruskal-Wallis H test was used for group comparisons. Spearman’s rho test was used to assess correlations among the markers under study. A p-value < 0.05 was considered statistically significant. Both markers and their ratio showed statistically significant differences among the groups (p-value < 0.001). Normal salivary gland tissue and pleomorphic adenoma showed negative Ki-67 expression, whereas Warthin tumor, mucoepidermoid carcinoma, and adenoid cystic carcinoma showed weak proliferation indices. Annexin V expression was highest in the normal salivary gland tissue. Within individual tumor types, Ki-67 and Annexin V exhibited no significant correlation. The combined evaluation of Ki-67 and Annexin V expression, along with their relationship, may provide preliminary insights into the biological behavior of salivary gland tumors and warrant further clinicopathological investigation. Full article

Background: Carinal resections remain a challenging and demanding surgical technique for both the patient and medical professionals. The most common indications are adenoid cystic carcinoma and bronchogenic carcinoma. There have been no randomized controlled trials because of the low incidence of pathologic processes suited to carinal resections and the difficulties associated with designing such studies. Methods: The known data are limited to a few single-institutional, retrospective studies over the last several decades. In this review article, we focus on the available data regarding surgical techniques and the types of ventilation that can help in the construction of the anastomosis—the most crucial part of the operation. Important issues regarding carinal resections are discussed in detail. Results: The available literature is reviewed in detail regarding indications, surgical techniques and approaches, types of ventilation, the rates of morbidity and mortality, and 5-year survival. The authors present their experience with two patients, where they utilized ECMO and crossfield ventilation. The role of minimally invasive surgery in carinal resections is also discussed. Conclusions: Carinal resections are complex surgical procedures, but acceptable mortality and morbidity rates can be achieved in carefully selected patients. Excellent cooperation between the surgeon and anesthesiologist is essential in the construction of the anastomosis. Various types of airway management, especially ECMO, help to reduce complication rates and facilitate secure airway reconstruction. Full article

Background/Objectives: Head and neck adenoid cystic carcinoma (HNAdCC) is characterized by indolent growth but sustained long-term risk of late recurrence and disease-related mortality. Data describing very long-term outcomes using analytic approaches that explicitly account for competing mortality remain limited. We aimed to characterize late failures, competing causes of death, and clinically interpretable long-horizon risk estimates after primary surgery for HNAdCC. Methods: We performed a retrospective single-center cohort study of patients with HNAdCC treated with curative-intent surgery between 1984 and 2020. Overall survival (OS) and cancer-specific survival (CSS) were estimated using Kaplan–Meier method. Competing risks of disease-related and other-cause death, as well as first-failure patterns, were analyzed using cumulative incidence functions, including a 5-year landmark analysis. Conditional mortality and restricted mean survival time (RMST; τ = 25 years) were additionally assessed. Results: Fifty-seven patients were included (median age 54 years). Median follow-up was 133 months overall and 212 months among survivors. A first failure occurred in 19/57 (33.3%) of patients, with distant metastasis as the most common pattern; 7/19 (36.8%) of failures occurred beyond 5 years. OS at 5, 10, and 25 years was 68.4%, 64.9%, and 37.5%, respectively; corresponding CSS was 78.9%, 74.8%, and 51.7%. At 25 years, cumulative incidence of disease-related death was 41.7%, compared with 20.9% for other-cause death. Older age and advanced T category were independently associated with worse OS, while older age and perineural invasion predicted worse CSS. Among 5-year survivors, conditional risk of disease-related death by 25 years remained 32.7%. RMST analyses demonstrated substantial long-term life-years lost associated with perineural invasion and T3–4 disease. Conclusions: HNAdCC exhibits persistent long-term risk with clinically meaningful late failures and substantial competing mortality over decades. Conditional and RMST-based estimates provide patient-centered measures that support lifelong, risk-adapted surveillance, particularly focused on detection of distant metastases. Full article

Background/Objectives: Treatment delays have been shown to be associated with overall survival (OS) in head and neck squamous cell carcinomas (HNSCCs). Given the slow tumor growth kinetics of adenoid cystic carcinoma (ACC), it is unclear if delays have a similar impact in this tumor histology. Methods: We queried the National Cancer Database for patients diagnosed with non-metastatic ACC between the years 2004 and 2019 and treated with surgery followed by RT. A multivariable Cox regression model was used to examine the associations between the time from diagnosis to surgery, the duration of RT, and OS. Results: A total of 1449 patients were included for analysis. Increased time from diagnosis to surgery (HR: 1.02, 95% CI: 1.01–1.03, p < 0.001) and duration of RT (HR: 1.14, 95% CI: 1.04–1.25, p = 0.004) were associated with worse survival on UVA, while time from surgery to RT start was not (p = 0.647). Increased duration of RT (aHR: 1.13, 95% CI: 1.03–1.24, p = 0.012) remained significantly associated with OS on multivariable analysis, while time from diagnosis to surgery (aHR: 1.00, 95% CI: 0.98–1.02, p = 0.979) did not. Conclusions: Delays in treatment initiation and in the interval from surgery to radiation did not result in clinically significant differences in survival in this analysis, while prolonged duration of radiation therapy was significantly associated with worse survival. These findings are hypothesis-generating and suggest that treatment delays for ACC may have different effects on oncologic outcomes than those for HNSCC; however, prospective data is paramount to verify these results before strong conclusions can be made. Full article

This study investigates whether dedicated tumor segmentation for radiomics (TRAD) offers any advantage over gross tumor volume (GTV) in CT radiomics for predicting adenoid cystic carcinoma (ACC) progression after proton therapy (PT). Fifty-six patients with histologically proven salivary gland ACC were included, and 107 original features were extracted using PyRadiomics v3.1.0. Signatures were selected (n = 3) with sequential backward elimination using multiple classifiers, all optimized for improving cross-validated area under the ROC curve (AUC). Signature similarity was quantified using the Spearman correlation coefficient. Random forest (RF) yielded the best discriminative performance, with no statistical difference in AUCs between contour choices (GTV: 0.87 vs. TRAD: 0.80; ΔAUC_median = 0.0, p = 0.589). Time-to-event analysis confirmed both signatures stratified patients into distinct progression-free survival risk groups (Log-rank p < 0.0001) and demonstrated robust prognostic accuracy (GTV: C-index = 0.74, HR = 11.63; TRAD: C-index = 0.72, HR = 7.01). Biologically, GTV and TRAD signatures were borderline associated with perineural spread (p = 0.056) and solid tumor patterns (p = 0.053), respectively. Overall, CT-based radiomics models performed comparably across both segmentation strategies, supporting GTV as a practical and efficient alternative to TRAD for predicting ACC progression after PT. Full article