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20 pages, 1630 KB  
Article
Mucosal Melanoma of the Head and Neck: A 45-Year Experience of a Tertiary Cancer Center
by Stefano Cavalieri, Benedetta Lombardi Stocchetti, Andrea Spagnoletti, Francesco Barretta, Andrea Anichini, Patrizia Boracchi, Gabrina Tragni, Lorenza Di Guardo, Alice Indini, Barbara Valeri, Roberto Bianchi, Sarah Colombo, Nicola Alessandro Iacovelli, Marzia Franceschini, Michele Del Vecchio and Marco Guzzo
Cancers 2026, 18(8), 1304; https://doi.org/10.3390/cancers18081304 (registering DOI) - 20 Apr 2026
Abstract
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 [...] Read more.
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
(This article belongs to the Section Cancer Therapy)
11 pages, 721 KB  
Systematic Review
Metastatic Colorectal Cancer Beyond Third-Line Treatment: Systematic Review and Meta-Analysis of Later-Line Therapies
by Jacopo Giuliani, Emilia Durante, Daniela Mangiola, Andrea Georgopulos, Beatrice Mantoan and Francesco Fiorica
J. Clin. Med. 2026, 15(8), 3128; https://doi.org/10.3390/jcm15083128 - 20 Apr 2026
Abstract
Objectives: To evaluate and indirectly compare overall survival (OS) and safety of regorafenib, fruquintinib, and trifluridine/tipiracil (TAS-102) monotherapy in refractory metastatic colorectal cancer (mCRC) beyond the third line. Methods: A systematic review and meta-analysis of phase II/III randomized controlled trials was [...] Read more.
Objectives: To evaluate and indirectly compare overall survival (OS) and safety of regorafenib, fruquintinib, and trifluridine/tipiracil (TAS-102) monotherapy in refractory metastatic colorectal cancer (mCRC) beyond the third line. Methods: A systematic review and meta-analysis of phase II/III randomized controlled trials was conducted according to PRISMA guidelines. PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from inception. Eligible studies included patients with mCRC previously treated with standard chemotherapy and biologic agents, receiving regorafenib, fruquintinib, or TAS-102 as monotherapy in the fourth line or later. OS data were reconstructed from published Kaplan–Meier curves. Pooled median and mean OS were estimated using a random-effects model, and heterogeneity was assessed using the I2 statistic. Safety outcomes were descriptively summarized. Results: Four RCTs were included. The pooled median OS was 7.83 months (95% CI: 6.98–8.80), and the pooled mean OS was 8.90 months (95% CI: 8.00–9.81), with no heterogeneity (I2 = 0%). Survival gains versus placebo ranged from 1.4 to 2.6 months. Survival curves largely overlapped, with differences below one month. Safety was consistent with known profiles. Conclusions: These agents provide comparable efficacy with modest survival benefit in late-line mCRC, highlighting the need for improved strategies and better treatment sequencing. Full article
(This article belongs to the Special Issue Metastatic Colorectal Cancer Beyond Second-Line Treatment)
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31 pages, 543 KB  
Article
Frequentist and Bayesian Predictive Inference for the Log-Logistic Distribution Under Progressive Type-II Censoring
by Ziteng Zhang and Wenhao Gui
Entropy 2026, 28(4), 466; https://doi.org/10.3390/e28040466 - 18 Apr 2026
Viewed by 39
Abstract
This paper investigates the prediction of unobserved future failure times for the heavy-tailed Log-Logistic distribution under Progressive Type-II censoring. We first develop point and interval estimates for the unknown parameters using both frequentist maximum likelihood and Bayesian approaches. For predicting future failures, we [...] Read more.
This paper investigates the prediction of unobserved future failure times for the heavy-tailed Log-Logistic distribution under Progressive Type-II censoring. We first develop point and interval estimates for the unknown parameters using both frequentist maximum likelihood and Bayesian approaches. For predicting future failures, we derive three distinct point predictors: the Best Unbiased Predictor (BUP), the Conditional Median Predictor (CMP), and the Bayesian Predictor (BP). Corresponding prediction intervals are constructed using frequentist pivotal quantities, Bayesian Equal-Tailed Intervals (ETIs), and Highest Posterior Density (HPD) methods. The Bayesian procedures are implemented via Markov chain Monte Carlo (MCMC) sampling. We evaluate the finite-sample performance of the proposed methodologies through a Monte Carlo simulation study and further validate them using two real-world datasets, namely bladder cancer remission times and guinea pig survival times. The numerical results indicate that the proposed BP, particularly under the empirical prior, provides the most accurate and stable overall performance for point prediction, while the frequentist predictors become less reliable in extreme heavy-tailed settings. For interval prediction, the Bayesian HPD method consistently outperforms the alternatives, substantially reducing interval lengths for right-skewed data while maintaining the nominal coverage probability. Full article
17 pages, 876 KB  
Review
Balancing Tumor Response and Rejection Risk After Pre-Transplant Immunotherapy: A Scoping Review
by Berkay Demirors, Matthew Yu-Sheng Lin, Francis J. Spitz, Abiha Abdullah, Vrishketan Sethi and Michele Molinari
Cancers 2026, 18(8), 1284; https://doi.org/10.3390/cancers18081284 - 18 Apr 2026
Viewed by 120
Abstract
Importance: Immune checkpoint inhibitors (ICIs) have expanded downstaging options for hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), enabling bridging to liver transplantation (LT). However, the immunologic consequences of pre-transplant checkpoint blockade, particularly the risk of allograft rejection mediated by persistent T-cell activation, remain insufficiently [...] Read more.
Importance: Immune checkpoint inhibitors (ICIs) have expanded downstaging options for hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), enabling bridging to liver transplantation (LT). However, the immunologic consequences of pre-transplant checkpoint blockade, particularly the risk of allograft rejection mediated by persistent T-cell activation, remain insufficiently characterized, creating a critical knowledge gap at the intersection of immuno-oncology and transplant medicine. Objective: To synthesize current evidence on oncologic outcomes, rejection risk, washout intervals, donor-type considerations, and immunosuppression strategies in LT recipients with pre-transplant ICI exposure. Evidence Review: A PRISMA-ScR-guided review was conducted using MEDLINE, Embase, Cochrane Library, and Web of Science from January 2015 through December 2025. Studies reporting outcomes in adult LT recipients with documented pre-transplant ICI exposure for HCC or CCA were included. Methodological quality was descriptively assessed using the Newcastle-Ottawa Scale and JBI tools. Given study heterogeneity, findings were narratively synthesized. Findings: Thirty studies were included. In HCC, neoadjuvant ICI therapy achieved downstaging to Milan criteria in 75.6% of candidates in the largest multicenter cohort (n = 117), with complete pathologic response rates ranging from 23.8% to 40%. Rejection rates ranged from 16.3% to 20.2% in large series but increased to 56.3% with short washout intervals. Washout intervals exceeding 50 days were associated with rejection rates approaching non-ICI controls, while an individual patient meta-analysis of 91 patients estimated each additional week of washout was associated with approximately 8% reduction in rejection risk, suggesting that approximately 94 days may be required to achieve a rejection probability of 20% or less. Rejection occurred at a median of 7–10 days post-transplantation, earlier than typical acute cellular rejection. Three-year overall survival exceeded 85.3% in major cohorts. Donor type was not consistently associated with rejection after adjustment for washout duration. CCA data remain limited. Immune-related adverse events during ICI therapy were associated with increased post-transplant rejection risk. Conclusions: Pre-transplant ICI therapy may expand transplant eligibility in advanced hepatobiliary malignancies but carries time-dependent rejection risk. Current evidence supports a minimum washout interval of at least 50 days, with emerging data favoring 90–94 days when feasible. Prospective multicenter studies, biomarker-guided risk stratification, and standardized immunosuppression protocols are needed to refine patient selection and optimize timing. Full article
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10 pages, 587 KB  
Article
Can Computed Tomography Findings for Kidney, Ureter and Bladder Correlate with Medical Comorbidity in Renal Colic Patients?
by Lara Sharpe, Basil Razi, Cheryl Fung, Rajni Lal, Marnique Basto and Henry H. Woo
Soc. Int. Urol. J. 2026, 7(2), 25; https://doi.org/10.3390/siuj7020025 - 17 Apr 2026
Viewed by 76
Abstract
Background/Objectives: Sarcopenia is a progressive skeletal muscle disorder linked to adverse outcomes. Computed Tomography (CT) can quantify skeletal muscle, while the Charlson Comorbidity Index (CCI) predicts mortality by categorising comorbidities. This study examined whether Computed Tomography of the Kidneys, Ureters, and Bladder (CT-KUB)-derived [...] Read more.
Background/Objectives: Sarcopenia is a progressive skeletal muscle disorder linked to adverse outcomes. Computed Tomography (CT) can quantify skeletal muscle, while the Charlson Comorbidity Index (CCI) predicts mortality by categorising comorbidities. This study examined whether Computed Tomography of the Kidneys, Ureters, and Bladder (CT-KUB)-derived skeletal muscle measurements correlate with CCI scores in hospitalised patients. Methods: This retrospective study included all patients admitted with renal colic to the Urology Department, Blacktown Hospital and underwent cystoscopy between June 2022 and June 2025. Data were obtained from electronic medical records. CCI scores, incorporating age and comorbidities, generated 10-year survival estimates. CT-KUB scans were reviewed for psoas muscle perimeter, area, height, width and Hounsfield unit at the aortic bifurcation. Skeletal Muscle Index (SMI) was calculated as skeletal muscle area (SMA)/height2. Associations between CCI, psoas muscle metrics and outcomes (length of stay, Intensive Care Unit (ICU) admission, Emergency Department (ED) re-presentation) were assessed using Pearson’s correlations and between-group comparisons. Results: A total of 397 patients were analysed. Median Length of Stay (LOS) was 1 day (mean = 1.92, SD = 1.88). ICU admission occurred in 2.3% of patients, and 18.6% re-presented to ED within 30 days. Both CCI survival percentage and psoas muscle metrics (including SMI) were significantly associated with LOS. Lower SMA, Hounsfield unit (HU), length and perimeter were linked to higher ICU admission risk. Neither CCI nor muscle measures predicted ED re-presentation. Conclusions: CCI and CT-derived muscle metrics were independently associated with outcomes such as LOS and ICU admission. Combining these measures may improve risk stratification, warranting further prospective evaluation. Full article
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16 pages, 1614 KB  
Article
Catheter Duration Threshold and Risk Factors for Central Line-Associated Bloodstream Infections in a Tertiary ICU with Endemic Carbapenem Resistance: A Case–Control Study
by Enes Dalmanoğlu, Mehmet Özgür Özhan, Bülent Atik and Tülin Akarsu Ayazoğlu
Antibiotics 2026, 15(4), 407; https://doi.org/10.3390/antibiotics15040407 - 17 Apr 2026
Viewed by 154
Abstract
Background/Objectives: Central line-associated bloodstream infections (CLABSIs) remain a leading healthcare-associated infection in intensive care units (ICUs), yet independent risk factors and evidence-based catheter duration thresholds have not been defined through analytical study designs in settings with endemic multidrug-resistant organisms (MDROs). Methods: A retrospective [...] Read more.
Background/Objectives: Central line-associated bloodstream infections (CLABSIs) remain a leading healthcare-associated infection in intensive care units (ICUs), yet independent risk factors and evidence-based catheter duration thresholds have not been defined through analytical study designs in settings with endemic multidrug-resistant organisms (MDROs). Methods: A retrospective case–control study was conducted in the ICU of a tertiary teaching university hospital in western Türkiye (January 2019–December 2024). Cases (n = 74) were patients with confirmed CLABSIs per CDC/NHSN criteria; controls (n = 148) were randomly selected central venous catheter (CVC)-bearing patients without CLABSIs. A reduced multivariate logistic regression model (seven variables; events-per-variable ratio 10.6) identified independent risk factors. Results: In multivariate analysis, catheter duration (adjusted OR: 1.19 per day; 95% CI: 1.13–1.24; p < 0.001), renal replacement therapy (aOR: 3.66; 95% CI: 1.68–7.95; p = 0.001), vasopressor support (aOR: 3.04; 95% CI: 1.50–6.17; p = 0.002), APACHE-II score (aOR: 1.07 per point; 95% CI: 1.02–1.11; p = 0.002), lower Glasgow Coma Scale (aOR: 0.86 per point; 95% CI: 0.78–0.94; p = 0.002), mechanical ventilation (aOR: 2.48; 95% CI: 1.24–4.95; p = 0.010), and total parenteral nutrition (aOR: 2.33; 95% CI: 1.12–4.86; p = 0.024) were independently associated with CLABSI. The model demonstrated good discrimination (C-statistic: 0.864) and calibration (Hosmer–Lemeshow p = 0.425). Kaplan–Meier analysis showed CLABSI-free survival declining from 98.9% at day 7 to 42.9% at day 21 (log-rank p < 0.001); these within-study estimates reflect relative risk patterns given the artificial 1:2 case-to-control ratio. Receiver operating characteristic (ROC) analysis identified day 13 as an exploratory optimal cutoff (AUC: 0.818; 95% CI: 0.762–0.874; sensitivity: 77.0%; specificity: 74.3%). CLABSI-attributable ICU mortality was 20.3% (47.3% vs. 27.0%; p = 0.004). Late-onset CLABSIs (>10 days) were dominated by Gram-negative pathogens (68.3%) versus 35.7% in early-onset infections (Fisher’s exact p = 0.012), with Acinetobacter baumannii as the predominant organism (27.0%; 83.3% carbapenem-resistant). Conclusions: Each additional catheter-day is independently associated with a 19% increment in CLABSI odds, with an exploratory critical threshold at day 13 beyond which enhanced surveillance measures should be considered, pending external validation. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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14 pages, 576 KB  
Article
Oligoprogression During First-Line Treatment of Metastatic Hormone-Sensitive Prostate Cancer: Comparative Outcomes of Metastasis-Directed Radiotherapy and Systemic Treatment Change
by Murat Günaltılı, Murad Guliyev, Zeliha Birsin, Emir Çerme, Vali Aliyev, Hamza Abbasov, Selin Cebeci, Seda Jeral, Ebru Çiçek, Süheyla Atak, Halil Cumhur Yıldırım, Nebi Serkan Demirci, Fazilet Öner Dinçbaş and Özkan Alan
J. Clin. Med. 2026, 15(8), 3067; https://doi.org/10.3390/jcm15083067 - 17 Apr 2026
Viewed by 103
Abstract
Background/Objectives: We evaluated the clinical outcomes of two commonly used approaches for managing oligoprogression arising during first-line therapy for metastatic hormone-sensitive prostate cancer (mHSPC): metastasis-directed radiotherapy (RT) with continuation of the ongoing systemic regimen and immediate transition to another systemic treatment. Methods: A [...] Read more.
Background/Objectives: We evaluated the clinical outcomes of two commonly used approaches for managing oligoprogression arising during first-line therapy for metastatic hormone-sensitive prostate cancer (mHSPC): metastasis-directed radiotherapy (RT) with continuation of the ongoing systemic regimen and immediate transition to another systemic treatment. Methods: A total of 81 patients with mHSPC who experienced radiologically confirmed oligoprogression during first-line systemic therapy were retrospectively evaluated. Oligoprogression was defined as progression involving three or fewer metastatic sites. Patients were categorized into an RT group (metastasis-directed RT with continuation of the same regimen) or a treatment-change group (immediate switch in systemic therapy without RT). Post-oligoprogression radiologic progression-free survival (rPFS) and overall survival (OS) were evaluated using Kaplan–Meier estimates and Cox proportional hazards models. Results: Thirty-one patients received metastasis-directed RT, whereas fifty underwent a change in systemic therapy. The median post-oligoprogression rPFS was 25.8 months (95% CI, 16.3–35.2) in the entire cohort and did not differ significantly between the treatment-change (26.8 months) and RT groups (22.7 months; p = 0.828). The median OS was 42.6 months overall, with comparable outcomes between the treatment-change (42.6 months) and RT groups (52.4 months; p = 0.452). Conclusions: In patients with mHSPC who developed oligoprogression during first-line systemic therapy, metastasis-directed RT with continuation of the same regimen and immediate change in systemic treatment were associated with comparable post-oligoprogression outcomes in our cohort. These findings suggest that both strategies may be feasible in selected patients. Prospective studies may help clarify which patients are more likely to benefit from each strategy. Full article
(This article belongs to the Section Oncology)
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19 pages, 1986 KB  
Article
Real-World Outcomes of Palbociclib with Endocrine Therapy in HR+/HER2− Metastatic Breast Cancer: A Retrospective Study from Saudi Arabia
by Abdalrhman H. Alanizi, Sarah N. Al-Shaiban, Reema Alotaibi, Reem Qubaiban, Esra’a Khader, Ahmed S. Alanazi, Hatoon Bakhribah, Nawal Alsubaie, Amani S. Alrossies, Sireen Abdul Rahim Shilbayeh and Ammena Y. Binsaleh
Cancers 2026, 18(8), 1270; https://doi.org/10.3390/cancers18081270 - 16 Apr 2026
Viewed by 271
Abstract
Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control [...] Read more.
Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice. Full article
(This article belongs to the Section Cancer Metastasis)
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27 pages, 1456 KB  
Article
Multiple Dental Agenesis with an Impacted Maxillary Canine in an Early Medieval Dog (Canis lupus familiaris) from Wolin, Poland—A Case Study
by Piotr Baranowski, Katarzyna Grocholewicz and Aleksandra Gawlikowska-Sroka
Animals 2026, 16(8), 1219; https://doi.org/10.3390/ani16081219 - 16 Apr 2026
Viewed by 113
Abstract
Dental developmental anomalies are well documented in clinical veterinary medicine but remain rarely reported in archeological dogs. This study presents a radiologically confirmed case of an unerupted left maxillary canine associated with the absence of an alveolus for the left maxillary first molar [...] Read more.
Dental developmental anomalies are well documented in clinical veterinary medicine but remain rarely reported in archeological dogs. This study presents a radiologically confirmed case of an unerupted left maxillary canine associated with the absence of an alveolus for the left maxillary first molar and incisors in a dog skull from early medieval Wolin. This study aimed to determine whether the observed absence of teeth resulted from congenital agenesis, developmental arrest, ante-mortem loss, or post-depositional processes. Radiographic examination revealed a fully formed but unerupted canine, while the M1 region exhibited a smooth bony surface without reactive remodeling, periapical radiolucencies, or signs of ante-mortem tooth loss. Differential diagnosis did not support canine agenesis, ante-mortem loss, or taphonomic damage as primary explanations. The findings most strongly support a congenital or very early developmental origin of the observed alterations. The estimated age of the individual (7–10 years) and the absence of secondary pathological changes suggest that these anomalies did not significantly impair masticatory function. Owing to the single-case nature of the material, broader population-level inferences cannot be made. This case underscores the methodological importance of radiographic imaging in archeological dental research and suggests that alveolar absence should not be automatically equated with impaired survival or poor health in this individual. Full article
(This article belongs to the Section Companion Animals)
16 pages, 862 KB  
Article
Characteristics and Clinical Outcomes of BRCA Germline Mutation Carriers with Advanced Breast Cancer Treated with PARP (Poly ADP-Ribose Polymerase) Inhibitors: A Single-Institution Experience
by Fatma Nihan Akkoc Mustafayev, Elena Fountzilas, Mark F. Munsell, Rachel M. Layman, Clinton Yam, Angelica M. Gutierrez, Constance T. Albarracin, Zamal Ahmed, Katharina Schlacher, John A. Tainer and Banu K. Arun
Cancers 2026, 18(8), 1258; https://doi.org/10.3390/cancers18081258 - 16 Apr 2026
Viewed by 226
Abstract
Background/Objectives: Several trials have highlighted the importance of PARP inhibitors (PARPi) in the treatment of BRCA-associated breast cancers (BC), initiating changes in practice. However, data on the real-life outcomes of PARPi therapy is limited. In this study, we characterized the clinical [...] Read more.
Background/Objectives: Several trials have highlighted the importance of PARP inhibitors (PARPi) in the treatment of BRCA-associated breast cancers (BC), initiating changes in practice. However, data on the real-life outcomes of PARPi therapy is limited. In this study, we characterized the clinical characteristics and outcomes of patients with advanced BC and germline BRCA pathogenic variants (PVs) who received PARPi therapy. Methods: We conducted a retrospective single-institution cohort study of patients with advanced BC and germline BRCA1/2 PVs treated with PARPi. Outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using Kaplan–Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: Of the 107 patients treated with PARPi, 48 (44.9%) and 59 (55.1%) had BRCA1 and BRCA2 PVs, respectively. Ninety-seven patients (90.7%) had invasive ductal carcinoma and 42 (39.3%) had triple-negative BC. Nineteen (17.8%) patients had de novo metastatic BC. Sixty-two (57.9%) patients received at least one line of systemic therapy before PARPi; 24 (22.4%) patients received prior platinum. ORR was 62.6%, and the median duration of response (DoR) was 7 months (range, 2.1–96.2). The median PFS was 9 months (95% CI, 6.9–10.5) and median OS was 25.8 months (95% CI, 18.7–31.5). In multivariable models for PFS, bone metastases (HR = 2.25; 95% CI, 1.40–3.61; p = 0.0008) and lung metastases (HR = 2.40; 95% CI, 1.45–3.98; p = 0.0007) were independently associated with increased risk of progression or death. In multivariable models for OS, brain metastases (HR = 3.54; 95% CI, 1.59–7.90; p = 0.0020), bone metastases (HR = 2.22; 95% CI, 1.27–3.88; p = 0.0050), and lung metastases (HR = 2.38; 95% CI, 1.38–4.11; p = 0.0018), were independently associated with increased risk of death. Conclusions: The clinical outcomes of our real-world patients are similar to those reported in previous clinical trials. In addition, metastatic site distribution was independently prognostic for survival outcomes and may support baseline risk stratification at the time of PARPi initiation. Further studies of predictive markers of response and resistance, as well as sequencing with platinums and combinations with other targeted agents, are needed to optimize the benefits of PARPi in this patient population. Full article
(This article belongs to the Section Clinical Research of Cancer)
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37 pages, 1793 KB  
Systematic Review
The Role of Artificial Intelligence in Prognosis, Recurrence Prediction, and Treatment Outcomes in Laryngeal Cancer: A Systematic Review
by Hadi Afandi Al-Hakami, Ismail A. Abdullah, Nora S. Almutairi, Rimaz R. Aldawsari, Ghadah Ali Alluqmani, Halah Ahmed Fallatah, Yara Saud Alsulami, Elyas Mohammed Alasiri, Rahaf D. Alsufyani, Raghad Ayman Alorabi and Reffal Mohammad Aldainiy
Cancers 2026, 18(8), 1257; https://doi.org/10.3390/cancers18081257 - 16 Apr 2026
Viewed by 270
Abstract
Background: Laryngeal cancer (LC), a common subtype of head and neck cancers (HNC), is most frequently represented by laryngeal squamous cell carcinoma (LSCC). Prognosis largely depends on early detection; however, traditional prognostic tools, including tumor-node-metastasis (TNM) staging, often show limited predictive accuracy. Artificial [...] Read more.
Background: Laryngeal cancer (LC), a common subtype of head and neck cancers (HNC), is most frequently represented by laryngeal squamous cell carcinoma (LSCC). Prognosis largely depends on early detection; however, traditional prognostic tools, including tumor-node-metastasis (TNM) staging, often show limited predictive accuracy. Artificial intelligence (AI), including machine learning (ML), natural language processing, and deep learning (DL), has emerged as a promising approach to improving cancer diagnosis, prognosis, and treatment planning by analyzing clinical data and medical imaging. Objective: This systematic review assesses the role of AI in prognosis, recurrence prediction, and treatment outcomes in LC. Methods: PubMed, MEDLINE, Scopus, Web of Science, IEEE Xplore, and ScienceDirect were searched up to January 2025. A total of 1062 records were identified; after title/abstract screening and full-text assessment, 29 studies were included. Eligible studies involved adult patients with LC and applied AI to diagnose, prognose, predict recurrence, or assess treatment outcomes using human datasets. Study quality and risk of bias were evaluated using the QUADAS-2 and QUIPS. Results: The 29 included studies were mostly retrospective, with sample sizes ranging from 10 to 63,000 patients. Most focused on LSCC, with a higher prevalence in males. The studies utilized various AI techniques, including deep learning models such as convolutional neural networks (CNNs) and DeepSurv, as well as ML algorithms like random survival forest, gradient boosting machines, random forest, k-nearest neighbors, naïve Bayes, and decision trees. AI models demonstrated strong prognostic performance, surpassing Cox regression and TNM staging in predicting survival and recurrence. Several studies reported outcomes related to treatment, such as chemotherapy response, occult lymph node metastasis, and the need for salvage surgery. Methodological quality varied, with biases related to patient selection and confounding factors. Conclusions: AI has the potential to improve prognosis estimation, recurrence prediction, and treatment outcome assessment in LC. However, although AI can be a helpful addition to clinical decision-making, more prospective studies, external validation, and standardized evaluation are necessary before these technologies can be confidently adopted in everyday clinical practice. Full article
(This article belongs to the Topic Machine Learning and Deep Learning in Medical Imaging)
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14 pages, 375 KB  
Article
Dietary Lead Exposure in Mealworm Larvae (Tenebrio molitor) and Its Implications for the Safety of Edible Insects
by Konrad Matyja, Justyna Rybak, Beata Hanus-Lorenz, Wojciech Dobicki and Przemysław Pokorny
Sustainability 2026, 18(8), 3931; https://doi.org/10.3390/su18083931 - 15 Apr 2026
Viewed by 167
Abstract
This study examined the toxicological, and bioaccumulative effects of dietary lead (Pb) on Tenebrio molitor larvae, increasingly considered for human and animal consumption within sustainable food and feed production systems. Larvae were exposed for 21 days to an oat-based diet contaminated with lead [...] Read more.
This study examined the toxicological, and bioaccumulative effects of dietary lead (Pb) on Tenebrio molitor larvae, increasingly considered for human and animal consumption within sustainable food and feed production systems. Larvae were exposed for 21 days to an oat-based diet contaminated with lead salts (125–2000 mg Pb/kg). Body mass, and Pb accumulation in the intestine, internal tissues, and cuticle were analyzed. Pb concentrations in larval compartments increased with increasing nominal Pb levels in feed, with concentrations in internal tissues and cuticle reaching 5–6 times higher than in the control. Estimated bioaccumulation factors (BAF) were below 1 in all cases, indicating no biomagnification. Despite high exposure levels, no significant effects on larval survival or biomass gain were observed. These findings indicate that growth-related parameters are not sensitive indicators of Pb exposure. At the same time, substantial Pb accumulation occurred, particularly in the gut and cuticle, highlighting a risk of “hidden” contamination in insect-based production systems. The results emphasize the need for substrate monitoring and the inclusion of sensitive chemical indicators in food safety risk assessment. Full article
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23 pages, 4772 KB  
Systematic Review
Liver Transplantation as a Salvage Therapy Option in Colorectal Liver Metastases: Feasibility, Oncologic Outcomes, and Survival After Failure of Conventional Therapy—A Systematic Review and Meta-Analysis
by Faiza Hashim Soomro, Tehreem Fatima Kazmi, Mehwish Ansar, Nadia Gulnaz, Rabia Arshad and Gulla Aiste
Cancers 2026, 18(8), 1254; https://doi.org/10.3390/cancers18081254 - 15 Apr 2026
Viewed by 250
Abstract
Introduction: Liver transplantation has re-emerged as a potential therapeutic option for patients with unresectable colorectal liver metastases after failure of standard treatments. This systematic review and meta-analysis evaluated survival outcomes, recurrence patterns, and prognostic factors associated with this approach. Materials and Methods: A [...] Read more.
Introduction: Liver transplantation has re-emerged as a potential therapeutic option for patients with unresectable colorectal liver metastases after failure of standard treatments. This systematic review and meta-analysis evaluated survival outcomes, recurrence patterns, and prognostic factors associated with this approach. Materials and Methods: A systematic review was conducted according to PRISMA 2020 guidelines and registered in PROSPERO. Electronic databases were searched for studies published between November 2015 and November 2025, that assessed liver transplantation in the context of unresectable colorectal liver metastases. Random-effect meta-analyses were conducted to estimate the pooled overall survival, disease-free survival and recurrence rates. Heterogeneity was assessed using I2 statistics. Results: Twenty-three studies involving patients with unresectable liver-only colorectal metastases were included. Pooled overall survival after liver transplantation was 96.6% at 1 year (95% CI 93.9–99.4; I2 = 44.3%), 73.4% at 3 years (95% CI 62.9–83.9; I2 = 95.4%), and 49.4% at 5 years (95% CI 35.4–63.3; I2 = 90.5%). Ten-year overall survival was approximately 27%. The pooled recurrence rate was 63.5% (95% CI 52.5–76.8), and the type of recurrence was mainly extrahepatic, most commonly pulmonary. Disease-free survival was 64.1% (95% CI 47.5–80.7) with substantial heterogeneity (I2 = 95.6%). Biological risk factors, including carcinoembryonic antigen levels, metabolic tumor volume, and composite risk scores, consistently influenced survival outcomes. Conclusions: In highly selected patients with unresectable colorectal liver metastases, liver transplantation is associated with favorable long-term survival despite frequent recurrence. Outcomes appear to be primarily driven by tumor biology rather than tumor burden, supporting the cautious use within specialized centers under structured selection protocols. Full article
(This article belongs to the Special Issue Colorectal Cancer Liver Metastases)
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18 pages, 2456 KB  
Article
Molecular Profiling and Survival Outcomes in Pancreatic Ductal Adenocarcinoma: A Multicenter Real-World Study from Turkey
by Selami Bayram, Bahadır Köylü, Maral Martin Mıldanoğlu, Mustafa Serkan Alemdar, Tahir Yerlikaya, Fatih Selçukbiricik, Ahmet Bilici, Ali Murat Tatli and Mustafa Ozdogan
Curr. Oncol. 2026, 33(4), 216; https://doi.org/10.3390/curroncol33040216 - 15 Apr 2026
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Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy. Next-generation sequencing (NGS) enables molecular characterization and may identify clinically actionable alterations; however, real-world multicenter data linking genomic subgroups to survival outcomes remain limited. We aimed to characterize the molecular landscape of NGS-tested [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy. Next-generation sequencing (NGS) enables molecular characterization and may identify clinically actionable alterations; however, real-world multicenter data linking genomic subgroups to survival outcomes remain limited. We aimed to characterize the molecular landscape of NGS-tested PDAC in a Turkish multicenter cohort and evaluate the association of key molecular alterations, including KRAS status and KRAS variant subgroups, with survival outcomes. Methods: We conducted a multicenter retrospective cohort study including patients with pathologically diagnosed PDAC between 2017 and 2025 who underwent tumor-based NGS in routine clinical practice. Overall survival (OS) was calculated from the date of metastasis, defined as the date of diagnosis for de novo metastatic disease and the date of first documented distant recurrence for recurrent cases. Progression-free survival (PFS) was calculated from the initiation of first-line systemic therapy for metastatic disease to progression or death. Survival was estimated using the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models were constructed for OS and PFS using clinically relevant covariates selected a priori. Results: A total of 98 patients underwent molecular profiling, and survival analyses were performed in 92 patients with available OS/PFS data. KRAS mutations were detected in 83.7% (82/98) of patients, with predominant variants G12D (47.6%), G12V (30.5%), and G12R (12.2%). TP53 mutations were present in 59.2% (58/98) of tumors, and all tumors were microsatellite stable. Tumor mutational burden data were available for 72 patients; the median TMB was 3.83 mutations/Mb, and 15.3% of evaluable tumors had a TMB ≥ 10 mutations/Mb. Excluding KRAS, clinically actionable alterations were identified in 4.1% of patients, whereas an additional 32.7% harbored potentially actionable or investigational alterations. Median OS was 14.0 months (95% CI, 11.7–16.3), and median PFS was 6.0 months (95% CI, 4.3–7.7). In unadjusted analyses, OS and PFS did not differ significantly according to KRAS mutation status (OS, p = 0.967; PFS, p = 0.652), TP53 mutation status (OS, p = 0.404; PFS, p = 0.510), or KRAS variant subgroup (OS, p = 0.332; PFS, p = 0.194). In multivariable Cox analyses, KRAS mutation status was not independently associated with OS (aHR 1.13, 95% CI 0.56–2.28; p = 0.727) or PFS (aHR 1.09, 95% CI 0.59–2.01; p = 0.780), whereas ECOG performance status remained the strongest adverse clinical factor. Conclusions: In this multicenter real-world PDAC cohort, the molecular landscape was dominated by KRAS and TP53 alterations, whereas clinically actionable non-KRAS alterations were identified in only a minority of patients. After adjustment for major clinical covariates, KRAS mutation status was not independently associated with OS or PFS. Molecular profiling may still be useful for identifying uncommon potentially targetable alterations; however, larger clinically annotated multicenter studies are needed to better define its prognostic and treatment-directing value in routine practice. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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12 pages, 1227 KB  
Article
Postoperative Day-28 Neutrophil-to-Lymphocyte Ratio as a Predictor of Early Mortality After Lung Transplantation
by Hyeon Kyeong Bae, Shihwan Chang, Ala Woo, Chanho Lee, Mindong Sung, Kyung Soo Chung, Song Yee Kim, Jin Gu Lee, Moo Suk Park, Young Sam Kim, Su Hwan Lee and Ah Young Leem
Diagnostics 2026, 16(8), 1170; https://doi.org/10.3390/diagnostics16081170 - 15 Apr 2026
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Abstract
Background/Objectives: Neutrophil-to-lymphocyte ratio (NLR) may predict outcomes after organ transplantation. This study evaluated the peri-transplant prognostic value of NLR in lung transplantation (LTx). Methods: This retrospective study included 282 LTx recipients (2012–2020). NLR measured on PODs 1, 3, 7, and 28 [...] Read more.
Background/Objectives: Neutrophil-to-lymphocyte ratio (NLR) may predict outcomes after organ transplantation. This study evaluated the peri-transplant prognostic value of NLR in lung transplantation (LTx). Methods: This retrospective study included 282 LTx recipients (2012–2020). NLR measured on PODs 1, 3, 7, and 28 predicted 6-month mortality. Generalized estimating equations analyzed serial trends. Multivariable regression and ROC analysis identified predictors for a composite model, assessing discrimination and calibration. Results: Among 282 recipients (mean age, 54.2 years; male, 65.2%; idiopathic pulmonary fibrosis, 54.3%), 24.1% died within 6 months, most commonly from infection. Median NLR increased sharply after LTx (pre-LTx, 5.4; POD 1, 23.1; POD 3, 31.2), then decreased (POD 7, 18.8; POD 28, 8.7). Non-survivors had significantly higher preoperative and postoperative NLRs, particularly on POD 28. POD 28 NLR independently predicted 6-month mortality (multivariable analysis: OR, 1.05 per unit; 95% CI, 1.02–1.07; p < 0.001), alongside age and donor lung PaO2/FiO2 (P/F) ratio. Notably, a composite model combining these variables demonstrated significantly superior discrimination (area under the curve [AUC], 0.742; p = 0.001) compared to the NLR-only model (AUC, 0.698; p < 0.05). GEE demonstrated significantly steeper post-transplant NLR decline among survivors than non-survivors after adjusting for age (p = 0.02). Patients with NLR > 9.20 at POD 28 (area under the curve, 0.698; 95% CI, 0.615–0.782; sensitivity, 71.4%; specificity, 59.8%)—showed significantly lower survival on Kaplan–Meier analysis (p < 0.001, log-rank). Conclusions: Persistent NLR elevation on POD 28 independently predicts early mortality post-LTx and may support routine post-transplant risk stratification. Full article
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