Background: Peritoneal metastasis represents an aggressive disease pattern in pancreatic ductal adenocarcinoma (PDAC), traditionally associated with poor survival and limited therapeutic options. Emerging intraperitoneal chemotherapy strategies—including hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX), and pressurized intraperitoneal aerosol chemotherapy (PIPAC)—have been investigated to improve local tumor control and survival outcomes. Methods: We systematically reviewed published studies evaluating HIPEC, NIPEC/IP-PTX, and PIPAC in PDAC, including adjuvant, cytoreductive, and palliative settings. Study characteristics, feasibility, perioperative outcomes, oncologic outcomes, and risk of bias were analyzed. Results: Across modalities, intraperitoneal treatment strategies demonstrated acceptable feasibility and safety profiles in appropriately selected patients. Adjuvant HIPEC following pancreatectomy showed reduced local–regional recurrence signals in limited cohorts. CRS + HIPEC among patients with isolated peritoneal metastases yielded encouraging multi-year survival in highly selected candidates achieving complete cytoreduction. NIPEC/IP-PTX demonstrated favorable ascites control, symptom relief, and potential conversion to resection in select patients. PIPAC was primarily used in unresectable, heavily pretreated, palliative peritoneal metastasis settings, with goals centered on disease stabilization, histologic regression, and symptom control rather than curative intent. Conclusions: Intraperitoneal chemotherapy strategies in PDAC appear feasible with signals of meaningful clinical benefit in select settings. While CRS + HIPEC may benefit carefully selected metastatic patients, NIPEC/IP-PTX and PIPAC hold value primarily in symptom control and disease stabilization. Larger prospective trials are needed to define patient selection, optimize treatment protocols, and clarify survival benefit.

Background: Osteoradionecrosis (ORN) of the jaw is a severe, progressive complication of radiation therapy for head and neck malignancies. ORN features radiologically overlaps osteomyelitis and tumor recurrence. This study analyzes jaw ORN imaging characteristics and progression and proposes an ORN CT-based grading system that builds on current ClinRAD grades. Materials and Methods: A retrospective cohort study of 35 patients with biopsy-proven or clinically diagnosed ORN following radiation therapy. Initial and follow-up imaging were assessed to evaluate the radiological evolution of ORN. The imaging findings were statistically analyzed using IBM SPSS v26, and literature comparisons were made. Results: The median onset of ORN post-radiotherapy was 27–28 months (range: 2–119 months). The most common clinical presentations included non-healing ulcers (49%), pain (34%), and discharging sinuses (31%). Mandibular involvement was predominant (51%), with focal bone alterations being more frequent (63%). CT findings at clinical suspicion of ORN included resorption (100%), erosions (100%), sclerosis (86%), and fragmentation (83%). Follow-up imaging showed increased bone erosion (77%), fragmentation (92%), and sclerosis (92%). A CT-based grading system is proposed to classify ORN progression. Conclusions: ORN follows a predictable radiological progression, beginning with trabecular resorption and cortical erosion, leading to fragmentation and sequestrum formation. The proposed grading system provides a structured approach for early diagnosis. The proposed grading system provides a structured approach for diagnosis. Larger studies of imaging analyses are required to validate these findings and refine diagnostic criteria.

Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance the solubility and stability of NPs. Acute myeloid leukemia (AML) is a poor-prognosis hematologic malignancy characterized by the clonal accumulation in the blood and bone marrow of myeloid progenitors with high proliferative capacity, survival and propagation abilities. A number of potential pathways and targets have been identified for development in AML, and include, but are not limited to, Fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenases resulting from genetic mutations, BCL2 family members, various signaling kinases and histone deacetylases, as well as tumor-associated antigens (such as CD13, CD33, P-gp). By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. However, the effective treatment of the disease remains challenging, in part due to the heterogeneity of the disease but also to the involvement of the bone marrow microenvironment and the immune system in favoring leukemic stem cell persistence. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism.

Background: Molecular classification has reshaped prognostication and treatment in endometrial carcinoma (EC). However, real-world evidence from Asian populations remains scarce. This study evaluated clinicopathologic characteristics and survival outcomes across molecular subtypes of EC in a Thai tertiary care center. Methods: This retrospective cohort included patients with histologically confirmed EC who underwent primary surgery at Chiang Mai University Hospital between 2015 and 2023, and had at least one investigation for molecular classification, including immunohistochemistry (IHC) for mismatch repair (MMR) proteins and p53, as well as POLE sequencing using the Idylla™ POLE–POLD1 Mutation Assay with confirmatory Sanger sequencing. Final molecular subtype assignment followed established hierarchical algorithms. Clinicopathologic variables were analyzed using Chi-square and logistic regression. Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan–Meier and compared using the log-rank test. Results: Among 803 EC cases diagnosed during the study period, 184 met the inclusion criteria. Of 184 patients, molecular subtypes were classified as POLE-mutated in 2.2%, dMMR in 38.6%, p53-abnormal (p53-abn) in 45.1% and NSMP (1.6%). dMMR tumors occurred predominantly in older women and exhibited mainly endometrioid histology, whereas p53-abn tumors were largely non-endometrioid and high-risk in the vast majority. In multivariate analysis, histologic type was the only independent predictor of both MMR deficiency (adjusted OR = 15.22; 95% CI 4.99–46.37; p < 0.001) and p53 abnormality (adjusted OR = 79.42; 95% CI 10.60–595.05; p = 0.003). Survival outcomes varied by molecular class: POLE-mutated tumors had excellent prognosis with no recurrence or death, dMMR tumors had intermediate outcomes, and p53-abn tumors showed the poorest PFS and OS. Overall survival differed significantly among subtypes. Conclusions: Molecular classification provides strong prognostic discrimination in EC, even with selective testing. MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management.

Background: While colorectal cancer (CRC) incidence and mortality have declined among patients aged ≥50 years (late-onset), rates are increasing in those aged <50 years (early-onset). Historically, non-Hispanic Whites (NHW) have had better 5-year survival compared with non-Hispanic Blacks (NHB), and rectal cancer has had better outcomes than colon cancer. Whether these disparities by race and tumor location are evident for both early-onset (EOCRC) and late-onset (LOCRC) CRC remains unclear. Methods: CRC cases diagnosed from 2011 to 2022 were identified from the Louisiana Tumor Registry. EOCRC was defined as diagnoses at ages 20–49 years, and LOCRC was defined as diagnoses at ages ≥50 years. Racial groups included NHW and NHB; tumor location was categorized as proximal colon, distal colon, or rectum. Cox regression was used to assess unadjusted and adjusted overall and cancer-specific survival. Results: Of 23,738 CRC patients, 10.7% were diagnosed at age <50 years. Compared to LOCRC, EOCRC patients included a higher proportion of NHB (37.5% vs. 32.6%) and rectal tumors (44.4% vs. 29.9%). NHB had worse overall survival than NHW in early-onset distal colon cancer (adjusted HR [aHR] = 1.358; 95%CI: 1.024–1.801). Conversely, NHB had better overall (aHR = 0.899; 95%CI: 0.831–0.973) and cancer-specific survival (aHR = 0.873; 95%CI: 0.793–0.960) in late-onset rectal cancer. Among EOCRC NHW, proximal tumors were associated with worse overall (aHR = 1.407; 95%CI: 1.102–1.796) and cancer-specific survival (aHR = 1.379; 95%CI: 1.057–1.799) compared with distal tumors. Conclusions: Survival differences by race and tumor subsite are observed between EOCRC and LOCRC, with NHB showing a lower hazard of death in some LOCRC subgroups. These findings highlight the need to consider the age of onset and tumor location when addressing racial disparities in CRC outcomes.

In the original publication [...]

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aimed to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified and stratified by use of a GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, lixisenatide, and albiglutide). Propensity score matching (PSM) was conducted between GLP1-RA users and non-users, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Five-year incidence of pancreatic cancer was compared between GLP-1 RA users and non-users in the matched cohort between 2015 and 2025. We then restricted the cohort to patients with CP and T2DM and repeated this analysis. Results: We identified 89,596 patients with CP, including 3183 GLP-1 RA users and 86,413 non-users. After PSM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.30–0.80, p < 0.005). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (HR 0.53, 95% CI 0.31–0.91, p < 0.05). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP, as well as the subpopulation with both CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential beneficial effect of GLP-1RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit.

Background: Accurate intraoperative assessment of sentinel lymph node (SLN) status is critical for staging and guiding surgical management in gynaecological malignancies. Frozen-section histopathology remains the gold standard, but it is time-consuming and resource-intensive. Shear-wave elastography (SWE) quantifies tissue stiffness in real time and may offer a rapid alternative. Methods: In this prospective single-centre study, 63 women (median age 62 years) undergoing primary surgery with sentinel lymph node biopsy (SLNB) for endometrial, cervical, vulvar, or early ovarian carcinoma were enrolled. A total of 172 SLNs were excised, submerged in coupling gel, and scanned ex vivo using a 9 MHz linear probe. Results: A total of 172 SLNs underwent SWE (mean 2.7 nodes/patient). Endometrial primaries accounted for 58% of nodes, mostly retrieved by robotic-assisted surgery (71.8%). Node dimensions were significantly larger in malignant lesions for sonographic (long-axis: 13.02 ± 3.31 mm vs. 10.80 ± 3.28 mm; p = 0.002) and pathological long-axis measurements (11.45 ± 2.83 mm vs. 9.75 ± 2.61 mm; p = 0.004). Mean SWE velocities were similar between groups (1.381 ± 0.307 vs. 1.343 ± 0.236 m/s; p = 0.541). Histopathology identified metastases in 18% of SLNs, comprising macrometastases (7%), micrometastases (5%), and isolated tumour cells (6%). Conclusions: Although ex vivo SWE is rapid, reproducible, and integrates seamlessly into the sterile field, stiffness measurements alone lack sufficient discriminatory power for SLN staging in gynaecological cancers. Future research should focus on three-dimensional SWE, advanced radiomic analyses, and machine-learning algorithms to improve the detection of low-volume metastatic disease.

Background/Objectives: Intensive chemotherapy is the cornerstone of lymphoma treatment but often leads to severe chemotherapy-induced thrombocytopenia (sCIT), resulting in treatment delays, reduced dose intensity, and the need for transfusions. While granulocyte colony-stimulating factors (G-CSFs) are commonly used to manage neutropenia, the use of thrombopoietic growth factors has not been adequately studied. Methods: This phase I dose-finding study evaluated the use of weekly romiplostim as prophylaxis for recurrent sCIT in patients undergoing chemotherapy for lymphoma. Eligible patients were those treated with a 21-day chemotherapy cycle who previously experienced sCIT, thus serving as their own “controls”. sCIT was defined as one of the following: (A) a platelet count (PLT) <50 × 109/L on day 1 of the subsequent cycle, leading to delay or dose reduction in chemotherapy, or (B) grade 4 thrombocytopenia (<25 × 109/L) and/or (C) platelet transfusion for bleeding. The primary endpoints were the incidence of sCIT and the rate of romiplostim-associated-adverse-events, with thromboembolic complications being an event of special interest. Results: Nine patients with sCIT requiring a PLT transfusion on the prior treatment cycle were treated across three dose schedules. The phase 2 recommended schedule was defined as a starting dose of 3–5 mcg/kg based on the baseline PLT count, with weekly adjustments for counts <150 × 109/L and >450 × 109/L. Romiplostim prevented recurrent grade 4 thrombocytopenia in 47% of the chemotherapy cycles and averted recurrent transfusion in 65% of cycles. Notably, low starting doses, as used in solid malignancies, were insufficient, leading to recurrent thrombocytopenia. Conclusions: Romiplostim was well-tolerated, with no thromboembolic events, and allowed most patients to complete their chemotherapy on schedule at full dose intensity.

Background/Objectives: Hepatocellular carcinoma (HCC) immunotherapy provides limited clinical benefits, partly due to the lack of reliable efficacy biomarkers. Radiomics, which non-invasively analyzes tumor heterogeneity, shows promising potential for predicting treatment outcomes. Methods: The present study systematically evaluated the predictive performance and methodological quality of radiomics models for assessing immunotherapy efficacy in patients with HCC. A literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library for studies published up to 21 June 2025, which developed CT- or MRI-based radiomics models to predict immunotherapy efficacy in HCC. Study quality was assessed using the radiomics quality score (RQS) and the METhodological RadiomICs Score (METRICS). Results: A total of 11 studies were included and categorized by immunotherapy regimen: ICIs alone (1/11), ICIs combined with targeted therapy (6/11), and ICIs combined with targeted therapy plus locoregional therapy (4/11). The models primarily predicted treatment response (7/11), overall survival (OS) (4/11), or progression-free survival (PFS) (4/11). In the ICI monotherapy cohort, AUC values for predicting treatment response ranged from 0.705 to 0.772. In the ICI plus targeted therapy cohorts, AUC or concordance index (C-index) values for predicting the above efficacy endpoints were 0.792–0.956, 0.63–0.77, and 0.54–0.837, respectively. In the combination therapy cohorts incorporating locoregional treatment, predictive models showed AUC or C-index values of 0.721–0.92, 0.817–0.838, and 0.59. Quality assessment revealed a median RQS of 15 (range: 11–19) and a median METRICS of 72.5% (range: 56.0–79.5%) across all studies. Conclusions: CT/MRI-based radiomics uses routine imaging to non-invasively quantify whole-tumor phenotype and heterogeneity, enabling repeatable, longitudinal assessment in hepatocellular carcinoma. Evidence suggests that it can help to identify patients likely to benefit from immunotherapy before treatment. However, clinical implementation requires standardized imaging and analysis protocols, external validation, and transparent reporting.