Search Results (16,419)

Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article

Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article

Background: In high-risk and frail patients with multivessel coronary artery disease (MV CAD), guidelines indicated complete revascularization with or without the use of cardiopulmonary bypass (CPB) bears a high morbidity and mortality risk. In cases where catheter interventions were deemed unsuitable and conventional coronary artery bypass grafting (CABG) posed an unacceptable perioperative risk, patients were scheduled for minimally invasive direct coronary artery bypass (MIDCAB) grafting or minimally invasive multivessel coronary artery bypass grafting (MICS-CABG). We called this approach “palliative revascularization.” This study assesses the safety and impact of palliative revascularization on clinical outcomes and overall survival. Methods: A consecutive series of 57 patients undergoing MIDCAB or MICS-CABG as a palliative surgery between 2008 and 2018 was included. The decision for palliative surgery was met in heart team after carefully assessing each case. The patients underwent single or double-vessel revascularization using the left internal thoracic artery and rarely radial artery/saphenous vein segments, both endoscopically harvested. Inpatient data could be completed for all 57 patients. The mean follow-up interval was 4.2 ± 3.7 years, with a follow-up rate of 91.2%. Results: Mean patient age was 79.7 ± 7.4 years. Overall, 46 patients (80.7%) were male, 26 (45.6%) had a history of atrial fibrillation and 25 (43.9%) of chronic kidney disease. In total, 13 patients exhibited a moderate EuroSCORE II, while 27 were classified as high risk, with a EuroSCORE II exceeding 5%. Additionally, 40 patients (70.2%) presented with three-vessel disease, 17 (29.8%) suffered an acute myocardial infarction within three weeks prior to surgery and 50.9% presented an impaired ejection fraction. There were 48 MIDCAB and nine MICS CABG with no conversions either to sternotomy or to CPB. Eight cases were planned as hybrid procedures and only 15 patients (26.3%) were completely revascularized. During the first 30 days, four patients (7%) died. A myocardial infarction occurred in only one case, no patient necessitated immediate reoperation. The one-, three- and five-year survival rates were 83%, 67% and 61%, respectively. Conclusions: MIDCAB and MICS CABG can be successfully conducted as less invasive palliative surgery in high-risk multimorbid patients with MV CAD. The early and mid-term results were better than predicted. A higher rate of hybrid procedures could improve long-term outcome in selected cases. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Objectives: Early death after trauma has been described several times. Little is known about it after traumatic brain injury (TBI) and decompressive craniectomy (DC). The aim of this study was to characterize patients who die after a TBI and DC during their in-hospital stay. Methods: In a subgroup analysis of a retrospective, multicenter, and observational study, non-survivors from in-hospital stays treated for severe TBI and DC were included. Propensity score matching (PSM) was used. Results: A total of 223 patients with severe TBI were treated with DC, and there were 65 (29.1%) patients who did not survive. Of these, 22 (33.8%) died within the first 24 h. Non-survivors were older (p = 0.010), and pupillomotor dysfunction and a higher heart rate on admission were more common (p < 0.001). PSM patients for overall survival (41, 18.4%) differed in mean heart rate from the deceased (p = 0.030). In a multivariate model, age (OR: 1.045, p = 0.013, CI95%: 1.010 to 1.082), Quick value (OR: 0.965, p = 0.049, CI95%: 0.931 to 1.000), and heart rate (OR: 1.099, p = 0.030, CI95%: 1.009 to 1.197) were confirmed as predictive factors. Conclusions: Even after DC, known factors, such as chronological age and comorbidities, have a significant influence on mortality. The value of DC in an aging society for a particular severity of TBI should be further assessed on the basis of prospective studies. Full article

The present study evaluated the effect of adding 0% (control), 30%, 40% and 50% SPMs (small-peptide chelating trace minerals) to replace ITMs (inorganic trace minerals) in the diets of Litopenaeus vannamei; 720 shrimp were randomly assigned to four treatments (six replicates per group, 30 shrimp per replicate) in a 42-day feeding trial. There were no significant differences (p > 0.05) among the control, 40% SPM and 50% SPM groups in terms of the survival rate, weight gain rate, specific growth rate, hepatosomatic index, condition factor, feed intake, feed conversion ratio, or protein efficiency ratio; however, protein efficiency ratio was reduced in the 30% SPM group (p < 0.05). Glucose, triglyceride, and aspartate aminotransferase levels in the hemolymph of the 30% SPM group were significantly increased (p < 0.05), while the glucose and aspartate aminotransferase levels were also significantly increased in the 40% SPM group (p < 0.05). In the 50% SPM group, the glucose and triglyceride levels were also significantly increased (p < 0.05). Hepatopancreatic alkaline phosphatase activity was elevated at 40% SPM, and alkaline phosphatase, acid phosphatase, glutathione peroxidase, and total antioxidant capacity activities were significantly increased in the 50% SPM group (p < 0.05). The moisture content and drip loss were reduced in both the 40% and 50% SPM groups (p < 0.05). Therefore, replacing 40–50% ITMs with SPMs can maintain growth performance while enhancing physiological functions. In conclusion, the results of this study demonstrate that the incorporation of 30–50% SPMs into one’s diet constitutes a viable alternative to 100% ITMs. Full article

Background: Papillary thyroid microcarcinoma (PTMC) is associated with certain features that carry an increased risk of local recurrence, underscoring the importance of preoperative risk assessment. This study investigated the clinicopathological factors associated with high-risk lymph node metastasis (HRLNM) and patient outcomes. HRLNM is defined as ≥5 metastatic lymph nodes and/or lateral neck metastasis. Methods: We conducted a retrospective review of 985 patients with PTMC who underwent thyroidectomy at the Kaohsiung Chang Gung Memorial Hospital from 2013 to 2022. Results: Among the 985 patients, 100 (10.2%) had lymph node metastasis (LNM), and 27% of these were classified as having HRLNM. Male sex (OR 3.61, p = 0.04) and extranodal extension (OR 3.76, p = 0.043) were independent predictors of HRLNM. Patients with LNM exhibited lower rates of excellent treatment response (75% vs. 87%, p = 0.001), higher recurrence rates (9.0% vs. 0.6%, p = 0.001), and an increased risk of distant metastasis (2.0% vs. 0%). Recurrence-free survival (RFS) was significantly shorter in patients with LNM (120.9 vs. 198.6 months, p < 0.001). Although HRLNM showed a trend toward reduced RFS (113.5 vs. 124.6 months, p = 0.177), its impact on long-term survival remains uncertain. Conclusions: Male sex and extranodal extension were significant risk factors for HRLNM in patients with PTMC. These findings highlight the need for individualized risk stratification to guide treatment strategies and improve patient outcomes. Full article

The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, its role in R-PDAC is less clearly defined. Additionally, the role of immunotherapy in PDAC is still being explored, with ongoing trials investigating new combinations to overcome the tumor’s immune-resistant microenvironment. This article provides a comprehensive narrative review of the current evidence comparing NAT with upfront surgery in pancreatic cancer management, focusing on randomized controlled trials and meta-analyses that assess outcomes in R-PDAC and BR-PDAC. The review aims to determine whether NAT offers a significant survival advantage over traditional post-operative strategies and to clarify which clinical scenarios may benefit most from NAT. The literature was identified through a systematic search of PubMed, Scopus, and Google Scholar databases up to March 2025. Article selection adhered to the PRISMA guidelines. Our review of existing evidence supports NAT as the standard of care for BR-PDAC. Meanwhile, management of R-PDAC should be tailored individually, guided by risk stratification that considers both clinical parameters and molecular features. Immunotherapy and targeted therapies are still in early research phases, and their further integration as NAT remains controversial. Full article

Grafting serves as a crucial propagation technique for superior Camellia oleifera varieties, where rootstock–scion compatibility significantly determines survival and growth performance. To systematically evaluate grafting compatibility in this economically important woody oil crop, we examined 15 rootstock–scion combinations using ‘Xianglin 210’ as the scion, assessing growth traits and conducting physiological assays (enzymatic activities of SOD and POD and levels of ROS and IAA) at multiple timepoints (0–32 days post-grafting). The results demonstrated that Comb. 4 (Xianglin 27 rootstock) exhibited superior compatibility, characterized by systemic antioxidant activation (peaking at 4–8 DPG), rapid auxin accumulation (4 DPG), and efficient sugar allocation. Transcriptome sequencing and WGCNA analysis identified 3781 differentially expressed genes, with notable enrichment in stress response pathways (Hsp70, DnaJ) and auxin biosynthesis (YUCCA), while also revealing key hub genes (FKBP19) associated with graft-healing efficiency. These findings establish that successful grafting in C. oleifera depends on coordinated rapid redox regulation, auxin-mediated cell proliferation, and metabolic reprogramming, with Comb. 4 emerging as the optimal rootstock choice. The identified molecular markers not only advance our understanding of grafting mechanisms in woody plants but also provide valuable targets for future breeding programs aimed at improving grafting success rates in this important oil crop. Full article

Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

Albumin-binding agents enhance tumor uptake of radiopharmaceuticals targeting prostate-specific membrane antigens (PSMAs) in radiotherapy. We synthesized PSMA-NARI-56, a molecule with both PSMA targeting activity and albumin-binding moiety, labeled with ¹⁷⁷Lu as the therapeutic agent. The aim of this study was to determine the specific binding of ¹⁷⁷Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of ¹⁷⁷Lu-PSMA-NARI-56 viability of PSMA-positive cell (LNCaP) was evaluated. Biodistribution and endoradiotherapy studies were utilized to determine the distribution, targeting, and anti-tumor efficacy by tumor-bearing mice identified by ¹¹¹In-PSMA-NARI-56. ¹⁷⁷Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of ¹⁷⁷Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), ¹⁷⁷Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to ¹⁷⁷Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of ¹⁷⁷Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, ¹⁷⁷Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by ¹¹¹In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to ¹⁷⁷Lu-PSMA-617. Full article

Skin cancer is the most common cancer worldwide, for which early detection is crucial to improve survival rates. Visual inspection and biopsies have limitations, including being error-prone, costly, and time-consuming. Although several deep learning models have been developed, they demonstrate significant limitations. An interpretable and improved transfer learning model for binary skin cancer classification is proposed in this research, which uses the last convolutional block of VGG16 as the feature extractor. The methodology focuses on addressing the existing limitations in skin cancer classification, to support dermatologists and potentially saving lives through advanced, reliable, and accessible AI-driven diagnostic tools. Explainable AI is incorporated for the visualization and explanation of classifications. Multiple optimization techniques are applied to avoid overfitting, ensure stable training, and enhance the classification accuracy of dermoscopic images into benign and malignant classes. The proposed model shows 90.91% classification accuracy, which is better than state-of-the-art models and established approaches in skin cancer classification. An interactive desktop application integrating the model is developed, enabling real-time preliminary screening with offline access. Full article

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article