Search Results (1,404)

Cholangiocarcinoma is a rare, highly aggressive malignancy of the hepatobiliary tract with poor prognosis, often diagnosed at advanced stages when curative surgical resection is not feasible. Management increasingly relies on advanced endoscopic interventions to address malignant biliary obstruction and improve clinical outcomes. Beyond conventional biliary stenting, adjunctive endoscopic ablation therapies have emerged as promising strategies to improve both stent patency and survival. This review comprehensively examines the evolving role of radiofrequency ablation and photodynamic therapy in the treatment of unresectable cholangiocarcinoma. Radiofrequency ablation utilizes localized thermal energy to induce coagulative tumor necrosis and offers advantages including procedural simplicity, favorable safety profile, and cost-effectiveness; however, its efficacy may be limited by tumor size, location, and proximity to critical structures. In contrast, photodynamic therapy employs light-activated photosensitizers to selectively induce cytotoxicity in malignant tissue, demonstrating superior outcomes in prolonging both stent patency and overall survival across multiple studies and meta-analyses. Photodynamic therapy’s ability to treat more diffuse and peripheral lesions represents an important advantage, though its use is limited by photosensitivity reactions and shallow tissue penetration. Ultimately, endoscopic ablation therapies represent valuable adjunctive options in the multidisciplinary care of patients with unresectable cholangiocarcinoma. As technological advances continue and more comparative data emerge, optimized patient selection and individualized integration of these therapies hold potential to significantly improve outcomes in this challenging malignancy. Full article

Urologic oncological surgery increasingly makes use of robotic systems to realize precise and minimally invasive resections, convent to shorter hospital stays and faster recovery times. The dexterity gains enabled through procedures such as robot-assisted (RA) prostatectomy have helped realize significant advancements in recent years. Complementing these effects via the used of hybrid tracers that illuminate surgical targets, i.e., cancerous tissue, has helped advance the surgical decision making via enhanced visualization. A well-known example is Indocyanine green (ICG)-Technetium-99m (^99mTc)-nanocolloid, a hybrid extension of the radiopharmaceutical ^99mTc-nanocolloid. These hybrid tracers provide a direct link between preoperative imaging roadmaps and intraoperative target identification, and improve efficiency, accuracy, and confidence of the urologist in procedures such as sentinel lymph node biopsy (SLNB). Receptor-targeted hybrid tracer analogues, for e.g., prostate specific membrane antigen (PSMA), are also being explored as an extension of the ongoing efforts that use radiotracers such as ^99mTc-PSMA-I&S. Together, these efforts jointly pave the way for novel techniques in intraoperative lesion localization in other urological malignancies. This narrative review discusses the potential use of hybrid tracers in robotic oncological urology, including different imaging techniques and their applications for tumor localization for prostate, bladder, and kidney cancer. Full article

Because hepatocellular carcinoma (HCC) is a radiosensitive cancer, radiation therapy has been used for the treatment of HCC; however, external beam therapies are currently not described in most of the guidelines for the treatment of HCC. External beam therapies include photon beam therapies and particle beam therapies, which are composed of X-rays or gamma rays and beams of carbon ions or protons, respectively. The focus of this narrative review is carbon-ion radiotherapy (C-ion RT). C-ion RT is well tolerated by elderly patients with HCC and/or sarcopenic patients. In general, a single HCC greater than 30 mm is a good indication for C-ion RT in patients with Child Grade A/B or ALBI Grade 1/2. The local control rates and overall survival rates at 5 years after C-ion RT for HCCs larger than 30 mm are excellent, with fewer adverse events, such as radiation-induced liver damage. Advanced HCC with portal vein tumor thrombus is also an indication for C-ion RT in certain selected patients. C-ion RT is a promising therapeutic option for patients with HCC. Full article

Rectal cancer remains a significant clinical challenge due to its complex anatomy and the critical need to balance oncological radicality with functional preservation. Multimodal treatment strategies, including neoadjuvant therapy, advanced endoscopic techniques, and precise surgical approaches, have evolved to optimize patient outcomes. Neoadjuvant chemoradiotherapy improves resectability and local control in locally advanced tumors, while endoscopic treatment offers organ-preserving options for carefully selected early-stage cancers. Surgical resection, primarily through total mesorectal excision (TME), remains the cornerstone of curative therapy, with minimally invasive and transanal approaches enhancing precision and recovery. In advanced and recurrent cases, extended procedures such as pelvic exenteration provide potential for cure despite substantial morbidity. This review summarizes current evidence on the indications, techniques, and outcomes of neoadjuvant, endoscopic, and surgical treatments for rectal cancer, emphasizing individualized treatment planning to achieve optimal oncological and functional results. Full article

Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer therapy by reactivating immune surveillance mechanisms against tumor cells. In the context of oral squamous cell carcinoma (OSCC) and broader head and neck squamous cell carcinoma (HNSCC), agents such as pembrolizumab, durvalumab, and ipilimumab target PD-1, PD-L1, and CTLA-4, respectively. This review comprehensively examines their clinical efficacy, safety profiles, mechanisms of action, and therapeutic potential in OSCC management, with an emphasis on strategies to overcome therapeutic resistance. A systematic analysis of the literature was conducted, focusing on clinical outcomes, ongoing trials, and emerging combination therapies. Pembrolizumab has demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) in OSCC patients. Durvalumab, mainly utilized in locally advanced or recurrent disease, has shown survival benefit, particularly in combination or maintenance settings. Ipilimumab exhibits durable responses in advanced OSCC, with enhanced efficacy observed when used alongside nivolumab in dual checkpoint blockade regimens. Although both pembrolizumab and nivolumab target PD-1, they differ in clinical indications and regulatory approvals. Notably, ICIs are associated with immune-related adverse events (irAEs), requiring careful monitoring. Collectively, these agents represent promising therapeutic options in oral cancer, though future studies must prioritize the identification of predictive biomarkers and the development of optimized combination strategies to maximize therapeutic benefit while minimizing toxicity. Full article

Background/Objectives: Identification of driver gene alterations helps determine first-line treatment for non-squamous non-small cell lung cancer (NSCLC). Precise assessment of tumor cell proportion is critical for accurate detection of gene alterations. ASTRAL was a multicenter, prospective, observational study to investigate the agreement in tumor cell proportion assessments between different raters. Methods: Tissues collected in daily clinical practice from patients with advanced NSCLC were used. Raters included local pathologists, a Central Pathology Committee (CPC), and an artificial intelligence (AI) algorithm. Hematoxylin and eosin-stained slides were assessed by local pathologists, and digitized images of those slides were assessed by the CPC and the AI algorithm. The primary endpoint was agreement in assessment of tumor cell proportion between local pathologists and the CPC, as determined using the intraclass correlation coefficient (ICC). Secondary endpoints included agreement between the AI algorithm and local pathologists or the CPC. Results: Tissue samples from 204 patients were assessed. The ICC for local pathologists vs. the CPC showed poor to moderate agreement (0.588 [95% confidence interval (CI) 0.483–0.674]). The AI algorithm showed moderate agreement with the CPC (ICC 0.652 [95% CI 0.548–0.733]), and poor to moderate agreement with local pathologists (ICC 0.465 [95% CI 0.279–0.604]). Conclusions: The ICC for the AI algorithm vs. the CPC was numerically highest among the rater pairs, indicating a level of usefulness for the algorithm. Continued efforts are needed to ensure the accurate estimation of tumor cell proportion. Integration of AI algorithms in real-world practice may contribute to this. Full article

Background: Young-onset colorectal cancer (YO-CRC) has emerged as a distinct clinical entity, often presenting at advanced stages. Despite the increasing incidence, the molecular and clinical underpinnings of YO-CRC remain underexplored. This study aims to characterize the clinical and molecular features of YO-CRC and to evaluate their impact on OS. Methods: We reviewed 110 patients diagnosed with YO-CRC at our institution who underwent next-generation sequencing. Demographic, clinical, and molecular data, including age, gender, race, tumor location, cancer stage, and mutation status (KRAS, NRAS, BRAF, POLE, ERBB-2/HER2, microsatellite status), were collected by reviewing electronic medical records. For OS analysis, we focused on patients diagnosed with de novo stage IV. Cox proportional hazards regression and Kaplan–Meier survival analysis were utilized to assess the association of these factors with OS, with statistical significance determined by a p-value threshold of <0.05. Results: Among 110 patients, n = 44 (40%) presented with local disease (stage 1–3), while n = 66 (60%) presented with de novo metastatic disease at the time of diagnosis. The median age at diagnosis was 44.5 years. The cohort consisted of 64% males and 36% females, with 84% of patients identified as White. Most tumors were left-sided (77%), including the distal colon/sigmoid (44%) and rectum (33%). KRAS and BRAF mutations were present in 36% and 5.5%, respectively. ERBB-2/HER2 amplification and microsatellite instability were observed in 4.5% and 6.4%, respectively. Tumor mutation burden (TMB) was <10 in 57% of patients, with 14% having TMB > 20. CNV analysis revealed that 14% of patients had copy gains, 12% had concurrent gains/losses, and 31% had copy losses. Among 66 patients with de novo metastatic disease, 44% had died by the time of analysis, with a median overall survival (OS) of 43.6 months (95% CI, 28.7—not reached). KRAS mutations were found to be significantly associated with worse survival outcomes. Cox regression analysis reveals the prognostic significance of KRAS status, with a hazard ratio (HR) of 3.52 (95% CI: 1.59–7.76, p = 0.002), indicating a significantly higher risk of death for KRAS-mutant YO-CRC patients. Conclusions: Patients with YO-CRC are more likely to present with de novo metastatic disease and left-sided tumors with distinct molecular characteristics. KRAS mutations are a key prognostic factor in YO-CRC, highlighting the need for therapeutic interventions to improve outcomes in this high-risk group. Full article

Objective: To investigate the survival prediction probability of the nomogram from retro-EMBRACE and the T-score in patients with locally advanced cervical cancer (LACC). Materials and Methods: A total of 204 patients with LACC who underwent curative chemoradiotherapy and brachytherapy (BT) between 2010 and 2021 were included in our single-center retrospective study. Clinical records, examinations, and magnetic resonance images (MRI) before and after external beam radiotherapy (EBRT) were retrospectively reviewed to obtain information on age, tumor size, parametrial involvement, ureteral involvement, bladder invasion, uterine involvement, high-risk clinical target volume at the first brachytherapy application, lymph node involvement, vaginal involvement, recurrence, metastasis, and last follow-up. The 5-year overall survival probabilities of the patients were determined by nomogram. T-score was calculated separately at diagnosis (TS_D) and brachytherapy (TS_BT), and their effects on local recurrence-free survival, disease-free survival, and overall survival were analyzed. Results: The median age was 52 (29–89). The 5-year survival rate of the patients was calculated to be 90.18%. The median nomogram’s survival estimate for 60 months was 70.35% (20.9–87.1). The median TS_D and TS_BT were 5.5 (1–16) and 1 (0–6), respectively. According to the multivariate Cox regression models, TS_D (HR = 1.203, 95% CI 1.021–1.417, p = 0.024) was significantly associated with local recurrence-free survival. Conclusions: This study demonstrated that the nomogram’s predictions for 60-month overall survival are underestimates. Prognosis can be estimated using the TS_D, which can be easily obtained with a clinical examination and detailed MRI examination. Full article

Hydrogels are water-rich polymeric networks mimicking the body’s extracellular matrix, making them highly biocompatible and ideal for precision medicine. Their “tunable” and “smart” properties enable the precise adjustment of mechanical, chemical, and physical characteristics, allowing responses to specific stimuli such as pH or temperature. These versatile materials offer significant advantages over traditional drug delivery by facilitating targeted, localized, and on-demand therapies. Applications range from diagnostics and wound healing to tissue engineering and, notably, cancer therapy, where they deliver anti-cancer agents directly to tumors, minimizing systemic toxicity. Hydrogels’ design involves careful material selection and crosslinking techniques, which dictate properties like swelling, degradation, and porosity—all crucial for their effectiveness. The development of self-healing, tough, and bio-functional hydrogels represents a significant step forward, promising advanced biomaterials that can actively sense, react to, and engage in complex biological processes for a tailored therapeutic approach. Beyond their mechanical resilience and adaptability, these hydrogels open avenues for next-generation therapies, such as dynamic wound dressings that adapt to healing stages, injectable scaffolds that remodel with growing tissue, or smart drug delivery systems that respond to real-time biochemical cues. Full article

Background: Neoadjuvant chemotherapy (NAC) is the important and effective approach to treat locally advanced breast cancer (LABC). The prediction of response to NAC prior to start is an efficient approach to obtaining perspective about the effectiveness of treatment. The objective of this study is to design a machine learning pipeline to predict tumor response to NAC treatment for patients with LABC using the combination of clinical features and radiomics computed tomography (CT) features. Method: A total of 858 clinical and radiomics CT features were determined for 117 patients with LABC to predict the tumor response to NAC treatment. Since the number of features is greater than the number of samples, dimensionality reduction is an indispensable step. To this end, we proposed a novel hybrid feature selection to not only select top features but also optimize the classifier hyperparameters. This hybrid feature selection has two phases. In the first phase, we applied a filter-based strategy feature selection technique using matrix rank theorem to remove all dependent and redundant features. In the second phase, we applied a genetic algorithm which coupled with the SVM classifier. The genetic algorithm determined the optimum number of features and top features. Performance of the proposed technique was assessed by balanced accuracy, accuracy, area under curve (AUC), and F1-score. This is the binary classification task to predict response to NAC. We consider three models for this study including clinical features, radiomics CT features, and a combination of clinical and radiomics CT features. Results: A total of 117 patients with LABC with a mean age of 52 ± 11 were studied in this study. Of these, 82 patients with LABC were the responder group (response to NAC) and 35 were the non-response group to chemotherapy. The best performance was obtained by the combination of clinical and CT radiomics features with Accuracy = 0.88. Conclusion: The results indicate that the combination of clinical features and CT radiomic features is an effective approach to predict response to NAC treatment for patients with LABC. Full article

Immune checkpoint inhibitors (ICIs) are a key treatment for advanced non-small cell lung cancer (NSCLC), but most patients will ultimately experience disease progression due to acquired resistance to ICI. Clinically, it is relevant to differentiate between systemic progression (SP) and oligoprogression (OP). Following SP, ICI treatment is usually discontinued, while in OP, patients are preferably treated with local ablative treatment with continuation of the ICI treatment. However, with progressive disease, it remains difficult to differentiate between true OP or SP. Circulating tumor DNA (ctDNA) analysis provides an accurate real-time reflection of the tumor burden. It remains elusive if ctDNA abundance and/or dynamics can discriminate between OP and SP. Therefore, the aim of this exploratory cohort study is to evaluate whether the sequential molecular tumor profiling of ctDNA is suitable for discriminating between true OP and SP in advanced NSCLC. Patients with stage III/IV NSCLC showing progression after ≥3 months of ICI were included. OP was defined retrospectively by RECIST response ≥ 6 months after local treatment and continued ICIs. Serial plasma samples were analyzed using the AVENIO ctDNA Expanded NGS assay targeting 77 cancer-related genes. Twenty patients (6 OP, 14 SP) were included. Somatic alterations were detected in 16 patients (median 4 mutations). No significant differences in baseline ctDNA levels, changes at progression, or mutation patterns were observed between OP and SP. Although ctDNA levels generally decreased early after the start of ICI treatment, and were increased at disease progression, mutational profiles of the 77 genes using the AVENIO Expanded ctDNA panel did not distinguish OP from SP. Full article

For 40 years, Intron Retention (IR) was dismissed as splicing noise and is now recognized as a dynamic and evolutionarily conserved mechanism of post-transcriptional gene regulation. Unlike canonical splicing, which excises all introns from pre-mRNAs, IR selectively retains intronic sequences, albeit at seemingly random places; however, current research now reveals that this process is strategic in its retention. IR influences mRNA stability, localization, and translational potential. Retained introns can lead to nonsense-mediated decay, promote nuclear retention, or give rise to novel protein isoforms that contribute to expanding proteomic and transcriptomic profiles. IR is finely regulated by splice site strength, splicing regulatory elements, chromatin structure, methylation patterns, RNA polymerase II elongation rates, and the availability of co-transcriptional splicing factors. IR plays critical roles in cell-type and tissue-specific gene expression with observed patterns, particularly during neuronal, cardiac, hematopoietic, and immune development. It also functions as a molecular switch during cellular responses to environmental and physiological stressors such as hypoxia, heat shock, and infection. Dysregulated IR is increasingly associated with cancer, neurodegeneration, aging, and immune dysfunction, where it may alter protein function, suppress tumor suppressor genes, or generate immunogenic neoepitopes. Experimental and computational tools like RNA-seq, RT-PCR, IRFinder, and IntEREst have enabled transcriptome-wide detection and validation of IR events, uncovering their widespread functional roles. This review will examine current knowledge on the function, regulation, and detection of IR, and also summarize recent advances in understanding its role in both normal and pathophysiological settings. Full article

Background: Spinal metastasis is the third most common site for metastatic localization, following the lung and liver. Manual detection through imaging modalities such as CT, MRI, PET, and bone scintigraphy can be costly and inefficient. Preliminary artificial intelligence (AI) techniques and computer-aided detection (CAD) systems have attempted to improve lesion detection, segmentation, and treatment response in oncological imaging. The objective of this review is to evaluate the current applications of AI across multimodal imaging techniques in the diagnosis of spinal metastasis. Methods: Databases like PubMed, Scopus, Web of Science Advance, Cochrane, and Embase (Ovid) were searched using specific keywords like ‘spine metastases’, ‘artificial intelligence’, ‘machine learning’, ‘deep learning’, and ‘diagnosis’. The screening of studies adhered to the PRISMA guidelines. Relevant variables were extracted from each of the included articles such as the primary tumor type, cohort size, and prediction model performance metrics: area under the receiver operating curve (AUC), accuracy, sensitivity, specificity, internal validation and external validation. A random-effects meta-analysis model was used to account for variability between the studies. Quality assessment was performed using the PROBAST tool. Results: This review included 39 studies published between 2007 and 2024, encompassing a total of 6267 patients. The three most common primary tumors were lung cancer (56.4%), breast cancer (51.3%), and prostate cancer (41.0%). Four studies reported AUC values for model training, 16 for internal validation, and five for external validation. The weighted average AUCs were 0.971 (training), 0.947 (internal validation), and 0.819 (external validation). The risk of bias was the highest in the analysis domain, with 22 studies (56%) rated high risk, primarily due to inadequate external validation and overfitting. Conclusions: AI-based approaches show promise for enhancing the detection, segmentation, and characterization of spinal metastatic lesions across multiple imaging modalities. Future research should focus on developing more generalizable models through larger and more diverse training datasets, integrating clinical and imaging data, and conducting prospective validation studies to demonstrate meaningful clinical impact. Full article

Objectives: This study aimed to assess the precision of dose delivery to the target in adaptive carbon ion radiotherapy (CIRT) for locally advanced non-small cell lung cancer (LA-NSCLC) in cumulative dosimetry. Methods: Forty-six patients who received CIRT were included (64 Gy[relative biological effectiveness, RBE] in 16 fractions) with treatment plan computed tomography (CT) and weekly CT scans. Offline adaptive radiotherapy (ART) was administered if the dose distribution significantly worsened. Daily doses were calculated from weekly CTs and integrated into plan CT scans using deformable image registration. The dosimetry parameters were compared between the as-scheduled plan and adaptive replan in patients receiving ART. Survival outcomes and toxicity were compared between the ART and non-ART groups. Results: ART was implemented for 27 patients in whom adaptive replans significantly increased the median V_98% of the clinical tumor volume from 96.5% to 98.1% and D_98% from 60.5 to 62.7 Gy(RBE) compared with the as-scheduled plans (p < 0.001). The conformity and uniformity of the dose distribution improved (p < 0.001), with no significant differences in the doses to normal tissues (lungs, heart, esophagus, and spinal cord) from the as-scheduled plans (p > 0.05). The ART and non-ART groups demonstrated comparable local control, progression-free survival, and overall survival (p > 0.05). No grade 3 or higher radiation-related toxicities were observed. Conclusions: ART enhanced target dose coverage while maintaining acceptable normal tissue exposure, supporting weekly CT monitoring integration during CIRT for the timely intervention for anatomical variations, ensuring precise dose delivery in LA-NSCLC. Full article

The optimal sequencing of chemotherapy in locally advanced gastric cancer (LAGC) remains controversial. This study aimed to compare survival outcomes between adjuvant (ACT) and neoadjuvant (NACT) chemotherapy and to identify clinicopathological factors associated with progression-free survival (PFS) and overall survival (OS) in a real-world setting. Methods: We retrospectively analyzed 103 patients with non-metastatic gastric cancer treated between 2014 and 2024. Patients were categorized into ACT (n = 56) and NACT (n = 47) groups. Kaplan–Meier and Cox regression analyses were used to assess survival outcomes and prognostic factors. Results: The NACT group was younger and had more proximal tumors. Median OS was 48.7 months in the ACT group versus 17.7 months in the NACT group (p = 0.048). Median PFS was not reached in the ACT group and was 15.6 months in the NACT group (p = 0.008). Negative surgical margin status was independently associated with improved survival, whereas age was an independent negative prognostic factor for OS. No significant associations were found between OS or PFS and histologic subtype, lymphovascular invasion, perineural invasion, gender, D2 dissection, or type of surgery. Notably, 21% of NACT patients did not proceed to surgery due to progression, treatment intolerance, or refusal. Conclusion: Although ACT was associated with longer PFS and OS in this cohort, these differences are most likely explained by baseline imbalances, patient selection factors, and survivorship bias rather than the timing of chemotherapy itself. These findings highlight the importance of careful patient selection for NACT and underscore the need for prospective, randomized studies to define optimal sequencing strategies in LAGC. Our study contributes descriptive, real-world data rather than definitive evidence of treatment superiority. Full article