Achieving optimal surgical margins is critical in breast-conserving surgery (BCS) to reduce local recurrence (LR) and the need for re-excision. This meta-analysis evaluated the impact of intraoperative margin optimization strategies on key surgical and oncologic outcomes in patients who underwent BCS.

The advent of targeted therapy and immunotherapy has revolutionised the management of hepatocellular carcinoma (HCC) patients with all stages, dramatically improving their survival outcomes. Currently, radical resection is still the preferred first-line treatment for early-stage HCC, nevertheless, the surgical outcomes remain unsatisfactory due to high recurrence rate of 70% within 5 years after surgery. Moreover, up to two thirds of diagnosed HCC patients are in the advanced stages of the disease, exhibiting intrahepatic or extrahepatic metastases and vascular invasion. In recent years, the combination of surgical and other local treatments with targeted therapy and immunotherapy has dramatically improved the overall survival for HCC patients and also increased the complexity of HCC management, demanding a dynamic adaptation of the available staging-based strategies and flexible therapeutic allocation. In this review, we mainly elaborate the fundamental principles and recent advancements in the surgical management of locally advanced HCC, such as neoadjuvant, adjuvant and conversion therapy, as well as the regulatory effects of local treatments on targeted therapy and immunotherapy. Finally, the value of splenectomy for unresectable HCC patients with hypersplenism is also discussed.

Local treatment of pelvic Ewing Sarcoma (EWS) is czhallenging due to complex anatomy and potential complications. Local therapy may be deferred to maintain chemotherapy dose-intensity, but the impact of this delay on outcomes remains unclear.

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.

Anti-programed cell death protein-1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies combined with anti-vascular endothelial growth factor (VEGF) or anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies are now standard therapeutic options for patients with treatment-naïve, advanced stage, hepatocellular carcinoma. Given the observed efficacy in the advanced setting, the unmet need for therapies for intermediate stage liver cancer, and compelling preclinical rationale for combination with liver-directed therapies, such as transarterial chemoembolization, immunotherapies have quickly moved into earlier stages of the disease. Several phase 1/2 clinical trials have collectively verified the safety of immune checkpoint blockade with regional therapy for intermediate stage, liver-limited, hepatocellular carcinoma. Recently, two global, randomized, double-blind, placebo-controlled studies have demonstrated superior efficacy, based on the surogate of progession free survial, for transarterial chemoembolization plus combination immunotherapy over chemoembolization alone. In this issue of the Journal, Li and colleagues present data for an anti-PD-1 inhibitor with chemoembolization in liver-limited hepatocellular carcinoma (HCC). This study, along with the status of the field, provides the opportunity to highlight key issues for implementation of combinatorial approaches in patients with liver-limited liver cancer, which are discussed in this Commentary. Regional treatment with immune checkpoint inhibition combinations for intermediate stage disease is now rightly at the forefront of HCC drug development, though specific biologic factors, ideal patient characteristics, and optimal combinations require deeper investigation prior to routine use for all patients.

This study investigates two cases of stage IVb de novo multi-metastatic nasopharyngeal carcinoma (NPC) that responded to immunotherapy but resulted in different outcomes. Case 1 involved a multi-metastatic NPC patient (T4N3M1) with extensive bone and lymphatic metastases and severely impaired physical condition (ECOG PS 2) who showed significant tumor reduction after one cycle of immunotherapy combined with non-platinum chemotherapy, with no radiation exposure. Due to financial difficulties, the patient received intermittent immunotherapy plus chemotherapy and survived 28 months with a good quality of life. Case 2 describes a multi-metastatic NPC patient (T3N2M1) with multi-organ (bone and liver) metastases and good performance status (ECOG PS 0) who underwent standard chemotherapy, immunotherapy, and radiotherapy but experienced rapid progression and died after 21 months. Immunotherapy combined with chemotherapy remains the standard for multi-metastatic NPC patients. Patients responsive to induction chemotherapy gain survival benefits from subsequent radiotherapy. However, the advantages and disadvantages of radiotherapy for immunotherapy-sensitive multi-metastatic NPC patients are still unclear. Radiotherapy (RT) can enhance local control and promote tumor antigen release, thereby complementing immunotherapy; yet it can also damage immune cells, leading to exhaustion and resistance. Therefore, balancing RT and chemotherapy is vital for optimizing immune synergy and preventing immune exhaustion.

Squamoid morules (SM) are rare in colorectal adenomas. Submucosal pseudoinvasion in adenomas is similar to that in invasive carcinomas and needs to be differentiated, especially in the presence of mucin spillage.

Machine learning (ML) applied to radiomics has revolutionized neuro-oncological imaging, yet the diagnostic performance of ML models based specifically on ^18F-FDG PET features in glioma remains poorly characterized.

Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is an autosomal dominant tumor predisposition syndrome with germline fumarate hydratase (FH) pathogenic variants. We describe the unusual clinical presentation, morphologic, and immunohistochemical features of bilateral renal cell carcinoma (RCC) occurring in polycystic kidneys in a 15-year-old male with HLRCC.

18p deletion (18p-) syndrome is a rare chromosomal abnormality with a wide range of phenotypes. Its main clinical features are short stature, intellectual disability, and facial dysmorphism, which are rarely accompanied by autoimmune thyroid disease (ATD) or pituitary abnormalities. Herein, we report the first Chinese patient with a de novo 18p deletion who presented with ATD and non-functioning pituitary adenoma.

Perivascular epithelioid cell tumor (PEComa) of the pancreas is a rare tumor of pancreatic mesenchymal origin with malignant potential. Critical to appropriate clinical management is determining whether the tumor is benign or malignant. Because of its rarity, morphologic and histologic characteristics and limited patient follow-up of pancreatic PEComa have precluded precise definition of malignancy. However, because malignant pancreatic PEComa appears to be distinctly uncommon, further improvements characterizing its preoperative imaging features could facilitate use of diagnostic endoscopic ultrasound biopsy and perhaps ablative treatment. This paper presents a case of pancreatic PEComa treated at the Affiliated Hospital of North Sichuan Medical College and includes a systematic literature review with special emphasis on the key imaging features of pancreatic PEComa.

Cancer immunotherapy has revolutionized clinical oncology; however, the inherent complexity and heterogeneity of cancer present substantial challenges to achieving broad therapeutic efficacy. Tumor heterogeneity manifests not only among different patients but also within individual tumors, further complicating personalized treatment approaches. Single-cell sequencing technologies encompassing genomics, transcriptomics, epigenomics, proteomics, and spatial omics have significantly enhanced our ability to dissect tumor heterogeneity at single-cell resolution with multi-layered depth. These approaches have illuminated tumor biology, immune escape mechanisms, treatment resistance, and patient-specific immune response mechanisms, thereby substantially advancing precision oncology strategies. This review systematically examines recent advances in single-cell multi-omics technologies across various cancer research areas, emphasizing their transformative impacts on understanding tumor heterogeneity, immunotherapy, minimal residual disease monitoring, and neoantigen discovery. Additionally, we discuss current technical and analytical limitations and unresolved questions associated with single-cell technologies. We anticipate single-cell multi-omics technologies will become central to precision oncology, facilitating truly personalized therapeutic interventions.

Digestive system cancers-including gastric, liver, colorectal, esophageal, and pancreatic malignancies-remain leading causes of cancer death, with treatment resistance posing major challenges in advanced disease. Patient-derived cancer organoids (PDCOs), 3D mini-tumors grown from patient biopsies, have revolutionized personalized oncology by faithfully replicating tumor biology and enabling predictive drug testing for chemotherapy, radiotherapy, targeted therapy, and immunotherapy. While demonstrating good predictive accuracy, current limitations include incomplete tumor microenvironments, variable establishment rates, and lengthy processing times. Emerging technologies like AI, organ-on-chip systems, and 3D bioprinting are addressing these challenges, while clinical trials explore applications in neoadjuvant therapy and real-time treatment guidance. This Review highlights key advances in PDCO technology and its transformative potential for treatment decision-making in digestive system cancers, bridging laboratory research with clinical care to enable truly personalized therapeutic strategies tailored to individual tumor biology.

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, accounting for millions of deaths annually. Its major subtypes-lung squamous carcinoma (LUSC), lung adenocarcinoma, and small-cell LC-exhibit distinct risk factors and genetic susceptibilities, necessitating the use of subtype-specific biomarkers. Two-sample Mendelian randomization (MR) analyses were conducted using protein quantitative trait loci from the UK Biobank Pharma Proteomics Project and deCODE datasets. A robust analytical framework, including reverse MR, meta-analysis, summary-data-based MR tests, and colocalization, cisMR-cML, MR.CUE and phenotype scanning analyses were used to identify proteins associated with LC risk. We conducted a systematic review to contextualize our research findings. Follow-up analyses, including pathway enrichment, protein-protein interaction network analysis, and druggability evaluations, were used to explore the mechanisms and therapeutic potential of the identified proteins. Significant proteins were validated using population-level proteomic data from the UK Biobank (UKB). The results showed that twenty-five proteins were significantly associated with LC or its subtypes, including 15 novel findings. 60S ribosomal protein L14 (RPL14) and advanced glycosylation end-product-specific receptor (AGER) emerged as the strongest discovery, demonstrating consistent and significant associations across both MR and population-level analyses. RPL14 exhibited positive associations with overall LC risk (MR_meta: odds ratio [OR]: 2.012, 95% confidence interval [CI]: 1.297-3.119; UKB: OR: 1.509, 95% CI: 1.015-2.244). Similarly, AGER showed significant protective effects against LUSC risk (MR_meta: OR: 0.572, 95%CI: 0.368-0.889; UKB: OR: 0.366, 95% CI: 0.158-0.850). Pathway analysis revealed the involvement of these proteins in immune regulation and tumorigenesis. Among the 13 identified druggable targets, RPL14 and AGER showed therapeutic potential as approved or investigational drugs targeting these proteins. These findings offer new insights into the pathogenesis of LC and potential therapeutic targets.

Recent evidence suggests that EpCAM and CD44 could serve as diagnosis or prognosis markers in pancreatic cancer (PC). In this meta-analysis, we evaluated their associations with clinicopathologic features. Specifically, we compared immunohistochemical-positive and -negative PC patients for T stage (T3-T4 vs. T1-T2), N stage (N1 vs. N0), M stage (M1 vs. M0), tumor grade (well/moderately vs. poorly differentiated), UICC Stage (III, IV vs. I, II), and overall survival (OS). The diagnostic meta-analysis was performed analysing the pooled sensitivity and specificity and evaluating overall accuracy to indicate the diagnostic efficacy of the markers. The protocol of this systematic review and meta-analysis was registered on the PROSPERO website under the registration number of CRD42024568390. A systematic search of PubMed, Scopus, and ISI Web of Science was conducted on January 30th, 2025. The statistical analysis was performed using the Review Manager 5.4 software and R language (R package Mada and Metafor). The quality of the studies included was assessed using the Newcastle-Ottawa scale and the QUADAS-2 tool. Data from relevant studies were independently screened and extracted using Rayyan, by at least two authors. A total of 19 studies were eligible (9 studies for EpCAM, 9 studies for CD44, and 2 studies for both EpCAM and CD44), comprising a total of 1370 patients. The diagnostic meta-analysis demonstrated moderate accuracy for EpCAM (AUC, 95% CI of 0.802, 0.69-0.96). A statistically significant association was found for CD44 expression and T-status (OR = 2.04, 95%CI = 1.18-3.51), or N-stage (OR = 2.68, 95%CI = 1.86-3.85), or TNM stage (OR = 3.79, 95%CI = 2.14-6.71). CD44v6 overexpression predicted worse OS (HR = 2.33, p < 0.00001), while EpCAM + CD44 + co-expression was prognostic (HR = 2.02, p = 0.02). Heterogeneity was not observed among the studies included, but further research is warranted to better understand the clinical implications of these markers' positivity in PC diagnosis and prognosis.

This Special Article provides a comprehensive review and expert commentary on the prospective clinical implementation of artificial intelligence (AI) in the detection of prostate cancer from digital prostate biopsies, as presented in the original research by Flach et al. It contextualizes the study within broader developments in digital pathology and AI, addressing barriers to adoption and the implications for diagnostic workflows and pathology practice.

Since cancer is often linked to the aging process, the importance of cellular senescence in cancer has come under the spotlight. While senescence in cancer cells can serve as a natural barrier against cancer due to its proliferation arrest, its secretory phenotypes and alterations in the surface proteome can paradoxically promote or suppress tumor progression. Senescent cancer-associated fibroblasts, endothelial cells, and immune cells can also contribute to cancer promotion. During therapeutic interventions for cancer, not only their therapeutic effects, but also therapy-induced senescence may have an impact on cancer outcomes. Senotherapeutics, therapy targeting senescent cells, have been reported as novel cancer therapy in recent studies, and the combination of senescence induction and senotherapeutics has been increasingly recognized. Although some clinical trials of senotherapeutic drugs for cancer with or without senescence-inducible therapy are ongoing, there is as yet no satisfactory clinical application. With further research into targeting senescence in oncology, it is expected that senotherapeutics, particularly in combination with senescence-inducing therapy, will become a novel therapeutic strategy.

Pulmonary carcinoids (PCs) are rare neoplasms involving typical and atypical carcinoids (TCs and ACs), defined histologically by absent or focal necrosis and mitotic counts (<2/mm2 vs. 2-10/mm2), respectively. Although uncommon overall, TCs and ACs represent the most frequent non-hematologic malignancies in the pediatric population. However, significantly less is known about PC in AYAs, a population often overlooked or analyzed within pediatric or adult cohorts. In this critical review, we analyzed existing literature on PCs in the AYA population using a question-and-answer format, emphasizing the substantial gap in current knowledge in this field and the urgent unmet clinical need for future scientific proposals. First, we analyzed epidemiology and the data availability about the association between PCs in AYA patients and genetic syndromes that typically reach the maximal diagnostic incidence within this age group. We then reviewed the available literature about the pathologic characteristics, clinical presentation, and treatment strategies for localized and metastatic disease in PC AYA patients. According to our findings, a significant lack of age-specific evidence and the need for international collaboration and prospective, AYA-focused clinical studies were underscored. Advancing research in this area is essential to improve understanding and develop tailored, evidence-based therapeutic approaches for this peculiar population.

The treatment landscape for EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) has evolved significantly with multiple combination regimens demonstrating superiority over single agent Osimertinib over the past two years. Recent trials such as FLAURA2 and MARIPOSA have explored intensified front-line regimens, with FLAURA2 demonstrating improvement in PFS with the addition of chemotherapy to Osimertinib and MARIPOSA, showing both a PFS and OS benefit with a novel combination regimen of Amivantamab and Lazertinib. However, these regimens are associated with significantly higher toxicity to patients and pose a huge financial and logistical burden to the health care system; therefore, treatment selection must therefore be individualized, considering disease biology, patient fitness, and toxicity burden. Post-progression strategies remain challenging due to resistance mechanisms like EGFR C797S mutations and MET amplification and the lack of data post-progression on novel first-line combinations. Ongoing trials are investigating fourth-generation EGFR TKIs, MET inhibitors, antibody-drug conjugates, and bispecific antibodies in subsequent lines. While regimens like Amivantamab-Lazertinib show promise even in second-line settings, toxicity, cost, and access remain barriers. As therapeutic options expand, biomarker-driven sequencing and personalized care will be critical to optimizing long-term outcomes in EGFR-mutated mNSCLC.

Treatment of locally advanced rectal cancer (LARC), clinical stages II-III, typically involves multimodal treatment options. Over the past decade, the role of radiation therapy as a neoadjuvant treatment for LARC has evolved and is currently a part of total neoadjuvant therapy (TNT). Some recently published studies advocate for the omission of radiation therapy entirely, while others report on a non-operative approach that emphasizes the use of higher radiation therapy doses. This review aims to evaluate the latest literature on the current role of radiation therapy in the management of LARC, with a discussion of how to best select the most appropriate treatment protocol based on individual patient and tumor characteristics, comorbidities, and personal needs and preferences.