The treatment of Cutaneous Squamous Cell Carcinoma (CSCC) has undergone significant changes with the introduction of Immune Checkpoint Inhibitors (ICIs). While promising results have been observed, their efficacy remains limited to a subset of patients. Soluble immune checkpoint molecules, Interferon-gamma (IFN-γ), and cell-free DNA (cfDNA) could serve as potential biomarkers, particularly in ICI-based therapies.

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.

Melanoma, a highly aggressive and immunogenic skin cancer, often develops resistance to immunotherapy due to the immunosuppressive tumor microenvironment (TME). Although PD-1/PD-L1 inhibitors have significantly improved treatment outcomes, 30%-40% of patients exhibit no response or develop resistance. Mechanisms such as T-cell exhaustion within the TME limit therapeutic efficacy, necessitating the exploration of novel strategies to enhance immune responses.

Current consensus guidelines lack robust evidence to advocate the optimal treatment approach for locoregional upper esophageal squamous cell carcinoma (L-UESCC). The purpose of this study was to conduct an in-depth investigation of the treatment patterns, outcomes, and prognostic factors among patients with L-UESCC.

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.

Acral melanoma (AM) is the predominant subtype of melanoma in Asians. Early detection and prevention can significantly improve patient outcomes; however, there is a lack of effective early biomarkers for predicting AM metastasis. Here, we employed single-cell and spatial transcriptomics analyses to investigate early microsatellite lesions of AM and identify biomarkers of invasiveness in these lesions. Our results characterize a highly immunosuppressive microenvironment and metabolic process shifts in early AM microsatellite lesions that promote the metastatic potential. The transcription factor SOX6 is overexpressed in microsatellite lesions and marks a population of highly invasive melanoma cells. The pro-invasive role of overexpressed SOX6 was validated in vivo and in vitro, including its ability to enhance tumor invasion by upregulating cellular glycolysis, disrupt fatty acid transport, and increase intracellular phosphatidylcholine content. This study suggests that SOX6-overexpressing melanoma cells are the main driver subpopulation promoting early invasion of AM and establishes SOX6 and fatty acid transport processes as biomarkers and potential therapeutic targets for early melanoma metastasis.

Small-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. Despite the initial chemosensitivity, survival for extensive-disease (ED) SCLC remains limited. Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have recently been redefined as the standard of care. We evaluated the efficacy of ICI combination therapy in clinical trials translated into real-world clinical practice for patients with ED-SCLC.

Pathologically, intrahepatic cholangiocarcinoma (ICC) is classified into small-duct (SD) type and large-duct (LD) type, each with distinct clinicopathological characteristics. The contrast-enhanced ultrasound (CEUS) features of the two ICC types remain insufficiently explored.

Brain metastases (BrMs) frequently manifest in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), and the optimal treatment approach for these individuals remains controversial. This study aimed to evaluate the cost-effectiveness of adding pemetrexed-platinum chemotherapy to first-line gefitinib in EGFR-mutant NSCLC patients with BrMs, considering the perspective of the Chinese healthcare system.

Nutritional risk assessment indices impact disease prognosis, yet their prognostic roles in preoperative digestive system tumor (DST) patients remain unclear.

Pathological diagnosis is important for the treatment of deep suprahyoid head and neck lesions, and tissue sampling needs to balance minimal invasiveness and accuracy. The purpose of this study was to evaluate diagnostic accuracy and factors associated with diagnostic failure of core needle biopsy (CNB) with CT-guided in deep suprahyoid head and neck lesions.

Angiosarcoma (AS), a rare and highly malignant tumour, can manifest spontaneously (primary AS, pAS) or secondary to previous radiation, exposure to chemical agents or Stewart-Treves syndrome (secondary AS, sAS). The aim of this study was to characterise the clinical presentation, management, treatment and outcome-including local recurrence, metastasis and overall survival-among patients diagnosed with AS and treated at Sahlgrenska University Hospital, Gothenburg, Sweden.

Conversion immunochemotherapy may enable curative surgery in patients with initially unresectable locally advanced gastric cancer, but its response rate remains low. Little evidence has shown how to easily predict therapeutic efficacy from hematological biomarkers, apart from tissue biomarkers. This study aimed to identify predictive factors for treatment response from hematological biomarkers and propose strategies for non-responsive patients.

Gastric cancer is the fourth most common cancer globally and the leading cause of cancer-related deaths in Peru. Current synthetic treatments often fail to distinguish cancerous cells from healthy cells, resulting in severe side effects and drug resistance. This study aimed to evaluate the effects of the chloroform fraction of Dracontium spruceanum bulb (DSBCl) on cancer stem cells (CSCs) from AGS and KATO III gastric cancer cell lines, which represent primary and metastatic cancers. The methanolic extract was prepared and characterized via thin-layer chromatography to isolate the chloroform fraction. CSCs were identified via the CD44 marker and isolated via magnetic assisted cell sorting. The cytotoxic effect of DSBCl was evaluated to determine the IC50, revealing its ability to modulate CSC markers and genes associated with tumorigenesis, chemoresistance, and metastasis. In AGS CSCs, DSBCl reduced CD24 expression and downregulated the expression of genes, including ID1, BCL2L2, ABCC2, NANOG, and OCT4, while it upregulated KLF17, BAX, and KLF4. In KATO III CSCs, DSBCl increased ID1 and MYC but decreased BCL2L1 and BAX. These findings suggest that DSBCl modulates critical markers and genes in gastric CSCs, highlighting its potential for gastric cancer treatment.

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.

T-cell activation and clonal expansion are essential to effective immunotherapy responses in non-small cell lung cancer (NSCLC). The distribution of T-cell clones may offer insights into immunogenic mechanisms and imply potential prognostic and predictive information.

The RAPID-RT study is part of a large-scale research programme investigating the use of routinely collected real-world patient data to rapidly and prospectively evaluate and optimise the impact of changes in radiotherapy practice on clinical outcome, an approach often referred to as 'rapid learning'. As a proof of concept, a prospective, observational clinical study using realworld data is embedded within the programme. This study implements a new dose limit to a defined region of the heart in patients with stage I-III lung cancer treated with curative-intent radiotherapy at The Christie NHS Foundation Trust. The RAPID-RT study includes both methodological and clinical objectives. Its primary aim is to assess the feasibility and clinical acceptability of using rapid learning with real-world data to evaluate outcomes following modifications to standard-of-care radiotherapy protocols. This work has the potential to establish rapid learning as a robust, evidence-based approach for the continuous optimisation of radiotherapy workflows.

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.

Osteosarcoma is one of the most common primary bone malignancies, typically occurring around the knee. However, the forearm is a rare site, with tumors in the proximal ulna being extremely uncommon. Primary sarcoma in this location presents a surgical challenge due to the complex anatomy and limited reconstructive options. We report a rare case of a 19-year-old female with non-metastatic, high-grade giant cell-rich osteosarcoma involving the right proximal ulna. To our knowledge, this is only the second reported adult case of this histological subtype in this location. The patient was treated at a specialized oncology center with neoadjuvant and adjuvant chemotherapy, along with wide intra-articular resection for local tumor control. Reconstruction was achieved using a novel, customized 3D-printed articulating cement spacer mold with plate osteosynthesis. Artificial elbow ligamentous reconstruction was performed using FiberTape and FiberWire sutures passed through drill holes, and the triceps tendon was reattached to the cement mold using an endobutton. This cost-effective and personalized surgical approach allowed successful joint reconstruction while maintaining elbow stability and function. Our case highlights a feasible reconstructive option for rare and anatomically challenging osteosarcoma presentations, contributing to the limited literature on proximal ulna giant cell-rich osteosarcoma.

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.