Journal of Cancer Research and Clinical Oncology最新文献

Leptomeningeal metastasis in patients with Epidermal Growth Factor Receptor-mutant non-small cell lung cancer carries a dismal prognosis and is associated with profound neurological morbidity. Historically, therapeutic efficacy has been severely limited, leading to poor overall survival. This review aims to synthesize the recent, albeit incremental, advances in the multidisciplinary management of this devastating complication. We delve into the evolving landscape of treatment modalities, with a particular focus on the latest generation of tyrosine kinase inhibitors and their superior central nervous system penetration. The roles of conventional approaches, including radiotherapy (both whole-brain and focal) for symptom palliation and tumor control, and intrathecal chemotherapy, are critically re-evaluated in the modern context. Furthermore, we explore the rationale and early evidence for novel combination strategies. A significant portion of our analysis is dedicated to evaluating the pharmacodynamic mechanisms of action, optimizing dosing strategies, and interpreting clinical outcomes from key trials and real-world evidence. Central to the discussion are the persistent challenges of adequate blood-brain barrier penetration, the emergence of therapeutic resistance, and the management of overlapping toxicities. We also address the parallel progress in diagnostic neuro-imaging and cerebrospinal fluid liquid biopsies, which are enhancing early detection and disease monitoring. Finally, this review outlines future research directions, emphasizing the need for randomized controlled trials and a deeper understanding of the tumor microenvironment to foster a paradigm shift in the care of patients with leptomeningeal metastasis.

Background/objectives: Malignant melanoma is an aggressive skin cancer with significant metastatic potential. Immune checkpoint inhibitors (ICIs), particularly those targeting the PD-1 pathway, have revolutionized treatment, improving survival rates. A PD-1 inhibitor, Nivolumab, has demonstrated durable responses in advanced melanoma patients. However, response variability necessitates predictive biomarkers for patient stratification.

Methods: The Gustave Roussy Immune Score (GRIm Score) is a prognostic tool integrating lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and albumin levels to predict ICI efficacy. This retrospective study evaluated the association between the GRIm Score and response to nivolumab monotherapy in 40 patients with stage IV malignant melanoma treated between 2020 and 2024. Patients were classified into low-risk (score 0-1) and high-risk (score 2-3) groups.

Results: Results showed that patients with a low GRIm Score had significantly longer median progression-free survival (21.4 vs. 6.3 months, p = 0.003) and overall survival (26.5 vs. 7.2 months, p < 0.001). Multivariate analysis confirmed the GRIm Score as an independent prognostic factor (HR: 1.593, 95% CI: 1.156-2.197, p = 0.004), surpassing the predictive power of its components.

Conclusions: This study is the first to validate the GRIm Score in malignant melanoma, suggesting it is a valuable biomarker for patient selection in immunotherapy trials. The findings highlight its potential in refining treatment decisions, though further validation in larger, multicenter cohorts is required.

Purpose: For non-muscle invasive bladder cancer (NMIBC), instillation with Bacillus Calmette-Guérin (BCG) is a standard therapy. With a still unclear mechanism, instillation activates the innate immune system, resulting in an immunological effect on the tumour. The aim of this work was to investigate which bladder cancer (BLCA) cells can be activated by interferon (IFN) exposure.

Methods: The BLCA cell lines RT4 and SW780 were stimulated with IFN-α2, -β and -λ1 over 4-72 h. Quantitative PCR (qPCR) was used to determine the expression of IFN receptor subunits (RS) and selected interferon-stimulated genes (ISGs). Luciferase reporter assay was performed to detect the activation of the IFN responsive element (ISRE). Different signal transduction molecules of the JAK/STAT pathway were assessed by Western Blot to prove its activation in BLCA cells. The viability of the stimulated cells was measured by WST-1 assay and the apoptosis induction by caspase-3/7 assay.

Results: The JAK/STAT pathway was activated via the four RS. Upon long-term treatment, type I and type III IFNs significantly induced increased ISG expression and apoptosis induction of RT4 and SW780 cells, emphasising their antiproliferative and immunomodulatory activity. This activation was mediated by ISRE. IFN-β activated the JAK/STAT pathway with the greatest potency, highlighting its superior efficacy in modulating cellular responses in BLCA.

Conclusion: Activation of the innate immune system has the ability to trigger further infiltration of the tumour microenvironment (TME) with immune cells, which positively influence the TME in its type, density and immunofunctional orientation against BLCA.

Purpose: Multidisciplinary team (MDT) consultations are crucial for managing pulmonary nodules, yet face challenges in efficiency, evidence-based decision support, and data utilization within the MDT process. We present an integrated artificial intelligence (AI)-MDT platform that serves as an assistive tool for lung cancer MDT workflows by incorporating AI across various processes.The aim of this study is to evaluate the clinical utility and preliminary efficacy of the AI-MDT platform.

Methods: The platform comprises three core modules: process automation, intelligent decision support, and diagnostic assistance. It integrates a real-time, evidence-based knowledge base powered by large language models and deep learning, with computer vision for automatic lesion detection and feature analysis. A web-based interface allows users to interact seamlessly with the AI-MDT platform.

Results: Since its implementation in November 2023 at a tertiary Grade A hospital in China, the platform has been involved in 879 consultations, including 811 patients. AI-generated diagnostic recommendations were utilized 852 times, and decision-making support was used in 744 cases. The platform significantly increased consultation volume, reduced expert time, and enhanced data utilization compared to traditional MDT.

Conclusions: It offers clinicians tools to improve diagnostic quality and work efficiency, highlighting its significant clinical application value. These findings suggest that the proposed platform contributes to the emerging research on advances precision lung cancer management by integrating a continually updated evidence base and intelligent imaging methodologies, having potential implications for MDT processes across various medical specialties.

Background: Albumin in combination with other inflammatory markers has shown prognostic value in malignancy, including biliary tract cancer (BTC). This study aimed to evaluate the prognostic value of hypoalbuminemia alone in patients with BTC, with stratified analyses according to tumor type, treatment and sex.

Methods: A retrospective regional referral center cohort study was conducted, including consecutive patients with a measurement of preoperative albumin and intended resection of suspected BTC: intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA) or gallbladder cancer (GBC) between 2009 and 2017. The primary outcome was overall survival (OS), analyzed by Kaplan-Meier estimate and Cox regression.

Results: Out of 221 patients, 191 underwent resection, while 30 patients were diagnosed with unresectable BTC (14%). In the resection group, 147 patients had confirmed BTC, while 44 (20%) were postoperatively diagnosed with a benign lesion. Hypoalbuminemia (< 35 g/L) was more frequent in pCCA (75%) and GBC (59%), compared to iCCA (34%, p < 0.001). The preoperative albumin level was positively associated with resectability (p = 0.025). In patients with resection, hypoalbuminemia was associated with a tumor positive resection margin (p < 0.001). Hypoalbuminemia was a negative prognostic factor in resectable (p < 0.001) and unresectable BTC (p < 0.001), and in both women (p = 0.002) and men (p = 0.004). Hypoalbuminemia was negatively associated with OS in iCCA (p < 0.001) and GBC (p = 0.022), but not in pCCA (p = 0.210).

Conclusion: Preoperative albumin was prognostic for survival in patients with iCCA and GBC, in both women and men and regardless of tumor resectability. Patients with pCCA more often had low albumin, and hypoalbuminemia alone was not prognostic in this subgroup.

Background: Acupuncture is a method of traditional Chinese medicine that has been adapted in the Western world. The objective of this study was to critically assess the evidence presented in randomized controlled trials (RCTs) about the effectiveness of acupuncture on fatigue in cancer patients.

Method: In April 2024 a systematic search was conducted searching five electronic databases to find studies concerning the use, effectiveness and potential harm of acupuncture therapy on cancer patients.

Results: From all (1599) search results, 15 studies with 1346 patients were included. Acupuncture methods varied (e.g., traditional-, electro-, mind-regulating and ATAS-acupuncture) and were compared to sham acupuncture, usual care, or other controls. Studies comparing acupuncture to sham acupuncture reported mixed results: while some found significant effects on cancer-related fatigue, others found no advantages. Studies comparing acupuncture to usual care or waitlist controls often reported positive effects. However, the reliability of these findings is limited, as 14 of 15 studies were rated as "high risk of bias" by the RoB-2 tool due to issues like insufficient blinding and incomplete data analysis. Only one study, with low risk of bias, showed a significant reduction in fatigue with acupuncture compared to sham acupuncture (p < 0.001). GRADE evaluation also showed very low certainty of evidence.

Conclusion: The heterogenous results and methodological limitations of the existing studies prevent us from drawing definitive conclusions about the effectiveness of acupuncture in the treatment of cancer-related fatigue. Despite the inclusion of 15 studies, the overall evidence remains insufficient due to widespread problems in study design and inconsistent results. This analysis highlights the need to use more rigorous designs and more comprehensive assessment tools in future studies to better understand the role of acupuncture in the management of fatigue after cancer treatment.

Purpose: This study investigated the anatomical and pathological mechanisms of immature squamous metaplastic epithelium in Weber's glandular ducts at the tongue base in human papillomavirus (HPV)-independent oropharyngeal squamous cell carcinoma (OPSCC).

Methods: An analysis of 80 tongue base carcinoma cases clarified the anatomical connection to Weber's glands. Histological and immunohistochemical studies of these glandular ducts identified areas susceptible to cancer. A mouse model using 4-nitroquinoline-N-oxide was employed to simulate carcinogenic development.

Results: 42.5% of cases were linked to Weber's glands, with 20 directly connected to glandular ducts. Only one case was p16-positive, indicating that carcinogenesis in Weber's glandular ducts is largely non-HPV-mediated. The transformation zone with immature squamous metaplastic epithelium and CK17/p63+ reserve cells at Weber's glandular ducts were found, akin to cervical cancer susceptibility. CK17 studies indicated that the immature epithelium had "compromised barrier function" and "hyperproliferative activity", accelerating mutation and carcinogenesis. An atypical opening of the Weber's gland exposed the ductal epithelium to oncogenic factors, increasing carcinogenic risk. A mouse model confirmed the progression from metaplasia to carcinoma and the oncogenic potential of Weber's glandular ducts.

Conclusions: Weber's glandular ducts are an important origin of HPV-independent OPSCC. The first animal model replicating this process offers an essential platform for studying HPV-independent OPSCC.

Purpose: High-dose ifosfamide (HD-IFO) remains an effective regimen for advanced bone and soft tissue sarcomas, but predictors of long-term benefit are poorly defined. This study evaluated clinical outcomes and prognostic factors using machine learning-assisted modeling in sarcoma patients treated with HD-IFO at a high-volume academic center.

Methods: We retrospectively analyzed 26 patients with histologically confirmed bone or soft tissue sarcoma who received HD-IFO (≥ 12 g/m² per cycle) between 2015 and 2025. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared across RECIST response categories using log-rank testing. Prognostic factors were identified using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with leave-one-out cross-validation. The top three variables were entered into multivariable logistic regression to estimate odds ratios (ORs) for OS > 24 months.

Results: Median PFS and OS from start of HD-IFO was 6.6 months (95% CI 4.4-9.8) and 24.7 months (95% CI, 14.7-34.2), respectively. Patients with progressive disease (PD) had significantly shorter OS than those with partial response (PR; p = 0.0047) or stable disease (SD; p = 0.0485). LASSO identified intervention prior to progression, prior tumor control ≥ 12 months, and absence of metastases as the strongest predictors for OS > 24 months. In multivariable analysis, intervention prior to progression (OR 24.18, 95% CI 1.81-1001.27, p = 0.037) and prior tumor control ≥ 12 months (OR 25.39, 95% CI 2.1-1008.9, p = 0.030) independently predicted OS > 24 months.

Conclusion: HD-IFO provides durable disease control in selected sarcoma patients, particularly those with sustained prior tumor control and intervention prior to progression.