Journal of Cancer Research and Clinical Oncology最新文献

Objective: To comprehensively evaluate the efficacy and safety of neoadjuvant therapy combined with immunotherapy in patients with MMR-proficient/microsatellite stable (pMMR/MSS) non-metastatic rectal cancer.

Methods: Major databases, including PubMed, Web of Science, Cochrane Library, Embase, ASCO, and ESMO, were systematically searched for studies on neoadjuvant therapy combined with immunotherapy in pMMR/MSS non-metastatic rectal cancer, up to April 2025. Statistical analysis utilized Stata 18 software, calculating outcomes with pathological complete response (pCR), major pathological response (MPR), clinical complete response (cCR), R0 resection, anal preservation rate, and the incidence of adverse events. Heterogeneity and publication bias were evaluated using I² and funnel plots.

Results: A total of 21 trial cohorts from 18 studies were included in the meta-analysis. The overall pooled pCR, MPR, and cCR rates were 35% (95% CI: 30-40%, I² = 48.8%, p < 0.001), 58% (95% CI: 51-64%, I² = 69.0%, p < 0.001), and 19% (95% CI: 11-26%, I² = 86.2%, p < 0.001), respectively. An R0 resection rate of 99% (95% CI: 99-100%, I² = 51.8%) and an anal preservation rate of 84% (95% CI: 79-90%, I² = 75.1%) were also achieved. Regarding safety, grade ≥ 3 immune-related adverse events (irAEs) and surgery-related adverse events (srAEs) occurred at rates of 1% and 6%, respectively. Notably, subgroup analyses demonstrated that short-course chemoradiotherapy (SCRT) yielded significantly higher pCR (46% vs. 31%, p < 0.001) and MPR (66% vs. 53%, p = 0.02) rates compared to Long-course chemoradiotherapy (LCRT), with a trend toward superior cCR (25% vs. 15%, p = 0.08). Comparison among neoadjuvant therapy (NAT) protocols revealed comparable pCR rates across consolidation (36%), induction (34%), and concurrent (35%) strategies (p = 0.97), although the MPR rate differed significantly (p < 0.05). Additionally, subgroup analysis based on immune checkpoint inhibitor type demonstrated similar efficacy between monotherapy (pCR: 36%) and dual therapy with PD-1 plus CTLA-4 inhibitors (pCR: 29%), with no statistically significant differences observed across endpoints.

Conclusion: Neoadjuvant therapy combined with immunotherapy in pMMR/MSS non-metastatic rectal cancer demonstrates promising efficacy-with high response rates, excellent R0 resection, and favorable anal preservation outcomes-and an acceptable safety profile. The improved outcomes observed with short-course radiotherapy underscore its potential role in optimizing treatment. However, the heterogeneous nature of current evidence and study designs highlight the need for further high-quality randomized trials.

Hematologic malignancies remain among the most difficult cancers to treat, challenged by profound heterogeneity, treatment-induced immune dysfunction, and the frequent emergence of drug resistance. Beyond tumor-intrinsic mechanisms, dysbiosis of the gut microbiome is increasingly recognized as a critical determinant of therapeutic outcomes, shaping hematopoiesis, immune responses, and drug metabolism. Bacteriophage (phage) therapy has re-emerged as a precision tool capable of selectively eradicating pathogenic taxa while preserving commensal short-chain fatty acid-producing communities. Preclinical and early human studies demonstrate that phages can recalibrate microbial ecosystems, disrupt antibiotic-tolerant biofilms, and enrich metabolites such as butyrate that support mucosal integrity and immune balance. Mechanistically, phage DNA enriched with CpG motifs engages Toll-like receptor 9, activating dendritic cells and enhancing cytotoxic T lymphocyte responses, suggesting dual benefits in infection control and anti-tumor immunity. Emerging applications extend further, with engineered phages serving as vectors for CRISPR-Cas gene editing, targeted cytokine delivery, and nanocarrier platforms for leukemia therapy. Despite translational promise, major hurdles persist, including immunogenicity, horizontal gene transfer, resistance evolution, and regulatory uncertainty. Addressing these challenges through GMP-compliant manufacturing, metagenomics-guided personalization, and AI-optimized cocktail design could establish phage therapy as a microbiome-informed adjunct to overcome drug resistance in blood cancers. However, direct clinical evidence of phage therapy efficacy in hematologic malignancies remains limited, and current data are largely derived from preclinical and compassionate-use contexts.

Objective: While cancer registry and health insurance data are valuable resources for oncological health services research, these are rarely linked at the individual level due to data protection concerns and technical limitations. The prospective, controlled cohort study DigiNet aims to optimize personalized care for patients with stage IV non-small cell lung cancer (NSCLC) in the German study regions Berlin, Saxony and North Rhine-Westphalia. The population-based control group (pCG) was identified through cohort matching within the participating cancer registries. For health economic analyses, case-specific linkage of cancer registry data with claims data without informed consent was required.

Methods: A privacy-preserving record linkage (PPRL) concept was developed, ensuring that no conclusions about individual identities can be drawn. The approach relied on irreversible encryption of the statutory health insurance number (KVNR) within the data-holding institutions, using a study-specific configuration of a publicly available software.

Results: Following cohort matching in the cancer registries, N = 9,597 pCG cases with stage IV NSCLC diagnosis between June 2022 and March 2024 were identified. Of these, n = 1,437 (15.0%) had insurance coverage with one of three participating statutory health insurance funds and were eligible for PPRL. Among those, 94.2% (N = 1,354) were successfully linked with claims data. A trusted third party performed the linkage based on encrypted identifiers, removed the linkage keys, and provided the data to the evaluating parties.

Conclusions: This study demonstrates the feasibility of PPRL of cancer registry and claims data in a real-world oncological research setting. The concept is transferable to other research contexts requiring secure, identifier-based linkage without disclosure of personal identifiers.

Gadolinium-neutron capture therapy (Gd-NCT) employs Gadolinium (Gd) isotopes and thermal neutrons to specifically target and kill cancer at cells level. This study investigates the targeting efficacy of ¹⁵⁷Gd-DOTA-HK (DHK), a novel agent designed for Gd-NCT and MRI. We synthesized ¹⁵⁷Gd-DHK, which combines a Gd-DOTA complex as a neutron capturer and MRI probe with αvβ6 binding peptide (HK) for targeted Pancreas adenocarcinoma (PDAC) therapy. ¹⁵⁷Gd-DHK demonstrated a significantly high binding affinity for BxPC-3 cells. scintigraphy revealed that the optimal time window for Gd-NCT was 26 h after injection. The conjugate's imaging capabilities and its potential as an MRI contrast agent were validated. The conjugate effectively triggered nuclear reactions via Gd-NCT, leading to efficient tumor cell destruction. Photon sensitization studies showed that ¹⁵⁷Gd-DHK induced photon-mediated phototoxicity in cancer cells while exhibiting minimal toxicity. ¹⁵⁷Gd-DHK shows great potential as a theranostic agent for targeted imaging of PDAC and Gd-NCT applications. It presents a novel strategy to enhance the specificity and efficacy of Gd-NCT in cancer treatment.

Background: Combination regimens and monotherapy are both employed in the treatment of hepatocellular carcinoma (HCC). However, the optimal combination regimen for specific scenarios remains unclear. Therefore, our aim is to identify predictors of survival and determine whether combination therapy or monotherapy provides better outcomes for HCC patients.

Methods: From August 2015 to July 2020, a total of 129 unresectable HCC patients receiving immune checkpoint inhibitors (ICI) were recruited. Patients were divided into high tumor burden and low tumor burden groups according to the up-to-7 criteria which is defined as the sum of the size of the largest tumor and the total number of tumors. The combination use of tyrosine kinase inhibitors (TKI) was documented and overall survival was analyzed.

Results: Among the 129 patients receiving ICI, the median age was 63.2 years old, and 76.6% were male. Eighty-five patients (65.9%) were beyond up-to-7 criteria. Patients receiving ICI had median overall survival time of 15 months and had progression-free survival time of 6.2 months. In multivariate Cox regression analysis, the Child-Turcotte-Pugh (CTP) score B (adjusted HR: 3.103 (CI: 1.629-5.912), P = 0.0006), AFP decreased more than 10% from the baseline (adjusted HR: 0.463 (CI: 0.270-0.794), P = 0.0052), and out of up-to-7 criteria (adjusted HR:1.808 (CI:1.007-3.245), P = 0.0472) were the independent predictive factors for mortality. Among patients beyond up-to-7 criteria, 23.5% (n = 20) received combination treatment with TKI and ICI. Moreover, patients using combination treatment showed significantly better survival than those without combination treatment (1st year cumulative survival rate 61% vs 30%, log-rank P = 0.018).

Conclusion: Baseline CTP score, tumor burden, as well as AFP response during ICI treatment were the independent predictive factors for survival. Furthermore, among HCC patients beyond up-to-7 criteria, combination treatment was associated with improved survival than those without combination treatment.

Gastric cancer remains a significant global health challenge due to its aggressive behavior, high mortality rates, and limited treatment success. Growing research underscores the critical role of SUMOylation, a reversible post-translational modification, in regulating key cellular processes such as DNA repair, gene expression, genomic stability, and signaling pathways. Aberrant SUMOylation is closely linked to gastric cancer development, metastasis, and resistance to therapies, positioning it as a potential therapeutic target. This review consolidates current knowledge of the SUMOylation system, which involves activating (E1), conjugating (E2), and ligating (E3) enzymes, alongside SUMO-specific proteases (SENPs) that reverse the modification. We explore how SUMOylation influences cancer-promoting and tumor-suppressing pathways by stabilizing or degrading critical proteins, modulating immune responses, driving epithelial-mesenchymal transition, and contributing to chemoresistance. Furthermore, we discuss promising therapeutic approaches targeting SUMOylation, including small-molecule inhibitors, natural bioactive compounds, and synthetic lethal strategies that exploit SUMO pathway weaknesses. Preclinical studies suggest these approaches could enhance chemotherapy and immunotherapy effectiveness, offering new precision treatment options. Deepening our understanding of SUMOylation in gastric cancer is vital for developing innovative, mechanism-driven therapies to improve patient outcomes.

Aim: The clinical management of gastric cancer (GC) is frequently challenged by the development of drug resistance, leading to poor patient outcomes. This review aims to explore the role of ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, in overcoming this therapeutic hurdle. Our objective is to provide a theoretical foundation for developing novel strategies to reverse drug resistance in GC by targeting the ferroptosis pathway.

Methods: This review systematically elucidates the core regulatory mechanisms of ferroptosis and analyzes its key role in mediating drug resistance in GC. We synthesize current literature to explore potential therapeutic strategies that leverage ferroptosis induction to sensitize cancer cells. Furthermore, we critically examine the complex interplay between ferroptosis and the tumor microenvironment (TME) and discuss the challenges associated with translating these findings into personalized treatment approaches, integrating insights from emerging technologies.

Results: Our analysis confirms that ferroptosis is governed by a precise regulatory network involving glutathione metabolism, lipid peroxidation, and iron homeostasis, which is frequently dysregulated in GC. We identify that key mechanisms of conventional drug resistance are linked to the evasion of ferroptosis. Consequently, several potential therapeutic strategies, including the use of ferroptosis inducers (FINs) and combination therapies, show promise in resensitizing resistant GC cells. The review also highlights the dual role of the TME, which can either suppress or promote ferroptosis, adding a layer of complexity. Finally, we identify significant challenges in patient stratification and the need for reliable biomarkers to achieve personalized ferroptosis-based therapies.

Conclusion: Targeting ferroptosis presents a promising and innovative research avenue for reversing drug resistance in gastric cancer. Strategies designed to induce ferroptosis effectively overcome common resistance mechanisms and hold significant therapeutic potential. Future research must focus on integrating multi-omics technologies and advanced drug delivery systems to decipher the complex regulatory networks of ferroptosis within the TME and to develop biomarkers for personalized treatment, thereby paving the way for improved clinical outcomes.

Objective: The management of pulmonary metastases (PM) from head and neck adenoid cystic carcinoma (ACC) remains controversial, with limited evidence guiding the choice between surgical and non-surgical strategies. This study aimed to compare long-term survival outcomes between patients undergoing surgical resection and those receiving non-surgical management for ACC-derived PM.

Methods: We conducted a retrospective analysis of 204 patients with pulmonary metastases from head and neck ACC treated at our institution between January 2010 and December 2024. Patients were categorized into Surgery (n = 108) and Non-Surgery (n = 96) groups. To address selection bias and improve causal inference in this observational study, propensity score matching (PSM) was performed based on key clinical variables, generating 68 well-matched pairs. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier analysis and Cox proportional hazards models.

Results: Before matching, the Surgery group demonstrated significantly higher 5-year OS (97.73% vs. 84.2%, P = 0.0004) and PFS (89.39% vs. 74.66%, P = 0.021). After PSM, the survival advantage persisted, with the Surgery group showing improved 5-year OS (95.75% vs. 82.91%, P = 0.0063) and PFS (86.93% vs. 73.86%, P = 0.0039). Multivariate analysis confirmed surgical resection as an independent prognostic factor for improved OS (HR = 0.08, 95% CI: 0.01-0.42, P = 0.0032), alongside tumor grade, presence of pleural effusion, and International Registry of Lung Metastases (IRLM) stage.

Conclusions: In this propensity-matched analysis, surgical metastasectomy was associated with significantly improved survival in selected patients with ACC lung metastases, supporting its consideration as a valuable therapeutic option for oligometastatic disease within a multidisciplinary framework.