Journal of Cancer Research and Clinical Oncology最新文献

Purpose: Genetic mutations contribute to around 10% of breast and 25% of ovarian cancers, with one third of patients having a familial cancer history. The German Consortium for Familial Breast and Ovarian Cancer was founded in 1996 to improve care for these patients. Certification of cancer centers, introduced in 2004, has been linked to improved survival rates and ensures adherence to evidence-based standards. This study investigates changes in care structures and quality before and after the initial certification of the HBOC center at the University Hospital Erlangen, certified from 2021 on.

Methods: This retrospective study analyzed patient data from January 2018 to December 2023 at the certified Hereditary Breast and Ovarian Cancer center at the University Hospital Erlangen. Eligibility for genetic counseling and germline testing followed the German Cancer Society criteria. After informed consent, Next Generation Sequencing was performed, and variants were classified according to Human Genome Variation Society and American College of Medical Genetics and Genomics standards. Medical histories and genetic results were recorded in electronic case report forms.

Results: From 2018 to 2023, a total of 2694 genetic tests were performed, increasing from 962 pre-certification to 1732 post-certification (+ 180%). Testing among affected female patients doubled. Genetic testing in breast cancer patients increased from 551 to 1,04, while testing for ovarian carcinoma rose from 117 to 159. Variants of uncertain significance were identified in approximately 9% of cases during both periods. Pathogenic findings were observed in 14.3% of cases pre-certification (with 9.2% involving BRCA1/2 mutations) and 11.5% post-certification (6.4% BRCA1/2 mutations). Enrollment in the intensified surveillance program (IBCS) increased by 182.5%, accompanied by a rise in recommendations for risk-reducing surgeries.

Conclusion: Certification of medical institutions ensures high-quality, evidence-based patient care and increases the utilization of preventive and counseling services, particularly for Hereditary Breast and Ovarian Cancer. Further studies are needed to confirm the long-term impact and necessity of certification.

Background: Clear cell renal cell carcinoma (ccRCC) is a major type of kidney cancer, making up about 80% of cases, with advanced stages showing low survival rates. Current treatments face challenges like toxicity and drug resistance. Studies indicate lactate, through the Warburg effect, promotes an immune-suppressive tumor microenvironment (TME), prompting the development of the LAC-TME classifier using machine learning to predict outcomes and personalize treatment.

Methods: The study used data from TCGA-KIRC set and E-MTAB-1980 set, analyzing gene expression, mutations, and clinical data. It employed differential expression analysis, immune infiltration assessment, and 101 machine learning algorithms to build the classifier, integrating lactate-related genes and TME features, with predictive capability verified.

Results: The LAC-TME classifier, constructed by integrating 9 lactate-related differentially expressed genes and TME cells, demonstrated high predictive accuracy (C-index of 0.92 in the training set and 0.73 in the validation set). Patients were categorized into three groups: Lactate^low + TME^low (best prognosis), Lactate^high + TME^high (poorest prognosis), and a mixed group. This classifier can predict 1- to 5-year survival rates, with an AUC of 0.88-0.92. Notably, the Lactate^high + TME^high subgroup was associated with immunosuppression and poor response to immunotherapy. As the core lactate-related gene of the LAC-TME classifier, the knockdown of LGALS1 significantly inhibits the proliferation and migration of ccRCC cells, verifying the biological rationality of the classifier.

Conclusion: The LAC-TME classifier, integrating metabolic and immune data, offers a new tool for ccRCC prognosis and treatment guidance. Further validation is needed to confirm its clinical potential, reflecting the ongoing need for robust medical research.

Objective: This systematic review and meta-analysis aimed to assess the prognostic value of pre-treatment hematological parameters, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV), in patients with oral squamous cell carcinoma (OSCC).

Methods: A systematic search of PubMed, Embase, Scopus, Web of Science, ScienceDirect, and Google Scholar was conducted until April 2025. We included English-language observational studies reporting associations between NLR, PLR, MPV, and survival or clinicopathological outcomes in OSCC. Data extraction and risk of bias assessment using the Newcastle-Ottawa Scale were performed independently by two reviewers. Hazard ratios (HRs) and odds ratios (ORs) were pooled using a random-effects model. The certainty of evidence was evaluated using the GRADE.

Results: Thirty-five studies (approximately 7940 patients) were included. A high NLR was associated with worse overall survival (pooled HR 1.59, 95% CI 1.32-1.92) and disease-free survival (HR 1.66, 95% CI 1.31-2.10). PLR showed similar associations with overall survival (HR 1.58, 95% CI 1.29-1.94) and disease-free survival (HR 1.50, 95% CI 1.18-1.90). Between-study heterogeneity was moderate to high in this study. MPV findings were inconsistent and not pooled.

Conclusions: Elevated NLR and PLR correlate with poorer outcomes in OSCC, with effect sizes varying by study design and cut-off selection. These blood-based indices may aid in risk stratification; however, prospective validation with standardized thresholds is required.

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.