Journal Of Cancer Research And Clinical Oncology[JOURNAL]
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200 papers
Commentary on early survival gains from adding radiotherapy to ımmunotherapy in bone-metastatic NSCLC.
Peker P
J Cancer Res Clin Oncol · 2025 Dec · PMID 41436873 · Full text
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Impact of comorbidities on treatment management and prognosis in patients with anaplastic thyroid cancer (ATC).
Augustin T, Oliinyk D, Haderlein M … +22 more , Frei C, Jacob J, Medenwald D, Trommer M, Mäurer M, Drozdz S, Rühle A, Grosu AL, Nicolay NH, Waltenberger M, Combs SE, Löser A, Oertel M, Eich HT, Janssen S, Rauch J, Gurtner R, Renollet R, Spitzweg C, Vordermark D, Belka C, Käsmann L
J Cancer Res Clin Oncol · 2025 Dec · PMID 41436662 · Full text
To evaluate the impact of comorbidities on treatment allocation and prognosis in anaplastic thyroid cancer, 137 patients from 10 German tertiary cancer centers treated with radiotherapy between 2001 and 2020 were analyze...
To evaluate the impact of comorbidities on treatment allocation and prognosis in anaplastic thyroid cancer, 137 patients from 10 German tertiary cancer centers treated with radiotherapy between 2001 and 2020 were analyzed. Four validated comorbidity scores were applied to assess comorbidity burden. The primary objective was to identify prognostic factors for the survival rate at 6 months after radiotherapy and discriminate the comorbidity scores using concordance statistics, ROC curve net reclassification index, and integrated discrimination improvement for 6-month survival. The median overall survival (OS) of the entire cohort was 4 months (95% CI = 2.72-5.28). The 6-, 12- and 24-months survival rates were 42.1%, 29.0% and 15.0%, respectively. In the univariate analysis, Karnofsky Performance Score (KPS) (> 70%, p < 0.001), UICC stage (p < 0.001), treatment modality (p < 0.001), intention of treatment (p < 0.001) as well as lower scores in the conventional Charlson Comorbidity Index (cCCI, p < 0.001), the updated Charlson Comorbidity Index (uCCI, p < 0.001) were associated with improved OS. KPS (> 70%, p = 0.06) and type of therapy (p = 0.087) showed a trend in multivariate analysis. Higher comorbidity burden (cCCI and uCCI) was associated with less intensive treatment and lower cumulative radiation doses in univariable analyses. However, after adjustment for age and metastatic status, none of the comorbidity indices remained independently associated with the use of multimodal therapy or the prescribed EQD2 dose (p > 0.05). Age, but not metastatic status, was linked to a reduced likelihood of receiving multimodal treatment. In contrast, KPS emerged as the only independent predictor of higher EQD2 dose levels in the multivariable models.
Extracellular vesicles-derived non-coding RNA in leukemias and pre-leukemic syndromes: a systematic review.
Seddighi N, Najafpour M, Riyahi M … +2 more , Mahmoudzadeh S, Talebi M
J Cancer Res Clin Oncol · 2025 Dec · PMID 41432781 · Full text
BACKGROUND: Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, are among the most aggressive cancers, with high mortality rates and limited early diagnostic tools. Exosomes, nano-sized extrac...
BACKGROUND: Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, are among the most aggressive cancers, with high mortality rates and limited early diagnostic tools. Exosomes, nano-sized extracellular vesicles secreted by numerous cells including tumor cells, have emerged as promising biomarkers due to their stability, non-invasive isolation, and disease-specific molecular cargo, particularly non-coding RNAs (ncRNAs). METHOD: This systematic review, conducted following PRISMA 2020 guidelines, evaluated the diagnostic and prognostic potential of exosomal ncRNAs in hematological malignancies by analyzing 16 studies from five databases (Scopus, PubMed, Embase, Web of Science, and ProQuest). RESULT: Key findings revealed that exosomal microRNAs, such as miR-532, miR-10b, and miR-21 in acute myeloid leukemia, miR-326 in acute lymphoblastic leukemia, and miR-494 in chronic myeloid leukemia, exhibit significant differential expression between patients and healthy controls, correlating with disease progression, treatment resistance, and survival outcomes. Moreover, long non-coding RNAs and circular RNAs were identified as potential biomarkers in myelodysplastic syndromes and leukemia. This review highlights the role of exosomal ncRNAs in liquid biopsies for early detection and monitoring. However, heterogeneity in isolation methods and sample sizes emphasizes the need for standardized protocols. CONCLUSION: These findings highlight the transformative potential of exosomal ncRNAs in precision oncology, offering novel ways for non-invasive diagnostics, prognostic stratification, and targeted therapies in hematological malignancies. Additional studies are necessary to validate these biomarkers and explore their clinical applications.
Neoadjuvant SBRT and intraoperative electron radiotherapy in pancreatic cancer resection.
Cornejo G, Pikarsky A, Hubert A … +11 more , Wygoda M, Skripai A, Popovtzer A, Feldman J, Hillman Y, Appelbaum L, Temper M, Khalaileh A, Imam A, Zamir G, Blumenfeld P
J Cancer Res Clin Oncol · 2025 Dec · PMID 41430468 · Full text
BACKGROUND/OBJECTIVES: Pancreatic cancer surgery frequently results in positive margins and local recurrence despite multimodal treatment. This study evaluated whether combining neoadjuvant stereotactic body radiotherapy...
BACKGROUND/OBJECTIVES: Pancreatic cancer surgery frequently results in positive margins and local recurrence despite multimodal treatment. This study evaluated whether combining neoadjuvant stereotactic body radiotherapy (SBRT) with intraoperative electron radiotherapy (IOeRT) during resection could improve local control and surgical outcomes. METHODS: A retrospective analysis was performed on 15 patients with resectable or borderline resectable pancreatic adenocarcinoma treated between 2021 and 2023. All patients received image-guided, motion-managed SBRT (35-40 Gy/5 fractions to PTV_high; 25 Gy/5 fractions to PTV_low) followed by surgical resection and IOeRT (median 10 Gy; 12 Gy when margins were at risk). Toxicities were graded by CTCAE v5.0 and postoperative complications by Clavien-Dindo criteria. Follow-up included imaging and CA 19-9 every 3 months. Survival was estimated using Kaplan-Meier analysis. RESULTS: Mean patient age was 66 years; 60% had tumors in the pancreatic body and 40% in the head. Two-thirds were borderline resectable and received neoadjuvant chemotherapy. Margin-negative resection was achieved in 86.7%, including two complete pathologic responses in BRCA2-mutated tumors. Median overall and progression-free survival were 30 and 16 months, respectively. One patient (6.7%) developed isolated local recurrence, while distant metastases occurred in over half. Toxicities were mainly grade 1-2 fatigue, nausea, or pain; surgical complications were grade 1-2 in 53%, grade 3 in 7%, and grade 5 in 7%. CONCLUSIONS: Neoadjuvant SBRT with IOeRT during pancreatic cancer resection is feasible, achieves high rates of negative margins, and provides promising local control. Distant progression remains the dominant mode of failure.
Brahmi (Bacopa monnieri) plant preparation facilitates to enhance the activities of dendritic cells to control non-small cell lung cancer (NSCLC).
Kumar RI, Jain K, Arora P … +5 more , Gururajan H, Rai KR, Mukherjee O, George M, Sarkar K
J Cancer Res Clin Oncol · 2025 Dec · PMID 41429965 · Full text
BACKGROUND: Brahmi (Bacopa monnieri) plant preparation (BPP) has been recognizedfor its immunomodulatory capabilities, but its molecular and epigenetic effects onimmune cells in non-small cell lung cancer (NSCLC) remain...
BACKGROUND: Brahmi (Bacopa monnieri) plant preparation (BPP) has been recognizedfor its immunomodulatory capabilities, but its molecular and epigenetic effects onimmune cells in non-small cell lung cancer (NSCLC) remain unknown. OBJECTIVE: Thisstudy investigated the way BPP influenced the molecular phenotype and functionalprofile of monocyte-derived dendritic cells (DCs) derived from an NSCLC patient anda healthy donor. RESULT: BPP treatment enhanced DC maturation, as demonstrated byelevated levels of CD1d and co-stimulatory molecules (CD80/CD86), and conditionedsupernatants that efficiently activated autologous T cells. BPP increased proinflammatorysignaling molecules STAT1, STAT2, STAT4, and total NF-κB, whiledecreasing STAT3, STAT5, STAT6, and the DNA-repair protein DNAPKcs.Transcriptional analysis indicated a Th1-oriented immune program, characterized bythe up-regulation of TBX21, IFNG, and TP53, alongside the down-regulation ofGATA3, FOXP3, RORC, IL10, and MYC. Chromatin profiling revealed an enrichmentof H3K4me3 and H3K14ac, alongside p53 recruitment at the IFNG/TBX21 loci,accompanied by diminished levels of H3K27me3, HDAC2, and reduced promoteroccupancy by c-Myc and NF-κB. BPP enhanced the secretion of IFN-γ, IL-2, and TNF-α while diminishing IL-4, IL-10, and IL-17, establishing a pro-inflammatoryenvironment indicative of Th1-type polarization. Co-culture experiments validatedincreased cytotoxic T-cell activity against A549 cells (NSCLC cells), assessed throughLDH release and statistically confirmed via ANOVA with Tukey post-hoc analysis. CONCLUSION: Overall, these findings demonstrate the ability of BPP to influence dendritic and T-cell responses in NSCLC via coordinated transcriptional and chromatinremodelling activities.
Performance of large language models in reporting oral health concerns and side effects in head and neck cancer: a comparative study.
Rast J, Wiegand S, Biermann J … +2 more , Wiegand A, Marschner F
J Cancer Res Clin Oncol · 2025 Dec · PMID 41420748 · Full text
PURPOSE: With increasing reliance on large language models (LLMs) for health information, this study evaluated reliability and quality, understandability, actionability, readability and misinformation risk of responses f...
PURPOSE: With increasing reliance on large language models (LLMs) for health information, this study evaluated reliability and quality, understandability, actionability, readability and misinformation risk of responses from LLMs to oral health concerns and oral side effects in head and neck cancer (HNC) patients. METHODS: Frequently asked questions on oral health and HNC therapy side effects were identified via ChatGPT-GPT-4-turbo and Gemini-2.5 Flash, then submitted to eight LLMs (ChatGPT-GPT-4-turbo, Gemini-2.5 Flash, Microsoft Copilot, Perplexity, Chatsonic, Mistral, Meta AI-Llama 4, DeepSeek-R1). Responses were assessed using DISCERN and modified DISCERN instruments (reliability and quality), Patient Education Materials Assessment Tool (PEMAT [understandability and actionability]), Flesch-Reading-Ease-Score (FRES [readability]), misinformation score, citations, and wordcounts. Statistical analysis was done by Scheirer-Ray-Hare-test followed by Dunn's post-hoc-tests and Bonferroni-Holm correction (p < 0.05). RESULTS: A total of 40 questions belonging to 12 oral health-related categories were identified. Statistically significant differences between LLMs were found for DISCERN, modified DISCERN, PEMAT-understandability, PEMAT-actionability, FRES, and word counts (p < 0.001). Median DISCERN and modified DISCERN scores amounted from 47.0 (ChatGPT-GPT-4-turbo) to 59.0 (Perplexity, Chatsonic) and from 2.0 (Gemini-2.5 Flash, Mistral) to 5.0 (Perplexity) indicating good to fair reliability. LLMs were understandable (median PEMAT-understandability scores ≥ 75.0), but provided limited specific guidance (median PEMAT-actionability scores ≤ 40) and used complex language (median FRES ≤ 40.2). Misinformation risk was generally low and not statistically significant among LLMs (p = 0.768). CONCLUSION: Despite a low overall misinformation risk, deficits in actionability highlight the need for cautious integration of LLMs into HNC patient education.
Safety and efficacy of zolbetuximab plus chemotherapy for claudin 18 isoform 2-positive advanced gastric cancer: initial report of real-world experience.
Shimozaki K, Ooki A, Fukuoka S … +9 more , Osumi H, Yoshikawa K, Yoshino K, Udagawa S, Wakatsuki T, Shinozaki E, Ogura M, Chin K, Yamaguchi K
J Cancer Res Clin Oncol · 2025 Dec · PMID 41413321 · Full text
PURPOSE: This study evaluated the safety and preliminary efficacy of zolbetuximab plus chemotherapy in patients with claudin 18 isoform 2 (CLDN18.2)-positive advanced gastric cancer (AGC). METHODS: This single-institutio...
PURPOSE: This study evaluated the safety and preliminary efficacy of zolbetuximab plus chemotherapy in patients with claudin 18 isoform 2 (CLDN18.2)-positive advanced gastric cancer (AGC). METHODS: This single-institutional retrospective study enrolled patients with HER2-negative CLDN18.2-positive AGC who were treated with zolbetuximab plus chemotherapy between July 2024 and August 2025. RESULTS: The cohort included 50 patients with a median age of 63 years (range 30-83; 44% male). The primary tumor location was the stomach in 86% of the patients. Meanwhile, 26% of the patients underwent prior gastrectomy. The PD-L1 combined positive score was < 5 in 87% of patients. Among 24 patients with measurable lesions at baseline, the objective response and disease control rates were 66.7% and 87.5%, respectively. After median follow-up of 7.3 months, median progression-free survival and the duration of response were 6.7 [95% confidence interval (CI) 5.3-10.7] and 6.7 months (95% CI 4.7-10.2), respectively. Grade ≥ 3 treatment-emergent adverse events occurred in 62% of the patients, most commonly hypoalbuminemia (22%), neutrophil count decreased (22%) and anorexia (12%). Subsequent treatment was received by 83% of the patients. CONCLUSIONS: Zolbetuximab plus chemotherapy was administered to real-world patients with CLDN18.2-positive AGC with acceptable safety profiles and showed preliminary antitumor efficacy. Nevertheless, some adverse events warrant careful monitoring.
Unveiling hidden players: the role of intratumoral microbiota in gastrointestinal cancer dynamics.
Tang W, Li F, Zheng H … +4 more , Zhou S, Li C, Xu X, Fu J
J Cancer Res Clin Oncol · 2025 Dec · PMID 41410942 · Full text
The intratumoral microbiota has emerged as a critical modulator of gastrointestinal (GI) tumour pathogenesis, influencing cancer initiation, progression, and treatment response. Recent studies have revealed that tumour-r...
The intratumoral microbiota has emerged as a critical modulator of gastrointestinal (GI) tumour pathogenesis, influencing cancer initiation, progression, and treatment response. Recent studies have revealed that tumour-resident microbes, such as Fusobacterium nucleatum (F. nucleatum) and Bacteroides fragilis, contribute to metabolic reprogramming, immune evasion, and metastatic spread via mechanisms including microbiota-derived metabolites, induction of epithelial-mesenchymal transition, and conditioning of the premetastatic niche. Advances in multiomics technologies have enabled the precise characterization of microbial composition and function within the tumour microenvironment, revealing prognostic and predictive microbial signatures. Furthermore, emerging evidence highlights the potential of targeting the intratumoral microbiota to enhance conventional therapies and immunotherapies. This review summarizes key developments in understanding the role of the intratumoral microbiota in GI cancers and discusses future directions for translating these insights into clinical applications.
TC check: a web app for thyroid cancer recurrence prediction using explainable machine learning.
Wen H, Li X, Zhao X
J Cancer Res Clin Oncol · 2025 Dec · PMID 41408410 · Full text
BACKGROUND: Thyroid cancer (TC) is one of the most prevalent endocrine malignancies, and its recurrence presents a major clinical challenge that can adversely affect patient prognosis and treatment outcomes. Despite the...
BACKGROUND: Thyroid cancer (TC) is one of the most prevalent endocrine malignancies, and its recurrence presents a major clinical challenge that can adversely affect patient prognosis and treatment outcomes. Despite the progress in diagnostic methods, traditional statistical models still face limitations in accurately predicting TC recurrence due to the intricate interactions between clinical and pathological factors. METHODS: To address this challenge, the study presented a novel stacking ensemble learning framework for TC recurrence prediction. The dataset included a total of 383 patients, comprising 108 recurrence and 275 non-recurrence cases, and was stratified into training set (n = 268) and testing set (n = 115) using a 70:30 ratio. The proposed stacking framework integrated three heterogeneous base learners, namely Stochastic Gradient Descent (SGD), Extra Trees (ET), and Decision Trees (DT) with eXtreme Gradient Boosting (XGBoost) as the meta learner. The hyperparameter optimization of various learners was performed through 5-fold cross-validation on the training set. The model performance was evaluated on testing set using accuracy, precision, recall, F1-score, AUC, and Brier score (BS). To enhance the model's interpretability, the Shapley Additive Explanations (SHAP) method was utilized to identify the overall top influential factor and provide local interpretation for specific individual patient based model outcome. RESULTS: The proposed stacking model achieved accuracy of 96.52%, precision of 96.67%, recall of 90.62%, and F1-Score of 93.55%, AUC of 0.9921 on the testing set. The SHAP analysis revealed the top 5 critical factors to TC recurrence, including treatment response, age, N-stage, risk stratification, and adenopathy. Furthermore, an interactive and user-friendly prediction tool, TCCheck, was developed based on optimized stacking model, accessible online at https://tccheck-prediction-tool.streamlit.app/ . CONCLUSION: The study presented an effective and interpretable stacking ensemble learning framework for predicting TC recurrence. By deploying the proposed framework as a web prediction tool, it enables explainable and individualized clinical decision support, thereby enhancing its translational value in real-world settings. Furthermore, the framework serves as a methodological reference for recurrence prediction in other cancer types.
Comprehensive analysis based on spatial domains identifies CD44 as a potential target of puerarin.
Xi SY, Zhang H, Wang QJ … +7 more , Liu YJ, Chang SC, Shi CF, Fang D, Tao LH, Cheng HB, Zou X
J Cancer Res Clin Oncol · 2025 Dec · PMID 41405724 · Full text
BACKGROUND: Melanoma, a highly metastatic and treatment-resistant malignancy, urgently requires novel therapeutic strategies. Puerarin, a natural isoflavone with established anti-tumorigenic effects in diverse cancers, r...
BACKGROUND: Melanoma, a highly metastatic and treatment-resistant malignancy, urgently requires novel therapeutic strategies. Puerarin, a natural isoflavone with established anti-tumorigenic effects in diverse cancers, remains underexplored in melanoma despite its potential to modulate melanogenesis and oxidative stress. This study investigates puerarin's spatial targeting mechanisms in melanoma to elucidate its therapeutic specificity. METHODS: A multi-omics approach integrating single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and structure-based docking plus normal-mode analysis was employed. Spatial domain analysis identified puerarin-responsive malignant cell clusters, while molecular docking and protein-ligand simulations prioritized CD44 as a candidate receptor. Functional validation included extracellular matrix (ECM) signaling pathway analysis, spatial colocalization studies, and in vitro experiments. RESULTS: Spatial analysis showed enrichment of puerarin-related signals in malignant-cell-dominated domains. ECM ligands (collagens, fibronectin, laminins) that signal through CD44/SDC1 were concentrated in these domains, where CD44 was overexpressed relative to surrounding compartments. Molecular modeling suggested CD44, a cell-surface receptor overexpressed in melanoma cells, as a putative mediator of puerarin's effects on these pathways. In vitro experiments further supported CD44's role in modulating puerarin-responsive domains. CONCLUSION: These observations are hypothesis-generating and provide a potential direction for future research on whether CD44 mediates puerarin's spatial effects in melanoma.
Quality of care before and after initial certification at a German certified hereditary breast and ovarian cancer center.
Amann N, Hörner M, Spannring H … +10 more , Brückner L, Gocke J, Müller C, Boesl C, Bader S, Heindl F, Hack CC, Fasching PA, Beckmann MW, Krückel A
J Cancer Res Clin Oncol · 2025 Dec · PMID 41405720 · Full text
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 foun...
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.
LAC-TME classifier: machine learning-driven model predicts survival and prioritizes targeted therapy in clear cell renal cell carcinoma.
He J, Qi L, Cai Y … +2 more , Chen M, Wang Y
J Cancer Res Clin Oncol · 2025 Dec · PMID 41402653 · Full text
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 dr...
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 + TME (best prognosis), Lactate + TME (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 + TME 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.
Hematological parameters as predictors of oral cancer prognosis: a systematic review and meta-analysis.
Alshahrani AM, Kaur K, Saini RS … +1 more , Heboyan A
J Cancer Res Clin Oncol · 2025 Dec · PMID 41402518 · Full text
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 plate...
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.
Efficacy and safety of neoadjuvant therapy combined with immunotherapy in MMR‑proficient/microsatellite stable non‑metastatic rectal cancer: a systematic review and meta‑analysis.
Li Y, Han C, Tang J
J Cancer Res Clin Oncol · 2025 Dec · PMID 41396282 · Full text
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: Ma...
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%, I = 48.8%, p < 0.001), 58% (95% CI: 51-64%, I = 69.0%, p < 0.001), and 19% (95% CI: 11-26%, I = 86.2%, p < 0.001), respectively. An R0 resection rate of 99% (95% CI: 99-100%, I = 51.8%) and an anal preservation rate of 84% (95% CI: 79-90%, I = 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.
Phage therapy and the microbiome in hematologic malignancies: opportunities, mechanisms, and early evidence.
Zhang J, Liu J, Bayani A
J Cancer Res Clin Oncol · 2025 Dec · PMID 41384994 · Full text
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...
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.
Impact of preoperative geriatric screening and comorbidity assessment in patients with vulvar and vaginal cancer.
Linz VC, Liebau E, Schepers M … +6 more , Gillen K, Battista MJ, Mohr M, Schmidt MW, Schmidt M, Hasenburg A
J Cancer Res Clin Oncol · 2025 Dec · PMID 41361593 · Full text
PURPOSE: Patients with vulvar (VC) and vaginal (VaC) cancer are often frail and should be prescreened before a time-consuming comprehensive geriatric assessment (CGA). This study assessed the impact of the preoperatively...
PURPOSE: Patients with vulvar (VC) and vaginal (VaC) cancer are often frail and should be prescreened before a time-consuming comprehensive geriatric assessment (CGA). This study assessed the impact of the preoperatively determined frailty status with the G8 geriatric screening tool (G8) and comorbidity assessment on the outcome of patients with VC/VaC. METHODS: We conducted an observational study with prospective data collection of patients aged ≥ 60 undergoing surgery for VC and VAC from 05/2020 to 01/2025. Patients were assessed with the G8 tool, age-adjusted Charlson-Comorbidity Index and the Lee-index. Positive G8 results led to CGA-based testing and, if indicated, geriatric consultation. Cox regression, Kaplan–Meier curves and propensity score matching (PSM) were used to analyze the predictive validity of the G8. RESULTS: 41 patients were screened. 26 patients were included with a mean follow-up of 23 months. 10 patients were considered G8 positive (G8 ≤ 14 points). Median age was 74.5 (interquartile range: 66–81.3) years. The G8 positive cohort was older, had more comorbidities and had higher ECOG and ASA performance status than the G8 negative cohort. 20% of the G8 positive patients did not receive standard surgical therapy and only one in five patients underwent standard adjuvant radio-/chemotherapy. The univariate Cox-model for overall survival (OS) for G8 positivity had a hazard ratio of 5.65 with 95% CI [1.14–28.1] and a significantly lower 2-year OS (40.0 vs. 85.1%), supported by PSM adjusted for residual confounding (p = 0.017). CONCLUSIONS: The G8 can be easily implemented in the clinical routine to identify VC and VaC patients with a reduced 2-year OS who may benefit from CGA.
Gd-DHK: enhancing targeted gadolinium neutron capture for pancreatic adenocarcinoma.
Xie L, Song C, Qin J … +8 more , Xu Q, Yin J, Ma Y, Chen H, Li C, Hong B, Chen N, Pang X
J Cancer Res Clin Oncol · 2025 Dec · PMID 41343059 · Full text
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 Gd-DOTA-HK (DHK),...
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 Gd-DOTA-HK (DHK), a novel agent designed for Gd-NCT and MRI. We synthesized Gd-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. Gd-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 Gd-DHK induced photon-mediated phototoxicity in cancer cells while exhibiting minimal toxicity. Gd-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.
Concept and feasibility of privacy-preserving record linkage of cancer registry data and claims data in Germany: results from the DigiNet study on stage IV non-small cell lung cancer.
Kästner A, Hampf C, Naumann P … +29 more , Fiedler-Lacombe L, Kron A, Spier A, Simic D, Eilers L, Graw A, Bartholomäus S, Stang A, Reil D, Kirschner-Schwabe R, Selig JI, Wulff J, Dröge P, Ruhnke T, Günster C, Nußbaum U, Marschall U, Mohnke J, Hebbelmann A, Lührig U, Rasokat A, Mildenberger V, Stock S, Kron F, Wolf J, Bialke M, Stahl D, van den Berg N, Hoffmann W
J Cancer Res Clin Oncol · 2025 Dec · PMID 41342956 · Full text
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 li...
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.
TKI plus ICI versus ICI alone in high tumor burden hepatocellular carcinoma: a retrospective cohort study.
Lin PT, Teng W, Chen WT … +5 more , Su CW, Hsieh YC, Lin CC, Lin CY, Lin SM
J Cancer Res Clin Oncol · 2025 Dec · PMID 41335134 · Full text
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 i...
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.
The c.1744G > C, p.(Glu582Gln) missense variant in coding exon 14 of APC increases skipping of a natural occurring isoform and causes Familial Adenomatous Polyposis.
Jelsig AM, Boelman MB, Birkedal U … +5 more , Hübertz J, Al-Zehawi L, Lautrup C, Karstensen JG, van Overeem Hansen T
J Cancer Res Clin Oncol · 2025 Dec · PMID 41329333 · Full text
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