Journal of Cancer Research and Clinical Oncology最新文献

{"title":"Temporal trends and socio-demographic disparities in COPD-lung cancer co-occurrence mortality in the United States: a 22 year analysis (1999-2020).","authors":"Abdullah Nadeem, Syed Muhammad Asjad Rizvi, Areeba Aamir Ali Basaria, Laiba Jalal, Rabeea Tariq, Taruba Rais, Hafiza Hafsa, Nahid Khalid Raufi, Eaman Fatima","doi":"10.1007/s00432-026-06571-0","DOIUrl":"https://doi.org/10.1007/s00432-026-06571-0","url":null,"abstract":"<p><strong>Background: </strong>Chronic Obstructive Pulmonary Disease (COPD) and lung cancer remain among the leading causes of mortality worldwide, with a high burden reported in the United States. While both conditions often coexist and share risk factors such as smoking and environmental exposure, temporal mortality trends and disparities across demographics remain underexplored.</p><p><strong>Objective: </strong>To analyze age-adjusted mortality rates (AAMRs) associated with the co-occurrence of COPD and lung cancer (COPD-LC) in the United States from 1999 to 2020, with a specific focus on temporal shifts and disparities across sex, race/ethnicity, and geographic regions.</p><p><strong>Methods: </strong>Mortality data were retrieved from the CDC WONDER database. The underlying causes of death were identified using ICD-10 codes (J40-J44 for COPD and C33-C34 for lung cancer). AAMRs were standardized to the 2000 U.S.</p><p><strong>Population: </strong>Joinpoint regression analysis was used to calculate Annual Percent Changes (APCs) and identify statistically significant shifts in mortality trends. Subgroup analyses were conducted by sex, race/ethnicity, and census regions. Mortality associated with the co-occurrence of COPD and lung cancer was identified using multiple-cause-of-death coding.</p><p><strong>Results: </strong>A total of 587,762 deaths involving co-occurring chronic obstructive pulmonary disease (COPD) and lung cancer were identified in the United States between 1999 and 2020. Overall age-adjusted mortality rates (AAMRs) declined from 8.904 per 100,000 population in 1999 to 7.128 in 2020. Joinpoint regression demonstrated a three-segment trend, including a non-significant decline from 1999 to 2006 (APC: - 0.40), a significant decline from 2006 to 2018 (APC: - 1.77%), and a non-significant increase from 2018 to 2020 (APC: 0.71%). Sex-stratified analysis showed persistently higher mortality among males, although mortality declined more substantially in males than in females over time. Non-Hispanic White individuals demonstrated the highest mortality burden, whereas Asian or Pacific Islander and Hispanic populations had the lowest AAMRs. Regionally, mortality rates remained highest in the Midwest and South, while the West exhibited the steepest decline. Non-metropolitan areas demonstrated persistently elevated mortality rates compared with metropolitan regions.</p><p><strong>Conclusion: </strong>While mortality among individuals with co-occurring COPD and lung cancer has declined significantly over two decades, demographic disparities based on sex, race, and geography persist. These findings highlight the need for equity-driven public health interventions and early detection strategies tailored to high-risk populations.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics analysis reveals that tumour cell-intrinsic DCLK1 is associated with an angiogenic tumour microenvironment in cholangiocarcinoma via NF-κB/CXCL5.","authors":"Ziqing Kong, Rui Yan, Ziwei Liang, Guangyu An, Yang Ge","doi":"10.1007/s00432-026-06568-9","DOIUrl":"10.1007/s00432-026-06568-9","url":null,"abstract":"<p><strong>Purpose: </strong>Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis and complex tumour microenvironment. We previously demonstrated that doublecortin-like kinase 1 (DCLK1) is associated with epithelial-mesenchymal transition (EMT) in CCA; however, its biological functions and clinical relevance remain unclear. Herein, we elucidated the role of DCLK1 in CCA progression, focusing on its effects on angiogenesis, and evaluated its potential as a prognostic marker.</p><p><strong>Methods: </strong>We analysed bulk and single-cell RNA sequencing data to characterise DCLK1 expression and function in CCA. Functional validation was performed using conditioned medium from DCLK1-modified CCA cells, as well as endothelial tube formation, migration, and invasion assays. Tumour vascular density was assessed using a xenograft model. We used a human angiogenesis-related antibody array, western blotting, quantitative real-time PCR, and nuclear translocation assays to examine CXCL5 expression and NF-κB pathway activity.</p><p><strong>Result: </strong>We found that DCLK1 was upregulated in CCA and correlated with advanced disease and poor survival. DCLK1⁺ malignant cells displayed pro-angiogenic features and increased paracrine interaction with endothelial cells. Conditioned medium from DCLK1-overexpressing tumour cells enhanced endothelial tube formation, migration, and invasion, whereas DCLK1 knockout reversed these effects. DCLK1-expressing tumours showed increased vascular density in vivo. Mechanistically, an angiogenesis antibody array and western blotting demonstrated that DCLK1 activated the NF-κB pathway to upregulate CXCL5 expression. Pharmacological inhibition of NF-κB or neutralization of CXCL5 significantly attenuated DCLK1-related pro-angiogenic responses in vitro.</p><p><strong>Conclusion: </strong>DCLK1 activated the NF-κB pathway to upregulate CXCL5 secretion; inhibiting NF-κB or CXCL5 reduced DCLK1-related pro-angiogenic capacity.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13710486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isorhamnetin inhibits bladder cancer progression by mediating glycolysis through targeting the SRC/PI3K/Akt axis.","authors":"Feng Haiya, Li Qianqian, Lu Yangjun, Wang Hui","doi":"10.1007/s00432-026-06577-8","DOIUrl":"10.1007/s00432-026-06577-8","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the anti-tumor effects of the natural flavonoid Isorhamnetin (ISO) on BC and elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>We integrated network pharmacology and bioinformatic analysis to predict the core targets and pathways between BC and ISO. In vitro functional assays were performed using the human BC cell line 5637. Cell viability, proliferation, apoptosis, migration, invasion, and adhesion were assessed via CCK-8, colony formation, flow cytometry, Transwell, and adhesion assays. Glycolytic function was evaluated by measuring extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose uptake, and lactate production. Molecular docking and cellular thermal shift assays (CETSA) were used to validate ISO-SRC binding. Western blot and RT-qPCR analyses were conducted to examine protein and mRNA expression of key signaling and glycolytic components. For the rescue experiments, SRC was overexpressed along with treatment using the PI3K inhibitor LY294002.</p><p><strong>Results: </strong>ISO significantly inhibited BC cell proliferation, migration, invasion, adhesion, and glycolysis while inducing G0/G1 phase arrest and apoptosis. Network pharmacology and molecular docking identified SRC as a direct target of ISO, with CETSA confirming their binding. ISO treatment downregulated phosphorylation of SRC and its downstream effectors (PI3K, Akt, mTOR), reduced the expression of glycolytic enzymes (HK2, GLUT1, PFKFB3), and decreased ECAR, OCR, glucose uptake, and lactate production. SRC overexpression reversed the anti-tumor and anti-glycolytic effects of ISO. Furthermore, administration of LY294002 on this basis counteracted the effects induced by SRC overexpression, confirming the critical role of the SRC/PI3K/Akt axis.</p><p><strong>Conclusion: </strong>ISO inhibits the malignant progression of BC by directly targeting SRC to suppress glycolysis mediated by the PI3K/Akt signaling pathway. These findings provide a mechanistic basis for considering ISO as a potential metabolic-targeting agent for BC, warranting further preclinical evaluation.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensity-modulated radiotherapy combined with albumin-bound paclitaxel and platinum-based chemotherapy for locoregional recurrent cervical cancer: a single-institutional phase II investigator-initiated nonrandomized clinical trial.","authors":"Chi Fang, Suping Liu, Jie Xia, Xiaohua Wu, Guihao Ke, Jun Zhu","doi":"10.1007/s00432-026-06555-0","DOIUrl":"10.1007/s00432-026-06555-0","url":null,"abstract":"<p><strong>Objective: </strong>To prospectively explore efficacy and safety of radiotherapy combined with albumin-bound paclitaxel and platinum-based chemotherapy for locoregional recurrent cervical cancer (CC).</p><p><strong>Methods: </strong>Patients with locoregional recurrent CC were enrolled in the analysis. The enrolled patients received radiotherapy and albumin-bound paclitaxel and platinum-based chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and safety.</p><p><strong>Results: </strong>99 patients were enrolled. For all patients, the 3-year PFS and 3-year OS were 48.5% and 58.6%. 17.2% of patients achieved CR and 67.7% of patients achieved PR. The ORR was 84.8%. Moreover, 10.1% of patients were confirmed SD. The DCR was 94.9%.</p><p><strong>Conclusion: </strong>Locoregional recurrent CC could benefit from radiotherapy combined with albumin-bound paclitaxel and platinum-based chemotherapy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13710511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pivotal role of macrophages in tumorigenesis and pioneering cancer immunotherapy across pre-clinical and clinical frontiers.","authors":"Mina Alimohammadi, Amir Mohammad Mirnejad, Najma Farahani, Neda Hedayati, Kiavash Hushmandi","doi":"10.1007/s00432-026-06566-x","DOIUrl":"10.1007/s00432-026-06566-x","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are among the most abundant cells in the tumor microenvironment (TME), with M1 and M2 polarization exhibiting anti-tumorigenic and tumorigenic functions, respectively. Originating from both embryonic precursors and circulating monocytes derived from hematopoietic stem cells, TAMs acquire distinct transcriptional, metabolic, and functional identities shaped by the TME. The interactions in the TME among various cells, including cancerous and non-cancerous cells, can determine the polarization and function of TAMs within the tumor. More recently, TAMs have garnered significant interest as a promising therapeutic target in oncology. The TAMs have been shown to enhance proliferation, metastasis, and angiogenesis in human cancers. Notably, cytokines and chemokines, among others, can regulate the infiltration of TAMs in TME. Given the crucial role of macrophages in regulating inflammation and immune responses, targeting these cells has become a significant focus in cancer immunotherapy. Currently, macrophages have been targeted through three strategies, including suppressing macrophage/monocyte recruitment, depletion of TAMs, and re-education of TAMs. Each of these approaches is being investigated in preclinical models and clinical trials, either as monotherapy or in combination with immune checkpoint inhibitors. TAMs can also be engineered to act as drug delivery tools, carrying nanoparticles directly into tumors. In the clinic, some types of TAMs, marked by proteins like CD163 and CD204, can help predict patient outcomes in several cancers. This review investigates the origins of TAMs and the mechanisms underlying their polarization and metabolism. Furthermore, we study macrophage-driven tumor progression and devising effective targeting strategies, as well as challenges that remain and where the field may go next in macrophage-based cancer treatment. Going forward, combining single-cell profiling with multi-target therapies may offer the best path toward more effective, TAM-based cancer treatments.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting the apparent benefit of thoracic radiotherapy in metastatic NSCLC: patient selection and analytical issues remain important-a comment on Xue et al.","authors":"Lili Qin, Shasha Wang, Haifeng Qin","doi":"10.1007/s00432-026-06567-w","DOIUrl":"10.1007/s00432-026-06567-w","url":null,"abstract":"<p><p>Thoracic radiotherapy (TRT) has been proposed as a potentially beneficial adjunct to first-line targeted therapy or chemoimmunotherapy in metastatic non-small cell lung cancer (NSCLC). This commentary discusses the retrospective study by Xue et al. and highlights several methodological issues that may influence interpretation of the reported survival benefit. Although the observed improvement in overall survival is clinically encouraging, imbalances in metastatic burden, inconsistent incorporation of key prognostic variables, and limited maturity of survival data may introduce residual confounding. Additional concerns include the causal interpretation of multivariable models, overlapping definitions of pulmonary toxicity, time-dependent adverse events, and unadjusted subgroup analyses. Overall, TRT may benefit carefully selected patients, but prospective studies and robust real-world analyses using causal-inference methods are needed to define optimal candidates and ensure safe implementation.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 7","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world insights into bone marrow carcinomatosis in metastatic breast cancer: a retrospective analysis from two large university breast cancer centers.","authors":"Nikolas Tauber, Melissa Neubacher, Niklas Amann, Jan P Cieslik, Irene Esposito, Franziska Fick, Catharina Freier, Verena Friebe, Martina Helbig, Franziska Hemptenmacher, Lisbeth Hilmer, Bernadette Jäger, Kerstin Muras, Anna E M Polkaehn, Henriette Princk, Eugen Ruckhäberle, Maximilian Seidl, Tanja Fehm, Achim Rody, Fabian Kohls, Maggie Banys-Paluchowski, Natalia Krawczyk","doi":"10.1007/s00432-026-06546-1","DOIUrl":"10.1007/s00432-026-06546-1","url":null,"abstract":"<p><strong>Purpose: </strong>Bone marrow carcinomatosis (BMC) is a rare but clinically relevant manifestation of metastatic breast cancer (mBC), characterized by diffuse marrow infiltration and hematologic dysfunction. Evidence on epidemiology, clinical presentation, prognosis, and optimal treatment is limited. We performed a bicentric retrospective real-world analysis of patients diagnosed with BMC, representing the largest reported European cohort to date.</p><p><strong>Methods: </strong>We retrospectively analyzed 37 patients diagnosed with BMC at two German university breast cancer centers between 2010 and 2023. Clinical characteristics, hematologic abnormalities, metastatic patterns, treatments, and overall survival (OS) were evaluated. Incidence estimates were calculated based on institutional breast cancer and mBC populations. A systematic literature review contextualized the findings.</p><p><strong>Results: </strong>The estimated incidence of BMC was 2.6% among patients with mBC and 0.5% among all breast cancer cases. Most patients had HR-positive/HER2-negative disease (89%). Hematologic abnormalities were frequent, including anemia (84%), thrombocytopenia (76%), and pancytopenia (57%). Median OS after BMC diagnosis was 12 months (95% CI 6.0-38.0). Patients with bone-only metastases did not reach median OS, whereas those with additional metastatic sites had a median OS of 9 months (95% CI 5.0-12.0). Patients receiving endocrine therapy plus CDK4/6 inhibition showed numerically longer OS (34 months, 95% CI 5.0-NA) compared with chemotherapy alone (12 months, 95% CI 5.0-38.0).</p><p><strong>Conclusions: </strong>BMC remains a rare but challenging complication of mBC. Endocrine-based targeted therapy may improve outcomes in selected HR-positive/HER2-negative patients. Larger multicenter studies are needed to optimize diagnosis and treatment strategies.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 7","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleotide excision repair in tumor response to DNA-damaging anticancer therapies: a comprehensive review.","authors":"Bartosz Maćkowiak, Kamila Ostrowska, Julia Kozikowska, Katarzyna Kulcenty, Wojciech Golusiński, Wiktoria Suchorska","doi":"10.1007/s00432-026-06563-0","DOIUrl":"10.1007/s00432-026-06563-0","url":null,"abstract":"<p><p>Nucleotide excision repair (NER) is a critical DNA repair pathway responsible for removing bulky, helix-distorting DNA lesions, including ultraviolet radiation-induced photoproducts and platinum drug-DNA adducts. This review provides a comprehensive overview of current understanding of NER in cancer, with particular emphasis on its role in therapeutic response. We discuss the molecular mechanisms of DNA repair in cancer, the significance of NER in platinum-based therapies, results from in vitro studies across various cancer types, findings from patient-based studies, and outcomes from clinical trials. Special attention is given to ERCC1, ERCC2/XPD, XPA, and XPC molecules as potential biomarkers of treatment response and therapeutic targets, and incorporating the most recent discoveries regarding NER inhibitors, mutational signatures, and synthetic lethality-based approaches.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic potential of an immunology score in patients treated with curative surgery for non-small cell lung cancer.","authors":"Sara Witting Christensen Wen, Signe Timm, Morten Borg, Ole Hilberg, Torben Frøstrup Hansen, Christa Haugaard Nyhus, Torben Schjødt Hansen, Line Nederby","doi":"10.1007/s00432-026-06562-1","DOIUrl":"10.1007/s00432-026-06562-1","url":null,"abstract":"<p><strong>Purpose: </strong>Curative surgery is the best treatment for patients with early-stage non-small cell lung cancer (NSCLC), but around 40% experience recurrence impacting survival. Does the individual immunological status affect the prognosis? This study investigated four immunology markers in relation to recurrence and survival after curative surgery for NSCLC.</p><p><strong>Methods: </strong>Natural Killer cell activity (NKA), C-reactive protein (CRP), Interleukin 6 (IL6) and Transforming growth factor beta (TGFβ) were analysed before surgery and at three months after surgery for NSCLC.</p><p><strong>Results: </strong>Of the 103 enrolled patients, 43 experienced recurrence over a period of median 71 months. The biomarkers were unsuitable for detecting recurrence with area under the receiver operating characteristics curve ranging from 0.52 to 0.58. Baseline CRP and TGFβ were significantly associated with overall survival (OS), and a score based on all four biomarkers demonstrated statistically significant prognostic impact on both recurrence free survival (RFS) and OS. The biomarker score was an independent prognostic factor when adjusting for stage and surgery type, hazard ratio 3.18 (95% CI 1.53-6.61, p = 0.002) for OS with borderline significance for RFS, hazard ratio 1.93 (95% CI 1.06-3.51, p = 0.032).</p><p><strong>Conclusion: </strong>Individually, NKA, CRP, IL6 and TGFβ were not suited for predicting disease recurrence after curative surgery for NSCLC. However, the combined biomarker score was significantly associated with OS. The score may give an indication of the immunological status of the patient, which could be useful for pre- or post-surgery assessment, in relation to immunotherapy or other oncologic treatments if future studies can prove clinical utility.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of early vs. delayed metastasis-directed therapy on clinical outcomes in high Gleason score metastatic prostate cancer: long-term results of a landmark cohort study (PROMPT-G).","authors":"Huizhu Chen, Xueying Ren, Yun Bai, Jiayan Chen, Wei Yu, Kaiwei Yang, Xiaoying Li, Shangbin Qin, Mingxia Sun, Xuesong Li, Hongzhen Li, Xianshu Gao, Mingwei Ma","doi":"10.1007/s00432-026-06552-3","DOIUrl":"https://doi.org/10.1007/s00432-026-06552-3","url":null,"abstract":"<p><strong>Purpose/objective(s): </strong>For patients who have received standard systemic treatment during the metastatic hormone-sensitive prostate cancer (mHSPC) stage, the optimal timing of radiotherapy (RT) is still not clear. We compared the efficacy and safety of early RT (≤ 6 months after systemic therapy initiation) versus delayed RT (> 6 months) in high Gleason Score patients.</p><p><strong>Materials/methods: </strong>Patients with high Gleason Score prostate cancer receiving standard systemic therapy in the metastatic hormone-sensitive phase followed by metastasis-directed radiotherapy (MDT, RT to all detectable lesions) from 2018 to 2025 were included. Patients were categorized into early RT (≤ 6 months) and delayed RT (> 6 months) groups. Inverse probability of treatment weighting (IPTW) balanced baseline characteristics. The primary endpoint was castration-resistant prostate cancer-free survival (CRPCFS) analyzed by IPTW-weighted Cox models.</p><p><strong>Results: </strong>Among 196 patients, 190 were analyzed (65 early RT, 125 delayed RT). IPTW achieved generally good balance in measured baseline covariates. Median follow-up was 33.1 months. Early RT significantly improved CRPCFS (HR 0.172, 95% CI 0.063-0.469, P = 0.001), with 5-year CRPCFS rates of 71.1% vs. 44.0%. Results were consistent in multivariable and competing risk analyses. Early RT also improved PFS (P = 0.007), PSAPFS (P = 0.002), and OS (P = 0.018), with benefits consistent across tumor volume subgroups (P-interaction = 0.191). Sensitivity analyses confirmed robustness.</p><p><strong>Conclusion: </strong>Earlier RT was associated with improved CRPCFS, with favorable signals in secondary outcomes. These findings warrant prospective evaluation of RT timing in high Gleason score mHSPC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}