Chia-Ni Lin, Jung-Der Wang, Wen-Yen Huang, Jing-Shiang Hwang, Li-Jung Elizabeth Ku, Fuhmei Wang
{"title":"Mammography screening reduced lifetime loss of employment duration and productivity for women with breast cancer: Real-world evidence of societal impacts.","authors":"Chia-Ni Lin, Jung-Der Wang, Wen-Yen Huang, Jing-Shiang Hwang, Li-Jung Elizabeth Ku, Fuhmei Wang","doi":"10.1002/ijc.70051","DOIUrl":"https://doi.org/10.1002/ijc.70051","url":null,"abstract":"<p><p>The objective of this study is to evaluate the personal and societal impacts of mammography screening by estimating the life expectancy (LE), LE loss, lifetime employment duration (LED), LED loss, lifetime productivity (LP), and LP loss of women with breast cancer (BC). We recruited 113,169 women with BC diagnosis (2002-2017) from the Taiwan Cancer Registry, following survival until 2018. The monthly employment-population ratio (EMRATIO) and insured salary were abstracted from the National Health Insurance (NHI) until 2017. Lifetime survivals were extrapolated using relative survival with age-, sex-, and calendar-year-matched referents from vital statistics through a rolling-over algorithm, which were used in hazard models estimating LED and LP, with losses calculated by comparing the BC cohort to matched referents and relative loss percentages. We summarized the overall losses of LED and LP weighted by stage shifts between those who received screening versus those who did non-screening. We found no LED or LP losses for stages 0-I. LED losses for stages II-IV were 0.8, 2.3, and 5.1 years, respectively, with relative losses of LP being 9.4%, 30.2%, and 69.0%, respectively. Younger women faced more significant losses, with those aged 18-39 experiencing at least triple LED loss in stages III and IV compared to stage II. Mammography screening led to overall reductions of 2.9 years in LE, 0.6 years in LED, and 7.1% in LP, equivalent to a savings of US$ 7169. The mammography screening program in Taiwan improved the health and productivity of the population, especially among younger women.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melissa Bello-Perez, Paula Mascarell, Marta Fernández-González, Jose Alberto García, Ana Gutiérrez-Ortiz de la Tabla, Christian Ledesma, Alba De la Rica, Antonio Galiana, Leo López, Maria Dolores Ocete, Carme Salvador, Concepción Gimeno, Javier García-Abellán, Sergio Padilla, Félix Gutiérrez, Mar Masiá
{"title":"ADAR1 mRNA quantification for predicting HSIL in persons with HIV and abnormal anal cytology.","authors":"Melissa Bello-Perez, Paula Mascarell, Marta Fernández-González, Jose Alberto García, Ana Gutiérrez-Ortiz de la Tabla, Christian Ledesma, Alba De la Rica, Antonio Galiana, Leo López, Maria Dolores Ocete, Carme Salvador, Concepción Gimeno, Javier García-Abellán, Sergio Padilla, Félix Gutiérrez, Mar Masiá","doi":"10.1002/ijc.70050","DOIUrl":"https://doi.org/10.1002/ijc.70050","url":null,"abstract":"<p><p>Anal squamous cell carcinoma is a significant concern among people with HIV (PWH), with high-grade squamous intraepithelial lesions (HSIL) as its precursor. Current screening, primarily based on abnormal anal cytology, often results in unnecessary high-resolution anoscopies (HRA) due to limited specificity. This study evaluates whether quantifying Adenosine Deaminase Acting on RNA-1 (ADAR1) mRNA in anal swabs improves HSIL prediction and optimizes HRA selection. In this prospective cohort, HIV-positive adults with abnormal anal cytology underwent HRA. ADAR1 mRNA levels were quantified from anal swabs, and human papillomavirus (HPV) genotyping was performed. The diagnostic performance of ADAR1 mRNA was assessed using receiver operating characteristic (ROC) curve analysis and compared with E6/E7 mRNA detection for high-risk HPV (HR-HPV). HSIL was confirmed by biopsy in 40 of 171 participants (23.4%). HSIL cases had significantly higher ADAR1 mRNA levels (median: 49.4 vs. 4.1 relative units [RU], p < .001) and a greater median number of HPV genotypes (5 vs. 3, p < .001). ROC analysis for ADAR1 mRNA yielded an area under the curve (AUC) of 0.83 (95% CI: 0.75-0.92). At a cut-off of ≥24.8 RU, it demonstrated 73% sensitivity, 92% specificity, 74% positive predictive value, and 92% negative predictive value. Compared to E6/E7 mRNA, ADAR1 mRNA improved screening accuracy (64%-88%) and reduced HRA referrals (77.2%-48.8%). ADAR1 mRNA quantification reliably predicts HSIL in PWH with abnormal anal cytology. Integrating ADAR1 mRNA measurement into anal cancer screening protocols may enhance diagnostic accuracy, reduce unnecessary invasive procedures, and alleviate the burden on limited HRA resources.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fenna de Vries, Leila-Sophie Otten, Berber Piet, Eric J F Franssen, Arthur A J Smit, Michel M van den Heuvel, Rob Ter Heine
{"title":"Early pembrolizumab clearance as prognostic biomarker for non-response in patients with advanced non-small cell lung cancer.","authors":"Fenna de Vries, Leila-Sophie Otten, Berber Piet, Eric J F Franssen, Arthur A J Smit, Michel M van den Heuvel, Rob Ter Heine","doi":"10.1002/ijc.70052","DOIUrl":"https://doi.org/10.1002/ijc.70052","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have improved survival rates in patients with advanced-stage non-small cell lung cancer; however, the majority obtain no long-term benefits. We investigated pembrolizumab clearance as an early prognostic biomarker and evaluated its accuracy using a limited sampling strategy. Pembrolizumab clearance was calculated using non-linear mixed effects modeling, and cut points were determined using maximally selected rank statistics. The prognostic value for survival was estimated using univariate Cox regression analysis. Sensitivity, specificity, and positive and negative predictive values were calculated to evaluate the performance in identifying response (defined as disease control at 6 months). The accuracy of a limited sampling strategy was evaluated using MPE and NRSME. Among 303 patients included, 65% experienced disease progression, and 60% died. Patients with pembrolizumab clearance above 0.232 L/day at the first dose were more likely to have disease progression (HR = 1.98, 95% CI [1.21, 3.26], p = .007) or poor survival (HR = 2.04, 95% CI [1.16, 3.59], p = .014). A diminished decrease in clearance (<15.8%) at 6 weeks was also significantly associated with progression (HR = 1.46, 95% CI [1.12, 1.92], p = .006) and poor survival (HR = 1.82, 95% CI [1.35, 2.45], p = .000). Pembrolizumab clearance showed high sensitivity (0.96, 95% CI [0.92, 0.99]), but moderate positive predictive value (0.48). Limited sampling matched comprehensive sampling accuracy (MPE = +4.5% vs. +3.2%, NRSME = 16.8% vs. 14.2%). Early pembrolizumab clearance is a feasible prognostic biomarker for survival, with opportunities to enhance its positive predictive value before clinical implementation.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Ding, Ben Schöttker, Hermann Brenner, Michael Hoffmeister
{"title":"Thirteen simple lifestyle scores and risk of cancer, cardiovascular disease, diabetes, and mortality: Prospective cohort study in the UK Biobank.","authors":"Jie Ding, Ben Schöttker, Hermann Brenner, Michael Hoffmeister","doi":"10.1002/ijc.70064","DOIUrl":"https://doi.org/10.1002/ijc.70064","url":null,"abstract":"<p><p>Numerous simple lifestyle scores have been developed for specific non-communicable diseases (NCDs). This research aimed to investigate and compare the associations of various lifestyle scores with the incidence and mortality of NCDs. In 76,399 participants from the UK Biobank, we investigated the associations of 13 lifestyle scores with the incidence and mortality of cancer, cardiovascular disease (CVD), type 2 diabetes (T2D), and a composite of these NCDs. Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for associations between lifestyle scores and NCD outcomes. During a median follow-up time of 10.5 years, 12,214 incident NCD cases and 2250 NCD deaths were documented. Higher lifestyle scores were generally associated with a reduced risk of overall NCDs (HRs ranging from 0.65 to 0.89) and NCD mortality (0.51-0.92). Cancer (HRs ranging from 0.72 to 0.98) and CVD (0.55-0.87) risk were less dependent on lifestyle behaviors than T2D (0.18-0.74). Notably, the top three scores associated with cancer outcomes included smoking as a component, and those for T2D included body mass index (BMI). For overall NCD outcomes, lifestyle scores including both smoking and BMI showed the strongest associations. Healthy Lifestyle Score and the Chronic Disease Risk Index were the overall best-performing scores to predict NCD risk and mortality. These findings suggest that the use of lifestyle scores designed for a single disease group can be extended for predicting multiple NCDs and mortality. Both smoking and BMI should be included in lifestyle scores aiming to predict overall NCD risk and mortality for future research and recommendations.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coline Ducrot, Derek Dinart, Mathilde Reich, Max Piffoux, Maeva Bonneau, Mathieu Larroquette, Simon Nannini, Juliane Berchoud, Helène Bellio, Gregory Cherrier, Berengère Narciso, Axel Le Cesne, Emmanuelle Bompas, Justine Gantzer, Thibaud Valentin, Philippe Anract, Sixtine de Percin, Pascaline Boudou-Rouquette, Gonzague de Pinieux, Francois Gouin, Mehdi Brahmi, Carine Bellera, Maud Toulmonde
{"title":"Metastatic chondrosarcoma, patterns of care, and outcomes of patients in a real-life national setting over a decade.","authors":"Coline Ducrot, Derek Dinart, Mathilde Reich, Max Piffoux, Maeva Bonneau, Mathieu Larroquette, Simon Nannini, Juliane Berchoud, Helène Bellio, Gregory Cherrier, Berengère Narciso, Axel Le Cesne, Emmanuelle Bompas, Justine Gantzer, Thibaud Valentin, Philippe Anract, Sixtine de Percin, Pascaline Boudou-Rouquette, Gonzague de Pinieux, Francois Gouin, Mehdi Brahmi, Carine Bellera, Maud Toulmonde","doi":"10.1002/ijc.70023","DOIUrl":"https://doi.org/10.1002/ijc.70023","url":null,"abstract":"<p><p>Metastatic chondrosarcoma (MCS) has a poor prognosis, and treatment options are scarce in this rare disease. This multicenter observational study provides real-world data on treatment patterns of patients with MCS in France. Treatment characteristics, outcomes in terms of time to next treatment (TTNT) and overall survival (OS), and prognostic factors of patients ≥12-year-old treated for a MCS in nine French reference network centers were retrieved from the French Sarcoma Group prospective database. From 2008 to 2018, 127 patients with MCS were included, 31 were metastatic from diagnosis (synchronous cohort), 89 had a metastatic relapse, and 7 had locally advanced unresectable disease, of whom 4 developed secondary metastases (metachronous cohort). Median age at diagnosis was 61 years (14-90), 58.9% of patients received a systemic treatment with a median of 2 lines (1-6), 40.3% had a locoregional procedure on metastasis, and 9.7% of patients participated in a clinical trial at least once in the metastatic setting. Median OS from metastatic diagnosis was 12.7 months [95%CI 8.2, 14.9], without significant difference between the metachronous and synchronous cohorts. Median TTNT was 4.6 months [95%CI 3.0, 5.9], 3.4 months [95%CI 2.7, 4.8], and 3.4 months [95%CI 2.0, 7.9] in first, second, and third lines, respectively. In MCS, benefits of chemotherapies are very limited. Tyrosine kinase inhibitors such as regorafenib or pazopanib show some activity from first line. Locoregional treatment of metastasis is associated with survival and should be proposed when feasible. Inclusion in clinical trials should be prioritized.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of long-term survival in childhood cancer patients using cancer registry data from eastern China: Period analysis outperforms traditional analysis.","authors":"Xin Bing, Qiqi Lei, Liangyou Wang, Xiaojiao Zhao, Xukai Chen, Luyao Zhang, Asta Försti, Jun Yang, Tianhui Chen","doi":"10.1002/ijc.70060","DOIUrl":"https://doi.org/10.1002/ijc.70060","url":null,"abstract":"<p><p>This study systematically evaluated whether period analysis outperforms traditional cohort and complete analyses in estimating 5-year relative survival (RS) for childhood cancer patients using data from nine cancer registries in Taizhou, Eastern China (2009-2018). Analyses included patients under 15 years diagnosed with childhood cancers, with 5-year RS estimates from cohort, complete, and period methods compared against observed actual survival (2014-2018: 70.1%). Accuracy and robustness were assessed via deviation value (DV) and standard error (SE). Cohort analysis yielded a 5-year RS of 55.8% (DV: -14.3%, SE: 2.4), complete analysis 61.1% (DV: -9.0%, SE: 1.7), and period analysis 68.2% (DV: -1.9%, SE: 2.1). Stratified evaluations by sex, region, age at diagnosis, and cancer types confirmed period analysis as the most accurate (lowest DV across subgroups) while complete analysis showed the smallest SE values, indicating superior robustness. Cohort analysis performed the worst in both accuracy and robustness. This study is the first in China to validate that period analysis offers superior accuracy in estimating 5-year RS for childhood cancer patients overall and across various stratifications compared to cohort and complete analyses. Findings underscore the utility of period analysis in generating timely survival estimates to inform early detection strategies and cancer control policies, offering critical methodological support for advancing pediatric oncology outcomes assessment in China.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Surachet Imlimthan, Katayun Bahrami, Henna Pehkonen, Alessia Centanni, Ahmed B Montaser, Arina Värä, Jelena Matović, Heidi Liljenbäck, Tatsiana Auchynnikava, Kristiina M Huttunen, Anne Roivainen, Anu J Airaksinen, Filip S Ekholm, Outi Monni, Jarkko Rautio, Mirkka Sarparanta
{"title":"Biological evaluation of a glucose-based boron carrier as a potential agent for boron neutron capture therapy.","authors":"Surachet Imlimthan, Katayun Bahrami, Henna Pehkonen, Alessia Centanni, Ahmed B Montaser, Arina Värä, Jelena Matović, Heidi Liljenbäck, Tatsiana Auchynnikava, Kristiina M Huttunen, Anne Roivainen, Anu J Airaksinen, Filip S Ekholm, Outi Monni, Jarkko Rautio, Mirkka Sarparanta","doi":"10.1002/ijc.70054","DOIUrl":"https://doi.org/10.1002/ijc.70054","url":null,"abstract":"<p><p>Boron neutron capture therapy (BNCT) is an innovative radiation oncology approach that targets tumors selectively, minimizing damage to healthy tissues through high-linear-energy-transfer particles released during the boron neutron capture reaction. Current boron carriers like sodium mercaptoundecahydrododecaborate (BSH) and L-p-boronophenylalanine (BPA) face limitations in specificity and solubility. Our recently developed 6-O-(o-carboranylmethyl)-d-glucopyranose (B-Glc) shows promise as an alternative, demonstrating strong interactions with glucose transporters in human head and neck squamous cell carcinoma (HNSCC) CAL 27 cells in vitro. This study aims to extend in vitro investigations to three additional patient-derived human HNSCC cell lines (UT-SCC-14, UT-SCC-28, and UT-SCC-42B) and to further evaluate in vivo pharmacokinetics in selected HNSCC tumor xenografts. The B-Glc showed superior uptake and favorable kinetic parameters compared to BPA and BSH in all tested cell lines. Initial positron emission tomography imaging using [<sup>18</sup>F]fluoro-2-deoxy-d-glucose ([<sup>18</sup>F]FDG) radiotracer confirmed increased glucose uptake in CAL 27 and UT-SCC-14 tumors in vivo, supported by glucose transporter 1 (GLUT1) expression observed in tumor section immunohistochemistry. Biodistribution studies of the B-Glc (75 mg/kg dose) revealed no significant impact of blood glucose levels on tumor uptake, with peak boron accumulation at 15-30 min post-injection, comparable uptake to the clinical BPA-fructose complex (400 mg/kg dose) performance at 60 min, achieving the required tumor boron concentration (>20 ppm) for effective BNCT. Overall, this study underscores an advancement in targeted BNCT, highlighting B-Glc as an effective GLUT1-targeting carrier for enhanced therapeutic outcome in HNSCC and the potential to use [<sup>18</sup>F]FDG as a companion diagnostic for the glucoconjugate.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The interplay between oxidative stress and epigenetic reprogramming in cancer.","authors":"Xuejiao Ma, Wei Fan, Tao Zhang, Li Luo, Kui Wang","doi":"10.1002/ijc.70058","DOIUrl":"https://doi.org/10.1002/ijc.70058","url":null,"abstract":"<p><p>Oxidative stress and epigenetic reprogramming are two crucial characteristics of cancer cells. Oxidative stress is defined as an imbalance between intracellular oxidation and antioxidation, while epigenetic modifications represent heritable alterations in gene expression without altering the DNA sequence. During the past decades, mounting evidence has suggested that oxidative stress profoundly impacts gene expression by regulating epigenetic events, including DNA methylation, histone modifications, and non-coding RNAs. In turn, epigenetic modifications can also influence oxidative stress through methylating mitochondrial DNA/RNA or regulating the expression of genes in mitochondrial electron transport chain (Mito-ETC) components and antioxidant systems. In this review, we summarize the crosstalk mechanisms between oxidative stress and epigenetic reprogramming, with an emphasis on their reciprocal regulation involved in carcinogenesis and cancer immune escape.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ramucirumab-containing chemotherapy for patients with gastrointestinal neuroendocrine carcinoma refractory/intolerant to platinum-based chemotherapy: A multicenter observational retrospective study (WJOG13420G).","authors":"Yuki Matsubara, Toshiki Masuishi, Waki Hosoda, Hidekazu Hirano, Saori Mishima, Hiroyuki Takahashi, Tomoyuki Otsuka, Kenta Kawasaki, Takeshi Kawakami, Kazuhiro Yanagihara, Takaya Shimura, Masato Komoda, Kozue Murayama, Keiko Minashi, Yoshiyuki Yamamoto, Yudai Shinohara, Shinichi Nishina, Nobuyuki Musha, Kyoko Kato, Kentaro Kawakami, Katsunori Shinozaki, Kenji Tsuchihashi, Takayuki Ando, Yosuke Kito, Akitaka Makiyama, Seiichiro Mitani, Kaori Hino, Naoki Izawa, Isao Oze, Kei Muro","doi":"10.1002/ijc.70053","DOIUrl":"https://doi.org/10.1002/ijc.70053","url":null,"abstract":"<p><p>No standard second-line chemotherapy has been established for gastrointestinal neuroendocrine carcinoma (NEC). This study aimed to determine whether ramucirumab (RAM) is a treatment candidate in this setting. We retrospectively collected data from patients with gastric and colorectal NEC who received second-line chemotherapy following platinum-based chemotherapy. The pathological diagnosis of NEC was confirmed centrally according to the World Health Organization 2019 classification. We compared the clinical outcomes between second- or later-line chemotherapy in the RAM group and second-line chemotherapy in the non-RAM group. One-hundred patients diagnosed with NEC by central pathological review were studied. The RAM and non-RAM groups included 44 (gastric/colorectal cancer, 34/10) and 56 (37/19) patients, respectively. In the RAM group, 68% of patients received RAM as second-line chemotherapy. RAM was most frequently combined with weekly paclitaxel for gastric NEC and FOLFIRI for colorectal NEC. The RAM group showed better trends in overall survival and progression-free survival than the non-RAM group, with a median of 9.0 versus 5.6 months and 4.3 versus 1.8 months, respectively (hazard ratios [HR]: 0.75 [95% CI: 0.45-1.28] and 0.45 [0.27-0.75]). Efficacy was more pronounced in gastric NEC (PFS HR: 0.32, OS HR: 0.56) compared to colorectal NEC (PFS HR: 0.82, OS HR: 1.47). The objective response rate was significantly higher in the RAM group (44%) than in the non-RAM group (6%), with notably higher responses observed in patients receiving paclitaxel plus RAM (62%). This study suggested that RAM-containing chemotherapy, especially paclitaxel plus RAM for gastric NEC, seems promising and should be further investigated.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiara Aiello, Eric Felli, Teresa Musarra, Lorenzo Nevi, Annamaria Altomare, Jordi Gracia-Sancho, Andrea Baiocchini, Simone Carotti
{"title":"Rewriting the MASLD-associated hepatocellular carcinoma script: Targeting epigenetics and metabolism.","authors":"Chiara Aiello, Eric Felli, Teresa Musarra, Lorenzo Nevi, Annamaria Altomare, Jordi Gracia-Sancho, Andrea Baiocchini, Simone Carotti","doi":"10.1002/ijc.70047","DOIUrl":"https://doi.org/10.1002/ijc.70047","url":null,"abstract":"<p><p>Abnormal epigenetic patterns are crucial for the progression of metabolic-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC) development. Recent research focused on the interplay between epigenetics and altered metabolic pathways in HCC from MASLD, suggesting that the reversibility of epigenetic changes offers potential for new therapeutic strategies. However, identifying effective epigenetic targets remains challenging due to the diverse etiologies of HCC. Targeting metabolic reprogramming, MASLD-associated HCC shows promise in reducing lipid anabolism. In this context, a more comprehensive understanding of metabolomic changes closely tied to druggable epigenetic modifications is of utmost importance. This review provides a concise summary of the key factors driving hepatocarcinogenesis in MASLD and delves deeper into the epigenetic mechanisms. Finally, we aim to present an overview of the primary mechanisms concerning the intricate bidirectional interplay between the metabolome and epigenetic modifications in MASLD-associated HCC, along with therapeutic strategies specifically targeting epigenetics and metabolomic alterations.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}