Aikaterini Liapi, Veronica Aedo-Lopez, Wendy Jeanneret-Sozzi, Athina Stravodimou, John O Prior, Marie Nicod Lalonde, Assia Ifticene Treboux, Loic Lelievre, Lana Kandalaft, Laetitia Rossier, Audrey Goupil, Marzio Bergomi, Jean-Paul Rivals, Jean-Philippe Brouland, Elsa Curtit, Jean-Yves Meuwly, Khalil Zaman
{"title":"Retrospective comprehensive analysis of regional lymph node recurrence in breast cancer patients (REASON study).","authors":"Aikaterini Liapi, Veronica Aedo-Lopez, Wendy Jeanneret-Sozzi, Athina Stravodimou, John O Prior, Marie Nicod Lalonde, Assia Ifticene Treboux, Loic Lelievre, Lana Kandalaft, Laetitia Rossier, Audrey Goupil, Marzio Bergomi, Jean-Paul Rivals, Jean-Philippe Brouland, Elsa Curtit, Jean-Yves Meuwly, Khalil Zaman","doi":"10.1007/s00432-025-06235-5","DOIUrl":"10.1007/s00432-025-06235-5","url":null,"abstract":"<p><strong>Background: </strong>Randomized trials have progressively enabled the de-escalation of axillary surgery in breast cancer (BC) patients, reducing adverse events without compromising survival. Despite a not negligible rate of residual disease in the axilla after sentinel lymph node (SLN) procedure, the risk of regional lymph node recurrence (RLNR) is very low, due probably to multimodal adjuvant treatments. The characteristics of the small number of patients with RLNR remain poorly characterized and warrant further investigation, especially given their poor prognosis and the current context of ongoing studies exploring further de-escalation of axillary surgery.</p><p><strong>Methods: </strong>In this retrospective and single institution study, we analyzed thoroughly a cohort of patients who experienced RLNR as first event between 2009 and 2020. MammaPrint and BluePrint analysis (MB) was performed in available primary invasive cancer tissues.</p><p><strong>Results: </strong>Forty patients, median age of 52, were analyzed. Disease-free interval was 8.7 years. Most of the patients (65%) had no special type BC. Majority (73%) had hormone receptor positive-HER2 negative (HR + /HER2-) BC, 13% triple negative (TNBC), 6% HER2 + , 8% ductal carcinoma in situ and 3% unknown. The median size of the primary tumor was 1.8 cm (range 0.3-7.0) and 57% had no initial LN involvement. Forty five percent had primary SLN procedure and 53% axillary LN dissection (ALND) of the patients received neo-/adjuvant chemotherapy, 63% endocrine therapy and 68% radiotherapy (50% only in breast). Sixty three percent had only RLNR and 38% had concomitant distant metastases. Among irradiated patients, 63% had some relapse in the radiation field. The MB analysis classified 70% of the analyzed cancers as low-risk luminal A (82% in HR + /HER2-), 15% high-risk luminal B, 10% high-risk basal type, and 5% high-risk HER2 type.</p><p><strong>Conclusion: </strong>Our study confirms that patients treated with SLN do not show a higher risk of LRNR compared to ALND. LRNR is often diagnosed incidentally. Younger age, residual disease post-NAC, no regional radiation, stage II, and initial LN involvement were more represented, as well as patients with endocrine sensitive disease classified as low-risk luminal A by MB. Ongoing trials, including SOUND, INSEMA, and BOOG 2013-08, are further exploring axillary surgery de-escalation.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"176"},"PeriodicalIF":2.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173878","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}
Zheng-Zheng Shen, En-Ze Li, Ruo-Lan Zhang, Meng-Xuan Cao, Yan-Qiang Zhang, Qing Yang, Can Hu, Si-Wei Pan, Zhi-Yuan Xu, Zai-Sheng Ye, Jing-Yang He
{"title":"Adjuvant chemotherapy may have no significant survival benefit in older patients with stage II/III gastric cancer: a multicenter retrospective study.","authors":"Zheng-Zheng Shen, En-Ze Li, Ruo-Lan Zhang, Meng-Xuan Cao, Yan-Qiang Zhang, Qing Yang, Can Hu, Si-Wei Pan, Zhi-Yuan Xu, Zai-Sheng Ye, Jing-Yang He","doi":"10.1007/s00432-025-06230-w","DOIUrl":"10.1007/s00432-025-06230-w","url":null,"abstract":"<p><strong>Aim: </strong>Postoperative adjuvant chemotherapy is known to enhance cure rates and is thus recommended for stages pII to pIII. However, specific guidelines for such treatment in elderly gastric cancer (GC) patients are currently lacking. This study examines the impact of adjuvant chemotherapy on the postoperative survival of these patients.</p><p><strong>Methods: </strong>We reviewed a total of 7749 patients with GC who underwent radical gastrectomy at Zhejiang Cancer Hospital and Fujian Cancer Hospital from January 2007 to December 2019. We conducted univariate and multivariate Cox regression analyses to investigate the impact of clinicopathological factors on overall survival (OS) and cancer-specific survival (CSS) in these patients. Additionally, we created a meta-analysis forest plot and employed propensity score matching (PSM) to mitigate confounding bias.</p><p><strong>Results: </strong>Age and adjuvant chemotherapy were independent risk factors for OS and CSS. Stratified analysis based on chemotherapy use revealed a statistically significant difference in OS and CSS between younger patients who did and did not receive adjuvant chemotherapy. In contrast, no significant differences in OS and CSS were observed between older patients with or without adjuvant chemotherapy. These findings remained consistent after propensity score matching (PSM).</p><p><strong>Conclusions: </strong>Age and adjuvant chemotherapy are independent risk factors for OS and CSS in patients with stage II/III GC; for patients with stage II/III gastric cancer aged ≥ 75 years, shared decision-making should be made taking into account functional status and comorbidities, rather than conventional adjuvant chemotherapy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"175"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150560","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":"Preclinical pharmacokinetics and in vitro ADME properties of PAT-1102: a novel HDAC inhibitor for cancer therapy.","authors":"Chandrashekar Mataguru Doreswamy, Srinivas Seekallu, Suresh Babu Venkataramaiah, Mohan Cheluru Umesh, C Subathra Devi","doi":"10.1007/s00432-025-06227-5","DOIUrl":"10.1007/s00432-025-06227-5","url":null,"abstract":"<p><strong>Background: </strong>Histone deacetylases (HDAC) are involved in chromatin remodelling, and histone deacetylases inhibitors have become the interest of research and shown promising antitumor effects against various cancer.</p><p><strong>Methods: </strong>In the current study, an attempt was made to characterize the preclinical ADME properties of a novel hydroxamic based HDAC inhibitor, PAT-1102, with the help of in vitro assays and in vivo pharmacokinetic experiments in rats.</p><p><strong>Results: </strong>PAT-1102 showed high aqueous solubility and high Caco-2 permeability in the in vitro assays. It was found to be not a substrate of efflux protein P-gp, found stable in metabolism experiments with incubations of rat and human liver microsomes. Inhibition experiments of human recombinant CYP enzymes revealed that PAT-1102 was not considerably inhibited the major CYP enzymes. PAT-1102 exhibited low plasma protein binding of 58.1% and 54.5% in humans and rats, respectively. In vivo pharmacokinetic studies of PAT-1102 in male and female rats showed bioavailability of 3.7% and 3.0% by oral route, respectively. Previous research findings suggested that PAT-1102 is a potent pan-HDAC inhibitor with good preclinical efficacy.</p><p><strong>Conclusion: </strong>Considering the overall ADME and pharmacokinetic profile of PAT-1102, as indicated by in vitro and in vivo experiments, the PAT-1102 could be considered as a potential candidate for the advancement of cancer therapy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"174"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136279","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}
Lijie Liang, Xue Meng, Li Xie, Na Li, You Feng, Ming Jiang
{"title":"Efficacy and safety of the R2-MTX regimen in primary central nervous system lymphoma (PCNSL): a single-center retrospective analysis.","authors":"Lijie Liang, Xue Meng, Li Xie, Na Li, You Feng, Ming Jiang","doi":"10.1007/s00432-025-06205-x","DOIUrl":"10.1007/s00432-025-06205-x","url":null,"abstract":"<p><strong>Purpose: </strong>Primary central nervous system lymphoma (PCNSL) has a poor prognosis, mainly because of the significant challenges with the efficacy and tolerability of induction chemotherapy. This retrospective study aimed to evaluate the efficacy and safety of the R2-MTX regimen in PCNSL patients.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 39 PCNSL patients treated with the R2-MTX regimen, focusing on treatment outcomes and adverse events (AEs).</p><p><strong>Results: </strong>The overall response rate (ORR) was 72.2%, with a complete response (CR) rate of 69.4% and a partial response (PR) rate of 2.8%. With a median follow-up of 37.2 months (interquartile range [IQR] 24.2-47.5), the estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 54.9% (95% CI, 37.2-69.5%) and 78.5% (95% CI, 59.8-89.2%), respectively. The most common grade 3 or 4 AEs included neutropenia (33.3%), leukopenia (13.9%), anemia (2.8%), and thrombocytopenia (2.8%). Consolidation or maintenance therapy was associated with prolonged survival in PCNSL patients (2-year OS rates 100% vs. 42.9%, P = 0.067). Survival analysis revealed that clinicopathological factors, such as double-expressor lymphoma (DEL), ECOG PS ≥ 2, and high-risk classification based on the Memorial Sloan Kettering Cancer Center model (MSKCC), predicted poor survival.</p><p><strong>Conclusions: </strong>Our results underscore the therapeutic potential of the R2-MTX regimen in managing newly diagnosed PCNSL patients. Further prospective studies with larger patient cohorts are imperative to solidify these preliminary findings.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"173"},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119732","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}
Marie Forster, Sophie Winkler, Martin R Fischer, Dirk Hempel, Valeria Milani
{"title":"Hemato-oncological outpatient care in medical education: a German pilot-project.","authors":"Marie Forster, Sophie Winkler, Martin R Fischer, Dirk Hempel, Valeria Milani","doi":"10.1007/s00432-025-06198-7","DOIUrl":"10.1007/s00432-025-06198-7","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the experience of online and practical medical teaching in the outpatient hemato-oncological primary care setting and to analyze challenges and chances for students and teachers in specialized outpatient institutions.</p><p><strong>Methods: </strong>The study involving medical students of the Ludwig-Maximilians-University (LMU) in their 6th-7th semester evaluates content and didactic methodology of online teaching seminars, bed-side clerkships and mentoring regarding one selected oncological center. The data was collected via questionnaires using Likert-scaled items.</p><p><strong>Results: </strong>In one outpatient cancer center a total of 279 students attended the online lessons (2020-2023). 102 evaluations were collected, and all aspects of teaching of the online seminars and clerkship were rated very well (mean score of 1.2 on the item \"overall evaluation\" with a small range of 1.0-1.3, n = 102). Criticism was mainly leveled at technical issues (n = 16). The evaluations (n = 10) of the students attending a one-day bed side teaching revealed high interest in learning the practice in the outpatient setting. 90% stated an improvement in understanding of outpatient practice as well as intersectoral processes due to the one-day bedside teaching and favored an integration of this new teaching format into the regular medical curriculum. Two students applied for a four-week internship and six chose a mentorship in hematology-oncology, resulting in four medical thesis projects in this field.</p><p><strong>Conclusion: </strong>Increased participation of outpatient centers in medical education improved knowledge on outpatient medicine and interprofessional care and generated interest in the field of oncology. Outpatient cancer specialists should be more involved in the curriculum of medical students.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"172"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110819","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}
Xi Wei, Rong Qin, Liang Yin, Muhammad Asad Iqbal, Zakari Shaibu, Guorui Li, Ting Wu
{"title":"Investigating the role of the Pon1-rs854560 (L55M) SNP in colorectal Cancer susceptibility.","authors":"Xi Wei, Rong Qin, Liang Yin, Muhammad Asad Iqbal, Zakari Shaibu, Guorui Li, Ting Wu","doi":"10.1007/s00432-025-06226-6","DOIUrl":"10.1007/s00432-025-06226-6","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with both genetic and environmental risk factors. The PON1 rs854560 (L55M) polymorphism has been implicated in cancer susceptibility through its role in oxidative stress regulation, but its association with CRC remains unclear, particularly in Asian populations.</p><p><strong>Aim: </strong>This study aimed to investigate the association between the PON1 rs854560 polymorphism and CRC susceptibility in a Chinese cohort, while assessing its impact on PON1 expression and enzymatic activity.</p><p><strong>Method: </strong>A case-control study was conducted on 1,003 CRC patients and 1,303 healthy controls. The impact of the Pon1-rs854560 SNP was assessed by comparing the genotypes of individuals diagnosed with CRC to those of controls without the disease.</p><p><strong>Results: </strong>Genotype distribution showed slight differences between the case and control groups. The frequency of the AA genotype was slightly lower in the case group (91.72%) than in the control group (93.71%). The AT genotype was observed at similar frequencies in both groups (8.28% in the case group and 6.14% in the control group). Notably, the TT genotype was absent in the case group but present in 0.15% of the control group. Genotype combination analysis suggested that individuals carrying the AT + TT genotype (8.28%) had a higher susceptibility to CRC compared to those with the AA + AT genotype (100%). Allele frequency analysis revealed a slightly higher frequency of allele T in the case group (8.28%) than in the control group (6.45%). Additionally, lower PON1 mRNA and protein expression were associated with CRC progression, including features such as poorer differentiation, deeper tumor invasion, and vascular, nerve, and lymphatic metastasis.</p><p><strong>Conclusion: </strong>The PON1 rs854560 polymorphism influences CRC risk in Chinese individuals, likely through reduced PON1 expression and detoxification capacity. These findings highlight its potential as a genetic biomarker for CRC susceptibility and suggest PON1's role in tumor progression. Further studies should validate these associations in diverse populations and explore therapeutic strategies targeting PON1 activity.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"170"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101928","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":"Integration of transcriptome-wide association study and gene-based association analysis identifies candidate genes for Hodgkin lymphoma.","authors":"Wen-Hui Jia, Chang-Ling Huang, Wen-Li Zhang, Yong-Qiao He, Wen-Qiong Xue, Ying Liao, Zhi-Yang Zhao, Meng-Xuan Yang, Lu Pei, Wei-Hua Jia, Tong-Min Wang","doi":"10.1007/s00432-025-06224-8","DOIUrl":"10.1007/s00432-025-06224-8","url":null,"abstract":"<p><strong>Background: </strong>Genome-wide association studies (GWASs) have pinpointed many susceptibility loci for Hodgkin Lymphoma (HL), but their underlying biological mechanisms remain unclear.</p><p><strong>Methods: </strong>Utilizing GWAS data from the UK Biobank and FinnGen, along with expression quantitative trait loci (eQTL) statistics from the Genotype-Tissue Expression (GTEx) and the eQTL Catalogue, we carried out a large-scale gene-level association study using Omnibus Transcriptome Test with Expression Reference Summary data (OTTERS), and gene-based analysis with eQTL Multi-marker Analysis of Genomic Annotation (E-MAGMA).</p><p><strong>Results: </strong>We identified sixteen susceptibility genes for HL (FDR < 0.01), primarily immune-related, including HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, HLA-DRB5, HLA-DMA, and HLA-DPB1, alongside genes involved in apoptosis, RNA processing, transcriptional regulation, and signal transduction. We identified five novel plausible genes, including HLA-DMA, HLA-DPB1, LSM2, AAR2, and NOTCH4.</p><p><strong>Conclusion: </strong>These findings highlight the role of the exogenous antigen presentation pathway in HL, shedding light on potential mechanisms.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"171"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110822","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}
Juan Xu, Haonan Yang, Jingcao Huang, Ting Niu, Chunyan Sun, Li Zhang, Yuhuan Zheng
{"title":"A comprehensive analysis of bone marrow-derived cytogenetic abnormalities in multiple myeloma patients with extramedullary disease.","authors":"Juan Xu, Haonan Yang, Jingcao Huang, Ting Niu, Chunyan Sun, Li Zhang, Yuhuan Zheng","doi":"10.1007/s00432-025-06223-9","DOIUrl":"10.1007/s00432-025-06223-9","url":null,"abstract":"<p><strong>Background: </strong>Extramedullary disease (EMD) in multiple myeloma (MM) remains a critical clinical challenge due to its aggressive behavior and resistance to conventional therapies. While cytogenetic abnormalities are recognized contributors to MM progression, their specific roles in EMD pathogenesis-particularly in distinguishing bone marrowderived profiles between EMD and non-EMD patients-remain inadequately characterized.</p><p><strong>Methods: </strong>In this comprehensive study, we analyzed 41 published studies involving 9424 MM patients, and identified EMD in 32.2% (3038) of cases. Our aim was to elucidate the bone marrow-derived cytogenetic profiles of MM patients with EMD, comparing them to those without EMD.</p><p><strong>Results: </strong>Among EMD-MM patients, the most prevalent abnormalities were del(13q)/del RB1 (32.3%), 1q21+ (29.6%), and hyperdiploidy (26.3%). High-risk cytogenetic abnormalities were led by 1q21+ (29.6%), del(17p)/del p53 (14.4%), and t(4;14) (13.6%). Notably, 1q21+ was the most frequent aberration in the EM-E subgroup, accounting for 32.2% of cases. Comparative analyses revealed significantly higher frequencies of del(17p)/del p53 and del(13q)/del RB1 in EMD patients compared to non-EMD patients, along with a slightly higher frequency of 1q21+. Conversely, EMD patients exhibited lower frequencies of hyperdiploidy and t(11;14) promoting MM evolution. Subgroup analyses confirmed these trends and revealed a more pronounced prevalence of del(13q)/del RB1 in the EM-E subgroup.</p><p><strong>Conclusions: </strong>Our findings underscore the importance of integrating cytogenetic data into risk stratification for MM patients with EMD. These results also highlight the need for further research to elucidate the mechanisms underlying cytogenetic abnormalities in EMD and their clinical implications.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"169"},"PeriodicalIF":2.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093913","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}
Alex Besson, Ke Cao, Ahmed Mardinli, Lara Wirth, Josephine Yeung, Rory Kokelaar, Peter Gibbs, Fiona Reid, Justin M Yeung
{"title":"Artificial intelligence generated 3D body composition predicts dose modifications in patients undergoing neoadjuvant chemotherapy for rectal cancer.","authors":"Alex Besson, Ke Cao, Ahmed Mardinli, Lara Wirth, Josephine Yeung, Rory Kokelaar, Peter Gibbs, Fiona Reid, Justin M Yeung","doi":"10.1007/s00432-025-06219-5","DOIUrl":"10.1007/s00432-025-06219-5","url":null,"abstract":"<p><strong>Purpose: </strong>Chemotherapy administration is a balancing act between giving enough to achieve the desired tumour response while limiting adverse effects. Chemotherapy dosing is based on body surface area (BSA). Emerging evidence suggests body composition plays a crucial role in the pharmacokinetic and pharmacodynamic profile of cytotoxic agents and could inform optimal dosing. This study aims to assess how lumbosacral body composition influences adverse events in patients receiving neoadjuvant chemotherapy for rectal cancer.</p><p><strong>Methods: </strong>A retrospective study (February 2013 to March 2023) examined the impact of body composition on neoadjuvant treatment outcomes for rectal cancer patients. Staging CT scans were analysed using a validated AI model to measure lumbosacral skeletal muscle (SM), intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue volume and density. Multivariate analyses explored the relationship between body composition and chemotherapy outcomes.</p><p><strong>Results: </strong>242 patients were included (164 males, 78 Females), median age 63.4 years. Chemotherapy dose reductions occurred more frequently in females (26.9% vs. 15.9%, p = 0.042) and in females with greater VAT density (-82.7 vs. -89.1, p = 0.007) and SM: IMAT + VAT volume ratio (1.99 vs. 1.36, p = 0.042). BSA was a poor predictor of dose reduction (AUC 0.397, sensitivity 38%, specificity 60%) for female patients, whereas the SM: IMAT + VAT volume ratio (AUC 0.651, sensitivity 76%, specificity 61%) and VAT density (AUC 0.699, sensitivity 57%, specificity 74%) showed greater predictive ability. Body composition didn't influence dose adjustment of male patients.</p><p><strong>Conclusion: </strong>Lumbosacral body composition outperformed BSA in predicting adverse events in female patients with rectal cancer undergoing neoadjuvant chemotherapy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"168"},"PeriodicalIF":2.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086349","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":"High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway.","authors":"RuiYang Hong, Su Min, Jia Huang, Mou Zou, DongYu Zhou, Yun Liang","doi":"10.1007/s00432-025-06211-z","DOIUrl":"10.1007/s00432-025-06211-z","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction is closely associated with cancer development. Colorectal cancer (CRC) cells often exhibit altered energy metabolism, characterized by increased glycolysis and reduced oxidative phosphorylation. Enhancing mitochondrial biogenesis and function may represent a promising therapeutic approach. High-dose vitamin C has demonstrated anti-tumor properties and the ability to reverse the Warburg effect, but its role in regulating mitochondrial biogenesis and function remains unclear.</p><p><strong>Methods: </strong>We evaluated the altered mitochondrial functional status of HCT116 colorectal cancer cells compared to FHC colorectal epithelial cells, assessed the effects of high-dose vitamin C on mitochondrial biogenesis and function in HCT116 cells, and explored the underlying regulatory mechanisms.</p><p><strong>Results: </strong>HCT116 cells exhibited mitochondrial dysfunction compared to FHC cells, including decreased expression of electron transport chain complexes III and IV, reduced TFAM levels, and lower mtDNA content. Vitamin C treatment significantly enhanced mitochondrial biogenesis and function, as reflected by increased AMPK phosphorylation, upregulation of PGC-1α, SOD2, NRF2, TFAM, MT-CYB, and MTCO1, elevated mtDNA content, restored membrane potential, enhanced oxidative phosphorylation, and reduced glycolytic activity. Furthermore, vitamin C markedly suppressed HCT116 cell viability and clonogenic capacity, while these effects were substantially diminished by cotreatment with Compound C.</p><p><strong>Conclusion: </strong>This study demonstrates that high-dose vitamin C ameliorates mitochondrial dysfunction and promotes mitochondrial biogenesis and function in colorectal cancer cells through activation of the AMPK-PGC-1α signaling pathway, thereby suppressing tumor cell proliferation. These findings suggest that vitamin C may serve as a promising therapeutic agent for targeting mitochondrial metabolism in colorectal cancer.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 5","pages":"167"},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078199","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}