Martina Caruso, Ludovica Rita La Rocca, Arnaldo Stanzione, Nicola Rocco, Tommaso Pellegrino, Daniela Russo, Maria Salatiello, Andrea de Giorgio, Roberta Pastore, Simone Maurea, Arturo Brunetti, Renato Cuocolo, Valeria Romeo
Background/Objectives: The aim was to assess whether a machine learning (ML) algorithm could empower the ability of ultrasound (US) integrated with shear-wave elastography (SWE) to preoperatively define the ALN status in breast cancer (BC). Methods: Patients with at least one histologically proven BC lesion, who underwent preoperative breast US and SWE were retrospectively enrolled. BC lesions were segmented on US and SWE images by three different operators and radiomics features were extracted. A multi-step US and SWE feature selection was performed. A Simple Logistic ML classifier was applied to the dataset to predict the ALN status, its performance assessed through the AUC and Matthews Correlation Coefficient (MCC). The performance of the ML classifier was compared to that of an expert radiologist, who evaluated the US B-mode lymph-node features included in the test set. Results: A total of 133 BC lesions were included and divided into a training set, composed of 89 BC lesions (ALN-: 52; ALN+: 37), and a test set, including 44 BC lesions (ALN-: 24; ALN+: 20). Eight features out of the 1098 radiomics features extracted from US and SWE images were selected to build the predictive model. Simple Logistic classifier showed AUC of 0.685 and 0.677, MCC of 0.387 and 0.375 in the training and test set, respectively. The performance of the expert radiologist was higher than that of the ML classifier (AUC = 0.817), but not significantly different (p = 0.481). Conclusions: The inclusion of SWE-derived radiomics features could aid in the preoperative assessment of ALN status in BC using an ML approach.
{"title":"Augmented Prediction of N Parameter in Breast Cancer: Is It Possible with Shear-Wave Elastography Ultrasound Radiomics?","authors":"Martina Caruso, Ludovica Rita La Rocca, Arnaldo Stanzione, Nicola Rocco, Tommaso Pellegrino, Daniela Russo, Maria Salatiello, Andrea de Giorgio, Roberta Pastore, Simone Maurea, Arturo Brunetti, Renato Cuocolo, Valeria Romeo","doi":"10.3390/cancers18050862","DOIUrl":"10.3390/cancers18050862","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The aim was to assess whether a machine learning (ML) algorithm could empower the ability of ultrasound (US) integrated with shear-wave elastography (SWE) to preoperatively define the ALN status in breast cancer (BC). <b>Methods:</b> Patients with at least one histologically proven BC lesion, who underwent preoperative breast US and SWE were retrospectively enrolled. BC lesions were segmented on US and SWE images by three different operators and radiomics features were extracted. A multi-step US and SWE feature selection was performed. A Simple Logistic ML classifier was applied to the dataset to predict the ALN status, its performance assessed through the AUC and Matthews Correlation Coefficient (MCC). The performance of the ML classifier was compared to that of an expert radiologist, who evaluated the US B-mode lymph-node features included in the test set. <b>Results:</b> A total of 133 BC lesions were included and divided into a training set, composed of 89 BC lesions (ALN-: 52; ALN+: 37), and a test set, including 44 BC lesions (ALN-: 24; ALN+: 20). Eight features out of the 1098 radiomics features extracted from US and SWE images were selected to build the predictive model. Simple Logistic classifier showed AUC of 0.685 and 0.677, MCC of 0.387 and 0.375 in the training and test set, respectively. The performance of the expert radiologist was higher than that of the ML classifier (AUC = 0.817), but not significantly different (<i>p</i> = 0.481). <b>Conclusions:</b> The inclusion of SWE-derived radiomics features could aid in the preoperative assessment of ALN status in BC using an ML approach.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eicke Schuermann, Sarah Peters, Jonas E Adolph, Julien Merta, Stefan Rutkowski, Michael C Frühwald, Philipp Dammann, Hermann L Müller, Christof M Kramm, Gudrun Fleischhack, Beate Timmermann, Stephan Tippelt
Background: Proton beam therapy (PBT) is a valuable alternative to photon radiotherapy of CNS tumors in children and adolescents. While most recent studies deal with the outcome or long-term side effects of PBT, the aim of this study was to investigate the feasibility of PBT with a particular focus on the acute toxicity of a simultaneous radiochemotherapy (sPBCT). Patients and methods: We enrolled 199 children [median age 7.4 years (range, 0.9-17.9)], who received altogether 200 courses of PBT/sPBCT at initial diagnosis (n = 121) or at relapse (n = 79) with sPBCT in 52 (26%) courses. Data collection to PBT/sPBCT was based on the medical records and the KiProReg (Registry study of Standard Proton Therapy in Children at West German Proton Therapy Center) with a primarily descriptive-statistical and logistic regression analysis. Results: During PBT/sPBCT a total of n = 704 adverse events (AEs, mean 3.4 per course) were observed. Eighty-seven of them were graded as high-grade adverse events (HGAEs, Common Terminology Criteria for Adverse Eventº ≥3 (CTCAE)) which occurred in 67 (33.5%) PBT/sPBCT courses. HGAEs were in particular hematotoxicity (n = 43; 64.1%) and infections (n = 18; 26.8%). A significantly higher rate of HGAEs was documented in patients treated with sPBCT (n = 33/52; 63.5%) compared to those with PBT only (n = 34/148; 23.0%) (p = 0.001). In children with sPBCT, 15 (28.8%) patients could not receive the recommended dose or schedule of the planned chemotherapy (CTx) due to HGAEs, with the rate of planned CTx courses performed being significantly lower in patients receiving intensive intravenous CTx (p < 0.001). Interruptions of PBT and of simultaneous CTx were both significantly associated with the occurrence of infections [Odds ratios 3.002 (95% CI 1.005-8.971, p = 0.049) and 3.905 (95% CI 1.005-15.174, p = 0.049)]. Total discontinuation of treatment did not occur. Conclusions: Concurrent CTx during proton therapy is associated with a significant increased risk for HGAE occurrence and therapy interruptions requiring individual dose and schedule adjustments dependent on CTx intensity, very experienced interdisciplinary teams as well as intensive care and in-/out-patient oncology facilities on site.
背景:质子束治疗(PBT)是替代光子放射治疗儿童和青少年中枢神经系统肿瘤的一种有价值的方法。虽然最近的研究大多涉及PBT的结果或长期副作用,但本研究的目的是研究PBT的可行性,并特别关注同步放化疗(sPBCT)的急性毒性。患者和方法:我们招募了199名儿童[中位年龄7.4岁(范围0.9-17.9岁)],他们在初次诊断时(n = 121)或复发时(n = 79)共接受了200个疗程的PBT/sPBCT治疗,其中52个疗程(26%)接受了sPBCT治疗。PBT/sPBCT的数据收集基于医疗记录和KiProReg(西德质子治疗中心儿童标准质子治疗注册研究),主要采用描述性统计和逻辑回归分析。结果:在PBT/sPBCT期间,共观察到n = 704例不良事件(ae,平均每疗程3.4例)。其中87例被分级为高级不良事件(HGAEs,不良事件º≥3的通用术语标准(CTCAE)),发生在67个(33.5%)PBT/sPBCT课程中。HGAEs主要表现为血液毒性(n = 43, 64.1%)和感染(n = 18, 26.8%)。接受sPBCT治疗的患者HGAEs发生率(n = 33/52; 63.5%)明显高于仅接受PBT治疗的患者(n = 34/148; 23.0%) (p = 0.001)。在sPBCT患儿中,由于HGAEs, 15例(28.8%)患者无法接受推荐剂量或计划化疗(CTx),而接受强化静脉CTx的患者计划CTx疗程的执行率显著降低(p < 0.001)。PBT中断和同时CTx中断均与感染发生显著相关[比值比为3.002 (95% CI 1.005-8.971, p = 0.049)和3.905 (95% CI 1.005-15.174, p = 0.049)]。没有发生完全停止治疗的情况。结论:质子治疗期间同时进行CTx与HGAE发生的风险显著增加和治疗中断相关,需要根据CTx强度调整个人剂量和计划,需要非常有经验的跨学科团队以及现场的重症监护和住院/门诊肿瘤设施。
{"title":"Acute Toxicities During Proton Therapy with or Without Simultaneous Chemotherapy in Pediatric CNS Tumors: A Retrospective Cohort Study.","authors":"Eicke Schuermann, Sarah Peters, Jonas E Adolph, Julien Merta, Stefan Rutkowski, Michael C Frühwald, Philipp Dammann, Hermann L Müller, Christof M Kramm, Gudrun Fleischhack, Beate Timmermann, Stephan Tippelt","doi":"10.3390/cancers18050859","DOIUrl":"10.3390/cancers18050859","url":null,"abstract":"<p><p><b>Background:</b> Proton beam therapy (PBT) is a valuable alternative to photon radiotherapy of CNS tumors in children and adolescents. While most recent studies deal with the outcome or long-term side effects of PBT, the aim of this study was to investigate the feasibility of PBT with a particular focus on the acute toxicity of a simultaneous radiochemotherapy (sPBCT). <b>Patients and methods:</b> We enrolled 199 children [median age 7.4 years (range, 0.9-17.9)], who received altogether 200 courses of PBT/sPBCT at initial diagnosis (<i>n</i> = 121) or at relapse (<i>n</i> = 79) with sPBCT in 52 (26%) courses. Data collection to PBT/sPBCT was based on the medical records and the KiProReg (Registry study of Standard Proton Therapy in Children at West German Proton Therapy Center) with a primarily descriptive-statistical and logistic regression analysis. <b>Results:</b> During PBT/sPBCT a total of <i>n</i> = 704 adverse events (AEs, mean 3.4 per course) were observed. Eighty-seven of them were graded as high-grade adverse events (HGAEs, Common Terminology Criteria for Adverse Eventº ≥3 (CTCAE)) which occurred in 67 (33.5%) PBT/sPBCT courses. HGAEs were in particular hematotoxicity (<i>n</i> = 43; 64.1%) and infections (<i>n</i> = 18; 26.8%). A significantly higher rate of HGAEs was documented in patients treated with sPBCT (<i>n</i> = 33/52; 63.5%) compared to those with PBT only (<i>n</i> = 34/148; 23.0%) (<i>p</i> = 0.001). In children with sPBCT, 15 (28.8%) patients could not receive the recommended dose or schedule of the planned chemotherapy (CTx) due to HGAEs, with the rate of planned CTx courses performed being significantly lower in patients receiving intensive intravenous CTx (<i>p</i> < 0.001). Interruptions of PBT and of simultaneous CTx were both significantly associated with the occurrence of infections [Odds ratios 3.002 (95% CI 1.005-8.971, <i>p</i> = 0.049) and 3.905 (95% CI 1.005-15.174, <i>p</i> = 0.049)]. Total discontinuation of treatment did not occur. <b>Conclusions:</b> Concurrent CTx during proton therapy is associated with a significant increased risk for HGAE occurrence and therapy interruptions requiring individual dose and schedule adjustments dependent on CTx intensity, very experienced interdisciplinary teams as well as intensive care and in-/out-patient oncology facilities on site.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Early assessment of tumor treatment response and elucidation of resistance mechanisms are critical for optimizing therapeutic strategies and improving patient outcomes. Functional and metabolic imaging technologies, particularly positron emission tomography (PET) combined with specific tracers, enable dynamic monitoring of tumor cell metabolism and microenvironmental changes during the initial phases of therapy. This capability facilitates early prediction of treatment efficacy and investigation into mechanisms underlying drug resistance. This review synthesizes recent advances in the application of functional and metabolic imaging for early tumor treatment response evaluation and resistance assessment. Emphasis is placed on integrating multimodal imaging techniques with molecular biology approaches to comprehensively analyze the relationships among imaging biomarkers, tumor heterogeneity, immune microenvironment, and molecular pathways. The article further explores the clinical translational potential of these imaging modalities while addressing current challenges and limitations. By providing an updated overview of this rapidly evolving field, this review aims to guide future research and clinical application toward more precise and personalized oncology care.
{"title":"Advances in Functional and Metabolic Imaging for Early Tumor Treatment Response and Resistance Evaluation: A Review.","authors":"Dengwei Gan, Wenhui Ma, Huan Jie, Cong Huang, Fang Xu","doi":"10.3390/cancers18050858","DOIUrl":"10.3390/cancers18050858","url":null,"abstract":"<p><p>Early assessment of tumor treatment response and elucidation of resistance mechanisms are critical for optimizing therapeutic strategies and improving patient outcomes. Functional and metabolic imaging technologies, particularly positron emission tomography (PET) combined with specific tracers, enable dynamic monitoring of tumor cell metabolism and microenvironmental changes during the initial phases of therapy. This capability facilitates early prediction of treatment efficacy and investigation into mechanisms underlying drug resistance. This review synthesizes recent advances in the application of functional and metabolic imaging for early tumor treatment response evaluation and resistance assessment. Emphasis is placed on integrating multimodal imaging techniques with molecular biology approaches to comprehensively analyze the relationships among imaging biomarkers, tumor heterogeneity, immune microenvironment, and molecular pathways. The article further explores the clinical translational potential of these imaging modalities while addressing current challenges and limitations. By providing an updated overview of this rapidly evolving field, this review aims to guide future research and clinical application toward more precise and personalized oncology care.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction and Background: High-grade serous ovarian carcinoma (HGSOC) is notorious for its poor prognosis owing to its inherent biological aggressiveness and development of chemoresistance. The mechanistic target of rapamycin (mTOR) pathway is dysregulated in 55% of epithelial ovarian cancers, representing an appealing therapeutic target. To date, the clinical trials of mTOR inhibitors have shown modest response. In this study, we investigated the mTOR pathway in a clinical cohort of primary, chemo-naive, high-grade ovarian cancer samples, along with its regulatory post-transcriptional miRNA regulation. Methodology: We performed differential gene expression analysis on 100 HGSOC patients from TCGA and 80 healthy controls (i.e., normal ovarian tissue) from GTEx. The differentially expressed genes (DEGs) were overlaid onto the KEGG mTOR signalling pathway, followed by functional enrichment analysis. Next, we conducted differential miRNA expression analysis on the same cohort and identified regulatory miRNA-mTOR gene pairs involved in cancer pathogenesis. Finally, we constructed an interaction network and identified key hub genes and miRNAs with potential prognostic significance. Results: We identified 95 mTOR pathway genes that were significantly differentially expressed, involving upstream regulators, core components, and downstream effectors. Functional pathway analysis revealed a prominent shift toward mTORC1 activation, accompanied by paradoxical activation of autophagy. The let-7 miRNA family was identified as a key regulator of the mTOR pathway, potentially facilitating disease progression. RICTOR downregulation, a key component of the mTORC2 complex, appears to play a critical role in this histotype. In addition, FNIP1, a tumour suppressor gene implicated in mTOR dysregulation, was found to correlate with survival outcomes. Conclusions: We propose a model of dual activation of mTORC1 and autophagy in HGSOC as the metabolic rewiring enabling cancer progression under nutrient and cellular stress.
{"title":"Integrative In Silico mRNA-miRNA Profiling of mTOR Pathway Dysregulation in High-Grade Serous Ovarian Carcinoma.","authors":"Radwa Hablase, Cristina Sisu, Emmanouil Karteris, Jayanta Chatterjee","doi":"10.3390/cancers18050866","DOIUrl":"10.3390/cancers18050866","url":null,"abstract":"<p><p><b>Introduction and Background</b>: High-grade serous ovarian carcinoma (HGSOC) is notorious for its poor prognosis owing to its inherent biological aggressiveness and development of chemoresistance. The mechanistic target of rapamycin (mTOR) pathway is dysregulated in 55% of epithelial ovarian cancers, representing an appealing therapeutic target. To date, the clinical trials of mTOR inhibitors have shown modest response. In this study, we investigated the mTOR pathway in a clinical cohort of primary, chemo-naive, high-grade ovarian cancer samples, along with its regulatory post-transcriptional miRNA regulation. <b>Methodology</b>: We performed differential gene expression analysis on 100 HGSOC patients from TCGA and 80 healthy controls (i.e., normal ovarian tissue) from GTEx. The differentially expressed genes (DEGs) were overlaid onto the KEGG mTOR signalling pathway, followed by functional enrichment analysis. Next, we conducted differential miRNA expression analysis on the same cohort and identified regulatory miRNA-mTOR gene pairs involved in cancer pathogenesis. Finally, we constructed an interaction network and identified key hub genes and miRNAs with potential prognostic significance. <b>Results</b>: We identified 95 mTOR pathway genes that were significantly differentially expressed, involving upstream regulators, core components, and downstream effectors. Functional pathway analysis revealed a prominent shift toward mTORC1 activation, accompanied by paradoxical activation of autophagy. The let-7 miRNA family was identified as a key regulator of the mTOR pathway, potentially facilitating disease progression. RICTOR downregulation, a key component of the mTORC2 complex, appears to play a critical role in this histotype. In addition, FNIP1, a tumour suppressor gene implicated in mTOR dysregulation, was found to correlate with survival outcomes. <b>Conclusions</b>: We propose a model of dual activation of mTORC1 and autophagy in HGSOC as the metabolic rewiring enabling cancer progression under nutrient and cellular stress.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lung cancer is one of the leading causes of mortality in the United States. Despite overall declines in incidence and mortality nationwide, rural communities continue to experience higher rates of lung cancer incidence and mortality than their urban counterparts, a disparity that has persisted over recent decades. This review synthesizes evidence from epidemiologic and clinical studies evaluating rural-urban differences in lung cancer incidence, mortality, diagnostic stage, access to screening, and treatment outcomes. Factors influencing these differences-tobacco use and environmental exposures, socioeconomic inequities, access to healthcare, and psychosocial and spiritual support-are examined as well. The review highlights the importance of increasing access to lung cancer screening and suggests interventions to improve early detection, access to treatment, and enhance psychosocial and spiritual support for patients and caregivers residing in rural areas. In this review, we have followed the urban-rural classification designated by the United States Census Bureau as a rural area consisting of populations, housing, and territory not included within an urban-classified area.
{"title":"Disparities in Lung Cancer Health Outcomes and Access to Lung Cancer Screening Between Rural and Urban Areas in the U.S.","authors":"Aishani Gargapati, James Fox, Erminia Massarelli","doi":"10.3390/cancers18050864","DOIUrl":"10.3390/cancers18050864","url":null,"abstract":"<p><p>Lung cancer is one of the leading causes of mortality in the United States. Despite overall declines in incidence and mortality nationwide, rural communities continue to experience higher rates of lung cancer incidence and mortality than their urban counterparts, a disparity that has persisted over recent decades. This review synthesizes evidence from epidemiologic and clinical studies evaluating rural-urban differences in lung cancer incidence, mortality, diagnostic stage, access to screening, and treatment outcomes. Factors influencing these differences-tobacco use and environmental exposures, socioeconomic inequities, access to healthcare, and psychosocial and spiritual support-are examined as well. The review highlights the importance of increasing access to lung cancer screening and suggests interventions to improve early detection, access to treatment, and enhance psychosocial and spiritual support for patients and caregivers residing in rural areas. In this review, we have followed the urban-rural classification designated by the United States Census Bureau as a rural area consisting of populations, housing, and territory not included within an urban-classified area.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12985160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glioblastoma stem cells (GSCs) function as dynamic regulators of tumor persistence, maintained by interconnected genetic, epigenetic, metabolic, and microenvironment-derived circuits. Rather than fixed entities, GSCs continuously recalibrate their functional state as transcriptional regulators, chromatin architecture, and non-coding RNA networks shift in response to microenvironmental cues. Hypoxic, vascular, and immune niches reinforce these adaptive states by stabilizing HIF signaling, modulating cytokine gradients, and sustaining immunosuppression. Metabolic flexibility further supports survival under therapeutic and environmental stress. Standard therapies inadvertently activate these same resilience pathways: TMZ enhances DNA repair and quiescent survival, while radiation promotes mesenchymal transition and immune evasion, thereby enriching GSC-associated circuits that drive recurrence. Understanding how these molecular circuits converge to sustain stemness, plasticity, and microenvironmental crosstalk highlights the need for combinatorial strategies that simultaneously disrupt epigenetic gating, metabolic rewiring, ncRNA-controlled repair, and niche-dependent signaling to achieve durable glioblastoma control.
{"title":"Translating Molecular Insights into Effective Targeting of Glioblastoma Stem Cells.","authors":"Shilpi Singh, Deepak Singh Kapkoti, Gatikrushna Singh","doi":"10.3390/cancers18050860","DOIUrl":"10.3390/cancers18050860","url":null,"abstract":"<p><p>Glioblastoma stem cells (GSCs) function as dynamic regulators of tumor persistence, maintained by interconnected genetic, epigenetic, metabolic, and microenvironment-derived circuits. Rather than fixed entities, GSCs continuously recalibrate their functional state as transcriptional regulators, chromatin architecture, and non-coding RNA networks shift in response to microenvironmental cues. Hypoxic, vascular, and immune niches reinforce these adaptive states by stabilizing HIF signaling, modulating cytokine gradients, and sustaining immunosuppression. Metabolic flexibility further supports survival under therapeutic and environmental stress. Standard therapies inadvertently activate these same resilience pathways: TMZ enhances DNA repair and quiescent survival, while radiation promotes mesenchymal transition and immune evasion, thereby enriching GSC-associated circuits that drive recurrence. Understanding how these molecular circuits converge to sustain stemness, plasticity, and microenvironmental crosstalk highlights the need for combinatorial strategies that simultaneously disrupt epigenetic gating, metabolic rewiring, ncRNA-controlled repair, and niche-dependent signaling to achieve durable glioblastoma control.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12985190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shray Malik, Vanessa Le, Farshid Dayyani, Maheswari Senthil, Oliver S Eng, Michael P O'Leary
Colorectal peritoneal metastases portend a poor prognosis when compared to other isolated sites of metastatic disease. The advent of regional therapies, including cytoreductive surgery, have improved outcomes for patients with peritoneal carcinomatosis. However, these options are typically only available in patients deemed to have resectable disease. For patients with unresectable peritoneal disease, non-surgical regional therapy has only been studied in early-phase clinical trials. This represents a gap in therapy in a population with a desperate need. In this review, we highlight the current limited data, as well as postulate on the future direction of regional therapies in patients with unresectable peritoneal metastases from colorectal adenocarcinoma.
{"title":"Regional Therapies Utilized in Treating Unresectable Colorectal Adenocarcinoma with Peritoneal Metastases.","authors":"Shray Malik, Vanessa Le, Farshid Dayyani, Maheswari Senthil, Oliver S Eng, Michael P O'Leary","doi":"10.3390/cancers18050863","DOIUrl":"10.3390/cancers18050863","url":null,"abstract":"<p><p>Colorectal peritoneal metastases portend a poor prognosis when compared to other isolated sites of metastatic disease. The advent of regional therapies, including cytoreductive surgery, have improved outcomes for patients with peritoneal carcinomatosis. However, these options are typically only available in patients deemed to have resectable disease. For patients with unresectable peritoneal disease, non-surgical regional therapy has only been studied in early-phase clinical trials. This represents a gap in therapy in a population with a desperate need. In this review, we highlight the current limited data, as well as postulate on the future direction of regional therapies in patients with unresectable peritoneal metastases from colorectal adenocarcinoma.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simonetta I Gaumond, Sophie Shrestha, Isabella Kamholtz, Gabriela E Beraja, Joaquin J Jimenez
Chemotherapy-induced alopecia (CIA) is one of the most common and visible toxicities of breast cancer treatment, yet its true incidence, severity, and long-term outcomes remain inconsistently reported. Although CIA is frequently cited as affecting approximately 65% of patients and persistent alopecia has historically been considered uncommon (1-15%), emerging data suggest a substantially greater burden. We conducted a scoping review of PubMed, EMBASE, SCOPUS, and Cochrane databases to synthesize regimen-specific evidence on the incidence, severity, and persistence of CIA in breast cancer patients. Anthracycline- and taxane-based regimens were associated with the highest risk, with severe alopecia reported in more than 70% of patients and rates approaching 90-100% in combination regimens. Cyclophosphamide further amplified acute CIA when combined with doxorubicin, with reported incidence up to 93%. In contrast, capecitabine and vinorelbine were consistently associated with lower alopecia incidence. Importantly, CIA was not uniformly reversible. Persistent CIA (pCIA) occurred in up to 67% of patients treated with doxorubicin-based regimens and nearly 50% of those receiving docetaxel combinations, substantially higher than historically reported. Despite its high frequency and potential permanence, CIA remains underreported in oncology trials and insufficiently addressed in survivorship care. Recognizing CIA as both an acute toxicity and a potential long-term survivorship concern underscores the need for standardized reporting, longitudinal follow-up, and development of effective preventive strategies in breast cancer care.
{"title":"Chemotherapy-Induced Alopecia in Breast Cancer Patients: Treatment-Specific Incidence and Risk of Persistent Hair Loss.","authors":"Simonetta I Gaumond, Sophie Shrestha, Isabella Kamholtz, Gabriela E Beraja, Joaquin J Jimenez","doi":"10.3390/cancers18050861","DOIUrl":"10.3390/cancers18050861","url":null,"abstract":"<p><p>Chemotherapy-induced alopecia (CIA) is one of the most common and visible toxicities of breast cancer treatment, yet its true incidence, severity, and long-term outcomes remain inconsistently reported. Although CIA is frequently cited as affecting approximately 65% of patients and persistent alopecia has historically been considered uncommon (1-15%), emerging data suggest a substantially greater burden. We conducted a scoping review of PubMed, EMBASE, SCOPUS, and Cochrane databases to synthesize regimen-specific evidence on the incidence, severity, and persistence of CIA in breast cancer patients. Anthracycline- and taxane-based regimens were associated with the highest risk, with severe alopecia reported in more than 70% of patients and rates approaching 90-100% in combination regimens. Cyclophosphamide further amplified acute CIA when combined with doxorubicin, with reported incidence up to 93%. In contrast, capecitabine and vinorelbine were consistently associated with lower alopecia incidence. Importantly, CIA was not uniformly reversible. Persistent CIA (pCIA) occurred in up to 67% of patients treated with doxorubicin-based regimens and nearly 50% of those receiving docetaxel combinations, substantially higher than historically reported. Despite its high frequency and potential permanence, CIA remains underreported in oncology trials and insufficiently addressed in survivorship care. Recognizing CIA as both an acute toxicity and a potential long-term survivorship concern underscores the need for standardized reporting, longitudinal follow-up, and development of effective preventive strategies in breast cancer care.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junyi Liu, Youwen Zhu, Kun Liu, Dongfeng Deng, Qiuping Yang, Weisong Wang, Xianyu Liu, Hong Zhu
Background: While surgery and radiotherapy are the standard of care for patients with cervical cancer (CC), debate persists regarding the choice of whether treatment should consist of surgery followed by radiotherapy or initial direct radical radiotherapy. The present study was therefore devised to compare real-world clinical outcomes and economic assessments associated with these different treatment approaches. Methods: Six tertiary medical centers retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage I-IVA CC who underwent surgery followed by radiotherapy (surgery-radiotherapy group) or radical radiotherapy (radiotherapy group) between 2015 and 2023 in China. The progression-free and overall survival (PFS and OS) of these patients were compared using Kaplan-Meier and propensity-score-weighted proportional risk models. Economic analyses were also conducted based on patient follow-up for up to 8 years from the start of treatment. Results: A total of 980 patients receiving surgery-radiotherapy and radiotherapy were identified for matching. Propensity score weighting revealed no significant statistical differences in PFS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.44-1.28; p = 0.29) and OS (HR, 0.49; 95% CI, 0.20-1.21; p = 0.12) when comparing these groups. Subgroup analysis found differences in PFS (HR, 0.17; 95% CI, 0.04-0.77; p = 0.02) among adenocarcinoma. Economic analyses revealed that the incremental cost-effectiveness ratio of the surgery-radiotherapy group versus the radiotherapy group was $40,831/quality-adjusted life-year (QALY), which is higher than the Chinese willingness-to-pay threshold of $35,841/QALY. Conclusions: Survival outcomes were similar for patients with CC who underwent surgery-radiotherapy and radiotherapy. Further, radical radiotherapy may be cost-effective for such patients considering economic factors in China.
背景:虽然手术和放疗是宫颈癌(CC)患者的标准治疗方法,但关于治疗应选择手术加放疗还是初始直接根治性放疗的争论仍然存在。因此,本研究旨在比较与这些不同治疗方法相关的实际临床结果和经济评估。方法:回顾性分析6家三级医疗中心2015 - 2023年间在中国接受国际妇产科联合会(FIGO) 2018期I-IVA期CC手术后放疗(手术-放疗组)或根治性放疗(放疗组)的患者。使用Kaplan-Meier和倾向评分加权比例风险模型比较这些患者的无进展生存期和总生存期(PFS和OS)。经济分析也基于患者从治疗开始长达8年的随访。结果:共确定980例接受手术放疗和放疗的患者进行匹配。倾向评分加权结果显示,两组间PFS(风险比[HR], 0.75; 95%可信区间[CI], 0.44-1.28; p = 0.29)和OS(风险比[HR], 0.49; 95% CI, 0.20-1.21; p = 0.12)差异无统计学意义。亚组分析发现腺癌患者的PFS差异(HR, 0.17; 95% CI, 0.04-0.77; p = 0.02)。经济分析显示,手术+放疗组相对于放疗组的增量成本-效果比为40,831美元/质量调整生命年(QALY),高于中国人的支付意愿阈值35,841美元/QALY。结论:接受手术放疗和放疗的CC患者的生存结果相似。此外,考虑到中国的经济因素,根治性放疗可能对这类患者具有成本效益。
{"title":"Comprehensive Comparison of Surgery Followed by Radiotherapy and Radical Radiotherapy for Cervical Cancer: A Multicenter Retrospective Propensity-Score-Matched Analysis.","authors":"Junyi Liu, Youwen Zhu, Kun Liu, Dongfeng Deng, Qiuping Yang, Weisong Wang, Xianyu Liu, Hong Zhu","doi":"10.3390/cancers18050865","DOIUrl":"10.3390/cancers18050865","url":null,"abstract":"<p><p><b>Background:</b> While surgery and radiotherapy are the standard of care for patients with cervical cancer (CC), debate persists regarding the choice of whether treatment should consist of surgery followed by radiotherapy or initial direct radical radiotherapy. The present study was therefore devised to compare real-world clinical outcomes and economic assessments associated with these different treatment approaches. <b>Methods:</b> Six tertiary medical centers retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage I-IVA CC who underwent surgery followed by radiotherapy (surgery-radiotherapy group) or radical radiotherapy (radiotherapy group) between 2015 and 2023 in China. The progression-free and overall survival (PFS and OS) of these patients were compared using Kaplan-Meier and propensity-score-weighted proportional risk models. Economic analyses were also conducted based on patient follow-up for up to 8 years from the start of treatment. <b>Results:</b> A total of 980 patients receiving surgery-radiotherapy and radiotherapy were identified for matching. Propensity score weighting revealed no significant statistical differences in PFS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.44-1.28; <i>p</i> = 0.29) and OS (HR, 0.49; 95% CI, 0.20-1.21; <i>p</i> = 0.12) when comparing these groups. Subgroup analysis found differences in PFS (HR, 0.17; 95% CI, 0.04-0.77; <i>p</i> = 0.02) among adenocarcinoma. Economic analyses revealed that the incremental cost-effectiveness ratio of the surgery-radiotherapy group versus the radiotherapy group was $40,831/quality-adjusted life-year (QALY), which is higher than the Chinese willingness-to-pay threshold of $35,841/QALY. <b>Conclusions:</b> Survival outcomes were similar for patients with CC who underwent surgery-radiotherapy and radiotherapy. Further, radical radiotherapy may be cost-effective for such patients considering economic factors in China.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12985006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As we enter 2026, we take a moment to reflect on the progress of Cancers over the past year [...].
当我们进入2026年,我们花点时间来反思过去一年巨蟹座的进展…
{"title":"<i>Cancers</i> 2025: Growing with Quality.","authors":"Samuel C Mok","doi":"10.3390/cancers18050853","DOIUrl":"10.3390/cancers18050853","url":null,"abstract":"<p><p>As we enter 2026, we take a moment to reflect on the progress of <i>Cancers</i> over the past year [...].</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}