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19 pages, 5703 KiB  
Article
Quality of Life Identifies High-Risk Groups in Advanced Rectal Cancer Patients
by Anna-Lena Zollner, Daniel Blasko, Tim Fitz, Claudia Schweizer, Rainer Fietkau and Luitpold Distel
Healthcare 2025, 13(15), 1782; https://doi.org/10.3390/healthcare13151782 - 23 Jul 2025
Viewed by 200
Abstract
Background/Objectives: Quality of life (QoL) is a valuable tool for evaluating treatment outcomes and identifying patients who may benefit from early supportive interventions. This study aimed to determine whether specific QoL results in patients with advanced rectal cancer could identify groups with [...] Read more.
Background/Objectives: Quality of life (QoL) is a valuable tool for evaluating treatment outcomes and identifying patients who may benefit from early supportive interventions. This study aimed to determine whether specific QoL results in patients with advanced rectal cancer could identify groups with an unfavourable prognosis in long-term follow-up. Methods: A total of 570 patients with advanced rectal cancer were prospectively assessed, during and up to five years after neoadjuvant radiochemotherapy, using the QLQ-C30 and QLQ-CR38 questionnaires. We analysed 27 functional and symptom-related scores to identify associations with overall survival, once at baseline, three times during therapy, and annually from years one to five post-therapy. Results: Poor quality of life scores were consistently associated with shorter overall survival. The functional scores of physical functioning, role functioning, and global health, as well as the symptom scores of fatigue, dyspnoea, and chemotherapy side effects, were highly significant for overall survival at nearly all time points except for the immediate preoperative assessment. Patients over the age of 64 with lower QoL scores showed a significantly reduced probability of survival in the follow-up period, and patients who reported poor QoL in at least two of the first three questionnaires during the initial phase of treatment showed significantly reduced overall survival. Conclusions: Early and repeated QoL assessments, particularly within the first weeks of therapy, offer critical prognostic value in advanced rectal cancer. Identifying patients with an unfavourable prognosis might allow faster interventions that could improve survival outcomes. Integrating QoL monitoring into routine clinical practice could enhance individualised care and support risk stratification. Full article
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14 pages, 273 KiB  
Article
From Blood to Outcome: Inflammatory Biomarkers in Rectal Cancer Surgery at a Romanian Tertiary Hospital
by Georgiana Viorica Moise, Catalin Vladut Ionut Feier, Vasile Gaborean, Alaviana Monique Faur, Vladut Iosif Rus and Calin Muntean
Diseases 2025, 13(7), 218; https://doi.org/10.3390/diseases13070218 - 13 Jul 2025
Viewed by 323
Abstract
Background: Systemic inflammatory markers have emerged as accessible and reproducible tools for oncologic risk stratification, yet their prognostic value in rectal cancer remains incompletely defined, particularly in acute surgical settings. This study aimed to assess six inflammation-based indices—NLR, PLR, MLR, SII, SIRI, and [...] Read more.
Background: Systemic inflammatory markers have emerged as accessible and reproducible tools for oncologic risk stratification, yet their prognostic value in rectal cancer remains incompletely defined, particularly in acute surgical settings. This study aimed to assess six inflammation-based indices—NLR, PLR, MLR, SII, SIRI, and AISI—in relation to tumor stage, recurrence, and outcomes among patients undergoing emergency versus elective resection for rectal cancer. Methods: We retrospectively evaluated 174 patients treated between 2018 and 2024. Pre-treatment blood counts were used to calculate inflammatory indices. Clinical and pathological parameters were correlated with biomarker levels using univariate and multivariate analyses. Results: Pre-treatment inflammation markers were significantly elevated in patients requiring emergency surgery (e.g., NLR: 3.34 vs. 2.4, p = 0.001; PLR: 204.1 vs. 137.8, p < 0.001; SII: 1008 vs. 693, p = 0.007), reflecting advanced tumor biology and immune activation. Notably, these patients also had higher rates of stage IV disease (p = 0.029) and permanent stoma (p = 0.002). Post-treatment, recurrence was paradoxically associated with significantly lower levels of SII (p = 0.021), AISI (p = 0.036), and PLR (p = 0.003), suggesting a potential role for immune exhaustion rather than hyperinflammation in early relapse. Conclusions: Inflammatory indices provide valuable insights into both tumor local invasion and host immune status in rectal cancer. Their integration into perioperative assessment could improve prognostication, particularly in emergency presentations. Post-treatment suppression of these markers may identify patients at high risk for recurrence despite initial curative intent. Full article
(This article belongs to the Section Oncology)
11 pages, 239 KiB  
Article
Carbapenem-Resistant Enterobacteriaceae (CRE) in Children with Cancer: The Impact of Rapid Diagnostics and Targeted Colonization Strategies on Improving Outcomes
by Youssef Madney, Sally Mahfouz, Ahmed Bayoumi, Omayma Hassanain, Omneya Hassanain, Ahmed A. Sayed, Deena Jalal, Maryam Lotfi, May Tolba, Ghada A. Ziad, Mervat Elanany, Mohamed Hashem, Gehad Taha, Lobna Shalaby and Alaa Elhaddad
Microorganisms 2025, 13(7), 1627; https://doi.org/10.3390/microorganisms13071627 - 10 Jul 2025
Viewed by 1020
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) pose an emerging threat, with a high mortality rate among children with cancer. This study aimed to evaluate the impact of routine rectal swab surveillance and rapid PCR-based detection of carbapenemase genes to facilitate the early initiation of appropriate treatment [...] Read more.
Carbapenem-resistant Enterobacteriaceae (CRE) pose an emerging threat, with a high mortality rate among children with cancer. This study aimed to evaluate the impact of routine rectal swab surveillance and rapid PCR-based detection of carbapenemase genes to facilitate the early initiation of appropriate treatment and assess its effects on outcomes. The study compared two groups of pediatric cancer patients with CRE bloodstream infections: a retrospective cohort of 254 patients from 2013 to 2017, and a prospective cohort of 186 patients from 2020 to 2022, following the implementation of these tools. A rapid diagnostic test in the prospective cohort resulted in the early initiation of proper antibiotics in 85% (165/186) of patients, compared to only 58% (147/254) in the retrospective group. This led to a decrease in the need for ICU admission related to sepsis from CRE and a significant reduction in the 30-day mortality rate (16% vs. 30%, p ≤ 0.01). Genotypic profiling revealed that class B carbapenemases were the most prevalent (69%), with the NDM type being identified in 67% of patients. OXA-48 and KPC enzymes were detected in 59% and 4% of patients, respectively. Multivariate analysis revealed that patients having Klebsiella pneumoniae, NDM genotype carbapenemases, presence of pneumonia, and septic shock requiring ICU admission were predictors of poor outcomes. Rapid diagnostics and targeted colonization lead to the appropriate use of targeted antibiotics, resulting in improved patient outcomes. Understanding carbapenemase-producing microorganisms and administering newer antibiotics may further reduce mortality and enhance treatment strategies for high-risk patients. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Challenges and Innovative Solutions)
17 pages, 2089 KiB  
Article
From Mutation to Prognosis: AI-HOPE-PI3K Enables Artificial Intelligence Agent-Driven Integration of PI3K Pathway Data in Colorectal Cancer Precision Medicine
by Ei-Wen Yang, Brigette Waldrup and Enrique Velazquez-Villarreal
Int. J. Mol. Sci. 2025, 26(13), 6487; https://doi.org/10.3390/ijms26136487 - 5 Jul 2025
Cited by 1 | Viewed by 478
Abstract
The rising incidence of early-onset colorectal cancer (EOCRC), particularly among underrepresented populations, highlights the urgent need for tools that can uncover clinically meaningful, population-specific genomic alterations. The phosphoinositide 3-kinase (PI3K) pathway plays a key role in tumor progression, survival, and therapeutic [...] Read more.
The rising incidence of early-onset colorectal cancer (EOCRC), particularly among underrepresented populations, highlights the urgent need for tools that can uncover clinically meaningful, population-specific genomic alterations. The phosphoinositide 3-kinase (PI3K) pathway plays a key role in tumor progression, survival, and therapeutic resistance in colorectal cancer (CRC), yet its impact in EOCRC remains insufficiently explored. To address this gap, we developed AI-HOPE-PI3K, a conversational artificial intelligence platform that integrates harmonized clinical and genomic data for real-time, natural language-based analysis of PI3K pathway alterations. Built on a fine-tuned biomedical LLaMA 3 model, the system automates cohort generation, survival modeling, and mutation frequency comparisons using multi-institutional cBioPortal datasets annotated with clinical variables. AI-HOPE-PI3K replicated known associations and revealed new findings, including worse survival in colon versus rectal tumors harboring PI3K alterations, enrichment of INPP4B mutations in Hispanic/Latino EOCRC patients, and favorable survival outcomes associated with high tumor mutational burden in FOLFIRI-treated patients. The platform also enabled context-specific survival analyses stratified by age, tumor stage, and molecular alterations. These findings support the utility of AI-HOPE-PI3K as a scalable and accessible tool for integrative, pathway-specific analysis, demonstrating its potential to advance precision oncology and reduce disparities in EOCRC through data-driven discovery. Full article
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31 pages, 922 KiB  
Review
Controversies and Perspectives in the Current Management of Patients with Locally Advanced Rectal Cancer—A Systematic Review
by Roxana Elena Stefan, Rodica Daniela Birla, Mircea Gheorghe, Daniela Elena Dinu, Petre Angel Hoara, Diana Ciuc, Valeriu-Gabi Dinca and Silviu Constantinoiu
Life 2025, 15(7), 1011; https://doi.org/10.3390/life15071011 - 25 Jun 2025
Viewed by 731
Abstract
Traditionally, the therapeutic approach to rectal cancer has involved neoadjuvant chemoradiotherapy followed by surgical resection, and, in some cases, adjuvant chemotherapy. This study aims to present current advances and ongoing controversies in the management of patients with locally advanced rectal cancer (LARC), with [...] Read more.
Traditionally, the therapeutic approach to rectal cancer has involved neoadjuvant chemoradiotherapy followed by surgical resection, and, in some cases, adjuvant chemotherapy. This study aims to present current advances and ongoing controversies in the management of patients with locally advanced rectal cancer (LARC), with a particular focus on clarifying the role of total neoadjuvant therapy (TNT) in contemporary treatment strategies. Methods: We conducted a systematic literature review in Medline/PubMed using various keyword combinations, including “rectal cancer/neoplasia” and“therapy” or “neoadjuvant therapy” or “TNT”, and included articles published between 2015 and 2025. Results: The association of neoadjuvant radiochemotherapy with preoperative systemic chemotherapy has led to the current concept of total neoadjuvant therapy. The advantages of preoperative chemotherapy include better patient compliance, a decrease in the rate of local recurrence and distant metastases via the early destruction of infra-clinical micrometastases, and higher rates of pathological complete response. All of these have led to the inclusion of this strategy in treatment guidelines for patients with locally advanced rectal cancer. Conclusions: However, the selection of patients with advanced rectal tumors for optimal therapy requires comprehensive imaging assessments, molecular and genetic testing, and a multidisciplinary team to determine the most appropriate total neoadjuvant therapy approach. Full article
(This article belongs to the Section Medical Research)
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24 pages, 691 KiB  
Review
Multimodal Preoperative Management of Rectal Cancer: A Review of the Existing Guidelines
by Ionut Negoi
Medicina 2025, 61(7), 1132; https://doi.org/10.3390/medicina61071132 - 24 Jun 2025
Viewed by 649
Abstract
Rectal cancer management necessitates a rigorous multidisciplinary strategy, emphasizing precise staging and detailed risk stratification to inform optimal therapeutic decision-making. Obtaining an accurate histological diagnosis before initiating treatment is essential. Comprehensive staging integrates clinical evaluation, thorough medical history analysis, assessment of carcinoembryonic antigen [...] Read more.
Rectal cancer management necessitates a rigorous multidisciplinary strategy, emphasizing precise staging and detailed risk stratification to inform optimal therapeutic decision-making. Obtaining an accurate histological diagnosis before initiating treatment is essential. Comprehensive staging integrates clinical evaluation, thorough medical history analysis, assessment of carcinoembryonic antigen (CEA) levels, and computed tomography (CT) imaging of the abdomen and thorax. High-resolution pelvic magnetic resonance imaging (MRI), utilizing dedicated rectal protocols, is critical for identifying recurrence risks and delineating precise anatomical relationships. Endoscopic ultrasound further refines staging accuracy by determining the tumor infiltration depth in early-stage cancers, while preoperative colonoscopy effectively identifies synchronous colorectal lesions. In early-stage rectal cancers (T1–T2, N0, and M0), radical surgical resection remains the standard of care, although transanal local excision can be selectively indicated for certain T1N0 tumors. In contrast, locally advanced rectal cancers (T3, T4, and N+) characterized by microsatellite stability or proficient mismatch repair are optimally managed with total neoadjuvant therapy (TNT), which combines chemoradiotherapy with oxaliplatin-based systemic chemotherapy. Additionally, tumors exhibiting high microsatellite instability or mismatch repair deficiency respond favorably to immune checkpoint inhibitors (ICIs). The evaluation of tumor response following neoadjuvant therapy, utilizing MRI and endoscopic assessments, facilitates individualized treatment planning, including non-operative approaches for patients with confirmed complete clinical responses who comply with rigorous follow-up. Recent advancements in molecular characterization, targeted therapies, and immunotherapy highlight a significant evolution towards personalized medicine. The effective integration of these innovations requires enhanced interdisciplinary collaboration to improve patient prognosis and quality of life. Full article
(This article belongs to the Special Issue Recent Advances and Future Challenges in Colorectal Surgery)
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11 pages, 1948 KiB  
Article
Factors Determining Postoperative Early Continence in Patients Undergoing Robotic Radical Prostatectomy
by Metin Mod, Hasan Samet Güngör, Hakan Karaca, Ahmet Tahra, Resul Sobay, Abdurrahman İnkaya and Eyüp Veli Küçük
J. Clin. Med. 2025, 14(13), 4405; https://doi.org/10.3390/jcm14134405 - 20 Jun 2025
Viewed by 400
Abstract
Background/Objectives: Prostate cancer is the second most common malignancy in men, and robot-assisted radical prostatectomy (RARP) has become a preferred treatment for localized disease. Postoperative urinary continence is a key determinant of quality of life. The aim of this study was to [...] Read more.
Background/Objectives: Prostate cancer is the second most common malignancy in men, and robot-assisted radical prostatectomy (RARP) has become a preferred treatment for localized disease. Postoperative urinary continence is a key determinant of quality of life. The aim of this study was to evaluate the preoperative patient characteristics and multiparametric magnetic resonance imaging (mpMRI) data that determine early postoperative continence in patients who underwent robotic radical prostatectomy at our clinic. Methods: In this study, patients who underwent robotic radical prostatectomy at our clinic between March 2020 and June 2022 were evaluated. The patients’ demographic data, preoperative PSA levels, digital rectal examination findings, preoperative lower urinary tract symptoms, sexual function, mpMRI findings, Briganti scores, surgical techniques used during the procedure and postoperative continence status were assessed. Results: A total of 111 patients were included in the study. The mean age of the patients was 61.1 years. The median follow-up duration was twelve months. According to the postoperative continence status, 22% of the patients were incontinent, 53% had moderate continence and 24% were fully continent in the first month. At the third month, 16.8% of the patients were incontinent, 31.3% had moderate continence and 51.8% were fully continent. At the one-year postoperative follow-up, the percentages of incontinent, moderately continent and fully continent patients were 4.8%, 13.2% and 81.9%, respectively. Urethral width in mpMRI (p: 0.012), pelvic transverse (p: 0.002) and AP (anterior–posterior) diameters (p: 0.033), preoperative IPSS scores (p: 0.033) and the presence of bilateral nerve-sparing surgery (p: 0.047) were found to be associated with postoperative urinary continence. No significant differences were found between groups regarding the relationship of other parameters evaluated by mpMRI with continence. Conclusions: In our study, preoperative IPSS scores, urethral width in mpMRI, pelvic transverse and AP diameters and the performance of nerve-sparing surgery were associated with early postoperative continence. Further studies with larger patient populations are needed to better understand the long-term predictors of postoperative urinary incontinence following radical prostatectomy. Full article
(This article belongs to the Special Issue Prostate Cancer: Diagnosis, Clinical Management and Prognosis)
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18 pages, 1176 KiB  
Article
Hand-Assisted Laparoscopic Rectal Resection—Experience of a Tertiary Oncology Center
by Beatriz Gonçalves, Beatriz Costeira, Filipa Fonseca, Francisco Cabral, André Caiado, Daniela Cavadas, João Maciel and Manuel Limbert
J. Clin. Med. 2025, 14(12), 4097; https://doi.org/10.3390/jcm14124097 - 10 Jun 2025
Viewed by 611
Abstract
Background: Hand-assisted laparoscopic surgery (HALS) is a possible approach for rectal anterior resection (RAR). However, evidence supporting this technique remains limited. This study aims to evaluate the perioperative and oncological outcomes of HALS for RAR at a single tertiary oncology center. Methods [...] Read more.
Background: Hand-assisted laparoscopic surgery (HALS) is a possible approach for rectal anterior resection (RAR). However, evidence supporting this technique remains limited. This study aims to evaluate the perioperative and oncological outcomes of HALS for RAR at a single tertiary oncology center. Methods: A retrospective observational study was conducted using a prospectively maintained database. Patients with primary adenocarcinoma of the rectosigmoid junction and rectum who underwent HALS for RAR between 1 January 2013 and 31 December 2022 were included. All surgeries were performed by a dedicated colorectal team composed of three surgeons. Results: Among the 1911 surgeries for primary colorectal cancer performed, 469 met the inclusion criteria. The median age was 66 (57–74) years and 63% of the patients were male. Most tumors were cT3-4 (78.9%) and cN+ (71.2%), and neoadjuvant therapy was administered in 70.0% of cases. Low RAR was performed in 73.1% of cases, and an anastomosis was constructed in 95% of cases. The median operative time was 152 (135–180) min, and the conversion rate was 3.8%. Major morbidity occurred in 10.0% of cases, with 30-day and 90-day mortality rates of 0.9% and 1.3%, respectively. The overall anastomotic leak rate was 12.1%, with 9.0% early leaks and 3.1% late leaks. A complete/near-complete mesorectal excision was achieved in 89.6% of cases and an R0 resection in 96.2% of cases. With a median follow-up of 87 months, the locoregional recurrence rate was 2.5%, whereas the distant recurrence rate was 5.9%. The 5-year overall survival was 82.6%. Conclusions: When performed by experienced teams, HALS for RAR is safe and feasible and is associated with a short operative time, low conversion rate, minimal morbidity, and optimal oncologic performance. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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18 pages, 833 KiB  
Review
The Knowledge Gap in Gut Microbiome Characterization in Early-Onset Colorectal Cancer Patients: A Systematic Scoping Review
by Rita Gomes de Sousa, Catarina Sousa Guerreiro, Inês Santos and Marília Cravo
Cancers 2025, 17(11), 1863; https://doi.org/10.3390/cancers17111863 - 31 May 2025
Viewed by 1144
Abstract
Background/Objectives: Over the past two decades, the incidence of early-onset colorectal cancer (EoCRC) has been increasing, although its underlying causes remain unclear. Gut microbiome is known to play a role in carcinogenesis of colorectal cancer. This scoping review aims to systematically map and [...] Read more.
Background/Objectives: Over the past two decades, the incidence of early-onset colorectal cancer (EoCRC) has been increasing, although its underlying causes remain unclear. Gut microbiome is known to play a role in carcinogenesis of colorectal cancer. This scoping review aims to systematically map and synthetize current evidence on gut microbiome characterization in EoCRC (vs. late-onset colorectal cancer (LoCRC) and healthy individuals), describe the methodology used, and identify knowledge gaps to inform and guide future research. Methods: This systematic scoping review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews. Searches were conducted in PubMed, Web of Science, and Scopus between January and February 2025. Two reviewers independently screened and selected the studies. One reviewer extracted the relevant information, using an adapted version of the JBI template. Results: Seven studies met eligibility criteria. Compared to healthy young adults, EoCRC patients had a predominance of lower α diversity, different β diversity, and greater abundance of Flavonifractor plautii, Akkermansia muciniphila, Bacteroides, and Fusobacteria. Comparisons with LoCRC showed that EoCRC had distinct β diversity and a higher abundance in Fusobacterium, Akkermansia, Bacteroides, and Actinomyces. Only three studies correlated the microbiota composition of EoCRC with clinicopathology features and suggested positive associations between Fusobacterium abundance, rectal tumors and lower survival and Akkermansia abundance with body mass index (BMI) ≥ 25 kg/m2, rectal EoCRC, and better survival. Conclusions: There is a lack of large, methodologically robust studies linking gut microbiota with clinicopathological, lifestyle, and tumor molecular features in EoCRC. Our review highlights critical knowledge gaps, the need for standardized methodologies, and key areas for future investigation. Full article
(This article belongs to the Special Issue Novel Strategies in the Prevention/Treatment of Colorectal Cancer)
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15 pages, 15327 KiB  
Article
Colorectal Cancer Biomarker Identification via Joint DNA-Methylation and Transcriptomics Analysis Workflow
by Olajumoke B. Oladapo and Marmar R. Moussa
Genes 2025, 16(6), 620; https://doi.org/10.3390/genes16060620 - 23 May 2025
Viewed by 808
Abstract
Background: Colorectal cancer (CRC) is a term that refers to the combination of colon and rectal cancer as they are being treated as a single tumor. In CRC, 72% of tumors are colon cancer, while the other 28% represent rectal cancer. CRC [...] Read more.
Background: Colorectal cancer (CRC) is a term that refers to the combination of colon and rectal cancer as they are being treated as a single tumor. In CRC, 72% of tumors are colon cancer, while the other 28% represent rectal cancer. CRC is a multifactorial disease caused by both genetic and epigenetic changes in the colon mucosal cells, affecting the oncogenes, DNA repair genes, and tumor suppressor genes. Currently, two DNA methylation-based biomarkers for CRC have received FDA approval: SEPT9, used in blood-based screening tests, and a combination of NDRG4 and BMP3 for stool-based tests. Although DNA methylation biomarkers have been explored in colorectal cancer (CRC), the identification of robust and clinically valuable biomarkers remains a challenge, particularly for early-stage detection and precancerous lesions. Patients often receive diagnoses at the locally advanced stage, which limits the potential utility of current biomarkers in clinical settings. Methods: The datasets used in this study were retrieved from the GEO database, specifically GSE75548 and GSE75546 for rectal cancer and GSE50760 and GSE101764 for colon cancer, summing up to a total of 130 paired samples. These datasets represent expression profiling by array, methylation profiling by genome tiling array, and expression profiling by high-throughput sequencing and include rectal and colon cancer samples paired with adjacent normal tissue samples. Differential analysis was used to identify differentially methylated CPG sites (DMCs) and identify differentially expressed genes (DEGs). Results: From the integration of DMCs with DEGs in colorectal cancer, we identified 150 candidates for methylation-regulated genes (MRGs) with two genes common across all cohorts (GNG7 and PDX1) highlighted as candidate biomarkers in CRC. The functional enrichment analysis and protein–protein interactions (PPIs) identified relevant pathways involved in CRC, including the Wnt signaling pathway, extracellular matrix (ECM) organization, among other enriched pathways. Conclusions: Our findings show the strength of our in silco computational approach in jointly identifying methylation-regulated biomarkers for colon cancer and highlight several genes and pathways as biomarker candidates for further investigations. Full article
(This article belongs to the Special Issue Bioinformatics and Computational Genomics)
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21 pages, 1986 KiB  
Article
Dynamic Prediction of Rectal Cancer Relapse and Mortality Using a Landmarking-Based Machine Learning Model: A Multicenter Retrospective Study from the Italian Society of Surgical Oncology—Colorectal Cancer Network Collaborative Group
by Rossella Reddavid, Ugo Elmore, Jacopo Moro, Paola De Nardi, Alberto Biondi, Roberto Persiani, Leonardo Solaini, Donato P. Pafundi, Desiree Cianflocca, Diego Sasia, Marco Milone, Giulia Turri, Michela Mineccia, Francesca Pecchini, Gaetano Gallo, Daniela Rega, Simona Gili, Fabio Maiello, Andrea Barberis, Federico Costanzo, Monica Ortenzi, Andrea Divizia, Caterina Foppa, Gabriele Anania, Antonino Spinelli, Giuseppe S. Sica, Mario Guerrieri, Roberto Polastri, Francesco Bianco, Paolo Delrio, Giuseppe Sammarco, Micaela Piccoli, Alessandro Ferrero, Corrado Pedrazzani, Michele Manigrasso, Felice Borghi, Claudio Coco, Davide Cavaliere, Domenico D’Ugo, Riccardo Rosati and Danila Azzolinaadd Show full author list remove Hide full author list
Cancers 2025, 17(8), 1294; https://doi.org/10.3390/cancers17081294 - 11 Apr 2025
Viewed by 1026
Abstract
Background: Almost 30% of patients with rectal cancer (RC) who submit to comprehensive treatment experience relapse. Surveillance plays a leading role in early detection. The landmark approach provides a more flexible and dynamic framework for survival prediction. Objective: This large retrospective [...] Read more.
Background: Almost 30% of patients with rectal cancer (RC) who submit to comprehensive treatment experience relapse. Surveillance plays a leading role in early detection. The landmark approach provides a more flexible and dynamic framework for survival prediction. Objective: This large retrospective study aims to develop a machine learning algorithm to profile the patient prognosis, especially the risk and the onset of RC relapse after curative resection. Methods: A cohort of 2450 RC patients were analyzed using landmark analysis. Model A applied a classical cause-specific Cox approach with a landmarking approach, while Model B implemented a landmarking-based RSF (random survival forest) competing risk algorithm. The two models were compared in terms of predictive and interpretative ability. A bootstrapped validation strategy was employed to validate the model’s performance and prevent overfitting. The best-performing hyperparameters were selected systematically, ensuring the model’s robustness within the landmark approach. The study assessed these factors’ importance and interactions using RSF and compared the predictive accuracy to that of the classical Cox model. Results: Model B outperformed Model A (mean C-index 0.95 vs. 0.78), capturing complex interactions and providing dynamic, individualized relapse predictions. Clinical factors influencing survival outcomes were identified across time with the landmark approach allowing for more accurate and timely predictions. Conclusions: The landmark approach offers an improvement over traditional methods in survival analysis. By accommodating time-dependent variables and the evolving nature of patient data, this approach provides a precise tool for profiling RC survival, thereby supporting more informed and dynamic clinical decision-making. Full article
(This article belongs to the Special Issue Application of Biostatistics in Cancer Research)
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12 pages, 1964 KiB  
Article
Radiomic Features of Mesorectal Fat as Indicators of Response in Rectal Cancer Patients Undergoing Neoadjuvant Therapy
by Francesca Treballi, Ginevra Danti, Sofia Boccioli, Sebastiano Paolucci, Simone Busoni, Linda Calistri and Vittorio Miele
Tomography 2025, 11(4), 44; https://doi.org/10.3390/tomography11040044 - 7 Apr 2025
Viewed by 771
Abstract
Background: Rectal cancer represents a major cause of mortality in the United States. Management strategies are highly individualized, depending on patient-specific factors and tumor characteristics. The therapeutic landscape is rapidly evolving, with notable advancements in response rates to both radiotherapy and chemotherapy. For [...] Read more.
Background: Rectal cancer represents a major cause of mortality in the United States. Management strategies are highly individualized, depending on patient-specific factors and tumor characteristics. The therapeutic landscape is rapidly evolving, with notable advancements in response rates to both radiotherapy and chemotherapy. For locally advanced rectal cancer (LARC, defined as up to T3–4 N+), the standard of care involves total mesorectal excision (TME) following neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) has emerged as the gold standard for local tumor staging and is increasingly pivotal in post-treatment restaging. Aim: In our study, we proposed an MRI-based radiomic model to identify characteristic features of peritumoral mesorectal fat in two patient groups: good responders and poor responders to neoadjuvant therapy. The aim was to assess the potential presence of predictive factors for favorable or unfavorable responses to neoadjuvant chemoradiotherapy, thereby optimizing treatment management and improving personalized clinical decision-making. Methods: We conducted a retrospective analysis of adult patients with LARC who underwent pre- and post-nCRT MRI scans. Patients were classified as good responders (Group 0) or poor responders (Group 1) based on MRI findings, including tumor volume reduction, signal intensity changes on T2-weighted and diffusion-weighted imaging (DWI), and alterations in the circumferential resection margin (CRM) and extramural vascular invasion (EMVI) status. Classification criteria were based on the established literature to ensure consistency. Key clinical and imaging parameters, such as age, TNM stage, CRM involvement, and EMVI presence, were recorded. A radiomic model was developed using the LASSO algorithm for feature selection and regularization from 107 extracted radiomic features. Results: We included 44 patients (26 males and 18 females) who, following nCRT, were categorized into Group 0 (28 patients) and Group 1 (16 patients). The pre-treatment MRI analysis identified significant features (out of 107) for each sequence based on the Mann–Whitney test and t-test. The LASSO algorithm selected three features (shape_Sphericity, shape_Maximum2DDiameterSlice, and glcm_Imc2) for the construction of the radiomic logistic regression model, and ROC curves were subsequently generated for each model (AUC: 0.76). Conclusions: We developed an MRI-based radiomic model capable of differentiating and predicting between two groups of rectal cancer patients: responders and non-responders to neoadjuvant chemoradiotherapy (nCRT). This model has the potential to identify, at an early stage, lesions with a high likelihood of requiring surgery and those that could potentially be managed with medical treatment alone. Full article
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16 pages, 970 KiB  
Article
Analytical Validation of MyProstateScore 2.0
by Jacob I. Meyers, Tabea M. Schatz, Cameron J. Seitz, Rachel Botbyl, Bradley S. Moore, Bill G. Crafts, John R. Kitchen and Spencer Heaton
Diagnostics 2025, 15(7), 923; https://doi.org/10.3390/diagnostics15070923 - 3 Apr 2025
Viewed by 898
Abstract
Background/Objectives: Prostate cancer (PCa) is a leading cause of cancer-related deaths among men, with early detection playing a crucial role in improving outcomes. MyProstateScore 2.0 (MPS2), a novel urinary biomarker test, predicts clinically significant PCa to reduce invasive biopsy procedures. This study [...] Read more.
Background/Objectives: Prostate cancer (PCa) is a leading cause of cancer-related deaths among men, with early detection playing a crucial role in improving outcomes. MyProstateScore 2.0 (MPS2), a novel urinary biomarker test, predicts clinically significant PCa to reduce invasive biopsy procedures. This study evaluates the analytical performance of MPS2 using both a post-digital rectal exam (DRE) and non-DRE urine samples. Methods: We assessed the reproducibility, precision, and detection limits of the eighteen MPS2 analytes. Analytical parameters including the linear range, upper and lower limits of quantification (ULOQ and LLOQ), and interference from substances commonly present in urine were evaluated. The reproducibility of the MPS2 scores was evaluated across post-DRE and non-DRE clinical urine samples. Results: MPS2 analytes demonstrated high linearity (R2 ≥ 0.975) across defined quantification ranges, with PCR efficiencies of 97–105%. The limits of detection (LOD) ranged from 40 to 160 copies/reaction, while the ULOQ was determined to be 106–107 copies/reaction for each analyte. Precision studies showed intra-run, inter-run, and inter-instrument standard deviations ≤0.5 Crt. Among the 12 potential interfering substances, only whole blood affected the performance of MPS2. The reproducibility of the MPS2 scores was consistent across post-DRE and non-DRE urine samples, meeting the acceptance criteria. Conclusions: The analytical validation confirms that MPS2 is robust and reliable in detecting biomarkers for clinically significant PCa. These findings, coupled with previous clinical validations, support the clinical use of MPS2 as a non-invasive diagnostic tool. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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21 pages, 5753 KiB  
Article
Serum-Based Proteomic Approach to Identify Clinical Biomarkers of Radiation Exposure
by Emeshaw Damtew Zebene, Biagio Pucci, Rita Lombardi, Hagos Tesfay Medhin, Edom Seife, Elena Di Gennaro, Alfredo Budillon and Gurja Belay Woldemichael
Cancers 2025, 17(6), 1010; https://doi.org/10.3390/cancers17061010 - 17 Mar 2025
Viewed by 747
Abstract
Background: Ionizing radiation (IR) exposure poses a significant health risk due to its widespread use in medical diagnostics and therapeutic applications, necessitating rapid and effective biomarkers for assessment. Objective: The aim of this study is to identify the serum proteomic signature of IR [...] Read more.
Background: Ionizing radiation (IR) exposure poses a significant health risk due to its widespread use in medical diagnostics and therapeutic applications, necessitating rapid and effective biomarkers for assessment. Objective: The aim of this study is to identify the serum proteomic signature of IR exposure in patients undergoing radiotherapy (RT). Methods: Blood samples were obtained from eighteen patients with head and neck cancer (HNC) and five patients with rectal cancer before and immediately after they underwent curative intensity-modulated radiotherapy (IMRT). The comprehensive serum proteome was analyzed in individual samples using nanoHPLC-MS/MS. Results: Forty radiation-modulated proteins (RMPs), 24 upregulated and 16 downregulated, with a fold change ≥1.5 and p-value < 0.05 were identified. About 40% of the RMPs are involved in acute phase response, DNA repair, and inflammation; the key RMPs were ADCY1, HGF, MCEMP1, CHD4, RECQL5, MSH6, and ZNF224. Conclusions: This study identifies a panel of serum proteins that may reflect the radiation response, providing a valuable molecular fingerprint of IR exposure and paving the way for the development of sensitive and specific biomarkers for early detection and clinical management of IR-related injuries. Full article
(This article belongs to the Section Cancer Biomarkers)
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10 pages, 1899 KiB  
Review
Surgery for Colorectal Cancer Associated with Crohn’s Disease—Toward a Medical Treatment Strategy Based on the Differences Between Japan and Western Countries
by Yuki Sekido, Takayuki Ogino, Mitsunobu Takeda, Tsuyoshi Hata, Atsushi Hamabe, Norikatsu Miyoshi, Mamoru Uemura, Tsunekazu Mizushima, Yuichiro Doki and Hidetoshi Eguchi
Cancers 2025, 17(5), 860; https://doi.org/10.3390/cancers17050860 - 3 Mar 2025
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Abstract
With advances in the treatment of Crohn’s disease (CD), the number of long-term cases is increasing, along with the incidence of CD-related cancers. Here, we discuss the clinical features, diagnosis, treatment, prognosis, and surveillance of CD-related cancers. There are regional differences in the [...] Read more.
With advances in the treatment of Crohn’s disease (CD), the number of long-term cases is increasing, along with the incidence of CD-related cancers. Here, we discuss the clinical features, diagnosis, treatment, prognosis, and surveillance of CD-related cancers. There are regional differences in the common sites and histological types of CD-related cancers, with right-sided colon cancer accounting for 40% of cases in Europe and the US, and squamous cell carcinoma being common. In Japan, rectal and anal cancers account for 80% of cases, and mucinous carcinoma is common. The prognosis of CD-associated colon cancer and sporadic colon cancer is the same; however, the prognosis of CD-associated rectal cancer is clearly worse than that of sporadic rectal cancer. Early diagnosis is important to improve the prognosis of CD-associated rectal cancer, and it is necessary to establish a surveillance method for CD-associated cancer that combines colonoscopy, anesthetic proctoscopy, and imaging, as appropriate. The basic treatment for CD-related cancer is surgical resection; however, the criteria for selecting the surgical procedure are unclear, and there is no clear evidence for multidisciplinary perioperative treatment including chemotherapy and radiotherapy. Additionally, CD-related rectal and anal cancers have a higher local recurrence rate than that of sporadic rectal cancers; therefore, thorough local control is important. Furthermore, CD-related cancers have different epidemiologies in different regions; therefore, unique diagnostic and treatment strategies must be established for each region. Full article
(This article belongs to the Special Issue Surgery for Colorectal Cancer)
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