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Keywords = neoadjuvant rectal score

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12 pages, 804 KB  
Article
Total Neoadjuvant Therapy Versus Conventional Chemoradiotherapy in Rectal Cancer: Impact on Tumor Regression Grade and the Predictive Value of CEA
by Aikaterini Sarafi, Aikaterini Leventi, Klaountia Athitaki, Konstantinos Stamou, Ioannis Papaconstantinou and Dimitrios Korkolis
Medicina 2026, 62(1), 226; https://doi.org/10.3390/medicina62010226 - 22 Jan 2026
Viewed by 74
Abstract
Background and Objectives: The introduction of total neoadjuvant therapy (TNT) in the preoperative stage has been associated with improved oncological outcomes. However, TNT may lead to tissue fibrosis and be accompanied by increased difficulty during surgery. Additionally, predicting tumor response to neoadjuvant [...] Read more.
Background and Objectives: The introduction of total neoadjuvant therapy (TNT) in the preoperative stage has been associated with improved oncological outcomes. However, TNT may lead to tissue fibrosis and be accompanied by increased difficulty during surgery. Additionally, predicting tumor response to neoadjuvant therapy is crucial for identifying patients who may achieve a complete pathological response (pCR) or qualify for organ-preserving strategies. The aim of this study is to evaluate the effect of TNT versus conventional chemoradiotherapy (CRT) on tumor regression grade (TRG) and the association between preoperative carcinoembryonic antigen (CEA) levels and good tumor response. A secondary endpoint is to investigate the effect of TNT on surgical difficulty, using indirect indicators like the quality of total mesorectal excision (TME), circumferential resection margin (CRM), and achievement of R0 resection. Materials and Methods: This is a retrospective, single-center study including 93 patients with locally advanced rectal cancer who received either TNT (n = 43) or CRT (n = 50). Results: The TNT group, compared to the CRT group, demonstrated a significantly higher rate of pCR (TRG0) (37.2% vs. 18%, p = 0.038) and good tumor regression (TRG 0–1) (53.5% vs. 28%, p = 0.019). Furthermore, patients with CEA < 5 ng/mL showed significantly higher rates of good tumor response (TRG 0–1) compared to those with CEA ≥ 5 ng/mL (45.3% vs. 16.7%, p = 0.032). When further categorized by treatment type, CEA levels did not demonstrate statistically significant differences Lastly, increased surgical difficulty could not be established, as no significant differences were observed in terms of positive CRM rates, R0 resection, and TME quality between groups. Conclusions: TNT was associated with improved TRG scores compared to CRT without increasing surgical difficulty. Lower pre-treatment CEAs were linked to better tumor response, irrespective of the type of treatment. These findings support the oncological benefit of TNT and suggest that CEA may have some predictive value for treatment response. Full article
(This article belongs to the Special Issue Novel Insights in Laparoscopic Surgery of Colorectal Carcinoma)
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14 pages, 570 KB  
Article
Impact on Clinical- and Patient-Reported Outcomes Measures of an Organ Preservation-Based Therapeutic Strategy in Locally Advanced Rectal Cancer: The FOREST Project
by Hector Guadalajara, Ion Cristóbal, Raquel Fuentes-Mateos, Eva Ruiz-Hispán, Jose Luis Domínguez-Tristancho, Miguel Leon-Arellano, Paula Sánchez-Moreno, Marta Sabater-Durán, Juan Antonio Álvaro de la Parra, Damián García-Olmo and Cristina Caramés
J. Clin. Med. 2026, 15(2), 844; https://doi.org/10.3390/jcm15020844 - 20 Jan 2026
Viewed by 227
Abstract
Background: Locally advanced rectal cancer is traditionally managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision, but radical surgery entails substantial morbidity, including bowel, urinary, and sexual dysfunction as well as permanent stomas. Organ-preserving strategies such as total neoadjuvant therapy (TNT) followed [...] Read more.
Background: Locally advanced rectal cancer is traditionally managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision, but radical surgery entails substantial morbidity, including bowel, urinary, and sexual dysfunction as well as permanent stomas. Organ-preserving strategies such as total neoadjuvant therapy (TNT) followed by a watch-and-wait (WW) approach aim to reduce morbidity while maintaining oncologic safety. A recent study from the FOREST cohort confirmed favorable survival outcomes with WW but did not assess the patient-centered impact. Methods: This retrospective observational study included locally advanced rectal cancer patients treated at a tertiary hospital. Following TNT, patients who achieved a complete clinical response entered WW, while others underwent radical surgery (RS). Patient-reported outcomes were assessed using an 18-item questionnaire grouped into domains and transformed to a 0–100 scale according to EORTC scoring methodology. All patients underwent a shared decision-making process. Comparisons between groups used Pearson chi-square tests for clinical and demographics associations and Mann–Whitney U tests for ordinal outcomes. The protocol was integrated into Quirónsalud’s value-based healthcare framework. Results: Clinical and demographics characteristics did not differ between WW and RS groups. PROMs favored WW in multiple domains: Symptoms/Complications (87 vs. 66; p < 0.001), Psychosocial adaptation (90 vs. 66; p < 0.001), Mental health (90 vs. 78; p = 0.006), and Global quality of life (80 vs. 67; p = 0.011). Bowel and sexual functions were similar between groups, and Care satisfaction was very high for both. Conclusions: TNT plus WW appears to be oncologically safe and confers significant quality-of-life benefits across several domains. These findings support the theory that WW is a value-based, patient-centered strategy for rectal cancer, and this warrants validation in larger, randomized cohorts. Full article
(This article belongs to the Special Issue Rectal Cancer: Screening, Treatment and Prevention)
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14 pages, 3030 KB  
Article
Potential Role of T2-Weighted Kurtosis in Improving Response Prediction of Locally Advanced Rectal Cancer as Additional Tool Gained from Standard MRI Examination
by Aleksandra Jankovic, Marko Ž. Daković, Milica Badza Atanasijevic, Milica Mitrovic-Jovanovic, Katarina Stosic, Dimitrije Sarac, Jelena Sisevic, Dusan Saponjski, Ivan Dimitrijević, Marko Miladinov, Jelenko Jelenković, Ljubica Lazic, Goran Barisic, Aleksandra Djuric-Stefanovic and Jelena Kovac
Biomedicines 2025, 13(12), 3003; https://doi.org/10.3390/biomedicines13123003 - 8 Dec 2025
Viewed by 355
Abstract
Background: Reliable and accurate prediction of treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) is usually demanding and continues to pose a challenge. Kurtosis as a histogram parameter calculated on T2-weighted MRI sequences might be an additional tool, as [...] Read more.
Background: Reliable and accurate prediction of treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) is usually demanding and continues to pose a challenge. Kurtosis as a histogram parameter calculated on T2-weighted MRI sequences might be an additional tool, as it represents a quantitative biomarker for response prediction. It is defined as a measure of distributions’ tails relative to the center of the distribution curve, which reflects tissue heterogeneity. The aim of the study was to evaluate the added value of T2-weighted kurtosis in predicting pathological response to nCRT in patients with LARC. Methods: a single-center cohort study included 71 patients with LARC who underwent both initial and post-nCRT MRI examinations followed by surgical resection in the form of the total mesorectal excision (TME). Histogram analysis was performed using software MIPAV (Medical Image Processing, Analysis, and Visualization, version 11.3.2, developed by the National Institutes of Health, Bethesda, MD, USA) on T2-weighted sequences, extracting kurtosis along with other histogram parameters. Pathological tumor regression grade (pTRG) in accordance with Mandard classification was considered the gold standard. Patients were classified as responders (pTRG 1–2) or non-responders (pTRG 3–5). Results: while other histogram parameters did not show statistically significant differences between groups, post-treatment values of kurtosis were significantly higher in responders compared to non-responders (4.28 ± 0.73 vs. 3.01 ± 0.17, p = 0.024). The F1 score as a classification metric (0.821) indicates an improvement in classification performance following therapy. Conclusions: T2-weighted kurtosis might be a significant tool in predicting pathological response to nCRT, representing a potentially valuable quantitative biomarker that could improve treatment response assessment. Full article
(This article belongs to the Special Issue Innovations in Radiation Oncology)
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19 pages, 5703 KB  
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 605
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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18 pages, 1231 KB  
Review
Narrative Review: Predictive Biomarkers of Tumor Response to Neoadjuvant Radiotherapy or Total Neoadjuvant Therapy of Locally Advanced Rectal Cancer Patients
by Joao Victor Machado Carvalho, Jeremy Meyer, Frederic Ris, André Durham, Aurélie Bornand, Alexis Ricoeur, Claudia Corrò and Thibaud Koessler
Cancers 2025, 17(13), 2229; https://doi.org/10.3390/cancers17132229 - 3 Jul 2025
Cited by 1 | Viewed by 2344
Abstract
Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely [...] Read more.
Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article
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18 pages, 3449 KB  
Article
Impact of Neoadjuvant Treatment on Target Expression in Rectal Cancer for Near-Infrared Tumor Imaging
by Elham Zonoobi, Lisanne K. A. Neijenhuis, Annelieke A. Lemij, Daan G. J. Linders, Ehsan Nazemalhosseini-Mojarad, Shadhvi S. Bhairosingh, N. Geeske Dekker-Ensink, Ronald L. P. van Vlierberghe, Koen C. M. J. Peeters, Fabian A. Holman, Rob A. E. M. Tollenaar, Denise E. Hilling, A. Stijn L. P. Crobach, Alexander L. Vahrmeijer and Peter J. K. Kuppen
Cancers 2025, 17(12), 1958; https://doi.org/10.3390/cancers17121958 - 12 Jun 2025
Cited by 1 | Viewed by 1202
Abstract
Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence [...] Read more.
Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence tumor imaging by endoscopy to differentiate responders and the effect of nCRT on their expression. Methods: RC samples (n = 51) were collected from both pre-treatment biopsies and corresponding post-treatment surgical specimens. Samples were categorized by treatment response and determined using tumor regression grade (TRG) scoring. Immunohistochemistry assessed the expression of CEA, EpCAM, EGFR, and c-MET in tumors and adjacent normal tissues. Expression levels were quantified using H-scores (0–3), combining the percentage and intensity of stained cells. Pre- and post-treatment H-scores were compared to evaluate the impact of nCRT. Results: CEA, EpCAM, and c-MET were overexpressed in tumor tissue as compared to adjacent healthy mucosa in 100% (51/51), 98.4% (50/51), and 92% (47/51) of tumor biopsies, respectively, while EGFR showed no overexpression. A tumor-to-normal (T/N) ratio ≥ 2 was considered sufficient for differentiation in molecular fluorescence imaging. In pre-treatment biopsy samples, c-MET showed the highest T/N expression ratio (53% of the samples ≥ 2), followed by CEA (26.3%) and EpCAM (16%). Following nCRT treatment, CEA and c-MET maintained a ≥ 2 differential expression in 45% of all samples, whereas EpCAM exhibited this difference in only 9.2% of cases. Neoadjuvant therapy even significantly improved the T/N expression ratio for CEA and c-MET (p < 0.01) and EpCAM (p < 0.05), while EGFR expression remained lower than adjacent normal tissue. Significant increases in all marker expressions were observed in minimal responders (TRG4/5, p < 0.01–0.001), while near-complete responders (TRG2) exhibited non-significant changes in CEA, c-MET, and EGFR expression. Conclusions: c-MET and CEA emerged as optimal tumor imaging targets, showing sustained differential expression after nCRT. In vivo fluorescence-guided endoscopy using probes against these markers could play a role in future clinical decision-making. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
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26 pages, 7367 KB  
Article
CD133 and CD166 Stem Cells Markers Expression, Clinicopathological Parameters, and Fragmentation Response Patterns of ypT3 Rectal Cancer Following Neoadjuvant Chemoradiotherapy
by Diana Lavinia Pricope, Adriana Grigoraș, Gabriel Mihail Dimofte, Cristina Terinte and Cornelia Amalinei
Biomedicines 2025, 13(6), 1300; https://doi.org/10.3390/biomedicines13061300 - 26 May 2025
Cited by 3 | Viewed by 1098
Abstract
Background: The effectiveness of neoadjuvant chemoradiotherapy (nCRT) is variable in locally advanced rectal cancer (LARC) patients, the ypT3 stage having a minimal or moderate response. The aim of our study was the evaluation of the association between CD133 (Prominin1) and CD166 (ALCAM) [...] Read more.
Background: The effectiveness of neoadjuvant chemoradiotherapy (nCRT) is variable in locally advanced rectal cancer (LARC) patients, the ypT3 stage having a minimal or moderate response. The aim of our study was the evaluation of the association between CD133 (Prominin1) and CD166 (ALCAM) expression, survival parameters, and clinicopathological characteristics of a subgroup of LARC patients who achieved ypT3, showing post-nCRT and TME tumor fragmentation response and the assessment of these CSCs biomarkers value as indicators of the nCRT tumor response. Methods: Our study group comprised 60 LARC patients who achieved ypT3 status and exhibited a tumor fragmentation pattern following nCRT. Clinicopathological parameter and survival evaluations, along with CD133 and CD166 immunohistochemistry and scoring, were performed and the associations between different parameters were tested. Results: High CD133 expression was significantly associated with ypN category (p = 0.018), lymphovascular invasion (LVI) (p = 0.009), perineural invasion (PnI) (p = 0.006), and tumor grading (p = 0.047), while high CD166 expression was significantly associated with LVI (p = 0.020) and PnI (p = 0.028). Tumors with high CD133 and CD166 expressions were associated with decreased overall survival (OS) (p = 0.004 and p = 0.006). Cox regression analysis identified high CD133 and CD166 expression as independent factors associated with reduced survival (HR = 3.237, p = 0.014 and HR = 2.866, p = 0.020). Conclusions: Our results support the hypothesis that CD133 and CD166 are putative CSC biomarkers associated with aggressive behavior and a poor prognosis in LARC, offering opportunities for personalized targeted therapies. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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10 pages, 1131 KB  
Article
Predictive Risk Factors for Low Anterior Resection Syndrome (LARS) in Rectal Cancer—An Observational Cohort Study
by Sorinel Lunca, Stefan Morarasu, Constantin Osman, Fadi Al Shatarat, Tudor Gramada, Mara Razniceanu, Monica Buzemurga, Emanuel Baltig, Raluca Zaharia, Wee Liam Ong and Gabriel Mihail Dimofte
J. Clin. Med. 2025, 14(8), 2831; https://doi.org/10.3390/jcm14082831 - 19 Apr 2025
Viewed by 2749
Abstract
Background/Objectives: The improved long-term survival of rectal cancer patients has led to a major increase in the prevalence of functional complications. Understanding which patients are prone to develop major LARS is important for their preoperative counselling and follow-up. Herein, we aimed to [...] Read more.
Background/Objectives: The improved long-term survival of rectal cancer patients has led to a major increase in the prevalence of functional complications. Understanding which patients are prone to develop major LARS is important for their preoperative counselling and follow-up. Herein, we aimed to assess the risk factors for LARS. Methods: This is a retrospective cohort study on rectal cancer patients. All patient and tumour variables, management plan, type of neoadjuvant therapy, radiation dose to anal sphincter, and perioperative outcomes were collected from the hospital electronic databases. We quantified LARS and compared the score before and after surgery (mean follow-up of 42.2 ± 32 months). Results: A total of 182 patients were included for the final analysis. LARS was present in 43.4% (n = 79) of patients, with 14.8% (n = 27) having minor LARS and 28.5% (n = 52) having major LARS. Age (p = 0.03), male gender (p < 0.00001), smoking (p = 0.04), neoadjuvant radiotherapy (p = 0.02), rectal stump length (p = 0.008), end-to-end anastomosis (p = 0.008), and ileostomy (p = 0.002) were found to significantly increase the rate of LARS. A logistic regression model based on the above variables was able to predict major LARS with good predictive value (AUC 0.700). Conclusions: LARS is highly common after sphincter-preserving surgery, and it is significantly more common in young, male patients with a history of smoking, having mid-lower rectal cancers with neoadjuvant radiotherapy, and undergoing TME surgery with end-to-end low anastomosis and ileostomy. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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11 pages, 212 KB  
Article
Prognostic and Inflammatory Differences Between Upper and Mid–Lower Rectal Cancers in Non-Metastatic Stage II–II Disease
by Fırat Mülküt, Cem Batuhan Ofluoğlu, Mustafa Kağan Başdoğan, İsa Caner Aydın, Akif Doğan and İsmail Ege Subaşı
Curr. Oncol. 2025, 32(4), 227; https://doi.org/10.3390/curroncol32040227 - 12 Apr 2025
Viewed by 1506
Abstract
Background: This study aimed to compare the clinical, pathological, and biochemical characteristics of upper rectal cancer (URC) and mid–lower rectal cancer (MLRC) in stage II and III non-metastatic rectal cancer and to identify distinct prognostic factors influencing survival and recurrence. Material and Methods: [...] Read more.
Background: This study aimed to compare the clinical, pathological, and biochemical characteristics of upper rectal cancer (URC) and mid–lower rectal cancer (MLRC) in stage II and III non-metastatic rectal cancer and to identify distinct prognostic factors influencing survival and recurrence. Material and Methods: This retrospective cohort study included 100 patients with stage II and III non-metastatic rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy (nCRT) followed by curative-intent surgery between 2021 and 2024. Patients were categorized into URC (n = 53) and MLRC (n = 47) groups. Parameters analyzed included demographic factors, ASA score, surgical characteristics, pathological features (tumor stage, lymph node involvement, lymphovascular invasion (LVI), perineural invasion (PNI), tumor budding, tumor regression grade (TRG)), and biochemical markers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), white blood cell (WBC) count, neutrophil count, platelet count (PLT), and C-reactive protein (CRP)). One-year overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan–Meier survival curves, and Cox regression models identified independent prognostic factors. Results: Preoperative CEA levels were higher in MLRC (p = 0.05), whereas WBC count (p = 0.01), neutrophil count (p = 0.02), PLT (p = 0.01), and CRP levels (p = 0.01) were higher in URC. Pathological analysis revealed higher LVI (p = 0.04), PNI (p = 0.04), and tumor budding (p = 0.03) in MLRC. At one-year follow-up, OS rates were 82.1% (URC) vs. 80.3% (MLRC) (p = 0.85), and DFS rates were 78.6% (URC) vs. 73.4% (MLRC) (p = 0.72). Multivariate Cox regression analysis identified age (HR: 1.04, p = 0.03), ASA score (HR: 1.22, p = 0.01), CRP (HR: 1.18, p < 0.001), preoperative CEA (HR: 1.12, p = 0.02), preoperative CA19-9 (HR: 1.09, p = 0.03), LVI (HR: 1.42, p < 0.001), PNI (HR: 1.35, p = 0.02), and tumor budding (HR: 1.28, p = 0.03) as independent prognostic factors for OS. Similar trends were observed for DFS, with T stage (HR: 1.35, p = 0.01) and tumor size (HR: 1.22, p = 0.01) also being found significant. Conclusions: Inflammatory markers, tumor burden indicators (LVI, PNI, budding, tumor size, T stage), and preoperative CEA/CA19-9 were identified as significant predictors, suggesting a risk-adapted approach to rectal cancer treatment. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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19 pages, 4144 KB  
Article
Assessment of Immunoscore, MRI Tumor Regression Grade, and Neoadjuvant Rectal Score in Predicting Pathologic Response in Locally Advanced Rectal Cancer in the Averectal Study
by Mustafa Natout, Ahmad Machmouchi, Hero Hussain, Laudy Chehade, Noura Abbas, Rim Turfa, Joseph Kattan, Sally Temraz, Ayman Tawil, Mousa Elkhaldi, Omar Jaber, Rula Amarin, Tala Alawabdeh, Maya Charafeddine, Monita Al Darazi and Ali Shamseddine
Diagnostics 2025, 15(7), 913; https://doi.org/10.3390/diagnostics15070913 - 2 Apr 2025
Viewed by 1848
Abstract
Background/Objectives: Predictive tools are needed to assess the response to treatment and guide treatment decisions for locally advanced rectal cancer (LARC). This study explores the value of combining the immunoscore (IS) and magnetic resonance imaging tumor regression grade (mrTRG) with pathologic and [...] Read more.
Background/Objectives: Predictive tools are needed to assess the response to treatment and guide treatment decisions for locally advanced rectal cancer (LARC). This study explores the value of combining the immunoscore (IS) and magnetic resonance imaging tumor regression grade (mrTRG) with pathologic and radiologic neoadjuvant rectal (NAR) scores in predicting pathologic complete response (pCRs). Methods: The scores were assessed for patients with LARC enrolled in the Averectal study (NCT03503630), who received five fractions of short-course radiotherapy, followed by six cycles of mFOLFOX-6 plus avelumab, and total mesorectal excision. The IS was calculated using the mean density percentiles of CD3- and CD8-positive T-cells on baseline biopsy samples. Baseline and post-treatment MRIs were reviewed to measure the mrTRG. NAR scores were calculated using the pre-treatment T stage and post-treatment pathologic and radiologic N and T stages. Results: Fifteen out of thirty-five patients whose data were available achieved pCR (42.8%), and seven out of fourteen patients with mrTRG = 1 (complete response) attained pCR. In patients with both a mrTRG = 1 and high IS, the pCR rate was 66.7% (6/9). All of the patients who achieved pCR had a low or intermediate pathologic NAR score with a significant correlation between pCR and pathologic NAR scores (p < 0.0001). Both pathologic and radiologic NAR scores were correlated with overall survival and disease-free survival. Conclusions: The IS can supplement the mrTRG to better predict TNT outcomes, along with the use of the NAR score. This combination could potentially help with patient selection for non-operative management and guide treatment strategies for those with different recurrence risks. Full article
(This article belongs to the Special Issue Diagnosis and Management of Colorectal Diseases)
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13 pages, 2019 KB  
Article
Efficacy of Neoadjuvant Hypofractionated Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer: A Single-Center Retrospective Analysis
by Jae Seung Kim, Jaram Lee, Hyeung-min Park, Soo Young Lee, Chang Hyun Kim and Hyeong Rok Kim
Cancers 2024, 16(24), 4280; https://doi.org/10.3390/cancers16244280 - 23 Dec 2024
Viewed by 1895
Abstract
Background/Objectives: The application of long-course chemoradiotherapy (LCRT) in elderly patients with locally advanced rectal cancer (LARC) can be challenging due to increased risks of complications associated with comorbidities and reduced functional status. This study aimed to assess the efficacy of neoadjuvant hypofractionated [...] Read more.
Background/Objectives: The application of long-course chemoradiotherapy (LCRT) in elderly patients with locally advanced rectal cancer (LARC) can be challenging due to increased risks of complications associated with comorbidities and reduced functional status. This study aimed to assess the efficacy of neoadjuvant hypofractionated chemoradiotherapy (HCRT) in elderly patients with mid-to-low LARC. Methods: We performed a retrospective review of patients diagnosed with LARC from January 2013 to December 2020 and included those aged 70 years or older. Patients were categorized into three groups based on their treatment strategies: neoadjuvant HCRT (33 or 35 Gy in 10 fractions), neoadjuvant LCRT, and upfront surgery. Comparative analyses were performed on clinicopathological characteristics, short-term outcomes, and long-term survival outcomes among these groups. Results: Among the 296 patients included, 30 (10.1%) received HCRT, 195 (65.9%) underwent standard LCRT, and 71 (24.0%) underwent upfront surgery. The baseline characteristics showed that the HCRT group had a higher American Society of Anesthesiologists (ASA) score (ASA score 3 or 4, HCRT 43.3% vs. LCRT 16.9% vs. upfront surgery 15.5%, p = 0.002). The HCRT group showed a significantly lower incidence of radiotherapy-related complications than the LCRT group (16.7% vs. 48.7%, p = 0.001). However, the rate of pathological complete response was significantly lower in the HCRT group (10.0% vs. 15.4%, p = 0.002). The 3-year relapse-free survival (83.0% vs. 77.2% vs. 83.2%; p = 0.411), 3-year local recurrence-free survival (93.1% vs. 93.2% vs. 93.5%; p = 0.464), and 5-year overall survival (65.1% vs. 67.0% vs. 67.7%; p = 0.682) were not significantly different between the three groups. Multivariate analysis also showed that the treatment strategy was not associated with survival outcomes. Conclusions: Neoadjuvant HCRT demonstrated reduced radiotherapy-related complications and acceptable long-term oncologic outcomes. Therefore, neoadjuvant HCRT may be considered as a viable alternative for elderly patients with LARC. Full article
(This article belongs to the Special Issue The Surgical Management of Colorectal Cancer)
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14 pages, 3364 KB  
Article
B7H3 Immune Checkpoint Overexpression Is Associated with Decreased Complete Response Rates to Neoadjuvant Therapy in Locally Advanced Rectal Cancer
by Sebastian Curcean, Raluca Maria Hendea, Rares Buiga, Alexandru Tipcu, Andra Curcean, Catalin Vlad, Zsolt Fekete, Alina-Simona Muntean, Daniela Martin and Alexandru Irimie
Diagnostics 2024, 14(18), 2023; https://doi.org/10.3390/diagnostics14182023 - 12 Sep 2024
Cited by 2 | Viewed by 2156
Abstract
Background and Objectives: Rectal cancer accounts for approximately one-third of colorectal cancers, with over 340,000 deaths globally in 2022. Despite advancements in treatment, the five-year overall survival for locally advanced rectal cancer (LARC) remains at 74%, with significant morbidity. B7H3 (CD276), an immune [...] Read more.
Background and Objectives: Rectal cancer accounts for approximately one-third of colorectal cancers, with over 340,000 deaths globally in 2022. Despite advancements in treatment, the five-year overall survival for locally advanced rectal cancer (LARC) remains at 74%, with significant morbidity. B7H3 (CD276), an immune checkpoint protein, plays a role in tumor progression and resistance to therapy, and correlates with poor prognosis in various cancers, including colorectal cancer. This study aims to evaluate the expression of B7H3 in LARC and its impact on overall complete response (oCR) rates to neoadjuvant therapy. Methods: A retrospective study was conducted on 60 patients with LARC who received neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision (TME). B7H3 expression was assessed using immunohistochemistry on surgical specimens. Expression levels were categorized as high or low based on a composite score, and their association with oCR rates was analyzed. Results: High B7H3 expression was observed in 60% of patients, with 73.5% showing expression in more than 50% of tumor cells. Patients who achieved oCR had significantly lower B7H3 expression compared to those with residual disease (p < 0.001). No nuclear expression of B7H3 was detected. No significant correlation was found between B7H3 expression and other clinicopathological variables, except for a higher likelihood of non-restorative surgery in patients with elevated B7H3 levels (p = 0.049). Mucinous adenocarcinoma had high expression of B7H3. Conclusions: Elevated B7H3 expression is associated with reduced oCR rates in LARC, highlighting its potential role as a prognostic biomarker. Further studies with larger cohorts are warranted to validate these findings and explore B7H3-targeted therapies as a treatment strategy for LARC. Full article
(This article belongs to the Special Issue Diagnosis and Management of Colorectal Lesions)
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14 pages, 990 KB  
Article
PD-L1 Expression in Paired Samples of Rectal Cancer
by Mina Coussement, Roberta Fazio, Alessandro Audisio, Reem El Khoury, Fatima-Zahra Abbassi, Irene Assaf, Chiara Conti, Chiara Gallio, Nada Benhima, Giacomo Bregni, Paraskevas Gkolfakis, Valentina Spagnolo, Geraldine Anthoine, Gabriel Liberale, Luigi Moretti, Philippe Martinive, Alain Hendlisz, Pieter Demetter and Francesco Sclafani
Cancers 2024, 16(14), 2606; https://doi.org/10.3390/cancers16142606 - 21 Jul 2024
Cited by 2 | Viewed by 2519
Abstract
Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to [...] Read more.
Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes. Full article
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14 pages, 4602 KB  
Article
Outcome of Patients with Locally Advanced Rectal Cancer Pursuing Non-Surgical Strategy in National Cancer Database
by Hanna Kakish, Fasih A. Ahmed, Lee M. Ocuin, Jennifer L. Miller-Ocuin, Emily Steinhagen, Richard S. Hoehn, Amit Mahipal, Christopher W. Towe and Sakti Chakrabarti
Cancers 2024, 16(12), 2194; https://doi.org/10.3390/cancers16122194 - 11 Jun 2024
Viewed by 2084
Abstract
Background: Survival data on patients with locally advanced rectal cancer (LARC) undergoing non-operative management (NOM) in a real-world setting are lacking. Methods: We analyzed LARC patients from the National Cancer Database with the following features: treated between 2010 and 2020, age 18–65 years, [...] Read more.
Background: Survival data on patients with locally advanced rectal cancer (LARC) undergoing non-operative management (NOM) in a real-world setting are lacking. Methods: We analyzed LARC patients from the National Cancer Database with the following features: treated between 2010 and 2020, age 18–65 years, Charlson comorbidity index (CCI) ≤ 1, received neoadjuvant multiagent chemotherapy plus radiation ≥ 45 Gray, and underwent surgery or NOM. Patients were stratified into two groups: (A) clinical T1-3 tumors with positive nodes (cT1-3N+) and (B) clinical T4 tumors, N+/− (cT4N+/−). We performed a comparative analysis of overall survival (OS) with NOM versus surgery by the Kaplan–Meier method and propensity score matching. Additionally, a multivariable analysis explored the association between NOM and OS. Results: NOM exhibited significantly lower OS than surgery in both groups. In cT1-3N+ patients, NOM resulted in a 5-year OS of 73.9% (95% confidence interval [CI] = 69.7–77.6%) versus 84.5% (95% CI = 83.6–85.3%) with surgery (p < 0.001). In the cT4N+/− group, NOM yielded a 5-year OS of 44.5% (95% CI = 37.0–51.8%) versus 72.5% (95% CI = 69.9–74.8%) with surgery (p < 0.001). Propensity score matching and multivariable analyses revealed similar conclusions. Conclusion: Patients with LARC undergoing NOM versus surgery in real-world settings appear to have inferior survival. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy for Locally-Advanced Rectal Cancer)
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15 pages, 2552 KB  
Article
Evaluation of PD-L1 Expression in Colorectal Carcinomas by Comparing Scoring Methods and Their Significance in Relation to Clinicopathologic Parameters
by Mirela Frančina, Mislav Mikuš, Marin Mamić, Tihomir Jovanović, Mario Ćorić, Božica Lovrić, Ivan Vukoja, Goran Zukanović, Kristijan Matković, Jasmina Rajc, Ferdinand Slišurić, Mateja Jurić-Marelja, Goran Augustin and Ilijan Tomaš
Diagnostics 2024, 14(10), 1007; https://doi.org/10.3390/diagnostics14101007 - 13 May 2024
Cited by 3 | Viewed by 5819
Abstract
Background: This study aims to evaluate PD-L1 expression in colorectal carcinomas (CRCs) by using the tumor proportion score (TPS) and the combined positive score (CPS), and to investigate whether there is a correlation with clinicopathologic features. Methods: A cross-sectional study was conducted that [...] Read more.
Background: This study aims to evaluate PD-L1 expression in colorectal carcinomas (CRCs) by using the tumor proportion score (TPS) and the combined positive score (CPS), and to investigate whether there is a correlation with clinicopathologic features. Methods: A cross-sectional study was conducted that included samples from patients with colorectal adenocarcinoma treated with colon resection and rectal resection after neoadjuvant radio- and chemotherapy at the Department of Abdominal Surgery at Požega Hospital in the period from 2017 to 2022. The study included 102 tumor tissue samples from patients after resection and the pathohistological diagnosis of adenocarcinoma. Results: In our study, the PD-L1 positivity rate after the TPS was 42 (41%) samples, and after the CPS, 97 (95%) of them (p < 0.001). The positive expression of PD-L1 in tumor cells using the TPS method showed a statistically significant association with adenocarcinoma (TPS ≥ 10–50% and ≥50%). There were significantly more that were moderately differentiated, with TPS ≥ 50%, and those poorly differentiated had values ≥ 10–50%. There were significantly more patients with a status of more than one positive lymph node with TPS values ≥ 10–50%. Patients without metastases in the lymph nodes are significantly more likely to have CPS values > 50%, compared with other lymph node statuses. Conclusions: These results suggest that the total number of PD-L1-expressing cells, including tumor and immune cells, is a more sensitive biomarker than the number of PD-L1-expressing tumor cells alone in CRC. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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