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Innovations in Diagnosis and Treatment of Colon and Rectal Cancer:...
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Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 26742

Special Issue Editor

Dr. Gianluca Pellino

E-Mail Website
Guest Editor
1. Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
2. Colorectal Surgery, Vall d'Hebron University Hospital, Barcelona, Spain
Interests: artificial intelligence; prehabilitation; technologies in coloproctology; rectal cancer management; biomolecular diagnosis; translational research; robotic surgery; transanal surgery; inflammatory bowel diseases; colorectal cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue is intended to cover the latest advancement in diagnosis and treatment of colon and rectal cancer. Over the last few years, new technologies have been proposed in colorectal surgery, as well as newer treatment regimens in terms of adjuvant and neoadjuvant therapies. The threshold for inoperability has been lowered in advanced colorectal cancer, thanks to the evolving multimodality approach to patients.

Indeed, several areas needs to be covered in the field. This Special Issue aims to offer a collection of articles that summarise the available evidence on diagnosis and treatment of early and advanced colon and rectal cancer (in the form of systematic review, ideally with metanalysis); report on original experiences from centres with expertise and from the innovators of the field; provide the perspective of non-surgical staff, as well as patients and the public in relation with colorectal cancer. The issue is open to both preclinical research (basic), translational research, and clinical reports.

The Special Issue will focus (but will not be limited to) the following topics:

- Risk factors for colorectal cancer;
- Pathways of colorectal cancer development and progression;
- Novel treatment targets and individualised approaches;
- Strategies to reduce the incidence of colorectal cancer and trends over time;
- Preoperative assessment and optimisation to improve short and long term outcomes;
- Innovations in imaging and preoperative surgical planning;
- Surgical innovations (newer technologies, techniques);
- Management of early colon and rectal cancer;
- Management of locally advanced and recurrent colon and rectal cancer;
- Patients, survivors, and public experience in colorectal cancer.

Dr. Gianluca Pellino
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neoadjuvant treatment
  • individualised treatment
  • colorectal cancer
  • robotic surgery
  • immunotherapy
  • 3D imaging

Published Papers (15 papers)

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11 pages, 594 KiB  
Article
The Impact of BRAF Mutation Status on Survival Outcomes and Treatment Patterns among Metastatic Colorectal Cancer Patients in Alberta, Canada
by R. Liam Sutherland, Devon J. Boyne, Darren R. Brenner and Winson Y. Cheung
Cancers 2023, 15(24), 5748; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15245748 - 08 Dec 2023
Viewed by 1084
Abstract
Colorectal cancer presents via multiple different clinical phenotypes that can arise from a variety of different genetic and molecular alterations. The aim of this study was to describe survival outcomes and treatment patterns of metastatic colorectal cancer (mCRC) patients by v-raf murine sarcoma [...] Read more.
Colorectal cancer presents via multiple different clinical phenotypes that can arise from a variety of different genetic and molecular alterations. The aim of this study was to describe survival outcomes and treatment patterns of metastatic colorectal cancer (mCRC) patients by v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation status. The Alberta Cancer Registry was used to identify all patients >18 years old who had been diagnosed with mCRC in Alberta between 1 January 2017 and 31 December 2019 and had received at least one cycle of systemic therapy. Treatment patterns were compared between wild-type and mutant BRAF mCRC patients. Cox regression models and Kaplan–Meier curves were created to assess survival differences by both treatment pattern and BRAF status. A total of 488 patients were identified with mCRC, of which 42 (11.4%) were confirmed to have a BRAF mutation. The most common first-line treatment regimen was either capecitabine and oxaliplatin (CAPOX) or leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX). The median overall survival for mCRC patients was 20.01 months. Mutant BRAF patients had a median survival of 8.21 months compared to 20.03 months among those with wild-type BRAF. BRAF mutations among mCRC patients are associated with a considerably poor prognosis, reinforcing the need for clinical BRAF testing among newly diagnosed patients to better understand their prognosis. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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12 pages, 4732 KiB  
Article
Alteration of the Exhaled Volatile Organic Compound Pattern in Colorectal Cancer Patients after Intentional Curative Surgery—A Prospective Pilot Study
by Julia Hanevelt, Ivonne J. H. Schoenaker, Richard M. Brohet, Ruud W. M. Schrauwen, Frederique J. N. Baas, Pieter J. Tanis, Henderik L. van Westreenen and Wouter H. de Vos tot Nederveen Cappel
Cancers 2023, 15(19), 4785; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15194785 - 29 Sep 2023
Viewed by 1013
Abstract
As current follow-up modalities for colorectal carcinoma (CRC) have restricted sensitivity, novel diagnostic tools are needed. The presence of CRC changes the endogenous metabolism, resulting in the release of a specific volatile organic compounds (VOC) pattern that can be detected with an electronic [...] Read more.
As current follow-up modalities for colorectal carcinoma (CRC) have restricted sensitivity, novel diagnostic tools are needed. The presence of CRC changes the endogenous metabolism, resulting in the release of a specific volatile organic compounds (VOC) pattern that can be detected with an electronic nose or AeonoseTM. To evaluate the use of an electronic nose in the follow-up of CRC, we studied the effect of curative surgery on the VOC pattern recognition using AeonoseTM. A prospective cohort study was performed, in which 47 patients diagnosed with CRC were included, all of whom underwent curative surgical resection. Breath testing was performed before and after surgery using the AeonoseTM. A machine learning model was developed by discerning between the 94 pre-and postoperative breath samples. The training model differentiated between the pre-and postoperative CRC breath samples with a sensitivity and specificity of 0.78 (95%CI 0.61–0.90) and 0.73 (95%CI 0.56–0.86), respectively, with an accuracy of 0.76 (95%CI 0.66–0.85), and an area under the curve of 0.79 (95%CI 0.68–0.89). The internal validation of the test set resulted in an accuracy of 0.75 (95%CI 0.51–0.91) and AUC of 0.82 (95%CI 0.61–1). In conclusion, our results suggest that the VOC pattern of CRC patients is altered by curative surgery in a short period, indicating that the exhaled VOCs might be closely related to the presence of CRC. However, to use AeonoseTM as a potential diagnostic tool in the clinical follow-up of CRC patients, the performance of the models needs to be improved through further large-scale prospective research. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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12 pages, 790 KiB  
Article
Colorectal Cancer Fast Tracks: Cancer Yield and the Predictive Value of Entry Criteria
by Linnea Uebel, Indy Kromodikoro, Nils Nyhlin and Michiel van Nieuwenhoven
Cancers 2023, 15(19), 4778; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15194778 - 28 Sep 2023
Viewed by 881
Abstract
Background: Fast-track pathways for diagnosing colorectal cancer (CRC) have been implemented in several European countries. In Sweden, a substantial number of CRC are diagnosed via the Swedish Standardized Course of Care for colorectal cancer (SCC-CRC). We evaluated the SCC-CRC in terms of CRC [...] Read more.
Background: Fast-track pathways for diagnosing colorectal cancer (CRC) have been implemented in several European countries. In Sweden, a substantial number of CRC are diagnosed via the Swedish Standardized Course of Care for colorectal cancer (SCC-CRC). We evaluated the SCC-CRC in terms of CRC yield, and predictive values and odds ratios (OR) for the entry criteria. Methods: We retrospectively analyzed all 2539 patients referred for SCC-CRC colonoscopy between September 2016 and December 2020. Entry criteria and colonoscopy outcomes were analyzed. Results: CRC yield was 16.4%. Highest positive predictive values (PPVs) were seen for abnormal radiology (PPV 30.5%, OR 4.7 (95% CI 3.4–6.4) p < 0.001), abnormal rectal examination (PPV 28%, OR 3.6 (95% CI 2.7–4.8) p < 0.001), and anemia (PPV 24.8%, OR 2.2 (95% CI 1.5–3.1) p < 0.001). Some entry criteria showed no significant risk increase, i.e., visible blood in stool/rectal bleeding, change in bowel habits, and the combination of changed bowel habits plus anemia. A positive fecal immunochemical test (FIT), although not part of the SCC-CRC, showed the highest OR: 9.9 (95% CI 4.5–21.7) p < 0.001) and PPV of 18.8%. Conclusions: CRC yield from the SCC-CRC is slightly higher compared to other European fast tracks. A number of entry criteria showed no benefit towards assessing CRC risk. FIT testing should be included in CRC fast tracks to increase diagnostic efficacy. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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11 pages, 266 KiB  
Article
Early Age of Onset Is an Independent Predictor for a Worse Response to Neoadjuvant Therapies in Sporadic Rectal Cancer Patients
by Caterina Foppa, Annalisa Maroli, Antonio Luberto, Carlotta La Raja, Paola Spaggiari, Cristiana Bonifacio, Stefano De Zanet, Marco Montorsi, Salvatore Piscuoglio, Luigi Maria Terracciano, Armando Santoro and Antonino Spinelli
Cancers 2023, 15(14), 3750; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15143750 - 24 Jul 2023
Cited by 1 | Viewed by 1011
Abstract
The incidence of rectal cancer (RC) is increasing in the population aged ≤ 49 (early-onset RC-EORC). EORC patients are more likely to present with locally advanced disease at diagnosis than late-onset RC (LORC; aged ≥ 50) patients. As a consequence, more EORC patients [...] Read more.
The incidence of rectal cancer (RC) is increasing in the population aged ≤ 49 (early-onset RC-EORC). EORC patients are more likely to present with locally advanced disease at diagnosis than late-onset RC (LORC; aged ≥ 50) patients. As a consequence, more EORC patients undergo neoadjuvant therapies. The response to treatment in EORC patients is still unknown. This study aims to explore the effect of age of onset on the pathological response to neoadjuvant therapies in sporadic locally advanced RC (LARC) patients. Based on an institutional prospectively maintained database, LARC patients undergoing neoadjuvant therapies and radical surgery between January 2010 and December 2022 were allocated to the EORC and LORC groups. The primary endpoint was the rate of incomplete response (Dworak 0–2). A total of 326 LORC and 79 EORC patients were included. Pre-neoadjuvant tumor features were comparable. A significantly higher rate of incomplete response was observed in EORC patients (49% vs. 35%; p = 0.028). From multivariable analysis, early age of onset, smoking and extramural invasion presented as independent risk factors for a worse response. This study demonstrates that an early age of onset is related to a worse response and calls for different multimodal strategies in this group of patients. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
21 pages, 4408 KiB  
Article
Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients
by Angel Lanas, Stefania Tacconelli, Annalisa Contursi, Elena Piazuelo, Annalisa Bruno, Maurizio Ronci, Simone Marcone, Melania Dovizio, Federico Sopeña, Lorenza Falcone, Cristina Milillo, Matteo Mucci, Patrizia Ballerini and Paola Patrignani
Cancers 2023, 15(9), 2457; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15092457 - 25 Apr 2023
Cited by 2 | Viewed by 1591
Abstract
Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial. Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether [...] Read more.
Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial. Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas. Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B2 generation ex vivo (serum TXB2). However, enhanced residual urinary 11-dehydro-TXB2 and urinary PGEM, primary metabolites of TXA2 and prostaglandin (PG)E2, respectively, were detected in association with incomplete acetylation of COX-1 in normal colorectal biopsies and adenomas. Proteomics of adenomas showed that Aspirin significantly modulated only eight proteins. The upregulation of vimentin and downregulation of HBB (hemoglobin subunit beta) distinguished two groups with high vs. low residual 11-dehydro-TXB2 levels, possibly identifying the nonresponders and responders to Aspirin. Conclusions: Although low-dose Aspirin appropriately inhibited the platelet, persistently high systemic TXA2 and PGE2 biosynthesis were found, plausibly for a marginal inhibitory effect on prostanoid biosynthesis in the colorectum. Novel chemotherapeutic strategies in FAP can involve blocking the effects of TXA2 and PGE2 signaling with receptor antagonists. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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15 pages, 1072 KiB  
Article
Ability of Delta Radiomics to Predict a Complete Pathological Response in Patients with Loco-Regional Rectal Cancer Addressed to Neoadjuvant Chemo-Radiation and Surgery
by Valerio Nardone, Alfonso Reginelli, Roberta Grassi, Giovanna Vacca, Giuliana Giacobbe, Antonio Angrisani, Alfredo Clemente, Ginevra Danti, Pierpaolo Correale, Salvatore Francesco Carbone, Luigi Pirtoli, Lorenzo Bianchi, Angelo Vanzulli, Cesare Guida, Roberto Grassi and Salvatore Cappabianca
Cancers 2022, 14(12), 3004; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14123004 - 18 Jun 2022
Cited by 12 | Viewed by 2613
Abstract
We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy [...] Read more.
We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefore, carried out in order to correlate the above-mentioned TA parameters with the frequency of pathological responses in the examined patients’ population focusing on the detection of complete pathological response (pCR, with no viable cancer cells: TRG 1) as main statistical endpoint. ROC curves were performed on three different datasets considering that on the 21 patients, only 21% achieved an actual pCR. In our training dataset series, pCR frequency significantly correlated with ADC GLCM-Entropy only, when univariate and binary logistic analysis were performed (AUC for pCR was 0.87). A confirmative binary logistic regression analysis was then repeated in the two remaining validation datasets (AUC for pCR was 0.92 and 0.88, respectively). Overall, these results support the hypothesis that D-TA may have a significant predictive value in detecting the occurrence of pCR in our patient series. If confirmed in prospective and multicenter trials, these results may have a critical role in the selection of patients with locally advanced rectal cancer who may benefit form radical surgery after neoadjuvant chemoradiotherapy. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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13 pages, 1280 KiB  
Article
Predictors of Long-Term Outcomes of Video-Laparoscopic Versus Open Surgery in Obese Patients with Colorectal Cancer: A Propensity Score Matching Study
by Cinzia Bizzoca, Roberta Zupo, Fabio Castellana, Annamaria Sila, Felicia Fiore, Fabrizio Aquilino, Rodolfo Sardone and Leonardo Vincenti
Cancers 2022, 14(11), 2669; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112669 - 27 May 2022
Cited by 1 | Viewed by 1697
Abstract
Background: Minimally invasive methods in colorectal surgery offer unquestionable advantages, especially in the context of obesity. The current study addresses the lack of scientific evidence on the long-term oncologic safety of video-laparoscopic (VL) approaches in excess-weight CRC patients undergoing surgery. Methods: We retrospectively [...] Read more.
Background: Minimally invasive methods in colorectal surgery offer unquestionable advantages, especially in the context of obesity. The current study addresses the lack of scientific evidence on the long-term oncologic safety of video-laparoscopic (VL) approaches in excess-weight CRC patients undergoing surgery. Methods: We retrospectively analyzed a surgical database consisting of 138 CRC patients undergoing VL (n = 87, 63%) and open CRC surgery (n = 51, 37%). To reduce selection bias, a propensity score matching was applied as a preliminary step to balance the comparison between the two surgery groups, i.e., VL and open surgery. Data from patients treated by the same surgeon were used.to minimize bias. Additional Cox regression models were run on the matched sample (N = 98) to explore the observed benefits of VL surgery in terms of overall and cancer-free survival. The nonparametric Kaplan-Meier method was used to compare the two surgical approaches and assess the likelihood of survival and cancer relapse. Results: The study sample was mostly male (N = 86, 62.3%), and VL outnumbered open surgery (63% versus 37%). Both before and after the matching, the VL-allocated group showed better overall survival (p < 0.01) with comparable cancer-free survival over more than five years of median observation time (66 months). Kaplan Meier survival probability curves corroborated the VL significant protective effect on survival (HR of 0.32; 95% CI: 0.13 to 0.81) even after adjusting for major confounding factors (age, gender, comorbidity index, BMI, tumor localization, tumor staging, tumor grading, clearance, CRM). Findings on oncologic performance by tumor relapse were comparable but lacked significance due to the small number of events observed. Conclusions: Comparing CRC surgical approaches, VL allocation showed comparable cancer-free survival but also a better performance on overall mortality than open surgery over more than five years of median observation. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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11 pages, 1518 KiB  
Article
Care Management and Survival of Patients Diagnosed with Synchronous Metastatic Colorectal Cancer: A High-Resolution Population-Based Study in Two French Areas
by Andrea Mulliri, Joséphine Gardy, Mélanie Cariou, Guy Launoy, Michel Robaszkiewicz, Arnaud Alves, Véronique Bouvier and Olivier Dejardin
Cancers 2022, 14(7), 1777; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071777 - 31 Mar 2022
Cited by 1 | Viewed by 1334
Abstract
Population-based studies provide the opportunity to assess the real-world applicability of current clinical practices. The present research evaluated the survival outcomes of different therapeutic strategies for colorectal cancer (CRC) with synchronous metastasis (SM). The differential impact of treatment sequence, viz. whether chemotherapy (CT) [...] Read more.
Population-based studies provide the opportunity to assess the real-world applicability of current clinical practices. The present research evaluated the survival outcomes of different therapeutic strategies for colorectal cancer (CRC) with synchronous metastasis (SM). The differential impact of treatment sequence, viz. whether chemotherapy (CT) or primary tumor resection (PTR) was performed first, was also evaluated. Methods: All CRC cases with SM diagnosed between 2006 and 2016 (N = 3062) were selected from two specialized digestive cancer registries from northwest France. Cox regression analysis was used to assess survival. Multivariable logistic regression was used to examine factors related to the combination of PTR and CT. Results: The longest survival was observed in patients treated by PTR combined with CT (Group 4; N = 1159). Overall survival was 51.80% at one year (95% Confidence Interval (CI) 50.00–53.60%) and 9.40% at five years (95% CI, 8.30–10.60%). Survival did not differ with respect to the order of treatment in multivariable analysis (hazard ratio, 1.05; 95% CI, 0.88–1.24; p = 0.55). Conclusion: Regardless of the sequence of treatment, a PTR + CT offered the best survival in patients with CRC and SM, even though few were eligible for combination therapy (38%). Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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11 pages, 1029 KiB  
Article
External Validation of a Radiomics Model for the Prediction of Complete Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer
by Anaïs Bordron, Emmanuel Rio, Bogdan Badic, Omar Miranda, Olivier Pradier, Mathieu Hatt, Dimitris Visvikis, François Lucia, Ulrike Schick and Vincent Bourbonne
Cancers 2022, 14(4), 1079; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14041079 - 21 Feb 2022
Cited by 11 | Viewed by 2282
Abstract
Objective: Our objective was to develop a radiomics model based on magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CE-CT) to predict pathological complete response (pCR) to neoadjuvant treatment in locally advanced rectal cancer (LARC). Material: All patients treated for a LARC [...] Read more.
Objective: Our objective was to develop a radiomics model based on magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CE-CT) to predict pathological complete response (pCR) to neoadjuvant treatment in locally advanced rectal cancer (LARC). Material: All patients treated for a LARC with neoadjuvant CRT and subsequent surgery in two separate institutions between 2012 and 2019 were considered. Both pre-CRT pelvic MRI and CE-CT were mandatory for inclusion. The tumor was manually segmented on the T2-weighted and diffusion axial MRI sequences and on CE-CT. In total, 88 radiomic parameters were extracted from each sequence using the Miras© software, with a total of 822 features by patient. The cohort was split into training (Institution 1) and testing (Institution 2) sets. The ComBat and Synthetic Minority Over-sampling Technique (SMOTE) approaches were used to account for inter-institution heterogeneity and imbalanced data, respectively. We selected the most predictive characteristics using Spearman’s rank correlation and the Area Under the ROC Curve (AUC). Five pCR prediction models (clinical, radiomics before and after ComBat, and combined before and after ComBat) were then developed on the training set with a neural network approach and a bootstrap internal validation (n = 1000 replications). A cut-off maximizing the model’s performance was defined on the training set. Each model was then evaluated on the testing set using sensitivity, specificity, balanced accuracy (Bacc) with the predefined cut-off. Results: Out of the 124 included patients, 14 had pCR (11.3%). After ComBat harmonization, the radiomic and the combined models obtained a Bacc of 68.2% and 85.5%, respectively, while the clinical model and the pre-ComBat combined achieved respective Baccs of 60.0% and 75.5%. Conclusions: After correction of inter-site variability and imbalanced data, addition of radiomic features enhances the prediction of pCR after neoadjuvant CRT in LARC. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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14 pages, 745 KiB  
Article
Factors Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer: The Experience of a Single Institution with 269 Patients (STONE-01)
by Michele Fiore, Pasquale Trecca, Luca E. Trodella, Roberto Coppola, Marco Caricato, Damiano Caputo, Alessandro Coppola, Gian M. Petrianni, Gabriele D’Ercole, Edy Ippolito, Rolando M. D’Angelillo and Sara Ramella
Cancers 2021, 13(23), 6074; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13236074 - 02 Dec 2021
Cited by 2 | Viewed by 1547
Abstract
Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort [...] Read more.
Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27–0.93 and p = 0.003; OR: 0.42, CI: 0.24–0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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14 pages, 3391 KiB  
Article
Stroma AReactive Invasion Front Areas (SARIFA)—A New Easily to Determine Biomarker in Colon Cancer—Results of a Retrospective Study
by Benedikt Martin, Bianca Grosser, Lana Kempkens, Silvia Miller, Svenja Bauer, Christine Dhillon, Bettina Monika Banner, Eva-Maria Brendel, Éva Sipos, Dmytro Vlasenko, Gerhard Schenkirsch, Stefan Schiele, Gernot Müller and Bruno Märkl
Cancers 2021, 13(19), 4880; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13194880 - 29 Sep 2021
Cited by 9 | Viewed by 2091
Abstract
Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor–stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct [...] Read more.
Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor–stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p < 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (<1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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14 pages, 1117 KiB  
Article
Chronic Obstructive Pulmonary Disease and Its Acute Exacerbation before Colon Adenocarcinoma Treatment Are Associated with Higher Mortality: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study
by Yen-Chang Chen, Ming-Chang Li, Ying-Hui Yu, Chih-Ming Lin and Szu-Yuan Wu
Cancers 2021, 13(18), 4728; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184728 - 21 Sep 2021
Cited by 3 | Viewed by 1944
Abstract
Purpose: To investigate whether chronic obstructive pulmonary disease (COPD) and COPD severity (acute exacerbation of COPD (AECOPD)) affect the survival outcomes of patients with colon adenocarcinoma receiving standard treatments. Methods: From the Taiwan Cancer Registry Database, we recruited patients with clinical stage I–III [...] Read more.
Purpose: To investigate whether chronic obstructive pulmonary disease (COPD) and COPD severity (acute exacerbation of COPD (AECOPD)) affect the survival outcomes of patients with colon adenocarcinoma receiving standard treatments. Methods: From the Taiwan Cancer Registry Database, we recruited patients with clinical stage I–III colon adenocarcinoma who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into COPD and non-COPD (Group 1 and 2) groups through propensity score matching. Results: In total, 1512 patients were eligible for further comparative analysis between non-COPD (1008 patients) and COPD (504 patients) cohorts. In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for all-cause mortality for Group 1 compared with Group 2 was 1.17 (1.03, 1.29). In patients with colon adenocarcinoma undergoing curative resection, the aHRs (95% CIs) for all-cause mortality in patients with hospitalization frequencies of ≥1 and ≥2 times for AECOPD within 1 year before adenocarcinoma diagnosis were 1.08 (1.03, 1.51) and 1.55 (1.15, 2.09), respectively, compared with those without AECOPD. Conclusion: In patients with colon adenocarcinoma undergoing curative resection, COPD was associated with worse survival outcomes. Being hospitalized at least once for AECOPD within 1 year before colon adenocarcinoma diagnosis was an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for AECOPD within 1 year before diagnosis was associated with poorer survival. Our study highlights the importance of COPD management, particularly the identification of frequent exacerbators and the prevention of AECOPD before standard colon adenocarcinoma treatments are applied. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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25 pages, 2110 KiB  
Systematic Review
Lymphatic Mapping in Colon Cancer Depending on Injection Time and Tracing Agent: A Systematic Review and Meta-Analysis of Prospective Designed Studies
by Katharina Lucas, Nathaniel Melling, Anastasios D. Giannou, Matthias Reeh, Oliver Mann, Thilo Hackert, Jakob R. Izbicki, Daniel Perez and Julia K. Grass
Cancers 2023, 15(12), 3196; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15123196 - 15 Jun 2023
Cited by 4 | Viewed by 1210
Abstract
An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic [...] Read more.
An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010–0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018–0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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17 pages, 452 KiB  
Systematic Review
Possible Value of Faecal Immunochemical Test (FIT) When Added in Symptomatic Patients Referred for Colonoscopy: A Systematic Review
by Henrike Jacoba Brands, Brigit Van Dijk, Richard M. Brohet, Henderik L. van Westreenen, Jan Willem B. de Groot, Leon M. G. Moons and Wouter H. de Vos tot Nederveen Cappel
Cancers 2023, 15(7), 2011; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15072011 - 28 Mar 2023
Cited by 1 | Viewed by 1327
Abstract
If Colorectal cancer (CRC) is detected and treated early, the survival rate is high. This is one of the reasons that population-based screening programs for the early detection of CRC using the faecal immunochemical test (FIT) started worldwide. These programs compete with regular [...] Read more.
If Colorectal cancer (CRC) is detected and treated early, the survival rate is high. This is one of the reasons that population-based screening programs for the early detection of CRC using the faecal immunochemical test (FIT) started worldwide. These programs compete with regular colonoscopy programs and increase the waiting time for symptomatic patients. However, the literature has shown that the correlation between intestinal complaints and the gain of colonoscopy is poor. The aim of this study is to assess the diagnostic utility of symptoms for the yield (CRC) of colonoscopy and to compare this with the diagnostic utility of FIT when offered to symptomatic patients. Methods: We performed a systematic review search for CRC as an outcome of colonoscopy in referred symptomatic patients and separately for CRC as an outcome in symptomatic patients with a positive FIT. We searched systematically for clinical trials or observational studies in databases, followed by hand-searching of reference lists. We used random Meta-Disc to evaluate the diagnostic performance, using the exploration of heterogeneity with a variety of test statistics and by computing the pooled estimates. Results: We included 35 studies, with almost 5 million symptomatic patients. In addition, we included nine prospective studies with a positive FIT in symptomatic patients, with more than 5000 patients. Significant heterogeneity was found for every symptom and the outcome of colonoscopy in the effect size of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio. In a random effect model, the pooled sensitivity of colonoscopy in symptomatic patients was very low (25%). However, the pooled sensitivity in symptomatic patients with a positive FIT was 83% and the pooled specificity 77%. A total of 75 symptomatic patients (1.4%) had a false-negative FIT. Conclusion: Adding FIT in symptomatic patients seems useful for predicting CRC as an outcome of colonoscopy. FIT seems a potential tool for an improved triage of colonoscopy in symptomatic patients. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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15 pages, 541 KiB  
Systematic Review
Retroperitoneal Lymph Node Dissection in Colorectal Cancer with Lymph Node Metastasis: A Systematic Review
by Michael G. Fadel, Mosab Ahmed, Gianluca Pellino, Shahnawaz Rasheed, Paris Tekkis, David Nicol, Christos Kontovounisios and Erik Mayer
Cancers 2023, 15(2), 455; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15020455 - 10 Jan 2023
Cited by 2 | Viewed by 2811
Abstract
The benefits and prognosis of RPLND in CRC have not yet been fully established. This systematic review aimed to evaluate the outcomes for CRC patients with RPLNM undergoing RPLND. A literature search of MEDLINE, EMBASE, EMCare, and CINAHL identified studies from between January [...] Read more.
The benefits and prognosis of RPLND in CRC have not yet been fully established. This systematic review aimed to evaluate the outcomes for CRC patients with RPLNM undergoing RPLND. A literature search of MEDLINE, EMBASE, EMCare, and CINAHL identified studies from between January 1990 and June 2022 that reported data on clinical outcomes for patients who underwent RPLND for RPLNM in CRC. The following primary outcome measures were derived: postoperative morbidity, disease free-survival (DFS), overall survival (OS), and re-recurrence. Nineteen studies with a total of 541 patients were included. Three hundred and sixty-three patients (67.1%) had synchronous RPLNM and 178 patients (32.9%) had metachronous RPLNM. Perioperative chemotherapy was administered in 496 (91.7%) patients. The median DFS was 8.6–38.0 months and 5-year DFS was 24.4% (10.0–60.5%). The median OS was 25.0–83.0 months and 5-year OS was 47.0% (15.0–87.5%). RPLND is a feasible treatment option with limited morbidity and possible oncological benefit for both synchronous and metachronous RPLNM in CRC. Further prospective clinical trials are required to establish a better evidence base for RPLND in the context of RPLNM in CRC and to understand the timing of RPLND in a multimodality pathway in order to optimise treatment outcomes for this group of patients. Full article
(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)
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