Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
5.2
Journals
Cancers
Special Issues
Advances in Radiotherapy and Prognosis of Rectal Cancer
share announcement

Advances in Radiotherapy and Prognosis of Rectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 26057

Special Issue Editors

Dr. Antonino De Paoli

E-Mail Website
Guest Editor
Radiation Oncology, Centro di Riferimento Oncologico (CRO)-IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy
Interests: gastrointestinal tumors; chemoradiotherapy intensification; organ preservation; translational research; radiomics
Dr. Maria Antonietta Gambacorta

E-Mail Website
Guest Editor
Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, Italy
Interests: rectal cancer, chemoradiotherapy intensification, organ preservation, prediction model, radiomics

Special Issue Information

Dear Colleagues,

Radiotherapy (RT) has evolved significantly in the multidisciplinary management of rectal cancer within recent years. While preoperative chemoradiotherapy (pCRT) or short-course RT (SCRT) followed by TME surgery and adjuvant chemotherapy is the standard of care for locally advanced, stage T3–4,N0–2,M0 disease, technological advances in planning and precision radiation delivery now allow for safe dose escalation in pCRT intensification for MRI-defined high-risk  patients, aiming to increase the response rate, R0 resection, local control, survival outcomes, and allowing organ preservation in selected complete responsive (CR) patients. Interest in RT dose escalation is also recently reported in intermediate-risk patients with less-advanced disease, addressing clinical investigations mainly oriented to rectal-sparing strategies.

Innovative functional imaging (DWI-MRI, CT-PET) continues to be investigated in tumor response characterization at restaging and throughout pCRT to identify CR patients early and explore response-adapted RT dose escalation approaches for poor responders in an attempt to overcome adverse outcomes.

Investigations of host and tumor molecular profiles, as well as radiomic features of MRI and CT-PET, as prognostic and predictive markers of responses to treatment are in progress to allow for the pre-treatment identification of CR patients and a more appropriate selection for pCRT-intensified regimens in patients at high risk of a poor outcome or for organ-preservation strategies in potentially good responders.

Major interest is emerging in combining pCRT with induction or consolidation chemotherapy in a total neoadjuvant therapy (TNT) strategy. After the positive results of the RAPIDO, PRODIGE 23, and CAO/ARO/AIO-12 trials, as well as the preliminary results of the OPRA trials, some issues, including patient selection, the best sequence of CT, and pCRT with a possible intensified RT component in TNT, are current areas of further investigations.

In this Special Issue, we aim to highlight the evolving role of radiotherapy in the multidisciplinary management of rectal cancer following the recent technological advances in planning and in precision radiation delivery either in the standard pCRT or SCRT than in the more recent investigational interest in pCRT intensification with RT dose escalation. To this end, researchers are invited to contribute with original manuscripts, short communications, and comprehensive reviews that explore the role of pCRT intensification with radiation dose escalation (or standard pCRT/SCRT) and its integration in TNT strategies for rectal cancer. These may include reports on advanced technologies playing a role in the modern RT of rectal cancer and investigations on functional imaging (DWI-MRI, CT-PET) in tumor response characterization. Translational research studies on potential prognostic and predictive molecular markers of tumor responses to pCRT and exploring radiomic predictive models will be eligible for publication.

In this Special Issue, original research articles and reviews are welcome.

We look forward to receiving your contributions.

Dr. Antonino De Paoli
Dr. Maria Antonietta Gambacorta
Guest Editors

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

  • rectal cancer
  • intensified preoperative chemoradiotherapy
  • radiation dose escalation
  • total neoadjuvant therapy
  • DWI-MRI
  • CT-PET
  • biomarkers
  • artificial intelligence

Published Papers (16 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

18 pages, 755 KiB  
Article
Preoperative Intensified Chemoradiation with Intensity-Modulated Radiotherapy and Simultaneous Integrated Boost Combined with Capecitabine in Locally Advanced Rectal Cancer: Long-Term Outcomes of a Real-Life Multicenter Study
by Marco Lupattelli, Elisa Palazzari, Jerry Polesel, Giuditta Chiloiro, Ilaria Angelicone, Valeria Panni, Luciana Caravatta, Saide Di Biase, Gabriella Macchia, Rita Marina Niespolo, Pierfrancesco Franco, Valeria Epifani, Elisa Meldolesi, Flavia de Giacomo, Marco Lucarelli, Giampaolo Montesi, Giovanna Mantello, Roberto Innocente, Mattia Falchetto Osti, Maria Antonietta Gambacorta, Cynthia Aristei and Antonino De Paoliadd Show full author list remove Hide full author list
Cancers 2023, 15(23), 5702; https://doi.org/10.3390/cancers15235702 - 4 Dec 2023
Cited by 1 | Viewed by 1648
Abstract
Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 [...] Read more.
Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

20 pages, 1353 KiB  
Article
Post-Chemoradiation Metastatic, Persistent and Resistant Nodes in Locally Advanced Rectal Cancer: Metrics and Their Impact on Long-Term Outcome
by Felipe A. Calvo, María Tudela, Javier Serrano, Mercedes Muñoz-Fernández, María Isabel Peligros, Pilar Garcia-Alfonso and Emilio del Valle
Cancers 2023, 15(18), 4591; https://doi.org/10.3390/cancers15184591 - 15 Sep 2023
Viewed by 750
Abstract
Background: The purpose of this study was to evaluate the long-term oncological progression pattern of locally advanced rectal cancer patients with post-neoadjuvant nodal metastatic disease (ypN+) and correlate potential prognostic features associated with proven radiochemoresistant nodal biology. Methods: Individual patient data (100 variables) [...] Read more.
Background: The purpose of this study was to evaluate the long-term oncological progression pattern of locally advanced rectal cancer patients with post-neoadjuvant nodal metastatic disease (ypN+) and correlate potential prognostic features associated with proven radiochemoresistant nodal biology. Methods: Individual patient data (100 variables) from a 20-year consecutive single-institution multidisciplinary experience (1995–2015), delivering multimodal therapy to rectal cancer patient candidates for radical treatment, including a neoadjuvant component and surgical resection with or without intraoperative radiotherapy followed by optional adjuvant chemotherapy. The ypN+ disease data was registered in the context of initial staging categories post-neoadjuvant T status (ypT). Results: Data on 487 patients showed histologically confirmed diagnoses of metastatic nodal disease in 108 specimens (ypN+, 22.1). There was a significant age difference (p = 0.009) between the ypN groups: age ≥ 65 was 57.6% in pN0 and 43.5% in ypN+ and patients aged < 65 constituted 42.4% of pN0 and 56.5% of ypN+. According to the clinical stage there were statistically significant differences (p = 0.001) in the categories’ distribution: ypN+ patients 10.8% were stage II and 89.2% were stage III. Univariant analysis on outcome variables showed statistically significant differences in overall survival at 7 years (63.8% vs. 55.7%, p = 0.016) disease-free survival (DFS) (78% vs. 53.8%, p = 0.000) and local recurrence-free survival (LRFS) (93.6% vs. 84%, p = 0.002). Conclusions: The presence of nodal metastases (ypN+) after neoadjuvant therapy containing long-course pelvic irradiation severely impacts the long-term outcome for patients with locally advanced rectal cancer and correlates with multiple clinical and therapeutic variable metrics. Implementation of local and systemic therapies should be adapted and intensified in relation to the finding of ypN+ category in surgical specimens. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

15 pages, 1510 KiB  
Article
Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study
by Benedikt Engels, Antonino De Paoli, Elena Delmastro, Fernando Munoz, Stefano Vagge, Darius Norkus, Hendrik Everaert, Gianna Tabaro, Elisabetta Gariboldi, Umberto Ricardi, Eugenio Borsatti, Pietro Gabriele, Roberto Innocente, Elisa Palazzari, Emilie Dubaere, Marc-André Mahé, Sven Van Laere, Thierry Gevaert and Mark De Ridder
Cancers 2023, 15(15), 3869; https://doi.org/10.3390/cancers15153869 - 29 Jul 2023
Cited by 1 | Viewed by 1065
Abstract
Background: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. Methods: cT3-4 rectal cancer patients were [...] Read more.
Background: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. Methods: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). Results: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were −55.8% (±24.0%) and −52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). Conclusions: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

11 pages, 1797 KiB  
Article
pCR and 2-Year Disease-Free Survival: A Combination of the Two Endpoints as a New Classification for Locally Advanced Rectal Cancer Patients—An Updated Pooled Analysis of Eleven International Randomized Trials
by Maria Antonietta Gambacorta, Giuditta Chiloiro, Carlotta Masciocchi, Silvia Mariani, Angela Romano, Alessandra Gonnelli, Jean-Pierre Gerard, Samuel Ngan, Claus Rödel, Krzysztof Bujko, Robert Glynne-Jones, Johan van Soest, Andre Dekker, Andrea Damiani and Vincenzo Valentini
Cancers 2023, 15(12), 3209; https://doi.org/10.3390/cancers15123209 - 16 Jun 2023
Cited by 2 | Viewed by 981
Abstract
LARC is managed by multimodal treatments whose intensity can be highly modulated. In this context, we need surrogate endpoints to help predict long-term outcomes and better personalize treatments. A previous study identified 2yDFS as a stronger predictor of OS than pCR in LARC [...] Read more.
LARC is managed by multimodal treatments whose intensity can be highly modulated. In this context, we need surrogate endpoints to help predict long-term outcomes and better personalize treatments. A previous study identified 2yDFS as a stronger predictor of OS than pCR in LARC patients undergoing neoadjuvant RT. The aim of this pooled analysis was to assess the role of pCR and 2yDFS as surrogate endpoints for OS in a larger cohort. The pooled and subgroup analyses were performed on large rectal cancer randomized trial cohorts who received long-course RT. Our analysis focused on the evaluation of OS in relation to the pCR and 2-year disease status. A total of 4600 patients were analyzed. Four groups were identified according to intermediate outcomes: 12% had both pCR and 2yDFS (the better); 67% achieved 2yDFS but not pCR (the good); 1% had pCR but not 2yDFS; and 20% had neither pCR nor 2yDFS (the bad). The pCR and 2yDFS were favorably associated with OS in the univariate analysis, and 2yDFS maintained a statistically significant association in the multivariate analysis independently of the pCR status. The combination of the pCR and 2yDFS results in a strong predictor of OS, whereas failure to achieve 2yDFS carries a poor prognosis regardless of the pCR status. This new stratification of LARC patients could help design predictive models where the combination of 2yDFS and pCR should be employed as the primary outcome. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

12 pages, 1141 KiB  
Article
Delta Radiomic Analysis of Mesorectum to Predict Treatment Response and Prognosis in Locally Advanced Rectal Cancer
by Giuditta Chiloiro, Davide Cusumano, Angela Romano, Luca Boldrini, Giuseppe Nicolì, Claudio Votta, Huong Elena Tran, Brunella Barbaro, Davide Carano, Vincenzo Valentini and Maria Antonietta Gambacorta
Cancers 2023, 15(12), 3082; https://doi.org/10.3390/cancers15123082 - 7 Jun 2023
Cited by 4 | Viewed by 1235
Abstract
Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy [...] Read more.
Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (nCRT). Methods: Pre- and post-nCRT MRIs of LARC patients treated at a single institution from May 2008 to November 2016 were retrospectively collected. Radiomic features were extracted from the GTV and mesorectum. The Wilcoxon–Mann–Whitney test and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the features in predicting pCR and 2yDFS. Results: Out of 203 LARC patients, a total of 565 variables were evaluated. The best performing pCR prediction model was based on two GTV features with an AUC of 0.80 in the training set and 0.69 in the validation set. The best performing 2yDFS prediction model was based on one GTV and two mesorectal features with an AUC of 0.79 in the training set and 0.70 in the validation set. Conclusions: The results of this study suggest a possible role for delta radiomics based on mesorectal features in the prediction of 2yDFS in patients with LARC. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

13 pages, 798 KiB  
Article
Integrated Intensified Chemoradiation in the Setting of Total Neoadjuvant Therapy (TNT) in Patients with Locally Advanced Rectal Cancer: A Retrospective Single-Arm Study on Feasibility and Efficacy
by Maria Chiara Lo Greco, Madalina La Rocca, Giorgia Marano, Irene Finocchiaro, Rocco Luca Emanuele Liardo, Roberto Milazzotto, Grazia Acquaviva, Antonello Basile, Stefano Palmucci, Pietro Valerio Foti, Stefano Pergolizzi, Antonio Pontoriero, Silvana Parisi and Corrado Spatola
Cancers 2023, 15(3), 921; https://doi.org/10.3390/cancers15030921 - 1 Feb 2023
Cited by 3 | Viewed by 1779
Abstract
While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on [...] Read more.
While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS). Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

11 pages, 681 KiB  
Article
Development of a Patient Decision Aid for Rectal Cancer Patients with Clinical Complete Response after Neo-Adjuvant Treatment
by Lien Smets, Annelies Debucquoy, Eva Oldenburger, Chantal Van Audenhove, Lynn Debrun, Jeroen Dekervel, Gabriele Bislenghi, André D’Hoore, Albert Wolthuis and Karin Haustermans
Cancers 2023, 15(3), 806; https://doi.org/10.3390/cancers15030806 - 28 Jan 2023
Viewed by 1946
Abstract
Surgery is the primary component of curative treatment for patients with rectal cancer. However, patients with a clinical complete response (cCR) after neo-adjuvant treatment may avoid the morbidity and mortality of radical surgery. An organ-sparing strategy could be an oncological equivalent alternative. Therefore, [...] Read more.
Surgery is the primary component of curative treatment for patients with rectal cancer. However, patients with a clinical complete response (cCR) after neo-adjuvant treatment may avoid the morbidity and mortality of radical surgery. An organ-sparing strategy could be an oncological equivalent alternative. Therefore, shared decision making between the patient and the healthcare professional (HCP) should take place. This can be facilitated by a patient decision aid (PtDA). In this study, we developed a PtDA based on a literature review and the key elements of the Ottawa Decision Support Framework. Additionally, a qualitative study was performed to review and evaluate the PtDA by both HCPs and former rectal cancer patients by a Delphi procedure and semi-structured interviews, respectively. A strong consensus was reached after the first round (I-CVI 0.85-1). Eleven patients were interviewed and most of them indicated that using a PtDA in clinical practice would be of added value in the decision making. Patients indicated that their decisional needs are centered on the impact of side effects on their quality of life and the outcome of the different options. The PtDA was modified taking into account the remarks of patients and HCPs and a second Delphi round was held. The second round again showed a strong consensus (I-CVI 0.87-1). Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

14 pages, 2148 KiB  
Article
Expression Pattern and Prognostic Value of CTLA-4, CD86, and Tumor-Infiltrating Lymphocytes in Rectal Cancer after Neoadjuvant Chemo(radio)therapy
by Xin-Ke Yin, Chao Wang, Li-Li Feng, Shao-Mei Bai, Wei-Xing Feng, Neng-Tai Ouyang, Zhong-Hua Chu, Xin-Juan Fan and Qi-Yuan Qin
Cancers 2022, 14(22), 5573; https://doi.org/10.3390/cancers14225573 - 14 Nov 2022
Cited by 3 | Viewed by 1650
Abstract
The synergistic effect of combining immune checkpoint inhibitors (ICIs) with neoadjuvant chemo(radio)therapy (nCRT) in colorectal cancer is still limited. We aimed to understand the impact of nCRT on the tumor microenvironment and to explore favorable immune markers of this combination. Herein, we investigated [...] Read more.
The synergistic effect of combining immune checkpoint inhibitors (ICIs) with neoadjuvant chemo(radio)therapy (nCRT) in colorectal cancer is still limited. We aimed to understand the impact of nCRT on the tumor microenvironment and to explore favorable immune markers of this combination. Herein, we investigated the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), CD86, CD4, and CD8 after nCRT and its association with clinicopathological characteristics. Immunostaining of immune-related molecules was performed in 255 surgically resected specimens from rectal cancer patients treated with nCRT. CD4 and CD8 expression on the tumor (tCD4/CD8), stroma (sCD4/CD8), and invasive front (iCD4/CD8) was evaluated. The expression levels of immune-related molecules were significantly lower in the nCRT-treated group, except for CTLA-4 and sCD8. However, patients with higher sCD8+ cell density and CTLA-4 expression had better progression-free survival (PFS) and distant metastasis-free survival (DMFS). In addition, higher CD86 expression was associated with poorer overall survival (OS). Higher CTLA-4 expression was associated with higher tCD8+ cell density, whereas CD86 expression was correlated with the cell density of t/sCD8. Prognostic analysis confirmed that the relationships between CTLA-4 and DMFS as well as CD86 and OS were significantly correlated in low rather than high CD8+ cell density. Further the combination of CD8+ cell density and CD86 expression was shown to be an independent prognostic factor of OS, whereas the combination of CTLA-4 was not for DMFS. Together, these results demonstrate significant correlations between CD86 expression and t/sCD8+ cell density in rectal cancer after nCRT and could potentially have clinical implications for combining ICIs and nCRT. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

14 pages, 2796 KiB  
Article
Features on Endoscopy and MRI after Treatment with Contact X-ray Brachytherapy for Rectal Cancer: Explorative Results
by Petra A. Custers, Monique Maas, Doenja M. J. Lambregts, Regina G. H. Beets-Tan, Geerard L. Beets, Femke P. Peters, Corrie A. M. Marijnen, Monique E. van Leerdam, Inge L. Huibregtse and Baukelien van Triest
Cancers 2022, 14(22), 5565; https://doi.org/10.3390/cancers14225565 - 13 Nov 2022
Cited by 1 | Viewed by 1331
Abstract
After neoadjuvant (chemo)radiotherapy for rectal cancer, contact X-ray brachytherapy (CXB) can be applied aiming at organ preservation. This explorative study describes the early features on endoscopy and MRI after CXB. Patients treated with CXB following (chemo)radiotherapy and a follow-up of ≥12 months were [...] Read more.
After neoadjuvant (chemo)radiotherapy for rectal cancer, contact X-ray brachytherapy (CXB) can be applied aiming at organ preservation. This explorative study describes the early features on endoscopy and MRI after CXB. Patients treated with CXB following (chemo)radiotherapy and a follow-up of ≥12 months were selected. Endoscopy and MRI were performed every 3 months. Expert readers scored all the images according to structured reporting templates. Thirty-six patients were included, 15 of whom obtained a cCR. On endoscopy, the most frequently observed feature early in follow-up was an ulcer, regardless of whether patients developed a cCR. A flat, white scar and tumor mass were common at 6 months. Focal tumor signal on T2W-MRI and mass-like high signal on DWI were generally absent in patients with a cCR. An ulceration on T2W-MRI and “reactive” mucosal signal on DWI were observed early in follow-up regardless of the final tumor response. The distinction between a cCR and a residual tumor generally can be made at 6 months. Features associated with a residual tumor are tumor mass on endoscopy, focal tumor signal on T2W-MRI, and mass-like high signal on DWI. Early recognition of these features is necessary to identify patients who will not develop a cCR as early as possible. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

12 pages, 1667 KiB  
Article
Development and Validation of a Predictive Model for Toxicity of Neoadjuvant Chemoradiotherapy in Rectal Cancer in the CAO/ARO/AIO-04 Phase III Trial
by Markus Diefenhardt, Daniel Martin, Ethan B. Ludmir, Maximilian Fleischmann, Ralf-Dieter Hofheinz, Michael Ghadimi, Rebekka Kosmala, Bülent Polat, Tim Friede, Bruce D. Minsky, Claus Rödel and Emmanouil Fokas
Cancers 2022, 14(18), 4425; https://doi.org/10.3390/cancers14184425 - 12 Sep 2022
Cited by 2 | Viewed by 1444
Abstract
Background: There is a lack of predictive models to identify patients at risk of high neoadjuvant chemoradiotherapy (CRT)-related acute toxicity in rectal cancer. Patient and Methods: The CAO/ARO/AIO-04 trial was divided into a development (n = 831) and a validation (n = 405) [...] Read more.
Background: There is a lack of predictive models to identify patients at risk of high neoadjuvant chemoradiotherapy (CRT)-related acute toxicity in rectal cancer. Patient and Methods: The CAO/ARO/AIO-04 trial was divided into a development (n = 831) and a validation (n = 405) cohort. Using a best subset selection approach, predictive models for grade 3–4 acute toxicity were calculated including clinicopathologic characteristics, pretreatment blood parameters, and baseline results of quality-of-life questionnaires and evaluated using the area under the ROC curve. The final model was internally and externally validated. Results: In the development cohort, 155 patients developed grade 3–4 toxicities due to CRT. In the final evaluation, 15 parameters were included in the logistic regression models using best-subset selection. BMI, gender, and emotional functioning remained significant for predicting toxicity, with a discrimination ability adjusted for overfitting of AUC 0.687. The odds of experiencing high-grade toxicity were 3.8 times higher in the intermediate and 6.4 times higher in the high-risk group (p < 0.001). Rates of toxicity (p = 0.001) and low treatment adherence (p = 0.007) remained significantly different in the validation cohort, whereas discrimination ability was not significantly worse (DeLong test 0.09). Conclusion: We developed and validated a predictive model for toxicity using gender, BMI, and emotional functioning. Such a model could help identify patients at risk for treatment-related high-grade toxicity to assist in treatment guidance and patient participation in shared decision making. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

12 pages, 1160 KiB  
Article
Total Neoadjuvant Therapy for Rectal Cancer in the CAO/ARO/AIO-12 Randomized Phase 2 Trial: Early Surrogate Endpoints Revisited
by Markus Diefenhardt, Anke Schlenska-Lange, Thomas Kuhnt, Simon Kirste, Pompiliu Piso, Wolf O. Bechstein, Guido Hildebrandt, Michael Ghadimi, Ralf-Dieter Hofheinz, Claus Rödel and Emmanouil Fokas
Cancers 2022, 14(15), 3658; https://doi.org/10.3390/cancers14153658 - 27 Jul 2022
Cited by 5 | Viewed by 1896
Abstract
Background: Early efficacy outcome measures in rectal cancer after total neoadjuvant treatment are increasingly investigated. We examined the prognostic role of pathological complete response (pCR), tumor regression grading (TRG) and neoadjuvant rectal (NAR) score for disease-free survival (DFS) in patients with rectal carcinoma [...] Read more.
Background: Early efficacy outcome measures in rectal cancer after total neoadjuvant treatment are increasingly investigated. We examined the prognostic role of pathological complete response (pCR), tumor regression grading (TRG) and neoadjuvant rectal (NAR) score for disease-free survival (DFS) in patients with rectal carcinoma treated within the CAO/ARO/AIO-12 randomized phase 2 trial. Methods: Distribution of pCR, TRG and NAR score was analyzed using the Pearson’s chi-squared test. Univariable analyses were performed using the log-rank test, stratified by treatment arm. Discrimination ability of non-pCR for DFS was assessed by analyzing the ROC curve as a function of time. Results: Of the 311 patients enrolled, 306 patients were evaluable (Arm A:156, Arm B:150). After a median follow-up of 43 months, the 3-year DFS was 73% in both groups (HR, 0.95, 95% CI, 0.63–1.45, p = 0.82). pCR tended to be higher in Arm B (17% vs. 25%, p = 0.086). In both treatment arms, pCR, TRG and NAR were significant prognostic factors for DFS, whereas survival in subgroups defined by pCR, TRG or NAR did not significantly differ between the treatment arms. The discrimination ability of non-pCR for DFS remained constant over time (C-Index 0.58) but was slightly better in Arm B (0.61 vs. 0.56). Conclusion: Although pCR, TRG and NAR were strong prognostic factors for DFS in the CAO/ARO/AIO-12 trial, their value in selecting one TNT approach over another could not be confirmed. Hence, the conclusion of a long-term survival benefit of one treatment arm based on early surrogate endpoints should be stated with caution. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

19 pages, 338 KiB  
Review
Selecting a TNT Schedule in Locally Advanced Rectal Cancer: Can We Predict Who Actually Benefits?
by Carlo Aschele and Robert Glynne-Jones
Cancers 2023, 15(9), 2567; https://doi.org/10.3390/cancers15092567 - 30 Apr 2023
Cited by 5 | Viewed by 2678
Abstract
Many consider the standard of care for locally advanced rectal cancer (LARC) to be preoperative chemoradiotherapy, radical surgery involving a total mesorectal excision, and post-operative adjuvant chemotherapy based on the pathology of the specimen. The poor impact on distant control is a major [...] Read more.
Many consider the standard of care for locally advanced rectal cancer (LARC) to be preoperative chemoradiotherapy, radical surgery involving a total mesorectal excision, and post-operative adjuvant chemotherapy based on the pathology of the specimen. The poor impact on distant control is a major limitation of this strategy, with metastasis rates remaining in the 25–35% range and recovery after radical surgery leading to reluctance with prescription and inconsistent patient compliance with adjuvant chemotherapy. A second limitation is the low rate of pathologic complete response (pCR) (around 10–15%) despite multiple efforts to potentiate preoperative chemoradiation regimens, which in turn means it is less effective at achieving non-operative management (NOM). Total neoadjuvant treatment (TNT) is a pragmatic approach to solving these problems by introducing systemic chemotherapy at an early timepoint. Enthusiasm for delivering TNT for patients with LARC is increasing in light of the results of published randomized phase III trials, which show a doubling of the pCR rate and a significant reduction in the risk of subsequent metastases. However, there has been no demonstrated improvement in quality of life or overall survival. A plethora of potential chemotherapy schedules are available around the radiotherapy component, which include preoperative induction or consolidation with a range of options (FOLFOXIRI, FOLFOX, or CAPEOX,) and a varying duration of 6–18 weeks, prior to long course chemoradiation (LCCRT) or consolidation NACT following short-course preoperative radiation therapy (SCPRT) using 5 × 5 Gy or LCCRT using 45–60 Gy, respectively. The need to maintain optimal local control is a further important factor, and preliminary data appear to indicate that the RT schedule remains a crucial issue, especially in more advanced tumors, i.e., mesorectal fascia (MRF) invasion. Thus, there is no consensus as to the optimum combination, sequence, or duration of TNT. The selection of patients most likely to benefit is challenging, as clear-cut criteria to individuate patients benefiting from TNT are lacking. In this narrative review, we examine if there are any necessary or sufficient criteria for the use of TNT. We explore potential selection for the individual and their concerns with a generalized use of this strategy. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)

Other

Jump to: Research, Review

12 pages, 619 KiB  
Systematic Review
Modern Techniques in Re-Irradiation for Locally Recurrent Rectal Cancer: A Systematic Review
by Giovanna Mantello, Elena Galofaro, Silvia Bisello, Giuditta Chiloiro, Angela Romano, Luciana Caravatta and Maria Antonietta Gambacorta
Cancers 2023, 15(19), 4838; https://doi.org/10.3390/cancers15194838 - 3 Oct 2023
Cited by 1 | Viewed by 1111
Abstract
Background: Radiotherapy (RT) plays an important role in the treatment of patients with previously irradiated locally recurrent rectal cancer (LRRC). Over the years, numerous technologies and different types of RT have emerged. The aim of our systematic literature review was to determine whether [...] Read more.
Background: Radiotherapy (RT) plays an important role in the treatment of patients with previously irradiated locally recurrent rectal cancer (LRRC). Over the years, numerous technologies and different types of RT have emerged. The aim of our systematic literature review was to determine whether the new techniques have led to improvements in both outcomes and toxicities. Methods: A computerized search was performed by MEDLINE and the Cochrane database. The studies reported data from patients treated with carbon ion radiotherapy (CIRT), intensity-modulated photon radiotherapy (IMRT), and stereotactic radiotherapy (SBRT). Results: Seven publications of the 126 titles/abstracts that emerged from our search met the inclusion criteria and presented outcomes of 230 patients. OS was reported with rates of 90.0% and 73.0% at 1 and 2 years, respectively; LC was 89.0% and 71.6% at 1 and 2 years after re-RT, respectively. Toxicity data vary widely, with emphasis on acute and chronic gastrointestinal and urogenital toxicity, even with modern techniques. Conclusion: data on toxicity and outcomes of re-RT for LRRC with new technologies are promising compared with 3D techniques. Comparative studies are needed to define the best technique, also in relation to the site of recurrence. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

20 pages, 1434 KiB  
Systematic Review
Validated Pretreatment Prediction Models for Response to Neoadjuvant Therapy in Patients with Rectal Cancer: A Systematic Review and Critical Appraisal
by Max D. Tanaka, Barbara M. Geubels, Brechtje A. Grotenhuis, Corrie A. M. Marijnen, Femke P. Peters, Stevie van der Mierden, Monique Maas and Alice M. Couwenberg
Cancers 2023, 15(15), 3945; https://doi.org/10.3390/cancers15153945 - 3 Aug 2023
Cited by 2 | Viewed by 1447
Abstract
Pretreatment response prediction is crucial to select those patients with rectal cancer who will benefit from organ preservation strategies following (intensified) neoadjuvant therapy and to avoid unnecessary toxicity in those who will not. The combination of individual predictors in multivariable prediction models might [...] Read more.
Pretreatment response prediction is crucial to select those patients with rectal cancer who will benefit from organ preservation strategies following (intensified) neoadjuvant therapy and to avoid unnecessary toxicity in those who will not. The combination of individual predictors in multivariable prediction models might improve predictive accuracy. The aim of this systematic review was to summarize and critically appraise validated pretreatment prediction models (other than radiomics-based models or image-based deep learning models) for response to neoadjuvant therapy in patients with rectal cancer and provide evidence-based recommendations for future research. MEDLINE via Ovid, Embase.com, and Scopus were searched for eligible studies published up to November 2022. A total of 5006 studies were screened and 16 were included for data extraction and risk of bias assessment using Prediction model Risk Of Bias Assessment Tool (PROBAST). All selected models were unique and grouped into five predictor categories: clinical, combined, genetics, metabolites, and pathology. Studies generally included patients with intermediate or advanced tumor stages who were treated with neoadjuvant chemoradiotherapy. Evaluated outcomes were pathological complete response and pathological tumor response. All studies were considered to have a high risk of bias and none of the models were externally validated in an independent study. Discriminative performances, estimated with the area under the curve (AUC), ranged per predictor category from 0.60 to 0.70 (clinical), 0.78 to 0.81 (combined), 0.66 to 0.91 (genetics), 0.54 to 0.80 (metabolites), and 0.71 to 0.91 (pathology). Model calibration outcomes were reported in five studies. Two collagen feature-based models showed the best predictive performance (AUCs 0.83–0.91 and good calibration). In conclusion, some pretreatment models for response prediction in rectal cancer show encouraging predictive potential but, given the high risk of bias in these studies, their value should be evaluated in future, well-designed studies. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

17 pages, 1134 KiB  
Systematic Review
Predictive and Prognostic Value of Oncogene Mutations and Microsatellite Instability in Locally-Advanced Rectal Cancer Treated with Neoadjuvant Radiation-Based Therapy: A Systematic Review and Meta-Analysis
by Elena De Mattia, Jerry Polesel, Silvia Mezzalira, Elisa Palazzari, Sara Pollesel, Giuseppe Toffoli and Erika Cecchin
Cancers 2023, 15(5), 1469; https://doi.org/10.3390/cancers15051469 - 25 Feb 2023
Cited by 5 | Viewed by 2011
Abstract
Markers of pathological complete response (pCR) to preoperative radiation-based therapy in locally advanced rectal cancer (LARC) are strongly needed. This meta-analysis aimed at elucidating the predictive/prognostic role of tumor markers in LARC. We systematically reviewed the impact of RAS, TP53, BRAF, [...] Read more.
Markers of pathological complete response (pCR) to preoperative radiation-based therapy in locally advanced rectal cancer (LARC) are strongly needed. This meta-analysis aimed at elucidating the predictive/prognostic role of tumor markers in LARC. We systematically reviewed the impact of RAS, TP53, BRAF, PIK3CA, and SMAD4 mutations and MSI status on response (pCR, downstaging) and prognosis (risk of recurrence, survival) in LARC according to PRISMA guidelines and the PICO model. PubMed, Cochrane Library, and Web of Science Core Collection were systematically searched to identify relevant studies published before October 2022. KRAS mutations were significantly associated with the risk of not achieving pCR after preoperative treatment (summary OR = 1.80, 95% CI: 1.23–2.64). This association was even more significant in patients not receiving cetuximab (summary OR = 2.17, 95% CI: 1.41–3.33) than in patients receiving cetuximab (summary OR = 0.89, 95% CI: 0.39–20.05). MSI status was not associated with pCR (summary OR = 0.80, 95% CI: 0.41–1.57). No effect of KRAS mutation or MSI status on downstaging was detected. Meta-analysis of survival outcomes was not possible due to the large heterogeneity among studies in endpoint assessment. The minimum number of eligible studies to assess the predictive/prognostic role of TP53, BRAF, PIK3CA, and SMAD4 mutations was not reached. KRAS mutation, but not MSI status, proved to be a detrimental marker for response to preoperative radiation-based therapy in LARC. Translating this finding into the clinic could improve the management of LARC patients. More data are needed to clarify the clinical impact of TP53, BRAF, PIK3CA, and SMAD4 mutations. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Graphical abstract

15 pages, 762 KiB  
Systematic Review
Rectal Sparing Approaches after Neoadjuvant Treatment for Rectal Cancer: A Systematic Review and Meta-Analysis Comparing Local Excision and Watch and Wait
by Quoc Riccardo Bao, Stefania Ferrari, Giulia Capelli, Cesare Ruffolo, Marco Scarpa, Amedea Agnes, Giuditta Chiloiro, Elisa Palazzari, Emanuele Damiano Luca Urso, Salvatore Pucciarelli and Gaya Spolverato
Cancers 2023, 15(2), 465; https://doi.org/10.3390/cancers15020465 - 11 Jan 2023
Cited by 6 | Viewed by 1873
Abstract
Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to [...] Read more.
Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to perform a systematic review of the literature, and to compare rectal-sparing approaches, in terms of rectum-preservation rate, local control, and distant recurrences. A systematic review and meta-analysis were performed of studies published until July 2022 (PROSPERO, registration CRD42022341480), and the quality of evidence was assessed using a GRADE approach. Seven retrospective studies and one prospective trial were included. In six studies, patients were treated with standard long-course nCRT, and in two with Total Neoadjuvant Therapy (TNT). Overall, there were 213 and 188 patients in WW and LE group, respectively, and no difference was found between WW and LE when considering rectum-preservation rate (OR 0.80 95%CI 0.31–2.01, p = 0.63), local disease (OR 1.60 95%CI 0.75–3.42, p = 0.22), locoregional failure (OR 0.85 95%CI 0.20–3.66, p = 0.83) and distant recurrence (OR 0.76 95%CI 0.37–1.55, p = 0.45). Studies directly comparing WW and LE are still lacking, even though no differences between WW and LE in terms of rectum-preservation, local control, and distant recurrences have been found. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-16
Back to TopTop