scholarly journals Pre-clinical modelling of rectal cancer to develop novel radiotherapy-based treatment strategies

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Michael A. Gillespie ◽  
Colin W. Steele ◽  
Tamsin R.M. Lannagan ◽  
Owen J. Sansom ◽  
Campbell S.D. Roxburgh
Keyword(s):  
Rectal Cancer ◽  
Mouse Models ◽  
Adjuvant Treatment ◽  
Relevant Literature ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Recurrence Rates ◽  
Advantages And Disadvantages

Pre-operative chemoradiotherapy reduces local recurrence rates in locally advanced rectal cancer. 10-20% of patients undergo complete response to chemoradiotherapy, however, many patients show no response. The mechanisms underlying this are poorly understood; identifying molecular and immunological factors underpinning heterogeneous responses to chemoradiotherapy, will promote development of treatment strategies to improve responses and overcome resistance mechanisms. This review describes the advances made in pre-clinical modelling of colorectal cancer, including genetically engineered mouse models, transplantation models, patient derived organoids and radiotherapy platforms to study responses to chemoradiotherapy. Relevant literature was identified through the PubMed and MEDLINE databases, using the following keywords: rectal cancer; mouse models; organoids; neo-adjuvant treatment; radiotherapy; chemotherapy. By delineating the advantages and disadvantages of available models, we discuss how modelling techniques can be utilized to address current research priorities in locally advanced rectal cancer. We provide unique insight into the potential application of pre-clinical models in the development of novel neo-adjuvant treatment strategies, which will hopefully guide future clinical trials.

scholarly journals Staging of Locally Advanced Rectal Cancer Beyond TME

2020 ◽  
Vol 33 (05) ◽  
pp. 258-267
Author(s):  
Deborah S. Keller
Keyword(s):  
Rectal Cancer ◽  
Best Practice ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Treatment Decision ◽  
Advanced Rectal Cancer ◽  
Cancer Staging ◽  
Locally Advanced Rectal Cancer ◽  
Multidisciplinary Teams ◽  
Treatment Decision Making

AbstractThe management of rectal cancer is complex and continually evolving. With advancements in technology and the use of multidisciplinary teams to guide the treatment decision making, staging, oncologic, and functional outcomes are improving, and the management is moving toward personalized treatment strategies to optimize each individual patient's outcomes. Key in this evolution is imaging. Magnetic resonance imaging (MRI) has emerged as the dominant method of pelvic imaging in rectal cancer, and use of MRI for staging is best practice in multiple international guidelines. MRI allows a noninvasive assessment of the tumor site, relationship to surrounding structures, and provides highly accurate rectal cancer staging, which is necessary for determining the appropriate treatment strategy. However, the applications of MRI extend far beyond pretreatment staging. MRI can be used to predict outcomes in locally advanced rectal cancer and guide the surgical or nonsurgical plan, serving as a predictive and prognostic biomarker. With continued MRI hardware improvement and new sequence development, MRI may offer new perspectives in the assessment of treatment response and new innovations that could provide better insight into the staging, restaging, and outcomes with rectal cancer.

scholarly journals Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

2020 ◽  
Vol 27 (11) ◽  
pp. 4319-4336 ◽  
Author(s):  
S. Hoendervangers ◽  
J. P. M. Burbach ◽  
M. M. Lacle ◽  
M. Koopman ◽  
W. M. U. van Grevenstein ◽  
...  
Keyword(s):  
Systematic Review ◽  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Abstract Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.

Effects of adjuvant oxaliplatin on anal function in locally advanced rectal cancer treated with preoperative chemoradiotherapy and low anterior resection.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 718-718
Author(s):  
Fernando Arias ◽  
Clara Eito ◽  
Antonio Viudez ◽  
Gemma Asin ◽  
Berta Ibañez ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Treatment ◽  
Anterior Resection ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Anal Function ◽  
Sphincter Function ◽  
Anal Sphincter Function ◽  
Incontinence Score

718 Background: The main purpose of the present study was to determine if the addition of adjuvant oxaliplatin (OXA) could have some influence on sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/radiotherapy followed by lower anterior resection (LAR). Methods: Those patients with LARC treated at our center with LAR and without two-years loco-regional relapse were retrospectively analyzed independent of the type of adjuvant treatment received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, being punctuation inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Comparisons of sphincter function measured with the Wexner test between patients with and without OX were conducted with the Mann-Whitney test. Statistical analyses were conducted using IBM SPSS Statistics, version 20. Results: From 2006, 92 consecutive patients were included in our study. Mean time from LAR to fecal function assessment was 58 months (25 to 96 months). Wexner test median values did not differ significantly (p=0.450) between patients with and without adjuvant OXA. The median (IQR) for the group without adjuvant OXA was 6.0 (1.0-11.25), being for group that received adjuvant OXA of 5.0 (1.0-10.0). Conclusions: Based on our findings, OXA could be used as adjuvant treatment in LARC, due to its absent of deleterious influence over the sphincter anal function. Because of the retrospective nature of our study, prospective studies should be warranted in similar scenarios. This study has been supported by a grant of “Mutua Madrileña Fundation.”

Multimodal treatment strategies for locally advanced rectal cancer

2012 ◽  
Vol 12 (4) ◽  
pp. 481-494 ◽  
Author(s):  
Georg F Weber ◽  
Robert Rosenberg ◽  
Janet E Murphy ◽  
Christian Meyer zum Büschenfelde ◽  
Helmut Friess
Keyword(s):  
Rectal Cancer ◽  
Multimodal Treatment ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Emerging strategies in the initial management of locally advanced rectal cancer

2019 ◽  
Vol 15 (25) ◽  
pp. 2955-2965 ◽  
Author(s):  
Lucy Gately ◽  
Hui-Li Wong ◽  
Jeanne Tie ◽  
Rachel Wong ◽  
Margaret Lee ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Plan ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Current Standard ◽  
Initial Management

The initial management of locally advanced rectal cancer continues to evolve and formulating the ideal treatment plan remains challenging, with a multitude of emerging treatment strategies and either limited or inconsistent data to support these. The main objective of neoadjuvant treatment is to maximize disease control and minimize toxicity and impact on quality of life. Ultimately, the optimal approach needs to be personalized to the individual. In this Review, we discuss the various strategies currently used and being further investigated in the initial treatment of patients presenting with locally advanced rectal cancer. We describe the evidence behind the current standard of care recommendations and emerging new options, as well as potential biomarkers that may assist with further refining treatment selection.

2056 Locally advanced rectal cancer with neoadyuvant treatment strategies: Our experiences

2015 ◽  
Vol 51 ◽  
pp. S347
Author(s):  
M.L. Blanco Villar ◽  
A. Rodriguez Gutierrez ◽  
A. Nieto Palacio ◽  
A. Matias Perez ◽  
P Soria Carreras ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

scholarly journals Multidisciplinary Management of Early-Stage Rectal Cancer

2012 ◽  
Vol 10 (12) ◽  
pp. 1577-1585 ◽  
Author(s):  
John G. Phillips ◽  
Theodore S. Hong ◽  
David P. Ryan
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Therapy ◽  
Early Stage ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
The United States ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Current Standard ◽  
Recurrence Rates

Because patients with locally advanced rectal cancer are at high risk for both recurrence and distant disease, they require adjuvant therapy. In the United States, the current standard of care is neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Neoadjuvant chemoradiation has been shown to improve local recurrence rates and decrease toxicity. However in the era of total mesorectal excision surgery, no study has shown a survival benefit to either chemoradiation or postoperative chemotherapy. Newer biologic therapies, although promising in initial early trials, have yet to show a significant benefit in adjuvant therapy for rectal cancer.

Sign in / Sign up

Export Citation Format

Share Document