The Prognostic Importance of ctDNA in Rectal Cancer: A Critical Reappraisal

Dizdarevic, Edina; Hansen, Torben Frøstrup; Jakobsen, Anders

doi:10.3390/cancers14092252

Cited by 12 publications

(8 citation statements)

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“…Eight of the nine studies showed some degree of correlation between ctDNA and either response to chemoradiation, risk of recurrence or disease-free survival. A second systematic review also included nine studies and investigated the association between clinical outcomes and ctDNA at different time points (at diagnosis, after chemoradiation, and after surgery) ( 38 ). No association was found between treatment response and ctDNA status at baseline.…”

Section: Discussionmentioning

confidence: 99%

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

et al. 2023

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BackgroundCirculating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer.MethodsA comprehensive search for studies published prior to the 4th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS).ResultsA total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 – 18.8]) and after surgery (HR for RFS: 15.5 [8.2 – 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA.ConclusionsThis literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice.

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Section: Discussionmentioning

confidence: 99%

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

et al. 2023

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“…Response to anti-cancer treatment is a multifactorial process that is not only dependent on tumor size and morphology, but also on other patient-factors and aspects of tumor biology that we cannot hope to capture by imaging. Important next steps in research will therefore be to combine image-based prediction methods with other clinical, histopathological, immunohistochemical and genetic biomarkers that have shown promise as predictors of response and that were unfortunately not available for analysis in this current retrospective study cohort [ 27 , 29 – 33 ]. Only this way can we hope to achieve a strong enough predictive performance to serve as a basis for clinical decision-making, aiming to further boost personalized therapy in rectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Predicting response to chemoradiotherapy in rectal cancer via visual morphologic assessment and staging on baseline MRI: a multicenter and multireader study

et al. 2023

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Purpose Pre-treatment knowledge of the anticipated response of rectal tumors to neoadjuvant chemoradiotherapy (CRT) could help to further optimize the treatment. Van Griethuysen et al. proposed a visual 5-point confidence score to predict the likelihood of response on baseline MRI. Aim was to evaluate this score in a multicenter and multireader study setting and compare it to two simplified (4-point and 2-point) adaptations in terms of diagnostic performance, interobserver agreement (IOA), and reader preference. Methods Twenty-two radiologists from 14 countries (5 MRI-experts,17 general/abdominal radiologists) retrospectively reviewed 90 baseline MRIs to estimate if patients would likely achieve a (near-)complete response (nCR); first using the 5-point score by van Griethuysen (1=highly unlikely to 5=highly likely to achieve nCR), second using a 4-point adaptation (with 1-point each for high-risk T-stage, obvious mesorectal fascia invasion, nodal involvement, and extramural vascular invasion), and third using a 2-point score (unlikely/likely to achieve nCR). Diagnostic performance was calculated using ROC curves and IOA using Krippendorf’s alpha (α). Results Areas under the ROC curve to predict the likelihood of a nCR were similar for the three methods (0.71–0.74). IOA was higher for the 5- and 4-point scores (α=0.55 and 0.57 versus 0.46 for the 2-point score) with best results for the MRI-experts (α=0.64-0.65). Most readers (55%) favored the 4-point score. Conclusions Visual morphologic assessment and staging methods can predict neoadjuvant treatment response with moderate–good performance. Compared to a previously published confidence-based scoring system, study readers preferred a simplified 4-point risk score based on high-risk T-stage, MRF involvement, nodal involvement, and EMVI. Graphical abstract

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“…A systematic review of 21 publications including 1499 patients 100 demonstrated that ctDNA could be used to predict pCR, whereas 3 other reviews suggested that it could not. [101][102][103] At this time, there is not enough high-level evidence to support using ctDNA to predict pathologic response.…”

Section: A Watch-and-wait Strategy Can Be Offered To Selected Patient...mentioning

confidence: 99%

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer 2023 Supplement

Langenfeld,

Davis,

Vogel

et al. 2023

Diseases of the Colon &Amp; Rectum

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he American Society of Colon and Rectal Surgeons (ASCRS) is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines (CPG) Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop CPG based on the best available evidence.Although not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician considering all the circumstances presented by the individual patient. STATEMENT OF THE PROBLEMColorectal cancer is the third most common cancer and the third most common cause of cancer-related deaths in the United States. 1 Approximately 30% of these cancers will originate in the rectum, and the American Cancer Society estimated a total of 44,850 new rectal cancer diagnoses in the United States for 2022. 2 Adenocarcinoma of the rectum is inherently complex. Surgery for rectal cancer is technically challenging and is associated with major alterations in GI, urinary, and sexual functions and with decreased quality of life. [3][4][5] The treatment of rectal cancer is also rapidly evolving, with new data emerging on a regular basis.In 2020, the ASCRS published its most recent CPG for rectal cancer. 6 This was a comprehensive assessment covering a wide spectrum of topics. Since then, there have been Earn continuing medical education (CME) credit online at cme.lww. com. This activity has been approved for AMA PRA category 1 credit.Funding/Support: None reported.

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The Prognostic Importance of ctDNA in Rectal Cancer: A Critical Reappraisal

Cited by 12 publications

References 50 publications

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

Predicting response to chemoradiotherapy in rectal cancer via visual morphologic assessment and staging on baseline MRI: a multicenter and multireader study

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer 2023 Supplement

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