Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer

Hofste, Lisa S.M.; Geerlings, Maartje J.; Rhein, Daniel von; Rütten, Heidi; Westenberg, A. Helen; Weiss, Marjan M.; Gilissen, Christian; Hofste, Tom; Post, Rachel S. van der; Wilt, Johannes de; Ligtenberg, Marjolijn J. L.; Garms, Linda M.; Liem, Maite; Rozema, Tom; Wasowicz, Dareczka K.; Burger, Pim; Polat, Fatih; Reijnders, Koen; Roos, Marnix A.J. de; Sietses, C.

doi:10.1016/j.ejso.2023.01.026

Cited by 8 publications

(11 citation statements)

References 30 publications

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“…Tumor-informed ctDNA detection using ultradeep sequencing in LARC patients may offer clinical value for predicting response following neoadjuvant therapy and surgery [87]. Our study, utilizing a personalized tumor-informed ctDNA assay (Signatera™) assay, demonstrated worse DFS in ctDNA-positive patients post-neoadjuvant therapy and surgery compared to ctDNA-negative counterparts [89].…”

Section: Circulating Tumor Dna (Ctdna) Evaluation In Larc Patientsmentioning

confidence: 79%

“…The relationship between preoperative ctDNA and surgical outcomes has been less explored, with recent interest emerging in the additive value of ctDNA levels for monitoring response in neoadjuvant settings [76][77][78][79][80][81]. Several studies confirmed the association between ctDNA and prognosis, but failed to find a significant association between ctDNA status and pCR [85][86][87][88]. No association was found between ctDNA status and pCR also in the GEMCAD 1402, a phase II randomized, multicentric clinical trial [76].…”

Section: Circulating Tumor Dna (Ctdna) Evaluation In Larc Patientsmentioning

confidence: 99%

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Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer

Sullo,

Passardi,

Gallio

et al. 2024

Preprint

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Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, tumor distant recurrence remains a concern, prompting exploration of Total Neoadjuvant Therapy (TNT) as a comprehensive treatment strat-egy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Non-operative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving clinical complete response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for treatment response assessment. This review synthesizes current evidence on TNT, ICIs, NOM and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

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Section: Circulating Tumor Dna (Ctdna) Evaluation In Larc Patientsmentioning

confidence: 79%

Section: Circulating Tumor Dna (Ctdna) Evaluation In Larc Patientsmentioning

confidence: 99%

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer

Sullo,

Passardi,

Gallio

et al. 2024

Preprint

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“…Until Oct 10, we have updated one study relevant to the included abstract. In the end, we included 18 abstracts 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 and 62 studies, 4 , 13 , 15 , 20 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 …”

Section: Resultsmentioning

confidence: 99%

Circulating tumour DNA-Based molecular residual disease detection in resectable cancers: a systematic review and meta-analysis

Zheng,

Qin,

Wang

et al. 2024

eBioMedicine

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“…Among these 42 full texts, 22 studies met the eligibility criteria and were consequently included in our analysis [ 25 – 46 ]. Notably, eight of the included studies provided adequate statistical data for incorporation into our quantitative analysis [ 30 , 32 – 34 , 36 , 42 , 44 , 45 ]. A detailed depiction of the literature screening process can be found in Supplementary material S1 .…”

Section: Resultsmentioning

confidence: 99%

“…Eight of the included studies provided sufficient statistical data to be included in our quantitative analysis [ 30 , 32 – 34 , 36 , 42 , 44 , 45 ]. We investigated for an association between recurrence-free survival and the presence of ctDNA at several timepoints in a meta-analysis, the results of which are demonstrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

Assessing circulating tumour DNA (ctDNA) as a prognostic biomarker in locally advanced rectal cancer: a systematic review and meta-analysis

O’Sullivan,

Temperley,

Kyle

et al. 2024

Int J Colorectal Dis

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Introduction Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC. Methods PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS). Results Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91–16.03) and 15.15 (95% CI 8.21–27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively. Conclusion Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.

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Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer

Cited by 8 publications

References 30 publications

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer

Circulating tumour DNA-Based molecular residual disease detection in resectable cancers: a systematic review and meta-analysis

Assessing circulating tumour DNA (ctDNA) as a prognostic biomarker in locally advanced rectal cancer: a systematic review and meta-analysis

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