Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study

Tie, Jeanne; Cohen, Joshua D.; Wang, Yuxuan; Li, Lü; Christie, Michael; Simons, Koen; Elsaleh, Hany; Kosmider, Suzanne; Wong, Rachel; Yip, Desmond; Lee, Margaret; Tran, Ben; Rangiah, David; Burge, Matthew; Goldstein, David; Singh, Madhu; Skinner, Iain; Faragher, Ian; Croxford, Matthew; Bampton, C. L.; Haydon, Andrew; Jones, Ian T.; Karapetis, Christos Stelios; Price, Timothy; Schaefer, Mary J; Ptak, Jeanne; Dobbyn, Lisa; Silliman, Natallie; Kinde, Isaac; Tomasetti, Cristian; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Volgestein, Bert; Gibbs, Peter

doi:10.1136/gutjnl-2017-315852

Cited by 254 publications

(281 citation statements)

References 25 publications

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“…61 Another study also reported the ability of ctDNA to detect MRD in patients with locally advanced rectal cancer (T3/T4 and/or nodal metastasis positive) planned for neoadjuvant chemoradiotherapy. 62 Although there was no difference in RFS between patients with detectable ctDNA at baseline Thus, ctDNA-based screening of patients with a higher risk of relapse may create opportunities for therapeutic intervention before the development of clinical metastasis.…”

Section: Minimal Residual Disease and Recurrence Monitoringmentioning

confidence: 93%

“…In patients treated with chemotherapy, presence of ctDNA after completion of chemotherapy was also associated with a shorter RFS ( P = .001) . Another study also reported the ability of ctDNA to detect MRD in patients with locally advanced rectal cancer (T3/T4 and/or nodal metastasis positive) planned for neoadjuvant chemoradiotherapy . Although there was no difference in RFS between patients with detectable ctDNA at baseline (pretreatment) and those without detectable ctDNA, patients with a ctDNA‐positive status after chemoradiotherapy or surgery had an increased risk of recurrence (chemoradiotherapy: hazard ratio [HR] 6.6, P < .001; surgery: HR 13.0, P < 0.001) .…”

Section: Clinical Relevance Of Ctdna For Advanced Crcmentioning

confidence: 99%

“…Another study also reported the ability of ctDNA to detect MRD in patients with locally advanced rectal cancer (T3/T4 and/or nodal metastasis positive) planned for neoadjuvant chemoradiotherapy . Although there was no difference in RFS between patients with detectable ctDNA at baseline (pretreatment) and those without detectable ctDNA, patients with a ctDNA‐positive status after chemoradiotherapy or surgery had an increased risk of recurrence (chemoradiotherapy: hazard ratio [HR] 6.6, P < .001; surgery: HR 13.0, P < 0.001) . Estimated 3‐year RFS was 33% for patients with postoperative ctDNA positivity and 87% for those with postoperative ctDNA negativity.…”

Section: Clinical Relevance Of Ctdna For Advanced Crcmentioning

confidence: 99%

“…• Absence of ctDNA after surgery is associated with a better prognosis and smaller chance of relapse, irrespective of the use of adjuvant chemotherapy [60][61][62][63] Treatment response, clonal evolution, and resistance…”

Section: Future Per S Pec Tive S and Con Clus Ionmentioning

confidence: 99%

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Clinical utility of circulating tumor DNA for colorectal cancer

et al. 2019

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Colorectal cancer (CRC) is currently the most common type of cancer in Japan, and its prognosis has improved because of development of diagnosis and advancement in treatments including surgery and chemotherapy. However, because of intratumor heterogeneity and clonal evolution, tumors often develop resistance to treatment. Genotyping tumor tissue in search of somatic genetic alterations for actionable information has become routine examination in clinical practice. However, the inherent molecular heterogeneity of metastatic tumors and the ability of cancer genomes to dynamically evolve are not properly captured by tissue specimens only. Circulating tumor DNA (ctDNA) carrying tumor‐specific genetic or epigenetic alterations is released into the circulation from tumor cells undergoing apoptosis or necrosis. Analysis of ctDNA has the potential to change clinical practice by exploiting blood rather than tissue, as a source of information. Here, we provide an overview of the characteristics of ctDNA and focus on detection methods for ctDNA, and the feasibility of use of ctDNA to monitor tumor dynamics for patients with colorectal cancer.

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Section: Minimal Residual Disease and Recurrence Monitoringmentioning

confidence: 93%

Section: Clinical Relevance Of Ctdna For Advanced Crcmentioning

confidence: 99%

Section: Clinical Relevance Of Ctdna For Advanced Crcmentioning

confidence: 99%

Section: Future Per S Pec Tive S and Con Clus Ionmentioning

confidence: 99%

See 2 more Smart Citations

Clinical utility of circulating tumor DNA for colorectal cancer

et al. 2019

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“…The use of ctDNA as biomarkers in clinical practice should meet the following requirements [72]: high analytical validity, combining established prognostic factors with validated prognostic/predictive biomarkers, and close evaluation of the accuracy, reliability, and reproducibility of a test [68]. Additionally, sufficient clinical validity (which assesses the ability of a test to divide a population into separate groups with significantly different clinical outcomes) and clinical utility (which evaluates whether changes in adjuvant therapy guided by ctDNA have a positive effect on prognosis [74]) must also be met.…”

Section: The Caveats and Technical Issues Associated With Ctdna As A mentioning

confidence: 99%

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

Zhang

Liang

et al. 2019

Mol Cancer

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Peripheral circulating free DNA (cfDNA) is DNA that is detected in plasma or serum fluid with a cell-free status. For cancer patients, cfDNA not only originates from apoptotic cells but also from necrotic tumor cells and disseminated tumor cells that have escaped into the blood during epithelial-mesenchymal transition. Additionally, cfDNA derived from tumors, also known as circulating tumor DNA (ctDNA), carries tumor-associated genetic and epigenetic changes in cancer patients, which makes ctDNA a potential biomarker for the early diagnosis of tumors, monitory and therapeutic evaluations, and prognostic assessments, among others, for various kinds of cancer. Moreover, analyses of cfDNA chromatin modifications can reflect the heterogeneity of tumors and have potential for predicting tumor drug resistance.

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Prognostic Potential of Circulating Tumor DNA Measurement in Postoperative Surveillance of Nonmetastatic Colorectal Cancer

et al. 2019

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IMPORTANCE For patients with resected, nonmetastatic colorectal cancer (CRC), the optimal surveillance protocol remains unclear. OBJECTIVE To evaluate whether serial circulating tumor DNA (ctDNA) levels detected disease recurrence earlier, compared with conventional postoperative surveillance, in patients with resected CRC. DESIGN, SETTING, AND PARTICIPANTS This study included patients (n = 58) with stage I, II, or III CRC who underwent radical surgical resection at 4 Swedish hospitals from February 2, 2007, to May 8, 2013. Eighteen patients received adjuvant chemotherapy at the discretion of their clinicians, who were blinded to the ctDNA results. Blood samples were collected at 1 month after the surgical procedure and every 3 to 6 months thereafter for ctDNA analysis. Patients were followed up until metachronous metastases were detected, or for a median of 49 months. Data analysis was performed from March 1, 2009, to June 23, 2018. MAIN OUTCOMES AND MEASURES Sensitivity and timing of ctDNA positivity were compared with those of conventional surveillance modalities (computed tomographic scans and serum carcinoembryonic antigen tests) for the detection of disease recurrence. RESULTS This study included 319 blood samples from 58 patients, with a median (range) age of 69 (47-83) years and 34 males (59%). The recurrence rate among patients with positive ctDNA levels was 77% (10 of 13 patients). Positive ctDNA preceded radiologic and clinical evidence of recurrence by a median of 3 months. Of the 45 patients with negative ctDNA throughout follow-up, none (0%; 95% CI, 0%-7.9%) experienced a relapse, with a median follow-up of 49 months. However, 3 (6%; 95% CI, 1.3%-17%) of the 48 patients without relapse had a positive ctDNA result, which subsequently fell to undetectable levels during follow-up. CONCLUSION AND RELEVANCE Although these findings need to be validated in a larger, prospective trial, they suggest that ctDNA analysis could complement conventional surveillance strategies as a triage test to stratify patients with resected CRC on the basis of risk of disease recurrence.

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Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study

Abstract: Postoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.

Cited by 254 publications

References 25 publications

Clinical utility of circulating tumor DNA for colorectal cancer

Clinical utility of circulating tumor DNA for colorectal cancer

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

Prognostic Potential of Circulating Tumor DNA Measurement in Postoperative Surveillance of Nonmetastatic Colorectal Cancer

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