ctDNA as a biomarker of progression in oesophageal adenocarcinoma

Bonazzi, Vanessa; Aoude, Lauren G.; Brosda, Sandra; Lonie, James; Patel, Kalpana; Bradford, Julia J.; Koufariotis, Lambros T.; Wood, Scott; Smithers, B. Mark; Waddell, Nicola; Barbour, Andrew P.

doi:10.1016/j.esmoop.2022.100452

Cited by 11 publications

(9 citation statements)

References 42 publications

(68 reference statements)

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“…As new treatment strategies are arising for patients with locally advanced esophageal cancer, monitoring of response to neoadjuvant treatment and recognition of patients at risk for recurrence need to be optimized to enable personalized treatment choices [ 34 ]. Few studies on ctDNA measurements in the neoadjuvant setting of esophageal cancer patients have been reported [ 20 , 21 , 22 , 23 ]. Ococks et al mainly focused on minimal residual disease detection at the postoperative timepoint and did not use their post-CRT timepoint to correlate ctDNA detection with recurrence [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…A limitation of our study is that, although we used tumor-informed mutation analysis with ultradeep sequencing to improve the sensitivity, ctDNA was still only detected prior to treatment in approximately half of the patients. Usage of a larger gene panel could have improved capturing the heterogeneous mutational landscape of esophageal cancers [ 23 , 40 ], thereby increasing the chance that more positions in the genome could be interrogated in the ctDNA which could increase sensitivity of the analysis. Copy number alterations are frequently found in esophageal tumors but the tumor load of patients in this cohort was too low for reliable copy number analysis in ctDNA [ 32 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, several studies used techniques that lack the sensitivity required for response monitoring in locally advanced patients [ 15 , 16 , 17 ]. Despite the high clinical need, evidence for the clinical utility of ctDNA measurements in locally advanced esophageal cancer patients remains sparse, as most of these studies represent relatively small and heterogeneous cohorts [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Circulating Tumor DNA-Based Disease Monitoring of Patients with Locally Advanced Esophageal Cancer

Hofste

Geerlings

Rhein

et al. 2022

Cancers

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Patients diagnosed with locally advanced esophageal cancer are often treated with neoadjuvant chemoradiotherapy followed by surgery. This study explored whether detection of circulating tumor DNA (ctDNA) in plasma can be used to predict residual disease during treatment. Diagnostic tissue biopsies from patients with esophageal cancer receiving neoadjuvant chemoradiotherapy and surgery were analyzed for tumor-specific mutations. These tumor-informed mutations were used to measure the presence of ctDNA in serially collected plasma samples using hybrid capture-based sequencing. Plasma samples were obtained before chemoradiotherapy, and prior to surgery. The association between ctDNA detection and progression-free and overall survival was measured. Before chemoradiotherapy, ctDNA was detected in 56% (44/78) of patients and detection was associated with tumor stage and volume (p = 0.05, Fisher exact and p = 0.02, Mann-Whitney, respectively). After chemoradiotherapy, ctDNA was detected in 10% (8/78) of patients. This preoperative detection of ctDNA was independently associated with recurrent disease (hazard ratio 2.8, 95% confidence interval 1.1–6.8, p = 0.03, multivariable Cox-regression) and worse overall survival (hazard ratio 2.9, 95% confidence interval 1.2–7.1, p = 0.02, multivariable Cox-regression).Ultradeep sequencing-based detection of ctDNA in preoperative plasma of patients with locally advanced esophageal cancer may help to assess which patients have a high risk of recurrence after neoadjuvant chemoradiotherapy and surgery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating Tumor DNA-Based Disease Monitoring of Patients with Locally Advanced Esophageal Cancer

Hofste

Geerlings

Rhein

et al. 2022

Cancers

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“…In this issue of ESMO Open , Bonazzi and colleagues 17 describe the results from a commercially available pancancer mutation panel evaluated in both ctDNA and tumor samples in a single cohort from resected EAC ( n = 57). Moreover, whole-genome and whole-exome sequencing was carried out on the primary tissue in a subset of patients ( n = 18).…”

mentioning

confidence: 99%

“…Bonazzi et al. 17 demonstrated that ctDNA variants can be detected in patients with EAC and has prognostic value for survival. However, the use of ctDNA as a predictive marker in patients with EAC is still limited.…”

mentioning

confidence: 99%

Minimal residual disease in gastroesophageal adenocarcinoma: the search for the invisible

Tarazona

Gimeno-Valiente

2022

ESMO Open

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Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment

Zhou,

Mo,

et al. 2023

Cancer Medicine

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BackgroundThe utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta‐analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment.MethodsA comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome.ResultsA total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post‐neoadjuvant treatment and post‐surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly.ConclusionOur comprehensive meta‐analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

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ctDNA as a biomarker of progression in oesophageal adenocarcinoma

Cited by 11 publications

References 42 publications

Circulating Tumor DNA-Based Disease Monitoring of Patients with Locally Advanced Esophageal Cancer

Circulating Tumor DNA-Based Disease Monitoring of Patients with Locally Advanced Esophageal Cancer

Minimal residual disease in gastroesophageal adenocarcinoma: the search for the invisible

Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment

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