National clinical study

Clinical Utility of circulating Tumor DNA in Gastro-Esophageal Cancer (CURE)

This is a prospective cohort study designed to evaluate the treatment effect as well as predictive and prognostic factors with special emphasis on the clinical utility of ctDNA in plasma in patients with gastroesophageal cancer. Patients with gastroesophageal cancer are included in 5 separate cohorts scheduled for

• Surgical resection + perioperative chemotherapy (cohort 1)
• Neoadjuvant chemoradiotherapy followed by surgical resection (cohort 2)
• Definitive chemoradiotherapy with curative intent (cohort 3)
• Systemic therapy with the intent to prolong survival (cohort 4)
• Palliative treatment without the use of chemotherapy (cohort 5)

ClinicalTrials.gov: NCT04576858

The project received funding in 2020 and 2022.

Abstract

Impact/relevance
The project addresses an unmet medical need for a genomic diagnostic tool able to efficiently diagnose patients with recurrent gastroesophageal cancer that could potentially benefit from a curative treatment strategy. The medical need is evident in the patient population under study, who carry a considerable risk of death due to  recurrence despite receiving treatment with curative intent. The diagnostic method is minimally invasive and include the isolation of ctDNA isolated from a standard blood sample.

Background
Patients with local, non-disseminated gastroesophageal cancer undergo abdominothoracic esophagectomy or gastrectomy combined with perioperative chemotherapy or preoperative chemoradiotherapy. Unfortunately, patients treated with curative intent carry a considerable risk of recurrence, which often ultimately will lead to death as more than 50 % of resected patients will die after 5 years of follow-up. In other cancer diseases, the detection of tumor specific mutations in ctDNA postoperatively is associated with a substantial increased risk of recurrence. The CURE study is a nationwide prospective cohort study supported by the Danish Esophageal-, Gastroesophageal junction,- and Gastric Cancer Group with the aim to investigate the utility of ctDNA in gastroesophageal cancer as a diagnostic tool for early recurrence.

Aim
The primary aim of the CURE study is to determine if detection of tumor specific mutations in ctDNA after therapy with curative intent is associated with increased risk of recurrence in patients with gastroesophageal cancer.

The secondary aims are to determine if baseline level or a decrease in mutant allele fraction in ctDNA during preoperative chemotherapy is predictive of resectability, pathological regression grade, radiological response, and time-to-recurrence and to generate data to plan an intervention study evaluating intensified imaging and treatment of low tumor burden recurrence detected with ctDNA in gastroesophageal cancer

Methods
Detection and analyses of ctDNA will be performed by use of digital droplet PCR using a tumor informed approach based on whole exome sequencing of the primary tumor of each individual participant.

Expected outcome
Based on data generated in the CURE study, a prospective national intervention study will be planed evaluating the benefit of intensified surveillance with PET/CT scans for patients with detectable ctDNA. Patients with local or oligometastatic recurrence will be offered stereotactic radiosurgery or re-resection.

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