According to study results released at ASCO GI 2022 neoadjuvant chemotherapy should become a standard of care for treating stage IB-III “locally advanced” esophageal gastroesophageal junction (GEJ) cancer. Chemotherapy administered prior to surgery is referred to as neoadjuvant therapy and the goal of neoadjuvant therapy is to decrease the size of the cancer, making it easier to remove with surgery.1
Following neoadjuvant therapy and definitive surgery, up to one-third of patients with esophageal, gastroesophageal junction (GEJ), and gastric cancer who achieve a pathologic complete response (pCR) will experience disease recurrence, and up to one- half of patients with a near-pCR experience disease recurrence.2 Efforts are underway to determine how to improve the outcomes of these individuals.
· Treatment of Locally Advanced Esophageal and GEJ Cancer
At the 2023 American Society of Clinical Oncology Annual Meeting researchers reported the results of a study evaluating whether postoperative circulating tumor DNA (ctDNA) is prognostic of recurrence in patients with pCR or near-pCR after curative-intent neoadjuvant treatment and surgery. Detection of minimal residual disease by ctDNA may help determine which patients benefit from additional adjuvant therapy.4
About ctDNA
Cancer is caused by genetic mutations, and these mutations can be detected by measuring ctDNA, in the blood. Detection of ctDNA allows for personalized cancer surveillance based on an individual’s unique set of cancer mutations. Circulating tumor DNA is 150–200-base-pair fragments of DNA, which originate from cancer cells and are present in the bloodstream or other body fluids. ctDNA is different than cell-free DNA (cfDNA) which is ALL the DNA in the bloodstream including germline DNA and tumor DNA. ctDNA is the portion of cfDNA that is derived specifically from the cancer.
Across all stages of surgically removed cancer, detection of ctDNA following surgery is a strong predictor of cancer recurrence. For example, measurement of ctDNA is performed routinely in early-stage colon cancer and can help clinicians decide when to intensify therapy in certain situations, and conversely, the absence of ctDNA can provide an opportunity to minimize surveillance or avoid adjuvant treatment.3
Surgery and (neo) adjuvant radiotherapy are the mainstay curative treatments for gastric and esophageal cancers. Despite treatment a majority of patients experience metastatic relapse. The presence of ctDNA in the blood following treatment is a potential biomarker for detecting residual cancer and may help identify which patients are likely to benefit from additional adjuvant therapy following surgery.
About Signatera
Signatera is a custom-built ctDNA test for treatment monitoring and molecular residual disease assessment in patients diagnosed with cancer. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood.
Researchers identified 45 patients from 11 institutions with stages I-IV esophagogastric cancers who completed neoadjuvant therapy and had a pCR or near-pCR at the time of curative-intent surgery. Postoperative plasma samples (n=250) were collected for ctDNA analysis within a 16-week molecular residual disease (MRD) window after definitive surgery and serially during routine clinical follow-up. Signatera was used to quantify ctDNA.3
The presence of ctDNA was found to correlate with a higher recurrence rate compared to the absence of ctDNA and detectable ctDNA was associated with a significantly shorter duration of cancer free survival. The recurrence rate was 89% in ctDNA-positive patients compared to 11% in ctDNA-negative patients.
The study suggests that the presence of ctDNA postoperatively identified patients with an elevated risk of recurrence. Post-operative ctDNA surveillance following neoadjuvant therapy can be used to identify patients at higher risk of recurrence and direct them toward appropriate adjuvant therapy or clinical trials.
References
- Kato K, Ito Y, Daiko H, et al. A randomized controlled phase III trial comparing two chemotherapy regimen and chemoradiotherapy regimen as neoadjuvant treatment for locally advanced esophageal cancer, JCOG1109 NExT study. Presented at ; January 20-22, 2022. Abstract 238.
- Murphy MB et al., Cancer. 2017; 123(21):4106-411
- https://www.nature.com/articles/s41591-022-02115-4
- American Society of Clinical Oncology (ASCO) | June 2-6, 2023 | Chicago, IL | Abstract ID: 3041
