Mini Oral Session 1

In mini-oral session one from ESMO GI 2024, the presentations were divided into three main sections. The first part focused on ctDNA analysis, the second broadly covered colorectal cancer, and the third addressed hepatobiliary tumours.

Dr Dasari from MD Anderson presented on the limitations of the TNM staging system for colorectal cancer, proposing the integration of ctDNA analysis for better prognostication. The study analysed ctDNA data from 3,148 patients across stages I to III, assessing minimal residual disease (MRD) after surgery. MRD was found in 13% of patients, with higher percentages in advanced stages. Comparison with ESMO guidelines showed ctDNA as a strong prognostic factor. The discussant noted that ctDNA combined with TNM staging offers superior prognostication. Despite ctDNA negativity being a good indicator, some patients still relapsed. The study’s 26-month follow-up is shorter than ideal. Integrating ctDNA with TNM staging could enhance prognostication but requires further research and longer follow-up.

Dr Martini from Naples presented the CAPRI2-GOIM trial, which explores the use of ctDNA in guiding treatment decisions across three lines of therapy in metastatic colorectal cancer. The trial evaluated mutations in genes like RAS and BRAF using both FoundationOne for tumour tissue and Foundation Liquid for ctDNA, finding a high concordance rate but with nearly 10% discordance, particularly in RAS mutations. This aligns with existing literature on assay discrepancies. The advantages of ctDNA include its non-invasive nature and ability to provide a systemic view of genomic alterations, making repeat testing feasible even without tumour tissue. However, variability in ctDNA shedding from different metastatic lesions poses a challenge. While liver metastases show higher ctDNA levels, lung or peritoneal metastases may not, affecting analysis accuracy. The study shows that ctDNA assessment is promising but not yet ready to replace traditional methods due to issues like cost, availability, and the need for more precise correlation with metastatic lesion types. Further refinement is needed for ctDNA to become a mainstream method for genomic profiling in metastatic colorectal cancer.

The second part of the session focused on colorectal cancer, beginning with a presentation by Dr Giacomo Bregni on the use of systemic chemotherapy in the context of radical resection of liver metastases. The role of systemic chemotherapy, used either perioperatively or postoperatively, in improving overall survival (OS) and disease-free survival (DFS) remains inconclusive due to the small size of previous studies. Dr. Bregni and his team conducted an individual patient data meta-analysis of four randomised phase 3 trials to determine the benefits of systemic chemotherapy. Their analysis showed a significant DFS advantage when systemic chemotherapy was used either perioperatively or postoperatively. Additionally, when pooling data from all four studies, there was an overall survival benefit, although this was not statistically significant when only considering the three postoperative trials. This lack of statistical significance may be due to insufficient power. The study found that patients with normal alkaline phosphatase levels and those with synchronous liver metastases benefited the most from systemic chemotherapy.

The second study of this part of the mini-oral session was a phase one trial of a PKMYT1 inhibitor in colorectal and gastrointestinal cancers, presented by Dr. Fontana from London. Mutations in FBXW7, found in about 13% of colorectal cancer patients, are common, but their prognostic impact remains unclear. Previous studies of the PKMYT1 inhibitor, lunresertib, in patients with FBXW7 and CCNE1 alterations showed limited benefit. In the current study, named MINOTAUR, the combination of lunresertib with FOLFIRI chemotherapy was tested. The combination was well tolerated, raising questions about whether the recommended phase two dose of the inhibitor is sufficiently high. Toxicities observed were similar to those typically seen with FOLFIRI alone. Importantly, the study showed promising efficacy in heavily pre-treated patients. Future randomised phase two trials are anticipated to further explore this combination’s potential.

To conclude, the third part of the mini-oral session featured two studies. The first study was a subgroup analysis of the phase III NETTER-2 study, a practice-changing trial of [177Lu]Lu-DOTATATE in grade 2 and grade 3 well-differentiated gastroenteropancreatic neuroendocrine tumours. This preplanned subgroup analysis focused on tumour grade (G2 and G3) and the primary origin of the neuroendocrine tumour (pancreatic or small intestine). The results showed that the advantage of [177Lu]Lu-DOTATATE was maintained across these subgroups, suggesting consistent efficacy. However, the study did not present overall survival data or long-term toxicity data, and patient selection was based on clinical rather than molecular characteristics. Despite the promising results, these limitations suggest that the subgroup analysis alone may not be sufficient to change the treatment paradigm for these specific subgroups without further data.

To conclude, the last study was a fascinating investigation from China on the early detection of hepatocarcinoma using AI-analysed blood tests. Detecting hepatocarcinoma early is challenging, and a non-invasive detection method would be highly beneficial. Researchers developed an AI-based blood test signature and tested it in over 3,000 patients, a large cohort. The AI classifier calculated a risk score and its performance was compared to AFP, a common blood marker. The AI test detected hepatocarcinoma one year earlier than AFP, with a specificity of 75%, showing promise as an early detection strategy. However, there are challenges to address, including the feasibility of clinical implementation, the need for prospective validation, and testing in different populations, such as Western cohorts. Additionally, demonstrating cost-effectiveness is crucial before it can impact clinical practice. This study presents promising data, and the future may see more AI-based tools in early cancer detection.