Unprecedented advances have been made in the treatment of gastrointestinal cancer over the past 25 years. At this year’s World Congress, nearly 3000 clinicians, researchers and practitioners discussed the latest findings and innovative therapies. The focus was on immunotherapy as well as new biomarkers for prevention and prognosis as well as possibilities for gene analysis.
Stomach cancer is the fifth most common cancer worldwide. Although its incidence has declined in the Western world, it is still the fourth leading cause of cancer-related death. The reason for the poor prognosis is mainly due to late diagnosis and lack of effective treatments for metastatic disease. Molecular subtyping was performed according to two classifications: A) The Cancer Genome Atlas (TCGA) classification in 1) Epstein-Barr virus (EBV) positive, 2) Microsatellite instability (MSI), 3) chromosomal instability (CIN) characterized by intestinal histology; and 4) genetically stable (GS) defined by diffuse histology. B) Asian Cancer Research Group (ACRG) classification into. 1) MSI, 2) Epithelial mesenchymal transition (EMT) defined by E-cadherin staining, 3) p53 positive and 4) p53 negative. The goal now is to find a set of immunohistochemical marker proteins that can be used to reliably subtype histological specimens [1]. This may reveal a new way to classify gastric cancer that is easier to integrate into clinical decision making compared to genome sequencing methods.
A cohort of 283 patients with gastric cancer operated on at Helsinki University Hospital between 2000 and 2009 was studied. A tumor tissue microarray (TMA) was created and stained for the following immunohistochemical markers: MSI markers MSH2, MSH6, MLH1 and PMS2, p53, E-cadherin and EBV in situ hybridization EBERISH. According to TCGA classification, 15.7% of patients were found with EBV+ subtype, 17.0% with MSI+, 28.3% with CIN or intestinal histology according to Laurén classification, and 39.0% with GS or diffuse histology. Using ACRG classification, there were 41 patients (20.0%) with MSI+, 21.5% with EMT+, 20.0% with p53+, and 38.5% with p53e. In univariate analysis, the EBV subtype had the worst prognosis compared with the most benign CIN subtype. Multivariate analysis showed that according to ACRG classification, p53+ had the best prognosis, whereas MSI, p53e, and EMT had a worse prognosis. EBERISH, MSI, p53, and Laurén classification are not statistically significant biomarkers individually, but in a molecular subtype model they proved to be effective tools.
All in all, immunohistochemical analysis can be used to identify molecular subtypes of gastric cancer. The method is inexpensive and fast, yet provides important information for clinical decision making. Determining the molecular subtype from a histologic sample could help better target treatments to the appropriate patient subgroups and could provide valuable information on prognosis.
Focus on pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is increasingly common and has a poor prognosis. Mainly, due to frequent and early resistance to standard of care (SOC) treatments. Patient tumor-derived organoids (PDO) are promising models for functional precision oncology (FPO). To be used in clinical practice and provide benefit to most patients, FPO must meet three conditions: 1) it must be feasible with a limited amount of material, 2) it must have a wide range of medicines and 3) it must provide the test results as soon as possible. The purpose of a study was to investigate whether PDO can be used in clinical practice for the treatment of patients with PAOD [2].
A total of 76 samples were collected. 91% of patients had previously received FOLFIRINOX, 53% gemcitabine, and 44% (nab)-paclitaxel. PDO adoption rates were 62% (n=47/76) and 55%, respectively, for metastatic biopsy, 40% (2/5) for pancreatic aspiration, 93% (14/15) for ascites, 25% (1/4) for pleural effusion, and 100% (3/3) for primary tumor resection. The average turnaround time to produce a chemogram was 7.7 weeks. Overall survival (OS) from metastatic diagnosis was 17.2 months. Median OS was higher in patients who were not found to have PDO (5.2 months) than in patients who were found to have PDO (3.3 months). The median number of hits was three. At least one hit was identified in 90% of cases, and in 87% of cases, at least one of the hits was not a SOC (i.e., fluorouracil, irinotecan, oxaliplatin, gemcitabine, or paclitaxel). The main hits identified were olaparib (n=15/47), gemcitabine (n=14/47), and everolimus (n=11/47). The major identified molecular alterations on PDO were KRAS (98%), TP53 (72%), CDKN2A/B (17%), and SMAD4 (17%). The genomic data (WES data) correlated with the original tumor with a good concordance rate (88%).
Congress:25th World Congress on Gastrointestinal Cancer 2023
Literature:
- Brofkin J, Kaprio T, Hagström J, et al.: Prognostic effect of immunohistochemically classified molecular subtypes in gastric cancer. PD-1. WGI 2023 Poster Discussion Abstracts. ESMO 25th World Congress on Gastrointestinal Cancer 2023.
- Boileve A, Goudarzi N, Cartry J, et al.: Organoids as tools for functional precision oncology in advanced pancreatic cancer. PD-10. ESMO 25th World Congress on Gastrointestinal Cancer 2023.
InFo ONKOLOGIE & HÄMATOLOGIE 2023; 11(4): 28
