Takayuki Yoshino
Leads CIRCULATE-Japan, the largest ctDNA-guided adjuvant programme in colorectal cancer, and the PARADIGM and SCRUM-Japan GI efforts.
Takayuki Yoshino directs GI oncology at NCC East and leads CIRCULATE-Japan (GALAXY, VEGA, ALTAIR), the PARADIGM trial of first-line panitumumab, and the GI arm of SCRUM-Japan, making him one of the most influential figures in colorectal cancer research.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
The blood test stratifies risk far better than stage or pathology. It supports treating ctDNA-positive patients and suggests ctDNA-negative patients gain little from chemotherapy, but because treatment was not randomised the de-escalation claim needs the randomised trials that are now under way.
Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of colorectal cancers that are mismatch-repair proficient.