GI cancer

Left versus right: a useful paradigm for mCRC

Patients with colorectal tumours located on the left side do better than patients with the less common right side tumours but there is no discrete switch point.

Professor Sebastian Stintzing, from the department of haematology and oncology at the University Hospital Munich, told the MOGA ASM that the colon was a continuum at the genetic level.

“For example when you look at the frequency of BRAF mutations you see they are very rare at the very left side, and they are relatively frequent on the right side. But it’s not a clear border between left and right sided tumours.”

“It’s pretty much the same with microsatellite instability frequency within the parts of the colon.  It progressively changes from left to right but it’s not like a step and you cannot draw a clear line.”

Professor Stintzing said there were also likely to be aberrations with tumours that behave like right side tumours on the left side and vice versa.

However from a clinical point of view, left versus right provided some guidance in the management of metastatic colorectal cancer.

“When it comes to first line decisions, keep it simple. Do a RAS test, if RAS wild type, check the pathology report as to which side the primary tumour derived from.”

Left side tumours should be treated with an EGFR inhibitor and chemotherapy while right side tumours with chemotherapy and an anti-VEGF.

He said the overall survival gain by adding cetuximab to chemotherapy for left sided tumours was about eight to ten months depending on the study.

While there was no similar clear benefit from adding bevacizumab to chemotherapy for right side tumours, Professor Stinting said there was a non-significant trend to benefit.

However the situation was more complex beyond first line treatment.

“Patients who survive through to second and further lines of treatment respond to anti-EGFR even though the tumour is on the right hand side.”

“In the second line the data is scarce, but the data we have so far shows that there is some activity of EGFR even on the right side which is actually quite interesting.”

Commenting on a recent meta-analysis that suggests chemotherapy in combination with SIRT may be effective in right-sided tumours but not left, Professor Stintzing said more data was still required.

“The SIRT study was disappointing when it comes to overall survival but looking to sub-groups there seems to be a benefit for right sided tumours.”

“In left sided tumours, the chemotherapeutic backbone may be so effective that the addition of SIRT doesn’t add any difference.  But on right side, when we know chemotherapy is not working as well because of the molecular make up of the tumour, here we may see the advantage of SIRT.”

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