ASH 2024 | Clonal evolution of lymphoid malignancies following the mutagenic impact of radiotherapy

So this is a very large collaboration where we were able to assemble a cohort of 580 patients with whole genome sequencing with lymphoma or myeloma. The collaborators are in Moffitt Cancer Center and Heidelberg University and Memorial Sloan-Kettering. So in this collaboration we found that when a tumor is exposed to radiotherapy, usually it acquires a certain number of mutations called indels that can be detected with our mathematical model with the whole genome sequencing data. So that’s kind of like already known in solid tumors, but they’ve never been shown in hematological cancers. What is interesting is that this kind of chemotherapy barcoding or radiotherapy barcoding can also be acquired by platinum chemotherapy exposure. And so we did some functional work in vitro to show that that’s actually true, like platinum can cause those alterations. 

What is also interesting is that because it’s sort of like a barcode on the tumor, well, the tumor that gets the radiotherapy gets the barcode, but the tumor that doesn’t get the radiotherapy doesn’t have the barcode, we can also track over time how these post-radiotherapy cells move around the body. And we show a few examples on how a post-radiotherapy cell that survived the radiotherapy in one location, seed to another location, which also makes the point that relapse, in lymphoma in particular after radiotherapy can be also driven by surviving cells in the radiotherapy field and not by cells that were hidden somewhere else not involved by the radiotherapy. So this of course doesn’t really change much our clinical practice but reinforces the idea that we need to look for full eradication of all the cells and don’t assume that radiotherapy is just eradication but there might still be some cells that survive and seed somewhere else.

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