Chris, This is a photograph of a 25 inch block cut away. As you can see the casting wall is a nominal thickness and has no extra metal due to bore spacing or lenth of block. The cross section thickness of a 251 block or a 218 block are probably about the same. I think your biggest problem boring that much would be finding a casting defect. Note the core shift in photo.
I would play it safe and bore casting to a minimun clean up dimension, and swap pistons with VPW.