I have a 55.1 450 GMC COE going onto an 88 Chevy 3/4 ton 4wd chassis. The cab is mounted and the bed is created. Steering was functional but I didn't like the angles so I'm going to use a Steer Clear steering column offset to improve steering geometry. I know that the cabs have gotten wider with each vintage body style. I think you'll find that the 46 would be quite narrow for the 2000+ chassis. On that note anything can be overcome. It just depends on how hard you want to overcome the the issues. Some of the issues you'll need to overcome:
1) Track width - Tires sticking out too far from the body.
2) Body height - Are you lowering the truck or keeping a taller ride height?
3) Cab intrusion - How willing are you to have the engine intrude above the cab floor?
4) Bed length - If you're using 4wd the bed length will have to be longer than if you run 2wd.
5) Steering column to box geometry - The short length of the cab/hood makes for steep alignment of the steering joints.
6) Insert more issues here.
7) Adopt a shop motto like mine - "I always win." That will provide motivation to overcome the struggles.
8) Theory - Planning - Testing (at wrecking yard) - THEN purchase frame to actually follow through on your theory.
