I have pondered this for a long time and have tried different things without any real resolve. My imaging train has remained the same for years and I have been taking panel flats for many years as well. First I should list my system:
I use an Optical Guidance Systems 12.5" RC. From the rear cell I have:
1) the flattener attached
2) MMOAG Off Axis Guider w/SBIG RGH for my STL-11000
3) Optec 3" Pyxis Rotator
4) SBIG CW8
5) SBIG STL-11000M
I image mostly LRGB and those exposures are typically -20 degree at 900 seconds each. The narrow band images are -20 degrees and 1800 second exposures. I take a library of dark and bias frames at -20 and 900/1800 darks. The masters are generally made using anywhere from 20-50 exposures. Master Bias frames are typically from 75-100 bias frames and produced by these guidelines
http://www.pixinsight.com/tutorials/master-frames/index.htmlWhen I run into a set of images that seem to have issues flat fielding I will generally try to make a new set of flats and try again but here lately that seems futile. For some reason the flats just don't seem to work. Now to cover my bases I have tried using both east and west masters to see if it makes a difference in the calibrated image but overall not much and neither satisfactory. I had seen in my early days an issue with the software not knowing East side from West side depending on how/where the telescope was parked. When I parked the telescope with the OTA level facing North and the counterweight shaft end facing east (AstroPhysics mount park position 1) it seemed what was my west masters worked for the east images and vice versa.
These days I park the mount with the OTA facing south and the counterweight shaft end facing west (AstroPhysics mount park position 4)
If I have a problem image my process is that I create a plan and have the telescope slew to the object in question at the desired PA and take a short exposure, download, plate solve and then any corrections for PA or object orientation is corrected. Then I'll proceed with new flats now that I'm 100% sure the system is at the desired position. This has yet to solve any of the issues. The flats are minimum of 1 second exposures, 16 each side (E/W), calibrated and combined using the above mentioned process. 99% of the time this works great but that last 1% I'll have a series of images that have poor results. The exposure times are calculated to give a 25,000-28,000 ADU level.
Results for this current series of images is typical of attached. Images taken in 2018 came out without these issues. Not sure what I'm missing.....