How do you approach management of non-resectable periampullary adenocarcinoma in an elderly patient with otherwise good PS?

The level of evidence is more limited to guide treatment decisions for ampullary/peri-ampullary adenocarcinoma compared to the neighboring pancreas. However, I have generally approached this situation similarly to locally advanced or inoperable pancreas cancer starting with systemic therapy and if there is no disease progression at interval assessment, consolidating the primary site with chemoradiotherapy. Radiotherapy dose and fractionation are limited by bowel tolerance. I would recommend sticking with conventional fractionation, 45-50.4 Gy in 25-28 fractions. Hypofractionated regimens or SBRT have increased risk of toxicity without added oncologic benefit.

Adding on here that NCCN now has an ampullary cancer guideline (disclosure: I was part of the writing team) so you can review primary references and level of data support for treatment options. There is a write up here https://www.onclive.com/view/nccn-establishes-standards-of-care-in-ampullary-adenocarcinoma. You will need to create an NCCN account but after that, you can access the guidelines for free. https://www.nccn.org/