How would you approach an isolated supraclavicular nodal recurrence involving the skin in a patient who has received standard chest wall and nodal radiation therapy?

Very challenging situation. Assuming it has been a few years out from the standard RT, and that the nodal mass is in relatively close proximity to the brachial plexus (as it cannot be too far), I would consider: Repeat external beam RT, hyperfractionated to increase the therapeutic ratio (i.e., reducing brachial plexus risk), with concurrent drug as a radiosensitizer. Perhaps 125 BID to 50-60 Gy. 

The anatomy in the supraclav area is such that the nodal masses are often very close to (often abutting) the plexus. And, given the limitations of imaging, the cancer target is perhaps closer to the nerves than we appreciate. It is for this reason that surgery is often not helpful. I worry about radiosurgery doses in this region, and this is a challenging location for CT-based IGRT (the images are hard to interpret); accurate immobilization can be challenging as well. MRI-guided IGRT "might" be better? I am sure that others who have used SBRT in this area can offer a more experienced and knowledgeable comment in this regard.

I have treated nodal recurrences in the supraclavicular area with SBRT with anecdotally good results for local control. Neoadjuvant systemic therapy can be considered to reduce the bulk of disease. The brachial plexus cumulative dose is the most important constraint to respect, though the BP likely tolerates significantly more doses than traditionally allowed, especially if there has been a long interval from prior radiation. Data from H&N re-irradiation (such as Chen et al., PMID 28587056) suggest a cumulative Dmax of <95 Gy. There is also a range of SBRT doses that can be used from palliative to definitive doses.

I agree with the above. If this is superficial, involving skin, brachytherapy is an option. Hyperfractionation after chemotherapy is a great option if this is deep. A limited field is what I would choose. Concurrent chemotherapy is also suggested. If this is superficial and you have hyperthermia, another choice. This requires a high dose for control >60 Gy.