How did you define and track clinical hypothyroidism in your study?
Strusberg: This was a retrospective study where our clinical end point was defined as recommendation or initiation of thyroid hormone replacement therapy. To our knowledge, this is the largest cohort and the longest follow-up of any series, with a median follow-up of 41.4 months. Instead of looking at labs during follow-up, we predefined a clinical end point, because these patients could develop this toxicity down the road with longer follow-up, which is something we noticed. If patients came back for a consultation in later years with newly diagnosed hypothyroidism, that was our clinical end point.
How should these findings factor into the choice between proton and photon therapy?
Strusberg: This is an individual, case-by-case analysis. Let me give an example. If you have a patient with left-sided breast cancer, you have proton availability, and that patient is going to benefit from an overall reduction in toxicities to the heart, the lungs, the thyroid, and the skin, then we could talk about it. The main goal should not be one modality or the other; it should be achieving an adequate threshold dose to the thyroid to minimize the risk of clinical hypothyroidism down the road.
Were there other toxicity differences between the 2 approaches worth noting?
Strusberg: We didn’t study any other toxicities in our retrospective cohort. It is important to say that there are large series and studies right now looking at heart doses, lung doses, skin doses, and capsular contracture, for instance, which are very troublesome and worrisome [adverse] effects. Last year, our group had an oral presentation and published a manuscript showing how, interestingly, protons were associated with a higher risk of capsular contracture in patients who were also treated to the supraclavicular fossa.2 At this point, we don’t know.
I don’t think this is a study that should change practice. What I think this study emphasizes, and what it made possible for us as physicians to notice, is that the thyroid should be considered an organ at risk in every single plan. The message here is that for every patient with breast cancer who needs treatment to the supraclavicular fossa, we need to aim for an adequate target field while also keeping in mind the thresholds for the organs at risk, especially the thyroid, because we know it’s a bothersome side effect that can eventually develop down the road.
What are the next steps for this research?
Strusberg: We are currently finalizing a study on the capsular contracture patients we discussed from last year, which we aim to publish this year or next year. Right now, we’re looking only at our proton cohort and evaluating something called linear energy transfer, because we want to determine the source of this very painful side effect in patients treated with protons.
References
1. Strusberg N, Herrera R, Wang D, et al. Does intensity modulated proton therapy reduce clinical hypothyroidism after supraclavicular irradiation for breast cancer? Presented at: 2026 ASTRO Annual Meeting; September 26–30, 2026; Boston, MA. Poster 2831.
2. Zerey MM, Gal O, Feenstra NA, et al. Does pencil beam scanning proton therapy impart a higher risk of capsular contracture when compared with intensity modulated photon radiotherapy in the post-mastectomy reconstruction setting? Int J Radiat Oncol Biol Phys. Published online April 18, 2026. doi:10.1016/j.ijrobp.2026.04.011