In advanced-stage disease, it is unclear how important it is because if we're going to follow a PET-adapted approach, the interim PET or the PET scan after two cycles of ABVD for advanced-stage disease really trumps the baseline prognostic factors such as the International Prognostic Score factors. Based upon that, it doesn't necessarily matter what the patient's baseline factors are and patients could all start off with the same treatment and then have a different approach based upon their response to therapy after two cycles of treatment. Historically, before we started using a PET-adapted approach or before that data became available, we treated patients with higher risk disease, which we defined as having an IPS score of 4 or more, with escalated BEACOPP, with the plan to deescalate for patients who have an early good response to therapy. There is support from that as there were recently reported results from the LYSA study using this approach where patients are started off with escalated BEACOPP and then deescalated if they have a negative PET scan after two cycles and they are deescalated to ABVD. There were excellent outcomes from that study, and so it could be considered for a patient who is presenting with many of the risk factors on the IPS score; but in my practice, I typically do start patients off with ABVD and then use the interim PET to decide further treatment. I don't believe that is always necessary to use these risk factors to guide therapy; and I think that going forward, we may find that we're using them less and less as we find that there are other factors such as interim response or, potentially in the future, maybe even using cell-free DNA or metabolic tumor volume to help guide therapy.

For early-stage disease, I think one of the most important prognostic factors is disease bulk, and that does have an impact on choosing treatment. Then it is important as far as which treatment course we're going to be following, such as if the patient is going to be treated as per the RAPID study or as per the SWOG study for early-stage disease where PET-adapted approaches were used. I think it's important that we're considering the risk factors for the patients that were enrolled in those studies to make sure that the patients would have been considered eligible for those studies. Particularly, the RAPID study which included only three cycles of ABVD as long as the patients became PET-negative after those three cycles and the patients did not receive any radiation therapy, that was a study only for patients with stage IA or IIA disease and they could not have bulky disease. It was a fairly more favorable group of patients that were involved in that study, so we need to just take note that the patients would've been eligible for these approaches.