Is there an optimal bridging radiation dose for aggressive B-cell NHL undergoing CAR T-cell therapy?

The perfect radiation dose for a given patient probably depends on a number of patient and disease-specific factors including tumor biology and genetics, the anatomy of the tumor and adjacent organs at risk, and the radiation technique used. We do not have the ability to recommend such individualized doses at this point, so instead we try to group this very heterogeneous group of lymphomas together and do the best we can. 

For the reasons described above, when it is safe and feasible to treat all lesions comprehensively with pre-CAR-T infusion radiation therapy, we will do that. When it is not possible, then focal treatment to symptomatic, potentially symptomatic, or bulky lesions can be utilized. Radiation dose depends on the volume and the adjacent organs, but it seems that an EQD2 of over 30 or 37.5 Gy may give an excellent chance of local control. 

In reality, the radiation dose and fractionation are often determined by the timeline for CAR-T infusion and the timing of referral by Hematology colleagues. This can necessitate creative dose fractionations for a given patient based on the number of days available. We have often utilized five fraction regimens to 20-25 Gy. In cases with large retroperitoneal targets, we have relatively frequently used BID fractionations of 30-36 Gy in 20 fractions over two weeks with good tolerability. 

There are no studies that clearly identify the optimal bridging radiation dose to use. Some studies showed no in-field recurrences with EQD2 doses of ≥37.5-39 Gy. I would tailor my bridging radiation dose to the treatment intent which is based on the extent of disease prior to CAR-T.

For patients who present with limited disease prior to CAR-T, that I can safely chase all of it with radiation, I would attempt a definitive dose of comprehensive bridging radiation to all sites of disease to an approximate dose of 2.5–2.67 Gy/fraction x 15 fractions, if possible. Twice a day (BID) treatment with 1.5–1.8 Gy/fraction to a total dose of 30 – 39.6 Gy may be considered if bridging time is limited to less than 3 weeks. A total equivalent 2 Gy dose (EQD2) of ≥ 37.5 Gy is desirable, but not obligatory and is dependent on the patient’s performance status, location of disease, history of prior RT, and the available bridging timeline window. Dose escalation is reasonable in the presence of high-risk features that predict RT local relapse such as Myc/BCL rearrangements, bulky tumor, and high MTV. In an urgent setting with a narrow bridging time window, where definitive comprehensive radiation is not feasible, consider treating with lower doses and shorter courses of radiation such as 4 Gy x 5 fractions, or 4 Gy x 2 fractions, or 8 Gy x 1 fraction for symptoms control and possible immune system priming.

For patients who present with diffuse disease prior to CAR-T, that is not reasonable to chase it all with radiation, I would favor low doses of bridging radiation for symptom control and possible immune system priming. This includes 4 Gy x 5 fractions or 4 Gy x 2 fractions or 8 Gy x 1 fraction. Higher doses of bridging radiation could be delivered to bulky disease sites for better local control/response if time allows. Different doses of BRT could also be considered depending on the context of disease, intent of treatment, and plan to deliver further radiation post-CART.