In the treatment of DTC in ESKD patients requiring HD, the timing of the first HD session after 131I administration and, to a lesser extent, the interval between subsequent sessions is critical in maximizing treatment efficacy and minimizing bone marrow toxicity. Previous studies have utilized a range of intervals to the first HD session, varying from 15-hours to 42-hours(4). The interval to subsequent HD sessions has also varied widely in these studies, ranging from 12-hours to 45-hours(4). The rationale behind the choice of HD scheduling in these treatments was dictated by differences in the administered activity of 131I, readings of dose-rates from the patient, individual patient dialysis requirements, as well as resource availability.
The timing of the first HD session after administration is crucial as it determines the majority of radiation dose to the bone marrow. For instance, we found that 60% and 47% of the total radiation dose to bone marrow, for patient 1 and 2 respectively, was delivered in the time between 131I administration and the first HD session. It follows that increases in the time between 131I administration and the first HD session will significantly increase the radiation dose delivered to bone marrow. We estimated that the radiation dose delivered to blood was 0.15Gy and 0.1Gy for patients 1 and 2 respectively. If the first HD session were scheduled at 48-hours post-administration instead of 24-hours, we calculated that the radiation dose delivered to bone marrow increases to 0.3Gy and 0.2Gy for patients 1 and 2 respectively.
In our study, we found that performing HD sessions at 24-, 72- and 144-hours (Days 1,3 and 6) post-131I produced a retained percentage radioactivity profile (i.e., overall clearance rate) similar to profiles of patients with normal renal function (Fig. 3). This HD regimen also mirrors the schedule for most patients who undergo 3 times/week intermittent HD, minimizing the risk of emergent dialysis (e.g., for fluid overload, hyperkalaemia) during radioablation treatment. As expected, clearance of 131I between HD sessions was mainly due to the physical decay of the radionuclide. This is demonstrated through Patient 2, who had a creatinine clearance of 6mL/min, but did not show any greater clearance of radioactivity than Patient 1, who was anephric, indicating that the typical residual renal function of a chronic HD patient is not able to significantly contribute to inter-dialytic 131I clearance. It should be noted that clearance of 131I between dialysis depends on 131I availability in blood and, to a lesser extent, on the amount of 131I excreted via other means (such as sweat and saliva). The amount of 131I circulating in blood relates to the volume of residual thyroid tissue after the surgery; patient 2 had greater 131I uptake in the thyroid bed than patient 1 explaining the lower inter-dialysis clearance.
The dosage of 131I is another uncertain factor, with conflicting evidence on whether to reduce, maintain or increase the standard dose of 131I given the prolonged half-life and reduced clearance of 131I in ESKD. Vermandel et al., in a case series of 6 patients, found a 30% reduction to standard 131I dosing to achieve a balance of treatment efficacy with bone marrow toxicity(6). Holst et al., reached similar conclusions using mathematical modelling(9). Other studies, conversely, have recommended equivalent dosing or increased dosing of 131I given higher clearance rates on HD and using individualized dosimetry to guide HD scheduling(10–12). Although our data is limited to only 2 patients, assuming that HD clearance of 131I is independent of administered dose, it suggests that the administration of higher levels of radioactivity (up to 4GBq) could be safely given to ESKD patients when the first HD session is scheduled at 24-hours post-administration. Decisions on dosing in this population are beyond the scope of our paper but multidisciplinary input from nuclear medicine specialists, nuclear medicine physicists, endocrinologists and nephrologists is a requirement due to the role of HD in 131I clearance and the influence on radiation dose to bone marrow.
Staff safety is another important consideration when administering 131I. Patients with normal renal function undergoing 131I radioablation treatment in hospital are usually isolated with minimal staff contact during their admission. However, patients requiring dialysis represent a deviation from routine practice, as dialysis nursing staff are required to be in close proximity to patients during sessions, when the g-radiation from 131I may pose a risk. These risks can be significantly mitigated with appropriate distancing, sensible positioning whilst preparing for HD and remote monitoring during HD. In our study, we achieved an overall cumulative radiation exposure to dialysis nursing staff that was very low, consistent with other studies(3). Furthermore, as the closest and most prolonged patient contact occurs during fistula cannulation, if the patient can be safely trained to self-cannulate, we showed that radiation exposure can be reduced even further, seen in the notably lower cumulative staff radiation exposure for patient 1 compared to patient 2 (Fig. 5).
Finally, our experiences with patient 1 during the study led to additional protocol modifications which were applied to patient 2. One such modification was the suspension of phosphate binders prior to treatment as we suspect this may have resulted in the aggregation of 131I in the gastrointestinal tract seen on the 4-hour scan for patient 1. There is no literature studying the affinity of phosphate binders with 131I, but given it is a non-critical medication, withholding all phosphate binders prior to therapy is a reasonable approach. We also found the reduction in thyrotropin alfa to a single dose from the standard of two, produced a more than sufficient response in TSH to proceed with treatment, in agreement with EANM guidance(6).