Matching Protocol and Practice: The Challenge of Meeting Lung and Kidney Total Body Irradiation Constraints for Scleroderma

Abstract

TBI, a form of immunomodulation, improves treatment outcomes for rapidly progressive scleroderma. The landmark Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial used strict 200 cGy lung and kidney dose restrictions to limit the likelihood of normal tissue toxicity. The protocol, as written, did not specify how or where the 200 cGy limit was to be measured, opening the door to variable techniques and outcomes. Following the SCOT protocol, a validated 18 MV TBI beam model was used to evaluate lung and kidney doses with varying Cerrobend half-value layers (HVLs). Block margins were constructed per the SCOT protocol. Using the 2 HVL SCOT block guidelines, the average central point dose under the lung block center was 353(±27) cGy, almost double the mandated 200 cGy. The mean lung dose was to 629(±30) cGy, triple the mandated 200 cGy. No block thickness could achieve the mandated 2 Gy, due to contribution from unblocked peripheral lung tissue. With 2 HVLs, the average kidney dose was 267(±7) cGy. Three HVLs were needed to reduce it below 200 cGy, meeting the mandated SCOT limit. There is considerable ambiguity (and inaccuracy) in lung and kidney dose modulation for TBI. It is not possible to achieve the mandated lung doses using the protocol-specified block parameters. Future investigators are encouraged to take these findings into account to develop more explicit, achievable, reproducible and accurate TBI methodology.