Vora, A, (2016) Journal of Clinical Oncology (Link to abstract)
Children with acute lymphoblastic leukemia (ALL) are at risk for relapse from the CNS, and therefore CNS directed therapy has become a mainstay of ALL treatment. Cranial radiotherapy (CRT) is declining in use and gets replaced increasingly by intrathecal therapy and chemotherapy with CNS penetrance such as high dose methotrexate. This is a meta-analysis of the results from all upfront ALL trials in 10 co-operative groups between 1996-2007 looking at whether CRT changes the rate of relapse. None of the trials were randomized to answer this question and each had slightly different indications for using CRT. Overall, there was no difference in outcome between those who received CRT and those who did not. There was a higher incidence of CNS relapse in CNS3 patients who did not get CRT but the overall relapse rate was not different regardless of therapy. The authors suggest that CRT may no longer have a role in the context of modern therapy.
* Is this study the straw that breaks the back of CRT in ALL? In this metaphor, the St Jude’s Total X
* study (Pui, NEJM 2009) was a whole load of straws that started this question. There is a lot of subtlety here – especially in the fact that the question has never been randomized and that every group has its own indications for the use of CRT. While CRT can probably be removed for the majority of patients the numbers do not seem big enough to remove it in CNS3 patients or high-risk T-ALL patients.