Abstract. The multileaf collimator sequencing problem is an important component of the effective delivery of intensity modulated radiotherapy used in the treatment of cancer. The problem can be formulated as finding a decomposition of an integer matrix into a weighted sequence of binary matrices whose rows satisfy a consecutive ones property. In this paper we extend the state-of-the-art optimisation methods for this problem, which are based on constraint programming and decomposition. Specifically, we propose two alternative hybrid methods: one based on Lagrangian relaxation and the other on column generation. Empirical evaluation on both random and clinical problem instances shows that these approaches can out-perform the state-of-the-art by an order of magnitude in terms of time. Larger problem instances than those within the capability of other approaches can also be solved with the methods proposed.