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Fractional frequency reuse (FFR) is one of the key concepts for interference mitigation in OFDMA networks. Previous work on FFR has focused on networks of relatively small size and standard hexagon-shaped cell layout. For real-life networks with very irregular cell layout and high variation in radio propagation, standard reuse schemes (e.g., reuse with a factor three) are inadequate; applying a standard scheme, if possible at all, is far from optimal due to the irregularity. We present an approach based on large-scale optimization to study FFR in networks with irregular cell layout. The approach goes beyond the conventional reuse schemes by optimizing the allocation of the cell-edge sub-band of every cell, taking into account the interference caused by the sub-band allocation of all other cells. What's more, whereas the conventional FFR scheme uses three sub-bands, our optimization process allows for considering the number of subbands as a parameter, and enables the analysis of the impact of this parameter on FFR performance. Performance evaluation for networks with realistic radio propagation conditions shows that the approach enables significant throughput improvement at cell-edge zones, and sometimes it is optimal to split the cell-edge band into more than the standard three sub-bands. These results along with the analysis demonstrate the potential benefits of the proposed approach in practicing FFR for large-scale networks, and illustrate the performance trade-off between the cell-edge and cell-center zones.