Incorporating advanced radiotherapy technology in management of locally advanced cervical cancers

Abstract

Cervical Cancer is a global cancer burden worldwide, and for advanced disease stages, cancer mortality is still high. With the advancement of radiotherapy from 2-dimensional to intensity-modulated radiotherapy, acute and late toxicities can be much reduced. Image-guided radiotherapy and brachytherapy is an important breakthrough, with the benefit of accurate tumor delineation, and transition to a volume-based concept, dose escalation can be achieved with low toxicities. Numerous clinical trials have demonstrated the survival benefit in such technique, and the European GEC ESTRO network has implemented guidelines for MRI guided brachytherapy as the preferred standard of care. In Hong Kong, over the past decade there is increasing adoption of image guided brachytherapy (IGBT). A multi-institutional Patterns of Care Studies have demonstrated some centers have already widely adopted such practice, while others were still in the preliminary stage. Resource limitations and training of expertise were the main reason for the delay in implementation. A clinical outcome analysis among all oncology centers in Hong Kong have demonstrated that there is an improved 3-year survival trend in both overall and progression-free survival in the IGBT compared with conventional cohort, at 80.8% vs. 78.9%, and 81.1% vs. 79.3%, respectively. While cumulative dose achieved beyond 84Gy has significant gain in overall survival at 3 years (68.5% to 87.7%, p=0.007) compared with dose below 84Gy in the IGBT cohort, advanced FIGO stage and use of interstitial needles have not demonstrated outcome difference. There was no increased toxicity in the IGBT arm, and there was a trend for higher late grade 3 toxicities in 2D cohort (11.3% versus 6.3%). A novel virtual and non-invasive pre-planning strategy is adopted before IGBT to improve accuracy of the brachytherapy treatment. Result showed excellent correlation of pre-planning dosimetry estimation with the actual high risk clinical target volume, and the use of interstitial needles can improve the final dosage significantly. A case series of MR Linac and tomotherapy of gynecological cancer patients showed excellent disease control, and no severe toxicity in the MR Linac cohort while tomotherapy cohort is the preferred modality in patients who have a longer treatment field due to more advanced stage. Future directions include the use of artificial intelligence to facilitate a more efficient workflow in image-guided radiotherapy, and dynamic imaging such as diffuse weighted imaging (DWI) and PET-CT guided hypoxia fraction assessment. Proton therapy has emerging evidence to further reduce toxicity compared to IMRT and longer follow up will establish its role in gynecological cancers.