Exploring the role of stereotactic body radiotherapy to sites of oligoprogression to improve outcomes

Abstract

mproved treatments for metastatic non-small cell lung cancer (NSCLC) and prostate cancer has unearthed a clinical state called oligoprogressive disease (OPD). OPD is poorly defined, broadly speaking it features progression in only a few sites of disease, on a background of other metastatic lesions remaining responsive to the current line of systemic treatment. Some patients are treated with stereotactic body radiotherapy (SBRT) to these resistant clones, to exploit the ongoing effects from systemic treatment to the responding lesions, although there is limited prospective evidence supporting this. SBRT is a well tolerated treatment in oligometastatic disease (OMD) but there are limited data on the efficacy of treating bone metastases with SBRT, and the toxicity associated with treating an older, frailer population with a higher burden of metastatic disease such as with OPD. Little is known about the prevalence of OPD in prostate cancer or in NSCLC during immunotherapy treatment which is now widely used. Methods Preliminary research into OPD in prostate and NSCLC are presented, including early toxcity results from the TRAP trial and the impact of a novel, trial specific virtual multi-disciplinary team meeting (vMDT) on eligibility and recruitment within the HALT trial. Both are prospective phase II trials assessing the outcomes of patients treated with SBRT for OPD in prostate and NSCLC. Retrospective electronic records at a single centre were interrogated to explore the patterns of progression amongst patients treated with abiraterone or enzalutamide for castration resistant prostate cancer (CRPC) and immunotherapy for NSCLC. Outcomes of patients treated for bone OMD with SBRT were evaluated. Results: The prevalence of OPD was between 21-35%, with a trend towards better progression free survival with the use of SBRT. SBRT to bone OMD achieved low rates of local failure (5.9%). Review of early toxcity data for the first 41 patients recruited to the TRAP trial found only one patient (2.4%) experienced grade 3+ toxicity possibly associated with SBRT. A central vMDT for eligible patients on recruitment of patients to the HALT trial deemed 27% of patients registered as not eligible for the trial. There is a need for further clarification of the definition of OPD to provide clarity of which patients would be eligible for SBRT. The results of this thesis support the need for randomised phase III trials.