ABSTRACT
Introduction: Following initial response to TKI, advanced NSCLC patients with actionable mutations ultimately develop treatment resistance. In a proportion of patients (15-40%), initial, limited progression (≤5 lesions) is observed, termed oligoprogressive disease (OPD). SBRT offers hypofractionated, targeted radiotherapy treatment hypothesised to prolong clinical benefit from TKI prior to widespread disease development. With limited evidence to date, and poor clinical/biological selection criteria, the potential benefit offered by SBRT to ablate OPD sites prior to change in systemic therapy is an important question to address. Methods: HALT is a randomised, multi-centre, phase II/III international trial with seamless transition to phase III incorporated. Eligible patients (stage IV NSCLC, actionable mutation, TKI response prior to OPD) are randomised 2:1 to SBRT/continued TKI or continued TKI alone. Eligibility is confirmed by a virtual MDT (vMDT) comprising trial clinicians and radiologists (confirmation of OPD, SBRT suitability). Follow-up assessments are aligned with routine care at 3-monthly intervals until change in systemic therapy is clinically indicated, with imaging and toxicity assessment at each visit. Results: Recruitment commenced November 2017 with 25 centres (17 UK;8 non-UK) open to date. Following the COVID-19 pandemic, recruitment is recovering with 129 registered and 74 randomised patients. Over the last 4 years, little evidence has emerged to confirm any potential benefit of SBRT in this patient group and the impact on patient toxicity remains unknown. Therefore, with persisting questions around clinical equipoise, HALT remains highly relevant. With an 18-month extension and a recent amendment to the HALT inclusion criteria (≤5 OPD lesions, ≤7cm and OPD assessments by PET-avidity), the target of 110 randomised patients remains achievable. Conclusions: As the first randomised trial assessing SBRT benefit in this mutation-positive NSCLC patient population, HALT will provide valuable treatment efficacy and safety information, informing subsequent trial design and contribute to the development of international guidelines for the identification and clinical management of oligoprogression in mutation positive lung cancer. Keywords: Stereotactic body radiotherapy, NSCLC, Phase II