Metastatic Ablation in Epidermal Growth Factor Receptor Mutated Oligometastatic Non-Small Cell Lung Cancer—Upfront or Outback After Systemic Tyrosine Kinase Inhibitors?

Outside of a clinical trial, our practice is to define oligometastatic disease as 1 to 3 sites of metastases. 1 Vitzhum LK Pollom EL Diverging roads in the management of metastatic EGFR mutated non small cell lung cancer: Ablate all, none, or some?. Intl J Radiat Oncol Bio Phys. 2023; 116: 479-480 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Because the patient had chest symptoms (leading to investigations for pulmonary embolism) and bone pain, the decision to offer upfront radiation therapy to both symptomatic sites is straightforward. Our practice is a single fraction of 28 Gy to the lung and 24 Gy in 2 fractions to the right acetabulum. How to best integrate local therapy for the intracranial site is a more complex question and is being explored in the OUTRUN trial (NCT03497767). This patient has an epidermal growth factor receptor L858R mutation and is likely to respond to third-generation epidermal growth factor receptor–targeted tyrosine kinase inhibitors (TKi), with intracranial response rates expected to be in the order of 80%. Although stereotactic radiosurgery is highly effective, there remains a 10% risk of symptomatic radionecrosis. Given that the metastasis is small and asymptomatic, initiation of osimertinib and close magnetic resonance imaging surveillance may spare the potential morbidity of local therapy. However, data from 401 patients from our institution suggest that Total Metastatic Ablation is associated with better progression-free survival and overall survival than subtotal ablation in patients with oligometastatic disease. 2 Siva S Jones G Bressel M et al. Impact of medical operability and total metastatic ablation on outcomes after SABR for oligometastases. Int J Radiat Oncol Biol Phys. 2022; 114: 862-870 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Thus, should metastatic ablation be offered Upfront, or Outback at the time of oligoresidual or oligoprogressive disease 3 Tjong MC Louie AV Iyengar P Solomon BJ Palma DA Siva S. Local ablative therapies in oligometastatic NSCLC—upfront or outback?—a narrative review. Transl Lung Cancer Res. 2021; 10: 3446-3456 Crossref PubMed Scopus (7) Google Scholar after commencing TKi? The SINDAS study (NCT02893332) provides compelling evidence for Upfront ablation in this context. Two further phase 3 trials are ongoing that we hope will address the optimal sequence: OITROLC (NCT02076477) and OMEGA (NCT03827577), which together with the OUTRUN study would provide prospective evidence to guide management in complex cases such as this.