title: SBRT for oligoprogressive oncogene addicted NSCLC.
abstract: Lung cancer is one of the leading causes of cancer death in men and women and treatment outcome continues to lag behind other common cancer types. A subset of lung adenocarcinoma patients exhibit a somatic mutation in EGFR or an ALK rearrangement. In these patients, targeted TKI therapy results in higher response rates, improved PFS and reduced side effects compared with platinum-based chemotherapy. Despite initial activity of the TKIs, ultimately all patients present with disease progression after about a year on TKI therapy due to resistance development. About 15-47% of patients present with limited oligoprogressive disease (OPD): such patients show only a limited number of metastases with progression in radiological imaging. Radical local treatment to all oligoprogressive lesions is thought to eradicate the de-differentiated clones and restore overall sensitivity of the metastatic disease. Retrospective studies suggest that aggressive local treatment using stereotactic body radiotherapy (SBRT), surgery or others can be used to eradicate TKI-resistant subpopulations enabling prolonged TKI treatment "beyond progression", which may lead to increased PFS and overall survival. This review focuses on the biological background of resistance development, systemic and local treatment options with a focus on SBRT, as well as challenges in defining the state of OPD and current clinical studies in oligoprogressive oncogene addicted NSCLC.
authors.affiliation: Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, CH 8091 Zurich, Switzerland. Electronic address: Lucas.Basler@usz.ch.
authors.forename: L
authors.initials: L
authors.lastname: Basler
authors.affiliation: Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, CH 8091 Zurich, Switzerland.
authors.forename: S G C
authors.initials: SG
authors.lastname: Kroeze
authors.affiliation: Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, CH 8091 Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Guckenberger
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D000074723:Oncogene Addiction / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016634:Radiosurgery / Q000379:methods*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: EGFR mutation; Oligoprogressive disease (OPD); Oncogene addicted lung cancer; Resistance to targeted therapy; Stereotactic body radiotherapy (SBRT); Tyrosine kinase inhibitors