ESTRO 2025 - Abstract Book

S84

Invited Speaker

ESTRO 2025

The first question to address is if EGFR-TKI are cytotoxic or merely cytostatic. In the latter case, combinations with cell killing agents such as radiotherapy is needed to eventually eradicate the tumor. A prospective study in early stage operable NSCLC with exon 19 or 21 EGFR mutations treated upfront with osimertinib demonstrated no pathological complete responses, supporting a merely cytostatic effect. The second question is if EGFR-mutated tumors are sensitive to radiotherapy. Both retrospective series, e.g. in brain metastases, and a RCT from China, demonstrate that EGFR-mutated tumors show a radiosensitivity that is probably similar to that of non-mutated NSCLC. The third is if adding radiotherapy to EGFR-TKI has beneficial effects for the patient. Retrospective series suggest that adding SRS to EGFR-TKI in patients with brain metastases highly significantly decreases the rate of local tumor progression, which may be beneficial for selected patients. The afore-mentioned Chinese RCT demonstrated a benefit in PFS and OS by upfront adding radiotherapy (60 Gy/ 30 fractions) to the primary tumor and involved lymph nodes to icotinib in patients with oligometastatic NSCLC. If confirmed in a non-Asiatic population, this could become the new SoC. The role of radiotherapy in patients with oligoprogressive NSCLC is promising in retrospective series, leading to improved PFS rates, but the results of ongoing RCTs are awaited. Finally, toxicity is somewhat increased, but should be balanced with the positive effects of combining radiotherapy with EGFR-TKI in appropriate patients.

4780

Speaker Abstracts EGFR-driven NSCLC and radiotherapy - contra Lizza Hendriks Pulmonary Diseases, Maastricht UMC+, Maastricht, Netherlands

Abstract:

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer. TKI improved overall survival (OS) as well as quality of life (QoL) compared with chemotherapy, first in the metastatic setting and thereafter in almost all disease stages. Third generation EGFR-TKI such as osimertinib have now become standard of care as an adjuvant treatment for fully resected stage IB-IIIA EGFR mutated NSCLC, or for EGFR-mutated stage III NSCLC treated with chemoradiation. In the metastatic setting, they can be given as monotherapy or in combination with chemotherapy or with amivantamab, a bispecific antibody against EGFR and MET. With the improving outcomes of systemic therapy, I will argue in this contra presentation, that radiotherapy should not automatically have a place in the treatment paradigm of EGFR-mutated NSCLC. I will focus on data in all disease settings with EGFR-TKI, special situations such as brain metastases and the risk of toxicity by combining EGFR-TKI with radiotherapy.

4783

Speaker Abstracts Uncertainty quantification and visualisation in dose prediction Zoltan Perko Radiation Science and Technology, Delft University of Technology, Delft, Netherlands. Radformation Inc., N/A, New York, USA