Long-term survival outcomes and quality of life of image-guided proton therapy for operable stage I non-small cell lung cancer: A phase 2 study.

• We performed a prospective phase 2 study to assess the 7-year treatment outcomes of image-guided proton therapy (IGPT) with fiducial markers in 43 operable stage I NSCLC cases. • IGPT yielded 3-year overall survival and local control rates of 95% each, with 7-year rates of 83% and 95%, respectively. • Grade 3 radiation pneumonitis was observed in one case (2.3%). • Quality of life (QOL) analysis revealed IGPT effectively maintained overall QOL; however, about 40% patients reported dyspnea after treatment. This study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC). This single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score. We enrolled 43 patients (median age: 68 years; range, 47–79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83–99), 95 % (82–99), and 86 % (72–94), respectively, at 3 years, and 83 % (66–92), 95 % (82–99), and 77 % (60–88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months. Our findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL. [ABSTRACT FROM AUTHOR]