Table 2. Proton therapy studies for locally advanced non-small cell lung cancer.

Reference	Sample size	Stage	Radiation dose	Technique	Median follow-up	Outcomes	Grade ≥3 toxicities
Sejpal et al. (33) [2011]	62	III	74 Gy (RBE) proton, 63 Gy photon	PBT, 3DCRT, IMRT	15.2 months	N/A	2% and 5% grade ≥3 pneumonitis and esophagitis (proton), 30% and 18% pneumonitis and esophagitis (3DCRT), 9% and 44% pneumonitis and esophagitis (IMRT)
Chang et al. (64) [2011]	44	III	74 Gy (RBE) in 2 Gy (RBE) fractions	PSPT	19.7 months	1 yr: OS 86%, PFS 63%	11.4% grade 3 dermatitis, 11.4% grade 3 esophagitis, 2.3% grade 3 pneumonitis, 2.3% pulmonary/pleural fistula
Nguyen et al. (65) [2015]	134	II (n=21), III (n=113)	74 Gy (RBE) or 60–72 Gy (RBE) in 2 Gy (RBE) fractions	PSPT	56.4 months	5 yr: OS 30% (II), 25.3% (IIIA), 44.5% (IIIB); DFS 19% (II), 17.4% (IIIA), 14.1% (IIIB)	4% grade 3 esophagitis, 2% grade 3 pneumonitis, 6% grade 3 dermatitis, 1% grade 4 esophagitis
Chang et al. (66) [2017]	64	III	74 Gy (RBE) in 2 Gy (RBE) fractions	PSPT	27.3 months	5 yr: OS 29%, PFS 22%	8% grade 3 esophagitis, 2% grade 4 esophagitis, 12% late grade 3 pneumonitis, 2% grade 4 bronchial fistula
Liao et al. (63) [2018]	149	IIB–IIIB	74 Gy (RBE)	PSPT (n=92), IMRT (n=57)	24.1 months	1 yr: LF 10.9% (IMRT), 10.5% (PSPT)	7% grade ≥3 pneumonitis (IMRT), 11% grade ≥3 pneumonitis (PSPT)

Gy (RBE), Gray (relative biological effectiveness); PBT, proton beam therapy; PSPT, passive scattering proton therapy; 3DCRT, 3D conformal radiotherapy; IMRT, intensity-modulated radiation therapy; OS, overall survival; PFS, progression-free survival; DFS, disease-free survival; LF, local failure