Optimal timing of thoracic irradiation for limited stage small cell lung cancer: Current evidence and future prospects

Table 1 Selected randomized studies of early and late thoracic radiation therapy for limited stage small cell lung cancer management

Ref.	Period	Number of patients	Age	Performance status	Timing of RT (start of TRT) (d)	RT dose fractionation schedule	Chemotherapy Schedule	PCI	Survival	P value
Murray et al[20], 1993, National Cancer Institute of Canada Clinical Trials Group Study	1985-1988	Total number of patients 308; 155 patients in early TRT group; 153 patients in late TRT group	Median age 61.8 yr in early TRT group; Median age 61.6 yr in late TRT group	ECOG 0-1 87% in early TRT group; ECOG 0-1 90% in late TRT group	Day 22 in early TRT group; Day 106 in late TRT group	40 Gy/2.67 Gy daily RT (hypofractionation)	Platinum based chemotherapy	86% of patients received PCI (2.5 Gy × 10 fractions)	Median survival 21.2 mo in early TRT group; 2-yr survival 40% in early TRT group; 3-yr survival 29.7% in early TRT group; Median survival 16 mo in late TRT group; 2-yr survival 34% in late TRT group; 3-yr survival 21.6% in late TRT group	0.006 in favor of early TRT
Work et al[21], 1997, Aarhus Lung Cancer Group Study	1981-1989	Total number of patients 199; 99 patients in early TRT group; 100 patients in late TRT group	Age range 36-70 yr in early TRT group; Age range 36-69 yr in late TRT group	KPS 80-100 82% in early TRT group; KPS 80-100 80% in late TRT group	Day 1 in early TRT group; Day 120 in late TRT group	40-45 Gy/2 Gy daily (conventional fractionation) split course RT over 7 wk	Platinum based chemotherapy	All early RT patients received PCI; 58% of late RT patients received PCI	Median survival 10.5 mo in early TRT group; 2-yr survival 20.2% in early TRT group; 3-yr survival 13.1% in early TRT group; Median survival 12 mo in late TRT group; 2-yr survival 19% in late TRT group; 3-yr survival 12% in late TRT group	Not statistically significant
Jeremic et al[22], 1997, University of Kragujevac, Yugoslavia study	1988-1992	Total number of patients 103; 52 patients in early TRT group; 51 patients in late TRT group	Age range 40-67 yr in early TRT group; Age range 44-66 yr in lateTRT group	KPS 90-100 52% in early TRT group; KPS 90-100 47% in late TRT group	Day 1 in early TRT group; Day 43 in late TRT group	54 Gy 1.5 Gy BID (hyperfractionation)	Platinum based chemotherapy	All patients with complete or partial response received PCI (2.5 Gy × 10 fractions)	Median survival 34 mo in early TRT group; 2-yr survival 71.2% in early TRT group; 3-yr survival 48.1% in early TRT group; Median survival 26 mo in late TRT group; 2-yr survival 52.9% in late TRT group; 3-yr survival 39.2% in late TRT group	0.027 in favor of early TRT
Gregor et al[23], 1997, EORTC Lung Cancer Co-operative Group Study	1989-1995	Total number of patients 335	Median age 61 yr (range: 33-75 yr)	ECOG 0-1 in 311 patients	Day 42 in early TRT group; Day 91 in late TRT group	12.5 Gy/2.5 Gy daily (1 wk on, 3 wk off) × 4 in early TRT group (hypofractionation); 50 Gy/2.5 Gy daily in late TRT group (hypofractionation)	No platinum based chemotherapy	PCI was not a formal part of the study, however, all patients with complete response were eligible	Median survival 14 mo in early TRT group; 2-yr survival 26% in early TRT group; 3-yr survival 12% in early TRT group; Median survival 15 mo in late TRT group; 2-yr survival 23% in late TRT group; 3-yr survival 15% in late TRT group	Not statistically significant
Perry et al[24], 1998, Cancer and Leukemia Group B (CALGB) study	1981-1984	Total number of patients 270; 125 patients in early TRT group; 145 patients in late TRT group	Age range 32-79	ECOG 0-1 86% in early TRT group; ECOG 0-1 87% in late TRT group	Day 1 in early TRT group; Day 64 in late TRT group	50 Gy/2 Gy daily conventionally fractionated RT over 5 wk	No platinum based chemotherapy	All patients received PCI (3 Gy × 10 fractions)	Median survival 13.04 mo in early TRT group; 2-yr survival 24% in early TRT group; 3-yr survival 7.2% in early TRT group; Median survival 14.54 mo in late TRT group; 2-yr survival 31.7% in late TRT group; 3-yr survival 13.8% in late TRT group	0.0072 in favor of lateTRT
Skarlos et al[25], 2001, Hellenic Cooperative Oncology Group (HeCOG) study	1993-1999	Total number of patients 81; 42 patients in early TRT group; 39 patients in late TRT group	Age range 40-76 yr in early TRT group; Age range 38-79 yr in late TRT group	ECOG 0-1 76% in early TRT group; ECOG 0-1 85% in late TRT group	Day 1 in early TRT group; Day 56 in late TRT group	45 Gy 1.5 Gy BID (hyperfractionation)	Platinum based chemotherapy	All patients with complete or near complete response received PCI (1.5 Gy BID × 6)	Median survival 17.5 mo in early TRT group; 2-yr survival 36% in early TRT group; 3-yr survival 22% in early TRT group; Median survival 17 mo in late TRT group; 2-yr survival 29% in late TRT group; 3-yr survival 13 % in late TRT group	Not statistically significant
Takada et al[26], 2002, Japan Clinical Oncology Group (JCOG) Study	1991-1995	Total number of patients 228; 114 patients in early TRT group; 114 patients in late TRT group	Age range 39-74 yr in early TRT group; Age range 30-74 yr in late TRT group	ECOG 0-1 95% in both early and late TRT groups	Day 2 in early TRT group; Day 85 in late TRT group	45 Gy 1.5 Gy BID (hyperfractionation)	Platinum based chemotherapy	All patients with complete response received PCI (4 Gy × 6)	Median survival 27.2 mo in early TRT group; 2-yr survival 54.4% in early TRT group; 3-yr survival 29.8% in early TRT group; Median survival 19.7 mo in late TRT group; 2-yr survival 35.1% in late TRT group; 3-yr survival 20.2% in late TRT group	0.097 in favor of early concurrent TRT but not statistically significant

TRT: Thoracic radiation therapy; PCI: Prophylactic cranial irradiation.