Purpose/Objective: To analyze failure patterns by pretreatment characteristics and treatment groups in unresectable lung cancer.Materials [amp ] Methods: Patients with inoperable stage II, IIIA and unresectable IIIB nonsmall cell lung cancer with KPS[ge ]70 and weight loss [le ]5% were randomized to 1 of 3 treatment groups: standard radiation therapy with 60 Gy at 2.0 Gy per day (STD RT), induction chemotherapy with cisplatin 100 mg/m 2 days 1 and 29 with vinblastine 5 mg/m 2 weekly for 5 weeks followed by 60 Gy at 2.0 Gy per day (CT +RT), or hyperfractionated radiation therapy with 69.6 Gy at 1.2 Gy bid (HFX RT). Of 490 patients enrolled, 458 were evaluable. Minimum and median periods of observation for this analysis were 4 years and 6 years, respectively.Results: Pretreatment characteristics including age, gender, KPS, body surface area, histology, T-stage, N-stage, AJCC stage, tumor size, location of the tumor, frequency of diagnostic thoractomy and atelectasis at presentation were equally distributed. Toxicities were similar to those previously reported (JNCI, 1995). There were 70 (47%) Gr 4 hematologic toxicities reported on the CT arm. There was one Gr 5 hematologic toxicity. There were 3 late Gr 5 lung toxicities. Two were treated by HFX and one by CT+RT. The comparisons of survivals showed 20%, 31%, and 24% at 2 years, 4%, 11%, and 9% at 4 years in the STD RT, CT+RT, and HFX RT groups, respectively. Median survival rates were 11.4, 13.6, and 12.3 months for STD RT, CT+RT, and HFX RT, respectively (log rank p=0.05, Wilcoxon p=0.04). The pattern of first failure showed that patients on the CT+RT arm had statistically significantly less distant metastasis (DM) (other than brain) than patients on the RT alone arms (p=0.04). These differences were most marked in patients with SCC histology (p=0.0015). Rates of other DM were 43%, 16%, 38% in patients with SCC, for STD RT, CT+RT, and HFX RT, respectively. This pattern was not observed in the non-SCC patients. Patients with peripheral/chest wall lesion were significantly more likely to fail first in the thorax when treated on STD RT compared to CT+RT and HFX RT (p=0.009).Conclusion: Patients on the CT+RT had a statistically significant reduction of DM compared to patients on the RT alone arms, especially among the patients with SCC. We are now comparing sequential and concurrent CT and RT in RTOG 94-10, building on the apparent advantages of these CT/RT interactions.