7158 Background: HFXRT has not been commonly used in community practice despite better 5-yr survival compared to QDRT with concurrent cisplatin and etoposide by randomized study. Methods: CT-staged LSCLC pts treated by HFXRT or QDRT with cisplatin-based ChT between 1985–1998 were reviewed. Complete responders received prophylactic cranial irradiation (PCI). The data were analyzed by Kaplan-Meier survival function and the Log Rank test. Results: 324 pts were treated and followed from 3–156M (median 47M). Median age: 60. Male (53%), KPS 90–100 (71%), wt loss <5% (80%). Pleural effusion (PE) in 24%. 217 received QDRT: median dose 50Gy/5W. 107 received HFXRT: median dose 45Gy/3W. 168 received PCI: 108 in QD group and 60 in HFXRT group. 5 yr-OS: 25% by HFXRT vs 12% by QDRT (p=0.02). In PCI pts, 5yr OS: 32.3% by HFXRT vs 18.9% by QDRT (p=0.02). MS of 24M by HFXRT vs 18M by QDRT. Acute Gr 3 esophagitis: 21.5% by HFXRT vs 9.2% QDRT (p=0.002). Gr 3 lung fibrosis: 30.8% by HFXRT vs 12.4% by QDRT (p< 0.0001). Multivariate analysis showed factors influencing OS were PCI (p=0.001), HFXRT (p<0.0001), and PE (p<0.0001). Conclusions: This retrospective study showed that OS was improved by concurrent ChT and HFXRT compared to QDRT and application of PCI. It is important to reduce normal tissue toxicities in the future when HFXRT and concurrent ChT are applied. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca MedImmune Speakers Bureau