RADIOTHERAPY ALONE FOR MEDICALLY INOPERABLE STAGE-I NON-SMALL-CELL LUNG-CANCER - THE DUKE EXPERIENCE

Purpose: To review our experience treating clinical Stage I non-small- cell lung carcinoma with radiotherapy alone using modern techniques an d staging. The effect of dose and volume on outcome is to be analyzed. Methods: Between January 1980 and December 1995, 156 patients with St age I medically inoperable non-small-cell lung cancer were irradiated at Duke University Medical Center and the Durham Veterans Administrati on Medical Center. Fifteen patients were excluded from analysis (7 tre ated with palliative intent, and 8 lost to follow-up immediately follo wing radiation). Characteristics of the 141 evaluable patients were as follows: Median age 70 years (range 46-95); gender: male 83%, female 17%; institution: DUMC 65%, DVAMC 35%; T1N0 54%, T2N0 46%; median size 3 cm (range 0.5 to 8); pathology: squamous cell carcinoma 52%, adenoc arcinoma 18%, large cell carcinoma 19%, not otherwise specified 11%; p resenting symptoms: weight loss 26%, cough 23%, none (incidental diagn osis) 57%. All patients underwent simulation prior to radiotherapy usi ng linear accelerators of greater than or equal to 4 MV. No patients r eceived surgery or chemotherapy as part of their initial treatment. Th e median dose of radiotherapy (not reflecting lung inhomogeneity corre ctions) was 64 Gy (50 to 80 Gy) given in 1.2 bid to 3 Gy qid fractiona tion. The majority of cases included some prophylactic nodal regions ( 73%). Results: Of the 141 patients, 108 have died; 33% of intercurrent death, 35% of cancer, and 7% of unknown causes. At last follow-up, 33 patients were alive (median 24 months, range 7-132 months). The 2- an d 5-year overall survival was 39% and 13%, respectively (median 18 mon ths). The corresponding cause-specific survival was 60%, and 32% (medi an 30 months). On multivariate analysis, significant factors influenci ng overall and/or cause-specific survival were age, squamous cell hist ology, incidental diagnosis, and pack-years of smoking. There was a no nsignificant trend towards improved cause-specific survival with highe r radiotherapy doses and larger treatment volumes. On patterns of fail ure analysis, 42% of failures were local-only and 38% were distant-onl y. Regional-only failure occurred in 4 patients (7%), 3 of whom failed solely in an unirradiated nodal site. Analysis of factors correlating with local failure at 2 years was performed using a multinominal logi stic regression analysis. Significant factors associated with a lower local failure included incidental diagnosis and absence of cough with a strong trend toward significance for higher radiotherapy dose (p = 0 .07) and larger treatment volume (p = 0.08). Patients who were locally controlled had an improved cause-specific survival at 5 years over th ose who were not controlled (46% vs. 12%,p = 0.03). Grade III-V compli cations occurred in 2 patients (1.5%). Conclusion: Patients with clini cal Stage I medically inoperable non-small-cell lung cancer treated wi th contemporary radiotherapy alone achieved a 5-year cause-specific su rvival of 32%. Uncontrolled lung cancer was the primary cause of death in these patients, and local failure alone represented the most commo n mode of failure (42%). Patients who were locally controlled had a si gnificantly improved cause-specific survival over those who failed loc ally. Because higher doses of radiotherapy appear to provide improved local control, studies of dose escalation are warranted until dose-lim iting toxicity is observed. (C) 1998 Elsevier Science Inc.