HYPERFRACTIONATED ACCELERATED RADIATION-THERAPY FOR NONSMALL CELL LUNG-CANCER - CLINICAL-PHASE I II TRIAL/

Purpose: In an attempt to improve local control and survival of nonsma ll cell lung cancer (NSCLC),hyperfractionated accelerated radiation th erapy (HART) was carried out as a clinical phase I/II trial. Methods a nd Materials: HART was delivered by 1.1 Gy/fraction, three fractions p er day with intervals of 4 h and five treatment days per week. The cli nical tumors were irradiated to 74.3 Gy (72.6-75.9)/66-69 fx, 33 days (29-40) (not corrected for lung density), and the subclinical lesions, to 50.0 Gy (48.4-50.6)/44-46 fx, 33 days (29-40). Sixty-nine patients with NSCLC were enrolled in this study. Nine patients were withdrawn from the study during HART due to different reasons. Sixty patients fo rmed the study for outcome analyses. They were 57 males and 3 females with median age of 61 years (21-77). There were 41 cases of squamous c ell carcinoma, 15 cases of adenocarcinoma, and 4 cases of large cell c arcinoma. Overall, favorable patients (KPS greater than or equal to 70 , weight loss <5% and Stages I, II, IIIa) accounted for 73% (44 of 60) of all patients. Forty-four patients (73%) received adjuvant chemothe rapy (DDP + VP16) with median cycles of 1.8 before and/or after HART. In order to compare the outcome of HART with conventional irradiation, 50 NSCLC patients treated by conventional fractionated irradiation (C FI) during the same period were chosen as the basis to evaluate relati ve effects of HART. They derived from the control group of another cli nical trial of hyperfractionated irradiation for NSCLC in the same dep artment. They received median tumor dose of 63.9 Gy (62.8-65.0)/34 fx (32-36), 48 days (45-53). Results: 1. Acute and late complications: (a ) In HART, 87% of patients (52 cases) developed acute radiation esopha gitis: Grade 1-2, 46 cases (77%) and Grade 3, 6 cases (10%), at 2.5 we eks (2-3.5 weeks) after HART began. Five patients with Grade 3 esophag itis had their HART interrupted for less than or equal to 7 days. In C FI, esophagitis was much less (44%, p < 0.05) with 38% of Grade 1-2 an d 6% of Grade 3. (b) In HART, acute pulmonary symptoms (RTOG Grade 1-2 ) occurred in 17% (10 cases), and acute radiation pneumonitis (Grade 3 ), in 8% (5 cases), while in CFI, they were 24% and 2% (p > 0.05), res pectively. Late lung fibrosis (RTOG Grade 1-2) appeared in 20% (12 cas es), whereas 18% in CFI (p > 0.05). (c), No other severe acute or late complications have been observed so far in HART. 2. Immediate respons e. In HART, 20% of patients (12 cases) achieved CR, 60% (36 cases), PR and 20% (12 cases), NR or PD. In CFI, the above three percentages wer e 10, 28, and 62%, respectively (p < 0.001). 3. Follow-up. The 1-, 2-, and 3-year actuarial survivals were 72, 47, and 28% for HART, and 60, 18, and 6% for CFI, respectively (p < 0.001). Better local control wa s seen in HART than in CFI with 1-, 2-, and 3-year local control rates being 71, 44, 29%, and 60, 20, and 5%, respectively (p = 0.001). Dist ant metastases developed less in HART than in CFI. The 1-, 2-, and 3-y ear distant metastasis rates were 23, 36, and 50% in HART, but 30, 48, and 80% in CFI (p = 0.021). Conclusion: 1. HART could be tolerated by most of the favorable NSCLC patients. The predominant complication wa s acute esophagitis. No other severe acute or late complications have been observed so far. 2. HART resulted in better survivals and local c ontrols, and less distant metastases than CFI. (C) 1997 Elsevier Scien ce Inc.