A PHASE-I/II STUDY TO EVALUATE ACCELERATED FRACTIONATION VIA CONCOMITANT BOOST FOR SQUAMOUS, ADENO, AND LARGE-CELL CARCINOMA OF THE LUNG - REPORT OF RADIATION-THERAPY ONCOLOGY GROUP 84-07

Purpose: A Phase I/11 trial was conducted by the Radiation Therapy Oncology Group from 1984 to 1989 for 355 evaluable patients with non-small-cell lung cancer to assess tolerance to and efficacy of accelerated fractionation irradiation via concomitant boost. Methods and Materials: ''Large'' fields (primary tumor and locoregional lymph nodes) received 1.8 Gy followed after 4 to 6 hr by 1.8 Gy two to three times weekly to reduced ''boost'' fields (primary and involved nodes only). The total doses escalated during the study and started with 63 Gy in 5 weeks (45 Gy ''large'' field and 18 Gy ''boost'') for 61 patients. After follow-up for ongoing toxicity assessment, the total dose was increased to 70.2 Gy in 5.5 weeks (50.4 Gy ''large'' field and 19.8 Gy ''boost'') for the next 180 patients. The last 114 patients received 70.2 Gy in 5 weeks (45 Gy ''large'' field and 25.2 Gy ''boost''). Results: Pretreatment patient characteristics were well balanced between the three treatment arms. Grade 3 acute toxicity was 7% for the 63 Gy arm; it was 14% and 17% for the two 70 Gy arms. Grade 4 or greater acute toxicities (esophagitis and pneumonitis) were 2 to 3% for all three arms. Late toxicities ranged between 5 and 9% (greater-than-or-equal-to Grade 3) and 0 to 2% (greater-than-or-equal-to Grade 4), not statistically different among the three arms. There was no difference between the three regimens in median survival (9 months) or 1-year survival (39 to 44%). However, the 2-year survivals ranged from 16% (63 Gy) to 21% (''shortened'' 70.2 Gy). Among 176 patients who had the same criteria as Cancer and Leukemia Group B protocol 84-33 (American Joint Committee on Cancer Staging, 1984, Stage III; Karnofsky performance status 70 to 100; < 6% weight loss), the 2-year survival rates ranged from 18 to 22%. Conclusion: Concomitant boost accelerated fractionation irradiation regimens for non-small cell lung cancer may offer improved long-term survival without enhanced late toxicity. While acute toxicity is somewhat increased, further refinement of the relationship of ''large'' to ''boost'' field doses may improve the therapeutic ratio. Further Phase I/II testing seems justified and necessary, before concomitant boost accelerated fractionation irradiation is tested in Phase III trials for NSCLC.