Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: Update of a phase I trial

Purpose: High-dose radiation may improve outcomes in non-small-cell lung ca ncer (NSCLC), By using three-dimensional conformal radiation therapy and li miting the target volume, we hypothesized that the dose could be safely esc alated, Materials and Methods: A standard phase I design was used. Five bins were c reated based on the volume of normal lung irradiated, and dose levels withi n bins were chosen based on the estimated risk of radiation pneumonitis. St arting doses ranged from 63 to 84 Gy given in 2.1-Gy fractions. Target volu mes included the primary tumor and any nodes greater than or equal to1 cm o n computed tomography, Clinically uninvolved nodal regions were not include d purposely. More recently, selected patients received neoadjuvant cisplati n and vinorelbine. Results: At the time of this writing, 104 patients had been enrolled. Twent y-four had stage I, four had stage II, 43 had stage IIIA, 26 had stage IIIB , and seven had locally recurrent disease. Twenty-five received chemotherap y, and 63 were assessable for escalation. All bins were escalated at least twice. Although grade 2 radiation pneumonitis occurred in five patients, gr ade 3 radiation pneumonitis occurred in only two. The maximum-tolerated dos e was only established for the largest bin, at 65.1 Gy, Dose levels for the four remaining bins were 102.9, 102.9, 84 and 75.6 Gy. The majority of pat ients failed distantly, though a significant proportion also failed in the target volume. There were no isolated failures in clinically uninvolved nod al regions. Conclusion: Dose escalation in NSCLC has been accomplished safely in most p atients using three-dimensional conformal radiation therapy, limiting targe t volumes, and segregating patients by the volume of normal lung irradiated . J Clin Oncol 19:127-136. (C) 2001 by American Society of Clinical Oncolog y.