The influence of field size and other treatment factors on pulmonary toxicity following hyperfractionated irradiation for inoperable non-small cell lung cancer (NSCLC)-analysis of a radiation therapy oncology group (RTOG) protocol

Abstract

Purpose : The risk of pulmonary toxicity, observed in an Radiation Therapy Oncology Group Phase I/II randomized dose escalation trial of hyperfractioned irradiation for nonsmall cell lung cancer, was analyzed with regard to custom vs.hand blocking and compliance to protocol specified treatment field parameters. Materials and Methods : There were 832 evaluable cases analyzed. The protocol required field margins 2 cm beyond primary tumor and involved nodes. In 674, the field margins were considered “per protocol” or as having minor protocol variations. In 94, margins exceeded protocol specification (“excessive margin” group). In this group, the area (cm 2) of the effective (blocked) field and the portion including lung was measured from simulator films with a computer scanning device. Based on size and location of the primary and nodal disease, “per protocol” fields were constructed and the area (cm 2) of lung included beyond these margins was estimated. Patients from both groups who received less than 30 Gy to normal lung were excluded from analysis of pulmonary toxicity. Results : Grade 1 acute lung toxicity was higher ( p = .009) in the “excessive margin” group compared to the “per protocol” group, whereas late lung toxicity was not significantly different ( p = .94). The risk of Grade 2 or greater acute toxicity increased as area of excess irradiated lung increased. Overall lung toxicity, defined as the greater of either acute or late toxicity, was evaluated by multivariate analysis, in relation to assigned dose, effective treated field area, and type of shielding. Overall maximum lung toxicity (≥ Grade 2) was significantly greater in the “excessive margin” group, when lung treated beyond protocol margins exceeded an area of 35 cm 2, than in the “per protocol” group, but only when the effective treated field size was ≥ 180 cm 2 (68% vs. 37%; p = .02). This effect was independent of assigned total dose or type of shielding. Conclusion : For nonsmall cell lung cancer treated with hyperfractionated irradiation, the risk of overall pulmonary toxicity was increased for patients treated with field sizes in excess of protocol specified margins of tumor coverage in comparison to patients treated with protocol specified margins. This effect was seen only when the area of lung treated beyond protocol margins exceeded 35 cm 2 and when the overall field size was below 180 cm 2.