Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis

摘要

A retrospective analysis was performed on the medical records of 119 patients with lung cancer treated between June 2009 and September 2013. The inclusion criteria were patients (i) with pathologically confirmed lung cancer, (ii) who were receiving chest radiotherapy for the first time, (iii) who had no treatment interruptions of longer than 5 days during radiotherapy, and (iv) who survived at least 6 months from the beginning of radiotherapy. Patients were excluded if (i) the follow-up time was less than 6 months or (ii) they received a second round of chest radiotherapy after recurrence. Of the 119 patients, 17 were excluded because they survived for less than 6 months, 8 were excluded because they received a second round of chest radiotherapy after recurrence, 6 were lost to follow-up and 5 were followed-up for less than 6 months. The median volume of the primary tumor was 64.2 cm3 (4.2–428.5 cm3), the median fractionated dose was 2.1 Gy (2.0–2.5 Gy) and the median equivalent dose at 2 Gy per fraction (EQD2) was 59.9 Gy (42.4–73.5 Gy). The dose limits for the organs at risk were as follows: bilateral lung, define (V20) ≤ 37% and MLD ≤ 20 Gy; spinal cord, maximum dose ≤ 45 Gy; heart, V40 ≤ 40%; and esophagus, V50 ≤ 50%. Lung was defined to exclude the gross target volume (GTV). The collapsed cone convolution was chosen for the treatment planning. All patients received 5-beam 6-MV X-ray IMRT, delivered by a linear accelerator (Clinac 600C/D; Varian Medical Systems, Palo Alto, CA, USA), with one fraction per day and five fractions per week. Seventy-two patients received induction chemotherapy; 11 patients did not receive induction chemotherapy. Patients with non–small cell carcinoma received a paclitaxel, docetaxel or gemcitabine plus platinum regimen; patients with small cell carcinoma received a VP-16 plus cisplatin regimen. Twelve patients received concurrent chemotherapy; of these cases, patients with non–small cell carcinoma received single agent paclitaxel or docetaxel chemotherapy and patients with small cell carcinoma received a VP-16 plus cisplatin regimen. Forty-four patients received adjuvant chemotherapy; of these cases, patients with non–small cell carcinoma received a regimen with paclitaxel, docetaxel or gemcitabine plus platinum or not, and patients with small cell carcinoma received a VP-16 plus cisplatin regimen. A dose–volume histogram (DVH) related to the treatment planning system (TPS, Pinnacle3; Philips Medical Systems, Andover MA) was used to calculate the normal lung volume receiving greater than 5, 10, 20 and 30 Gy (V5, V10, V20, V30), MLD, and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5, AVS10, AVS20, AVS30) of the bilateral lung and the ipsilateral lung. The symptoms of the patients were reviewed weekly during radiotherapy. The symptoms and the lung CT images were reviewed 3–4 weeks after completion of treatment, every 2–3 months in the first two years, and at 6-month intervals during the third to fifth year. RILI was assessed and graded according to the RTOG criteria [7]. Chi-squared tests or Student's t-tests were used for univariate analysis of the association of clinical factors or dose–volume parameters with the occurrence of RILI. Pearson's correlation analysis was performed to examine the colinearity of the AVS5 of ipsilateral lung and quantitative indicators. Student's t-test analysis was performed to examine the correlation between the AVS5 of the ipsilateral lung and qualitative indicators. Logistic regression analysis was used to identify the factors associated with RILI; receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of the significant factors for predicting RILI. Chi-squared tests were used to examine the rates of RILI occurrence. P 0.05 was considered significant for all analysis. The software of SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. The median follow-up time for the entire cohort was 12.3 months (6.1–52.0 months). Of the 83 patients with lung cancer who received IMRT, 56 patients (67.5%) developed Grade ≤ 1 RILI, 18 patients (21.7%) developed Grade 2 RILI, 7 patients (8.4%) developed Grade 3 RILI, 2 patients (2.4%) developed Grade 4 RILI, and no patients developed Grade 5 RILI. Univariate analysis showed that the lobe in which the primary tumor was located was associated with the occurrence of Grade ≥2 RILI (P 0.05; Table 1). Additionally, there were significant associations between the occurrence of Grade ≥2 RILI and the V5, V10, V20 and MLD of the ipsilateral lung, the V5, V10, V20, V30 and MLD of the bilateral lung, and the AVS5 and AVS10 of the ipsilateral lung (all P 0.05; Table 2). The occurrence of Grade ≥2 RILI in lung cancer patients receiving IMRT could be predicted with a sensitivity of 60.7% and a specificity of 70.4% on the basis of the AVS5 of the ipsilateral lung using an area under the R