| Objective1. To determine a method to be able to accurately register computed tomography (CT) with single photon emission computed tomography (SPECT) lung perfusion images by comparing accuracy of various registration methods.2. To explore the dose distribution difference between two intensity modulated radiotherapy (IMRT) plans with and without SPECT lung perfusion images. 3. To evaluate the feasibility of the dose escalation using SPECT lung perfusion images for the stageⅢnon-small cell lung cancer patients(NSCLC), and to determine the maximal tolerance dose(MTD) of V20 (the volume of the whole lung receiving≥20 Gy) using SPECT lung perfusion images, and to provide the dose-limited criteria for further II clinical trial.Methods and Materials1. Thoracic CT and SPECT lung perfusion images were acquired for 9 non-small cell lung cancer patients with 9 external markers attached in the thoracic region of each patient prior imaging. The CT and SPECT lung perfusion images were registered with a visual method and methods of using different numbers and combinations of the external markers based on Pinnacle3 treatment planning system. After registration, the coordinates of the 9 external markers were recorded. The registration errors were assessed by using the absolute differences in the coordinates of the 9 external markers between the two types of images.2. 32 patients with stageⅢNSCLC, who were candidated for radiotherapy, were enrolled. All patients had PET-CT scans and SPECT scans in the same treatment position. The two types of images were accurately registered using methods of the external markers based on Pinnacle3 treatment planning system. PET/CT images were used to define the gross target volume(GTV), and SPECT lung perfusion images were used to define the functional lung (FL) and the non-functional lung (NFL). Two IMRT plans were generated for each patient (Trial-1 and Trial-2). Trial-1 was generated ignoring FL, and Trial-2 was generated considering to the dose to FL of Trial-1. Both Trial-1 and Trial-2 were prescribed 60Gy at 90% isodose line.. A Paired-Samples T Test was applied to compare the differences between the two IMRT plans, and a P-value less than 0.05 was regarded as significant.3. 33 patients with stageⅢNSCLC who were candidated for radiotherapy were enrolled. All patients had PET-CT scans and SPECT scans in the same treatment position. The two types of images were accurately registered using methods of the external markers based on Pinnacle3 treatment planning system. PET/CT images were used to define the gross target volume(GTV), and SPECT lung perfusion images were used to define the functional lung (FL) and the non-functional lung (NFL). 3DCRT or IMRT plans were optimized using SPECT lung perfusion images. According to the order of the hospitalization, 8 patients were one group. The prescription doses were given according to V20=27%, 30%, 33%, 35%, 37%, respectively. The criteria for cessation of further dose escalation was that more than 25 % of patients developed Grade≥3 acute radiation pneumonitis, Grade 4 acute esophageal toxicities or Grade≥3 chronic esophageal toxicities.Results1. The registration using 9 external markers showed the largest error in the anterior-posterior direction, 2.20±2.55mm. Comparing with that using 9 external markers, the registration with the visual method, and 2, 3, and 4 external markers was significantly different, with P =0.000, 0.000, 0.000, 0.000, respectively. There was no statistical difference between the registration with 9 external markers and those with 5, 6, 7 and 8 external markers (P =0.304, 0.662, 0.678, 0.204, respectively). There was no statistical difference in three registrations using 5 external markers (P= 0.681, 0.268, 0.166, respectively). 2. Comparing with those of Trial-1, FV10 (FVX is the percentage of FL receiving dose above X Gy in FL, fllowing the same), FV20, FV30 and the mean dose FL received (DmeanFL) decreased, and there were statistical differences (P =0.000, 0.000, 0.019, 0.000, respectively); WV10 (WVX is the percentage of WL receiving dose above X Gy in WL, fllowing the same) and WV20 also decreased, and there were statistical differences (P =0.000, 0.000, respectively); NFV50 (NFV50 is the percentage of NFL receiving dose above 50 Gy in NFL) increased, and there was statistical difference (P=0.019). Comparing with those of Trial-1, the dose-volume parameters of other organs at risk of Trial-2 also changed, and there was no statistical difference (P<0.05).3. The planned dose escalation was finished in all patients, The tumor dose was (65.47±6.87) Gy. The immediate responses were CR in 3 (9.09%) patients, PR in 22 (66.67%) patients and NC in 8 (24.24%) patients. Grade 1 or 2 acute radiation pneumonitis developed in 15 (45.45%) patients; Grade 1 or 2 acute radiation esophagitis occurred in 14 (42.42%) patients; Grade 3 or 4 acute radiation pneumonitis or esophagitis didn't occurr in all patients; Grade 1, 2 or 3 myelosuppression developed in 23 (69.70%) patients; Grade 4 myelosuppression occurred in 1 (3.03%) patients; Grade 1, 2 or 3 gastrointestinal acute toxicity developed in 27 (81.82%) patients, Grade 4 gastrointestinal acute toxicity didn't occurr in all patients. 8 (24.24 %) patients developed grade 1 or 2 radiation pulmonary fibrosis, and no patients developed chronic radiation esophagus injury.Conclusions1. The CT and SPECT lung perfusion images can be accurately and reproducibly registered with errors less than 3 mm by a simple method using 5 external markers distributed on multiple plane.2. IMRT plans Optimized using SPECT lung perfusion images can reduce the dose to FL, and the dose to other organs at risk did not increase for NSCLC patients, which could potentially reduce lung toxicity and increase the dose to tumor.3. IMRT plans optimized using SPECT lung perfusion images could reduce the dose to FL significantly, while the dose to other organs at risk did not increase for NSCLC patients, which could potentially reduce lung toxicity and increase the dose to tumor. The maximum tolerated dose has yet to be reached.
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