| Objective: To evaluate prospectively the different clinical target volume (CTV) margins by analyzing the patterns of primary failure, prognosis and toxicities after three dimensional conformal radiotherapy (3DCRT) for patients with thoracic esophageal squamous cell carcinoma (SCC) and to analyze the prognostic factors of 3DCRT for patients with thoracic esophageal SCC in order to clarify the CTV margin suitable for 3DCRT for esophageal SCC. The irradiation dose to the lungs and spinal cord in different CTVs was also evaluated.Methods: From May 2006 to October 2007, 60 patients with thoracic esophageal SCC for definitive radiotherapy were included in this study. All the patients received 3DCRT. They were grouped into N0 group (with the enlargement of lymph node and N1 group (without the enlargement of lymph node) according to the CT before radiotherapy respectively. Then they were randomized into the elective nodal irradiation group and involved nodal irradiation group respectively. There were 30 patients in each group. In involved nodal irradiation group, the GTV was defined as any visible tumor on the image. The CTV was defined as the GTV plus a 3-cm margin superior and inferior to the primary tumor and a 0.8-1.0 cm radial margin. The PTV was defined as the CTV plus a 1.0-cm longitudinal margin and a 0.5-cm radial margin. The involved lymphatic region was also included in the CTV. The PTV1 was defined as GTV plus a 1.5cm margin superior and inferior to the primary tumor and a 0.8-1.0 cm radial margin, and also the involved lymphatic region. In the elective nodal irradiation group, the GTV, PTV and PTV1 were defined the same as that in the involved nodal irradiation group. Besides the same margins outside the primary tumor as that in the involved nodal irradiation group, the adjacent regional lymphatics was included in the CTV according to the different location of the primary tumor. The prescribed dose to PTV was 50 Gy in 5 weeks followed by 10 to 12Gy to PTV1. A complete blood test was taken every week during the treatment, and once at the end of treatment. The tumor response was assessed at one month after the end of treatment, and acute radiation esophagitis was assessed twice a week during treatment, once a month in the first three months after radiotherapy, and once every months subsequently. Acute and late toxicities were graded according to the RTOG criteria (1995).Results: (1) The tumor response rates were same in the two groups and were 96.67% in elective nodal irradiation group and involved nodal irradiation group respectively. No statistical difference was found in the two groups (P>0.05). (2) Prognostic factors affecting the survival rate: The 6-month and 12-month overall survival rates were 79.04% and 58.02%, 76.08% and 53.14% respectively in the involved nodal irradiation group and the elective nodal irradiation group. To eliminate the effect of N stage on prognosis, we compared the survival rates for patients who had the same stage of disease but were treated with different CTVs: For patient of N0 stage, The 6-month and 12-month survival rates were 90.91% and 60.61%, 85.71% and 42.86% respectively in the involved nodal irradiation group and the elective nodal irradiation group; And For patient of N1 stage, the 6-month and 12-month survival rates were 72.55% and 55.28%, 72.05% and 53.37% respectively in the involved nodal irradiation group and the elective nodal irradiation group. The 6-month and 12-month survival rates were 87.41% and 68.84%, 68.59% and 50.22% respectively in≤5cm group and>5cm group. The patients were divided into two groups according to the median volume of 40cm3. The 6-month and 12-month survival rates were 96.15% and 75.55%, 59.0% and 38.04% respectively in≤40cm3 group and≥40cm3 group with a statistical difference (P=0.0004). In Cox multivariate analysis, GTV volume before radiotherapy was an independent factor for the overall survival. While The CTV size had no effect on the overall survival. (3) Prognostic factors affecting locoregional control rate: The 6-month and 12-month locoregional control rate were 85.92% and 85.92%, 83.47% and 64.59% respectively in the involved nodal irradiation group and the elective nodal irradiation group. To eliminate the effect of N stage on prognosis, we compared the locoregional control rates for patients who had the same stage of disease but were treated with different CTVs. For patient of N0 stage, The 6-month and 12-month locoregional control rates were 87.80% and 87.80%, 78.00% and 65.75% respectively in the involved nodal irradiation group and the elective nodal irradiation group; And For patient of N1 stage, the 6-month and 12-month locoregional control rates were 82.54% and 82.54%, 74.90% and 66.58% respectively in the involved nodal irradiation group and the elective nodal irradiation group. N0 statistical difference was found between the two groups. In Cox multivariate analysis, CT-T stage and GTV volume before radiotherapy were the independent factors for locoregional control rate. T stage had the tendency to improve the local control. The CTV had no effect on the locoregional control rate. (4) Prognostic factors affecting progression-free survival rate: The 6-month and 12-month progression-free survival rates were 70.83% and 63.75%, 69.56% and 53.83% respectively in the involved nodal irradiation group and the elective nodal irradiation group. The 6-month and 12-month progression-free survival rates were 81.43% and 67.86%, 64.57% and 55.04% respectively in the CT-N0 group and the CT-N1 group. (5) Toxicities during and after Radiotherapy: Radiation esophagitis rate was 56.67%(17/30)and 63.33%(19/30)respectively in the involved nodal irradiation group and the elective nodal irradiation group. It was higher in the elective nodal irradiation group than that in the involved nodal irradiation group. But no statistical difference was found between the two groups(P=0.488). The symptomatic radiation pneumonitis of the elective nodal irradiation group was higher than that of the involved nodal irradiation group. No statistical difference was found in the two groups either (P =0.488). The morbidity of gastrointestinal toxicities such as nausea and vomiting in the elective nodal irradiation group was higher than in the involved nodal irradiation group (P=0.014). (6) The comparison of dosimetry: The V10,V20,V30 and the mean dose of the lungs in the elective nodal irradiation group were higher than those in the involved nodal irradiation group. And the maximum dose and the mean dose to the spinal cord were higher in the elective nodal irradiation group than those in the involved nodal irradiation group. (7) Patterns of failures: The total failure rate in the study was 30.00% (18/60). Locoregional failure alone was 20.00%(6/30)and 26.67%(8/30) respectively for the involved nodal irradiation group and the elective nodal irradiation group .About 13.33 % of esophageal SCC patients relapsed duo to distant metastasis. There was only one patient in the involved nodal irradiation group with regional failure outside the CTV.Conclusion: (1) Conformal radiotherapy with elective nodal irradiation for thoracic esophageal SCC showed no significant advantage over the conformal radiotherapy with the involved nodal irradiation in overall survival, locoregional control and progression-free survival.(2)Conformal radiotherapy with elective nodal irradiation conferred a higher radiation esophagitis,pneumonitis and higher morbidity of gastrointestinal toxicities compared to conformal radiotherapy with involved nodal irradiation. (3) Volume of GTV before radiotherapy was an independent factor for overall survival and locoregional control rate. (4) Dose to lungs and spinal cord was higher with elective nodal irradiation than that with involved nodal irradiation. |
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