The Clinical Outcomes Of Stereotactic Body Radiotherapy For Pulmonary Oligometastases And The Dosimetric Effects For The Radiation-induced Fibrosis

Objective(1)To assess the clinical outcomes and prognostic factors of stereotactic body radiotherapy(SBRT)for pulmonary oligometastases and to further explore which patients are more suitable for SBRT.(2)To explore the clinical and dosimetric effects for the radiation-induced fibrosis after pulmonary stereotactic body radiotherapy.Method(1)A total of 51 patients with 76 oligometastatic lung tumors were treated withSBRT.42 patients received one course of SBRT(35 patients with solitary nodule,4patients with 2 nodules,3 patients with 3 nodules),7 patients received 2 courses of SBRT(6 patients with solitary nodule,1 patients with 2 nodules),2 patients received 4 courses of SBRT(all solitary nodule).Primary tumor was lung cancer in 27 patients,and 24 cases of patients were extrapulmonary tumor including.gastrointestinal tumor in 11 patients,gynecological tumors in 6 patients,bladder tumor,head and neck,mediastinal tumors in 2 patients respectively,breast tumor in 1 case.7 patients were squamous carcinoma,35 adenocarcinoma,9 other pathogic types.44 tumors performed 50Gy in five fractions,17 tumors a dose of 60Gy in three fractions and 15 tumors a dose of 30-60Gy in 2-8 fractions(3a dose of 40Gy in 5 fractions,4 a dose of 40Gy in 2 fractions,2 a dose of 45Gy in 3 fractions,2 a dose of 42Gy in 7 fractions,1 a dose of 60Gy in 8 fractions,54Gy in 3 fractions,30Gy in 3 fractions and 40Gy in 4 fractions respectively).The median size was 4.4 cm3(0.2-65cm3).The median follow-up was 24.5 months(2-57months).(2)91 lesions in 71 consecutive patients including the 20 primary lung cancer and 51 metastatic lung cancer used by stereotactic body radiotherapy.There were total 20 patients diagnosed lung fibrosis.The follow-up computed tomography(CT)were evaluated at approximately 3,6,12,18 and 24 months after treatment.The relationship between the lung fibrosis and dose curve was speculated by using the increasing CT number compared the pre-SBRT to the post-SBRT in the fibrosis legion.By using the NTCP(normal tissue complication probability)model,the relationship for the lung mean dose(MLD)and fibrosis was estimated.We also revealed the correlations between the clinical,dose values and fibrosis used Logistics regression analysis.Results(1)The complete response was observed in 35.5%(27to76),partial response in 50%(38to76),stable disease in 9.2%(7to76)and progressive disease 5.3%(4to76).The effective rate was 85.5%(65to76).The local contral rate at 1 and 2 year was 85.5%(65to76)and 80.3%(61to76),overall survival 80.4%(41to51)and 54.9%(28to51).The median survival time was 30 months,while median progressive-free survival time was 8 months.Toxicity profiles were within acceptable range,with 21 case of grade 1,1 case of grade 2 pneumonitis and 12 pulmonary fibrosis.Univariate analysis by subgroup showed that the GTV size and dose-fraction modality were not associated with overall survival(P>0.05)But the multivanriate analysis revealed that ECOG performance status,the number of lung oligometastses and progression-free interval were the independent factors for predicting the overall survival(P<0.05).(2)There was a significant peak of the CT number at the time of 35 Gy.It was the most apparent at 6 months and was in stable at 12 months.By using the Equivalent Dose in 2 Gy per fraction(EQD2),the MLD was switched to the biological effective dose(BED)(?/?=3).The NTCP was calculated with the mathematical formula and then made the diagraph for the MLD and NTCP.It showed the MLD was related to the fibrosis from the diagraph.The univariate logistic regression analysis showed the V15,V17.5,V20,V22.5,V25,V27.5,V30,V32.5,V35,V40 and MLD was associated with fibrosis.But multiple logistic regression analysis showed the lung fibrosis correlated only with V35 and MLD.Conclusions(1)The SBRT for pulmonary oligometastases is an effective and safe local treatment option.Choosing the right patients and the appropriate timing of treatment is the key to ensuring the efficacy of SBRT.(2)The V35 and MLD was related with the lung fibrosis after pulmonary stereotactic body radiotherapy.