Influence of combined treatment sequence of stereotactic body radiation therapy and chemotherapy on the survival of very elderly patients with locally advanced pancreatic cancer / 中华胰腺病杂志

ABSTRACT

Objective To investigated the influence of different combined treatment sequence of stereotactic body radiation therapy (SBRT) and chemotherapy (CT) on the survival of very elderly patients with locally advanced pancreatic cancer ( LAPC) .Methods The data of LAPC patients ≥60 years old treated by CyberKnife SBRT at Shanghai Changhai Hospital from January 2012 to December 2016 was retrospectively analyzed.According to treatment sequences , patients were divided into three groupsCT+SBRT group ( first chemotherapy and then SBRT ) , SBRT+CT group ( first SBRT and then chemotherapy ) and CT+SBRT+CT group ( first chemotherapy , then SBRT and finally chemotherapy ) .Patients were recommended to receive a 6-month chemotherapy .Intravenous administration of 1000 mg/m2 gemcitabine was initiated on day 1, 8, and 15 every 4 weeks or S-1 was orally given at a dose of 80 mg/m2 for 28 days followed by a 14-day rest , which repeated for 6 cycles.Radiotherapy parameters the median total prescription dose was 36(30-45)Gy; the median per fraction dose was 7(5-9)Gy;the median number of fractions was 5(5-8) fractions;the median biological equivalent dose (BED10) were 61.92(48-85.5) Gy, respectively.The interval between SBRT and chemotherapy ranged from 2 to 3 weeks.Patients were followed every 3 months.The main outcome measures were overall survival ( OS) and median progression free survival ( PFS) .Second outcome measure was adverse events.Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) was employed to evaluate adverse events , and RTOG/EORTC was used to assess the adverse events of radiotherapy .Overall survival (OS) and PFS were calculated by Kaplan-Meier method.Univariate and multivariate logistic regression model were used to analyze the independent risk factors .Results A total of 260 patients were enrolled in the study , including 28 patients treated with CT+SBRT, 163 patients undergoing SBRT +CT and 69 patients treated with CT+SBRT+CT.The median OS and PFS were 13.2(95％CI 12.8-13.6)months and 8.2(95％CI 7.7-8.7)months, respectively.OS in CT +SBRT, SBRT +CT and CT +SBRT +CT group was 12.2 (10.9-13.9),13.4 ( 12.9-13.9 ) and 13.1 ( 12.7-13.5 ) months, and the differences were not statistically significant(P=0.425).PFS in CT+SBRT, SBRT+CT and CT+SBRT+CT group was 6.4(5.9-6.9), 8.3(7.8-8.8) and 8.2(7.2-9.2)months, and the differences were statistically significant (P=0.008).In univariate analysis , ECOG, SIRI, the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In multivariate analysis, the CA19-9 response and BED10 were independent factors for OS . Multivariate analysis showed that the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In CT+SBRT group, patients had lower ECOG score (χ2 =115.325,P<0.001) and earlier clinical staging (χ2 =24.788, P<0.001 ).In SBRT +CT group, patients had advanced staging (χ2 =159.759,P<0.001) and lymph node metastasis(χ2 =40.925,P<0.001).Only 1 patient experienced grade 3 radiotherapy associated duodenitis .The adverse events of patients who were first treated by chemotherapy included grade 3 neutropenia in 4 patients and grade 3 gastrointestinal reaction in 5 patients.The adverse events of patients who were first treated by radiotherapy included grade 3 neutropenia or/and leucopenia in 18 patients and grade 3 abdominal pain, nausea or vomit in 16 patients.The adverse events of CT +SBRT+CT patients included grade 3 neutropenia or/and leucopenia in 4 patients and grade 3 abdominal pain or nausea in 5 patients.There was no grade ≥4 adverse events.Conclusions For very elderly patients with LAPC , the survival of patients who received pre-SBRT chemotherapy , post-SBRT chemotherapy and pre-and post-SBRT chemotherapy was comparable , but SBRT+CT group and CT +SBRT+CT group had longer PFS than CT +SBRT group.