| 抄録 |
Rationale：The treatment of patients with locally advanced pancreatic ductal adenocarcinoma（PDAC）varies, with some advocating prompt surgery, usually with vascular resection and others employing a brief course of neoadjuvant therapy followed by operation. At UCLA, we have used the latter approach, but employed a more prolonged course of preoperative treatment（6-10 months）than commonly used. Here we present the results of that experience.
Design：This is a retrospective study of 49 consecutive patients with AJCC stage III PDAC, initially unresectable, who received protracted neoadjuvant treatment and were then resected.
Results：All 49 patients had vascular involvement（PV/SMV）. After completing preoperative chemotherapy for a median of 7.1 months（5.4-9.6）, a majority（76%）underwent a pylorus-preserving Whipple operation；only 3 patients（6%）required a vascular resection. Three quarters of the patients（37/49）were lymph node negative（N0）, 86%（42/49）had negative margins（R0）, and 46% of evaluable patients had a complete histopathologic（HP）response. The overall median survival（OS）was 40.1 months（22.7-65.9）. Univariate analysis of HP prognostic biomarkers revealed that perineural invasion（PNI, HR 5.5, P=0.007）and HP treatment response（HR 9.0, P=0.009）were most significant. LN involvement, as a marker of systemic disease, was also significant on univariate analysis（P=0.047）. Patients with N0 disease had longer OS（44.4 vs. 23.2 months, P=0.04）than N1 patients. SMAD4 protein loss（P=0.01）in tumor cells and microRNA-21 expression in the stroma（P=0.049）also correlated with OS. On MVA of HP and prognostic biomarkers, only SMAD4 protein loss was significant（HR 9.3, P=0.004）.
Conclusions：Prolonged neoadjuvant therapy in this select group of patients with Stage III PDAC was associated with a high incidence of N0 and R0 disease and excellent OS. This suggests that the longer course of preoperative treatment effectively obliterates much of the microscopic disease, and may be preferred to the standard 3-4 month treatment now more commonly employed. |
