Neoadjuvant chemoradiation therapy for cholangiocarcinoma to improve R0 resection rate: The first report of phase II study.

Abstract

402 Background: With the much-improved surgical techniques of hepatic lobectomy, but the long-term survival of patients undergoing such surgery remains far from satisfactory. Then, to improve the prognosis of cholangiocarcinoma patients, we have applied neoadjuvant chemoradiation therapy followed by conventional resection for possibly resectable cholangiocarcinoma, named NACRAC. Here, we analyzed and evaluated the Phase II (P-2) study. Methods: Patients with histologically or cytologically confirmed adenocarcinoma of the extra- and hilar cholangiocarcinoma were enrolled from 2008 to 2013 at Department Surgery, Tohoku University Hospital. The dose of gemcitabine was determined 600mg/m2 of gemcitabine with external beam radiation therapy (1.8-Gy daily fractions to a total dose of 45 Gy) ( Hepatogastroenterology. 2011;58(112):1866-72.). The primary endpoint of P-2 is R0-resection rate. We hypothesized that R0-resection rate become from 60% to 80%. Results: Total numbers of enrolled patients were 25 cases. 22 cases were operated, and 20 cases were resected. After chemoradiation, 3 cases were not operated by liver metastases, tumor progression, and heart failure. 2 cases were not resected by peritoneal carcinomatosis. One case was diagnosed as pancreatic cancer at the final pathological diagnosis. R0-resectinn cases were 17 cases. R0 resection rate was 89.6% (17/19) among operated cases. In recruited 24 cases (A pancreatic cancer was not included), R0 resection rate was 70.8% (17/24). Grade 3 and 4 adverse events (AE) were neutropenia, leukocytopenia, and Thrombocytopenia. No grade 5 AE and no fatal AE in this P-2 study. Conclusions: Neoadjuvant chemoradiation therapy with conventional resections appears to be effective and well tolerated. After both disease free survival and overall survival are going to be fixed, we will decide a proper indication of neoadjuvant therapy for cholangiocarcinoma. Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN UMIN000000992 and UMIN000001754 Clinical trial information: 000001754.

Outcomes of neoadjuvant therapy for cholangiocarcinoma: A review of existing evidence assessing treatment response and R0 resection rate

“…Several additional retrospective studies demonstrated neoadjuvant CRT can successfully convert patients with unresectable to resectable disease and with a high R0 rate (Table 2). 25,31‐33 Meta‐analyses of these studies were done by neoadjuvant regimen. The random‐effects model suggests an overall R0 resection rate 0.81 (95% CI: 0.54, 0.94).…”

Role of adjuvant and neoadjuvant therapy for resectable biliary tract cancer

“…In the NACRAC phase I study, gemcitabine 600 mg/m 2 (days 1 and 8) for two cycles every 3 weeks plus 45 Gy of radiation therapy was reported as the recommended preoperative regimen for biliary tract cancer [35]. In NACRAC phase II study, 25 patients received the above-mentioned neoadjuvant chemoradiation and 17 patients achieved R0 resection (70.8%) [36]. The longterm follow-up data have not been published yet.…”

Chronological analysis of surgical and oncological outcomes after the treatment of perihilar cholangiocarcinoma

“…[22][23][24][25] Recently, studies on neoadjuvant therapy have been conducted as a bridge modality to improve the rate of radical resection of locally advanced hilar cholangiocarcinoma. [26][27][28] In view of these trends, especially those from 2000, the impact of surgical skills and methods remains important; however, the perioperative support and management are also thought to contribute to the oncological outcomes in patients with hilar cholangiocarcinoma.…”