Background and Aims: The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node–positive extrahepatic cholangiocarcinoma. Approach and Results: Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m², cisplatin 25 mg/m² on days 1 and 8) or capecitabine (1250 mg/m² twice daily on days 1–14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1. Between July 2017 and November 2020, 101 patients (50 in the GemCis and 51 in the capecitabine group) were included in the intention-to-treat population. Perihilar and distal bile ducts were the primary sites in 45 (44.6%) and 56 (55.4%) patients, respectively, and 32 (31.7%) had R1 resections. Median (1-sided 90% CI) follow-up duration was 33.4 (30.5–35.8) months. In the GemCis and capecitabine group, 2-year disease-free survival rates were 38.5% (29.5%–47.4%) and 25.1% (17.4%–33.5%) [HR=0.96 (CI, 0.71–1.30), p=0.430], and median overall survival was 35.7 months (29.5–not estimated) and 35.7 months (30.9–not estimated) [HR=1.08 (CI, 0.71–1.64), 1-sided p=0.404], respectively. Grade 3–4 adverse events occurred in 42 (84.0%) and 8 patients (16.0%) in the GemCis and capecitabine groups, respectively. No treatment-related deaths were reported. Conclusions: In resected lymph node–positive extrahepatic cholangiocarcinoma, adjuvant GemCis did not improve survival outcomes compared with capecitabine.

The clinical benefit and potential risks of conversion surgery after neoadjuvant chemotherapy (NACT) have not been fully investigated in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). Therefore, this has been evaluated in a retrospective, prospective cohort-based analysis. Between October 2005 and April 2017, 135 patients (65 with BRPC and 70 with LAPC) received conversion surgery after NACT. Exploratory analysis to assess clinical outcomes in comparison with patients who underwent upfront surgery in the same time period (n = 359) was also conducted. NACT with gemcitabine-based regimens (including gemcitabine monotherapy, gemcitabine-capecitabine combination, and gemcitabine-erlotinib combination) was used in 69 patients (51%) and FOLFIRINOX in 66 patients (49%). The median overall survival (OS) and disease-free survival (DFS) from the time of surgery was 25.4 months (95% CI, 18.6–32.2 months) and 9.0 months (95% CI, 6.8–11.2 months), respectively. The median OS and progression-free survival from the initiation of NACT was 29.7 months (95% CI, 22.5–36.8 months) and 13.4 months (95% CI, 12.5–14.4 months), respectively. In the exploratory analysis, conversion surgery after NACT was associated with a better median OS and DFS than upfront surgery (vs. 17.1 months; 95% CI, 15.5–18.7 months; p = 0.001 and vs. 7.1 months; 95% CI, 6.4–7.8 months; p = 0.005, respectively). There was no difference in length of hospital stay between the two groups, and conversion surgery after NACT showed a significantly lower incidence of postoperative complications than upfront surgery (38% vs. 27%, p = 0.03). Conversion surgery after NACT is a feasible and effective therapeutic strategy for the treatment of patients with BRPC and LAPC. Further clinical trials investigating optimal therapeutic strategies for BRPC and LAPC are warranted.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis even after curative resection. A deep learning-based stratification of postoperative survival in the preoperative setting may aid the treatment decisions for improving prognosis. This study was aimed to develop a deep learning model based on preoperative data for predicting postoperative survival. The patients who underwent surgery for PDAC between January 2014 and May 2015. Clinical data-based machine learning models and computed tomography (CT) data-based deep learning models were developed separately, and ensemble learning was utilized to combine two models. The primary outcomes were the prediction of 2-year overall survival (OS) and 1-year recurrence-free survival (RFS). The model's performance was measured by area under the receiver operating curve (AUC) and was compared with that of American Joint Committee on Cancer (AJCC) 8th stage. The median OS and RFS were 23 and 10 months in training dataset (n = 229), and 22 and 11 months in test dataset (n = 53), respectively. The AUC of the ensemble model for predicting 2-year OS and 1-year RFS in the test dataset was 0.76 and 0.74, respectively. The performance of the ensemble model was comparable to that of the AJCC in predicting 2-year OS (AUC, 0.67; P = 0.35) and superior to the AJCC in predicting 1-year RFS (AUC, 0.54; P = 0.049). Our ensemble model based on routine preoperative variables showed good performance for predicting prognosis for PDAC patients after surgery.

Han JH, et al. Ann Hepatobiliary Pancreat Surg. 2018 Nov;22(4):359-366. https://doi.org/10.14701/ahbps.2018.22.4.359

We aimed to examine the predictive value of changes in perioperative carbohydrate antigen (CA) 19-9 levels for patients operated for perihilar cholangiocarcinoma (pCCA). A total of 322 patients who underwent curative resection for pCCA were divided into three groups: normal preoperative CA19-9 (CA19-9 ≤ 37 U/mL), normalization (preoperative CA19-9 > 37 U/mL, postoperative CA19-9 ≤ 37 U/mL), and non-normalization (pre- and postoperative CA19-9 > 37 U/mL) groups. The association of clinicopathological factors with overall survival (OS) was investigated. The non-normalization group (n = 82) demonstrated significantly worse OS than the normal CA19-9 (n = 114) and normalization (n = 126) groups (5-year OS, 16.9%, 29.4%, and 34.4%, respectively; both p ≤ 0.001). The cutoff points of 300 U/mL for preoperative (p = 0.001) and 37 U/mL for postoperative (p < 0.001) CA19-9 levels showed the strongest prognostic values. In the non-normalization group, patients who underwent R1 resection displayed significantly worse OS than those who underwent R0 resection (median OS, 10.2 vs. 15.7 months; p = 0.016). Multivariate analysis revealed that lymph node metastasis (hazard ratio (HR), 2.07; p < 0.001), postoperative CA19-9 > 37 U/mL (HR, 1.94; p < 0.001), transfusion (HR, 1.74; p = 0.002), and T stage (T3,4) (HR, 1.67; p = 0.006) were related to worse OS. Persistent high CA19-9 level after resection of pCCA and R1 resection, especially in the non-normalization group, was associated with poor OS. A high postoperative CA19-9 level was an independent prognostic factor in resected pCCA.