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 (
= 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;
= 0.001 and vs. 7.1 months; 95% CI, 6.4⁻7.8 months;
= 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%,
= 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.
The optimal prognostic markers for neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer are not yet established.
Patients who received neoadjuvant ...chemotherapy prior to surgery and underwent FDG-PET/CT between July 2012 and December 2017 were included. Metabolic parameters including standardized uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) on PET/CT, and response evaluations using PERCIST criteria, were investigated for its impact on survival and recurrence. Cox proportional hazards model was performed. Differences in risk were expressed as hazard ratio (HR) with 95 per cent confidence interval.
The patients with borderline resectable (N = 106) or locally advanced pancreatic cancer (N = 82) were identified. The median survival was 33.6 months. Decreased metabolic parameters of PET/CT after neoadjuvant chemotherapy were associated with positive impacts on survival and recurrence such as SUVmax (HR 1.16, 95 per cent c.i. 1.01 to 1.32, P = 0.025), SUVpeak (HR 1.26, 95 per cent c.i. 1.05 to 1.51, P = 0.011), and MTV (HR 1.15, 95 per cent c.i. 1.04 to 1.26, P = 0.005). Large delta values were related to a positive impact on recurrence such as SUVmax (HR 1.21, 95 per cent c.i. 1.06 to 1.38, P = 0.005). Post-neoadjuvant chemotherapy SUVmax ≥3 (HR 3.46, 95 per cent c.i. 1.21 to 9.91; P = 0.036) was an independent prognostic factor for negative impact on survival. Patients with post-neoadjuvant chemotherapy SUVmax <3 showed more chemotherapy cycles (8.7 versus 6.2, P = 0.001), more frequent complete metabolic response (25 versus 2.2 per cent, P = 0.002), smaller tumour size (2.1 versus 3.1 cm, P = 0.002), and less frequent lymphovascular invasion (23.7 versus 51.1 per cent, P = 0.020) than patients with SUVmax ≥3.
Reduction in metabolic tumour parameters of FDG- PET/CT after neoadjuvant chemotherapy indicates improved overall survival and recurrence-free survival.
Summary It has been reported that HER2 expression is different in gastric and breast cancers, and a gastric cancer scoring system (GCSS) has recently been suggested. We investigated HER2 protein ...expression using GCSS and a breast cancer scoring system (BCSS) and correlated it with HER2 gene amplification. HER2 status was evaluated in 1091 cases by analyzing tissue microarrays constructed using 2 different cores from each case. Polyclonal (HercepTest) and monoclonal (Pathway) antibodies were used for immunohistochemistry (IHC), and results were scored by BCSS and GCSS. Gene amplification was evaluated by automated dual-color silver-enhanced in situ hybridization (SISH) in all cases and correlated with the results from fluorescence in situ hybridization (FISH) in 590 cases. The concordance between the IHC results using polyclonal and monoclonal antibodies was high ( κ = 0.785). The results of dual-color SISH and FISH showed very high concordance as well ( κ = 0.918). GCSS was significantly more sensitive for detecting SISH positivity than was BCSS in both antibodies (polyclonal, P = .003; monoclonal, P < .001), but specificity was higher in BCSS than GCSS (polyclonal, P = .004; monoclonal, P < .001). It has been recently shown that HER2-overexpressing patients with unresectable gastric cancer benefited from trastuzumab therapy. Because IHC is recommended before gene amplification studies in HER2 testing, GCSS should be used for evaluating HER2 expression in gastric cancers.
Summary
Background Nab
-paclitaxel plus gemcitabine (AG) is standard first-line chemotherapy for patients with metastatic pancreatic cancer (mPC). However, prognostic factors for patients with mPC ...treated with AG, are largely unknown. We retrospectively identified prognostic factors, including inflammation-based prognostic scores, in patients with mPC, and recurrent pancreatic cancer treated with AG as first-line treatment.
Method
A total of 203 patients with histologically-confirmed recurrent or metastatic pancreatic cancer who were treated with first-line AG in Asan Medical Center, Seoul, Korea, between February 2016 and December 2016 were included in this analysis. As inflammation-based scores, baseline neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and modified Glasgow prognostic scores (mGPS) were tested.
Result
Median age was 62 years and 116 patients (57%) were male. With median follow-up duration of 21.5 months, median progression-free survival (PFS) was 7.1 (95% CI 6.2–7.9) months, and overall survival (OS) was 15.1 (95% CI 12.6–17.6) months. In the multivariate analysis, PFS was significantly associated with liver metastasis (HR 1.43), distant lymph node metastasis (HR 1.48), and elevated CA19–9 (HR 1.56). In multivariate analysis for OS, elevated CA19–9 (HR 1.75), liver metastasis (HR 1.76), distant lymph node metastasis (HR 1.41), and high mGPS (mGPS ≥1 vs.0: HR 1.64) were independent prognostic factors. NLR and PLR were not significantly associated with PFS and OS.
Conclusion
Among the inflammation based prognostic scores, mGPS was a reliable prognostic indicator that could stratify survival outcomes in patients with recurrent or mPC who received AG as first-line chemotherapy
.
Background:
Despite the scarcity of data based on randomized trials, FOLFIRINOX is widely used in the management of borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable ...pancreatic cancer (LAPC). We investigated the clinical outcomes of neoadjuvant FOLFIRINOX in patients with BRPC and LAPC.
Methods:
This single-center retrospective analysis included a total of 199 consecutive patients with BRPC or LAPC who received conventional or modified FOLFIRINOX between February 2013 and January 2017. An independent radiologist reviewed all baseline computed tomography or magnetic resonance imaging scans were reviewed for vascular invasion status.
Results:
With median follow-up duration of 40.3 months 95% confidence interval (CI), 36.7–43.8 in surviving patients, median progression-free survival (PFS) and overall survival (OS) were 10.6 (95% CI, 9.5–11.7) and 18.1 (95% CI, 16.0–20.3) months, respectively. The 1-year PFS rate was 66.0% (95% CI, 65.3–66.7%), and the 2-year OS rate was 37.2% (95% CI, 36.5–37.9%). PFS and OS did not differ between BRPC and LAPC groups median PFS, 11.1 months (95% CI, 8.8–13.5) versus 10.1 months (95% CI, 8.4–11.8), p = 0.47; median OS, 18.4 months (95% CI, 16.1–20.8) versus 17.1 months (95% CI, 13.2–20.9), p = 0.50. Curative-intent conversion surgery (R0/R1) was performed in 63 patients (31.7%). C•A 19-9 response, objective tumor response to FOLFIRINOX, and conversion surgery were independent prognostic factors for OS.
Conclusion:
FOLFIRINOX was effective for management of BRPC and LAPC. Given the potential for cure, a significant proportion of patients can undergo conversion curative-intent surgery following FOLFIRINOX.
Purpose
Biliary tract cancer (BTC) is a heterogeneous group of diseases comprising intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer. Although gemcitabine plus cisplatin ...(GEMCIS) was established as the standard first-line chemotherapy based on the ABC-02 trial, more data are needed to define the clinical course of BTC and its prognostic factors with the standard GEMCIS treatment.
Methods
Between April 2010 and June 2016, 740 patients with histologically documented cholangiocarcinoma and gallbladder cancer were treated with first-line GEMCIS in Asan Medical Center, Seoul, Korea.
Results
In 389 patients with measurable disease (53%), the objective response rate was 13% (
n
= 50) and there was no significant difference between primary tumor sites (
p
= 0.45). With a median follow-up duration of 27.3 months (95% CI 24.2–30.5), the median PFS and OS were 5.2 months (95% CI 4.7–5.6) and 10.4 months (95% CI 9.6–11.2), respectively. In multivariate analysis, male gender (female versus male, hazard ratio HR 0.83), baseline CA 19-9 level (elevated versus normal, HR 1.31), initially metastatic disease (versus locally advanced disease, HR 1.92), poor performance status (2 versus 0–1, HR 1.45), and measurable disease by RECIST criteria (versus non-measurable, HR 1.40) were significantly associated with a poorer OS (all
p
< 0.05).
Conclusions
Our retrospective analysis of a large number of patients in a real-world setting found comparable efficacy outcomes to the ABC-02 trial. The prognostic factors identified here may help to predict clinical outcomes and design future clinical trials for advanced BTC.
Aim: It remains unclear whether capecitabine combined with cisplatin would show similar effects compared with standard therapy using gemcitabine and cisplatin in advanced biliary tract cancer (BTC).
...Methods: Patients with advanced BTC who were treated with first‐line chemotherapy at Asan Medical Center were retrospectively analyzed. All patients received either cisplatin followed by gemcitabine on days 1 and 8 every 3 weeks (GP group), or capecitabine on days 1–14 with cisplatin on day 1 every 3 weeks (XP group).
Results: Of the 134 patients who met the inclusion criteria, 78 received XP and 56 were treated with GP. After a median follow‐up of 26.2 months, the progression‐free survival was 5.7 months for XP versus 4.1 months for GP (hazard ratio HR = 0.81, P = 0.31). The overall survival (OS) was 11.0 months for XP versus 9.8 months for GP (HR = 0.84, P = 0.36). In the multivariate analysis, there were no significant differences in PFS and OS between the two groups.
Conclusion: XP seems to be as effective as GP in patients with advanced BTC. The XP regimen is feasible and might offer increased convenience regarding the schedule of drug administration.
In locally advanced pancreatic cancer (LAPC), stereotactic body radiation therapy (SBRT) has been applied as an alternative to concurrent chemoradiotherapy (CCRT); however, direct comparative ...evidence between these two modalities is scarce. The aim of this study was to compare the clinical outcomes of SBRT with CCRT for LAPC. We retrospectively reviewed the medical records of patients with LAPC who received SBRT (
= 95) or CCRT (
= 66) with a concurrent 5-FU-based regimen between January 2008 and July 2016. The clinical outcomes of freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS), and toxicities were analyzed before and after propensity score (PS) matching. After a median follow-up duration of 15.5 months (range, 2.3-64.5), the median OS, PFS, and FFLP of the unmatched patients were 17.3 months, 11 months, and 19.6 months, respectively. After PS matching, there were no significant differences between the SBRT and CCRT groups in terms of the 1-year rates of OS (66.7% vs. 80%,
= 0.455), PFS (40.0% vs. 54.2%,
= 0.123), and FFLP (77.2% and 87.1%,
= 0.691). Our results suggest SBRT could be a feasible alternative to CCRT in treating patients with LAPC.
Imatinib plasma trough levels (C(min)) have been reported to correlate with treatment outcomes in patients with gastrointestinal stromal tumors (GISTs). We therefore have evaluated the correlation ...between imatinib C(min) and the clinical characteristics of patients with GIST.
Steady-state imatinib C(min) in 107 patients with GIST who were taking imatinib 300 to 800 mg/d was measured.
In patients treated with imatinib 400 (n = 92), 300 (n = 7), 600 (n = 2), or 800 (n = 11) mg/d, imatinib C(min) was 1,305 +/- 633 ng/mL, 1,452 +/- 830 ng/mL, 1,698 +/- 725 ng/mL, and 3,330 +/- 1,592 ng/mL, respectively. Of the 92 patients treated with 400 mg/d imatinib, 59 patients (63%) were men; the median age was 55 years (range, 28 to 76 years), and the median duration of imatinib use before sampling was 8.8 months (range, 0.5 to 67.6 months). The mean inter- and intrapatient variability rates were 44.7% and 26.5%, respectively. In univariate analyses, high C(min) was correlated with advanced age (P = .02), low creatinine clearance (P = .001), low hemoglobin (P = .03), and low albumin (P < .001) concentrations. Imatinib C(min) was also significantly lower in patients with (n = 18; 942 +/- 330 ng/mL) than without (n = 74; 1,393 +/- 659 ng/mL) major (ie, total or subtotal) gastrectomy (P = .002). In multivariate analysis, albumin (P = .001) concentrations, creatinine clearance (P = .002), and major gastrectomy (P = .003) were significantly correlated with C(min).
In patients with GIST, imatinib C(min) at steady state was significantly associated with albumin concentration, creatinine clearance, and previous major gastrectomy. Although its clinical impact is unclear at present time, monitoring of imatinib C(min) might be particularly important for optimal treatment with imatinib in patients who have undergone major gastrectomy.
To determine whether concurrent pyridoxine therapy can prevent the development of hand-foot syndrome (HFS) in patients being treated with capecitabine.
Chemotherapy-naive patients with GI tract ...cancers scheduled for capecitabine-containing chemotherapy were randomly assigned to concurrent oral pyridoxine (200 mg/d) or placebo. Patients were stratified by chemotherapy regimen and monitored until development of National Cancer Institute Common Toxicity Criteria grade 2 or worse HFS or capecitabine-containing chemotherapy ended. Patients in the placebo group who developed grade 2 or worse HFS were randomly assigned again to receive pyridoxine or placebo in the next chemotherapy cycle to determine whether pyridoxine could improve HFS.
The median number of chemotherapy cycles to grade 2 or worse HFS was three in both groups. Grade 2 or worse HFS developed in 55 (30.6%) of 180 placebo-treated patients and in 57 (31.7%) of 180 pyridoxine patients. The cumulative dose of capecitabine to grade 2 or worse HFS was not different between the two groups (median not reached in either group; hazard ratio HR = 0.95; P = .788). Randomization of the 44 patients in the placebo group with grade 2 or worse HFS to placebo or pyridoxine for the next cycle resulted in no significant difference in the proportion showing improvement of HFS (42.9% v 47.8%; HR = 1.12; P = .94). By multivariate analysis, age > or = 56 years (HR = 1.768; 95% CI, 1.190 to 2.628; P = .005) was an independent risk factor for grade 2 or worse HFS, and combined use of docetaxel (HR = 2.046; 95% CI, 0.880 to 4.755; P = .096) was of borderline significance.
Pyridoxine is not effective in prevention of capecitabine-associated HFS.
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