The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to ...assess the survival benefit of adjuvant chemotherapy in this patient population.
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months 95% confidence interval (CI), 11.0 to 19.1 vs. 8.2 months 95% CI, 6.5 to 12.0; p < 0.001; and OS: median, 38.0 months 95% CI, 32.2 to not assessable vs. 25.7 months 95% CI, 18.3 to not assessable; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio HR, 0.51 95% CI, 0.36 to 0.71; p < 0.001; OS: HR, 0.45 95% CI, 0.29 to 0.71; p < 0.001).
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.
Purpose:
Hepatitis B virus infection is a well-known risk factor for intrahepatic cholangiocarcinoma. However, its prognostic impact has rarely been investigated in advanced intrahepatic ...cholangiocarcinoma.
Methods:
Between April 2010 and May 2015, 296 patients with unresectable or metastatic intrahepatic cholangiocarcinoma who received gemcitabine plus cisplatin (GemCis) were categorized into a hepatitis B virus group (n=62; 21%) and a non-hepatitis B virus group (n=234; 79%). Clinicopathological features and survival outcomes were retrospectively reviewed and analyzed.
Results:
The median age of patients was 59 years (range, 27–78). The median overall survival with first-line GemCis was 9.4 months (95% CI 8.4, 10.4). Compared to the non-hepatitis B virus group, the hepatitis B virus group was younger (median age, 57 vs. 61 years, P = 0.001), mainly male (74% vs. 57%, P = 0.02), and had lower frequency of elevated cancer antigen (CA) 19-9 (34% vs. 59%, P = 0.001) and alkaline phosphatase (43% vs. 61%, P = 0.01). In a univariate analysis, the hepatitis B virus infection showed a marginal relationship with poor overall survival compared to the non-hepatitis B virus infection (median, 8.3 vs. 10.0 months; P=0.13). A multivariate analysis of potential prognostic factors revealed a significant association with poor overall survival in the hepatitis B virus group (hazard ratio (HR) =1.50, P = 0.02). Initial metastatic disease (vs. recurrent/unresectable disease; HR=1.50), metastatic sites ⩾ 2 (vs. 0–1; HR=1.51), Eastern Cooperative Oncology Group performance status ⩾ 2 (vs. 0–1; HR=1.93), elevated total bilirubin (vs. normal; HR=1.83), and low albumin (vs. normal; HR=1.52) were significantly related to an unfavorable overall survival.
Conclusions:
This study suggests that the hepatitis B virus infection may be associated with distinctive clinicopathological characteristics and poor outcome in advanced intrahepatic cholangiocarcinoma treated with GemCis.
Purpose
To improve the efficacy of adjuvant chemotherapy with mitomycin-C and fluoropyrimidine (Mf) in gastric cancer, we designed a new regimen (iceMFP) and investigated in a phase III study.
...Methods
We randomly assigned 640 patients with resectable and macroscopically recognizable serosa-invading gastric cancer to Mf or iceMFP group during operation. The Mf consisted of intravenous mitomycin-C (20 mg/m
2
) at 3–6 weeks after surgery and oral doxifluridine (460–600 mg/m
2
/day) starting 4 weeks after the administration of mitomycin-C and continuing for 3 months. The iceMFP consisted of intraoperative intraperitoneal cisplatin (100 mg), intravenous mitomycin-C (15 mg/m
2
) on postoperative day 1, followed by oral doxifluridine for 12 months, and six monthly intravenous cisplatin (60 mg/m
2
). The primary endpoint was 3-year recurrence-free survival (RFS).
Results
A total of 521 patients (258 in Mf, 263 in iceMFP) were eligible for analysis after excluding patients with stage I disease, distant metastasis, or R1 resection. With a median follow-up of 3.5 years, the iceMFP group had a higher RFS (hazard ratio HR 0.70; 95 % confidence interval CI 0.54–0.90;
p
= 0.006; 3-year RFS 60 % vs. 50 %) and overall survival (HR 0.71; 95 % CI 0.53–0.95;
p
= 0.02; 3-year overall survival, 71 vs. 60 %) compared with the Mf group. This was confirmed at extension analysis after a median 6.6 years of follow-up. Both regimens were well tolerated with no differences in surgical complications.
Conclusion
The efficacy of adjuvant Mf was significantly improved by the additional therapeutic strategies of iceMFP. Considering negative results of AMC0201, these suggest that early initiation of chemotherapy and/or intraperitoneal cisplatin played a distinct role in the improved efficacy.
To investigate the prognostic impact of lymph node ratio (LNR) on survival in the patients with Stage III rectal cancer.
We retrospectively reviewed the data of 421 consecutive patients who underwent ...total mesorectal excision followed by chemoradiotherapy for rectal cancer from 1996 to 2006. The 232 patients with positive lymph nodes (LNs) were divided into four groups according to LNR quartiles: LNR <or=0.1 (n = 69), <or=0.2 (n = 49), <or=0.4 (n = 54), and >0.4 (n = 60). The association between LNR and survival was evaluated by the Kaplan-Meier method and multivariate analysis with covariates of prognostic significance in univariate analysis.
The median numbers of examined and positive LNs were 17 and 3, respectively, and the median LNR was 0.20 (range, 0.03-1). There was a strong correlation between the number of positive LNs and LNR (r = 0.724, p < 0.001). After a median follow-up of 53 months (range, 9-138 months), the actuarial overall survival and disease-free survival rates at 5 years were 69% and 56%, respectively. The 5-year survival rate decreased as LNR increased (<or=0.1, 89%; <or=0.2, 67%; <or=0.4, 64%; >0.4, 50%; p < 0.001). Lymph node ratio was also a significant prognostic factor on Cox regression analysis (<or=0.1, hazard ratio HR = 1; <or=0.2, HR = 1.3, p = 0.623; <or=0.4, HR = 2.4, p = 0.047; >0.4, HR = 3.7, p = 0.005). Lymph node ratio had a prognostic effect on overall survival in subgroups of patients with N1 (p = 0.032) and N2 (p = 0.034) tumors.
Lymph node ratio was the most significant predictor of survival in the patients with Stage III rectal cancer who had undergone postoperative chemoradiation.
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated ...the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval CI, 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.
Although sorafenib has shown survival benefits in patients with hepatocellular carcinoma (HCC), many patients require discontinuation or dose reduction due to adverse events (AEs). We applied a dose ...escalation scheme to increase patient compliance and avoid AEs.
Of 267 HCC patients treated with first-line sorafenib, 25 at increased risk of AEs, including those with advanced liver cirrhosis, a history of liver transplantation, or cytopenia, received the dose escalation scheme. They started on a reduced dose of sorafenib which increased to the standard dosage according to tolerance in each patient. We analyzed the efficacy and safety of the dose escalation scheme.
Patients with risk factors showed a lower disease control rate, shorter survival, and more frequently grade 3/4 AEs. Among patients presenting risk factors, the dose scheme did not affect the efficacy of sorafenib or survival, but reduced the incidence of grade 3/4 AEs. Rates of sorafenib discontinuation and dose reduction related to AEs were also lower in the dose escalation group. Dose escalation to the standard dose of sorafenib was achieved in 16 of the 25 patients in the dose escalation group (64.0%). After 2 weeks, the dose intensity of sorafenib did not differ between the two dose schemes.
The sorafenib dose escalation scheme may increase patient compliance and tolerance to prolonged treatment, thus enhancing the efficacy of sorafenib in patients at high risk of AEs or with poor tolerance. Further prospective analyses are needed to determine the usefulness of the dose escalation scheme.
To evaluate the effect of postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy and to identify the prognostic factors that influence survival in patients with ...extrahepatic bile duct cancer.
We retrospectively analyzed the data from 101 patients with extrahepatic bile duct cancer who had undergone postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy. Of the 101 patients, 52 (51%) had undergone complete resection (R0 resection) and 49 (49%) had microscopic or macroscopic residual tumors (R1 or R2 resection). The median radiation dose was 50 Gy. Also, 85 patients (84%) underwent concurrent chemotherapy with 5-fluorouracil.
The median follow-up period was 47 months for the surviving patients. The 5-year overall survival rate was 34% for all patients. A comparison between patients with R0 and R1 resection indicated no significant difference in the 5-year overall survival (44% vs. 33%, p=.2779), progression-free survival (35% vs. 22%, p=.3107), or locoregional progression-free survival (75% vs. 63%, p=.2784) rates. An analysis of the first failure site in the 89 patients with R0 or R1 resection indicated isolated locoregional recurrence in 7 patients. Elevated postoperative carbohydrate antigen 19-9 level was an independent prognostic factor for overall survival (p=.001) and progression-free survival (p=.033). A total of 3 patients developed Grade 3 or greater late toxicity.
Adjuvant concurrent chemoradiotherapy using three-dimensional conformal radiotherapy appears to improve locoregional control and survival in extrahepatic bile duct cancer patients with R1 resection. The postoperative carbohydrate antigen 19-9 level might be a useful prognostic marker to select patients for more intensified adjuvant therapy.
Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after ...progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM.
Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors.
Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy.
2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.
This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.
Data from 646 patients who underwent surgical resection at Asan Medical ...Center between 2000 and 2017 were retrospectively reviewed.
The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio HR, 0.74; 95% confidence interval CI, 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).
AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.
Summary
Background
To assess the efficacy and safety of sunitinib with regards to primary genotypes of tumor in Korean patients with advanced gastrointestinal stromal tumors (GISTs) who failed an ...initial therapy of imatinib.
Methods
Clinical data were collected from 88 consecutive patients with metastatic/unresectable GISTs treated with sunitinib at the Asan Medical Center.
Results
The median time-to-progression (TTP) and overall survival (OS) times were 7.1 months and 17.6 months, respectively. Of the 74 patients tested for
KIT
(exons 9, 11, 13, 17) and
PDGFRA
(exons 12 and 18), patients with
KIT
exon 9 mutant GIST (
n
= 11, 14.9%) showed numerically better clinical benefit (objective response or stable disease ≥24 weeks) rate (63.6% vs 46.8%,
p
= 0.504) and TTP (median 13.6 mo vs 6.9 mo,
p
= 0.631) than those with
KIT
exon 11 mutant GIST (
n
= 47, 63.5%). The most common grade 3/4 adverse events included neutropenia (34.1%), thrombocytopenia (33.0%) and hand-foot skin reaction (25.0%).
Conclusions
Sunitinib is an effective and safe second-line therapy for Korean patients with advanced GIST. The superior efficacy of sunitinib against GISTs with
KIT
exon 9 mutations appears to be similar in Korean patients to Western experience although statistical significance was not secured.
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