Summary Background D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient ...outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II–IIIB gastric cancer. Methods The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II–IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m2 twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m2 on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov ( NCT00411229 ). Findings 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4–41·7) in the chemotherapy and surgery group and 34·3 months (25·6–41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69–79) in the chemotherapy and surgery group and 59% (53–64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44–0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). Interpretation Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. Funding F Hoffmann-La Roche and Sanofi-Aventis.
Summary Background The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned ...interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. Methods CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II–IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m2 twice daily on days 1–14 plus intravenous oxaliplatin 130 mg/m2 on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov , NCT00411229. Findings We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54–70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio HR 0·58, 95% CI 0·47–0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63–73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47–58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51–0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74–82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64–73) in the observation group. Adverse event data were not collected after the primary analysis. Interpretation Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer. Funding F Hoffmann La-Roche and Sanofi.
Aim
Much attention has been paid to conversion therapy for stage IV gastric cancer, however, its operative comorbidities and survival benefit have not yet been clarified. CONVO‐GC‐1, an international ...retrospective cohort study, was designed to investigate the role of conversion surgery in Japan, Korea, and China.
Methods
The rate of operative complications was the primary endpoint and the overall survival (OS), according to the four‐category criteria previously published (Gastric Cancer:19; 2016), was analyzed as the secondary endpoint.
Results
A total of 1206 patients underwent surgery after chemotherapy with curative intent. Operative complications were observed in 290 (24.0%) patients in all grades, including pancreatic fistula and surgical site infection. The median survival time (MST) of all resected patients was 36.7 mo (M) and those of R0, R1, and R2 resection were 56.6 M, 25.8 M, and 21.7 M, respectively. Moreover, the MST of R0 patients were 47.8 M, 116.7 M, 44.8 M in categories 1, 2, and 3, respectively, and not reached in category 4. Interestingly, the MST of P1 patients was as favorable as that of P0CY1 patients if R0 resection was achieved. The MST of patients with liver metastasis was also favorable regardless of the number of lesions, and the MST of patients with para‐aortic lymph node (LN) No 16a1/b2 metastasis was not inferior to that of patients with para‐aortic LN No 16a2/b1 metastasis.
Conclusion
Conversion therapy for stage IV gastric cancer is safe and could be a new therapeutic strategy to improve the survival of patients, especially those with R0 resection.
R0 resection of conversion therapy can be a new strategy for gastric cancer.
Although the incidence of inflammatory bowel disease IBD is increasing in Asia, data on long-term epidemiological trends are limited. We performed a 30-year longitudinal study to investigate temporal ...trends in the epidemiology of Crohn's disease CD and ulcerative colitis UC in Seoul, Korea.
This population-based study included 1431 IBD patients 418 CD, 1013 UC diagnosed between 1986 and 2015 in the Songpa-Kangdong district of Seoul, Korea. Temporal trends in incidence, prevalence, and disease phenotype at diagnosis were analysed.
The adjusted mean annual incidence rates of CD and UC per 100 000 inhabitants increased from 0.06 (95% confidence interval CI, 0.05-0.07) and 0.29 95% CI, 0.27-0.31, respectively, in 1986-1990 to 2.44 95% CI, 2.38-2.50 and 5.82 95% CI, 5.73-5.92, respectively, in 2011-2015. Average annual percentage change in IBD incidence was 12.3% in 1986-1995, 12.3% in 1996-2005, and 3.3% in 2006-2015. The male-to-female ratio of the adjusted incidence rate was 3.3:1 for CD and 1.2:1 for UC. Perianal fistula/abscess was present in 43.3% of patients before or at CD diagnosis. At diagnosis, 54.3% of UC patients presented only with proctitis. The adjusted prevalence rate in 2015 was 31.59/100 000 95% CI, 31.10-32.07 for CD and 76.66/100 000 95% CI, 75.91-77.42 for UC.
The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Korean patients have distinct demographic and phenotypic characteristics, including a male predominance and high frequency of perianal fistula/abscess in CD and high proportion of proctitis in UC.
Background and Aims Perforation is the adverse event of greatest concern during colorectal endoscopic submucosal dissection (ESD). Accurate risk prediction of perforation may enable prevention ...strategies and selection of the most efficient therapeutic option. This study aimed to develop and validate a risk prediction model for ESD-induced perforation. Methods A multicenter cross-sectional study was performed on 2046 patients who underwent colorectal ESD at 9 Korean ESD Study Group–affiliated hospitals. The enrolled patients were randomly divided into either a derivation set or a validation set. In the derivation set, a prediction score was constructed to assess the risk of perforation using preoperative and procedural-related predictors selected via logistic regression. Discrimination and calibration of the prediction model was assessed using the validation set. Results An ESD-induced perforation occurred in 135 patients (6.6%). In the derivation set, multivariate logistic regression identified endoscopist experience (≥50 ESDs: odds ratio OR = 0.59; 95% confidence interval CI, 0.35-1.00), tumor size (+1-cm increments: OR = 1.39; 95% CI, 1.19-1.62), colonic location (OR = 2.20; 95% CI, 1.24-3.89), and submucosal fibrosis (OR = 2.00; 95% CI, 1.04-3.87) as predictive factors (C-statistic = 0.678; 95% CI, 0.617-0.739). In the validation set, the model showed good discrimination (C-statistic = 0.675; 95% CI, 0.615-0.735) and calibration ( P = .635). When a simplified weighted scoring system based on the OR was used, risk of perforation ranged from 4.1% (95% CI, 2.8%-5.9%) in the low-risk group (score ≤4) to 11.6% (95% CI, 8.5%-15.6%) in the high-risk group (score >4). Conclusions This study developed and internally validated a score consisting of simple clinical factors to estimate the risk of colorectal ESD-induced perforation. This score can be used to identify patients at high risk before colorectal ESD.
In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable ...gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value.
We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials. Prognostic analyses used multivariable Cox models (MVM). The predictive role of MSI was assessed both in an all-comer population and in MAGIC and CLASSIC trials by MVM testing of the interaction of treatment (chemotherapy plus surgery
surgery) with MSI.
MSI status was available for 1,556 patients: 121 (7.8%) had MSI-high status; 576 were European, and 980 were Asian. In MSI-high versus MSI-low/microsatellite stable (MSS) comparisons, the 5-year disease-free survival (DFS) was 71.8% (95% CI, 63.8% to 80.7%) versus 52.3% (95% CI, 49.7% to 55.1%); the 5-year overall survival (OS) was 77.5% (95% CI, 70.0% to 85.8%) versus 59.3% (95% CI, 56.6% to 62.1%). In MVM, MSI was associated with longer DFS (hazard ratio HR, 1.88; 95% CI, 1.28 to 2.76;
< .001) and OS (HR, 1.78; 95% CI, 1.17 to 2.73;
= .008), as were pT, pN, ethnicity, and treatment. Patients with MSI-low/MSS GC benefitted from chemotherapy plus surgery: the 5-year DFS compared with surgery only was 57% versus 41% (HR, 0.65; 95% CI, 0.53 to 0.79), and the 5-year OS was 62% versus 53% (HR, 0.75; 95% CI, 0.60 to 0.94). Conversely, those with MSI-high GC did not: the 5-year DFS was 70% versus 77% (HR, 1.27; 95% CI, 0.53 to 3.04), and the 5-year OS was 75% versus 83% (HR, 1.50; 95% CI, 0.55 to 4.12).
In patients with resectable primary GC, MSI is a robust prognostic marker that should be adopted as a stratification factor by clinical trials. Chemotherapy omission and/or immune checkpoint blockade should be investigated prospectively in MSI-high GCs according to clinically and pathologically defined risk of relapse.
No population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based ...cohort.
This Korean population-based, Songpa-Kangdong IBD cohort included all patients (n=1013) newly diagnosed with UC during 1986-2015. Disease outcomes and their predictors were evaluated.
During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines and antitumour necrosis factor (anti-TNF) agents was 40.8%, 13.9% and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20 and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1% and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (HR 8.249, 95% CI 2.394 to 28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440 to 28.773) and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057 to 0.886) were independent predictors of colectomy. The standardised mortality ratio in patients with UC was 0.725 (95% CI 0.508 to 1.004).
Korean patients with UC may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.
AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancer (GC), especially Epstein-Barr virus (EBV)-associated and microsatellite instability high GC. The loss of ARID1A ...expression has been reported as a poor prognostic marker in GC. However, the relationships between ARID1A alteration and EBV-associated and microsatellite instability high GC, which are known to have a favorable prognosis, has hampered proper evaluation of the prognostic significance of ARID1A expression in GC. We aimed to analyze the true prognostic significance of ARID1A expression by correcting confounding variables.
We evaluated the ARID1A expression in a large series (n=1,032) of advanced GC and analyzed the relationships between expression pattern and variable parameters, including clinicopathologic factors, key molecular features such as EBV-positivity, mismatch repair protein deficiency, and expression of p53 and several receptor tyrosine kinases including human epidermal growth factor receptor 2, epidermal growth factor receptor, and mesenchymal-epithelial transition factor. Survival analysis of the molecular subtypes was done according to the ARID1A expression patterns.
Loss of ARID1A expression was found in 52.5% (53/101) of mutL homolog 1 (MLH1)-deficient and 35.8% (24/67) of EBV-positive GCs, compared with only 9.6% (82/864) of the MLH1-proficient and EBV-negative group (p<0.001). The loss of ARID1A expression was associated only with MLH1 deficiency and EBV positivity. On survival analysis, the loss of ARID1A expression was associated with worse prognosis only in MLH1-proficient and EBV-negative GC. Multivariate analysis revealed that both loss of ARID1A and decreased ARID1A expression were independent worse prognostic factors in patients with advanced GC.
Only in MLH1-proficient and EBV-negative GC, the loss of ARID1A expression is related to poorer prognosis.
Background
Initial experiences with robotic gastrectomy (RG) for gastric cancer have demonstrated favorable short-term outcomes, suggesting that RG is an effective alternative to laparoscopic ...gastrectomy (LG). However, data on long-term survival and recurrence after RG for gastric cancer have yet to be reported. The objective of this study was to assess long-term outcomes after RG compared with LG.
Methods
We retrospectively evaluated 313 and 524 patients who underwent RG or LG, respectively, for gastric cancer between July 2005 and December 2009. We compared long-term outcomes using the entire and a propensity-score matched cohort.
Results
The entire cohort analysis revealed no statistically significant differences in 5-year overall survival(OS) or relapse-free survival(RFS) (
p
= 0.4112 and
p
= 0.8733, respectively): 93.3% 95% confidence interval (CI) 89.9–95.6 and 90.7% (95% CI, 86.9–93.5) after RG and 91.6% (95% CI 88.9–93.7) and 90.5% (95% CI 87.6–92.7) after LG, respectively; hazard ratios for death and recurrence in the robotic group were 0.828 (95% CI, 0.528–1.299;
p
= 0.4119) and 0.968 (95% CI, 0.649–1.445;
p
= 0.8741), respectively. The propensity-matched cohort analysis demonstrated no statistically significant differences for 5-year OS or RFS (
p
= 0.5207 and
p
= 0.2293, respectively): 93.2% and 90.7% after RG and 94.2% and 92.6% after LG, respectively; hazard ratios for death and recurrence in the robotic group were 1.194 (95% CI, 0.695–2.062;
p
= 0.5214) and 1.343 (95% CI, 0.830–2.192;
p
= 0.2321), respectively.
Conclusion
The potential technical superiority of robotic system over laparoscopy did not improve oncological outcomes after gastrectomy. Long-term oncological outcomes were not different between RG and LG. Nevertheless, robotic applications in minimally invasive gastric cancer surgery may be an oncologically safe alternative.
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