A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Clinicopathological features and outcome of type 3 gastric neuroendocrine tumours.

BACKGROUND: With the widespread use of endoscopy, small and low-grade type 3 gastric neuroendocrine tumours (NETs) are increasingly being detected. The clinicopathological features, biological behaviour and appropriate treatment strategy for these NETs remain unclear. METHODS: Patients with biopsy-proven gastric NET and a normal fasting serum gastrin level were identified from a prospectively maintained database. Clinicopathological features and long-term outcome of local resection for type 3 NETs were reviewed retrospectively and compared according to tumour grade. RESULTS: Some 32 patients with type 3 gastric NETs were included (25 patients with NET grade G1, 5 with G2 and 2 with G3). Pathological tumour size was 2·0 cm or less in 30 patients. All tumours were well differentiated, even G3 lesions, and all tumours but one were confined to the submucosal layer. G1 NETs were significantly smaller and had a significantly lower lymphovascular invasion rate than G2 and G3 NETs. Twenty-two patients with a G1 NET without lymphovascular invasion were treated with wedge or endoscopic resection. After a median follow-up of 59 (range 6-102) months, no patient with a G1 NET of 1·5 cm or smaller developed recurrence and one patient with a G1 NET larger than 1·5 cm had recurrence in a perigastric lymph node. Among seven patients with a G2 or G3 NET, two had lymph node metastasis and one had liver metastases. CONCLUSION: Low-grade type 3 gastric NET has non-aggressive features and a favourable prognosis. Wedge or endoscopic resection may be a valid option for patients with type 3 gastric G1 NET no larger than 1·5 cm without lymphovascular invasion.

Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients.

Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples. Results: Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications. Conclusions: The present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.

Clinical significance of skip lymph node metastasis in gastric cancer patients.

PURPOSE: Given the recent increase in the incidence of early gastric cancer, there is greater interest in identifying a minimally invasive therapy. The purpose of this study was to analyze the patterns of lymph node metastasis in patients with gastric cancer and to elucidate the clinical significance of skip metastasis. METHODS: We retrospectively analyzed patterns of lymph node metastasis (LNM) and clinicopathologic factors related to skip metastasis. RESULTS: Among 2963 patients with gastric cancer, 997 patients (33.6%) were detected as having LNM, and 27 patients (2.7%) with skip metastasis were detected among 997 patients with LNM. Skip metastasis were detected more frequently in the elderly. Compared with the N1 group, the skip metastasis group showed lower frequency of vascular invasion, and compared with the stepwise N2 group, the skip metastasis group showed smaller tumor size and a significantly higher incidence of negative lymphatic, vascular, and perineural invasion. CONCLUSIONS: Currently there is no way to predict N2 station LNM including skip metastasis, D2 LN dissection for gastric cancer is thought to be the appropriate treatment, even during early stage disease. Minimally invasive therapy should be performed cautiously in consideration of possible skip metastasis.

Impairment of the proximal to distal tonic gradient in the human diabetic stomach.

BACKGROUND: Little has been known about the contractile characteristics of diabetic stomach. We investigated spontaneous contractions and responses to acetylcholine in the gastric muscle in diabetic patients and non-diabetic control subjects according to the region of stomach. METHODS: Gastric specimens were obtained from 26 diabetics and 55 controls who underwent gastrectomy at Samsung Medical Center between February 2008 and November 2011. Isometric force measurements were performed using circular muscle strips from the different regions of stomach under basal condition and in response to acetylcholine. KEY RESULTS: Basal tone of control was higher in the proximal stomach than in the distal (0.63 g vs 0.46 g, p = 0.027). However, in diabetics, basal tone was not significantly different between the proximal and distal stomach (0.75 g vs 0.62 g, p = 0.32). The distal stomach of diabetics had higher basal tone and lower frequency than that of control (0.62 g vs 0.46 g, p = 0.049 and 4.0/min vs 4.9/min, p = 0.049, respectively). After exposure to acetylcholine, dose-dependent increases of basal tone, peak, and area under the curve (AUC) were noticed in both proximal and distal stomach of the two groups. In the proximal stomach, however, the dose-dependent increase of basal tone and AUC was less prominent in diabetics than in control. CONCLUSIONS & INFERENCES: On the contrary to control, the proximal to distal tonic gradient was not observed in diabetic stomach. Diabetic stomach also had lower frequency of spontaneous contraction in the distal stomach and less acetylcholine-induced positive inotropic effect in the proximal stomach than control.

Predictive factors for lymph node metastasis in patients with poorly differentiated early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection is gaining popularity in the treatment of early gastric cancer. This study aimed to identify clinicopathological factors predictive of lymph node metastasis in patients with the poorly differentiated early gastric cancer to assess the feasibility of using endoscopic submucosal dissection for these cancers. METHODS: The records of patients with poorly differentiated early gastric cancer who had undergone gastric cancer surgery between January 2002 and December 2009 were reviewed. Associations between clinicopathological factors and the presence of lymph node metastasis were analysed by univariable and multivariable logistic regression analysis. RESULTS: Some 1005 patients were included in the analysis. Univariable analysis indicated that lymph node metastasis was associated with sex, ulceration, tumour size, depth of invasion, macroscopic type, lymphatic invasion and venous invasion. Logistic regression revealed that lymph node metastasis was significantly associated with sex, tumour size, depth of tumour invasion and lymphatic involvement. In the group with none of these risk factors (men with mucosal tumour no larger than 2 cm in size, with no lymphatic involvement), lymph node metastasis was present in four (3·2 per cent) of 124 patients. CONCLUSION: In the present study 3·2 per cent of patients who were negative for all identified risk factors had lymph node metastasis. The use of endoscopic submucosal dissection should be considered carefully in the treatment of poorly differentiated early gastric cancer.

Comparison of cystatin C- and creatinine-based estimation of glomerular filtration rate according to glycaemic status in Type 2 diabetes.

AIMS: The influence of hyperglycaemia on the performance of glomerular filtration rate (GFR) estimating equations remains to be determined. We compared the performance of creatinine-based GFR with cystatin C-based GFR in patients with Type 2 diabetes according to glycaemic status. METHODS: In a cross-sectional study of 210 patients with Type 2 diabetes, we staged glycaemic status by HbA(1c) tertiles [HbA(1c) ≤ 75 mmol/mol (9.0%) (n = 70), HbA(1c) 76-95 mmol/mol (9.1-10.8%) (n = 70), HbA(1c) >95 mmol/mol (10.8%) (n = 70)] and measured GFR. Isotopic GFR was measured using renal dynamic imaging with (99m) Tc-diethylene-triamine-penta-acetic acid. Estimated GFR (eGFR) was measured using creatinine-based formulae (Cockcroft-Gault-eGFR, the Modification of Diet in Renal Disease equation-eGFR and the Chronic Kidney Disease Epidemiology Collaboration formula-eGFR) and a cystatin C-based formula (cystatin C-eGFR). RESULTS: The isotopic GFR of all patients was 93.1 ± 34.1 ml min(-1) 1.73 m(-2). All methods for estimating GFR underestimated isotopic GFR [Cockcroft-Gault-eGFR (68.8 ± 38.6 ml min(-1) 1.73 m(-2) ) (P < 0.05), Modification of Diet in Renal Disease-eGFR (74.8 ± 31.3 ml min(-1) 1.73 m(-2) ) (P < 0.05), Chronic Kidney Disease Epidemiology Collaboration-eGFR (72.9 ± 26.6 ml min(-1) 1.73 m(-2)) (P < 0.05) and cystatin C-eGFR (83.5 ± 33.2 ml min(-1) 1.73 m(-2)) (P < 0.05)]. In all patient groups, cystatin C-eGFR was less biased and more accurate than the creatinine-based formulae, especially in the group with HbA(1c) > 95 mmol/mol (10.8%) where there was no difference between cystatin C-eGFR and isotopic GFR. CONCLUSIONS: Performance of cystatin C-eGFR was superior to creatinine-based GFR in patients with Type 2 diabetes with HbA(1c) >95 mmol/mol (10.8%).

Surgical outcome after incomplete endoscopic submucosal dissection of gastric cancer.

BACKGROUND: Endoscopic resection of early gastric cancer is a relatively new and attractive treatment, but occasionally fails to remove all cancer lesions completely. This study aimed to elucidate clinicopathological factors that could be helpful in predicting residual tumour in the surgical specimen after incomplete endoscopic submucosal dissection (ESD). METHODS: Patients who underwent gastrectomy because of incomplete ESD between August 2004 and August 2008 were analysed. Clinicopathological characteristics were reviewed retrospectively from prospectively collected medical records. Patients were classified into groups with and without residual tumour. Pathology results following gastrectomy were compared with those of incomplete ESD. RESULTS: A total of 118 patients were included. The incidence of residual tumour in the surgical specimen was 24·6 per cent after incomplete ESD. Elevated/flat-type cancers, large tumours (at least 2 cm) and those limited to the mucosa had significantly higher incomplete ESD rates. Cancer limited to the mucosa and the presence of tumour in the lateral margin were associated with residual tumour in the surgical specimen (both P = 0·001). CONCLUSION: Radical gastrectomy should be performed if pathological examination reveals a positive lateral resection margin after ESD.

Decreased expression of p12 is associated with more advanced tumor invasion in human gastric cancer tissues.

BACKGROUND/AIMS: p12(DOC-1) is a well-known growth suppressor; however, its role in gastric carcinogenesis is still unclear. We investigated the expression of p12(DOC-1) in gastric cancer tissues and its possible correlation with p53 expression, and determined its clinical significance. METHODS: Immunohistochemical staining using the tissue array method was performed on 180 human gastric carcinomas. The clinicopathological features and prognostic significance were analyzed. RESULTS: Of the 180 tissue samples, p53 expression was positive in 85 (47.2%) and p12(DOC-1) expression was negative in 140 (77.8%). The negative expression of p12(DOC-1) was significantly associated with a more advanced depth of tumor invasion and stage (p < 0.05). No apparent correlation was found between p12(DOC-1) and p53 expressions. The 5-year survival rate of the p12(DOC-1)-positive cases (53.7%) was higher than that of the p12(DOC-1)-negative cases (39.3%); however, neither p12(DOC-1) nor p53 expression status had any statistically significant prognostic value. Multivariate analysis revealed that lymph node metastasis, distant metastasis, lymphatic invasion and perineural invasion were independent prognostic factors. CONCLUSIONS: This is the first report that suggests that p12(DOC-1) may be involved in the development and progression of gastric cancer. Further studies are required to clarify its exact role in the mechanism of gastric carcinogenesis.

Employment status and work-related difficulties in stomach cancer survivors compared with the general population.

Little was known about work situation and work-related difficulties, including housework after stomach cancer diagnosis. We aimed to compare employment status and work-related difficulties between stomach cancer survivors and the general population. We enrolled 408 stomach cancer survivors from two hospitals 28 months after diagnosis and 994 representative volunteers from the general population from 15 geographic districts. Working was defined as being employed (including self-employed) and nonworking as being retired or a homemaker. Nonworking was significantly higher among stomach cancer survivors (46.6%) than in the general population (36.5%). Compared with the general population, the survivors had more fatigue in performing both housework (adjusted odds ratio (aOR)=2.08; 95% confidence interval (95% CI)=1.01-4.29) and gainful work (aOR=4.02; 2.55-6.33). More cancer survivors had reduced working hours (aOR=1.42; 95% CI=4.60-28.35) and reduced work-related ability (aOR=6.11; 95% CI=3.64-10.27) than did the general population. The association of nonworking with older age and being female was significantly more positive for survivors than for the general population. Among survivors, poorer Eastern Cooperation Oncology Group Performance Status and receiving total gastrectomy were positively associated with nonworking. Stomach cancer survivors experienced more difficulties in both housework and gainful employment than did the general population. Our findings on stomach cancer survivors' work-related difficulties and the predictors of nonworking will help physicians guide patients towards more realistic postsurgical employment plans.

Indication for endoscopic mucosal resection in early signet ring cell gastric cancer.

BACKGROUND: The aim of this study was to compare the clinicopathological characteristics of an early signet ring cell carcinoma (SRC) with an early undifferentiated carcinoma (mucinous, poorly differentiated adenocarcinoma) and early differentiated carcinoma (well or moderately differentiated tubular adenocarcinoma, papillary adenocarcinoma) and find indications for endoscopic mucosal resection (EMR) in early SRC. METHODS: 1520 patients with early gastric cancer (EGC), who underwent a curative gastrectomy, were analyzed retrospectively. Among them, 388 patients with SRC were compared with 253 patients with undifferentiated carcinoma (UDC) and 879 with a differentiated carcinoma (DC). RESULTS: SRC was more common in young female patients than UDC. SRC had a tendency to be confined to the mucosa, with smaller size than UDC. The lymph node metastasis rate for SRC was lower than that for UDC, but similar to that of DC. Multivariate analysis revealed lymph node metastasis (LNM) to be associated with the depth of invasion, tumor size, histological type, and lymphatic involvement. SRC had no LNM in the case of a mucosal tumor, smaller than 2 cm, and in the absence of lymphatic involvement. The prognosis of SRC was more favorable than UDC. CONCLUSIONS: Early SRC has different characteristics from early UDC. In view of the lower rate of lymph node metastasis and better prognosis, we suggest that EMR can be performed on patients with early SRC limited to the mucosa, less than 2cm in size, and with no lymphatic involvement.

Gastric GIST: a single institutional retrospective experience with surgical treatment for primary disease.

AIMS: Because gastric GISTs show variable clinical behavior, we reviewed our experience with primary gastric GISTs after surgical treatment and imatinib mesylate treatment for advanced disease. METHODS: Between December 1995 and December 2005, 111 patients who underwent surgical treatment for primary gastric GISTs were enrolled in this study. Patients were grouped according to the risk assessment classification, and clinicopathological features, tumor recurrence and patient survival were assessed. RESULTS: One patient was included in the very low risk group, 35 in the low risk group, 31 in the intermediate risk group and 44 in the high-risk group. All patients with very low, low and intermediate risk GISTs and 70% of patients with high risk GISTs underwent R0 resection. While there was no recurrence or metastasis in patients with very low, low and intermediate risk GISTs, 23% of those with high risk GISTs showed a distant metastasis at diagnosis and 35% of these patients had a recurrence after R0 resection. The overall 5-year survival rate of the high risk patients was 77.1%. Nineteen patients received imatinib mesylate therapy due to an incomplete resection or recurrence; 7 with no measurable lesion at the CT scan by a local tumor control showed no tumor progression after imatinib mesylate therapy, however, 12 patients with measurable lesions showed variable clinical courses after treatment. The overall 5-year survival rate of 19 patients with imatinib mesylate treatment was 80.0%. CONCLUSIONS: The clinical outcome of the very low, low and intermediate risk gastric GISTs was excellent, while high risk gastric GISTs had a high rate of recurrence and therefore a less favorable outcome. A complete resection is the most important treatment for cure; however imatinib mesylate treatment may improve the clinical outcome of the patients with metastatic or recurrent gastric GISTs.

Prognostic model to predict survival following first-line chemotherapy in patients with metastatic gastric adenocarcinoma.

BACKGROUND: This study was to devise a prognostic model for metastatic gastric cancer patients undergoing first-line chemotherapy. PATIENTS AND METHODS: A retrospective analysis was carried out on 1455 gastric cancer patients, who received first-line chemotherapy from September 1994 to February 2005. RESULTS: At multivariate level, poor prognostic factors were no previous gastrectomy [P = 0.003; relative risk (RR), 1.191; 95% confidence interval (CI) 1.061-1.338], albumin < 3.6 g/dl (P = or <0.001; RR, 1.245; 95% CI 1.106-1.402), alkaline phosphatase > 85 U/l (P = or <0.001; RR, 1.224; 95% CI 1.092-1.371), Eastern Cooperative Oncology Group performance status of two or more (P = or <0.001; RR, 1.690; 95% CI 1.458-1.959), the presence of bone metastases (P = 0.001; RR, 1.460; 95% CI 1.616-1.836), and the presence of ascites (P = or < 0.001; RR, 1.452; 95% CI 1.295-1.628). Of 1434 patients, 489 patients (34.1%) were categorized as low-risk group (zero to one factors), 889 patients (62.0%) as intermediate-risk group (two to four factors), and 56 patients (3.9%) as high-risk group (five to six factors). Median survival durations for low, intermediate, and high-risk groups were 12.5 months, 7.0 months, and 2.7 months, respectively. CONCLUSIONS: This model should facilitate the individual patient risk stratification and thus, more appropriate therapies for each metastatic gastric cancer patient.

Primary malignant retroperitoneal tumors: analysis of a single institutional experience.

AIMS: In order to achieve complete resection in the surgical management of retroperitoneal tumors, it is crucial to know the tumor's anatomical location relative to neighboring organs. METHODS: Forty-nine patients with primary malignant retroperitoneal tumors were divided by tumor location into two groups [upper abdomen (group 1) or lower abdomen (group 2)], and clinicopathological features, tumor recurrence, and patient survival were assessed. RESULTS: No significant differences in preoperative clinical characteristics existed between two groups, and liposarcoma was the most frequently observed tumor type. The difference in the rates of complete resection between the two groups was not statistically significant (75.9% for group 1 and 85% for group 2). En-bloc combined resection was performed in 52% and 30% of patients in groups 1 and 2, respectively. The local recurrence rate in group 2 (31.3%) was higher than that in group 1 (9.5%), despite the fact that the differences in rates of complete resection and distant recurrence rates (14.3% in group 1 and 12.5% in group 2) between the two groups were not statistically significant. The overall 5-year survival rates were 67.9% for group 1 and 43.2% for group 2 (p=0.038). The 5-year survival rate of patients with tumors smaller than 10 cm was 78.4%, while that of patients with tumors larger than 10 cm was 38.1% (p=0.017). The 5-year survival rate after complete excision was 61%, whereas that after incomplete resection or biopsy only was 40.0% (p<0.0001). CONCLUSIONS: An upper abdominal tumor location is a positive prognostic factor even if small tumor size (<10 cm) and complete resection of the tumor are still more important factors to improve outcome in patients with malignant primary retroperitoneal tumors. Because complete resection was shown to be the most important prognostic factor, an aggressive and careful surgical approach is recommended for the treatment of such tumors.

The role of follow-up endoscopy after total gastrectomy for gastric cancer.

BACKGROUND: Follow-up endoscopy after total gastrectomy for gastric cancer is commonly performed without there being any definite evidence of clinical relevance. Therefore, we investigated the role of the upper endoscopic examinations after total gastrectomy for gastric cancer. METHODS: The medical records of 212 early gastric cancer (EGC) patients and 622 advanced gastric cancer (AGC) patients who underwent follow-up endoscopic examination after total gastrectomy between 1994 and 2001 were reviewed. RESULTS: Two of 212 EGC patients and 233 of 622 AGC patients revealed tumour recurrence at all sites. All the endoscopically accessible local tumour recurrences (n=24) were found in the AGC group. Anastomosis site stenosis was detected in 72 of 834 patients. CONCLUSION: Follow-up endoscopy after total gastrectomy for gastric cancer is useful in detecting complications and tumour recurrence. However, this procedure has a limited role in the clinical management and overall survival for patients with recurrent gastric adenocarcinoma.

Characteristics of submucosal gastric carcinoma with lymph node metastatic disease.

AIM: To study the correlation between lymph node metastatic disease and various pathological parameters. Lymph node metastasis is the most important factor in determining the prognosis of patients with early gastric cancer and is significantly associated with the submucosal invasion of neoplastic cells. However, the depth of submucosal layer as well as the depth of submucosal tumour invasion varies among different cases. METHODS AND RESULTS: We studied various pathological parameters including the macroscopic appearance, location, size, area, differentiation, invasion depth, vascularity and fibrosis of submucosal gastric carcinomas (SMGC), using 248 age- and sex-matched tissue samples. The presence of lymphatic emboli, a larger area, greater size, a non-flat gross type and an increased vascularity of the tumour were significantly associated with node-positive SMGC. Among the three depth-related parameters, the ocular scale measurement, the sm3 method and the sm2 method, only the ocular scale measurement showed a significant correlation with node-positive SMGC. Using multivariate analysis, the incidence of lymph node metastasis increased in the lymphatic tumour emboli and in the tumours that invaded more than half of the submucosal layer. CONCLUSIONS: These histological indicators seem to be a feasible and easy way to predict lymph node metastatic disease from limited surgery specimens. Pathologists should carefully investigate the lymphatic invasion of tumour cells and measure the invasion depth of the tumour.

Patterns of failure in gastric carcinoma after D2 gastrectomy and chemoradiotherapy: a radiation oncologist's view.

The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500 cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed.

Postoperative chemoradiotherapy for gastric cancer.

BACKGROUND: We report the results of postoperative chemoradiotherapy after curative resection in gastric cancer patients. PATIENTS AND METHODS: Patients with gastric cancer staged IB to IV(M0) were treated with chemoradiotherapy after curative resection with extensive (D2) lymph node dissection. Nodal metastases were observed in 261 (90%) patients. The chemotherapy consisted of fluorouracil 400 mg/m(2) plus leucovorin 20 mg/m(2) for 5 days, followed by 4500 cGy of radiotherapy for 5 weeks with fluorouracil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two 5-day cycles of chemotherapy were given 4 weeks after the completion of radiotherapy. RESULTS: Of 290 patients accrued, 229 (79%) patients completed chemoradiotherapy as planned. With a median follow-up of 49 months, 114 (34%) patients have relapsed: 33 (29%) locoregional relapses, 76 (67%) peritoneal relapses and 41 (36%) distant metastases. The 5-year overall and relapse-free survivals were 60% and 57%, respectively. Tolerance was acceptable, the main toxicity being neutropenia. CONCLUSIONS: This postoperative chemoradiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities. Whether this adjuvant therapy in gastric cancer patients that have undergone a D2 lymph node dissection impacts on survival or reduces the incidence of relapses remains to be studied.