R0 Gastrectomy Research Articles

Postoperative chemoradiation FOLFOX 4-based for R1 resected gastric cancer: A retrospective mono-institutional study.

143 Background: Improved DFS and OS were seen in curatively resected patients (pts.) with gastric and gastroesophageal adenocarcinoma treated with the Int0116 protocol of postoperative adjuvant chemoradiotherapy compared to surgery alone. However, there are very limited data about the efficacy of this approach in pts. with R1 resection. To evaluate the efficacy of a combined chemoradiation regimen in this setting, we reviewed our case records from 43 pts. with R1 resection treated between May 2008 and July 2012. Methods: 43 pts. with histologically confirmed gastric adenocarcinoma, received combined adjuvant chemotherapy with FOLFOX-4 for 8 cycles and concomitant radiotherapy (45 Gy in 25 daily fractions over 5 weeks). Radiotherapy was begun after 2 cycles of CT, (reduced by 20% during the period of concomitant radiotherapy). Pts. were followed at 3-month intervals for 2 years, at 6-month intervals for the next 3 years and yearly thereafter. Results: The median age was 62 years (range, 22-74) and the majority of pts. (76.7%) were males. Tumor location was equally distributed in the stomach. Most of the patients had locally advanced disease: 93% had T3-4 tumors and 74.4% had lymph node involvement. There was no treatment related death. Gastrointestinal G3 toxicity was observed in 11.6% of pts., while haematologic G3-4 toxicity was observed in 9.3%. Experienced toxicities led to chemotherapy dose reductions in 9 pts. and dose delay in 11 patients; 7 pts. had a delay in radiotherapy. With a median follow-up of 36 months (range 2-49) for the 43 R1 pts., 74.4% died of gastric cancer, 11.6% are alive with no evidence of recurrence and 13.9% are alive with disease. 66.6% of the relapses in this group occurred at distant sites and 33.3% were locoregional. The estimated 3-year OS was 19%. The median DFS was 14.5 months and the median OS was 16 months. Conclusions: These results seem to imply some benefit for the postoperative treatment, as nearly 19% of the R1 pts. in our study remained free of recurrence at 3 years from surgery. In the absence of phase III data and consequently lack of clear guidelines in this setting, our results support the common practice of adding postoperative chemoradiation after R1 gastrectomy.

Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

Clinical utility of perioperative staging laparoscopy for advanced gastric cancer.

BackgroundPerioperative staging laparoscopy is a useful tool for the detection of occult peritoneal metastases in gastrointestinal cancers. This retrospective study aimed to determine the clinical value of staging laparoscopy for advanced or recurrent gastric cancer.MethodsA total of 178 patients with advanced or recurred gastric cancer who underwent perioperative staging laparoscopy were enrolled. In the absence of peritoneal deposits (P1) and positive peritoneal cytology (CY1), gastrectomy with lymph node dissection was indicated with curative intent. If P1 or CY1 was detected intraoperatively, patients received intensive chemotherapy and laparoscopic surgical intervention.ResultsCurative gastrectomy was performed in 104 patients after confirmation of P0 and CY0 status. P1 or CY1 was detected for the first time in 23 (15%) patients. A total of 13 patients were converted from gastrectomy to intensive chemotherapy after detection of P1 or CY1. Additional laparoscopic interventions included insertion of intraperitoneal reservoir port in 54 patients, insertion of a metallic stent in five, ileostomy for colon stricture in six, jejunostomy in 19, and gastrojejunostomy in 16. Of eight patients treated with intensive chemotherapy who underwent R0 gastrectomy after second-look laparoscopy, five are currently free from recurrence of gastric cancer for 25.5 months.ConclusionsOccult peritoneal dissemination was detected in about 14% in patients with tumors deeper than T2. Moreover, additional laparoscopic interventions can be utilized for P1 or CY1 patients. The excellent surgical outcomes of R0 gastrectomy after chemotherapy and second-look laparoscopy indicate that confirmation of P0 and CY0 status by staging laparoscopy is of value to determine treatment strategy in patients with advanced gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/1477-7819-12-350) contains supplementary material, which is available to authorized users.

The Impact of Preoperative Lymph Node Size on Long-Term Outcome Following Curative Gastrectomy for Gastric Cancer

Multidetector-row computed tomography (MDCT) is widely used to predict pathological nodal status. However, an appropriate nodal size cutoff value to predict pathological nodal status has not been determined, and the impact of preoperative lymph node size on long-term outcomes is unclear. This study included 137 gastric cancer patients with nodal involvement who underwent R0 gastrectomy between September 2002 and December 2006. Lymph nodes with a short-axis diameter of 10 mm or more as measured by MDCT were regarded as metastasized. An appropriate cutoff value with a high positive predictive value (PPV) and high specificity also was identified, and the subsequent clinicopathological characteristics and long-term outcomes were investigated. A cutoff value of 15 mm was found to be appropriate for grouping patients into large (≥15 mm) and small (<15 mm) lymph node metastasis (LLNM and SLNM) groups, with a high PPV (98.6 %) and specificity (99.8 %). There were no differences in clinicopathological characteristics between the groups except for pathological nodal status. In the LLNM group, the 5-year survival rate was 55 %, which was significantly lower than in the SLNM group (73.2 %; P = 0.008). After stratification by tumor depth, the same trend was observed in patients with pT3 disease (46.8 % vs. 72.7 %; P = 0.015) and those with pT4 disease (14.3 % vs. 64.8 %; P = 0.035). Gastric cancer patients with lymph nodes measuring 15 mm or more preoperatively have worse long-term outcomes. These patients would therefore be suitable candidates for future clinical trials investigating the efficacy of neoadjuvant chemotherapies.

Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.

Clinical impact of tumor infiltration at the transected surgical margin during gastric cancer surgery

When transected surgical margins are involved by tumor cells during gastrectomy for gastric cancer, dissemination of tumor cells to the peritoneal cavity may be a concern. The aim of this study is to evaluate the prognostic value of tumor infiltration at the transected surgical margin during gastrectomy. A total of 1,717 patients with gastric cancer who underwent R0 gastrectomy were included. The relationship between positive margins on frozen biopsy during gastrectomy and clinicopathologic data was examined. The prognostic impact of this intraoperative event was evaluated by univariate and multivariate analysis. The intraoperative positive resection margin occurred in 69 patients (4.01%). Tumor size >5 cm, tumor located in the upper third or whole stomach, Bormann type IV gastric cancer, and signet ring cell histology were independent factors associated with that intraoperative event. pT and pN stages were significant prognostic factors associated with locoregional and/or peritoneal recurrence and overall recurrence. Tumor infiltration at the transected margin was not an independent prognostic factor associated with any recurrence. Microscopic tumor involvement at the margin during gastric cancer surgery does not increase locoregional and/or peritoneal recurrence or overall recurrence independently if R0 resection is achieved by re-resection of the margin.

Cancerous HLA class I expression and regulatory T cell infiltration in gastric cancer.

Since antitumor immune reactions between tumors and intratumoral immunocytes have been verified in several human tumors, immunological therapeutic strategies must be considered to obtain the proper efficacy of tumor shrinkage under these conditions. Human leukocyte antigen (HLA) class I expression in cancer cells and degree of infiltration of regulatory T cells (Tregs) in the stroma have been regarded as important markers of antitumor immune reactions in the context of independent immunological mechanisms. In the current study, we investigated HLA class I expression and Treg cells infiltration in gastric cancer and discussed the clinical implications of this combinatory analysis in gastric cancer. A total of 141 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were studied. Immunohistochemically, in 141 gastric cancer patients, HLA class I expression and Treg cell infiltration in cancerous tissue were evaluated using HLA class I (EMR8-5) and forkhead box p3 (FOXP3) monoclonal antibodies. The correlation between clinical factors and tumor-infiltrating Treg cells was analyzed. HLA class I expression was positively associated with depth of tumor invasion (P<0.05). Infiltration of Foxp3-positive cells did not correlate with any clinicopathological markers. HLA class I expression had no association with Treg cell infiltration (r=0.04). A better postoperative outcome was associated with fewer numbers of Treg infiltration (P=0.034). A combination of HLA and Treg analysis may lead to a more accurate prediction of postoperative outcome (P=0.02). Two different antitumor immunological markers, Treg infiltration and HLA class I expression, affected clinicopathological factors in gastric cancer by different mechanisms. Thus, an immunological combination of HLA class I expression and Treg cell infiltration may more accurately predict postoperative outcome. Immunological balance needs to be restored after evaluation of each immunological deficit in gastric cancer.

Morbilidad y mortalidad operatoria de la gastrectomía subtotal y total por cáncer gástrico 2004 a 2010: Parte I de un estudio prospectivo

Complications and mortality of total and subtotal gastrectomy for gastric cancer Background: Surgery for gastric cancer may have high rates of complications and mortality. Aim: To analyze operative mortality of total and subtotal gastrectomy in the period 2004-2010. Material and Me- thods: Prospective study 345 patients with gastric cancer, mean age 62 years, 64% males, subjected to a total or subtotal R0, R1 or R2 gastrectomy. All patients were assessed in the postoperative period and all com- plications were recorded. Results: Total and subtotal gastrectomies were performed in 224 and 69 patients respectively. Postoperative complications consisted in anastomotic leaks, duodenal stump leaks, hemoperi- toneum, pulmonary infections and intestinal obstruction. Mortality of total gastrectomy R1 or R2 was 2.1% whereas palliative gastrectomy, to improve quality of life, had 15% mortality. Subtotal gastrectomy had 1.4% mortality. Conclusions: There has been a reduction in operative mortality of gastrectomy for gastric cancer, however the rate of complications has not changed.

Surgical outcomes of laparoscopy-assisted gastrectomy versus open gastrectomy for gastric cancer: a case-control study

The aim of this study was to clarify the technical feasibility and oncological efficacy of laparoscopy-assisted gastrectomy (LAG) for gastric cancer compared with open gastrectomy (OG). Between April 2002 and March 2008, a series of 623 patients with gastric cancer underwent R0 gastrectomy (314 LAG patients and 309 OG patients). Age, gender, lymph node dissection, and pathological stage were matched by propensity scoring, and 212 patients (106 LAG and 106 OG) were selected for analysis after the exclusion of 40 patients who had proximal gastrectomy. Intraoperative factors, postoperative morbidity, long-term quality of life (QOL), and survival were evaluated. Moreover, these outcomes were also compared between the laparoscopy-assisted total gastrectomy (LATG) and the open total gastrectomy (OTG). There was no significant difference in preoperative characteristics between the two patient groups. Regarding intraoperative characteristics, blood loss was significantly lower in the LAG group (143 ml) than in the OG group (288 ml), while operation time was significantly longer in the LAG group (273 min) than the OG group (231 min). The degree of lymph node dissection and number of retrieved lymph nodes did not differ between the two groups. There were no significant differences in postoperative courses or overall and disease-specific survival (89.8% vs. 83.6%, P = 0.0886; 100% vs. 95.2%, P = 0.1073) except time to first flatus and time to use of nonsteroidal anti-inflammatory derivatives between the two groups. Significantly fewer patients felt wound pain in the LAG group 1 year after surgery. Analyses between the LATG and OTG groups showed similar results. LAG for gastric cancer may be both feasible and safe. However, it will be necessary to conduct a well-designed randomized controlled trial comparing short-term and long-term outcomes between LAG and OG in a larger number of patients.

Surgical management of gastric perforation in the setting of gastric cancer

Gastric perforation is a rare presentation of gastric cancer and is thought to be a predictor of advanced disease and, thus, poor prognosis. Guidelines do not exist for the optimal management strategy. We aimed to identify, review, and summarize the literature pertaining to perforation in the setting of gastric cancer. A qualitative, systematic review of the literature was performed from January 1, 1985, to January 1, 2010. Searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were performed using search terms related to gastric cancer surgery. Abstracts were examined by two independent reviewers and a standardized data collection tool was used to extract relevant data points. Summary tables were created. Nine articles were included. Perforation was reported to occur in fewer than 5% of gastric cancer patients. Preoperative diagnosis of a gastric cancer was rated and occurred in 14-57% of patients in the papers reviewed. Mortality rates for emergency gastrectomy ranged from 0 to 50% and for simple closure procedures the rates ranged from 8 to 100%. Patients able to receive an R0 gastrectomy demonstrated better long-term survival (median 75 months, 50% 5-year) compared with patients who had simple closure procedures. Gastric cancer patients presenting with a gastric perforation demonstrate improved overall survival with an R0 resection; however, implementation of this management technique is complicated by infrequent preoperative gastric cancer diagnosis, and inability to perform an oncologic resection due to patient instability and intra-abdominal contamination.

Multimodal Treatment of Resectable Gastric Cancer with Intensive Neoadjuvant Radiation Therapy: Obninsk Radiological Center Experience

Introduction: We performed a retrospective analysis to clarify the role of neoadjuvant radiation therapy in the management of resectable gastric cancer. Methods and Methodology: All patients underwent R0 gastrectomy between 1974 and 2008 were retrospectively evaluated. Among them 597 patients underwent multimodal treatment with various schemes of intensive preoperative radiation therapy (total dose of 20-27 Gy) and 433 patients were treated with surgery alone. Results: Radiation therapy was completed in 98% of the patients without the delay of the surgery and any increase in postoperative morbidity or mortality including cases with D2 lymphadenectomy. Subgroup analysis showed that neoadjuvant radiotherapy provided statistically significant survival improvement comparing with surgery alone in pN+ cases (p=0.035); Borrmann 3 and 4 types (p=0.029); poorly differentiated, undifferentiated and signet ring cell carcinomas (p=0.005). Multivariate analysis in the latter group confirmed that neoadjuvant radiation therapy was an independent factor of the favorable prognosis (p=0.001). Conclusions: Intensive neoadjuvant radiotherapy is safe, feasible and could improve survival in selected groups of patients. Patients with poorly differentiated, undifferentiated and signet ring cell carcinomas should be considered as the target group for the multimodal treatment including radiation therapy.

Mesothelin expression correlates with prolonged patient survival in gastric cancer

Mesothelin expression is found in normal mesothelium, and cancerous mesothelin has been recently reported in ovarian and pancreas cancer. The clinicopathological implications of mesothelin expression have been discussed with respect to antitumor immunological mechanisms. However, there is no information on mesothelin expression in gastric cancer. The purpose of the current study is to identify the clinical significance of mesothelin in gastric cancer. A total of 212 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were enrolled in this study. Mesothelin was detected immunohistochemically and visualized by ABC method. Intensity of cancerous mesothelin was divided into two categories (0-50%: negative group and 51-100%: positive group). Mesothelin expression was detected in the cellular membrane. In accordance with the previous evaluation, patients were divided into two groups [mesothelin-positive group: 124 (59%) and mesothelin-negative group: 88 (41%)]. The mesothelin-positive group had significantly more nodal involvement and significantly deeper tumor invasion than the mesothelin-negative group (P < 0.05). However, by analysis confined to the 117 advanced gastric cancer patients, the 5-year survival rate of the mesothelin-positive group was 55%, which was significantly better than that of the mesothelin-negative group. Multivariate analysis revealed that mesothelin expression is one of the independent prognostic factors of gastric cancer. Cancerous mesothelin expression in gastric cancer may be a useful tool to predict patient survival.

Phase II study of biweekly docetaxel and S-1 combination chemotherapy as first-line treatment for advanced gastric cancer

We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer. Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0-2 and no prior chemotherapy history were eligible for inclusion (n = 45). Patients received a total of 215 treatment courses (median, 4; range, 2-12) of S-1 oral administration twice daily for 1 week followed by a drug-free interval of 1 week. Docetaxel (40 mg/m(2)) was administered intravenously on days 1 and 15. We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3 months, the median time to progression was 6.9 months, and the median duration of response in 26 patients was 8.0 months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths. S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.

Impact of adjuvant chemoradiation for adenocarcinoma of stomach after curative gastrectomy in Chinese: A 7-year audit

Background and Aim: Adjuvant chemoradiation (CRT) after curative gastrectomy was introduced to our hospital in 1998. The present study aims to examine the impact of CRT on survival among Chinese. Methods: From our gastric cancer registry, patients who received R0 gastrectomy, with UICC stage II or above, M0 disease and ASA grades I and II were analyzed. Adjuvant CRT was offered and given if patients agreed. The regimen consisted of five cycles of 5-fluoruracil (5FU)/leucovorin chemotherapy and 45 Gy/25 fractions concurrent with cycles 2 and 3. Results: From January 1998 to December 2004, 134 patients fulfilled the criteria. Sixty had surgery alone and 74 patients received CRT after gastrectomy. One hundred and two (76%) patients received radical gastrectomy with D2 lymphadenectomy. Toxicity ≥ grade 3 was seen in 65% of patients without mortality. The overall and relapse-free 5-year survival rates were 45.8% and 42.0%, respectively. On univariate analysis, early disease stage and adjuvant CRT were associated with better prognosis. Cox regression analysis showed that adjuvant CRT (P = 0.01, HR 2.31, 95% CI: 1.4–3.9) predict better survival after adjustment with the other factors. Conclusion: In the present study, postoperative adjuvant chemoradiation is associated with better overall survival in patients with adenocarcinoma of the stomach after curative gastrectomy.

Laparoscopic surgery for gastric cancer: comparative-effectiveness research and future trends

Research and technology have revolutionized surgery. Patient-oriented scientific efforts drive biomedical science advances. Improving patient’s outcomes dramatically, minimally invasive approaches represent a rapidly growing field. However, high-quality evidence for incorporating new medical devices, technology and surgical techniques into public healthcare with safety, efficiency and considering cost–effectiveness ana lysis is required [1]. In the beginning of the new decade, laparoscopic surgery in the multidisciplinary and multimodal treatment of solid tumors will probably experience a boom in clinical practice. In a 2020 vision, a progressive increase in the clinical use rates of laparoscopic and robotic-assisted tumor resections can be expected. We discuss here the perspectives, questions, limitations, potential harms in individual patients and public health, and challenges of laparoscopic gastrectomy for gastric cancer. Among gastrointestinal cancers, tumors located in the colorectum and stomach are the most common, with approximately 1.9 million new cases each year worldwide, resulting in high mortality rates [2]. Over the past few decades, open surgery has been standard. Adequate resection of the primary tumor and of regional lymph nodes resulting in complete resection with no macroscopic or microscopic evidence of residual tumor (R0 resection) has been established as standard approach either before or after adjuvant chemotherapy and radiotherapy. Is laparoscopic R0 gastrectomy feasible, safe and equally effective, compared with open surgery? Patient-friendly minimal invasive approaches in the treatment of gastrointestinal cancer include endoscopic submucosal dissection for very early, small-size tumors and laparoscopic or robotic resection for more advanced, larger tumors. Any new development or innovation, including medical devices, surgical techniques, drugs and biomarkers, requires rigorous evaluation and validation before it can be approved for wide clinical use. For example, it is now recommended by the editors of high-impact journals, such as Nature, that scientists straddling the boundary between bench and bedside must conduct and report their research with the rigor that each individual community expects [3].

Metastatic lymph node in gastric cancer; is it a real distant metastasis?

BackgroundCurrently, the TNM staging system is a widely accepted method for assessing the prognosis of the disease and planning therapeutic strategies for cancer. Of the TNM system, the extent of lymph node involvement is the most important independent prognostic factor for gastric cancer. The aim of our study is to evaluate the survival and prognosis of gastric cancer patients with LN#12 or #13 involvement only and to assess the impact of anatomic regions of primary gastric tumor on survival in this particular subset of patients.MethodsAmong data of 1,008 stage IV gastric cancer patients who received curative R0 gastrectomy, a total of 79 patients with LN#12 (n = 68) and/or #13 (n = 11) were identified. All patients performed gastrectomy with D2 or D3 lymph node dissection.ResultsIn 79 patients with LN#12/13 involvement, the estimated one-, three- and five-year survival rate was 77.2%, 41.8% and 26.6% respectively. When we compared the patients with LN#12/13 involvement to those without involvement, there was no significant difference in OS (21.0 months vs. 25.0 months, respectively; P = 0.140). However, OS was significantly longer in patients with LN#12/13 involvement only than in those with M1 lymph node involvement (14.3 months; P = 0.001). There was a significant difference in survival according to anatomic locations of the primary tumor (lower to mid-body vs. high body or whole stomach): 26.5 vs. 9.2 months (P = 0.009). In Cox proportional hazard analysis, only N stage (p = 0.002) had significance to predict poor survival.ConclusionIn this study we found that curatively resected gastric cancer patients with pathologic involvement of LN #12 and/or LN #13 had favorable survival outcome, especially those with primary tumor location of mid-body to antrum. Prospective analysis of survival in gastric cancer patients with L N#12 or #13 metastasis is warranted especially with regards to primary tumor location.

Neoadjuvant therapy of gastric cancer with cetuximab added to both irinotecan and cisplatin, followed by surgical resection and adjuvant chemoradiation

e15552 Background: We previously demonstrated the efficacy of irinotecan (CPT) and cisplatin (Cis) combination therapy as neoadjuvant therapy for locally advanced gastric cancer [Newman E et al. J Gastrointest Surg. 2002.]. This trial was designed to add cetuximab (C) to both induction treatment and adjuvant chemoradiation (CRT) with bolus 5-FU/LV. Methods: Pts with untreated locally advanced (T3, T4 or N+) gastric/GE cancers were eligible. Neoadjuvant therapy consisted of Cis 25mg/m2 + CPT 75mg/m2 on d1,8 q21d x 4, C 400mg/m2 on d1, then 250mg/m2 qwk. Curative (R0) resection was performed 4–6 wks later. Adjuvant CRT with 5-FU/LV (425/20/m2 qd x 5 on wks 1,14,19; 400/20/m2 qd x 4 on wk 5, x 3 on wk 9) was given with C 250mg/m2 qwk. Results: Since 11/05, 21 pts [median age 59 (32–82); 9 Caucasian, 11 Asian, 1 Hispanic; 15 male, 20 PS 0–1] received neoadjuvant therapy. The most common toxicities were gr 3 neutropenia (38%), gr 2 rash (33%), gr 2 fatigue (29%); gr 4 included 1 pt each of diarrhea, neutropenia, &amp; hypomagnesemia. 3 did not complete neoadjuvant therapy, due to gr 3 rash, diarrhea and GI bleeding (2 had gastrectomy; 1 lost to f/u). All 18 pts who completed neoadjuvant therapy were surgically explored. 4 had occult metastases, and went off study. 14 underwent R0 gastrectomy (see table); 8 were downstaged, 2 had stable disease, 4 were upstaged compared to the preoperative EUS. There was no postoperative mortality. Of 14 resected pts, 2 did not receive adjuvant therapy (prolonged postoperative recovery), 1 too early to assess, and 11 remaining receiving CRT. The most common toxicities for CRT were gr 3 nausea, gr 3 emesis, gr 2 and 3 fatigue, 3 pts each and 1 each of gr 4 neutropenia and thrombocytopenia. Among the 18 pts who completed neoadjuvant therapy, 5 died of disease, 1 is alive with disease, 12 remain NED with median f/u of 11.6mos (4.1–27.7mos). Conclusions: The addition of C to CPT/Cis as neoadjuvant therapy and to postoperative adjuvant CRT is well tolerated. The regimen induces a favorable pathologic response on the primary tumor. Ongoing evaluation includes K-ras mutation status on outcome and survival benefit. [Supported in part by a grant from BMS.] [Table: see text]

A pilot study of biological markers (BM) as predictors for response and prognosis in patients (pts) with R0 resected gastric cancer (GC)

e22076 Background: To evaluate clinical value of biological markers and their prognostic significance in gastric cancer as well as prediction to clinic outcome; To select preference marker for targeted therapy in high risk patients hence to guide personalized treatment. Methods: Retrieved from total 394 patients treated during the period of Jan 2004 to June 2006 of Cancer Hospital, Fudan University with complete medical records and follow up data, 84 patients with pre- and post- operative biological markers examined were selected. All of these patients underwent R0 gastrectomy, 61 (72.6%) patients underwent D2 resection. Forty- one (48.8%) patients received ≥ 4 cycles adjuvant chemotherapy. Preoperative tumor markers include: CEA, AFP, CA199, CA50, CA72–4, CA24–2 and postoperative immunohistochemical examination include: Bax, Bcl-2, P27, CyclinD1, TOPO2, MDR, GST-π, Ki67, AgNOR, EGFR, P21, P53, PCNA, C-myc and Neu were analyzed. Univariate, multivariate and Logistic regression analysis were performed and Kapan-Meier estimates were calculated. Results: For the whole group, 2-year OS and PFS were 76% and 66% respectively. Logistic regression analysis showed bcl-2, ki67, c-myc2 and Neu were relative with more nodal involvement. Patients with lower level of CEA, CA72–4 and higher level of cyclin D1 suivived longer than the other patients. There were different clinical significance with those biomarkers. Patients with lower level of cyclinD1, CEA had more local regional recurrence (p=0.026) while patients with higher PCNA experienced more distant metastasis (p=0.005). Univariate analysis showed that clinical staging, level of cyclinD1 and CEA were correlated with OS (p&lt;0.05). Conclusions: Biological markers may be helpful in predicting the clinical outcome and prognosis for R0 resected gastric cancer patients. Further study are needed to confirm their clinical significance. No significant financial relationships to disclose.

Prognostic significance of gastrin expression in patients undergoing R0 gastrectomy for adenocarcinoma

Gastrointestinal (GI) hormones regulate several GI functions, including the proliferation and repair of normal mucosa, and hormone receptors may therefore be implicated in the growth, invasion, and metastasis of cancers of the GI tract. The aim of this study was to determine the cellular distribution of gastrin in intestinal-type gastric cancers, and to determine its relationship to outcomes after R0 gastrectomy. Eighty-six consecutive patients undergoing R0 gastrectomy for adenocarcinoma were studied. Normal gastric mucosa and tumor were stained for gastrin and their specific cellular distribution was determined. The duration of survival of patients whose tumors exhibited well-differentiated gastrin-positive tumor (GPT) cells (n = 12) was significantly poorer than that of patients whose tumors were GPT-negative (5-year survival, 30% vs 54%; P = 0.037). Patients with GPT-positive intestinal-type gastric cancer (5 of 47 patients) had the poorest survival of all (median, 14 months; 5-year survival, 0%; P = 0.006). In a multivariate analysis, only lymph node metastases (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.2 to 3.79; P = 0.01) and the presence of GPT cells (HR, 6.61; 95% CI, 1.74 to 25.09; P = 0.01) were independently and significantly associated with durations of survival in patients with intestinal-type gastric cancer. The presence of GPT cells in patients with gastric adenocarcinoma is a significant and independent prognostic indicator.

Adjuvant Chemoradiation for Gastric Cancer: Experience in the Chinese Population

Aims The role of adjuvant chemoradiation for gastric cancer after curative R0 gastrectomy was first established by the US Intergroup 0116 study. Although confirmatory studies are in progress, few data are available regarding its application to the Chinese population. We describe our radiotherapy technique and report the treatment results in Hong Kong. Materials and methods This was a single centre retrospective study on 63 Chinese patients who underwent adjuvant chemoradiation for gastric adenocarcinoma between June 2000 and December 2004. The treatment protocol was based on that of the Intergroup study. Computed tomography planned anteroposterior opposing field arrangement and treatment under breath hold at deep inspiration position were adopted. Results In total, 63 patients, mean age 50 years, with gastric cancer stage IB to limited metastatic IV disease were analysed. The median follow-up time was 27.2 months. The relapse-free survival and overall survival at 3 years were 50 and 54%, respectively. The recurrence pattern was dominated by distant failure and only one patient developed isolated locoregional recurrence. Of the 10 patients who had positive microscopic surgical margins after surgery, seven had recurred and died. On multivariate analysis, margin status was the only significant prognosticator for survival. Thirty per cent of patients experienced grade 3 or above acute toxicity (24% haematological, 14% gastrointestinal) and one patient died of neutropenic sepsis. There was one case of grade 3 late toxicity. Conclusions The outcome after adjuvant chemoradiation for gastric cancer seemed to be favourable, with manageable toxicities, in the Chinese population. Locoregional failure was uncommon. Patients with microscopic surgical margin involvement had a very high failure rate despite adjuvant chemoradiation.