Most studies exploring the role of staging laparoscopy in gastric cancer are limited by low sample size and are predominantly conducted in Asian countries. This study sets out to determine the value of staging laparoscopy in patients with advanced gastric cancer in a Western population.

All patients with gastric cancer from a tertiary referral center without definite evidence of non-curable disease after initial staging, and who underwent staging laparoscopy between 2013 and 2020, were identified from a prospectively maintained database. The proportion of patients in whom metastases or locoregional non-resectability was detected during staging laparoscopy was established. Secondary outcomes included the avoidable surgery rate (detection of non-curable disease during gastrectomy with curative intent) and diagnostic accuracy (sensitivity, specificity, accuracy, negative and positive predictive value).

A total of 216 patients were included. Staging laparoscopy revealed metastatic disease in 46 (21.3 %) patients and a non-resectable tumor in three (1.4 %) patients. During intended gastrectomy, non-curable disease was revealed in 13 (8.6 %) patients. Overall sensitivity, specificity and diagnostic accuracy were 76.6 %, 100 % and 92.6 %, respectively. The positive predictive value was 100 % and the negative predictive value was 90.3 %.

Staging laparoscopy is valuable in the staging process of gastric cancer with a high accuracy in detecting non-curable disease, thereby preventing futile treatment and its associated burden.

Over the last 2 decades, outcomes for oesophageal cancer have improved due to advances in surgical and oncological practice. Optimizing outcomes by centralization of oesophagectomy to high-volume centres has been observed. The aim of this study was to establish if technical and oncological outcomes after oesophagectomy in southern New Zealand are comparable to recent benchmarks.

Consecutive patients undergoing oesophagectomy for cancer and benign pathology at Dunedin Hospital from 1995 to 2019 were prospectively audited. For malignant cases, histology was obtained retrospectively along with details of neo-adjuvant and adjuvant therapy. The primary outcome was disease-specific survival, stratified by time, resection margin, and TNM staging. Secondary outcomes included mortality and morbidity of oesophagectomy. Complications were graded using the Clavien-Dindo classification.

Oesophagectomy was performed in 108 patients, and 99 patients had surgery for oesophageal malignancy. The median survival was 35.3 (95% confidence interval (CI) 30.0-93.4) months and the 5-year survival overall was 41.7%. Comparing survival in patients undergoing oesophagectomy up to 2006 and afterwards showed an improvement in 5-year survival (30.3%, 95% CI (14.2-60.0) versus 47.8%, 95% CI (32.5, not reached), respectively, P = 0.041). There were two perioperative deaths (1.8%), six clinical anastomotic leaks (5.5%), four anastomotic strictures (3.7%) and five chylothoraces (4.6%).

This 25-year survey of oesophagectomy in southern New Zealand audits the results of a low volume centre, where a variety of neo-adjuvant treatments have been used. Despite this, perioperative morbidity, mortality and survival are comparable to those achieved by international high-volume centres.

Approximately 17%-40% of para-aortic lymph node (PAN) metastasis occurs in patients with advanced gastric cancer. As the third tier of lymphatic drainage of the stomach and the final station in front of the systemic circulation, PAN infiltration is defined as distant metastasis and plays a key role in the evaluation of the prognosis of advanced gastric cancer. Many clinical factors including tumor size ≥ 5 cm, pT3 or pT4 depth of tumor invasion, pN2 and pN3 stages, the macroscopic type of Borrmann III/IV, and the diffuse/mixed Lauren classification are indicators of PAN metastasis. Whether PAN dissection (PAND) should be performed on patients with or without the macroscopic PAN invasion remains unascertained, regardless of the numerous retrospective comparative studies reported on the improved prognosis over D2 alone. Another paradoxical result from many other studies showed no significant difference in the overall survival between these two lymphadenectomies. A phase II trial launched by the Japan Clinical Oncology Group indicated that two or three courses of S-1 and cisplatin preoperatively followed by radical surgery with D2 + PAND and postoperative S-1 is the current standard strategy for the treatment of patients with extensive lymph node metastasis, and this regimen could be substituted by a promising strategy with effective combination chemotherapy or suitable chemotherapy duration. This review focuses on the advances in radical gastrectomy plus PAND with or without chemotherapy for patients with advanced gastric cancer.

Contention exists within the field of oncology with regards to gastroesophageal junction (GEJ) tumors, as in the past, they have been classified as gastric cancer, esophageal cancer, or a combination of both. Misclassifications of GEJ tumors ultimately influence treatment options, which may be rendered ineffective if treating for the wrong cancer attributes. It has been suggested that misclassification rates were as high as 45%, which is greater than reported for junctional cancer occurrences. Here, we aimed to use the methylation profiles of GEJ tumors to improve classifications of GEJ tumors. Four cohorts of DNA methylation profiles, containing ~27,000 (27k) methylation sites per sample, were collected from the Gene Expression Omnibus and The Cancer Genome Atlas. Tumor samples were assigned into discovery (nEC = 185, nGC = 395; EC, esophageal cancer; GC gastric cancer) and validation (nEC = 179, nGC = 369) sets. The optimized Multi-Survival Screening (MSS) algorithm was used to identify methylation biomarkers capable of distinguishing GEJ tumors. Three methylation signatures were identified: They were associated with protein binding, gene expression, and cellular component organization cellular processes, and achieved precision and recall rates of 94.7% and 99.2%, 97.6% and 96.8%, and 96.8% and 97.6%, respectively, in the validation dataset. Interestingly, the methylation sites of the signatures were very close (i.e., 170-270 base pairs) to their downstream transcription start sites (TSSs), suggesting that the methylations near TSSs play much more important roles in tumorigenesis. Here we presented the first set of methylation signatures with a higher predictive power for characterizing gastroesophageal tumors. Thus, they could improve the diagnosis and treatment of gastroesophageal tumors.

There remains debate as to whether quality of life (QoL) is better for patients following sub-total gastrectomy (SG) or total gastrectomy (TG) for cancer. Both have similar survival rates provided an R0 resection is performed and in many series the morbidity and mortality after TG is higher than SG. The aim of this study was to evaluate the QoL in patients after TG and SG for cancer.

All surviving patients who had undergone TG or SG between 1994 and 2009 were identified from a prospectively collected database and sent the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30 v.3) and the gastric module (QLQ-STO22).

From a total of 261 patients who had undergone TG or SG in the study period, 91 were still alive and 53 responded. There was no significant difference between the QoL between TG and SG based on functional scales and global health status. However dysphagia and eating restrictions were significantly worse in the TG group.

This study has demonstrated that there is no difference in overall QoL in patients with TG or SG although eating restrictions and dysphagia are worse after TG.

Gastric cancer is the 9th most common malignancy in Hungary, being the 4th most frequent cause of death among all cancers. The traditional treatment approaches did not turn out to be effective against advanced gastric cancer. On the other hand, due to better understanding of the underlying molecular biology of tumors, targeted therapeutics emerge resulting in longer survival times. Dank M. Recent advances in the treatment of gastric cancer.

Whether the combination of high dose-rate brachytherapy (HDRBT) and External Beam Radiation Therapy (EBRT) is superior to HDRBT alone for the palliation of oesophageal cancer has only been explored in a previous IAEA pilot randomized trial.

Two hundred and nineteen patients were randomized to adding EBRT or not, after receiving two fractions of HDRBT within 1 week. Each HDRBT consisted of 8 Gy prescribed at 1cm from source centre. Patients randomized to EBRT received 30 Gy in 10 fractions. The primary outcome was dysphagia-relief experience (DRE). Additional outcomes included various scores, performance status, weight and adverse events. A majority of charts, imaging and radiotherapy plans were externally audited.

Median follow-up was 197 days, with a median OS of 188 days and an 18% survival rate at 1 year. DRE was significantly improved with combined therapy, for an absolute benefit of +18% at 200 days from randomization (p=0.019). In longitudinal regression analyses, scores for dysphagia (p=0.00005), odynophagia (p=0.006), regurgitation (p=0.00005), chest pain (p=0.0038) and performance status (p=0.0015) were all significantly improved. In contrast, weight, toxicities and overall survival were not different between study arms.

Symptom improvement occurs with the addition of EBRT to standard HDRBT. The combination is well tolerated and relatively safe.

The aim of this study was to evaluate the efficacy and toxicity of docetaxel (TAX), cisplatin (CDDP), and fluorouracil (5-FU) plus leucovorin (CF) as the neoadjuvant chemotherapy (NACT) regimens in the treatment of nonresectable advanced gastric cancer. Twelve patients with nonresectable advanced gastric cancer were treated with NACT regimens consisted of docetaxel, cisplatin, fluorouracil, plus leucovorin before operation. Nine of the 12 patients were downstaged and 8 were radically operated after the end of the NACT. The overall response rate was 75% with 8.3% complete response and 66.7% partial response, and the ascites disappeared in 63.6%. The most common toxicities were bone marrow suppression, nausea, vomiting, alopecia, and heptoses. The toxicities were recoverable after symptomatic treatment. The results confirmed that the combination of docetaxel, cisplatin, fluorouracil plus leucovorin (CF) is a very effective and well-tolerated regimen as NACT for the patients with nonresectable advanced gastric cancer.

Historically, radiotherapy has been occasionally used in the treatment of gastric cancer. More recently, the results of INT-0116 trial have shown an improvement of disease-free and overall survival by chemoradiation with a significant impact on the management of this tumor. Based on these data, there has been an increasing interest in radiotherapy and its association with chemotherapy for patients with locoregional disease as a part of an adjuvant treatment after surgery in high-risk patients. However, many questions remain to evaluate; first of all the toxicity of this approach and its efficacy after adequate surgery.

Positron-emission-tomography with the glucose analog fluorodeoxyglucose (FDG-PET) has shown encouraging results for prediction of tumor response to chemotherapy. However, there is no consensus as to what time after initiation of therapy FDG-PET should be performed. To address this question we studied the time course of changes in tumor FDG-uptake in patients with locally advanced adenocarcinomas of the esophagogastric junction (AEG) treated with preoperative chemotherapy.

Twenty-four patients with AEG were included and underwent FDG-PET prior to therapy (PET1), 2 weeks after initiation of therapy (PET2), and preoperatively (PET3). Tumor metabolic activity was assessed by standardized uptake values (SUV) and correlated with histopathologic response and patient survival.

Baseline tumor SUV was 8.3 +/- 3.5 and decreased to 5.0 +/- 1.8 at PET2 (p < 0.0001). At PET3 there was further decrease to 3.5 +/- 1.9 (p < 0.0001). The relative decrease of tumor FDG-uptake from PET1 to PET2 and from PET1 to PET3 were both significantly correlated with histopathologic response. Reduction of tumor SUV from PET1 to PET2 was significantly correlated with survival (p = 0.03) and there was a similar trend for changes from PET1 to PET3 (p = 0.09). In contrast, absolute SUVs did not demonstrate a significant correlation with histopathological response or patient survival at any of the studied time points.

In patients with AEG, relative changes in tumor FDG uptake are better predictors for treatment outcome than absolute SUVs. Metabolic changes within the first 2 weeks of therapy are at least as efficient for prediction of histopathologic response and patient survival as later changes.

This article provides perspectives on the surgical approaches required optimally to manage patients with respectable gastric adenocarcinoma. The status of techniques of surgical resection in the management of gastric cancer is reviewed. The premise of this approach is that extended gastrectomy with D2 lymph node dissection is good. Also addressed are prognostic and predictive factors in the surgical treatment of stomach cancer.

Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX-CTXRT). However, the influence of CTX-CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX-CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma.

A prospectively collected database on 71 consecutive patients who underwent CTX-CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis.

Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50-50.6)] and body mass index (BMI) of 26 kg/m(2) or above [relative risk 4.08 (95% confidence interval 1.08 to 15.4)] were significant risk factors for overall complications.

CTX-CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity.

Recently, a survival advantage has been shown using adjuvant chemoradiotherapy after complete resection of gastric cancer. If survival advantages are to be maintained, treatment-related complications must be minimised. In this study, we explored the dosimetric implications and toxicity of conventional large field gastric bed irradiation.

Between 2000 and 2002, 16 patients received adjuvant 5-fluorouracil (5-FU) chemoradiotherapy after complete resection of gastric cancer. Radiotherapy was simulator planned using anterior-posterior parallel opposed fields to 45 Gy in 25 daily fractions over 5 weeks.

Thirteen patients (81%) completed radiotherapy and eight patients (50%) completed chemotherapy as planned. Toxicity was the main factor for discontinuation. Substantial dose inhomogeneities were shown using retrospective computed tomography recreation of dose-volume histograms (DVHs) of the organs at risk.

Although the delivery of chemoradiotherapy using conventional two-dimensional simulator planning is a feasible technique, significant under-appreciation of dose inhomogeneity exists. Conformal computed tomography planning is vital to document doses received by organs at risk, especially the spinal cord and kidneys, which may receive high doses, and prospectively correlate these with acute and long-term toxicity in order to redefine organ at risk tolerances in the setting of chemoradiation.

Radical surgery with extended lymph-node dissection is the treatment of first choice and the only curative treatment for locally advanced gastric cancer. While recent combination chemotherapy with S-1 (a combination of tegafur with two biomodulators, gimeracil and oteracil) has achieved high response rates, controversy still remains regarding the significance of adjuvant cancer chemotherapy after surgery. We have been applying chemosensitivity testing in evaluating the appropriate adjuvant cancer chemotherapy for advanced gastric cancer. Our multiple studies have indicated that this chemosensitivity testing would be useful to improve the results of adjuvant chemotherapy, by increasing survivals in the sensitive group. The chemosensitivity testing is approved as "advanced clinical medicine" by the Japanese Ministry of Health, Welfare, and Labor at 11 institutes at present. While complete lymph-node dissection and chemosensitivity test-guided adjuvant chemotherapy has been reported to result in a survival benefit for patients with advanced gastrointestinal cancer, the clinical utility of the testing should be established by means of prospective, randomized clinical trials. Two pivotal clinical trials have been initiated to clarify the utility of chemosensitivity testing in the selection of the appropriate adjuvant cancer chemotherapy for gastric cancer.

Adjuvant chemotherapy for gastric cancer after potentially curative surgery has been under clinical investigation for more than four decades. However, potentially curative resection can be performed in only 30%-50% of patients. The objective of this article is to review briefly the clinical trials available in the current literature using adjuvant cytotoxic chemotherapy in patients with gastric cancer after potentially curative surgical resection.

Computerized (MEDLINE) and manual searches were performed to identify papers published on this topic between 1965 and 2005. Only articles with an English abstract were reviewed for inclusion; information abstracted included histologic proof of diagnosis, number of patients, dose and modality of treatment, survival duration, and side effects.

Forty-three reports were identified. Single-agent chemotherapy was evaluated in four clinical trials, and postoperative combination chemotherapy was evaluated in 33 trials. Furthermore, we identified five meta-analyses. Five-year survival rates ranged from 12%-91.2%, and the median survival durations were 13-60+ months. Adjuvant chemotherapy, when compared with surgery alone, seems to result in longer survival.

The high rate of recurrence, even in patients undergoing state-of-the art curative resection, suggests that effective adjuvant chemotherapy might indeed be an attractive concept to improve the overall outcome of patients with gastric cancer. However, because there is no standard regimen for postoperative treatment at the moment, patients with R0-resected (no residual tumors) gastric cancer should be offered the opportunity to participate in prospective clinical trials.

Very few studies from Western centers have compared D2 and D3 dissection in the surgical treatment of gastric cancer. The aim of the prospective observational study reported here was to analyze the postoperative outcome and potential risk factors for complications following D2 and D3 lymphadenectomy.

A total of 330 consecutive patients, of which 251 submitted to D2 lymphadenectomy and 79 were treated by D3 lymphadenectomy, were enrolled in the study. Twenty potential risk factors for morbidity and mortality were studied by means of univariate and multivariate analysis.

Overall morbidity and mortality rates were 34% (111 patients) and 4% (14 patients), respectively. Abdominal abscess, anastomotic leakage, pleuropulmonary diseases and pancreatitis were the most commonly observed complications. No differences in morbidity, surgical morbidity, mortality rates and mean hospital stay between D2 and D3 lymphadenectomy were found. Multivariate analysis revealed that American Society of Anesthesiologists' (ASA) class II/III versus class I, perioperative blood transfusions, and low albumin serum levels were independent predictors of postoperative complications. Age, surgical radicality (R1/R2 vs. R0) and low albumin serum levels independently predicted mortality. Mortality rate was .5% in the 203 patients aged 75 years or younger who underwent curative surgery. Most of deaths were observed in patients older than 75 years with low albumin serum levels or treated by non-curative surgery.

D2 lymphadenectomy represents a feasible procedure associated to acceptable morbidity and mortality rates. In specialized centers, D3 lymphadenectomy may be performed without increasing the risk of postoperative complications and associated deaths in carefully selected patients. These techniques should be avoided in subgroups of patients with a high risk of postoperative mortality.

A previous study suggested that measurement of therapy-induced changes in tumor glucose metabolism by positron emission tomography (PET) with the glucose analog [18F]fluorodeoxyglucose (FDG) allows to select patients most likely to benefit from preoperative chemotherapy in adenocarcinomas of the esophagogastric junction (AEG). The aim of this study was to prospectively validate these findings by using an a priori definition of metabolic response.

Sixty-five patients with locally advanced AEGs were included. Tumor glucose utilization was quantitatively assessed by FDG-PET before chemotherapy and 14 days after initiation of therapy. Patients were classified as metabolic responders when the metabolic activity of the primary tumor had decreased by more than 35% at the time of the second PET.

Metabolic responders showed a high histopathologic response rate (44%) with a 3-year survival rate of 70%. In contrast, prognosis was poor for metabolic nonresponders with a histopathologic response rate of 5% (P = .001) and a 3-year survival rate of 35% (P = .01). A multivariate analysis (covariates: ypT-, ypN-category, histopathologic response) demonstrated that metabolic response was the only factor predicting recurrence (P = .018) in the subgroup of completely resected (R0) patients.

This study prospectively demonstrates that changes in tumor metabolic activity during chemotherapy predict response, prognosis, and recurrence. These data provide the basis for clinical trials in which preoperative treatment is changed for patients without a metabolic response early in the course of therapy. PET-guided induction therapy may even be applicable to earlier tumor stages because surgery is only minimally delayed in nonresponding patients.

Aim of this study is the evaluation of the effects induced by neoadjuvant chemotherapy (NACT) and its impact on survival on a series of locally advanced gastric carcinomas.

Downstaging was assessed comparing pre-treatment clinical and laparoscopic staging with post-operative pathologic staging on 30 consecutive patients who completed a 3-year follow-up. Tumor downstaging and the grade of pathologic response were included in a statistical correlation between tumor regression induced by NACT and 3-year survival.

In this series tumor downstaging was obtained in 13 out of 30 patients. After the completion of 3-year follow-up, overall survival was >37.5months with an overall survival rate of 56.7%; this figure reached up to 70.8% in those cases who benefited from a R0-resection (24/30 patients: R0-resection rate 80.0%).

In this study the 3-year survival for locally advanced gastric cancer treated by NACT prior to "D2" surgical resection, compares favourably with historical series treated by surgery alone. Patients who obtained T-downstaging and subsequently benefited from a R0-resection had a definitely better chance of cure, according to a complete 3-year follow-up.

The availability of different treatment options for radically resectable gastric cancer reopened the question of treatment selection and correct definition of high-risk categories. Lymphatic, blood vessel and perineural invasion (LBVI/PNI) seem to possess the necessary potential to provide useful information for the clinical management of this disease. Seven hundred and thirty-four patients with advanced gastric cancer who underwent curative gastrectomy were analysed according to the presence of LBVI/PNI. Patients were divided into two groups: group A for patients with LBVI/PNI (189 patients 26%) and group B for patients without LBVI/PNI (545 patients, 74%). The disease-free survival (DFS) for patients in group A was 32.1 months, whereas it was not reached for patients in group B (P=0.0001); the median overall survival was 45.5 months for patients in group A, whereas it was not reached for patients in group B (P=0.0001). At multivariate analysis, the presence of LBVI/PNI appeared an independent prognostic factor for DFS and OS. Our results were confirmed in subgroup analysis, separately considering stage I and early gastric cancer patients with and without LBVI/PNI. Taken together, our findings suggest the importance of LBVI/PNI in gastric cancer as it may provide additional information for identifying patients at high risk, who may be candidates for further medical treatment after or before surgery.

This article has reviewed the current role of radiation in the treatment of gastrointestinal malignancies and discussed the data supporting its use. Radiation treatment in this setting continues to evolve with the increasing implementation of more conformal delivery techniques. Further scientific investigation is needed to establish the optimal role of radiation and to better define its integration with novel systemic and biologic modalities.

The purpose of this review is to comment on the current status and the place of the (neo)adjuvant therapy of gastric cancer, and on the standardization of care in this setting.

The definition of optimal surgery remains controversial in gastric cancer. A recent review by the Dutch Gastric Cancer Group supports the so-called 'over-D1' extended lymphadenectomy, without pancreatectomy and splenectomy, as the optimal procedure, avoiding an increased postoperative mortality. The results from the phase III INT 116 trial should not definitively assign adjuvant chemoradiation as a robust standard of care, mainly due to the lack of optimal surgery in this trial. However, the concept of adjuvant chemoradiation will likely become more and more used, and will influence the design of future studies, reinforced by the incorporation of novel agents. If adjuvant chemotherapy failed to significantly increase survival, the use of perioperative chemotherapy (ECF regimen x 3 pre- and postoperative) was recently reported to improve survival, without affecting postoperative mortality and morbidity; mature results from this large phase III Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy trial should be considered as an important step implementing neoadjuvant chemotherapy as a new standard of care. Neoadjuvant therapy of locally advanced tumors also offers an ideal setting to assess new combinations, including cytotoxics, biologics and conformational radiation, coupled with translational research.

Much remains to be done before anticipating an incontestable standard of care in gastric cancer, although the recent phase III trials indicate that multimodality therapy could impact on the prognosis of gastric cancer.

There are still remarkable disparities in the treatment of gastric cancer between the East and West. Treatment outcomes for this disease have improved in Japan due to early detection and surgical resection with systematic node dissections, such as D2, whereas gastric cancer remains a virulent disease in Western countries. Differences in the types of surgery and their outcomes affect how adjuvant trials are conducted and interpreted. Recent Western randomized trials demonstrated the significant survival benefit of adjuvant chemoradiotherapy or intensive combination chemotherapy. However, baseline surgical quality and outcomes were quite different from those in Japan, and Japanese surgical/medical oncologists have not accepted the Western results. Several disparities are also evident in the results of chemotherapy trials for advanced gastric cancer. Although similar results were obtained with randomized studies using older regimens, the interpretation of the results differed between Japan and other countries. A combination of cisplatin and fluorouracil was used as the reference arm in ongoing randomized trials in most countries, whereas single-agent fluorouracil or S-1 alone was used in Japanese trials. Two triplet regimens have already demonstrated significant prolongation of survival in Western studies. However, these benefits seem to be marginal and these regimens may be replaced by newer regimens, which will soon be available in Europe and Asia, where a total of 2,600 patients have been accrued. Although these disparities between regions must be overcome, it is time for both Eastern and Western investigators to pursue further benefits by incorporating new agents into treatment regimens.

We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m-2 on day 1; capecitabine 850 mg m-2 12-hourly on days 1-9. Level 2: as level 1 but capecitabine 1000 mg m-2. Level 3: as level 2 but irinotecan 180 mg m-2. Level 4: as level 3 but capecitabine 1250 mg m-2. In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3-4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16-52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.

The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT).

Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial.

Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years.

Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase III trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United States exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced (T2-stage) cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase II trials using active drug combinations. In 2005, a large phase III trial testing pre- and postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. Since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase III studies testing this strategy may be warranted in the near future.

Ionizing radiation (IR) is a potent agent in enhancing tumor control of locally advanced cancer and has been shown to improve disease-free and overall survival in several entities. However, the role of radiotherapy (RT) in the treatment of gastrointestinal tumors remains controversial because of the marked radiation sensitivity of neighboring organs frequently compromising application of high doses of ionizing radiation.

The Medline and the Cochrane Library from 1980 until 2005 were searched using subject heading (MeSH) terms including "esophageal neoplasm", "gastric neoplasm", "pancreatic neoplasm" and "rectal neoplasm", in combination with the subheadings "radiotherapy", "chemotherapy". The term, "randomized controlled trial", was used to identify randomized trials. The proceedings of the annual meeting of the American Society for Therapeutic Radiology and Oncology from 1999 to 2004 and the annual meeting of the American Society of Clinical Oncology from 1999 until 2005 were searched. Ongoing trials were identified through the Physician Data Query database (www.cancer.gov/search/clinical_trials).

RT in combination with surgery enhances tumor control of locally advanced cancer disease and has been shown to improve disease-free and overall survival in rectal cancer. In esophageal adenocarcinoma, survival was prolonged with pre-operative chemo-radiation in a meta-analysis. In gastric cancer, post-operative chemo-radiation can be considered after limited lymphadenectomy. Evidence for improving survival remains to be shown for pancreatic cancer and hepatobiliary carcinoma. In colon cancer, post-operative chemotherapy has proven to prolong survival. The impact of RT seems to be most prominent in the pre-operative setting in patients treated with curative intent.

Pre-operative RT or pre-operative chemo-radiation may be considered in individual cases, but should not be used routinely for gastro-intestinal carcinoma, except for rectal carcinoma. In many studies, pre-operative radiotherapy/chemo-radiation yielded promising results and merits validation in large controlled trials.

Gastric cancer is often diagnosed in locally advanced or metastatic stages and, therefore, of poor prognosis. Many controversies exist about surgery, neoadjuvant, adjuvant and palliative treatments of gastric cancer. So we need to explore a variety of novel management options including the use of new agents and new combinations. Some of these agents include oral fluoropyrimidine, irinotecan, docetaxel and oxaliplatin. Oxaliplatin is a diaminocyclohexane-platinum compound that is significantly different from cisplatin and carboplatin with respect to its activity and toxicity. Oxaliplatin is an alkylating agent inhibiting DNA replication by forming adducts between two adjacent guanines or guanine and adenine molecules. However, the adducts of oxaliplatin appear to be more effective than cisplatin adducts in regard to the inhibition of DNA synthesis. In contrast to cisplatin, oxaliplatin has demonstrated efficacy alone and in combination with 5-fluorouracil in advanced colorectal cancer. Many studies are ongoing to test the combination in noncolorectal gastrointestinal tumors and other malignancies. This review focuses on the increasing amount of data concerning the clinical activity of oxaliplatin-based regimens in advanced gastric cancer.

The poor outcome associated with surgical resection alone for most patients with locoregional esophageal cancer has generated intensive investigation of combined-modality treatment approaches that include systemic chemotherapy. This review discusses the current role of chemotherapy in the treatment of patients with adenocarcinoma of the esophagus, given in either the pre-operative (neoadjuvant) or post-operative (adjuvant) setting compared to surgery alone, highlighting the results of large, randomized clinical trials that included patients with adenocarcinoma of the esophagus as well as some of the approaches being evaluated with novel therapies in earlier phase clinical trials. Although no definitive recommendations for pre-operative or post-operative treatment can be made for patients with adenocarcinoma of the esophagus based on outcomes reported in randomized clinical trials performed to date, the results from these trials suggest chemotherapy or chemoradiation in the peri-operative period may have benefit, especially in certain sub-groups. Newer, more effective agents are needed as well as methods to identify which tumors will respond to therapy. Improvement in outcomes for patients with this disease will require rigorous evaluation of newer multi-modality regimens in well-designed and appropriately powered clinical trials.

This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care. As you will read, there is much good news from the front lines of cancer research. These pages report on new chemotherapy regimens that sharply reduce the risk of recurrence for very common cancers; the "coming of age" of targeted cancer therapies; promising studies of drugs to prevent cancer; and improvements in quality of life for people living with the disease, among many other advances. Survival rates for cancer are on the rise, increasing from 50% to 64% over the last 30 years. Cancer still exacts an enormous toll, however. Nearly 1.4 million Americans will be diagnosed this year, and some 570,000 will die of the disease. Clearly, more research is needed to find effective therapies for the most stubborn cancer types and stages. We need to know more about the long-term effects of newer, more targeted cancer therapies, some of which need to be taken over long periods of time. And we need to devote far greater attention to tracking and improving the care of the nearly 10 million cancer survivors in the United States today. Despite these and other challenges, the message of this report is one of hope. Through the dedicated, persistent pursuit of clinical research and participation in clinical trials by people with cancer, we steadily uncover new and better ways of treating, diagnosing, and preventing a disease that touches the lives of so many. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report, and I hope you find it useful.