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Background

For gastric cancer surgery is the mainstay treatment. Chemotherapy seems lớn improve the survival results. But chemotherapy is not a complication‐free therapy và its role has been questioned by some trials.

Objectives

To determine whether post‐surgical chemotherapy should be used routinely in resectable gastric cancer.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (July 2013).

Selection criteria

Randomised controlled trials (RCT) comparing post‐surgical chemotherapy versus surgery alone for resectable gastric cancer.

Data collection & analysis

Two authors independently assessed trials for inclusion và independently extracted the data. We analysed the data with both the fixed‐effect và the random‐effects models using the RevMan analysis software. We calculated the hazard ratio (HR) with 95% confidence interval (CI) based on intention‐to‐treat or available case analysis.

Main results

The authors identified 34 studies (7824 patients) reporting overall survival (OS) và only 15 reporting disease free survival (DFS) as well. Post‐surgical chemotherapy showed an improvement in OS (HR 0.85; 95% CI 0.80 to lớn 0.90) và an improvement in DFS (HR 0.79; 95% CI 0.72 lớn 0.87), although all the trials had a high risk of bias.

The planned analysis of quality of life, return khổng lồ work, and number of hospital admissions was impossible to complete as the outcome data for the analysis were not available from any trials.

Authors"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg conclusions

Post‐surgical chemotherapy should be used routinely for resectable gastric cancer where possible. Further RCTs are needed lớn determine the role at each stage of disease.

PICOs

PICOs

Population
Intervention

Chemotherapy after surgery versus surgery alone for stomach cancer

Stomach cancer is the second leading cause of cancer‐related death worldwide. Surgery is the only curative treatment offered khổng lồ patients suffering from this cancer. Survival rates, however, are still poor. Chemotherapy given after surgery has been developed in order to lớn improve these results. We identified 34 trials with 7824 patients which randomised patients lớn surgery with post‐surgical chemotherapy versus surgery alone. The group who received chemotherapy had a survival benefit và improvement in disease free survival (15% & 21%, respectively), although all the trials had a high risk of bias. There was no significant difference due khổng lồ the stage of disease or the chemotherapy agent used.

Visual summary

Implications for practice

Post‐surgical chemotherapy should be use for patients with resectable gastric cancer following the results of this review, however it is important to lưu ý that some of the included trials present limitations và definitive assessments on this topic may be delayed until future trials are properly developed.

Implications for research

Further low bias‐risk trials are necessary khổng lồ determine wether post‐surgical chemotherapy should be used routinely in every stage of gastric cancer. The chemotherapy agent and the standard regimen và duration are still topics that require clarification. Chất lượng of life và cost‐effectiveness represent two important topics that should be considered in future studies.

Summary of findings

Post‐surgical chemotherapy compared khổng lồ surgery alone for resectable gastric cancer

Patient or population: patients with resectable gastric cancer Settings: Intervention: Post‐surgical chemotherapy Comparison: Surgery alone

Outcomes

Relative effect (95% CI)

No of Participants (studies)

Quality of the evidence (GRADE)

Overall Survival (OS)

HR 0.85 (0.80 to 0.90)

7523 (34 studies)

High quality

Disease không tính phí Survival

HR 0.79 (0.72 to lớn 0.87)

4133 (15 studies)

High quality

*The basis for the assumed risk (e.g. The median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; HR: Hazard ratio;

GRADE Working Group grades of evidence High quality: Further research is very unlikely khổng lồ change confidence in the estimate of effect. Moderate quality: Further research is likely to lớn have an important impact on confidence in the estimate of effect & may change the estimate. Low quality: Further research is very likely lớn have an important impact on confidence in the estimate of effect và is likely to change the estimate. Very low quality: Very uncertain about the estimate.

Open in table viewer
Summary of findings 2.Subgroup analysis for resectable gastric cancer

Subgroup analysis for resectable gastric cancer
Patient or population: patients with resectable gastric cancer Settings: Intervention: Subgroup analysis
Outcomes	Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)
Chemobased OS ‐ 5‐FU based chemotherapy OS	HR 0.88 (0.83 lớn 0.94)	5694 (28 studies)	Moderate quality
Chemobased OS ‐ Platinum‐based chemotherapy OS	HR 0.9 (0.81 to lớn 1)	1504 (9 studies)	Moderate quality
Chemobased DFS ‐ 5‐FU based chemotherapy DFS	HR 0.86 (0.78 to 0.95)	2944 (13 studies)	Moderate quality
Chemobased DFS ‐ Platinum‐based chemotherapy DFS	HR 0.89 (0.75 to 1.06)	969 (4 studies)	Moderate quality
*The basis for the assumed risk (e.g. The median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; HR: Hazard ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely khổng lồ change confidence in the estimate of effect. Moderate quality: Further research is likely khổng lồ have an important impact on confidence in the estimate of effect và may change the estimate. Low quality: Further research is very likely lớn have an important impact on confidence in the estimate of effect và is likely lớn change the estimate. Very low quality: Very uncertain about the estimate.

Open in table viewer
Summary of findings 3.Subgroup analysis for resectable gastric cancer

Subgroup analysis for resectable gastric cancer
Patient or population: patients with resectable gastric cancer Settings: Intervention: Subgroup analysis
Outcomes	Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)
Stage OS analysis ‐ T1/2 OS	HR 0.86 (0.71 to lớn 1.05)	1146 (5 studies)	Moderate quality
Stage OS analysis ‐ T3/4 OS	HR 0.66 (0.41 to lớn 1.08)	1008 (4 studies)	Moderate quality
Lymph node mets analysis ‐ N‐ OS	HR 0.74 (0.41 to lớn 1.33)	402 (2 studies)	Moderate quality
Lymph node mets analysis ‐ N+ OS	HR 0.78 (0.67 to 0.91)	877 (4 studies)	Moderate quality
*The basis for the assumed risk (e.g. The median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; HR: Hazard ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely lớn change confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on confidence in the estimate of effect & may change the estimate. Low quality: Further research is very likely to lớn have an important impact on confidence in the estimate of effect và is likely khổng lồ change the estimate. Very low quality: Very uncertain about the estimate.

Background

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Description of the condition

Gastric cancer is an important disease worldwide and it represents the second leading cause of cancer‐related death in the world (CRUK 2012). In 2008, 3052 deaths due lớn gastric cancer were reported in the United Kingdom & 6450 in the United States of America (GLOBOCAN 2008).

Adenocarcinoma represents 90% of all gastric cancers. It has been classified as well‐differentiated or intestinal type, and undifferentiated or diffuse type (Crew 2006). Other histological types like epidermoid tumours or stromal tumours have a significantly lower incidence và a very different clinical course, management và prognosis than adenocarcinoma.

Surgical resection is, khổng lồ date, the main management and the only curative treatment that can be offered to patients with gastric cancer (Alberts 2003). Partial gastric resection or total gastrectomy are the surgical options commonly performed and both try lớn maximize elimination of tumour, with no significant difference in terms of survival when they are compared (Bozzetti 1999). Extended lymphadenectomy procedures aim to eradicate any residual disease or tumour cell progression through lymph nodes but the role of these procedures is controversial và there is an important disparity of results in the demonstration of real improvement in survival and the morbidity of this additional therapy (McCulloch 2003; Memon 2011).

The role of chemotherapy remains unclear & the presence in the literature ofat least seven meta‐analyses regarding this topic tư vấn this notion (Earle 1999; Hermans 1993; Hu 2002; Jeung 2009; Mari 2000; Oba 2006; Paoletti 2010). Chemotherapy và surgery can be combined in different regimes as chemotherapy can be administrated previous khổng lồ or after surgery. Commonly, it is accepted as "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgadjuvant chemotherapy"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg if it is administrated after surgery, "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgneoadjuvant chemotherapy"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg when it takes place previous to surgery, và "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgperioperative chemotherapy"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg when both neoadjuvant & adjuvant chemotherapy are combined. However, sometimes this is unclear in some trials, hence we refer lớn our intervention as post‐surgical chemotherapy in order to avoid confusion.

Surgery alone is described as adequate treatment for early stage tumours (Kim 1992b), và it is commonly accepted that chemotherapy should be given to those patients with an advanced stage tumour (Wagner 2005). This is supported by recent publications (Sun 2009) but other well‐defined trials and older meta‐analyses vày not nói qua these results (Di Costanzo 2008; Hermans 1993). Secondly, early recurrence and disease không lấy phí survival period are not described in some of the current reviews. Finally, morbidity & mortality related khổng lồ chemotherapy have not been properly reported and they both may modify the recommendation for chemotherapy.

Analysis of old and new trials comparing chemotherapy versus surgery alone, once curative resection has been performed, may clarify the role of adjuvant chemotherapy in overall survival và disease không tính phí survival in patients with gastric cancer.

Description of the intervention

After potentially curative surgical resection for gastric cancer, chemotherapy using a single drug or a combination of drugs may be given (post‐surgical chemotherapy).

How the intervention might work

Post‐surgical chemotherapy may remove residual cancer cells or cancer cells in the systemic circulation that surgery cannot remove and which could be the reason for recurrence and death (Eguchi 2008).

Why it is important to vị this review

The treatment options for resectable gastric cancer include resection alone, resection with pre‐surgical và post‐surgical chemotherapy (perioperative chemotherapy), and post‐surgical chemotherapy. The role of gastric resection with pre‐surgical và post‐surgical chemotherapy is being assessed in another Cochrane review (Slanger 2009). The role of post‐surgical chemotherapy for gastric cancer in improving patient survival remains unclear. In addition, the use of chemotherapeutic agents is not risk không tính phí and they should be used only if justified. Post‐surgical chemotherapy has been found khổng lồ be effective in the treatment of other cancers such as breast cancer (EBCTCG 2008; Ferguson 2007; Mauri 2008). However, while some trials seem to tư vấn the use of post‐surgical chemotherapy for resectable gastric cancers (Nakajima 2007; Paoletti 2010) others bởi vì not (Di Costanzo 2008b; Hu 2002). The aim of this nhận xét was khổng lồ determine whether post‐surgical chemotherapy improves overall survival and disease không lấy phí survival in patients with resectable gastric cancer.

Objectives

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Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCT). We excluded quasi‐randomised studies for survival outcomes but included them for evaluation of the adverse effects of chemotherapy, such as anaemia and gastrointestinal toxicity.

Types of participants

Patients undergoing partial or total gastrectomy for gastric cancer, irrespective of the location of the cancer (distal, proximal or oesophagogastric junction).

Types of interventions

Post‐surgical chemotherapy (irrespective of whether a single drug or a combination of drugs were used and the duration of the treatment) versus surgery alone without post‐surgical chemotherapy in patients undergoing partial or total gastrectomy, irrespective of nodal status, whether pancreatosplenectomy was performed, or the presence of microscopic involvement of the resection margins.

We excluded trials assessing the following interventions.

Combination of pre‐surgical and post‐surgical chemotherapy in patients undergoing resection for gastric cancer.

Combination of post‐surgical chemotherapy and radiotherapy in patients undergoing resection for gastric cancer.

Combination of post‐surgical chemotherapy and immunotherapy using drugs which have generic immunomodulation potential in patients undergoing resection for gastric cancer. However, we included any trials which used monoclonal antibodies that were targeted against specific proteins in combination with post‐surgical chemotherapy. We only excluded non‐specific immunotherapy, such as interferon or bacillus Calmette‐Guerin (BCG) as it would be difficult to lớn assess the effectiveness of the chemotherapy.

Types of outcome measures Primary outcomes

Overall survival:

hazard ratio.

Disease free survival:

hazard ratio.

Secondary outcomes

unique of life (however defined by authors).

Number of hospital admissions after discharge.

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Return khổng lồ work.

Search methods for identification of studies

We searched the following resources.

Electronic searches

Searching other resources

Reference lists from trials selected by electronic searching were handsearched to identify further relevant trials. Published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut), Digestive Disease Week (published in Gastroenterology) & ENT news also were handsearched.

In addition, members of the Cochrane Upper Gastrointestinal và Pancreatic Diseases (UGPD) Group & experts in the field were contacted & asked to provide details of outstanding clinical trials and any relevant unpublished materials. We also contacted the Cochrane Ear, Nose và Throat Diseases Group to lớn confirm that our search was comprehensive.

The đánh giá authors carried out the tìm kiếm independently from each other. Reference lists of identified publications were scanned for additional trials & authors contacted if necessary. In addition, the reference lists of any previous đánh giá on the subject và the reviews authors"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg own files were scanned for relevant studies. No language restrictions were applied. The full text articles of the retrieved trials were reviewed by at least two nhận xét authors and the inclusion criteria applied independently. Any differences in opinion about which studies khổng lồ include in the reviews were resolved by discussion between the review authors. Possible additional tìm kiếm terms were discussed at one of the conferences where the subject was presented.

Data collection & analysis

Selection of studies

Two authors (RDN và ROR) identified the trials for inclusion, independent of each other. We also listed the excluded trials with the reasons for exclusion in the "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgCharacteristics of excluded studies"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg table.

Data extraction & management

RDN and ROR extracted the data for the đánh giá independently. In addition, we extracted the population characteristics (such as sex, age, type of gastrectomies) & the interventions used in each trial. We clarified any unclear or missing information by contacting the authors of the individual trials. If there was any doubt as to whether the trials shared the same patients, completely or partially (by identifying common authors and centres), we contacted the authors of the trials khổng lồ establish whether the trial report had been duplicated. We resolved any differences in opinion through discussion.

For overall survival & disease không lấy phí survival, we extracted the logarithm of hazard ratios và the standard error (SE) of ln(HR) using the methods described by Parmar et al (Parmar 1998) and the Excel sheet provided by Tierney et al (Tierney 2007).

We followed the instructions given in the Cochrane Handbook for Systematic đánh giá of Interventions (Higgins 2008) and the Cochrane Upper GastrointestinaI và Pancreatic Diseases Group Module (Forman 2009). We imputed the standard deviation from p. Values according lớn the Cochrane Handbook for Systematic đánh giá of Interventions & used the median for the meta‐analysis when the mean was not available. If it was not possible lớn calculate the standard deviation from phường values or confidence intervals, we imputed the standard deviation as the highest standard deviation noted for that group under that outcome.

Assessment of risk of bias in included studies

According khổng lồ empirical evidence (Kjaergard 2001; Moher 1998; Schulz 1995; Wood 2008), we assessed the risk of bias in the trials based on sequence generation, allocation concealment, blinding (of participants, personnel và outcome assessors), incomplete outcome data, selective outcome reporting và other sources of bias. We assessed the risk of bias in the trials independently, without masking of the trial names. Unique components were based on the Cochrane Handbook for Systematic đánh giá of Interventions (Gurusamy 2009; Higgins 2008).

Sequence generation

Low risk of bias (the method used is either adequate (e.g. Computer‐generated random numbers, table of random numbers) or unlikely lớn introduce confounding).

Uncertain risk of bias (there is insufficient information lớn assess whether the method used is likely khổng lồ introduce confounding).

High risk of bias (the method used (e.g. Quasi‐randomised trials) is improper and likely to lớn introduce confounding).

Allocation concealment

Low risk of bias (the method used (e.g. Central allocation) is unlikely to lớn induce bias in the final observed effect).

Uncertain risk of bias (there is insufficient information to lớn assess whether the method used is likely khổng lồ induce bias in the estimate of effect).

High risk of bias (the method used (e.g. Mở cửa random allocation schedule) is likely to induce bias in the final observed effect).

Blinding of participants, personnel and outcome assessors

Low risk of bias (blinding was performed adequately, or the outcome measurement is not likely khổng lồ be influenced by lack of blinding).

Uncertain risk of bias (there is insufficient information lớn assess whether the type of blinding used is likely khổng lồ induce bias in the estimate of effect).

High risk of bias (no blinding or incomplete blinding, & the outcome or the outcome measurement is likely to lớn be influenced by lack of blinding).

Incomplete outcome data

Low risk of bias (the underlying reasons for missing data are unlikely to lớn make treatment effects depart from plausible values, or proper methods have been employed to lớn handle missing data).

Uncertain risk of bias (there is insufficient information lớn assess whether the missing data mechanism in combination with the method used khổng lồ handle missing data is likely to lớn induce bias in the estimate of effect).

High risk of bias (the crude estimate of effects (e.g. Complete case estimate) will clearly be biased due to the underlying reasons for missing data, và the methods used khổng lồ handle missing data are unsatisfactory).

Selective outcome reporting

Low risk of bias (the trial protocol is available and all of the trial"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgs prespecified outcomes that are of interest in the đánh giá have been reported, or similar).

Uncertain risk of bias (there is insufficient information to assess whether the magnitude and direction of the observed effect is related lớn selective outcome reporting).

High risk of bias (not all of the trial"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgs prespecified primary outcomes have been reported, or similar).

Other bias Baseline imbalance

Low risk of bias (there was no baseline imbalance in important characteristics).

Uncertain risk of bias (the baseline characteristics were not reported).

High risk of bias (there was a baseline imbalance due lớn chance or due lớn imbalanced exclusion after randomisation).

Early stopping

Low risk of bias (sample kích thước calculation was reported and the trial was not stopped or the trial was stopped early by a formal stopping rule at a point where the likelihood of observing an extreme intervention effect due to chance was low).

Uncertain risk of bias (sample kích cỡ calculations were not reported and it is not clear whether the trial was stopped early or not).

High risk of bias (the trial was stopped early due to lớn an informal stopping rule or the trial was stopped early by a formal stopping rule at a point where the likelihood of observing an extreme intervention effect due lớn chance was high).

Source of funding bias

Low risk of bias (the trial"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgs source(s) of funding was from no parties that might have conflicting interest (e.g. Pharmaceutical company)).

Uncertain risk of bias (the source of funding was not clear).

High risk of bias (the trial was funded by a pharmaceutical company).

We considered trials which were classified as low risk of bias in sequence generation, allocation concealment, blinding, incomplete data và selective outcome reporting as low bias‐risk trials.

Measures of treatment effect

The hazard ratio (HR) was measured with 95% confidence interval (CI) for overall survival and disease free survival. For dichotomous outcomes, the risk ratio (RR) was calculated with 95% CI. For continuous outcomes, we calculated the mean difference (MD) or standardised mean difference (SMD) with 95% CI. The risk difference (RD) was also estimated with 95% CI for dichotomous outcomes & results were only reported if they were different from the RR.

Unit of analysis issues

The unit of analysis was each patient recruited into the trials.

Dealing with missing data

Analysis was performed on an "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgintention‐to‐treat"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg basis (Newell 1992) whenever possible. Otherwise, the "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgavailable case"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg analysis was adopted.

Assessment of heterogeneity

Heterogeneity was explored by the Chi² test with significance phối at a p. Value of 0.10, & we measured the quantity of heterogeneity with the I² statistic (Higgins 2002). An I² statistic of > 50% was considered statistically significant heterogeneity. We calculated the 95% CI for I² using StatsDirect statistical software (StatsDirect 2008). Meta‐regression would have been performed in the presence of at least 10 trials.

Assessment of reporting biases

Asymmetry in a funnel plot of trial kích cỡ against treatment effect was used khổng lồ assess bias (Egger 1997; Macaskill 2001). The linear regression approach described by Egger et al was performed khổng lồ determine the funnel plot asymmetry (Egger 1997).

Data synthesis

The meta‐analyses was performed according to the recommendations of The Cochrane Collaboration (Higgins 2008). The software package RevMan 5 provided by the Cochrane Collaboration was used (RevMan 2008). A random‐effects mã sản phẩm (DerSimonian 1986) and a fixed‐effect mã sản phẩm were used (DeMets 1987). In the case of discrepancy between the two models, both results were reported; otherwise only the results from the fixed‐effect mã sản phẩm were mentioned. HRs of overall survival & disease không tính tiền survival obtained from the different trials were combined using the generic inverse variance method.

Subgroup analysis & investigation of heterogeneity

The following subgroup analyses were planned.

Trials with low risk of bias versus those with high risk of bias.

Different types of chemotherapy as well as number of regimens & rate of cycles completed.

Different surgical procedures (partial versus total gastrectomy).

Different lymphadenectomy procedures (D1 versus D2 resection).

Different approaches (open versus laparoscopic approach).

Microscopically clear resection margin versus microscopically involved tumour margin.

Different locations of tumour.

Different histological types of gastric cancer.

Different stages of gastric cancer (T1, T2 versus T3, T4).

The Chi² chạy thử for subgroup differences was mix at a p value of 0.05.

Sensitivity analysis

Sensitivity analysis was performed by excluding the trials which included gastric cancers at the gastro‐oesophageal junction.

Results

Description of studies

Results of the tìm kiếm

A total of 3391 references were identified through the electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded. The flow of references are shown in Figure 1. A total of 467 duplicates & 2879 clearly irrelevant references were excluded through reading abstracts. Forty‐five references were retrieved for further assessment. Of the 45 references, 11 references were excluded because of the reasons listed in the table "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgCharacteristics of excluded studies"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg. Three references corresponded lớn the same study (Alcobendas 1983; Estape 1991; Grau 1993) & hence the inclusion of two studies under the excluded studies. Of the remaining references, 34 randomised trials fulfilled the inclusion criteria. Once the full analysis of data was achieved the search strategy was rerun up to July 2013, in order to assure the presence of the most recent trials. This new search resulted in 189 new citations (MEDLINE=129, EMBASE=27, CENTRAL=21, Science Citation Index= 68) of which only three were considered relevant. One of these remaining was excluded & listed in the table "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgCharacteristics of excluded studies"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg (Chen 2011) and the other two trials were added to the section “studies awaiting classification” (Bang 2012; Sasako 2011).

Included studies

All 34 trials were completed trials và could provide data for the analyses. Details of the trials are shown in the table "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgCharacteristics of included studies"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg. Overall the 34 trials included 7824 patients. The mean age of the individuals in the trials varied between 54 (Kim 1992) và 65 years (Tentes 2006). The mean proportion of females varied between 19% (Popiela 2004) to 47% (Hallissey 1994). There was no difference in the characteristics of patients in the intervention group và control group in any of the trials that reported these baseline characteristics. However, a wide variation was found between trials as the interventions were not exactly the same in all the studies. Differences were in terms of the drugs, doses & duration of the treatments as well as the kiến thiết of the studies; but almost every trial based their intervention on 5‐fluorouracil (5‐FU) or platinum‐based chemotherapy (Platino), considered for separate analysis by subgroup.

Excluded studies

The reasons for exclusion of the studies are listed in the table "https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpgCharacteristics of excluded studies"https://baoninhsunrise.com/1gom7m/imager_2_15483_700.jpg.

Risk of bias in included studies

The risk of bias is summarised in the risk of bias graph (Figure 2) and risk of bias summary (Figure 3).

Allocation

The generation of allocation sequence was adequate in six trials (Bajetta 2002; Chipponi 2004;Nakajima 1999; Nakajima 2007; Nitti 2006 EORTC; Sakuramoto 2007) and allocation concealment was adequate in 11 trials (Bonfanti 1988; Cirera 1999; Coombes 1990;Hallissey 1994; Higgins 1983; Huguier 1980; Nakajima 2007; Nashimoto 2003; Ochiai 1983; Popiela 2004; Sakuramoto 2007).

Blinding

Blinding was adequate in one trial (Allum 1989) where the authors reported the use of placebo for the surgery alone arm in the same regimen as the chemotherapy was administrated to lớn the intervention arm.

Incomplete outcome data

Five trials were miễn phí from bias due khổng lồ incomplete outcome data (Allum 1989; Bonfanti 1988; Douglas 1982; Engstrom 1985; Higgins 1983). In 28 trials, there were post‐randomisation dropouts resulting in high risk of bias from incomplete outcome data.

Selective reporting

Twenty‐eight trials were không tính tiền from bias due to lớn selective reporting (Allum 1989; Bajetta 2002; Bouché 2005; Chipponi 2004; Chou 1994; Cirera 1999; Coombes 1990;De Vitta 2007; Di Costanzo 2008; Douglas 1982; Engstrom 1985; Fielding 1983; Fujimoto 1977; Hallissey 1994; Higgins 1983; Huguier 1980;Krook 1991; Lise 1995; Macdonald 1995; Nakajima 1999; Nakajima 2007; Neri 2001; Nitti 2006 EORTC; Nitti 2006 ICCG; Ochiai 1983; Popiela 1982; Popiela 2004; Sakuramoto 2007).

Other potential sources of bias

Fifteen trials were free from other potential sources of bias (Allum 1989; Bajetta 2002; Bonfanti 1988; Bouché 2005; Cirera 1999; Coombes 1990; Di Costanzo 2008; Douglas 1982; Engstrom 1985; Fielding 1983; Fujimoto 1977; Hallissey 1994; Huguier 1980; Macdonald 1995; Nakajima 1999).

Effects of interventions

See: Summary of findings for the main comparison Post‐surgical chemotherapy compared lớn surgery alone for resectable gastric cancer; Summary of findings 2 Subgroup analysis for resectable gastric cancer; Summary of findings 3 Subgroup analysis for resectable gastric cancer

Primary outcomes Overall survival

A total of 34 trials (7523 participants) provided data on overall survival with homogeneous results (I² = 31%). Post‐surgical chemotherapy showed a significant beneficial effect on overall survival (HR 0.85; 95% CI 0.80 lớn 0.90) (Figure 4; Figure 5).