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Perioperative chemotherapy more of a benefit for overall survival than adjuvant chemotherapy for operable gastric cancer: an updated Meta-analysis.

Yang Y, Yin X, Sheng L, Xu S, Dong L, Liu L - Sci Rep (2015)

Bottom Line: Subgroup analysis showed that the OS of the treatment arm that involved both adjuvant chemotherapy (AC) and NAC was significantly improved over the control arm (AC only) (HR = 0.48, 95% CI: 0.35-0.67; P < 0.001).While NAC alone plus surgery did not show any survival benefit over surgery alone.Perioperative chemotherapy (PC) also showed a significant increase in PFS and a significant reduction in distant metastasis compared to surgery alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China.

ABSTRACT
To clarify the effect of neoadjuvant chemotherapy (NAC) on the survival outcomes of operable gastric cancers, we searched PubMed, Embase, and Cochrane Library for randomized clinical trials published until June 2014 that compared NAC-containing strategies with NAC-free strategies in patients with adenocarcinoma of the stomach or the esophagogastric junction, who had undergone potentially curative resection. The adjusted pooled hazard ratio (HR) for overall survival (OS) was insignificant when comparing the NAC-containing arm with the NAC-free arm. Subgroup analysis showed that the OS of the treatment arm that involved both adjuvant chemotherapy (AC) and NAC was significantly improved over the control arm (AC only) (HR = 0.48, 95% CI: 0.35-0.67; P < 0.001). While NAC alone plus surgery did not show any survival benefit over surgery alone. Perioperative chemotherapy (PC) also showed a significant increase in PFS and a significant reduction in distant metastasis compared to surgery alone. Therefore, in patients with resectable gastric cancer, NAC alone is not enough and AC alone is not good enough to definitely improve their OS. Collectively, PC combined with surgery could maximize the survival benefit for patients with resectable gastric cancer.

No MeSH data available.


Related in: MedlinePlus

Overall HR for survival outcomes of resectable gastric cancers when comparing NAC-containing arm and NAC-free arm.(A) Forest plot showing the OS of resectable gastric cancer patients in the seven NAC-containing RCTs. (B) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by therapeutic strategies. (C) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by whether or not the regimen contained platinum. (D) Forest plot showing the PFS of resectable gastric cancer patients in three NAC-containing RCTs. HR, hazard ratio; 95% CI, 95%confidence interval; OS, overall survival; PFS, progression-free survival; NAC, neoadjuvant chemotherapy; AC, adjuvant chemotherapy; S, surgery; RCTs, randomized controlled trials.
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f2: Overall HR for survival outcomes of resectable gastric cancers when comparing NAC-containing arm and NAC-free arm.(A) Forest plot showing the OS of resectable gastric cancer patients in the seven NAC-containing RCTs. (B) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by therapeutic strategies. (C) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by whether or not the regimen contained platinum. (D) Forest plot showing the PFS of resectable gastric cancer patients in three NAC-containing RCTs. HR, hazard ratio; 95% CI, 95%confidence interval; OS, overall survival; PFS, progression-free survival; NAC, neoadjuvant chemotherapy; AC, adjuvant chemotherapy; S, surgery; RCTs, randomized controlled trials.

Mentions: The HR and 95% CIs of OS could be obtained directly320242527 or indirectly1922 in seven of the eight full-text articles investigating NAC in operable gastric cancer patients. The adjusted pooled estimate of the treatment effect appeared to be statistically significant (adjusted HR for death, 0.70; 95% CI: 0.55–0.88; P = 0.003; Fig. 2A). However, the therapeutic strategies in the seven trials varied geographically to some extent. Only two trials1920 focused primarily on NAC alone with the treatment arm receiving NAC plus surgery and the control arm receiving surgery alone. Trials by Nio24, Yonemura22, and Qu25 had PC (i.e. NAC and AC) plus surgery in the treatment arm and AC following surgery in the control arm. Because the only variation was whether or not NAC was performed, these three trials were regarded as being qualified in evaluating the effect of NAC and had been combined with the two trials above. However, the rest two trials327 compared the effects of PC plus surgery and surgery alone. It was impossible to determine the relative contribution of NAC regarding survival benefit. As shown in Fig. 2A, the pooled HR for OS in these two trials was 0.72 (95% CI: 0.60–0.87; P = 0.001), revealing a substantial survival benefit. Considering the high weight of these two trials in this meta-analysis (43%), the evaluation of the effect of NAC was interfered with by the performance of AC. Therefore, we excluded these two trials and combined the other five trials. The pooled, adjusted estimate of the treatment effect then became insignificant (HR = 0.68; 95% CI: 0.44–1.05; P = 0.08; Fig. 2B), although there was a trend toward favoring NAC. In addition, exclusion of the study24 with high risk of bias doesn’t have significant impact on the pooled estimate of the treatment effect (HR = 0.74; 95% CI: 0.41–1.25; P = 0.248).


Perioperative chemotherapy more of a benefit for overall survival than adjuvant chemotherapy for operable gastric cancer: an updated Meta-analysis.

Yang Y, Yin X, Sheng L, Xu S, Dong L, Liu L - Sci Rep (2015)

Overall HR for survival outcomes of resectable gastric cancers when comparing NAC-containing arm and NAC-free arm.(A) Forest plot showing the OS of resectable gastric cancer patients in the seven NAC-containing RCTs. (B) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by therapeutic strategies. (C) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by whether or not the regimen contained platinum. (D) Forest plot showing the PFS of resectable gastric cancer patients in three NAC-containing RCTs. HR, hazard ratio; 95% CI, 95%confidence interval; OS, overall survival; PFS, progression-free survival; NAC, neoadjuvant chemotherapy; AC, adjuvant chemotherapy; S, surgery; RCTs, randomized controlled trials.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525358&req=5

f2: Overall HR for survival outcomes of resectable gastric cancers when comparing NAC-containing arm and NAC-free arm.(A) Forest plot showing the OS of resectable gastric cancer patients in the seven NAC-containing RCTs. (B) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by therapeutic strategies. (C) Forest plot showing the OS of resectable gastric cancer patients in the five NAC-containing RCTs subgrouped by whether or not the regimen contained platinum. (D) Forest plot showing the PFS of resectable gastric cancer patients in three NAC-containing RCTs. HR, hazard ratio; 95% CI, 95%confidence interval; OS, overall survival; PFS, progression-free survival; NAC, neoadjuvant chemotherapy; AC, adjuvant chemotherapy; S, surgery; RCTs, randomized controlled trials.
Mentions: The HR and 95% CIs of OS could be obtained directly320242527 or indirectly1922 in seven of the eight full-text articles investigating NAC in operable gastric cancer patients. The adjusted pooled estimate of the treatment effect appeared to be statistically significant (adjusted HR for death, 0.70; 95% CI: 0.55–0.88; P = 0.003; Fig. 2A). However, the therapeutic strategies in the seven trials varied geographically to some extent. Only two trials1920 focused primarily on NAC alone with the treatment arm receiving NAC plus surgery and the control arm receiving surgery alone. Trials by Nio24, Yonemura22, and Qu25 had PC (i.e. NAC and AC) plus surgery in the treatment arm and AC following surgery in the control arm. Because the only variation was whether or not NAC was performed, these three trials were regarded as being qualified in evaluating the effect of NAC and had been combined with the two trials above. However, the rest two trials327 compared the effects of PC plus surgery and surgery alone. It was impossible to determine the relative contribution of NAC regarding survival benefit. As shown in Fig. 2A, the pooled HR for OS in these two trials was 0.72 (95% CI: 0.60–0.87; P = 0.001), revealing a substantial survival benefit. Considering the high weight of these two trials in this meta-analysis (43%), the evaluation of the effect of NAC was interfered with by the performance of AC. Therefore, we excluded these two trials and combined the other five trials. The pooled, adjusted estimate of the treatment effect then became insignificant (HR = 0.68; 95% CI: 0.44–1.05; P = 0.08; Fig. 2B), although there was a trend toward favoring NAC. In addition, exclusion of the study24 with high risk of bias doesn’t have significant impact on the pooled estimate of the treatment effect (HR = 0.74; 95% CI: 0.41–1.25; P = 0.248).

Bottom Line: Subgroup analysis showed that the OS of the treatment arm that involved both adjuvant chemotherapy (AC) and NAC was significantly improved over the control arm (AC only) (HR = 0.48, 95% CI: 0.35-0.67; P < 0.001).While NAC alone plus surgery did not show any survival benefit over surgery alone.Perioperative chemotherapy (PC) also showed a significant increase in PFS and a significant reduction in distant metastasis compared to surgery alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China.

ABSTRACT
To clarify the effect of neoadjuvant chemotherapy (NAC) on the survival outcomes of operable gastric cancers, we searched PubMed, Embase, and Cochrane Library for randomized clinical trials published until June 2014 that compared NAC-containing strategies with NAC-free strategies in patients with adenocarcinoma of the stomach or the esophagogastric junction, who had undergone potentially curative resection. The adjusted pooled hazard ratio (HR) for overall survival (OS) was insignificant when comparing the NAC-containing arm with the NAC-free arm. Subgroup analysis showed that the OS of the treatment arm that involved both adjuvant chemotherapy (AC) and NAC was significantly improved over the control arm (AC only) (HR = 0.48, 95% CI: 0.35-0.67; P < 0.001). While NAC alone plus surgery did not show any survival benefit over surgery alone. Perioperative chemotherapy (PC) also showed a significant increase in PFS and a significant reduction in distant metastasis compared to surgery alone. Therefore, in patients with resectable gastric cancer, NAC alone is not enough and AC alone is not good enough to definitely improve their OS. Collectively, PC combined with surgery could maximize the survival benefit for patients with resectable gastric cancer.

No MeSH data available.


Related in: MedlinePlus