Gastric Cancer. 2013 Apr;16(2):233-8. doi: 10.1007/s10120-012-0171-4. Epub 2012 Jun 29.

Effect of adjuvant chemoradiotherapy on overall survival of gastric cancer patients submitted to D2 lymphadenectomy.

1Department of Gastrointestinal Medical Oncology, Barretos Cancer Hospital, Str Antenor Duarte Villela 1331, Barretos, SP, 14784-400, Brazil. jacome@usp.br

Abstract

BACKGROUND:

Adjuvant chemoradiotherapy (CRT) is the standard treatment in Western countries for gastric cancer patients submitted to curative resection. However, the role of adjuvant CRT in gastric cancer treated with D2 lymphadenectomy has not been well defined.

METHODS:

We conducted a retrospective study in patients with stage II to IV gastric adenocarcinoma with no distant metastases, who underwent curative resection with D2 lymphadenectomy between January 2002 and December 2007. The present study compared the 3-year overall survival of two treatments (adjuvant CRT according to the INT 0116 trial versus resection alone). Survival curves were estimated by the Kaplan-Meier method and compared with a log-rank test. Multivariate analysis of prognostic factors was performed by the Cox proportional hazards model.

RESULTS:

A total of 185 patients were included, 104 patients (56 %) received adjuvant CRT and 81 received resection alone. The 3-year overall survival was 64.4 % in the CRT group and 61.7 % in the resection-alone group (p: 0.415). However, according to the Cox proportional hazards model, adjuvant CRT was a prognostic factor for 3-year overall survival (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.26-0.82, p: 0.008).

CONCLUSIONS:

In the present study, adjuvant CRT was associated with a lower risk of death over a 3-year period in gastric cancer patients treated with D2 lymphadenectomy.

PMID: 22740060

 

SUPPLEMENT:

Gastric cancer is the second cause of cancer-related death and the fourth commonest cancer in the world. South America, Eastern Europe and Asia are the most affected geographical areas. Surgical resection is the cornerstone of treatment of localized gastric cancer. However, surgery alone provides unsatisfactory outcomes, with high recurrence rates and poor disease-free and overall survival.

In the past decade, randomized trials evaluated the potential benefit of adjuvant therapies in recurrence rates and survival. The pivotal trial INT0116 revealed that adjuvant chemoradiotherapy composed of 5-fluorouracil and leucovorin improved disease-free and overall survival (MacDonald JS et al, 2001). However, the trial was hampered by a suboptimal surgical treatment, because only a minority of patients have undergone D2 lymphadenectomy, which is considered to reduce the risk of locoregional recurrence and the risk of death related to gastric cancer (Songun I et al, 2010). The presence of residual disease in nonresected lymph nodes, which can be measured with a quantitative estimator denoted as the Maruyama index, is an independent prognostic factor in patients with gastric cancer (Peeters KC et al, 2005). The addition of radiotherapy to adjuvant therapy could be a useful strategy in patients submitted to more limited dissections, with a higher risk of microscopic locoregional disease. In patients with more extensive dissections, radiotherapy might not be of additional benefit in terms of survival and may actually have a deleterious effect by increasing the toxicity of treatment. The addition of radiotherapy is associated to higher toxicity, mainly gastrointestinal and mielotoxicity. Despite of these limitations, adjuvant chemoradiotherapy was widely adopted in Western countries.

Other adjuvant therapies evaluated in the past decade were perioperative chemotherapy and adjuvant chemotherapy. MAGIC trial studied the benefit of perioperative chemotherapy versus surgery alone, and it was demonstrated a superior disease-free and overall survival with three cycles of ECF (epirubicin, cisplatin and 5FU) preoperatively and three cycles postoperatively (Cunningham D et al, 2006). Likewise INT0116 trial, MAGIC trial did not have standardized surgical procedures.

Adjuvant chemotherapy was evaluated in ACTS-GC trial, which involved eastern population, and it was showed that adjuvant S-1, an oral fluoropyrimidine, improved survival after curative resection plus D2 lymphadenectomy (Sakuramoto S et al, 2007). The adoption of adjuvant chemotherapy in gastric cancer was reinforced by an interesting meta-analysis, which demonstrated a decrease of 18% of the risk of death with the incorporation of chemotherapy in the treatment of localized gastric cancer (Paoletti X et al, 2010).

Despite of availability of studies supporting the use of adjuvant therapies, there are no randomized trials comparing adjuvant chemoradiotherapy versus surgery alone in gastric cancer patients submitted exclusively to D2 lymphadenectomy. Retrospective study involving eastern population demonstrated that 5FU-based chemoradiotherapy reduced the risks of recurrence and death (Kim S et al, 2005).

In the attempt of contributing to clarify the role of adjuvant chemoradiotherapy in gastric cancer population who have undergone curative resection plus D2 lymphadenectomy, we performed this retrospective study, which was comprised of 201 western patients. Based on multivariate analysis, we found a meaningful reduction in the risk of death with the use of adjuvant chemoradiotherapy, corroborating the initial findings of the INT0116 trial. Our study was the only comparative study which reproduced the INT0116 trial in a western population submitted exclusively to D2 lymphadenectomy.

Recently, ARTIST trial compared chemoradiotherapy composed of capecitabine and cisplatin versus chemotherapy alone in a phase III study. It was showed a similar disease-free survival in the both arms, but a superior outcome in node-positive patients who have received combined modality treatment (Lee J et al, 2012). Based on this recent study and the previous ones, adjuvant chemoradiotherapy remains as the standard of care after curative resection of gastric cancer.

Through the lessons learned from breast and colon cancers, in which benefits derived from adjuvant therapy have been noted to differ according to the presence of prognostic and predictive factors, and in consideration of the findings of the ARTIST (Lee J et al, 2012) and ToGA trials (Bang YJ et al, 2010), maybe it would be interesting to examine carefully the design of more personalized randomized trials for adjuvant therapy in gastric cancer that take into account tailored therapies.

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