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      Adjuvant Radiochemotherapy versus Chemotherapy Alone for Gastric Cancer: Implications for Target Definition

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          Abstract

          The INT0116 trial was a milestone study and laid the foundation for the adjuvant radiotherapy (RT) associated to concurrent chemotherapy (CT) for the treatment of gastric cancer (GC) after gastrectomy. However, it is still controversial whether adding RT to CT could further benefit D2-dissected GC patients. The ARTIST trial indicated that the addition of RT to CT did not have a positive impact on disease-free survival (DFS). Nevertheless, in a subgroup of 396 patients with positive pathological lymph nodes, combined treatment with RT was superior to CT alone. A similar randomized Chinese trial confirmed the superiority of adding RT to CT in terms of DFS for patients with D2 lymphadenectomy. However, several previous randomized studies provided inconsistent results with the benefits of combined treatment of RT and CT. The inconsistent results of several studies may be due to the differences between tumor epidemiology, treatment policies, and treatment outcomes. During the past decade, major progress in accurate target delineation utilizing RT technology has been observed. However, even though the use of adjuvant RT doubled after the INT-0116 trial results became public, the fraction of patients receiving adjuvant RT was still low according to the SEER database. The low rate of adjuvant RT can partially be explained by concern over toxicity while undergoing RT. Several studies have also defined the specific location of locoregional recurrence for postoperative RT in GC, but these studies are still limited. A number of retrospective studies demonstrated that the most prevalent nodal recurrence was outside the D2 dissection field. In order to overcome the restricted nature of a retrospective study and provide more individual radiation field determination, additional large-scale prospective multicenter studies are required to evaluate the optimal RT target.

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          Most cited references43

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          Extended lymph-node dissection for gastric cancer.

          Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection, as recommended by the Japanese medical community, or a limited (D1) dissection. We conducted a randomized trial in 80 Dutch hospitals in which we compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery. Between August 1989 and July 1993, a total of 996 patients entered the study. Of these patients, 711 (380 in the D1 group and 331 in the D2 group) underwent the randomly assigned treatment with curative intent, and 285 received palliative treatment. The procedures for quality control included instruction and supervision in the operating room and monitoring of the pathological results. Patients in the D2 group had a significantly higher rate of complications than did those in the D1 group (43 percent vs. 25 percent, P<0.001), more postoperative deaths (10 percent vs. 4 percent, P= 0.004), and longer hospital stays (median, 16 vs. 14 days; P<0.001). Five-year survival rates were similar in the two groups: 45 percent for the D1 group and 47 percent for the D2 group (95 percent confidence interval for the difference, -9.6 percent to +5.6 percent). The patients who had R0 resections (i.e., who had no microscopical evidence of remaining disease), excluding those who died postoperatively, had cumulative risks of relapse at five years of 43 percent with D1 dissection and 37 percent with D2 dissection (95 percent confidence interval for the difference, -2.4 percent to +14.4 percent). Our results in Dutch patients do not support the routine use of D2 lymph-node dissection in patients with gastric cancer.
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            Recurrence following curative resection for gastric carcinoma.

            The diagnosis and treatment of recurrent gastric cancer remains difficult. The aim of this study was to determine the risk factors for recurrence of gastric cancer and the prognosis for these patients. Of 2328 patients who underwent curative resection for gastric cancer from 1987 to 1995, 508 whose recurrence was confirmed by clinical examination or reoperation were studied retrospectively. The risk factors that determined the recurrence patterns and timing were investigated by univariate and multivariate analysis. The mean time to recurrence was 21.8 months and peritoneal recurrence was the most frequent (45.9 per cent). Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence patterns and early recurrence (at 24 months or less). In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence; older age and larger tumour size for disseminated, haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. Reoperation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative operation was less than 12 months. The risk factors for each recurrence pattern and timing of gastric cancer can be predicted by the clinicopathological features of the primary tumour. Since the results of treatment remain dismal, studies of perioperative adjuvant therapy in an attempt to reduce recurrence are warranted.
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              Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial

              Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2019
                1 January 2019
                : 10
                : 2
                : 458-466
                Affiliations
                [1 ]Department of Radiation Oncology, the Second Affiliated Hospital and Cancer Institute (National Ministry of Education Key Laboratory of Cancer Prevention and Intervention), Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
                [2 ]Ben May Department for Cancer Research, University of Chicago, Chicago, IL, 60637, USA
                Author notes
                ✉ Corresponding author: Dr. Qichun Wei, Department of Radiation Oncology, the Second Affiliated Hospital and Cancer Institute (National Ministry of Education Key Laboratory of Cancer Prevention and Intervention), Zhejiang University School of Medicine, Hangzhou 310009, P.R. China. Postal address: Jiefang Road 88, Hangzhou 310009, PR China. Tel: +86-571-87783522; Fax: +86-571-87214404; E-mail: qichun_wei@ 123456zju.edu.cn

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav10p0458
                10.7150/jca.27335
                6360300
                30719140
                97f24582-7a70-4b78-81d4-e5ed6db67d45
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 18 May 2018
                : 28 October 2018
                Categories
                Review

                Oncology & Radiotherapy
                gastric cancer,radiotherapy,chemoradiotherapy,target definition
                Oncology & Radiotherapy
                gastric cancer, radiotherapy, chemoradiotherapy, target definition

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