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Postoperative chemoradiotherapy vs. preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy.

ABSTRACT: BACKGROUND:Worldwide, almost one million new cases of stomach cancer were diagnosed in 2012, making it the fifth most common cancer, and the third leading cause of cancer deaths. The current tumor node metastasis (TNM) staging system represents a consensus between the East and the West, and will serve as a strong foundation upon which to build future evidence. In this review article, we first discuss the definition and optimal surgery for locally advanced gastric cancer, followed by the general principles when considering a pre vs. postoperative radiotherapy (RT) strategy. We then provide a synthesis of the existing randomized trial evidence in an attempt clarify the role of pre and postoperative RT in the management of locally advanced gastric cancer. METHODS:A Medline search 1966-Jun 2014 was undertaken. Randomized trials including patients with locally advanced gastric cancer (using established definitions), comparing RT [with or without chemotherapy (CT)], with surgery alone or other treatment modalities were included. Systematic reviews and evidence based practice guidelines that include this body of primary studies were preferentially discussed. Medline, Cochrane Library, Clinicaltrial.gov, Guidelines Clearinghouse were searched. RESULTS:Sixteen randomized trials, three systematic reviews and one practice guideline were included as the evidence base. In this group of studies, two reports compared postoperative chemoradiotherapy (CRT) with surgery alone. Driven predominantly by INT0116, they established the role of postoperative CRT to provide a survival benefit in a patient group that underwent surgery with predominantly D0-1 dissections. Preoperative RT (four studies) showed promise for survival benefit but the risks of bias in these trials were high. Postoperative CRT compared with CT alone (eight trials) showed no survival benefit with the addition of radiation although some evidence of activity can be observed with improved local regional control. CONCLUSIONS AND FUTURE DIRECTIONS:Technical expertise to enable the delivery of high quality RT to complex target volumes as is required in gastric cancer, and surgical standards to ensure the delivery of high quality surgery, have matured in recent years. Six trials with large sample sizes are currently ongoing to better define the role of preoperative CRT (two studies) and postoperative CRT (four studies), when used in conjunction with high quality surgery and RT, and contemporary CT regimens. The moderate likelihood of locoregional recurrences and the favorable therapeutic ratio with using RT preoperatively in other settings, provide optimism that preoperative CRT would have a pivotal role to play in locally advanced gastric cancer. Active accrual into ongoing trials is strongly encouraged.

SUBMITTER: Wong RK

PROVIDER: S-EPMC4294828 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Postoperative chemoradiotherapy vs. preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy.

Wong Rebecca K S RK Jang Raymond R Darling Gail G

Journal of gastrointestinal oncology 20150201 1

<h4>Background</h4>Worldwide, almost one million new cases of stomach cancer were diagnosed in 2012, making it the fifth most common cancer, and the third leading cause of cancer deaths. The current tumor node metastasis (TNM) staging system represents a consensus between the East and the West, and will serve as a strong foundation upon which to build future evidence. In this review article, we first discuss the definition and optimal surgery for locally advanced gastric cancer, followed by the ...[more]

PMID: 25642342

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Project description:PurposeAlthough adjuvant chemoradiotherapy (CRT) used to be recommended as a standard of care for locally advanced gastric cancer, this suggestion has been strongly challenged recently. However, clear evidence regarding the optimization of radiotherapy is lacking. The purpose of this study was to compare the effectiveness of preoperative CRT versus that of postoperative CRT for resectable or potentially resectable gastric cancer.MethodsFrom January 2005 to December 2017, patients with clinical stage III/IVa (i.e., T3-4aN+M0 or T4bNxM0) locally advanced gastric cancer were retrospectively identified. Survival after preoperative CRT and postoperative CRT was assessed by unadjusted, propensity score matching (PSM) and inverse probability of treatment weight (IPTW) analyses. Moreover, exploratory subgroup analyses were performed, and toxicity and patterns of failure were also investigated.ResultsThe median follow-up time was 32.5 months. A total of 82 and 463 patients were enrolled in the preoperative and postoperative CRT groups, respectively. After propensity score matching, preoperative CRT was associated with improved overall survival (OS) and disease-free survival (DFS) compared with postoperative CRT (3-year OS: 72.6 vs. 54.4%, log-rank p = 0.0021; 3-year DFS: 61.7 vs. 44.7%, log-rank p = 0.002). The unadjusted and IPTW analyses yielded consistent results. A complete pathologic response was achieved in 13.4% of the preoperative CRT group. Although the incidence of grade 3 or 4 adverse effects and surgical complications were similar between the two groups, significantly fewer patients experienced treatment interruptions or dose reductions due to toxic effects in the preoperative CRT setting than in the postoperative CRT setting (3.7 vs. 10.6%, p = 0.049).ConclusionsCompared with postoperative CRT, preoperative CRT was associated with improved OS and DFS, superior treatment compliance and comparable surgical complications for patients with locally advanced gastric cancer. Our findings provide important evidence for the optimal combination modalities of surgery and CRT in the absence of randomized clinical data.

Project description:BackgroundThe treatment for locally advanced breast cancer (LABC) is a severe clinical problem. The postoperative radiotherapy is a conventional treatment method for patients with LABC, whereas the effect of preoperative radiotherapy on outcome of LABC remains controversial. This study aimed to examine and compare the overall survival (OS) in patients with LABC who underwent preoperative radiotherapy or postoperative radiotherapy.MethodsThis retrospective cohort study included 41,618 patients with LABC from the National Cancer Database (NCDB) between 2010 and 2014. We collected patients' demographic, clinicopathologic, treatment and survival information. Propensity score was used to match patients underwent pre-operative radiotherapy with those who underwent post-operative radiotherapy. Cox proportional hazard regression model was performed to access the association between variables and OS. Log-rank test was conducted to evaluate the difference in OS between groups.ResultsThe estimated median follow-up of all included participants was 69.6 months (IQR: 42.84-60.22); 70.1 months (IQR: 46.85-79.97) for postoperative radiotherapy, 68.5 (IQR: 41.13-78.23) for preoperative radiotherapy, and 67.5 (IQR: 25.92-70.99) for no radiotherapy. The 5-year survival rate was 80.01% (79.56-80.47) for LABC patients who received postoperative radiotherapy, 64.08% (57.55-71.34) for preoperative radiotherapy, and 59.67% (58.60-60.77) for no radiotherapy. Compared with no radiation, patients receiving postoperative radiotherapy had a 38% lower risk of mortality (HR=0.62, 95%CI: 0.60-0.65, p<0.001), whereas those who received preoperative radiotherapy had no significant survival benefit (HR=0.88, 95%CI: 0.70-1.11, p=0.282). Propensity score matched analysis indicated that patients treated with preoperative radiotherapy had similar outcomes as those treated with postoperative radiotherapy (AHR=1.23, 95%CI: 0.88-1.72, p=0.218). Further analysis showed that in C0 (HR=1.45, 95%CI: 1.01-2.07, p=0.044) and G1-2 (AHR=1.74, 95%CI: 1.59-5.96, p=0.001) subgroup, patients receiving preoperative radiotherapy showed a worse OS than those who received postoperative radiotherapy.ConclusionsPatients with LABC underwent postoperative radiotherapy had improved overall survival, whereas no significant survival benefit was observed in patients receiving preoperative radiotherapy. Preoperative radiotherapy did not present a better survival than postoperative radiotherapy for LABC patients.

Project description:ImportanceDistant recurrence following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma is common. Adjuvant chemotherapy may improve survival.ObjectiveTo compare adjuvant chemotherapy with postoperative observation following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma.Design, setting, and participantsPropensity score-matched analysis using the National Cancer Database. We included adult patients who received a diagnosis between 2006 and 2013 of clinical stage T1N1-3M0 or T2-4N0-3M0 adenocarcinoma of the distal esophagus or gastric cardia who were treated with preoperative chemoradiotherapy and curative-intent resection. Patients receiving adjuvant chemotherapy were matched by propensity score to patients undergoing postoperative observation.ExposuresAdjuvant chemotherapy and postoperative observation.Main outcomes and measuresOverall survival.ResultsWe identified 10 086 patients (8840 [88%] male; mean [SD] age, 61 [9.5] years), 9272 in the postoperative observation group and 814 in the adjuvant chemotherapy group. Patients receiving adjuvant chemotherapy were younger (18-54 years: 252 [31%] vs 1989 [21%]; P < .001) and were more likely to have advanced disease (ypT3/4: 458 [62%] vs 3531 [46%]; P < .001; ypN+: 572 [72%] vs 3428 [39%]; P < .001), as well as shorter postoperative inpatient stays (>2 weeks: 94 [13%] vs 1589 [20%]; P < .001). A total of 732 patients in the adjuvant chemotherapy group were matched by propensity score to 3660 patients in the postoperative observation group. Adjuvant chemotherapy was associated with improved overall survival compared with postoperative observation (median survival: 40 months; 95% CI, 36-46 months vs 34 months; 95% CI, 32-35 months; stratified log-rank P < .001; hazard ratio, 0.79; 95% CI, 0.72-0.88). Overall survival at 1, 3, and 5 years was 88%, 47%, and 34% in the observation group, and 94%, 54%, and 38% in the adjuvant chemotherapy group, respectively. Adjuvant chemotherapy was associated with a survival benefit compared with postoperative observation in most patient subgroups.Conclusions and relevanceFor patients with locally advanced gastroesophageal adenocarcinoma treated with preoperative chemoradiotherapy and resection, adjuvant chemotherapy was associated with improved overall survival. Our findings have important implications for the postoperative treatment of this patient group for which few data are available.

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Postoperative chemoradiotherapy vs. preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy.

Publications

Postoperative chemoradiotherapy vs. preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy.

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