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Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or the gastroesophageal junction: A meta-analysis based on clinical trials.

ABSTRACT: BACKGROUND:The benefit of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy for treating cancer of the esophagus or the gastroesophageal junction remains controversial. In the present study, we conducted a comprehensive meta-analysis to examine the efficacy of these two management strategies. METHODS:The MEDLINE (PubMed), SinoMed, Embase, and Cochrane Library databases were searched for eligible studies. We searched for the most relevant studies published until the end of September 2017. Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (Cochrane Collaboration, http://tech.cochrane.org/revman/download). Weighted mean differences, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's risk of bias tool was used to assess the risk of bias. In this comprehensive meta-analysis, we examined the efficiency of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy for the treatment of cancer of the esophagus or the gastroesophageal junction as reported in qualified clinical trials. RESULTS:Six qualified articles that included a total of 866 patients were identified. The meta-analysis showed that for 3-year and 5-year survival rates in primary outcomes, the results favored neoadjuvant chemoradiotherapy strategies compared with neoadjuvant chemotherapy (RR = 0.78, 95% CI = 0.62-0.98, P = 0.03; RR = 0.69, 95% CI = 0.50-0.96, P = 0.03, respectively). In terms of secondary outcomes, neoadjuvant chemoradiotherapy significantly increased the rate of R0 resection and pathological complete response as well (RR = 0.87, 95% CI = 0.81-0.92, P < 0.0001; RR = 0.16, 95% CI = 0.09-0.28, P < 0.00001, respectively). However, there were no significant differences in postoperative mortality between the two groups (RR = 1.85, 95% CI = 0.93-3.65, P = 0.08). For the results of postoperative complications, revealed that there was a statistically significant difference between the two groups in the incidence of postoperative complications such as pulmonary, anastomotic leak and cardiovascular complications. The subgroup analysis of patients with esophageal adenocarcinoma or squamous cell carcinoma showed that both esophageal adenocarcinoma and squamous cell carcinoma patients achieved a high rate of R0 resection (RR = 0.85, 95% CI = 0.77-0.93, P = 0.0006; RR = 0.88, 95% CI = 0.81-0.96, P = 0.005, respectively) and pathological complete response benefit of neoadjuvant chemoradiotherapy (RR = 0.23, 95% CI = 0.09-0.57, P = 0.001; RR = 0.18, 95% CI = 0.03-0.96, P = 0.05, respectively). CONCLUSION:Our findings suggested that compared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy should be recommended with a significant long-term survival benefit in patients with cancer of the esophagus or the gastroesophageal junction. In view of the clinical heterogeneity, whether these conclusions are broadly applicable should be further determined.

SUBMITTER: Zhao X

PROVIDER: S-EPMC6107145 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or the gastroesophageal junction: A meta-analysis based on clinical trials.

Zhao Xin X Ren Yiming Y Hu Yong Y Cui Naiqiang N Wang Ximo X Cui Yunfeng Y

PloS one 20180823 8

<h4>Background</h4>The benefit of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy for treating cancer of the esophagus or the gastroesophageal junction remains controversial. In the present study, we conducted a comprehensive meta-analysis to examine the efficacy of these two management strategies.<h4>Methods</h4>The MEDLINE (PubMed), SinoMed, Embase, and Cochrane Library databases were searched for eligible studies. We searched for the most relevant studies published until the end of ...[more]

PMID: 30138325

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Project description:BackgroundNeoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy.MethodsPatients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups.Results40 patients participated (chemoradiotherapy, n=17; chemotherapy, n=23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p=0.02, p=0.01, and p=0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p=0.09 and p=0.09). NT-proBNP increased following chemoradiotherapy (p=0.05) but not after chemotherapy (p>0.99), and there was a trend towards an interaction effect (p=0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p=0.03) and was more pronounced after chemoradiotherapy with a trend towards an interaction effect (p=0.10).ConclusionsNeoadjuvant chemoradiotherapy but not chemotherapy before surgery for cancer of the esophagus or GE-junction seems to induce an acute negative effect on both systolic and diastolic left ventricular function. Future studies on neoadjuvant treatment for esophageal cancer are suggested to add measurements of cardiac function.Trial registrationClinical Trials.gov NCT01362127 .

Project description:This study compares neoadjuvant chemoradiotherapy (nCRT) with perioperative chemotherapy (pCT) for patients with resectable esophageal or gastroesophageal junction (GEJ) adenocarcinoma in terms of toxicity, postoperative complications, pathologic response, and survival.This study retrospectively analyzed and compared 313 patients with resectable esophageal or GEJ adenocarcinoma treated with either nCRT (carboplatin/paclitaxel 41.4 Gy, n = 176) or pCT (epirubicin, cisplatin and capecitabine, n = 137).The baseline and tumor characteristics were similar in both groups. The ability to deliver all planned preoperative cycles was greater in the nCRT group (92.0 vs. 76.6%). Whereas nCRT was associated with a higher rate of grades 3 and 4 esophagitis, pCT was associated with a higher rate of grades 3 and 4 thromboembolic events, febrile neutropenia, nausea, vomiting, diarrhea, hand-foot syndrome, mucositis, cardiac complications, and electrolyte imbalances. Two patients in the pCT group died during neoadjuvant treatment due to febrile neutropenia. More postoperative cardiac complications occurred in the nCRT group. All other postoperative complications and the in-hospital mortality rate (nCRT, 4.7%; pCT, 2.3%) were comparable. The pathologic complete response (pCR) rate was 15.1% after nCRT and 6.9% after pCT. Radicality of surgery was comparable (R0: 93.0 vs. 91.6%). The median overall survival was 35 months after nCRT versus 36 months after pCT.For patients with esophageal or GEJ adenocarcinoma, chemoradiotherapy with paclitaxel, carboplatin and concurrent radiotherapy, and perioperative chemotherapy with epirubicin, cisplatin, and capecitabin lead to equal oncologic outcomes in terms of radical resection rates, lymphadenectomy, patterns of recurrent disease, and (disease-free) survival. However, neoadjuvant chemoradiotherapy is associated with a considerably lower level of severe adverse events and should therefore be the preferred protocol until a well-powered randomized controlled trial provides different insights.

Project description:Background:Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is associated with improved survival in patients treated for esophageal cancer. While proton beam therapy (PBT) has been demonstrated to reduce toxicities with nCRT, no data comparing pCR rates between modalities exist to date. We investigated pCR rates in patients with distal esophageal/GEJ adenocarcinomas undergoing trimodality therapy with nCRT-PBT or photon-based nCRT with the hypothesis that pathologic responses with PBT would be at least as high as with photon therapy. Methods:A single-institutional review of patients with distal esophageal adenocarcinoma treated with trimodality therapy from 2015-2018 using PBT was completed. PBT patients were matched 1:2 to patients treated with photons. Chi square and two-sample t-tests were utilized to compare characteristics, and the Kaplan Meier method was used to estimate oncologic endpoints. Results:Eighteen consecutive PBT patients were identified and compared to 36 photon patients. All patients received concurrent chemotherapy; 98% with carboplatin/paclitaxel. Most patients were male (91%) and White (89%); median age was 62 years (range, 31-76 years). Median radiation dose in both cohorts was 50.4 Gy (range, 41.4-50.4 Gy); all courses were delivered in 1.8Gy fractions. Age, gender and race were well balanced. Patients treated with PBT had a significantly higher pre-treatment nodal stage (N) and AJCC 7th edition stage grouping (P=0.02, P=0.03). Despite this, tumoral and nodal clearance and pCR rates were equivalent between cohorts (P=0.66, P=0.11, P=0.63, respectively). Overall pCR and individual primary and nodal clearance rates, overall survival (OS), locoregional control (LRC), and distant metastatic control did not significantly differ between modalities (all P>0.05). Major perioperative events were balanced; however, there were 5 (14%) perioperative deaths in the photon cohort compared to 0 (0%) in the proton cohort (P=0.06). Conclusions:The use of PBT in trimodality therapy for distal esophageal adenocarcinoma yields pCR rates comparable to photon radiation and historical controls. Pathologic responses and oncologic outcomes in this study did not differ significantly between modalities despite PBT patients having higher AJCC stages and nodal disease burdens.

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Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or the gastroesophageal junction: A meta-analysis based on clinical trials.

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Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or the gastroesophageal junction: A meta-analysis based on clinical trials.

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