Dataset Information

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

ABSTRACT:

Purpose

The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups.

Patients and methods

All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158).

Results

IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively).

Conclusion

Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

SUBMITTER: Faron M

PROVIDER: S-EPMC10553121 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

Faron Matthieu M Cheugoua-Zanetsie Maurice M Tierney Jayne J Thirion Pierre P Nankivell Matthew M Winter Kathryn K Yang Hong H Shapiro Joel J Vernerey Dewi D Smithers B Mark BM Walsh Thomas T Piessen Guillaume G Nilsson Magnus M Boonstra Jurjen J Ychou Marc M Law Simon S Cunningham David D de Vathaire Florent F Stahl Michael M Urba Susan S Valmasoni Michele M Williaume Danièle D Thomas Janine J Lordick Florian F Tepper Joel J Roth Jack J Gebski Val V Burmeister Bryan B Paoletti Xavier X van Sandick Johanna J Fu Jianhua J Pignon Jean-Pierre JP Ducreux Michel M Michiels Stefan S

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20230712 28

<h4>Purpose</h4>The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups.<h4>Patients and methods</h4>All, published or unpublished, RCTs closed to accrual before December 31 ...[more]

PMID: 37467395

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Project description:Simple Summary The optimal neoadjuvant treatment modality for locally advanced gastroesophageal junction (GEJ) adenocarcinoma is still debated. Although chemoradiotherapy is set as the standard of treatment for squamous cell cancer, offering high rates of complete clinical and histologic response, the optimal treatment for adenocarcinoma remains a matter of debate. This study retrospectively compared 94 patients with locally advanced adenocarcinoma of the esophago-gastric junction treated with neoadjuvant chemoradiotherapy (n = 27) versus chemotherapy (n = 67) followed by curative surgery. Chemoradiotherapy offered better histological response of the primary tumor, but no benefit in terms of negative resection margins or long-term survival or recurrence. Patients undergoing chemoradiation were shown to have higher rates of cardiovascular complications after surgery. Based on these findings, the added benefit of external beam radiation in the neoadjuvant treatment of locally advanced esophageal adenocarcinoma remains unclear. Abstract Background: Locally advanced gastroesophageal junction adenocarcinoma (GEJ) is treated with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. The aim of this study was to compare pathologic response and long-term outcomes in junction adenocarcinoma treated with neoadjuvant RCT versus CT. Methods: All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 were retrospectively analyzed. Results: A total of 94 patients were included, 67 (71.2%) RCT and 27 (28.8%) CT. Complete pathologic response was more frequent in RCT patients (13.4% vs. 7.4%, p = 0.009) with a trend to better lymph node control (ypN0) (55.2% vs. 33.3%; p = 0.057). RCT offered no benefit in R0 resection (66.7% vs. 72.1% CT, p = 0.628) and was related to higher postoperative cardiovascular complications (35.8% vs. 11.1%; p = 0.017). Long-term overall and disease-free survival were similar (5-year OS 61.1% RCT vs. 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs. 22.8% CT; p = 0.763). NAT type was neither independently associated with pathologic response nor long-term survival. Discussion: Patients with locally advanced GEJ adenocarcinoma treated with RCT had more postoperative cardiovascular complications but higher rates of complete pathologic response and a trend to superior locoregional lymph node control. This did not translate in a survival or recurrence benefit.

Project description:BackgroundThis 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.MethodsThis 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).ResultsThe 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.ConclusionFor 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: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.

Project description:ImportanceThe association of neoadjuvant chemoimmunotherapy (NCIT) vs chemoradiotherapy (NCRT) with tumor downstaging and survival in locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of limited evidence.ObjectiveTo compare the associations of NCIT and NCRT with tumor regression and long-term survival in patients with locally advanced ESCC.Design, setting, and participantsIn this comparative effectiveness research study, from January 2016 to March 2023, patients with locally advanced ESCC who underwent esophagectomy following NCRT or NCIT were identified from a prospective database of 8 high-volume esophageal surgery centers in China. Follow-up began on the date of surgery and continued until the last recorded contact or March 2024, whichever occurred first. Data were analyzed between April and September 2024.Main outcomes and measuresThe primary end points were 2-year overall survival (OS) and disease-free survival (DFS). Secondary end points included major pathologic response (MPR) and pathologic complete response (pCR). Cox proportional hazard regression analysis was used to investigate the risk factors for OS and DFS.ResultsThe study included 1428 patients (median [IQR] age, 63 [57-68] years; 1184 men [82.9%]), with 704 patients in the NCRT group and 724 patients in the NCIT group. After propensity score matching, there were 532 patients in each group. The 2-year OS (81.3% vs 71.3%; hazard ratio, 1.57; 95% CI, 1.26-1.96; P < .001) and DFS (73.9% vs 63.4%; hazard ratio, 1.37; 95% CI, 1.11-1.69; P < .001) rates were significantly higher in NCIT group than in the NCRT group. The NCRT group had a higher MPR rate than that of the NCIT group (71.8% vs 61.5%), whereas the pCR rates were similar (25.9% vs 22.9%). Multivariable Cox analysis demonstrated that NCIT and MPR were independently associated with both OS and DFS. The NCIT group exhibited a lower overall recurrence rate (126 patients [23.7%] vs 190 patients [35.7%]) and distant metastasis rate (72 patients [13.5%] vs 133 patients [25.0%]), although locoregional metastasis rates were similar (98 patients [18.4%] vs 111 patients [20.9%]). Better OS and DFS were obtained for the NCIT group than for the NCRT group, regardless of whether adjuvant immunotherapy was given.Conclusions and relevanceCompared with NCRT, patients with locally advanced ESCC receiving NCIT had better 2-year OS and DFS. The decrease in distant metastasis may be the main reason, but further prospective randomized clinical trials are needed to verify this finding.

Dataset Information

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

Purpose

Patients and methods

Results

Conclusion

Publications

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

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