Survival after neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for resectable esophageal carcinoma: A meta-analysis.
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ABSTRACT:
SUBMITTER: Fan M
PROVIDER: S-EPMC4773296 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
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Project description:Background and purposeWith the advent of more intensive chemotherapy regimens, neoadjuvant chemoradiotherapy (NACRT) for patients with locally advanced rectal cancer (LARC) has always been questioned due to its inevitable radiation toxicity. Hence, we conducted a meta-analysis to compare the clinical efficacy of neoadjuvant chemotherapy (NAC) and NACRT.Materials and methodsEligible studies were searched using PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science up to 31 July 2020, comparing the clinical efficacy of NAC versus NACRT for LARC. Short- and long-term outcomes were determined using the odds ratio (OR) with 95% confidence interval (CI).ResultsSix studies with 12,812 patients were eligible for this meta-analysis, including 677 patients in the NAC group and 12,135 patients in the NACRT group. There were no significant differences between the two groups in terms of pathological complete response rate (OR=0.62, 95%CI=0.27~1.41), N down-staging rate (OR=1.20, 95%CI=0.25~5.79), R0 resection rate (OR=1.24, 95%CI=0.78~1.98), and local relapse rate (OR=1.12, 95%CI=0.58~2.14). The pooled OR for the total response rate and T down-staging were in favor of NACRT (OR=0.41, 95%CI=0.22~0.76 versus OR=0.67 95%CI=0.52~0.87). However, the pooled OR for the sphincter preservation rate favored NAC compared with NACRT (OR=1.87, 95%CI=1.24~2.81). Moreover, NAC was found to be superior to NACRT in terms of distant metastasis (14.3% vs. 20.4%), but the difference was not significant (OR=0.84, 95%CI=0.31~2.27).ConclusionWe concluded that NAC was superior to NACRT in terms of the sphincter preservation rate, and non-inferior to NACRT in terms of pCR, N down-staging, R0 resection, local relapse, and distant metastasis. However, the conclusion warrants further validation.
| S-EPMC8101236 | biostudies-literature
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.
| S-EPMC5491642 | biostudies-literature
Project description:BackgroundThe efficacy and safety of neoadjuvant treatment over surgery alone and that of neoadjuvant chemoradiotherapy (NCRT) over neoadjuvant chemotherapy (NCT) in resectable esophageal carcinoma remains inconclusive. This study (NewEC) used global data to comprehensively evaluate these comparisons and to provide a preferable strategy for patient subsets.MethodsThis study included a meta-analysis of randomized controlled trials (RCTs) identified from inception to May 2019 from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congresses and a registry-based cohort study with patients from Massachusetts General Hospital (Massachusetts, USA) and Guangdong Provincial People's Hospital (Guangzhou, China) recruited from November 2000 and June 2017, to cross-validate the comparisons among NCRT versus NCT versus surgery. The GRADE approach was used to assessed quality of evidence in meta-analysis. Neural network machine learning propensity score-matched analysis was used to account for confounding by patient-level characteristics in the cohort study. The primary endpoint was overall survival (OS). The study was registered with PROSPERO CRD42017072242 and ClinicalTrials.gov NCT04027543.FindingsOf 22,070 studies assessed, there were 38 (n = 6,993 patients) eligible RCTs. Additionally, 423 out of 467 screened patients were included in the cohort study. The results from trials showed that NCT had a better OS than surgery alone (hazard ratio [HR] 0·88, 95% confidence interval [CI] 0·79-0·98; high quality) and was only favorable for adenocarcinoma (HR 0·83, 95% CI 0·72-0·96; moderate quality). High-quality evidence showed a significantly better OS for NCRT than surgery alone (HR 0·74, 95% CI 0·66-0·82) for both adenocarcinoma (HR 0·73, 95% CI 0·62-0·86) and squamous cell carcinoma (SCC) (HR 0·73, 95% CI 0·65-0·83). The OS benefit of NCRT over NCT was seen in the pairwise (HR 0·78, 95% CI 0·62-0·99; high quality) and network (HR 0·82, 95% CI 0·72-0·93; high quality) meta-analyses, with similar results before (HR 0·60, 95% CI 0·40-0·91) and after (HR 0·44, 95% CI 0·25-0·77) matching in the cohort study, leading to a significantly increased 5-year OS rate in both adenocarcinoma and SCC before and after matching. The increased benefits from NCT or NCRT were not associated with the risk of 30-day or in-hospital mortality.InterpretationNewEC Study provided high-quality evidence supporting the survival benefits of NCRT or NCT over surgery alone, with NCRT presenting the greatest benefit for resectable esophageal carcinoma.FundingNational Science and Technology Major Project, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Guangzhou Science and Technology Major Program, the Medical artificial intelligence project of Sun Yat-Sen Memorial Hospital, the Guangdong Science and Technology Department, the Guangdong Province Medical Scientific Research Foundation, and Guangdong Provincial People's Hospital Intermural Program.
| S-EPMC7327891 | biostudies-literature
Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p?<?0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p?=?0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p?=?0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p?=?0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p?=?0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.
| S-EPMC5870479 | biostudies-literature
Project description:BackgroundNeoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by surgery are two standard strategies in treating locally advanced esophageal cancer (EC). We aim to compare NCRT and NCT in the management of locally advanced EC patients.MethodsMEDLINE, Embase, CENTRAL, and conferences were systematically searched for clinical trials published up to September 2021. Pairwise comparisons and Bayesian network meta-analyses were conducted to compare overall survival (OS) and disease-free survival (DFS) by reporting the hazard ratio (HR) and 95% credible intervals (CrIs). The study was registered at PROSPERO (CRD42020170619).Findings25 trials with 4563 EC patients met inclusion criteria. NCRT improved OS (HR: 0·72, 95%CrI: 0·63-0·82) and DFS (HR: 0·72, 95%CrI: 0·63-0·81) compared to surgery alone. NCRT improved OS (HR: 0·83, 95%CrI: 0·69-0·99) and DFS (HR: 0·83, 95%CI: 0·69-0·99) compared to NCT. Subgroup analysis demonstrated that both NCRT (HR: 0·77, 95%CrI: 0·65-0·90) and NCT (HR: 0·81, 95%CrI: 0·67-0·99) improved OS than surgery in esophageal squamous cell carcinoma (ESCC) patients. No significant differences were observed between NCRT and NCT regarding OS (HR: 0·95, 95%CrI: 0·75-1·19) and DFS (HR: 0·90, 95%CrI: 0·50-1·62) in ESCC. The short-term outcomes were similar between NCRT and NCT. The three treatment strategies were comparable in esophageal adenocarcinoma (EAC) subpopulations.InterpretationThe study corroborated current guidelines in addressing the importance of analysing EC according to histopathological types. The analysis suggested that in locally advanced ESCC patients, both NCRT and NCT improved OS as compared to surgery alone, whereas no clear evidence supported the optimal strategies between NCRT and NCT. More RCTs comparing different therapeutic strategies in EAC patients are warranted.FundingKöln Fortune Program, University of Cologne.
| S-EPMC8585620 | biostudies-literature
Project description:BackgroundThe impact of neoadjuvant chemoradiotherapy (nCRT) on early stage esophageal cancer is unknown. Here, we compared the outcomes after esophagectomy alone or nCRT plus surgery for clinically staged node-negative esophageal cancer.MethodsWe searched the Surveillance, Epidemiology, and End Results database for patients with clinically node-negative (cN0) esophageal cancer from 2004 to 2016 who underwent surgery alone or nCRT plus surgery. Propensity score matching and Cox regression analysis were used to identify covariates associated with overall survival and cancer-specific survival.ResultsA total of 1587 patients were retrospectively identified, of whom 49.8% (n = 791) received nCRT and 80.2% (n = 1273) were truly node-negative diseases. For the entire cohort, surgery alone was associated with a statistically significant but modest absolute increase in survival outcomes (P < 0.01). After matching, nCRT was associated with improved five-year overall survival for pT3-4N0 (localized) disease (59.6% vs. 37.7%; P < 0.001) and pathological node-positive disease (60.5% vs. 40.7%; P = 0.002). Cox multivariate regression analysis revealed that the addition of nCRT for truly node-negative patients with tumor length ≥ 3 cm, pT1-2N0 (early-staged) and localized disease were independent risk factors for survival than surgery alone (P < 0.01).ConclusionsCompared with surgery alone, patients with cN0 esophageal cancer with pathological node-positive or localized true node-negative disease gain a significant survival benefit from nCRT. However, nCRT plus surgery was associated with decreased survival for early-staged true node-negative patients. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN0 disease.
| S-EPMC7471040 | biostudies-literature
Project description:BackgroundEsophageal cancer is a highly malignant cancer with a very poor prognosis. For resectable esophageal cancer, neoadjuvant treatment could improve the prognosis of esophageal cancer. However, current clinical neoadjuvant treatment options for esophageal cancer are still limited. The application of immunotherapy is a potentially beneficial new neoadjuvant treatment option for esophageal cancer. The objective of this meta-analysis is to evaluate the efficacy and safety of immunotherapy for the neoadjuvant treatment of esophageal cancer.MethodsWe will search Wanfang Database, SinoMed, China National Knowledge Infrastructure, Embase, Web of Science, Pubmed, and Cochrane Library for relevant articles published before July, 2021. We will also search the unpublished clinical trials of neoadjuvant immunotherapy in esophageal cancer in preprint website (such as bioRXiv and medRxiv) up to July, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of neoadjuvant immunotherapy for resectable esophageal cancer. Randomized controlled trials (RCTs) will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data.ResultsThe results of this study will provide evidence of immunotherapy using as neoadjuvant treatment for esophageal cancer. This meta-analysis will be submitted to a peer-reviewed journal seeking for publication.ConclusionThe results of this study will provide a reliable basis for clinicians and patients to formulate the best pre-surgical treatment plan for resectable esophageal cancer.Systematic review registrationINPLASY202120026.
| S-EPMC8177427 | biostudies-literature
Project description:BACKGROUND:We performed a meta-analysis to compare the efficacy of definitive chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially resectable esophageal cancer. METHODS:To assess both strategies, the combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen studies (N?=?2071; dCRT?=?869 and surgery?=?1202) were included. In all, 90.39% of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC). RESULTS:The 2-year (OR?=?1.199, 95% CI 0.922-1.560; P?=?0.177) and 5-year overall survival (OS) rates (OR?=?0.947, 95% CI 0.628-1.429; P?=?0.796) were not significantly different. No significant differences were identified in the 2-year OS among patients with stage I disease (OR?=?1.397, 95% CI 0.740-2.638; P?=?0.303) or stage II-III (OR?=?0.418, 95% CI 0.022-7.833; P?=?0.560). Patients with lymph node metastases tended to have a better 5-year OS when treated with dCRT than with surgery (OR?=?0.226, 95% CI 0.044-1.169; P?=?0.076); however, the difference between the two methods was not significant. Western patients who received dCRT had poorer prognoses than patients who underwent surgery (OR?=?1.522, 95% CI 1.035-2.238; P?=?0.033). dCRT and surgery led to similar 5-year progression-free survival rates (OR?=?1.06, 95% CI 0.79-1.42; P?=?0.70). CONCLUSIONS:dCRT and surgery are equally effective as initial treatments for potentially resectable esophageal cancer. These results apply primarily to Asian populations as they have an increased incidence of ESCC.
| S-EPMC6097217 | biostudies-literature
Project description:Esophageal cancer is the eighth most common cancer worldwide, and especially in some areas of China is the fourth most common cause of death and is of squamous cell carcinoma (SCC) histology in >90% of cases. Surgery alone was the mainstay of therapeutic intervention in the past, but high rates of local and systemic failure have prompted investigation into multidisciplinary management. In this review, we discuss the key issues raised by the recent availability of esophageal SCC treatment with the addition of chemotherapy, radiotherapy, and chemoradiotherapy to the surgical management of resectable disease and discuss how clinical trials and meta-analysis inform current clinical practice. None of the randomized trials that compared neoadjuvant radiotherapy or chemotherapy with surgery alone in esophageal SCC has demonstrated an increase in overall survival in those patients treated with neoadjuvant radiotherapy or chemotherapy. Neoadjuvant chemoradiotherapy has been accepted recently for esophageal cancer because such a regimen offers great opportunity for margin negative resection, improved loco-regional control and increased survival. The majority of the available evidence currently reveals that only selected locally advanced esophageal SCC are more likely to benefit from the adjuvant therapy. The focus of future trials should be on identification of the optimum regimen and should aim to minimize treatment toxicities and effect on quality of life, as well as attempt to identify and select those patients most likely to benefit from specific treatment options.
| S-EPMC3495900 | biostudies-literature
Project description:OBJECTIVE:Definitive chemoradiotherapy (CRT) remains the most commonly used treatment for locally advanced esophageal squamous cell carcinoma (SCC), because of perceptions that esophagectomy offers an unclear survival advantage. We compare recurrence, overall survival (OS), and disease-free survival (DFS) in patients treated with definitive CRT or neoadjuvant CRT followed by surgery (trimodality). METHODS:This was a retrospective cohort study of patients with stage II and III SCC of the middle and distal esophagus in patients who completed CRT. Treatment groups were matched (1:1) on covariates using a propensity score-matching approach. The effect of trimodality treatment, compared with definitive CRT, on OS, DFS, and site-specific recurrence was evaluated as a time-dependent variable and analyzed using Cox regression with a gamma frailty term for matched units. RESULTS:We included 232 patients treated between 2000 and 2016: 124 (53%) with definitive CRT and 108 (47%) with trimodality. Trimodality was used less frequently over time (61% before 2009 and 29% after 2009; P < .0001). After matching, each group contained 56 patients. Median OS and DFS were 3.1 and 1.8 years for trimodality versus 2.3 and 1.0 years for CRT. Surgery was independently associated with improved OS (hazard ratio, 0.57; 95% confidence interval, 0.34-0.97; P = .039) and DFS (hazard ratio, 0.51; 95% confidence interval, 0.32-0.83; P = .007). CONCLUSIONS:CRT followed by surgery might decrease local recurrence and increase DFS and OS in patients with esophageal SCC. Until better tools to select patients with pathological complete response are available, surgery should remain an integral component of the treatment of locally advanced esophageal SCC.
| S-EPMC5960990 | biostudies-literature