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Role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma.

ABSTRACT: We reviewed the current status and future perspectives regarding the role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma (ESCC). The treatment and management of ESCC have been improved by dramatic advances in diagnostic techniques and the development of surgery, chemotherapy, radiotherapy, and immunotherapy. The current standard treatment for locally advanced ESCC is preoperative chemotherapy followed by surgery in Japan, whereas preoperative chemoradiotherapy is a globally recommended approach. Differences of recognition regarding the role for surgery between Japan and many Western countries may have created peculiar preferences for preoperative therapy. The clinical significance of conversion strategy and salvage surgery for patients with ESCC should be further evaluated in terms of curability and safety. Although strategies to identify patients who would benefit from preoperative therapy are strongly required to avoid performing unnecessary treatment, it remains difficult to predict the efficacy of preoperative therapy prior to treatment. Prospective clinical trials and basic research to identify predictive biomarkers for response to chemotherapy, radiotherapy, and immunotherapy are needed to promote the development of multidisciplinary treatment strategies for patients with ESCC.

SUBMITTER: Saeki H

PROVIDER: S-EPMC7511562 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma.

Saeki Hiroshi H Sohda Makoto M Sakai Makoto M Sano Akihiko A Shirabe Ken K

Annals of gastroenterological surgery 20200622 5

We reviewed the current status and future perspectives regarding the role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma (ESCC). The treatment and management of ESCC have been improved by dramatic advances in diagnostic techniques and the development of surgery, chemotherapy, radiotherapy, and immunotherapy. The current standard treatment for locally advanced ESCC is preoperative chemotherapy followed by surgery in Japan, whereas preo ...[more]

PMID: 33005843

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Project description:Background and purpose: The aim of this study is to develop a prognostic nomogram, quantify survival benefit, and guide risk-dependent adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) after esophagectomy. Materials and methods: This was a single-center, retrospective study of consecutive LA-ESCCs treated by curative-intent esophagectomy with internal validation and independent external validation in a randomized controlled trial. After factor selection by the least absolute shrinkage and selection operator regression, a nomogram was developed to estimate 5-year overall survival (OS) based on the Cox proportional hazards model. The area under the curve (AUC) and calibration plot were used to determine its discriminative and predictive capacities, respectively. Survival improvement from adjuvant therapy was quantified and plotted corresponding to nomogram score. Results: A total of 1077, 718, and 118 patients were included for model development, internal validation, and external validation, respectively. The nomogram identified eight significant prognostic factors: gender, pathological T and N stages, differentiation, surgical margin, lymphovascular invasion, number of lymph node resection, and adjuvant therapy. The nomogram showed superior discriminative capacity than TNM stage (AUC: 0.76 vs. 0.72, p < 0.01), with significant survival differences among different risk stratifications. The calibration plot illustrated a good agreement between nomogram-predicated and actual 5-year OS. Consistent results were concluded after external validation. At least 10% 5-year OS improvement from adjuvant chemoradiotherapy and chemotherapy was expected in almost all patients (nomogram score 110 to 260) and patients mainly with high-intermediate risk (nomogram score 159 to 207), respectively. Conclusions: The clinicopathological nomogram predicting 5-year OS for LA-ESCC after esophagectomy was developed with high accuracy. The proposed nomogram showed better performance than TNM stage and provided risk-dependent and individualized adjuvant treatment recommendations.

Project description:ImportanceThe prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival.ObjectiveTo compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC.Design, setting, and participantsThe Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020.InterventionsPatients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization.Main outcomes and measuresThe primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival.ResultsA total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively.Conclusions and relevanceIn this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC.Trial registrationClinicalTrials.gov Identifier: NCT01216527.

Project description:PurposeThe present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and methodsIn this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.ResultsOne hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.ConclusionOur results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

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Role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma.

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Role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma.

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