Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for nonsurgical esophageal cancer (EC). However, esophageal cancer patients receiving CCRT alone are still unsatisfactory in terms of local control and overall survival (OS) benefit. Clinicians generally add consolidation chemotherapy (CCT) after CCRT. It remains controversial whether CCT following CCRT is beneficial for esophageal cancer. We, therefore, undertook a meta-analysis to assess the need for CCT in inoperable esophageal cancer. Materials and Methods We combed PubMed, Embase, Cochrane Library, Web of Science, and CNKI for relevant published articles up to July 2020 that compared CCRT plus CCT to CCRT alone for patients with nonsurgical EC. Our primary endpoint was OS and progression-free survival (PFS), and the secondary endpoint was treatment toxicity. We analyzed the hazard ratio (HR) to estimate the time-to-event data and the odds ratio (OR) to compare the treatment-related effect. To assess heterogeneity, we performed the I2 test and examined publication bias using funnel plots analysis. Results The 11 retrospective studies involved 2008 patients. Of these 2008 patients, 1018 received CCRT plus CCT, and 990 received CCRT. Compared to CCRT alone, CCT after CCRT did not improve disease control rate (DCR) (OR 1.66; 95% CI 0.53-5.15, p=0.384) and objective response rate (ORR) (OR 1.44; 95% CI 0.62-3.35, p=0.393). However, OS (HR 0.72; 95% CI 0.59-0.86, p < 0.001) and PFS (HR 0.61; 95% CI 0.44-0.84, p=0.003) did increase. Our results show that CCT plus CCRT had a clear survival advantage over CCRT alone. The risk of treatment toxicity did not increase for EC patients who received CCT. Conclusion CCT after CCRT significantly increases OS and PFS in patients with nonsurgical EC and could provide them remarkable survival benefits. The results provide an evidence-based framework for the use of CCT after CCRT.

/pdf/long-term-survival-in-nonsurgical-esophageal-cancer-patients-16chmp0zxh.pdf

Long-Term Survival in Nonsurgical Esophageal Cancer Patients Who Received Consolidation Chemotherapy Compared With Patients Who Received Concurrent Chemoradiotherapy Alone: A Systematic Review and Meta-Analysis.

Background Concurrent chemoradiotherapy (CCRT) has become the standard of care in esophageal carcinoma patients who are not surgical candidates. The efficacy of induction chemotherapy (IC) or consolidation chemotherapy (CCT) for unresectable esophageal cancer (EC) treated with CCRT is unclear. We performed a systematic review and meta-analysis of published papers to evaluate the potential benefit of IC or CCT for patients with EC. Methods Eligible studies of IC followed by CCRT (IC-CCRT) vs. CCRT alone or CCRT followed by CCT (CCRT-CCT) vs. CCRT alone were retrieved through extensive searches of the PubMed, Science Direct, Embase, and Cochrane Library databases from the establishment of the database to July 31, 2021. Data such as 1-, 2-, 3-, and 5-year overall survival (OS), local recurrence rate (LRR), and distant metastasis rate (DMR) were collected for meta-analysis to evaluate the efficacy of IC/CCT. Results Four studies of IC-CCRT vs. CCRT including 836 EC patients and six studies of CCRT-CCT vs. CCRT including 1,339 patients with esophageal squamous cell carcinoma (ESCC) were finally identified in our analysis. Both IC-CCRT group [hazard ratio (HR) 0.446, 95% CI 0.286-0.693; p < 0.001] and CCRT-CCT group (HR 0.542, 95% CI 0.410-0.716; p < 0.001) exhibited statistically significant improvement in 1-year OS rate compared to that of CCRT, while the 2-year OS rate of IC-CCRT (HR 0.803, 95% CI 0.589-1.095; p = 0.166) or CCRT-CCT (HR 0.783, 95% CI 0.600-1.022; p = 0.072) was similar with that of CCRT. And the 3-year OS rate between IC-CCRT and CCRT was similar (HR 1.065, 95% CI 0.789-1.439; p = 0.680). However, comparing with CCRT alone, the CCRT-CCT group had lower DMR [odds ratio (OR) 1.562, 95% CI 1.090-2.240; p = 0.015] and higher 3-year OS rate (HR 0.786, 95% CI 0.625-0.987; p = 0.039). Besides, no differences were observed between the CCRT-CCT and CCRT groups in 5-year OS rate (HR 0.923, 95% CI 0.706-1.205; p = 0.555) and LRR (OR 0.899, 95% CI 0.686-1.179; p = 0.441). Conclusion The study revealed the short-time survival benefit of additional IC or CCT compared to CCRT alone for patients with unresectable EC, and CCRT followed by CCT could significantly reduce the risk of distant metastases.

/pdf/addition-of-induction-or-consolidation-chemotherapy-in-17hwiawl37.pdf

Addition of Induction or Consolidation Chemotherapy in Definitive Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Alone for Patients With Unresectable Esophageal Cancer: A Systematic Review and Meta-Analysis.

Despite 3‐year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression‐free survival at 3 years (3‐year PFS) and overall survival (OS) among patients with ESCC.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.4751

Progression‐free survival at 3 years is a reliable surrogate for 5‐year overall survival for patients suffering from locally advanced esophageal squamous cell carcinoma

Purpose: The primary tumor regression patterns of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT) were investigated to determine an optimal surveillance scheme.

Method: The clinical data and radiology images of patients before CRT, at completion of CRT and every 1–3 months for the subsequent 12 months or until disease progression were retrospectively reviewed to define the patterns of primary tumor regression after CRT. Survival rates were analyzed statistically in order to determine an optimal surveillance scheme.

Results: A total of 82 patients were enrolled in the present study for analysis. At the first surveillance visit date at the end of CRT, a total of 21 patients achieved complete response (early-CR), 29 patients reached incomplete response (IR), 25 patients maintained stable disease (SD) and 7 patients encountered progression of disease (PD). During subsequent surveillance, a total of 14 IR patients regressed continuously to CR (later-CR), 15 patients maintained IR (early-IR) and 9 SD patients gradually regressed to IR (later-IR). At full tumor regression (FTR), a total of 21, 14, 15, 9, 16 and 7 patients were defined as early-CR, later-CR, early-IR, later-IR, SD and PD, respectively. The median FTR time for later-CR and later-IR was 7.5 and 7 weeks, respectively. The 3-year overall survival rate of the early-CR group was 85.7% (P<0.001), which was higher compared with the later-CR (16.7%), early-IR (20%), later-IR (11.1%), SD (6.3%) and PD (0%) groups.

Conclusion: The early-CR following CRT is a robust prognostic predictor in patients with ESCC. To optimize the determination of tumor regression, ≥7 weeks after CRT is an optimal initial surveillance visit date. The surveillance of non-CR patients should concentrate on symptoms, nutrition and psychosocial support, rather than screening for recurrence of the disease.

/pdf/primary-tumor-regression-patterns-in-esophageal-squamous-3ymt7v3une.pdf

Primary tumor regression patterns in esophageal squamous cell cancer treated with definitive chemoradiotherapy and implications for surveillance schemes.

Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

With or without consolidation chemotherapy using cisplatin/5-FU after concurrent chemoradiotherapy in stage II–III squamous cell carcinoma of the esophagus: A propensity score-matched analysis

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With or without consolidation chemotherapy using cisplatin/5-FU after concurrent chemoradiotherapy in stage II–III squamous cell carcinoma of the esophagus: A propensity score-matched analysis