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

Abstract

BackgroundConcurrent 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.MethodsEligible 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.ResultsFour 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).ConclusionThe 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.

Consolidative chemotherapy after definitive concurrent chemoradiotherapy for esophageal squamous cell carcinoma patients: a population based cohort study

“…In our mind, our results were compatible with the results in the above-mentioned systematic review in that the point estimate of HR for OS was in favor of CCT [11]. In another systematic review published in 2021 (not limited to SqCC but consisted of mainly SqCC patients) [37], favorable OS (HR 0.72; 95% CI 0.59-0.86, P < 0.001) and response rate (OR 1.44; 95% CI 0.62-3.35, P = 0.393) were reported.…”

“…Our results were relatively close to these results. When we looked at the relevant individual studies [12][13][14][15][16][17] included in the above systematic review [11], the details were summarized below. Wu et al compared 67 patients in the CCT group vs 142 patients in control group treated at a single institute and found CCT improved the overall survival with HR 0.67 [12].…”

“…RT dose was classified as low (50–50.4 Gy) or high (50.4–70 Gy) dose. The induction chemotherapy (ICT) was classified as with ICT (according to the recording in TCR plus systemic therapy at least 3 weeks before radiotherapy [ 11 , 21 ]) or without ICT (patients started systemic therapy no earlier than 1 week before radiotherapy was started [ 11 , 21 ]).…”

“…The role of CCT was also not clearly addressed in the current treatment guidelines [3][4][5][6]. A systematic review published in 2021 reported overall survival (OS) was significantly improved in the short term (1 year hazard ratio (HR) 0.542, P < 0.001) but not in the long term (5 year HR 0.923 P = 0.555) when CCT was compared to without CCT [11]. However, all the six studies regarding CCT in this systematic review were retrospective reviews from limited institutes [12][13][14][15][16][17].…”

Consolidation Chemotherapy Rather than Induction Chemotherapy Can Prolong the Survival Rate of Inoperable Esophageal Cancer Patients Who Received Concurrent Chemoradiotherapy

“…With the efficacy of CCT in cervical cancer [ 17 ] and lung cancer gradually emerging [ 18 , 19 ], the role of CCT in the treatment of esophageal cancer is also being revealed. Two meta-analyses published in 2021 also demonstrated that patients with esophageal cancer can achieve survival benefits in CCT after CRT [ 20 , 21 ].…”