Esophageal Cancer Radiotherapy Dose Escalation Meta Regression Commentary: “High vs. Low Radiation Dose of Concurrent Chemoradiotherapy for Esophageal Carcinoma With Modern Radiotherapy Techniques: A Meta-Analysis”

102 Background: In treating esophageal cancer chemo-radiation is used in the definitive as well as neo-adjuvant setting. Optimal dosage of radiation for best outcome has been debated. The aim of this study is to evaluate clinical outcomes of lower radiation dosage compared to higher. Methods: Online search for studies comparing radiation dose from 1990 to present was performed. Primary outcome was overall-survival rates for up to 5 years. Secondary outcomes included post-treatment complications and treatment response. A cut point of 51 Gy and less was considered as lower dose and greater than 51 Gy was considered higher dose. Quality of included studies was evaluated by STROBE criteria. Relative Risk (RR) and 95% Confidence Intervals (CI) were calculated from pooled data. Results: The search strategy yielded 142 studies, 12 met our selection criteria and included 1876 patients receiving radiation for resectable esophageal carcinoma. Of these patients, 1057 received lower and 819 were treated with greater than 51 Gy. Median age was 63 and 64 years for lower and higher radiation dose respectively. Meta-analysis showed no statistically significant difference in survival and toxicities between the two groups. 1 year overall survival (RR = 0.97, 95% CI 0.84-1.13, p = 0.69), 2 year overall survival (RR = 1.29, 95% CI 0.76-2.19, p = 0.34), 3 year overall survival (RR = 1.18, 95% CI 0.83-1.68, p = 0.37), 4 year overall survival (RR = 1.37, 95% CI 0.64-2.94, p = 0.41), 5 year overall survival (RR = 1.11, 95% CI 0.72-1.69, p = 0.64), Esophagitis (RR = 0.76, 95% CI 0.39-1.50, p = 0.43), Dermatitis (RR = 0.98, 95% CI 0.12-7.94, p = 0.99), Fistula formation (RR = 0.72, 95% CI 0.32-1.60, p = 0.42), Hematologic complications (RR = 1.10, 95% CI 0.20-6.02, p = 0.91), Stricture formation (RR = 1.39, 95% CI 0.54-3.58, p = 0.5). Conclusions: Lower radiation dose appears to be as effective as higher dose in esophageal carcinoma with similar toxicity profile and survival rates. Larger prospective randomized trials, focusing on patient-reported quality-of-life are required to consolidate these results.

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Using Real-world Historical Controls to Evaluate Radiation Dose Escalation in Esophageal Cancer

JAMA Oncology ◽

10.1001/jamaoncol.2019.6406 ◽

2020 ◽

Vol 6 (4) ◽

pp. 583

Author(s):

Liyuan Fan ◽

Baosheng Li ◽

Chen Hu

Keyword(s):

Esophageal Cancer ◽

Radiation Dose ◽

Dose Escalation ◽

Real World ◽

Historical Controls

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A randomized controlled phase III multicenter study on dose escalation in definitive chemoradiation for patients with locally advanced esophageal cancer: ARTDECO study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.281 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 281-281 ◽

Cited By ~ 14

Author(s):

Maarten C.C.M. Hulshof ◽

Debby Geijsen ◽

Tom Rozema ◽

Vera Oppedijk ◽

Jeroen Buijsen ◽

...

Keyword(s):

Esophageal Cancer ◽

Radiation Dose ◽

Lymph Nodes ◽

Local Control ◽

Dose Escalation ◽

Primary Tumor ◽

Progression Free Survival ◽

Locoregional Control ◽

Free Survival ◽

Definitive Chemoradiation

281 Background: To analyze the effect of radiation dose escalation to the primary tumor on local control, locoregional control, survival and toxicity in definitive chemoradiation for esophageal cancer. Methods: Patients with clinical stage T2-4, N0-3, M0 carcinoma of the esophagus were randomized between a standard dose of 50.4 Gy/1.8 Gy/5,5 weeks to the tumor and regional lymph nodes (SD) versus the same dose combined with an integrated boost of 0,4 Gy per fraction (total 61,6 Gy) to the primary tumor (HD). Chemotherapy consisted of 6 weekly concurrent carboplatin (AUC 2) and paclitaxel (50 mg/m2) in both arms. The primary endpoint was local progression free survival (LPFS) and 260 patients were needed to detect a difference of 15% (power: 80%). Secondary endpoints were locoregional progression free survival (LRPFS), overall survival (OS) and toxicity. Patients were stratified for histological subtype. Results: Between September 2012 and June 2018, 260 patients were included. Reasons for inoperability were proximal localization and patient preference (44%), comorbidity (30%), unresectable lymph nodes (11%), T4 (5%), local recurrence 2% and combinations (7%). 61% of the patients had a squamous cell carcinoma (SCC) and 39% had an adenocarcinoma (AC). 94% completed radiation treatment and 85% had at least 5 courses chemotherapy. Median follow up time was 45 months. 3-year LPFS was 70% in the SD arm versus 76% in the HD arm (ns). LPFS for SCC and AC was 74% versus 81% and 62% versus 65% for SD and HD, resp. (ns). 3-year LRPFS was 53% and 63% for the SD and HD arm resp. (p = 0.08). 1 year any progression free survival was 60% for SCC and 50% for AC, without a significant difference between SD and HD (p = 0,5). 3-year OS was 41% versus 40% for SD and HD resp. Overall grade 4 and 5 CTC toxicity was 12% and 4% in the SD arm versus 14% and 10% in the HD arm, resp. Conclusions: In definitive chemoradiation for esophageal cancer, radiation dose escalation up to 61,6 Gy to the primary tumor did not result in a significant increase in local control over 50,4 Gy. Numerical improvement of locoregional control after HD was observed with an increase in toxicity and without improving OS. Clinical trial information: NL38343.018.11.

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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

Frontiers in Oncology ◽

10.3389/fonc.2020.604657 ◽

2021 ◽

Vol 10 ◽

Author(s):

Xiaojie Xia ◽

Zeyuan Liu ◽

Qin Qin ◽

Xiaoke Di ◽

Zhaoyue Zhang ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Patients ◽

Concurrent Chemoradiotherapy ◽

Meta Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Cochrane Library ◽

Consolidation Chemotherapy ◽

Term Survival ◽

Treatment Toxicity

BackgroundConcurrent 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 MethodsWe 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.ResultsThe 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.ConclusionCCT 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.

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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

Frontiers in Oncology ◽

10.3389/fonc.2021.665231 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jianing Wang ◽

Linlin Xiao ◽

Shuai Wang ◽

Qingsong Pang ◽

Jun Wang

Keyword(s):

Systematic Review ◽

Esophageal Cancer ◽

Concurrent Chemoradiotherapy ◽

Meta Analysis ◽

Standard Of Care ◽

Distant Metastases ◽

Cochrane Library ◽

Consolidation Chemotherapy ◽

Metastasis Rate ◽

Short Time

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.

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