The role of palliative interventional radiotherapy (brachytherapy) in esophageal cancer: An AIRO (Italian Association of Radiotherapy and Clinical Oncology) systematic review focused on dysphagia-free survival
Abstract:PURPOSE: The aim of this review was to examine efficacy of palliative interventional radiotherapy (IRT) in esophageal cancer compared with other treatment in terms of dysphagia-free survival (DyFS) and safety. METHODS AND MATERIAL: A systematic research using PubMed, Scopus, and Cochrane library was performed to identify full articles evaluating the efficacy of IRT as palliation in patients with esophageal cancer. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was search… Show more
“…A brachytherapy boost was not implemented in the protocol, since this is not a standard therapy for the primary treatment of esophageal cancer. However, it can be a reasonable option for a local recurrence or symptom relief in a palliative situation [ 14 ]. Fig.…”
Purpose
To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer.
Methods
This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H
0
), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H
0
was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable.
Results
Two-year OS was 71% in arm A (95% CI: 55–87%) vs. 53% in arm B (95% CI: 36–71%); H
0
was rejected. Median OS was 49.1 vs. 24.1 months (
p
= 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30–1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25–1.04) for progression, 0.43 (0.13–1.40) for locoregional failure, and 0.43 (0.17–1.05) for distant metastasis. Overall response was 81% vs. 69% (
p
= 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (
p
= 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%,
p
= 0.044).
Conclusion
Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.
“…A brachytherapy boost was not implemented in the protocol, since this is not a standard therapy for the primary treatment of esophageal cancer. However, it can be a reasonable option for a local recurrence or symptom relief in a palliative situation [ 14 ]. Fig.…”
Purpose
To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer.
Methods
This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H
0
), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H
0
was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable.
Results
Two-year OS was 71% in arm A (95% CI: 55–87%) vs. 53% in arm B (95% CI: 36–71%); H
0
was rejected. Median OS was 49.1 vs. 24.1 months (
p
= 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30–1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25–1.04) for progression, 0.43 (0.13–1.40) for locoregional failure, and 0.43 (0.17–1.05) for distant metastasis. Overall response was 81% vs. 69% (
p
= 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (
p
= 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%,
p
= 0.044).
Conclusion
Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.
“…After SEMS placement, brachytherapy is the second most studied approach for the palliation of dysphagia in esophageal cancer [1,22,23]. Besides the SIREC trial, head-to-head comparison between SEMS and brachytherapy (in 3 fractions of 7 Gy) has been performed in one other RCT in 65 patients, which confirmed improved rapid dysphagia relief with SEMS after 1 month, but not at !3 months [24].…”
Background and purpose: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in patients with incurable esophageal cancer. The aim of this analysis was to compare patient-reported outcomes (PROs) after EBRT versus brachytherapy. Materials and methods: In a multicenter prospective cohort study, patients with incurable esophageal cancer requiring palliation of dysphagia were included to undergo EBRT (20 Gy in 5 fractions). This EBRT cohort was compared to the single-dose 12 Gy brachytherapy cohort of the previously reported SIRECtrial. Propensity score matching was applied to adjust for baseline imbalances. The primary endpoint of dysphagia improvement was reported previously. PROs were secondary outcomes and assessed at baseline and 3 months after treatment using EORTC QLQ-C30 and QLQ-OES18 questionnaires. Results: A total of 115 enrolled EBRT patients and 93 brachytherapy patients were eligible. After matching, 69 well-balanced pairs remained. At follow-up, significant deteriorations in functioning (i.e. physical, role, social), pain, appetite loss, and trouble with taste were observed after brachytherapy. In the EBRT group, such deterioration was observed only for role functioning, while significant improvements in trouble with eating and pain were found. Between-group comparison showed mostly comparable PRO changes, but significantly favored EBRT with regard to nausea, vomiting, pain, and appetite loss. Conclusion: Short course EBRT results in similar or better PROs at 3 months after treatment compared to single-dose brachytherapy for the palliation of malignant dysphagia. These findings further support its use and inclusion in clinical practice guidelines.
“…Lancelotta et al, in a metaanalysis, highlighted the safety and efficacy of radiotherapy over other modalities. Radiotherapy techniques are highly effective, leading to complete resolution of dysphagia in 87% of patients within one month, in two-thirds within three months, and in 50% of patients at six months after treatment [30]. Fuccio et al showed the effectiveness of brachytherapy and considered it the most effective treatment for malignant dysphagia.…”
Esophageal cancer is a disease with difficult clinical management, and palliative therapy is the only predominant treatment. This retrospective study analyses the results of clinical management of elderly patients (>75 years of age) who were treated with esophageal stenting for malignant dysphagia due to primary esophageal cancer, including squamous cell carcinoma (SCC), esophageal adenocarcinoma (EAC), as well as secondary esophageal malignant strictures due to non-small cell lung cancer (NSCLC). Patients with esophago-respiratory fistula (ERF) were also included in the study. This study included 166 patients aged 75–88 (mean age, 78) years. Nine (5.4%) patients had upper malignant esophageal stenosis, 48 (28.1%) had the middle, 43 (25.9%) in the lower part of the esophagus, 49 (29.5%) patients had EAC-related stenosis, and 17 (10.2%) patients reported lung cancer-related esophageal stenosis. Dysphagia was rated at 2.8 (range, 2–3) before stenting and at 1.2 (range, 1–2) after the stenting procedure. Seven (4%) patients experienced stenting migration, 12 (7.2%) had granulation tissue overgrowth and prosthesis obstruction, two (1.2%) developed respiratory failure, and one (0.6%) patient died. Twelve (7.2%) patients were treated for ERF with double-stenting, and three (1.8%) patients developed a secondary fistula after the stent implantation. The mean survival of patients with esophageal cancer and ERF was 101.8 days and 62.5 days, respectively. Esophageal stenting has proven a safe procedure in patients over 75 years of age. It has a low rate of stenting obstruction and migration. Patients with ERF are a particularly difficult group to treat, show very poor outcomes and short survival rates.
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