Effect of Radiotherapy Dose Escalation in Definitive Chemoradiation for Locally Advanced Esophageal Cancer

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In a Dutch phase III trial (ARTDECO) reported in the Journal of Clinical Oncology, Hulshof et al found that increasing the dose of radiation therapy in a definitive chemoradiation regimen did not improve local progression-free survival in patients with inoperable, locally advanced esophageal cancer.

Study Details

In the multicenter trial, 260 patients with medically inoperable or nonresectable disease (all T1–4N0–3M0 or M1) were randomly assigned between September 2012 and June 2018 to receive chemoradiation with high-dose (n = 130) or standard-dose radiotherapy (n = 130). The standard-dose group received a total of 50.4 Gy in 28 1.8 Gy fractions to the tumor and regional lymph nodes 5 days per week over 5.5 weeks. The high-dose group received the same regimen with a simultaneous integrated boost dose of 0.4 Gy to the primary tumor, resulting in a total dose of 61.6 Gy in 2.2 Gy fractions. Concurrent chemotherapy consisted of carboplatin at AUC 2 and paclitaxel at 50 mg/m2 once weekly starting at day 1 for 6 weeks. Patients received no adjuvant or neoadjuvant chemotherapy. Among patients with a known histologic type, 81 (63%) in the high-dose group vs 78 (61%) in the standard-dose group had squamous cell carcinoma, and 46 (36%) vs 49 (38%) had adenocarcinoma. The primary endpoint was local progression–free survival.

Local Progression–Free Survival

Radiotherapy was completed in 92% of the high-dose group vs 96% of the standard-dose group, and 59% vs 69% completed six courses of chemotherapy.


  • Increased radiotherapy dose did not improve local progression–free survival.
  • Local progression–free survival at 3 years was 73% in the high-dose radiotherapy group vs 71% in the standard-dose group.

Median follow-up was 50 months. Local progression–free survival at 3 years was 73% (95% confidence interval [CI] = 64%–83%) in the high-dose group vs 71% (95% CI = 62%–81%) in the standard-dose group (P = .62). No significant differences in rates were observed among patients with squamous cell carcinoma (79% vs 75%) or those with adenocarcinoma (61% vs 61%).

At 3 years, locoregional progression–free survival was 59% (95% CI = 49%–70%) in the high-dose group vs 53% (95% CI = 43%–64%) in the standard-dose group (P = .24), with no significant differences observed among patients with squamous cell carcinoma (64% vs 58%) or those with adenocarcinoma (49% vs 42%). Progression-free survival at 3 years was 25.4% vs 33.1% (P = .31); overall survival at 3 years was 39% vs 42% (P = .22).

Adverse Events

In the high-dose vs standard-dose groups, grade 3 adverse events occurred in 64% vs 55%, grade 4 events occurred in 14% vs 12%, and grade 5 events occurred in 10% vs 5% (P = .15 for grade 4–5 events). Grade 5 toxicity in the high-dose group included esophageal bleeding in three patients, esophageal fistula in two, respiratory failure in two, sepsis in one, and bronchopulmonary bleeding in one. In the standard-dose group, grade 5 events included esophageal fistula in two patients, esophageal bleeding in one, and sepsis in one.

The investigators concluded: “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. The absence of a dose effect was observed in both adenocarcinoma and squamous cell carcinoma.”

Maarten C.C.M. Hulshof, MD, PhD, of the Department of Radiotherapy, Amsterdam UMC, is the corresponding author of the Journal of Clinical Oncology article.

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