Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study)

Abstract

PURPOSE To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. PATIENTS AND METHODS Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. RESULTS Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively ( P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively ( P = .15). CONCLUSION In dCRT 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 AC and SCC.

Treatment patterns and survival in advanced unresectable esophageal squamous cell cancer: A population‐based study

“…As the phase III ARTDECO study showed that dose escalation up to 61.6 Gy did not improve outcomes in patients with esophageal cancer, including patients with ESCC. 24 Currently, clinical trials are underway to explore the addition of PD-1 inhibitors and/or TGFβ to definitive chemoradiotherapy and will hopefully improve outcomes for patients with ESCC who are eligible for definitive chemoradiotherapy. 25,26 The phase III CheckMate 648 trial reported a survival time of 10.7 months for patients receiving chemotherapy alone, and an increased survival of 12.8 and 13.2 months for patients receiving nivolumab plus chemotherapy and nivolumab plus ipilimumab, respectively.…”

“…To improve outcomes after definitive chemoradiotherapy, radiation dose escalation was considered an option until recently. As the phase III ARTDECO study showed that dose escalation up to 61.6 Gy did not improve outcomes in patients with esophageal cancer, including patients with ESCC 24 . Currently, clinical trials are underway to explore the addition of PD‐1 inhibitors and/or TGF‐β to definitive chemoradiotherapy and will hopefully improve outcomes for patients with ESCC who are eligible for definitive chemoradiotherapy 25,26 …”

Long-term clinical outcomes of lipiodol marking using standard gastroscopy for image-guided radiotherapy of upper gastrointestinal cancers

“…The use of F-IGRT has many potential benefits over S-IGRT, including facilitating a higher dose focused on the tumor with a lower dose delivered to cover the submucosal spread, and more accurate treatment delivery (matching to the tumor rather than surrounding bony structures)[ 17 , 28 ]. There are conflicting data regarding the efficacy of increased radiation dose in treating oesophageal cancer[ 29 , 30 ]. While some retrospective studies demonstrated a dose-response, recent randomized control trials failed to find a difference in outcomes[ 31 - 33 ].…”

Kein Vorteil für die lokale Kontrolle nach Dosiseskalation der Strahlentherapie bei Patienten mit Ösophaguskarzinom nach einer definitiven Radiochemotherapie: randomisierte Phase-III-Studie ARTDECO

“…In der hier kommentierten, randomisierten Phase-III-Studie ARTDECO wurde nach einer medianen Nachbeobachtungszeit von 50 Monaten der primäre Endpunkt des lokal progressionsfreien Überlebens (LPFS) nach einer Dosiseskalation der Strahlentherapie von 50,4 Gy auf 61,6 Gy auf den Primärtumor nicht signifikant verbessert [ 4 ]. Einige Aspekte der Studie sind deshalb hier erwähnenswert.…”