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, vol. 38, pp. 281

Abstract

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.

Authors 14

1. Maarten C.C.M. Hulshof

   Amsterdam University Medical Centers · Cancer Center Amsterdam · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of Radiotherapy, Cancer Center Amsterdam, Amsterdam, Netherlands;

2. Debby E. Geijsen

   Amsterdam University Medical Centers

   Affiliation as printed

   Amsterdam UMC, Amsterdam, Netherlands;

3. Tom Rozema

   Instituut Verbeeten

   Affiliation as printed

   Verbeeten Institute, Department of Radiotherapy, Tilburg, Netherlands;

4. Vera Oppedijk

   Radiotherapeutisch Instituut Friesland

   Affiliation as printed

   Radiotherapeutisch Instituut Friesland, Leeuwarden, Netherlands;

5. Jeroen Buijsen
   Affiliation as printed

   Maastro, Maastricht, Netherlands;

6. Karen J. Neelis Aachen

   Leiden University Medical Center

   Affiliation as printed

   LUMC, Leiden, Netherlands;

7. Joost J.M.E. Nuyttens

   Erasmus MC · Erasmus MC Cancer Institute

   Affiliation as printed

   Department of Radiation Oncology, Erasmus Medical Center Cancer Insitute, Rotterdam, Netherlands;

8. Maurice van der Sangen

   Catharina Ziekenhuis

   Affiliation as printed

   Catharina Hospital, Eindhoven, Netherlands;

9. Paul M. Jeene

   Radiotherapiegroep

   Affiliation as printed

   Radiotherapiegroep, Deventer, Netherlands;

10. Janny G. Reinders
    Affiliation as printed

    ZRTI Roosendaal, Nijmegen, Netherlands;

11. Mark I. van Berge Henegouwen

    Amsterdam University Medical Centers · Cancer Center Amsterdam · University of Amsterdam

    Affiliation as printed

    Amsterdam UMC, University of Amsterdam, Department of Surgery, Cancer Center Amsterdam, Amsterdam, Netherlands;

12. Jeanin Elise van Hooft

    Amsterdam UMC Location University of Amsterdam

    Affiliation as printed

    Academic Medical Center, Amsterdam, Netherlands;

13. Hanneke W.M. van Laarhoven

    Amsterdam University Medical Centers · Cancer Center Amsterdam · University of Amsterdam

    Affiliation as printed

    Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, Netherlands;

14. Ate van der Gaast

    Erasmus MC

    Affiliation as printed

    Erasmus MC, Rotterdam, Netherlands;