Preoperative chemoradiotherapy for esophageal or junctional cancer
P. van Hagen1, M.C.C.M. Hulshof2, J.J.B. van Lanschot1,3, E.W. Steyerberg4, M.I. van Berge Henegouwen3, B.P.L.
Wijnhoven1, D.J. Richel5, G.A.P. Nieuwenhuijzen6, G.A.P. Hospers7, J.J. Bonenkamp8, M.A. Cuesta9, R.J.B.
Blaisse10, O.R.C. Busch3, F.J.W. ten Kate11,12, G. J.Creemers13, C.J.A. Punt14, J.Th.M. Plukker15, H.M.W. Verheul16,
E.J. Spillenaar Bilgen17, H. van Dekken11,18, M.J.C. van der Sangen19, T. Rozema20,21, K. Biermann11, J.C.
Beukema22, A.H.M. Piet23, C.M. van Rij24, J.G. Reinders25, H.W. Tilanus1A. van der Gaast26, for the CROSS-study
Group
1 Department
of Surgery, Erasmus MC Rotterdam, 2 Department of Radiation Oncology, Academic Medical Center
Amsterdam, 3 Department of Surgery, Academic Medical Center Amsterdam, 4 Department of Public Health, Erasmus MC
Rotterdam, 5Department of Medical Oncology, Academic Medical Center Amsterdam, 6Department of Surgery, Catharina
Hospital Eindhoven, 7Department of Medical Oncology, University Medical Center Groningen, 8Department of Surgery,
Radboud University Nijmegen Medical Center Nijmegen, 9Department of Surgery, VU Medical Center Amsterdam,
10Department of Medical Oncology, Rijnstate Hospital Arnhem, 11Department of Pathology, Erasmus MC Rotterdam,
12Department of Pathology, Academic Medical Center Amsterdam, 13Department of Medical Oncology, Catharina Hospital
Eindhoven, 14 Department of Medical Oncology, Radboud University Nijmegen Medical Center Nijmegen,15Department of
Surgery, University Medical Center Groningen, 16Department of Medical Oncology, VU Medical Center Amsterdam, 17
Department of Surgery, Rijnstate Hospital Arnhem, 18Department of Pathology, St. Lucas Andreas Hospital Amsterdam,
19Department of Radiation Oncology, Catharina Hospital Eindhoven, 20Department of Radiation Oncology, Radboud
University Nijmegen Medical Center Nijmegen, 21Verbeeten Institute Tilburg, 22Department of Radiation Oncology,
University Medical Center Groningen, 23Department of Radiation Oncology, VU Medical Center Amsterdam, 24 Department
of Radiation Oncology, Erasmus MC Rotterdam, 25Arnhem Radiotherapeutic Institute ARTI, 26Department of Medical
Oncology, Erasmus MC Rotterdam/Daniel den Hoed Cancer Center
The role of neoadjuvant chemoradiotherapy in esophageal cancer remains unclear. The aim of this
study was to compare preoperative chemoradiotherapy (CRT) followed by surgery vs. surgery alone
in patients with esophageal or esophagogastric junction cancer.
Patients with resectable cT1N1M0 or cT2-3N0-1M0 tumors were randomly assigned to preoperative
CRT of weekly administrations of carboplatin AUC of 2 and paclitaxel 50 mg·m-2 for 5 weeks and
concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery (CRT+S) or
surgery alone (S).
From 2004 through 2008, 368 patients were enrolled, of whom 366 could be analyzed: 275/366
(75%) had adenocarcinoma and 84/366 (23%) had squamous cell carcinoma. Some 178 patients were
randomized for CRT followed by surgery, 188 patients for surgery alone. The most common major
hematologic toxicities in the CRT+S arm were leukopenia (6%) and neutropenia (2%), the most
common major non-hematologic toxicities were anorexia (5%) and fatigue (3%). Complete resection
with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the
CRT+S arm vs. 69% in the S arm (p<0.001). In 47/161 (29%) patients who underwent resection after
CRT, a pathologically complete response was achieved. Postoperative complications and in-hospital
mortality (4% in both treatment arms) were comparable between treatment arms. Median overall
survival was 49.4 months in the CRT+S arm vs. 24.0 months in the S arm. Overall survival was
significantly better (p= 0.003) in the CRT+S arm (HR 0.657; 95% CI 0.495-0.871).
Conclusion: Preoperative chemoradiotherapy was well tolerated and improved survival in patients
with potentially curable esophageal or esophagogastric junction cancer.