title: The prognostic value of irradiated lung volumes on the prediction of intra-/ post-operative mortality in patients after neoadjuvant radiochemotherapy for esophageal cancer. A retrospective multicenter study.
abstract: OBJECTIVE
  To assess the association between dosimetric factors of the lung and incidence of intra- and postoperative mortality among esophageal cancer (EC) patients treated with neoadjuvant radiochemotherapy (N-RCT) followed by surgery (S).
  
  
  METHODS
  Inclusion criteria were: age < 85 years, no distant metastases at the time of diagnosis, no induction chemotherapy, conformal radiotherapy, total dose ≤ 50.4 Gy, and available dose volume histogram (DVH) data. One-hundred thirty-five patients met our inclusion criteria. Median age was 62 years. N-RCT consisted of 36 - 50.4 Gy (median 45 Gy), 1.8 - 2 Gy per fraction. Concomitant chemotherapy consisted of 5-Fluoruracil (5-FU) and cisplatin in 113 patients and cisplatin and taxan-derivates in 15 patients. Seven patients received a single cytotoxic agent. In 130 patients an abdominothoracal and in 5 patients a transhiatal resection was performed. The following dosimetric parameters were generated from the total lung DVH: mean dose, V5, V10, V15, V20, V30, V40, V45 and V50. The primary endpoint was the rate of intra- and postoperative mortality (from the start of N-RCT to 60 days after surgical resection).
  
  
  RESULTS
  A total of ten postoperative deaths (7%) were observed: 3 within 30 days (2%) and 7 between 30 and 60 days after surgical intervention (5%); no patient died during the operation. In the univariate analysis, weight loss (≥10% in 6 months prior to diagnosis, risk ratio: 1.60, 95%CI: 0.856-2.992, p=0.043), Eastern Cooperative Oncology Group-performance status (ECOG 2 vs. 1, risk ratio: 1.931, 95%CI: 0.898-4.150, p=0.018) and postoperative pulmonary plus non-pulmonary complications (risk ratio: 2.533, 95%CI: 0.978-6.563, p=0.004) were significantly associated with postoperative mortality. There was no significant association between postoperative mortality and irradiated lung volumes. Lung V45 was the only variable which was significantly associated with higher incidence of postoperative pulmonary plus non-pulmonary complications (Exp(B): 1.285, 95%CI 1.029-1.606, p=0.027), but not with the postoperative pulmonary complications (Exp(B): 1.249, 95%CI 0.999-1.561, p=0.051).
  
  
  CONCLUSIONS
  Irradiated lung volumes did not show relevant associations with intra- and postoperative mortality of patients treated with moderate dose (36 - 50.4 Gy) conventionally fractionated conformal radiotherapy combined with widely used radiosensitizers. Postoperative mortality was significantly associated with greater weight loss, poor performance status and development of postoperative complications, but not with treatment-related factors. Limiting the volume of lung receiving higher radiation doses appears prudent because of the observed association with risk of postoperative complications.
authors: 1. Department of Radiation Oncology, Marien Hospital Herne, Clinic of Ruhr-Universität Bochum, Herne, Germany.
authors: Philipp Günther
authors: PG
authors: Kup
authors: 2. Department of Oncology and Palliative Medicine, Nordland Hospital Bodø, Norway.
authors: Carsten
authors: C
authors: Nieder
authors: 3. Department of Radiation Oncology, Krankenhaus der Barmherzigen Schwestern Linz, Linz, Austria. ; 4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Hans
authors: H
authors: Geinitz
authors: 5. Department of Radiation Oncology, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Christoph
authors: C
authors: Henkenberens
authors: 6. Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors: Angela
authors: A
authors: Besserer
authors: 4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Markus
authors: M
authors: Oechsner
authors: 4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Sabine
authors: S
authors: Schill
authors: 1. Department of Radiation Oncology, Marien Hospital Herne, Clinic of Ruhr-Universität Bochum, Herne, Germany. ; 7. Department of Radiation Oncology, Lippe Hospital, Lemgo, Germany.
authors: Ralph
authors: R
authors: Mücke
authors: 4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Vera
authors: V
authors: Scherer
authors: 4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Stephanie E
authors: SE
authors: Combs
authors: 1. Department of Radiation Oncology, Marien Hospital Herne, Clinic of Ruhr-Universität Bochum, Herne, Germany. ; 8. Department of Radiation Oncology, Sankt Josef Hospital Bochum, Clinic of Ruhr-University Bochum, Bochum, Germany.
authors: Irenäus A
authors: IA
authors: Adamietz
authors: 1. Department of Radiation Oncology, Marien Hospital Herne, Clinic of Ruhr-Universität Bochum, Herne, Germany. ; 4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany ; 8. Department of Radiation Oncology, Sankt Josef Hospital Bochum, Clinic of Ruhr-University Bochum, Bochum, Germany.
authors: Khashayar
authors: K
authors: Fakhrian
keywords: Dose-volume histogram; Esophageal cancer; Lung toxicity; Neoadjuvant radiochemotherapy; Postoperative mortality