title: Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer.
abstract: BACKGROUND
  To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution.
  
  
  METHODS
  Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4-6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival.
  
  
  RESULTS
  Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twenty-six (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, disease-free survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively.
  
  
  CONCLUSIONS
  Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patients' cure.
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Ivica
authors.initials: I
authors.lastname: Ratosa
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Irena
authors.initials: I
authors.lastname: Oblak
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Franc
authors.initials: F
authors.lastname: Anderluh
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Vaneja
authors.initials: V
authors.lastname: Velenik
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Jasna
authors.initials: J
authors.lastname: But-Hadzic
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Ajra Secerov
authors.initials: AS
authors.lastname: Ermenc
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Ana
authors.initials: A
authors.lastname: Jeromen
keywords: gastroesophageal junction cancer; preoperative radiochemotherapy; surgery; toxicity; unresectable gastric cancer