title: Neoadjuvant chemoradiotherapy followed by D2 gastrectomy in locally advanced gastric cancer.
abstract: OBJECTIVE
  To investigate the efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectability of locally advanced gastric cancer (LAGC).
  
  
  METHODS
  Between November 2007 and January 2014, 29 patients with LAGC (clinically T3 with distal esophagus invasion/T4 or bulky regional node metastasis) that were treated with NACRT followed by D2 gastrectomy were included in this study. Resectability was evaluated with radiologic and endoscopic exams before and after NACRT. Using three-dimensional conformal radiotherapy, patients received 45 Gy, with a daily dose of 1.8 Gy. The entire tumor extent and the regional metastatic lymph nodes were included in the gross tumor volume. Patients presenting with a resectable tumor after NACRT received a total or subtotal gastrectomy with D2 dissection. The pathologic tumor response was evaluated using Japanese Gastric Cancer Association histologic evaluation criteria. Postoperative morbidity was evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and progression-free survival (PFS) rates were estimated using a Kaplan-Meier analysis and compared using the log-rank test.
  
  
  RESULTS
  All patients were assessed as unresectable cases. Twenty-four patients (24/29; 82.8%) showed LAGC on positron emission tomography-computed tomography (CT) and contrast-enhanced CT, whereas four patients (4/29; 13.8%) with vague invasion or abutment to an adjacent organ underwent diagnostic laparoscopy. One patient (1/29; 3.4%), initially assessed as a resectable case, underwent an "open and closure" after the tumor was found to be unresectable. Abutment to an adjacent organ (34.5%) was the most common reason for NACRT. The clinical response rate one month after NACRT was 44.8%. After NACRT, 69% (20/29) of patients had a resectable tumor. Of the 20 patients with a resectable tumor, 18 patients (62.1%) underwent a D2 gastrectomy. The R0 resection rate was 94.4% and two patients (2/18; 11.1%) showed a complete response. The median follow-up duration was 13.5 mo. The one-year OS and PFS rates were 72.4 and 48.9%, respectively. The one-year OS, PFS, local failure-free survival, and distant metastasis-free survival were higher in patients with a resectable tumor after NACRT (P < 0.001, P < 0.001, P < 0.001, and P = 0.078, respectively). No grade 3-4 late treatment-related toxicities or postoperative mortalities were observed.
  
  
  CONCLUSIONS
  NACRT with D2 gastrectomy showed a high rate of R0 resection and promising local control, which may increase the R0 resection opportunity resulting in survival benefit.
authors.affiliation: Mi Sun Kim, Ki Chang Keum, Woong Sub Koom, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Mi Sun Kim, Ki Chang Keum, Woong Sub Koom, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Mi Sun Kim, Ki Chang Keum, Woong Sub Koom, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Hyung
authors.affiliation: Mi Sun Kim, Ki Chang Keum, Woong Sub Koom, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Mi Sun Kim, Ki Chang Keum, Woong Sub Koom, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Mi Sun Kim, Ki Chang Keum, Woong Sub Koom, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Ki Chang
authors.initials: KC
authors.lastname: Keum
authors.affiliation: Mi Sun Kim, Ki Chang Keum, Woong Sub Koom, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Woong Sub
authors.initials: WS
authors.lastname: Koom
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005743:Gastrectomy / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden
keywords: Advanced gastric cancer; Combined modality therapy; D2 gastrectomy; Neoadjuvant chemoradiotherapy; Treatment outcome