title: Upfront Systemic Chemotherapy and Short-Course Radiotherapy with Delayed Surgery for Locally Advanced Rectal Cancer with Distant Metastases: Outcomes, Compliance, and Favorable Prognostic Factors.
abstract: OBJECTIVE
  Optimal treatment for locally advanced rectal cancer (LARC) with distant metastasis remains elusive. We aimed to evaluate upfront systemic chemotherapy and short-course radiotherapy (RT) followed by delayed surgery for such patients, and to identify favorable prognostic factors.
  
  
  METHODS
  We retrospectively reviewed 50 LARC patients (cT4 or cT3, <2 mm from the mesorectal fascia) with synchronous metastatic disease. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival, treatment-related toxicity, and compliance. We considered P values <0.05 significant.
  
  
  RESULTS
  At 22 months median follow-up, the median PFS time was 16 months and the 2-year PFS rate was 34.8%. Thirty-five patients who received radical surgery for primary and metastatic tumors were designated the curable group. Six patients with clinical complete response (ypCR) of metastases who underwent radical surgery for only the primary tumor were classified as potentially curable. Nine patients who received no radical surgery (3 received palliative surgery) were deemed the palliative group. The ypCR rate among surgery patients was 13.6%. PFS rates for the curable or potentially curable groups were significantly longer than that of the palliative group (P<0.001). On multivariate analysis, solitary organ metastasis and R0 status were independent prognostic factors for PFS.
  
  
  CONCLUSIONS
  These findings demonstrated that a strong possibility that upfront chemotherapy and short-course RT with delayed surgery are an effective alternative treatment for LARC with potentially resectable distant metastasis, owing to achievement of pathologic down-staging, R0 resection, and favorable compliance and toxicity, despite the long treatment duration.
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Hong In
authors.initials: HI
authors.lastname: Yoon
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Woong Sub
authors.initials: WS
authors.lastname: Koom
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Minkyu
authors.initials: M
authors.lastname: Jung
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Tae Il
authors.initials: TI
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.|Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D012007:Rectum / Q000601:surgery; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents