title: FOLFOX and intensified split-course chemoradiation as initial treatment for rectal cancer with synchronous metastases.
abstract: BACKGROUND
  Optimal initial management of rectal carcinoma with synchronous metastases (RCSM) is controversial - both for patients being treated with curative and palliative intent. This study aims to evaluate the use of an upfront treatment strategy combining FOLFOX chemotherapy with split-course pelvic chemoradiation (FOLFOX + CRT) for patients with RCSM.
  
  
  METHODS
  An analysis of all patients who commenced treatment with FOLFOX + CRT at our institutions between January 2009 and June 2014 was performed. The regimen consisted of a total of 12 weeks of treatment with split-course pelvic chemoradiation (50.4Gy with concurrent oxaliplatin and 5-FU) alternating with FOLFOX chemotherapy. Restaging imaging was performed following treatment, with subsequent management as per local standard of care.
  
  
  RESULTS
  78 patients (15 with resectable liver-only metastases) were identified. 77 (99%) completed at least 45Gy of radiation and 87% completed ≥75% of planned dose intensity of both oxaliplatin and 5FU. Two (2.6%) patients died within 30 days of treatment. Rates of radiological complete or partial response for local and metastatic disease were 90% and 66%, respectively. 24% patients had radiological disease progression of metastatic disease. Median overall survival for patients with unresectable metastatic disease at baseline was 23 months (95%CI: 19-28). 12 patients underwent radical surgery to both the rectum and liver and had an estimated 3-year overall survival rate of 62% (95%CI: 37-100). For those patients who did not proceed to rectal surgery, only 7% required palliative re-irradiation or surgery at a later date and all >20months from initial treatment.
  
  
  CONCLUSIONS
  In patients with unresectable metastatic disease, FOLFOX + CRT provides durable pelvic control for the majority without the need for additional local treatment. For patients with an advanced primary tumor and synchronous resectable liver-only metastases, FOLFOX + CRT can be considered a feasible and tolerable upfront treatment option.
authors.affiliation: a Department of Radiation Oncology , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: T
authors.initials: T
authors.lastname: Bird
authors.affiliation: b Department of Medicine , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: M
authors.initials: M
authors.lastname: Michael
authors.affiliation: c Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: M
authors.initials: M
authors.lastname: Bressel
authors.affiliation: a Department of Radiation Oncology , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: J
authors.initials: J
authors.lastname: Chu
authors.affiliation: a Department of Radiation Oncology , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: S
authors.initials: S
authors.lastname: Chander
authors.affiliation: d Department of Medical Oncology , Eastern Health , Box Hill, Melbourne , Australia.
authors.forename: P
authors.initials: P
authors.lastname: Cooray
authors.affiliation: d Department of Medical Oncology , Eastern Health , Box Hill, Melbourne , Australia.
authors.forename: J
authors.initials: J
authors.lastname: McKendrick
authors.affiliation: b Department of Medicine , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: M
authors.initials: M
authors.lastname: Jefford
authors.affiliation: e Department of Surgery , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: A
authors.initials: A
authors.lastname: Heriot
authors.affiliation: f Department of Surgical Oncology , Eastern Health , Box Hill, Melbourne , Australia.
authors.forename: M
authors.initials: M
authors.lastname: Steel
authors.affiliation: a Department of Radiation Oncology , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: T
authors.initials: T
authors.lastname: Leong
authors.affiliation: a Department of Radiation Oncology , Peter MacCallum Cancer Centre , Melbourne , Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ngan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000556:secondary / Q000628:therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil