title: Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.
abstract: BACKGROUND
  Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy.
  
  
  METHODS
  Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls.
  
  
  RESULTS
  76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%).
  
  
  CONCLUSIONS
  This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: rmyerson@radonc.wustl.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Myerson
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tan
authors.affiliation: Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Steven
authors.initials: S
authors.lastname: Hunt
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Elisa
authors.initials: E
authors.lastname: Birnbaum
authors.affiliation: Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: James
authors.initials: J
authors.lastname: Fleshman
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lannis
authors.initials: L
authors.lastname: Hall
authors.affiliation: Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Ira
authors.initials: I
authors.lastname: Kodner
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: A Craig
authors.initials: AC
authors.lastname: Lockhart
authors.affiliation: Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Matthew
authors.initials: M
authors.lastname: Mutch
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Michael
authors.initials: M
authors.lastname: Naughton
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Caron
authors.initials: C
authors.lastname: Rigden
authors.affiliation: Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Bashar
authors.initials: B
authors.lastname: Safar
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Steven
authors.initials: S
authors.lastname: Sorscher
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Rama
authors.initials: R
authors.lastname: Suresh
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wang-Gillam
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Parag
authors.initials: P
authors.lastname: Parikh
mesh_terms: D001003:Anal Canal; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D059351:Organ Sparing Treatments; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011300:Preoperative Care / Q000379:methods; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin; D002955:Leucovorin; D005472:Fluorouracil