title: NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer.
abstract: OBJECTIVE
  To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer.
  
  
  METHODS
  Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided).
  
  
  RESULTS
  Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥ 2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively.
  
  
  CONCLUSIONS
  The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts. Electronic address: tshong1@mgh.harvard.edu.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moughan
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Garofalo
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.
authors.forename: Johanna
authors.initials: J
authors.lastname: Bendell
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Berger
authors.affiliation: North Main Radiation Oncology, Providence, Rhode Island.
authors.forename: Nicklas B E
authors.initials: NB
authors.lastname: Oldenburg
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Pramila Rani
authors.initials: PR
authors.lastname: Anne
authors.affiliation: London Regional Cancer Program/Western Ontario, London, Ontario.
authors.forename: Francisco
authors.initials: F
authors.lastname: Perera
authors.affiliation: Intermountain Medical Center, Salt Lake City, Utah.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
authors.forename: Salma K
authors.initials: SK
authors.lastname: Jabbour
authors.affiliation: Piedmont Hospital, Atlanta, Georgia.
authors.forename: Adam
authors.initials: A
authors.lastname: Nowlan
authors.affiliation: Main Line Community Clinical Oncology Program, Wynnewood, Pennsylvania.
authors.forename: Albert
authors.initials: A
authors.lastname: DeNittis
authors.affiliation: University of Texas-MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher
authors.initials: C
authors.lastname: Crane
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000069287:Capecitabine; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011300:Preoperative Care; D011788:Quality of Life; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil