title: Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group.
abstract: BACKGROUND
  Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines.
  
  
  METHODS
  Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS).
  
  
  RESULTS
  Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS.
  
  
  CONCLUSIONS
  When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Postlewait
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Cecilia G
authors.initials: CG
authors.lastname: Ethun
authors.affiliation: Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Thuy B
authors.initials: TB
authors.lastname: Tran
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Prescott
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Wang
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Jason
authors.initials: J
authors.lastname: Glenn
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, NY.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Hatzaras
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, NY.
authors.forename: Rivfka
authors.initials: R
authors.lastname: Shenoy
authors.affiliation: Department of Surgery, The Ohio State University, Columbus, OH.
authors.forename: John E
authors.initials: JE
authors.lastname: Phay
authors.affiliation: Department of Surgery, The Ohio State University, Columbus, OH.
authors.forename: Kara
authors.initials: K
authors.lastname: Keplinger
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Linda X
authors.initials: LX
authors.lastname: Jin
authors.affiliation: Department of General Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.affiliation: Department of General Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Salem
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Sicklick
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Shady
authors.initials: S
authors.lastname: Gad
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Yopp
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: John C
authors.initials: JC
authors.lastname: Mansour
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, CA.
authors.forename: Quan-Yang
authors.initials: QY
authors.lastname: Duh
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, CA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Seiser
authors.affiliation: Department of Surgery, Vanderbilt University, Nashville, TN.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Solorzano
authors.affiliation: Department of Surgery, Vanderbilt University, Nashville, TN.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Kiernan
authors.affiliation: Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Votanopoulos
authors.affiliation: Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Levine
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Staley
authors.affiliation: Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: George A
authors.initials: GA
authors.lastname: Poultsides
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: smaithe@emory.edu.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D000315:Adrenalectomy; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane