Lauren M Postlewait1, Cecilia G Ethun1, Thuy B Tran2, Jason D Prescott3, Timothy M Pawlik3, Tracy S Wang4, Jason Glenn4, Ioannis Hatzaras5, Rivfka Shenoy5, John E Phay6, Kara Keplinger6, Ryan C Fields7, Linda X Jin7, Sharon M Weber8, Ahmed Salem8, Jason K Sicklick9, Shady Gad9, Adam C Yopp10, John C Mansour10, Quan-Yang Duh11, Natalie Seiser11, Carmen C Solorzano12, Colleen M Kiernan12, Konstantinos I Votanopoulos13, Edward A Levine13, Charles A Staley1, George A Poultsides2, Shishir K Maithel14. 1. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA. 2. Department of Surgery, Stanford University School of Medicine, Stanford, CA. 3. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD. 4. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI. 5. Department of Surgery, New York University School of Medicine, New York, NY. 6. Department of Surgery, The Ohio State University, Columbus, OH. 7. Department of Surgery, Washington University School of Medicine, St Louis, MO. 8. Department of General Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI. 9. Department of Surgery, University of California San Diego, San Diego, CA. 10. Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX. 11. Department of Surgery, University of California San Francisco, San Francisco, CA. 12. Department of Surgery, Vanderbilt University, Nashville, TN. 13. Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC. 14. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: smaithe@emory.edu.
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. STUDY DESIGN: 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.
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. STUDY DESIGN: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: Alfredo Berruti; Massimo Terzolo; Paola Sperone; Anna Pia; Silvia Della Casa; David J Gross; Carlo Carnaghi; Paolo Casali; Francesco Porpiglia; Franco Mantero; Giuseppe Reimondo; Alberto Angeli; Luigi Dogliotti Journal: Endocr Relat Cancer Date: 2005-09 Impact factor: 5.678
Authors: B Wängberg; A Khorram-Manesh; S Jansson; B Nilsson; O Nilsson; C E Jakobsson; S Lindstedt; A Odén; H Ahlman Journal: Endocr Relat Cancer Date: 2010-02-18 Impact factor: 5.678
Authors: Jame Abraham; Susan Bakke; Ann Rutt; Beverly Meadows; Maria Merino; Richard Alexander; David Schrump; David Bartlett; Peter Choyke; Rob Robey; Elizabeth Hung; Seth M Steinberg; Susan Bates; Tito Fojo Journal: Cancer Date: 2002-05-01 Impact factor: 6.860
Authors: J P Luton; S Cerdas; L Billaud; G Thomas; B Guilhaume; X Bertagna; M H Laudat; A Louvel; Y Chapuis; P Blondeau Journal: N Engl J Med Date: 1990-04-26 Impact factor: 91.245
Authors: T M A Kerkhofs; L J J Derijks; M H T Ettaieb; E M W Eekhoff; C Neef; H Gelderblom; J den Hartigh; H J Guchelaar; H R Haak Journal: Eur J Endocrinol Date: 2014-09-08 Impact factor: 6.664
Authors: Thomas M A Kerkhofs; Luc J J Derijks; Hester Ettaieb; Jan den Hartigh; Kees Neef; Hans Gelderblom; Henk-Jan Guchelaar; Harm R Haak Journal: Ther Drug Monit Date: 2015-02 Impact factor: 3.681
Authors: Thuy B Tran; Lauren M Postlewait; Shishir K Maithel; Jason D Prescott; Tracy S Wang; Jason Glenn; John E Phay; Kara Keplinger; Ryan C Fields; Linda X Jin; Sharon M Weber; Ahmed Salem; Jason K Sicklick; Shady Gad; Adam C Yopp; John C Mansour; Quan-Yang Duh; Natalie Seiser; Carmen C Solorzano; Colleen M Kiernan; Konstantinos I Votanopoulos; Edward A Levine; Ioannis Hatzaras; Rivfka Shenoy; Timothy M Pawlik; Jeffrey A Norton; George A Poultsides Journal: J Surg Oncol Date: 2016-09-16 Impact factor: 3.454
Authors: Caroline E Poorman; Lauren M Postlewait; Cecilia G Ethun; Thuy B Tran; Jason D Prescott; Timothy M Pawlik; Tracy S Wang; Jason Glenn; Ioannis Hatzaras; Rivfka Shenoy; John E Phay; Kara Keplinger; Ryan C Fields; Linda X Jin; Sharon M Weber; Ahmed Salem; Jason K Sicklick; Shady Gad; Adam C Yopp; John C Mansour; Quan-Yang Duh; Natalie Seiser; Carmen C Solorzano; Colleen M Kiernan; Konstantinos I Votanopoulos; Edward A Levine; Charles A Staley; George A Poultsides; Shishir K Maithel Journal: Am Surg Date: 2017-07-01 Impact factor: 0.688
Authors: Caroline E Poorman; Cecilia G Ethun; Lauren M Postlewait; Thuy B Tran; Jason D Prescott; Timothy M Pawlik; Tracy S Wang; Jason Glenn; Ioannis Hatzaras; Rivfka Shenoy; John E Phay; Kara Keplinger; Ryan C Fields; Linda X Jin; Sharon M Weber; Ahmed Salem; Jason K Sicklick; Shady Gad; Adam C Yopp; John C Mansour; Quan-Yang Duh; Natalie Seiser; Carmen C Solórzano; Colleen M Kiernan; Konstantinos I Votanopoulos; Edward A Levine; Charles A Staley; George A Poultsides; Shishir K Maithel Journal: Ann Surg Oncol Date: 2017-11-21 Impact factor: 5.344
Authors: Shawn Sam Thomas; Arundhati Marathe; Anish Jacob Cherian; N Siddhartha; Gowri Mahasampath; Manipadam Marie Therese; Chandramohan Jagan; Hesarghatta Shyamasunder Asha; Nihal Thomas; Ashish Singh; B Selvamani; Mazhuvanchary Jacob Paul; Deepak Thomas Abraham Journal: Indian J Surg Oncol Date: 2021-09-13
Authors: Thuy B Tran; Shishir K Maithel; Timothy M Pawlik; Tracy S Wang; Ioannis Hatzaras; John E Phay; Ryan C Fields; Sharon M Weber; Jason K Sicklick; Adam C Yopp; Quan-Yang Duh; Carmen C Solorzano; Konstantinos I Votanopoulos; George A Poultsides Journal: J Am Coll Surg Date: 2016-09-13 Impact factor: 6.113