Does Adjuvant Mitotane Impact Cure Rates in Adrenocortical Carcinoma? Insights From the ICARO-GETTHI/SEEN Registry

被引：0

作者：

Carmona-Bayonas, Alberto ^{[1
]}

alvarez-Escola, Cristina ^{[2
]}

Ballester Navarro, Inmaculada ^{[3
]}

Hernando Cubero, Jorge ^{[4
]}

Mangas Cruz, Miguel angel ^{[5
]}

Garcia-Centeno, Rogelio ^{[6
]}

Iglesias, Clara ^{[7
]}

Garcia-Donas, Jesus ^{[8
]}

Picon, Maria Jose ^{[9
]}

Paja, Miguel ^{[10
]}

Gonzalez Batanero, Lorena ^{[11
]}

Garcia, Lourdes ^{[12
]}

Alonso Gordoa, Teresa ^{[13
]}

Lopez, Carlos ^{[14
]}

Hanzu, Felicia ^{[15
]}

Martinez-Trufero, Javier ^{[16
]}

Febrero, Beatriz ^{[17
]}

Saiz-Lopez, Patricia ^{[18
]}

Blanco Carrera, Concepcion ^{[19
]}

Cajal, Teresa Ramon ^{[20
]}

Veiguela, Brenda ^{[21
]}

Gressani, Oswaldo ^{[22
]}

Valdes, Nuria ^{[23
]}

Jimenez-Fonseca, Paula ^{[7
]}

机构：

[1] Univ Murcia UMU, Hosp Univ Morales Meseguer, Inst Murciano Invest Biosanit IMIB Pascual Parrill, Dept Hematol & Hemotherapy, Murcia, Spain

[2] Hosp Univ La Paz, Pathol Dept, Madrid, Spain

[3] Hosp Univ Morales Meseguer, Dept Med Oncol, Murcia 30008, Spain

[4] Hosp Univ Val Hebron, Vall Hebron Inst Oncol VHIO, Med Oncol Dept, Gastrointestinal & Endocrine Tumors Unit, Barcelona 08035, Spain

[5] Hosp Univ Virgen Rocio, Dept Oncol, Seville 41013, Spain

[6] Hosp Gen Univ Gregorio Maranon, Dept Pahol, Madrid 28007, Spain

[7] Hosp Univ Cent Asturias, Med Oncol Dept, ISPA, Oviedo 33011, Spain

[8] Hosp Univ HM Sanchinarro, Med Oncol Dept, Madrid, Spain

[9] Virgen Victoria Univ Hosp, Inst Biomed Res Inst Malaga IBIMA, Dept Endocrinol & Nutr, CIBER Pathophysiol Obes & Nutr CIBERON, Malaga 29010, Spain

[10] Univ Basque Country UPV EHU, Univ Pais Vasco, Leioa, Spain

[11] Hosp Univ Canarias, Dept Med Oncol, Tenerife 38320, Spain

[12] Hosp Univ Jerez, Dept Surg, Carretera Circunyalac S-N, Jerez de la Frontera 11407, Spain

[13] Hosp Univ Ramon y Cajal, Med Oncol Dept, Madrid 28034, Spain

[14] Univ Cantabria, Univ Hosp Marques Valdecilla, Inst Invest Marques Valdecilla IDIVAL, Dept Radiol, E-39005 Santander, Spain

[15] Hosp Clin Barcelona, Endocrinol & Nutr Dept, E-08036 Barcelona, Spain

[16] Hosp Univ Miguel Servet, Dept Med Oncol, Zaragoza, Spain

[17] Univ Murcia, Hosp Univ Virgen Arrixaca, Dept Gen Surg, Endocrine Surg Unit,Inst Murciano Invest Biosanit, Murcia 30120, Spain

[18] Hosp Univ Burgos, Ophtalmol Dept, Burgos 09006, Spain

[19] Hosp Univ Principe Asturias, Hematol Serv, Alcala De Henares 28805, Madrid, Spain

[20] Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

[21] Hosp Univ Cabuenes, Dept Endocrinol, Gijon 33394, Spain

[22] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat I BioSta, Data Sci Inst, Hasselt, Belgium

[23] Univ Pais Vasco UPV EHU, Hosp Univ Cruces, Dept Patol, Biobizkaia,IBERDEM,CIBERER,Endo ERN, Baracaldo, Spain

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2025年

关键词：

adrenocortical carcinoma; adjuvant; mixture cure model; mitotane; survival; recurrence; GASTROINTESTINAL STROMAL TUMOR; IMATINIB; THERAPY; CANCER; DURATION;

D O I：

10.1210/clinem/dgaf082

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Context Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with a high risk of postoperative recurrence. Although adjuvant mitotane is commonly used, its potential for achieving cure rather than simply postponing inevitable recurrence remains uncertain.Objective This study investigates whether mitotane impacts ACC recurrence patterns by preventing or delaying recurrence.Methods This retrospective analysis used data from the ICARO-GETTHI/SEEN registry, which includes 36 Spanish hospitals. Recurrence in nonmetastatic ACC patients after resection was analyzed using Cox models, flexible longitudinal models, and mixture cure models to evaluate the impact of mitotane.Results Among 244 patients, 133 (52%) received adjuvant mitotane, with therapeutic levels monitored in 84%. Findings suggest a possible "cure fraction" with a 32.5% estimated 30-year cure rate (95% CI, 23.4%-45.0%). Cox regression indicated a 39% reduced recurrence risk (HR 0.61; 95% CI, 0.39-0.95) for mitotane-treated patients, with effects diminishing over 24 months. Mixture cure models suggest mitotane primarily delays rather than prevents recurrence. Effect modification analysis showed significant benefit in male patients (HR 0.33; 95% CI, 0.16-0.69), younger patients, tumors with higher Ki-67% (modeled as a continuous variable), and those with venous invasion (HR 0.47; 95% CI, 0.27-0.82), with potential synergy when combined with radiotherapy.Conclusion This study underscores the intriguing possibility that adjuvant mitotane delays recurrence, yet questions remain as to its curative capacity. The early benefit suggests a cytostatic effect, but certain subgroups-especially males, younger individuals, and those with high-risk tumors-may experience a more durable outcome. Further research is needed to explore mitotane's curative potential in ACC management.

引用

页数：13