Aggressive pituitary tumours and carcinomas, characteristics and management of 171 patients

被引:73
作者
Burman, Pia [1 ]
Trouillas, Jacqueline [2 ]
Losa, Marco [3 ]
McCormack, Ann [4 ]
Petersenn, Stephan [5 ]
Popovic, Vera [6 ]
Theodoropoulou, Marily [7 ]
Raverot, Gerald [8 ]
Dekkers, Olaf M. [9 ]
机构
[1] Lund Univ, Skane Univ Hosp Malmo, Dept Endocrinol, Lund, Sweden
[2] Univ Claude Bernard Lyon 1, Fac Med Lyon Est, Lyon, France
[3] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Marco Losa Dept Neurosurg, Milan, Italy
[4] St Vincents Hosp, Garvan Inst Med Res, Sydney, Australia
[5] ENDOC Ctr Endocrine Tumors, Hamburg, Germany
[6] Univ Belgrade, Belgrade, Serbia
[7] Ludwig Maximilians Univ Munchen, Med Klin & Poliklinik 4, LMU Klinikum, Munich, Germany
[8] Univ Lyon Est Lyon, Federat Endocrinol Groupement Hospi Est, Hosp Civils Lyon, Bron, France
[9] Leiden Univ Med Ctr, Dept Internal Med Sect Endocrinol & Clin Epidemiol, Leiden, Netherlands
关键词
CHECKPOINT INHIBITOR THERAPY; EUROPEAN-SOCIETY; CUSHINGS-DISEASE; ADENOMAS; TEMOZOLOMIDE; PROGRESSION; ADRENALECTOMY; DIAGNOSIS; GROWTH;
D O I
10.1530/EJE-22-0440
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
ObjectiveTo describe clinical and pathological characteristics and treatment outcomes in a large cohort of aggressive pituitary tumours (APT)/pituitary carcinomas (PC). DesignElectronic survey August 2020-May 2021. Results96% of 171 (121 APT, 50 PC), initially presented as macro/giant tumours, 6 were microadenomas (5 corticotroph). Ninety-seven tumours, initially considered clinically benign, demonstrated aggressive behaviour after 5.5 years (IQR: 2.8-12). Of the patients, 63% were men. Adrenocorticotrophic hormone (ACTH)-secreting tumours constituted 30% of the APT/PC, and the gonadotroph subtypes were under-represented. Five out of 13 silent corticotroph tumours and 2/6 silent somatotroph tumours became secreting. Metastases were observed after median 6.3 years (IQR 3.7-12.1) from diagnosis. At the first surgery, the Ki67 index was >= 3% in 74/93 (80%) and >= 10% in 38/93 (41%) tumours. An absolute increase of Ki67 >= 10% after median of 6 years from the first surgery occurred in 18/49 examined tumours. Tumours with an aggressive course from outset had higher Ki67, mitotic counts, and p53. Temozolomide treatment in 156/171 patients resulted in complete response in 9.6%, partial response in 30.1%, stable disease in 28.1%, and progressive disease in 32.2% of the patients. Treatment with bevacizumab, immune checkpoint inhibitors, and peptide receptor radionuclide therapy resulted in partial regression in 1/10, 1/6, and 3/11, respectively. Median survival in APT and PC was 17.2 and 11.3 years, respectively. Tumours with Ki67 >= 10% and ACTH-secretion were associated with worse prognosis. ConclusionAPT/PCs exhibit a wide and challenging spectrum of behaviour. Temozolomide is the first-line chemotherapy, and other oncological therapies are emerging. Treatment response continues to be difficult to predict with currently studied biomarkers.
引用
收藏
页码:593 / 605
页数:13
相关论文
共 58 条
[1]   Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma [J].
Ali, Abir Salwa ;
Gronberg, Malin ;
Federspiel, Birgitte ;
Scoazec, Jean-Yves ;
Hjortland, Geir Olav ;
Gronbaek, Henning ;
Ladekarl, Morten ;
Langer, Seppo W. ;
Welin, Staffan ;
Vestermark, Lene Weber ;
Arola, Johanna ;
Osterlund, Pia ;
Knigge, Ulrich ;
Sorbye, Halfdan ;
Grimelius, Lars ;
Janson, Eva Tiensuu .
PLOS ONE, 2017, 12 (11)
[2]   An Institutional Experience of Tumor Progression to Pituitary Carcinoma in a 15-Year Cohort of 1055 Consecutive Pituitary Neuroendocrine Tumors [J].
Alshaikh, Omalkhaire M. ;
Asa, Sylvia L. ;
Mete, Ozgur ;
Ezzat, Shereen .
ENDOCRINE PATHOLOGY, 2019, 30 (02) :118-127
[3]   Corticotroph tumor progression after adrenalectomy in Cushing's disease:: A reappraisal of Nelson's syndrome [J].
Assie, Guillaume ;
Bahurel, Helene ;
Coste, Joel ;
Silvera, Stephane ;
Kujas, Michele ;
Dugue, Marie-Annick ;
Karray, Foued ;
Dousset, Bertrand ;
Bertherat, Jerome ;
Legmann, Paul ;
Bertagna, Xavier .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (01) :172-179
[4]   Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide [J].
Bengtsson, Daniel ;
Schroder, Henrik Daa ;
Andersen, Marianne ;
Maiter, Dominique ;
Berinder, Katarina ;
Rasmussen, Ulla Feldt ;
Rasmussen, Ase Krogh ;
Johannsson, Gudmundur ;
Hoybye, Charlotte ;
van der Lely, Aart Jan ;
Petersson, Maria ;
Ragnarsson, Oskar ;
Burman, Pia .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2015, 100 (04) :1689-1698
[5]   Rapid disease progression in patient with mismatch-repair deficiency pituitary ACTH-secreting adenoma treated with checkpoint inhibitor pembrolizumab [J].
Caccese, Mario ;
Barbot, Mattia ;
Ceccato, Filippo ;
Padovan, Marta ;
Gardiman, Marina Paola ;
Fassan, Matteo ;
Denaro, Luca ;
Emanuelli, Enzo ;
D'Avella, Domenico ;
Scaroni, Carla ;
Zagonel, Vittorina ;
Lombardi, Giuseppe .
ANTI-CANCER DRUGS, 2020, 31 (02) :199-203
[6]   Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations [J].
Casar-Borota, Olivera ;
Boldt, Henning Bunsow ;
Engstrom, Britt Eden ;
Andersen, Marianne Skovsager ;
Baussart, Bertrand ;
Bengtsson, Daniel ;
Berinder, Katarina ;
Ekman, Bertil ;
Feldt-Rasmussen, Ulla ;
Hoybye, Charlotte ;
Jorgensen, Jens Otto L. ;
Kolnes, Anders Jensen ;
Korbonits, Marta ;
Rasmussen, Ase Krogh ;
Lindsay, John R. ;
Loughrey, Paul Benjamin ;
Maiter, Dominique ;
Manojlovic-Gacic, Emilija ;
Pahnke, Jens ;
Poliani, Pietro Luigi ;
Popovic, Vera ;
Ragnarsson, Oskar ;
Schalin-Jantti, Camilla ;
Scheie, David ;
Toth, Miklos ;
Villa, Chiara ;
Wirenfeldt, Martin ;
Kunicki, Jacek ;
Burman, Pia .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2021, 106 (04) :1183-1194
[7]  
DeLellis RA., 2004, WHO CLASSIFICATION T
[8]   Sex-related difference in the growth of prolactinomas: A clinical and proliferation marker study [J].
Delgrange, E ;
Trouillas, J ;
Maiter, D ;
Donckier, J ;
Tourniaire, J .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (07) :2102-2107
[9]   Clinical and Pathological Aspects of Silent Pituitary Adenomas [J].
Drummond, Juliana ;
Roncaroli, Federico ;
Grossman, Ashley B. ;
Korbonits, Marta .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2019, 104 (07) :2473-2489
[10]   Immunotherapy in Corticotroph and Lactotroph Aggressive Tumors and Carcinomas: Two Case Reports and a Review of the Literature [J].
Duhamel, Camille ;
Ilie, Mirela Diana ;
Salle, Henri ;
Nassouri, Adjoa Sika ;
Gaillard, Stephan ;
Deluche, Elise ;
Assaker, Richard ;
Mortier, Laurent ;
Cortet, Christine ;
Raverot, Gerald .
JOURNAL OF PERSONALIZED MEDICINE, 2020, 10 (03) :1-12