Risk of Recurrence in Pituitary Neuroendocrine Tumors: A Prospective Study Using a Five-Tiered Classification

Raverot, Gérald; Dantony, Emmanuelle; Beauvy, J.; Vasiljevic, Alexandre; Mikolasek, Sara; Borson‐Chazot, Françoise; Jouanneau, Emmanuel; Roy, Pascal; Trouillas, Jacqueline

doi:10.1210/jc.2017-00773

Cited by 140 publications

(136 citation statements)

References 26 publications

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“…Ki-67 ≥3% was the most frequent positive marker in aggressive pituitary tumours (79/97, 81%) and carcinomas (29/34, 85%); also p53 positivity (35/48; 73% and 18/23; 78%, respectively) and a mitotic count >2 mitoses/10HPFs were also frequently observed (26/41, 63% and 18/20, 90%, respectively, P = 0.03). The frequency of these markers was not different between aggressive pituitary tumours and carcinomas, but higher than observed in surgical series (6,36).…”

Section: Reasoningcontrasting

confidence: 55%

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European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

Raverot

Burman

McCormack

et al. 2018

European Journal of Endocrinology

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477

611

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Background: Pituitary tumours are common and easily treated by surgery or medical treatment in most cases. However, a small subset of pituitary tumours does not respond to standard medical treatment and presents with multiple local recurrences (aggressive pituitary tumours) and in rare occasion with metastases (pituitary carcinoma). The present European Society of Endocrinology (ESE) guideline aims to provide clinical guidance on diagnosis, treatment and follow-up in aggressive pituitary tumours and carcinomas. Methods: We decided upfront, while acknowledging that literature on aggressive pituitary tumours and carcinomas is scarce, to systematically review the literature according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The review focused primarily on first-and second-line treatment in aggressive pituitary tumours and carcinomas. We included 14 single-arm cohort studies (total number of patients = 116) most on temozolomide treatment (n = 11 studies, total number of patients = 106). A positive treatment effect was seen in 47% (95% CI: 36-58%) of temozolomide treated. Data from the recently performed ESE survey on aggressive pituitary tumours and carcinomas (165 patients) were also used as backbone for the guideline. In patients responding to first-line temozolomide, we suggest continuing treatment for at least 6 months in total. Furthermore, the guideline offers recommendations for patients who recurred after temozolomide treatment, for those who did not respond to temozolomide and for patients with systemic metastasis.

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Section: Reasoningcontrasting

confidence: 55%

“…The combination of invasion (determined radiologically) and use of proliferative markers (Ki-67 index ≥3% and mitotic count >2) and p53 (assessed by IHC pathologically) has been proposed to be superior in identifying pituitary tumours with a higher risk of progression/recurrence (6,36).…”

Section: Reasoningmentioning

confidence: 99%

European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

Raverot

Burman

McCormack

et al. 2018

European Journal of Endocrinology

Self Cite

477

611

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“…Pituitary adenomas (PAs) are relatively common intracranial tumours arising from the adenohypophysis and accounting for 10-15% of all intracranial neoplasms (1,2,3,4). Although typically benign under a histological point of view, they can exhibit an aggressive clinical and radiological behaviour, characterised by rapid growth with gross invasion of the surrounding tissues, together with resistance, or early recurrence, after treatment (4,5,6,7,8).…”

Section: Introductionmentioning

confidence: 99%

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre

Asioli

Righi

Iommi

et al. 2019

European Journal of Endocrinology

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Objective and design: A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods: The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results: In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH-and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions: Our data confirmed the validity of Trouillas' score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

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“…The study is part of the PITUICARE-Lyon study (clinicaltrials.org NCT02854228). Prolactin pituitary tumours operated by a single surgeon (E J) were classed as non-invasive, invasive and proliferative-invasive upon radiological and histological examination at the time of the first surgery according to the Five-Tiered clinicopathological classification (Trouillas et al 2013, Raverot et al 2017. All frozen tumour samples used for gene expression and Formalin-Fixed Paraffin embedded (FFPE) histological samples were obtained from the NeuroBioTec bank (http://www.neurobiotec.net/).…”

Section: Human Tissues and Materialsmentioning

confidence: 99%

“…The classification of pituitary neoplasms is misleading because of the simplistic distinction between adenoma and carcinoma, based on a metastatic capacity and a poor predictive value of mitoses and Ki67 or p53 expression (Asa et al 2017). In addition, the current classification of anterior pituitary neoplasms does not reflect the clinical spectrum of behaviour such as invasion, regrowth of proliferative lesions and persistence of hormone hypersecretion (Raverot et al 2017). Aggressive pituitary tumours are frequently multi-recurrent and resistant to surgery and radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

ALK7 expression in prolactinoma is associated with reduced prolactin and increased proliferation

Principe¹,

Chanal²,

Karam³

et al. 2018

Endocrine-Related Cancer

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Prolactinoma represents the most frequent hormone-secreting pituitary tumours. These tumours appear in a benign form, but some of them can reach an invasive and aggressive stage through an unknown mechanism. Discovering markers to identify prolactinoma proliferative and invading character is therefore crucial to develop new diagnostic/prognostic strategies. Interestingly, members of the TGFβ-Activin/BMP signalling pathways have emerged as important actors of pituitary development and adult function, but their role in prolactinomas remains to be precisely determined. Here, using a heterotopic allograft model derived from a rat prolactinoma, we report that the Activins orphan type I receptor ALK7 is ectopically expressed in prolactinomas-cells. Through immunohistological approaches, we further confirm that normal prolactin-producing cells lack ALK7-expression. Using a series of human tumour samples, we show that ALK7 expression in prolactinomas cells is evolutionary conserved between rat and human. More interestingly, our results highlight that tumours showing a robust expression of ALK7 present an increased proliferation as address by Ki67 expression and retrospective analysis of clinical data from 38 patients, presenting ALK7 as an appealing marker of prolactinoma aggressiveness. Beside this observation, our work pinpoints that the expression of prolactin is highly heterogeneous in prolactinoma cells. We further confirm the contribution of ALK7 in these observations and the existence of highly immunoreactive prolactin cells lacking ALK7 expression. Taken together, our observations suggest that Activin signalling mediated through ALK7 could therefore contribute to the hormonal heterogeneity and increased proliferation of prolactinomas.

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Risk of Recurrence in Pituitary Neuroendocrine Tumors: A Prospective Study Using a Five-Tiered Classification

Cited by 140 publications

References 26 publications

European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre

ALK7 expression in prolactinoma is associated with reduced prolactin and increased proliferation

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