| 1. |
- Burman, Pia, et al.
(författare)
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Temozolomide therapy for aggressive pituitary tumours – current understanding and future perspectives
- 2020
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Ingår i: Reviews in Endocrine and Metabolic Disorders. - : Springer Science and Business Media LLC. - 1389-9155 .- 1573-2606. ; 21:2, s. 263-276
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Forskningsöversikt (refereegranskat)abstract
- The use of temozolomide (TMZ) for the management of aggressive pituitary tumours (APT) has revolutionised clinical practice in this field with significantly improved clinical outcomes and long-term survival. Its use is now well established however a large number of patients do not respond to treatment and recurrence after cessation of TMZ is common. A number of challenges remain for clinicians such as appropriate patient selection, treatment duration and the role of combination therapy. This review will examine the use of TMZ to treat APT including mechanism of action, treatment regimen and duration; biomarkers predicting response to treatment and patient selection; and current evidence for administration of TMZ in combination with other agents.
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| 2. |
- Eleftheriou, Despina, et al.
(författare)
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Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD) : the KD CAA prevention (KD-CAAP) trial protocol
- 2023
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD. The Kawasaki disease CAA prevention (KD-CAAP) trial will test the hypothesis that immediate adjunctive corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe. Methods: KD-CAAP is a multicentre, randomised, controlled, open-label, blinded endpoint assessed trial that will be conducted across Europe supported by the conect4children pan-European clinical trials network. Patients with KD who satisfy the eligibility criteria will be randomised (1:1) to receive either oral prednisolone 2 mg/kg/day plus standard of care therapy IVIG (2 g/kg) and aspirin (40 mg/kg/day); or IVIG and aspirin alone. Further management is dictated by temperature and C-reactive protein (CRP) responses. Co-primary outcomes are as follows: (i) any CAA within the 3 months of trial follow-up; (ii) average estimate of maximum coronary Z-score at weeks 1, 2 and 6 adjusting for rescue treatment. Additional outcomes will be assessed including cost effectiveness, quality of life, corticosteroid toxicity and other safety outcomes. Discussion: Several recent studies have indicated that coronary complications associated with KD across Europe are much higher than early trials of IVIG had initially suggested. KD-CAAP directly addresses this issue by exploring the therapeutic benefit of adjunctive corticosteroids in unselected KD cases. If we find that corticosteroids prevent CAA and are safe, this is a cheap and widely available intervention that could be implemented immediately for the benefit of children. Trial registration: ISRCTN71987471- March 31, 2020; Eudract 2019–004433-17.
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| 3. |
- Trouillas, Jacqueline, et al.
(författare)
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Are aggressive pituitary tumors and carcinomas two sides of the same coin? Pathologists reply to clinician’s questions
- 2020
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Ingår i: Reviews in Endocrine and Metabolic Disorders. - : Springer Science and Business Media LLC. - 1389-9155 .- 1573-2606. ; 21:2, s. 243-251
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Forskningsöversikt (refereegranskat)abstract
- Pituitary adenohypophyseal tumors are considered as benign and termed “adenomas”. However, many tumors are invasive and a proportion of these exhibit an “aggressive behavior” with premature death due to progressive growth. Only very rare (0.2%) tumors with metastases are considered malignant and termed “carcinomas”. Taking into account this variability in behavior and the oncological definition, pathologists have proposed changing the term adenoma to tumor. Here we explain why use the term tumor instead of adenoma and identify tumor characteristics, associated with a high risk for poor prognosis. In a cohort of 125 tumors with aggressive behavior (APT) and 40 carcinomas with metastases (PC), clinical and pathological features were very similar. The comparison of this cohort (APT+PC) with a reference surgical cohort of 374 unselected patients clearly shows that the two cohorts differ greatly, especially the percentage of tumors with Ki67 ≥ 10% (35%vs3%; p < 0.001). A five-tiered prognostic classification, associating invasion and proliferation, identified grade 2b tumors (invasive and proliferative), with a high risk of recurrence/progression. Because half of the APT+ PC tumors have a Ki67 index ≥10%, and 80% of them show 2 or 3 positive markers of proliferation, we suggest that tumors that are clinically aggressive, invasive and highly proliferative with a Ki67 ≥ 10%, represent tumors with malignant potential. The percentage of grade 2b tumors, suspected of malignancy, which will become aggressive tumors or carcinomas is unknown. It is probably very low, but higher than 0.2% in surgical series. Early identification and active treatment of these aggressive tumors is needed to decrease morbidity and prolong survival.
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| 4. |
- Trouillas, Jacqueline, et al.
(författare)
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Initial pathology in aggressive pituitary tumours and carcinomas : 2b or not 2b?-that is the question
- 2023
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:4, s. 5-8
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Tidskriftsartikel (refereegranskat)abstract
- From a cohort of 171 patients comprising 121 aggressive pituitary tumours (APT) and 50 pituitary carcinomas (PC), the clinicopathological or five-tiered classification based on tumour invasion and proliferation evaluated by at least 2 proliferative markers over the cut-offs (Ki-67 ≥3% or ≥10%, p53 positive or expressed in %, mitotic count >2%), could be applied on 43 tumours: 20 PC and 23 APT. At the initial surgery, 29/43 tumours (67.4%) were grade 2b (invasive and proliferative) of which 44.8% developed metastases during follow-up (PC, grade 3). Out of these 29 tumours, 55.1% had a Ki-67 ≥10%, and were classified grade 2b* (invasive and highly proliferative). There was one tumour grade 1b* (non-invasive and highly proliferative) which metastazed. Out of the 43 tumours, 30.2 % were grade 2a (invasive and non-proliferative). The sensitivity and the specificity of grade 2b for the diagnosis of APT at the initial surgery, were 68% and 90% respectively. The comparison of the high percentage (67.4%) of grade 2b tumours in this selected cohort of APT/PC with the low percentage (8.8%) in a surgical cohort of unselected tumours shows that the initial pathological diagnosis of grade 2b tumour may be considered, in the clinic, as representing a diagnosis of APT. In addition, a significant subgroup of tumours, which will develop metastases supports the proposal that an aggressive grade 2b tumour is “a tumour with malignant potential” or “a malignant tumour without metastases”. So, the clinician may take into account the pathological diagnosis, at the initial surgery, to propose a strict follow-up and to consider earlier use of radiotherapy and/or of temozolomide in the presence of tumours with aggressive behaviour.
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