Summary and update on the management of differentiated thyroid cancer in 2023.

The 6-fold increase in the incidence of differentiated thyroid cancer over the past 30 years in industrialized countries can be mainly attributed to improved detection. At the same time, in addition to the excellent prognosis for low-risk cancers, improved survival in metastatic forms has been also reported, likely due to the progress made recently in the treatment of aggressive forms, for which there is now an extensive therapeutic arsenal. Today, clinical management of differentiated thyroid cancer represents a paradigm of precision oncology, with personalized, risk-adapted therapeutic strategies. This has led to therapeutic de-escalation in those forms with a good prognosis, while targeted treatments play an increasingly important role in the management of radioiodine-refractory or advanced cancers. While endocrinologists will not always have the opportunity to prescribe these treatments, they will be called on to support and monitor patients during treatment. The aim of this article is to provide an overview of treatment options for differentiated thyroid cancer in 2023.

Prognostic factors for significant 6-month recovery in dysthyroid optic neuropathy in a tertiary center: A series of 69 eyes in 38 patients.

PURPOSE: To identify initial features associated with significant recovery in patients with Graves' disease dysthyroid optic neuropathy (DON) treated according to EUGOGO guidelines by intravenous glucocorticoids (ivGC) and decompression surgery in first and second-line, respectively. PATIENTS AND METHODS: Consecutive patients referred to our expert multidisciplinary consultation over a 6-year period underwent systematic exploration: endocrine assessment, ophthalmic examination and radiological exploration. Visual recovery, based on best-corrected visual acuity (BCVA) and visual field (VF), were evaluated at baseline, 1week and 6months. Baseline parameters were then tested for prognostic value on univariate and multivariate analyses. RESULTS: Thirty-eight patients (69 eyes) with DON were included. Significant recovery at 6months was found in 48/69 eyes (70%), partial recovery in 18/69 (26%), and no recovery in 3/69 (4%). Fifty-one eyes (28 patients) required surgical decompression after ivGC. These patients showed more severe presentation at diagnosis, had received significantly less GC for Graves' orbitopathy before onset of DON, and showed greater fat prolapse on CT scans compared to non-operated patients. On multivariate analysis, male gender (P=0.001), cumulative GC dose>1g before DON diagnosis (P=0.048) and initial BCVA≤0.3 (P=0.004) were significantly associated with better outcomes, whereas Clinical Activity Score>5 (P=0.013) was associated with a poorer outcome. CONCLUSION: This study confirms a generally favorable 6-month recovery rate in DON treated according to EUGOGO guidelines and provides new information on baseline predictors of poor evolution. These results may help the respective indications for medical and surgical treatment to be more effectively combined in the future.

Outcome and prognostic factors for pituitary carcinomas: lessons from a systematic review.

Purpose: The purpose of this work was toinvestigate the clinicopathological characteristics at the initial diagnosis of the pituitary tumor and at pituitary carcinoma (PC) diagnosis, alongside with the management and outcomes of PCs, and identify potential prognostic factors and therapeutic strategies associated with the clinical outcome. Methods: PubMed was searched in May 2021 for articles in English and French reporting PCs, the diagnosis of which was made on the presence of metastases. The cases without histological proof and with either another cancer present or an atypical history for a pituitary tumor were excluded. Results: One hundred and eighty-one articles reporting 207 cases were included, which included 38% corticotroph and 29% lactotroph carcinomas. An initial Ki67 index ≥10% was associated with shorter survival after the initial diagnosis (P = 0.01). Cases with early metastases were associated with both higher initial Ki67 index (P = 0.01) and shorter survival after PC diagnosis (P = 0.001). Interestingly, cases with short survival after PC diagnosis were associated with shorter time between the initial diagnosis and PC diagnosis (P = 0.0006) and had both higher initial Ki67 index (P = 0.003) and higher Ki67 index of the metastasis (P = 0.03). In addition, cases with long survival after PC diagnosis had received more frequently both systemic treatment after PC diagnosis (P = 0.0005) and local treatment for metastases (P < 0.0001). Conclusions: An initial Ki67 index ≥10% is associated with worse outcome and appears as a promising early marker of future metastasis. Its presence should lead to an intensified surveillance and to a more timely management. Clinicians should not hesitate to use local treatment, independent of whether systemic treatment is used.

Inhibition of activin signalling reduces the growth of LßT2 gonadotroph pituitary tumours in mouse.

Pituitary tumours are benign neoplasms that derive from hormone-producing cells of the pituitary gland. While medical treatments have emerged for most subtypes, gonadotroph tumours that express follicle-stimulating hormone (FSH) and/or luteinizing hormone still lack therapeutic options apart from surgery and radiotherapy. Activin ligands are physiological regulators of production and secretion of FSH by gonadotroph cells, but their role in gonadotroph tumourigenesis remains little explored. Using the LßT2 mouse gonadotroph cell line which produces FSH under activin stimulation, we first tested whether subcutaneous xenografts of LßT2 cells resulted in tumour formation in Rag2KO mice. Histological analysis confirmed the presence of LßT2 tumours with endothelial cells and macrophages in their microenvironment. FSH expression was found in a subset of clusters of LßT2 cells in the tumours. We subsequently addressed the consequences of targeting activin signalling via injection of a soluble activin decoy receptor (sActRIIB-Fc). sActRIIB-Fc treatment resulted in significantly decreased LßT2 tumour volume. Reduced Smad2 phosphorylation as well as inhibition of tumour-induced FSH production confirmed the efficient targeting of activin-downstream signalling in treated tumours. More interestingly, treated tumours showed significantly fewer endothelial cells associated with reduced Vegfa expression. In vitro treatment of LßT2 cells with sActRIIB-Fc had no effect on cell proliferation or apoptosis, but Vegfa expression was inhibited, pointing to a likely paracrine effect of LßT2 cells on endothelial cells through activin-mediated Vegfa regulation. Further in vitro and in vivo studies are now needed to pinpoint the exact roles of activin signalling in these processes prior to translating these observations to the clinic.

High prevalence of anterior pituitary deficiencies after cranial radiation therapy for skull base meningiomas.

BACKGROUND: Cranial irradiation represents one of the first line treatment proposed in skull base meningiomas. While cranial irradiation is associated with a high risk of secondary hypopituitarism, few studies focused on the specific location of skull base meningiomas. METHODS: Fifty-two adults receiving photon-beam therapy for skull base meningiomas between 2003 and 2014 in our Institution were included. Anterior pituitary (ACTH, FSH, GH, LH, TSH and prolactin) as well as corresponding peripheral hormones (8 am-Cortisol, IGF-1, fT3, fT4, 17ßestradiol or testosterone) were biologically screened before radiotherapy (baseline), then yearly until March 2019. The pituitary gland (PG) was delineated on CT and the mean dose delivered to it was calculated. RESULTS: Mean age at diagnosis was 56 +/- 14 years. Median follow-up was 7 years. Up to 60% of patients developed at least ≥2 pituitary deficiencies, 10 years after radiotherapy. Gonadotroph, thyrotroph, corticotroph and somatotroph deficiencies occurred in 37, 28, 18 and 15% of patients, respectively. Hyperprolactinemia was found in 13% of patients. None patient had only one pituitary deficiency. In the multivariate analysis, a delivered dose to the PG ≥ 50 Gy or a meningioma size ≥40 mm significantly increased the risk of developing hypopituitarism. CONCLUSIONS: Over a long-term follow-up, cranial radiation therapy used in skull base meningiomas led to a high prevalence of hypopituitarism, further pronounced in case of tumor ≥4 cm. These results advocate for an annual and prolonged follow-up of the pituitary functions in patients with irradiated skull base meningiomas.

[Myxoid variant of adrenocortical carcinoma]. / Carcinome corticosurrénalien variante myxoïde : aspects clinico-pathologiques et immunohistochimiques d'une variante rare et agressive.

We report two cases of patients presenting myxoid variant of adrenocortical carcinoma (ACC). This very rare variant is characterized by a tumoral proliferation organized in trabeculae, cords or even pseudo-glands within an acellular myxoid materiel stained by Alcian Blue and negative for PAS. Tumor cells have a small to medium size and have little atypia. Their immunohistochemical profil (positivity of Synaptophysin, SF1, Melan A, Vimentin and Inhibin, with a weak or negative pancytokeratin expression) eliminate the main differential diagnoses (metastasis of a myxoid adenocarcinoma and soft tissue myxoid tumor). Many scoring systems have been proposed in order to evaluate the risk of malignancy of these lesions: the Weiss score seems less efficient to evaluate malignancy in this variant than the reticulinic algorithm or the Helsinki score. Prognosis of myxoid variant of ACC seems worse than classical ACC.

Intrapericardial instillation of bleomycin prevents recurrence of malignant pericardial effusions: Series of 46 cases and comprehensive literature review.

INTRODUCTION: Malignant pericardial effusion is a severe complication of lung and breast cancer. The median survival is less than 4 months and recurrences occurs in about 40% of cases. Systemic chemotherapy and/or local treatments are necessary, even if there is no consensus. METHODS: We collected data from patients in our center from 1997 to 2016 who received at least one intrapericardial instillation of bleomycin (60mg). At the same time, we conducted a review of the relevant literature on the subject. RESULTS: We included 46 patients in the analysis. Median survival was 2.6 months [95% CI: 1.7; 4.7]. Overall survival was 49% [33%; 63%] at 3 months and 28% [15%; 42%] at 6 months. In the lung cancer subgroup, overall survival was 18% [3%; 44%] at 3 months. In the breast cancer subgroup, overall survival was 73% [44%; 89%] at 3 months and 46% [21%; 69%] at 6 months. DISCUSSION: The best response rates in the literature are obtained with local instillation of bleomycin or cisplatin. Malignant pericardial effusions in breast cancer patients had a better prognosis. This is certainly related to the prognosis of the underlying disease. We have not found an increase in overall survival with intrapericardial chemotherapy injections, but preventing recurrence of malignant pericardial effusions is a benefit in itself, thus avoiding a lethal complication.