Locally unresectable differentiated thyroid cancer: outcomes and perspectives.

PURPOSE: Differentiated thyroid cancer (DTC) patients with an unresectable primary tumor cannot benefit from curative surgery, and radioiodine treatment for locoregional and distant disease is not possible with the thyroid gland still in place. Due to local invasion, these patients cannot be included in clinical trials, so that treatment options are limited. The aim of this study was to describe the characteristics and the prognosis of patients with these locally unresectable DTC. PATIENTS AND METHODS: A retrospective and multicentric analysis of consecutive cases of unresectable DTC diagnosed between 2000 and 2015 was performed. RESULTS: The study population consisted in 22 patients, 13 females (59%); median age: 77 years (range: 52-91). Thyroid tumors were papillary in six, follicular in seven, Hürthle cell in one and poorly differentiated in eight patients. Patients were treated with external beam radiation therapy (EBRT) (57%), locoregional therapy of distant metastases (41%), cytotoxic chemotherapy (38%) and tyrosine kinase inhibitors (TKIs) (33%). TKI treatment resulted in median disease control duration of 7 months with a grade 3-4 toxicity rate of 44%. Only one patient had a total thyroidectomy after neo-adjuvant EBRT. The 1, 3 and 5-year cumulative survival rate was 81%, 27.7% and 21.5%, respectively. The cause of death was DTC in 11 cases (local progression in 7), and to other causes in 7 cases; no patient died from treatment toxicity. CONCLUSIONS: Clinical trials and approved treatments are lacking for unresectable DTC. TKI treatment may allow prolonged disease control with acceptable toxicity.

Efficacy of molecularly targeted agents given in the randomised trial SHIVA01 according to the ESMO Scale for Clinical Actionability of molecular Targets.

BACKGROUND: A randomised trial SHIVA01 compared the efficacy of matched molecularly targeted therapy outside their indications based on a prespecified treatment algorithm versus conventional chemotherapy in patients with metastatic solid tumours who had failed standard of care. No statistical difference was reported between the two groups in terms of progression-free survival (PFS), challenging treatment algorithm. The European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) recently defined criteria to prioritise molecular alterations (MAs) to select anticancer drugs. We aimed to retrospectively evaluate the efficacy of matched molecularly targeted agents (MTAs) given in SHIVA01 according to ESCAT tiers. PATIENTS AND METHODS: MAs used in SHIVA01 were retrospectively classified into ESCAT tiers, and PFS and overall survival (OS) were compared using log-rank tests. RESULTS: One hundred fifty-three patients were treated with matched MTAs in SHIVA01. MAs used to allocate MTAs were classified into tiers II, IIIA, IIIB and IVA according to the ESCAT. Median PFS was 2.0 months in tier II, 3.1 in tier IIIA, 1.7 in tier IIIB and 3.2 in tier IVA (p = 0.13). Median OS in tier IIIB was worse than that in tiers II, IIIA and IVA (6.3 months versus 11.7, 11.2 and 12.1, p = 0.002). CONCLUSIONS: Most MAs used to allocate therapy in SHIVA01 were shown to improve outcomes in other tumour types (tier IIIA). Worst outcome was observed in patients treated based on another type of alteration than the one reported to improve outcomes (tier IIIB), highlighting the crucial impact of the type of the alterations beyond the gene and the signalling pathway.

French Endocrine Society Guidance on endocrine side effects of immunotherapy.

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using 'common terminology criteria for adverse events' (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.

Expert opinions on adrenal complications in immunotherapy.

Primary adrenal insufficiency during immunotherapy is rare and does not warrant systematic screening during treatment. It should be suspected in case of typical clinical and biological presentation, but also in case of subclinical presentation with impaired general health status and/or hyponatremia. Diagnosis is based on low cortisol levels, measured at any time in case of emergency or else at 8 am, associated to elevated ACTH to rule out pituitary origin. Secondarily, anti-21-hydroxylase antibody assay may be performed, with screening for mineralocorticoid deficiency. Imaging is recommended, although not urgent, to screen for "adrenalitis" or adrenal atrophy and rule out differential diagnosis of adrenal metastasis. Primary adrenal insufficiency during immunotherapy is a medical emergency requiring hydrocortisone replacement adapted to the clinical and biological context. Management by an endocrinologist is essential, in order to adapt hydrocortisone and fludrocortisone replacement therapy and to educate both patient and oncologist in hydrocortisone dose adaptation. Current data suggest that treatment needs to be life-long, even after termination of immunotherapy. The present article does not deal with secondary adrenal insufficiency, which is included in the section on "Pituitary toxicity".

[Tumor-to-tumor metastasis in a renal carcinoma: A rare and surprising event]. / Métastase d'une tumeur primitive dans un carcinome rénal : un évènement rare et surprenant.

Tumor-to-tumor metastasis is a very rare event. We report three cases of tumor metastasizing in a clear cell renal cell carcinoma: two breast carcinomas and a sigmoid carcinoma. So we objectified a prevalence of 1.5% of renal tumors in our series. It's a rare situation but to be considered in daily practice because it changes oncological management offered to the patient. According to the literature, clear cell renal cell carcinoma is the most common tumor recipient of metastasis. Several physiopathological mechanisms can explain this phenomenon, but many of them are still unknown. A better understanding of this phenomenon makes it possible to improve the diagnosis and thus the management of patients with several cancers.

[Targeted therapies, prognostic and predictive factors in endocrine oncology]. / Thérapies ciblées en oncologie endocrinienne: facteurs pronostiques et prédictifs de réponse.

A better understanding of molecular mechanisms responsible for tumorigenesis has allowed the development of targeted drugs designed to improve the outcome of cancer. In endocrine tumors, several molecules have demonstrated efficacy in terms of progression free survival during phase III trials such as vandetanib and cabozantinib in medullary thyroid carcinoma, sorafenib in differentiated thyroid carcinoma and everolimus or sunitinib for pancreatic neuroendocrine tumors. Rare cancer network has allowed ongoing phase III trials in malignant pheochromocytoma and adrenocortical carcinoma. However, to date no specific predictive biomarker has yet been identified for a personalized cancer medicine. We review recent advances in endocrine oncology concerning molecular targets identification, targeted therapies and predictive or prognostic markers.