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.

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Patients lost to follow-up in acromegaly: results of the ACROSPECT study.

OBJECTIVE: The complex management of acromegaly has transformed this disease into a chronic condition, with the risk of patients being lost to follow-up. The objective of this study was to estimate the proportion of acromegalic patients lost to follow-up in France and to determine the impact that abandoning follow-up has on the disease and its management. DESIGN: ACROSPECT was a French national, multicentre, cross-sectional, observational study. METHODS: Acromegalic patients were considered lost to follow-up if no new information had been entered in their hospital records during the previous 2 years. They were traced where possible, and data were collected by means of a recall visit or questionnaire. RESULTS: In the study population, 21% of the 2392 acromegalic patients initially followed in 25 tertiary endocrinology centres were lost to follow-up. At their last follow-up visit, 30% were uncontrolled, 33% were receiving medical therapy and 53% had residual tumour. Of the 362 traced, 62 had died and 77% were receiving follow-up elsewhere; the leading reason for abandoning follow-up was that they had not been informed that it was necessary. Our analysis of the questionnaires suggests that they were not receiving optimal follow-up. CONCLUSIONS: This study underlines the need to better inform acromegalic patients of the need for long-term follow-up, the absence of which could be detrimental to patients' health, and to develop shared care for what must now be regarded as a chronic disease.

[Endoscope-assisted microsurgery for invasive endo- and suprasellar pituitary macroadenomas: a consecutive retrospective study with 13 patients]. / Endoscopie et traitement chirurgical des macroadénomes hypophysaires endo- et suprasellaires invasifs. Une série consécutive rétrospective de 13 patients.

BACKGROUND AND PURPOSE: Surgery of invasive endo- and suprasellar pituitary macroadenomas remains difficult. The records of 13 consecutive patients who underwent transsphenoidal surgery were analyzed in order to evaluate advantages and limitations of endoscopy for surgery of invasive pituitary macroadenomas. METHODS: A transseptal transsphenoidal intersepto-columellar approach was performed with a nasal 0-degree endoscope. Removal of the macroadenoma was performed under the control of a microscope. When the tumor seemed to be completely removed with microscope, a rigid 30-degree endoscope was inserted in the intrasellar and suprasellar regions in order to detect residual adenoma tissue. These residues were removed when technically possible. RESULTS: No rhinologic complication was noted. In 7 patients, the intra- and suprasellar endoscopic view detected a tumor residue which could be removed in each case. Two cases of cerebrospinal fluid leakage occurred during the complementary tumor resection. Two cases of diabetes insipidus and two of rhinorrhea were reported postoperatively. The analysis of the postoperative MRIs showed a complete removal in 23% of the patients (3/13), 75 to 100% removal in 54% of the patients (7/13), 50 to 75% removal in 8% of the patients (1/13) and 50% removal in 15% of the patients (2/13). More than 75% removal was thus achieved in 77% of the patients (10/13). The mean follow-up was 27.2 months. CONCLUSIONS: Rhinologic morbidity was reduced with the endoscopic endonasal approach. Endoscopy complemented with a microscope offered an optimal view of the intra- and suprasellar regions. Endoscopy also improved tumor resection of the invasive endo- and suprasellar pituitary macroadenomas by visualizing hidden suprasellar tumor residues. However, endoscopy was associated with a higher rate of postoperative rhinorrhea.