SDHB exon 1 deletion: A recurrent germline mutation in Colombian patients with pheochromocytomas and paragangliomas.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) (known as PPGL in combination) are rare neuroendocrine tumors of the adrenal medulla and extra-adrenal ganglia. About 40% of the patients with PPGL have a hereditary predisposition. Here we present a case-series of 19 unrelated Colombian patients with a clinical diagnosis of PPGL tumors that underwent germline genetic testing as part of the Hereditary Cancer Program developed at the Instituto Nacional de Cancerología, Colombia (INC-C), the largest reference cancer center in the country. Ten of 19 patients (52.63%) were identified as carriers of a pathogenic/likely pathogenic (P/LP) germline variant in a known susceptibility gene. The majority of the P/LP variants were in the SDHB gene (9/10): one corresponded to a nonsense variant c.268C>T (p.Arg90*) and eight cases were found to be carriers of a recurrent CNV consisting of a large deletion of one copy of exon 1, explaining 42% (8/19) of all the affected cases. Only one additional case was found to be a carrier of a missense mutation in the VHL gene: c.355T>C (p.Phe119Leu). Our study highlights the major role of SDHB in Colombian patients with a clinical diagnosis of PGL/PCC tumors and supports the recommendation of including the analysis of large deletions/duplications of the SDHB gene as part of the genetic counselling to improve the detection rate of hereditary cases and their clinical care.

Safety and efficacy of sorafenib in patients with advanced thyroid carcinoma: a phase II study (NCT02084732)

ABSTRACT Objective: Sorafenib significantly prolonged progression-free survival in patients with iodine-refractory advanced thyroid cancer. The present study was initiated before sorafenib was approved in Colombia and therefore represents an effort by an oncology institution to evaluate its efficacy and safety in this population. Subjects and methods: This phase II clinical trial had a single treatment arm. We included adult patients with progressive metastatic iodine-refractory thyroid cancer who received treatment with sorafenib 800 mg/day (400 mg every 12 hours) up to a maximum of 24 months or until the occurrence of limiting related toxicity, the progression of the disease, or voluntary withdrawal. Results: Nineteen patients received the treatment and were included in the safety analysis. However, for the efficacy analysis, 6 patients were excluded because they received only one month of therapy. Thirteen (68%) patients were women, and the mean age at diagnosis was 61.8 years. No complete responses were observed; 5 patients had a partial response (35.7%), 6 patients had stable disease, and 3 showed progression. Mean progression-free survival was calculated at 18 months (95% CI 10.7-20.3). Overall survival was estimated at 21.3 months (95% CI 17.8-24.8). Conclusion: For the first time in Colombia, the efficacy of sorafenib was evaluated in patients with advanced and progressive thyroid carcinoma refractory to radioactive iodine, with an efficacy and a safety profile similar to those previously reported.

Exposure to radiotherapy for first primary cancer as a risk factor for second primary thyroid cancer: A case-control study.

BACKGROUND: Second primary neoplasms are associated with high mortality and morbidity rates in cancer survivors successfully treated for the first malignancy. Studies suggested an association between the type of first neoplasm and risk of subsequent thyroid cancer, with part of this risk attributable to exposure to radiotherapy during treatment of the first primary tumor. This study aimed to determine whether radiotherapy is a risk factor for thyroid cancer in patients previously treated for another neoplasm. METHODS: This retrospective case-control study included patients diagnosed with their first cancer between 2007 and 2017. Patients who subsequently developed thyroid cancer as a second primary neoplasm were defined as "cases", and patients who did not develop a second cancer were defined as "controls". Exposure to radiotherapy was the primary risk factor of interest; other risk factors were the site to which radiotherapy was delivered and the first neoplasm type. RESULTS: Exposure to radiotherapy was associated with an increased risk of thyroid cancer (odds ratio [OR]=2.410, 95% confidence interval [CI]: 1.219-4.764), in particular, in women (OR=3.121, 95% CI: 1.232-7.907) and in patients receiving radiotherapy to the thorax (OR=6.298, 95% CI: 2.581-15.370). The median survival time from first cancer recovery to thyroid cancer occurrence was 63.80 months; there was no difference in survival between patients who did and did not receive radiotherapy (P=0.899). CONCLUSION: Radiation to the thorax can increase the risk of thyroid cancer as a second neoplasm among patients with cancer successfully treated for their first cancer.

Embolización de metástasis hepáticas en insulinoma maligno: de la hipoglicemia a la hiperglicemia / Embolisation of liver metastasis in malignant insulinoma: from hyperglycaemia to hypoglycaemia

Resumen Se describe el caso de un paciente de 75 años sin antecedentes de relevancia, que fue diagnosticado con insulinoma maligno en estado avanzado, con metástasis hepáticas, con síntomas por hipoglucemia hiperinsulinémica refractaria al tratamiento, y con diazóxido y octreotide de acción corta. El paciente presentó una respuesta clínica poco esperada a la embolización transarterial de metástasis hepáticas, pues a pesar de que persisten las lesiones tumorales, desarrolló hiperglucemia persistente y requirió manejo con insulina. Adicionalmente, se hace una breve revisión de la literatura sobre las opciones terapéuticas disponibles para el tratamiento sintomático de la hipoglucemia hiperinsulinémica.

Abstract The case is presented of a 75 year-old man who was diagnosed with malignant insulinoma in an advanced stage with diffuse liver metastases and symptoms due to hyperinsulinaemic hypoglycaemia refractory to treatment with diazoxide and short-acting octreotide. The patient had an unexpected clinical response to trans-arterial embolisation of liver metastases, since, despite still having the tumour, he developed persistent hyperglycaemia that required insulin treatment. A brief review of the literature is also presented on the treatment options for hyperinsulinaemic hypoglycaemia.