RESUMO
BACKGROUND: The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR. METHODS: Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded. RESULTS: Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2-4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4-4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1-6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4-3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4-8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3-6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3-20.0). CONCLUSION: Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.
Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Somatostatina/análogos & derivados , Acromegalia/metabolismo , Acromegalia/patologia , Adenoma/tratamento farmacológico , Adenoma/metabolismo , Adenoma/patologia , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Estudos Transversais , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Somatostatina/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
Although the craniocervical junction is involved in a variety of conditions including trauma, neoplastic lesions, and inflammatory processes, isolated inflammatory conditions involving the occipital condyle exclusively are not known. The authors report this unusual condition in two cases. Unless the patient is of poor medical risk, excision of the lesion is the treatment of choice to decompress the neural structures.
