ABSTRACT
Initial reports of a clinical response in patients treated with the radioligand [177Lu]-PSMA-617 for castration-resistant prostate cancer (CRPC) are promising, despite known inter- and intrapatient heterogeneity. In metastatic CRPC, we examined the association of baseline immunohistochemical (IHC) expression of prostate-specific membrane antigen (PSMA) in a single lesion and responsiveness to [177Lu]-PSMA-617 therapy, measured as the PSMA maximum standardized uptake value (SUVmax). Between 2015 and 2020, 19 patients with multiple metastases underwent single-lesion biopsy, [68Ga]-PSMA positron emission tomography (PET) imaging, and treatment with [177Lu]-PSMA-617. A monoclonal anti-PSMA antibody was used to semiquantitatively assess PSMA IHC in the biopsy specimen. Imaging evaluation of the biopsied single lesion and overall response was performed according to Positron Emission Tomography Response Criteria in Solid Tumors. The PSMA IHC histoscore correlated positively with pretreatment same-site PSMA SUVmax (r s = 0.6). Nine patients had imaging after three cycles of [177Lu]-PSMA-617 and were included in the lesion-specific analysis. Of these, five patients (55.6%) had an SUVmax response at the biopsy site, but three experienced overall progression. The histoscore was unable to predict the lesion-specific change in SUVmax (95% confidence interval [CI] -44.2 to 69.2) or PSA (95% CI-125.2 to 17.2). There was no correlation between single-lesion SUVmax and overall progression (r s = 0.1) on [68Ga]-PSMA PET imaging. Additional studies need to interrogate the clinical consequence of PSMA expression heterogeneity in metastases and the association with response to [177Lu]-PSMA-671. PATIENT SUMMARY: Treatment with a radioactive binding molecule called [177Lu]-PSMA-617 for men with prostate cancer resistant to castration (CRPC) is showing promise. We investigated the association between the presence of PSMA protein in metastatic lesions at biopsy and response to [177Lu]-PSMA-617 among men with metastatic CRPC. We found that assessment of PSMA presence at biopsy is not a reliable predictor of response to [177Lu]-PSMA-617. Additional studies are needed to better determine which CRPC metastatic sites will respond to this therapy.
ABSTRACT
Las mucormicosis son infecciones generalmente agudas, angioinvasivas, que provocan necrosis difusas no supurantes y gran destrucción tisular. Representan el 1,6% de todas las infecciones fúngicas invasivas, y predominan en pacientes inmunodeprimidos con factores de riesgo. Su incidencia se ha incrementado de forma significativa, incluso en pacientes sin inmunodeficiencias. A propósito de un caso de mucormicosis diseminada producida por Rhizomucor pusillus en un paciente joven sin inmunodeficiencias conocidas, hemos realizado una revisión bibliográfica de los casos de mucormicosis en pacientes adultos sin inmunodeficiencias reportados en PubMed, según sus principales localizaciones anatómicas y con referencia especial a los casos de mucormicosis diseminadas. Se revisan los principales factores de riesgo y la patogenia de la enfermedad, las formas clínicas de presentación y sus posibilidades diagnósticas, incidiendo en las técnicas de diagnóstico precoz, y la terapia actual disponible, discutiendo la indicación del tratamiento de combinación de antifúngicos y el pronóstico. Además, se revisa la taxonomía actual del género Mucor y su clasificación (AU)
Mucormycosis is usually an acute angioinvasive infections, which leads to non-suppurative necrosis and significant tissue damage. It represents 1.6% of all the invasive fungal infections and predominates in immunosuppressed patients with risk factors. Incidence has been significantly increased even in immunocompetent patients. Due to finding a case of disseminated mucormycosis caused by Rhizomucor pusillus in a young immunocompetent patient, a systematic review was carried out of reported cases in PubMed of mucormycosis in immunocompetent adults according to the main anatomic locations, and especially in disseminated cases. A review of the main risk factors and pathogenicity, clinical manifestations, techniques of early diagnosis, current treatment options, and prognosis is presented. Taxonomy and classification of the genus Mucorhas also been reviewed (AU)
Subject(s)
Humans , Mucormycosis/epidemiology , Amphotericin B/therapeutic use , Fungemia/epidemiology , Mucorales/pathogenicity , Rhizomucor/pathogenicity , Mycoses/complications , Risk Factors , Immunosuppression TherapyABSTRACT
Mucormycosis is usually an acute angioinvasive infections, which leads to non-suppurative necrosis and significant tissue damage. It represents 1.6% of all the invasive fungal infections and predominates in immunosuppressed patients with risk factors. Incidence has been significantly increased even in immunocompetent patients. Due to finding a case of disseminated mucormycosis caused by Rhizomucor pusillus in a young immunocompetent patient, a systematic review was carried out of reported cases in PubMed of mucormycosis in immunocompetent adults according to the main anatomic locations, and especially in disseminated cases. A review of the main risk factors and pathogenicity, clinical manifestations, techniques of early diagnosis, current treatment options, and prognosis is presented. Taxonomy and classification of the genus Mucor has also been reviewed.