Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Fluordesoxiglucose F18 , Degeneração Paraneoplásica Cerebelar , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Feminino , Degeneração Paraneoplásica Cerebelar/diagnóstico por imagem , Degeneração Paraneoplásica Cerebelar/patologia , Neoplasias das Tubas Uterinas/diagnóstico por imagem , Neoplasias das Tubas Uterinas/patologia , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Pessoa de Meia-Idade , Diagnóstico DiferencialRESUMO
PURPOSE: Neoadjuvant chemotherapy is often administered for high-grade serous ovarian carcinoma (HGSC) prior to cytoreductive surgery. We evaluated treatment response by CT (simplified peritoneal carcinomatosis index [S-PCI]), pathology (chemotherapy response score [CRS]), laboratory markers (serum CA-125), and surgical outcomes, to identify predictors of disease-free survival. METHODS: For this retrospective, HIPAA-compliant, IRB-approved study, we identified 396 women with HGSC receiving neoadjuvant chemotherapy between 2010 and 2019. Two hundred and ninety-nine patients were excluded (surgery not performed; imaging/pathology unavailable). Pre- and post-treatment abdominopelvic CTs were assigned CT S-PCI scores 0-24 (higher score indicating more tumor). Specimens were assigned CRS of 1-3 (minimal to complete response). Clinical data were obtained via chart review. Univariate, multivariate, and survival analyses were performed. RESULTS: Ninety-seven women were studied, with mean age of 65 years ± 10. Interreader agreement was good to excellent for CT S-PCI scores (ICC 0.64-0.77). Despite a significant decrease in CT S-PCI scores after treatment (p < 0.001), mean decrease in CT S-PCI did not differ significantly among CRS categories (p = 0.20) or between patients who were optimally versus suboptimally debulked (p = 0.29). In a survival analysis, lower CRS (more viable tumor) was associated with shorter time to progression (p < 0.001). A joint Cox proportional-hazard models showed that only residual pathologic disease (CRS 1/2) (HR 4.19; p < 0.001) and change in CA-125 (HR 1.79; p = 0.01) predicted progression. CONCLUSION: HGSC response to neoadjuvant therapy by CT S-PCI did not predict pathologic CRS score, optimal debulking, or progression, revealing discordance between imaging, pathologic, biochemical, and surgical assessments of tumor response.
Assuntos
Progressão da Doença , Terapia Neoadjuvante , Neoplasias Ovarianas , Tomografia Computadorizada por Raios X , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Estudos Retrospectivos , Idoso , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Quimioterapia Adjuvante , Gradação de Tumores , Procedimentos Cirúrgicos de Citorredução , Antígeno Ca-125/sangue , Resultado do TratamentoRESUMO
The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no noninvasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc - maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here, we show that tumor cell retention of a system xc --specific PET radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds. The decrease in [18F]FSPG retention correlated with a depletion of intracellular cystine resulting from increased de novo glutathione biosynthesis, shown through [U-13C6, U-15N2]cystine isotopic tracing. In vivo, treatment with the chemotherapeutic doxorubicin decreased [18F]FSPG tumor uptake in a mouse model of ovarian cancer, coinciding with markers of oxidative stress but preceding tumor shrinkage and decreased glucose utilization. Having already been used in pilot clinical trials, [18F]FSPG PET could be rapidly translated to the clinic as an early redox indicator of tumor response to treatment. SIGNIFICANCE: [18F]FSPG PET imaging provides a sensitive noninvasive measure of tumor redox status and provides an early marker of tumor response to therapy.See related commentary by Lee et al., p. 701.
Assuntos
Sistema y+ de Transporte de Aminoácidos/metabolismo , Cistadenocarcinoma Seroso/patologia , Radioisótopos de Flúor/metabolismo , Glutamatos/metabolismo , Neoplasias Ovarianas/patologia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/metabolismo , Acetilcisteína/farmacologia , Animais , Apoptose , Proliferação de Células , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/metabolismo , Feminino , Sequestradores de Radicais Livres/farmacologia , Humanos , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Oxirredução , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , terc-Butil Hidroperóxido/farmacologiaRESUMO
In our study we used transvaginal color Doppler ultrasonography in a token of 127 women presenting with unilateral ovarian tumor. The characteristics of the tumors were analyzed, the presence of vascularization was checked and the resistance index (RI) was calculated. Consequently, based on a concrete scoring system, we attempted to discriminate these tumors as benign or malignant. It was proven that 24 of 127 ovarian tumors were malignant. Transvaginal color Doppler correctly identified 21 of the 24 malignant tumors, as well as 94 of the 103 benign tumors. In nine other cases we had false-positive results. The sensitivity and the specificity of the method was 87.5% and 91.2%, while the positive and negative predictive values were 70% and 96.9%, respectively.
Assuntos
Neoplasias Ovarianas/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Cistadenocarcinoma Mucinoso/diagnóstico por imagem , Cistadenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Disgerminoma/diagnóstico por imagem , Disgerminoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Valor Preditivo dos TestesRESUMO
AIM: To determine whether three-dimensional power Doppler can improve the recognition of pelvic tumor morphology and angiogenesis. METHODS: Using this technique we analyzed 180 adnexal masses and 110 uterine lesions. Tumor volume, morphology, and vascularity were evaluated in each patient. Irregular and randomly dispersed vessels with complex branching depicted by comprehensive three dimensional display were suggestive of pelvic malignancy, while linear-like vascular morphology, single vessel arrangement and regular branching were typical for benign structures. RESULTS: Addition of qualitative analysis of vascular architecture of adnexal tumor to morphological parameters reached 96.15% sensitivity and 98.73% specificity. When endometrial lesions were prospectively analyzed, sensitivity and specificity were 91.67% and 98.49%, respectively. Because the lowest positive predictive value of 16.67% was obtained for myometrial lesions, this method should not be advised for their eva luation. CONCLUSION: Good results achieved by three dimensional ultrasound can be explained by improved recognition of the pelvic lesion anatomy, characterization of the surface features, detection of the tumor infiltration, and precise depiction of the size and volume. Three dimensional power Doppler imaging can detect structural abnormalities of the malignant tumor vessels, such as arteriovenous shunts, microaneurysms, tumoral lakes, disproportional calibration, coiling, and dichotomous branching. Therefore it enhances and facilitates the morphologic and functional evaluation of both benign and malignant pelvic tumors.