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BACKGROUND: Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. METHODS: In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants. FINDINGS: From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98-3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2-74·0) in the conventional imaging group versus 75·5% (95% CI 62·5-84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3-20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06-3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). INTERPRETATION: Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. FUNDING: National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Prostatectomía/métodos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Radiografía Intervencional/métodos , Terapia Recuperativa/métodos , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Anciano , Ácidos Carboxílicos , Ciclobutanos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Accurate identification and discrimination of post treatment changes from recurrent disease remains a challenge for patients with intracranial malignancies despite advances in molecular and magnetic resonance imaging. We have explored the ability of readily available Rubidium-82 chloride (82RbCl) positron emission tomography (PET) to identify and distinguish progressive intracranial disease from radiation necrosis in patients previously treated with radiation therapy. METHODS: Six patients with a total of 9 lesions of either primary (N.=3) or metastatic (N.=6) intracranial malignancies previously treated with stereotactic radiation surgery (SRS) and persistent contrast enhancement on MRI underwent brain 82RbCl PET imaging. Two patients with arteriovenous malformations previously treated with SRS, also had brain 82RbCl PET imaging for a total of 11 lesions studied. Histological confirmation via stereotactic biopsy/excisional resection was obtained for 9 lesions with the remaining 2 classified as either recurrent tumor or radiation necrosis based on subsequent MRI examinations. 82RbCl PET time activity curve analysis was performed which comprised lesion SUV
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Neoplasias Encefálicas , Cloruros , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética/métodos , Necrosis/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/radioterapia , Tomografía de Emisión de Positrones/métodosRESUMEN
This study aimed to explore the effect of infertility on self-esteem and depression, and to identify the sociodemographic and infertility characteristics associated with self-esteem and depression among infertile women in Ekiti State, Nigeria. Self-esteem and depression were assessed in 100 infertile women and 100 women seeking family planning (controls) using the Rosenberg Self-Esteem Scale (RSES) and Patient Health Questionnaire (PHQ-9), respectively. Infertile women had significantly lower RSES score (19.4 ± 4.5 vs. 20.7 ± 4.4, p=.038) and higher PHQ-9 score (5.1 ± 4.1 vs. 3.8 ± 3.5, p=.023) compared to controls. Among infertile women, marital status, being remarried, duration of infertility, and RSES score were associated with PHQ-9 score on simple linear regression. On multiple linear regression analysis, the RSES score had a negative association with the PHQ-9 score (ß= -0.32, p<.001). In conclusion, infertile women have lower self-esteem and higher depression scores. Mental health screening and management should be an integral part of care administered to infertile women.Impact StatementWhat is already known on this subject? Infertility is a global health problem with negative effects on the mental health and quality of life of couples, especially women.What the results of this study add? Infertile women have lower self-esteem and higher depression scores. The prevalence of major depressive disorder (MDD) is higher among infertile women. Longer duration of infertility, older age, ≤6 years of formal education, and low self-esteem are significant associations of MDD among infertile women.What the implications are of these findings for clinical practice and/or further research? Mental health screening and management should be included in the care given to women undergoing evaluation and treatment for infertility. Larger community-based studies evaluating other aspects of mental health among infertile couples are encouraged.
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Trastorno Depresivo Mayor , Infertilidad Femenina , Depresión/epidemiología , Femenino , Humanos , Infertilidad Femenina/epidemiología , Infertilidad Femenina/psicología , Calidad de Vida/psicología , AutoimagenRESUMEN
PURPOSE: Accurate preoperative staging of prostate cancer is essential for treatment planning. Conventional imaging is limited in detection of metastases. Our primary aim was to determine if [18F]fluciclovine positron emission tomography/computerized tomography is an early indicator of subclinical metastasis among patients with high risk prostate cancer. MATERIALS AND METHODS: A total of 68 patients with unfavorable intermediate to very high risk prostate cancer without systemic disease on conventional imaging were recruited before robotic radical prostatectomy with extended pelvic lymph node dissection. Diagnostic performance of [18F]fluciclovine positron emission tomography/computerized tomography and conventional imaging for detection of metastatic disease, and correlation of positivity to node and metastatic deposit size were determined. RESULTS: Overall 57 of 68 patients completed the protocol, of whom 31 had nodal metastasis on histology. [18F]Fluciclovine positron emission tomography/computerized tomography sensitivity and specificity in detecting nodal metastasis was 55.3% and 84.8% per patient, and 54.8% and 96.4% per region (right and left pelvis, presacral and nonregional), respectively. Compared with conventional imaging [18F]Fluciclovine positron emission tomography/computerized tomography had significantly higher sensitivity on patient based (55.3% vs 33.3%, p <0.01) and region based (54.8% vs 19.4%, p <0.01) analysis, detecting metastasis in 7 more patients and 22 more regions, with similar high specificity. Four additional patients had distant disease or other cancer detected on [18F] fluciclovine positron emission tomography/computerized tomography which precluded surgery. Detection of metastasis was related to size of metastatic deposits within lymph nodes and overall metastatic burden. CONCLUSIONS: [18F]Fluciclovine positron emission tomography/computerized tomography detects occult metastases not identified on conventional imaging and may help guide treatment decisions and lymph node dissection due to high specificity for metastatic disease.
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Ácidos Carboxílicos , Ciclobutanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Periodo Preoperatorio , Estudios Prospectivos , Neoplasias de la Próstata/cirugíaRESUMEN
PURPOSE: We assessed the feasibility and cancer detection rate of fluciclovine (18F) positron emission tomography-ultrasound fusion targeted biopsy vs standard template biopsy in the same patient with biochemical failure after nonsurgical therapy for prostate cancer. MATERIALS AND METHODS: A total of 21 patients with a mean ± SD prostate specific antigen of 7.4 ± 6.8 ng/ml and biochemical failure after nonoperative prostate cancer treatment underwent fluciclovine (18F) positron emission tomography-computerized tomography (mean 364.1 ± 37.7 MBq) and planning transrectal prostate ultrasound with 3-dimensional image reconstruction. Focal prostatic activity on positron emission tomography was delineated and co-registered with planning ultrasound. During the subsequent biopsy session computer generated 12-core template biopsies were performed and then fluciclovine defined targets were revealed and biopsied. Histological analysis of template and targeted cores were completed. RESULTS: Template biopsy was positive for malignancy in 6 of 21 patients (28.6%), including 10 of 124 regions and 11 of 246 cores, vs targeted biopsy in 10 of 21 (47.6%), including 17 of 50 regions and 40 of 125 cores. Five of 21 patients had positive findings on targeted biopsy only and 1 of 21 had positive findings on template biopsy only. An additional case was upgraded from Grade Group 2 to 3 on targeted biopsy. Extraprostatic disease was detected in 8 of 21 men (38.1%) with histological confirmation in all 3 who underwent lesion biopsy. CONCLUSIONS: Fluciclovine positron emission tomography real-time ultrasound fusion guidance for biopsy is feasible in patients with biochemical failure after nonsurgical therapy for prostate cancer. It identifies more recurrent prostate cancer using fewer cores compared with template biopsy in the same patient. Further study is required to determine in what manner targeted biopsy may augment template biopsy of recurrent prostate cancer.
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Ácidos Carboxílicos , Ciclobutanos , Biopsia Guiada por Imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/instrumentación , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía/instrumentaciónRESUMEN
BACKGROUND: Ideal management of sexually transmitted infections (STI) may require risk markers for pathology or vaccine development. Previously, we identified common genetic variants associated with chlamydial pelvic inflammatory disease (PID) and reduced fecundity. As this explains only a proportion of the long-term morbidity risk, we used whole-exome sequencing to identify biological pathways that may be associated with STI-related infertility. METHODS: We obtained stored DNA from 43 non-Hispanic black women with PID from the PID Evaluation and Clinical Health Study. Infertility was assessed at a mean of 84 months. Principal component analysis revealed no population stratification. Potential covariates did not significantly differ between groups. Sequencing kernel association test was used to examine associations between aggregates of variants on a single gene and infertility. The results from the sequencing kernel association test were used to choose "focus genes" (P < 0.01; n = 150) for subsequent Ingenuity Pathway Analysis to identify "gene sets" that are enriched in biologically relevant pathways. RESULTS: Pathway analysis revealed that focus genes were enriched in canonical pathways including, IL-1 signaling, P2Y purinergic receptor signaling, and bone morphogenic protein signaling. CONCLUSIONS: Focus genes were enriched in pathways that impact innate and adaptive immunity, protein kinase A activity, cellular growth, and DNA repair. These may alter host resistance or immunopathology after infection. Targeted sequencing of biological pathways identified in this study may provide insight into STI-related infertility.
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Infecciones por Chlamydia/genética , Secuenciación del Exoma , Infertilidad/genética , Enfermedad Inflamatoria Pélvica/genética , Transducción de Señal/genética , Adulto , Proteínas Morfogenéticas Óseas/análisis , Infecciones por Chlamydia/complicaciones , Femenino , Humanos , Infertilidad/microbiología , Interleucina-1/análisis , Enfermedad Inflamatoria Pélvica/complicaciones , Enfermedad Inflamatoria Pélvica/microbiología , Análisis de Componente Principal , Receptores Purinérgicos P2Y/análisisRESUMEN
Fetal-sex-specific changes to placental immunity and metabolism occur in response to obesity. Few studies have determined if fetal sex interacts with maternal characteristics to alter risk of gestational diabetes mellitus (GDM). Among 43,727 singleton pregnancies, we examined the association between male fetal sex and GDM using log-binomial logistic regression to calculate relative risks (RR) and 95% confidence intervals (CI). Interactions were examined between fetal sex and maternal characteristics on the risk of GDM by calculating relative excess risk due to interaction. After adjusting for body mass index, race/ethnicity, maternal age, education, and gravidity, male fetal sex was not associated with GDM (RRadj. 0.95, 95% CI 0.93, 1.04). We found a positive interaction between male fetal sex and obesity (p = 0.04). Nonobese women with male fetuses were less likely to develop GDM, but in the presence of obesity, an opposite trend was observed. There was a positive interaction between male fetal sex and GDM on the risk of preterm delivery < 37-weeks gestation (p = 0.0006). In response to underlying maternal obesity, fetal sex may modify the risk of GDM. In addition, male fetal sex may increase the occurrence of preterm birth among women with GDM.
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Diabetes Gestacional , Nacimiento Prematuro , Femenino , Embarazo , Masculino , Humanos , Recién Nacido , Diabetes Gestacional/epidemiología , Placenta , Nacimiento Prematuro/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Edad Materna , Índice de Masa CorporalRESUMEN
Prostate cancer is a highly heterogeneous disease and mortality is mainly due to metastases but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that, while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor. We demonstrate that genes related to oxidative phosphorylation are upregulated in LNM and in African-American patients relative to White patients. We further show that mutations in TP53, FLT4, EYA1, NCOR2, CSMD3, and PCDH15 are enriched in prostate cancer metastases. These findings were validated in a meta-analysis of 3929 primary tumors and 2721 metastases and reveal a pattern of molecular alterations underlying the pathology of metastatic prostate cancer. We show that LNM contain multiple subclones that are already present in primary tumor foci. We observed enrichment of mutations in several genes including understudied genes such as EYA1, CSMD3, FLT4, NCOR2, and PCDH15 and found that mutations in EYA1 and CSMD3 are associated with a poor outcome in prostate cancer.
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PURPOSE: We aimed to evaluate the impact of 18 F-fluciclovine PET/CT imaging on failure-free survival (FFS) post-salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence. METHODS: Seventy-nine patients were recruited in a phase 2/3 clinical trial to undergo 18 F-fluciclovine PET/CT before SRT for PCa. Four patients with extrapelvic disease were excluded. All patients were followed up at regular intervals up to 48 months. Treatment failure was defined as a serum prostate-specific antigen level of ≥0.2 ng/mL above the nadir after SRT, confirmed with an additional measurement, requiring systemic treatment or clinical progression. Failure-free survival was computed and compared between patients grouped according to 18 F-fluciclovine PET/CT imaging findings. RESULTS: Eighty percent (60/75) of patients had a positive finding on 18 F-fluciclovine PET/CT, of which 56.7% (34/60) had prostate bed-only uptake, whereas 43.3% (26/60) had pelvic nodal ± bed uptake. Following SRT, disease failure was detected in 36% (27/75) of patients. There was a significant difference in FFS between patients who had a positive versus negative scan (62.3% vs 92.9% [ P < 0.001] at 36 months and 59.4% vs 92.9% [ P < 0.001] at 48 months). Similarly, there was a significant difference in FFS between patients with uptake in pelvic nodes ± bed versus prostate bed only at 36 months (49.8% vs 70.7%; P = 0.003) and at 48 months (49.8% vs 65.6%; P = 0.040). Failure-free survival was also significantly higher in patients with either negative PET/CT or prostate bed-only disease versus those with pelvic nodal ± prostate bed disease at 36 (78% vs 49.8%, P < 0.001) and 48 months (74.4% vs 49.8%, P < 0.001). CONCLUSIONS: Findings on pre-SRT 18 F-fluciclovine PET/CT imaging, even when acted upon to optimize the treatment decisions and treatment planning, are predictive of post-SRT FFS in men who experience PCa recurrence after radical prostatectomy. A negative 18 F-fluciclovine PET/CT is most predictive of a lower risk of failure, whereas the presence of pelvic nodal recurrence portends a higher risk of SRT failure.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/cirugía , Ácidos Carboxílicos , Insuficiencia del Tratamiento , Terapia Recuperativa , Recurrencia Local de Neoplasia , Antígeno Prostático Específico , ProstatectomíaRESUMEN
The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement 1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by 18F-fluciclovine PET/CT versus conventional imaging. We performed a post hoc analysis of the EMPIRE-1 cohort stratified by protocol-specified criteria, comparing failure-free survival (FFS) between study arms. Methods: EMPIRE-1 randomized patients to SRT planning via either conventional imaging only (bone scanning plus abdominopelvic CT or MRI) (arm A) or conventional imaging plus 18F-fluciclovine PET/CT (arm B). Randomization was stratified by prostate-specific antigen (PSA) level (<2.0 vs. ≥ 2.0 ng/mL), adverse pathology, and androgen-deprivation therapy (ADT) intent. We subdivided patients in each arm using the randomization stratification criteria and compared FFS between patient subgroups across study arms. Results: Eighty-one and 76 patients received per-protocol SRT in study arms A and B, respectively. The median follow-up was 3.5 y (95% CI, 3.0-4.0). FFS was 63.0% and 51.2% at 36 and 48 mo, respectively, in arm A and 75.5% at both 36 and 48 mo in arm B. Among patients with a PSA of less than 2 ng/mL (mean, 0.42 ± 0.42 ng/mL), significantly higher FFS was seen in arm B than arm A at 36 mo (83.2% [95% CI, 70.0-91.0] vs. 66.5% [95% CI, 51.6-77.8], P < 0.001) and 48 mo (83.2% [95% CI, 70.0-91.0] vs. 56.2% [95% CI, 40.5-69.2], P < 0.001). No significant difference in FFS between study arms in patients with a PSA of at least 2 ng/mL was observed. Among patients with adverse pathology, significantly higher FFS was seen in arm B than arm A at 48 mo (68.9% [95% CI, 52.1-80.8] vs. 42.8% [95% CI, 26.2-58.3], P < 0.001) though not at the 36-mo follow-up. FFS was higher in patients without adverse pathology in arm B versus arm A (90.2% [95% CI, 65.9-97.5] vs. 73.1% [95% CI, 42.9-89.0], P = 0.006) at both 36 and 48 mo. Patients in whom ADT was intended in arm B had higher FFS than those in arm A, with the difference reaching statistical significance at 48 mo (65.2% [95% CI, 40.3-81.7] vs. 29.1 [95% CI, 6.5-57.2], P < 0.001). Patients without ADT intent in arm B had significantly higher FFS than patients in arm A at 36 mo (80.7% [95% CI, 64.9-90.0] vs. 68.0% [95% CI, 51.1-80.2]) and 48 mo (80.7% [95% CI, 64.9-90.0] vs. 58.6% [95% CI, 41.0-72.6]). Conclusion: The survival advantage due to the addition of 18F-fluciclovine PET/CT to SRT planning is maintained regardless of the presence of adverse pathology or ADT intent. Including 18F-fluciclovine PET/CT to SRT leads to survival benefits in patients with a PSA of less than 2 ng/mL but not in patients with a PSA of 2 ng/mL or higher.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Antagonistas de Andrógenos , Recurrencia Local de Neoplasia/patología , Prostatectomía/métodosRESUMEN
Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, [68Ga]Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of [68Ga]Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: [68Ga]Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those, 2/17 had NePC. A semiquantitative analysis with standardized uptake values (SUV) (e.g., SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. [68Ga]Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastatic lesion with identifiable [68Ga]Ga-DOTATATE uptake. Marked [68Ga]Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. Three patients had mild [68Ga]Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after [68Ga]Ga-DOTATATE imaging. Conclusions: [68Ga]Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with [68Ga]Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.
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The purpose of this study was to evaluate 18F-fluciclovine PET/CT detection rates in the evaluation of biochemical recurrence in prostate cancer patients with very low (≤0.3 ng/mL) serum prostate-specific antigen (PSA) levels following definitive treatment. Prostate cancer patients with biochemical recurrence and very low serum PSA (≤0.3 ng/mL) who underwent clinical 18F-fluciclovine PET/CT were included in this single-institution retrospective study. PET/CT clinical reports at the time of interpretation were reviewed and categorized as positive or negative. In patients who had further evaluation with imaging and/or biopsy, the results were recorded to determine the true detection rate. Of the 64 eligible patients with very low serum PSA (median serum PSA of 0.17 ng/mL), 57.8% (37/64) scans were categorized as positive. Stratified by PSA levels, positivity rates were 43.8% (7/16), 60.0% (15/25) and 65.2% (15/23) for PSA<0.1 ng/mL, 0.1-<0.2 ng/mL and 0.2-≤0.3 ng/mL, respectively. The most common location of disease was the prostate bed (73%), followed by pelvic lymph nodes (22%) and distant disease (14%). In the small subset of patients who had further evaluation after a positive study (n=7), all had confirmed disease with a positive predictive value of 100%. In conclusion, among prostate cancer patients with biochemical recurrence, 18F-fluciclovine PET/CT is useful in patients with very low serum PSA of ≤0.3 ng/mL, with a 57.8% positivity rate, higher than previously reported. Though standard of truth could only be ascertained in 19% (7/37) of patients with a positive study, the positive predictive value was 100%.
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ABSTRACT: Prostate cancer osteoblastic metastases may have different morphologies, and some of these may overlap with certain benign bone lesions. In this series of 5 prostate cancer patients, we describe bone lesions with central lucency and surrounding peripheral sclerosis and their varying appearances on different imaging modalities. Although prostate cancer metastases are commonly associated with sclerotic lesions, they can also present as osteolytic or lucent lesions, and these lesions should be carefully evaluated. The findings emphasize the importance of correlation with prior imaging, comparing findings on different imaging techniques and follow-up to differentiate benign disease from metastatic disease in these situations.
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Neoplasias de la Próstata/complicaciones , Esclerosis/complicaciones , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias de la Próstata/patología , Esclerosis/diagnóstico por imagenRESUMEN
ABSTRACT: 18F-Fluciclovine is an amino acid-based radiopharmaceutical used primarily for PET imaging of patients with biochemical recurrence of prostate cancer. We report a case of a 66-year-old man with recently diagnosed metastatic castrate-resistant prostate cancer and a left supraclavicular lymph node with incidental radiotracer uptake on 18F-fluciclovine PET/CT. Left neck core needle biopsy confirmed high-grade, poorly differentiated carcinoma with neuroendocrine features positive for synaptophysin and chromogranin, and negative for prostate markers.
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Ácidos Carboxílicos/metabolismo , Ciclobutanos/metabolismo , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración/patología , Anciano , Transporte Biológico , Humanos , Masculino , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patologíaRESUMEN
Monitoring therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC) can be challenging. We set out to determine if 18F-fluciclovine PET/CT could be a useful imaging biomarker for response to docetaxel chemotherapy in patients with mCRPC. Seven patients with mCRPC had 18F-fluciclovine PET/CT scheduled at baseline and after 1 and 6 cycles of chemotherapy. The sum of SUVmax from the prostate/bed and up to 5 metastatic bone and soft tissue/visceral lesions were recorded. The SUVpeak of the hottest lesion (PERCIST-like) was also recorded. In comparison to the baseline scan, a decrease of ≥30% was considered response; new lesions or >30% increase was progressive disease; change of <30% was stable disease. Bone scintigraphy and CT were acquired at baseline and after the 6th cycle. Response assessment was based on the Prostate Cancer Clinical Trial Working Group 3 recommendations. All (7/7) enrolled patients completed the 1st and 2nd scans, while 4/7 patients completed all 3 scans. PET response correlated with PSA response in 3/7 (42.9%) patients after 1 cycle of docetaxel, and 3/4 (75%) patients after 6 cycles of docetaxel, respectively. Bone scan and CT correlated with PSA response in 1/4 (25%) patients. There was no significant correlation between baseline 18F-fluciclovine PET parameters or changes in PET parameters and time to PSA progression. In conclusion, this exploratory study showed that 18F-fluciclovine PET/CT has better correlation with PSA response than CT or bone scan in patients with mCRPC treated with docetaxel. 18F-fluciclovine PET/CT however did not predict time to PSA progression.
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Imaging with novel PET radiotracers has significantly influenced radiotherapy decision making and radiation planning in patients with recurrent prostate cancer (PCa). The purpose of this analysis was to report the final results for management decision changes based on 18F-fluciclovine PET/CT findings and determine whether the decision change trend remained after completion of accrual. Methods: Patients with detectable prostate-specific antigen (PSA) after prostatectomy were randomized to undergo either conventional imaging (CI) only (arm A) or CI plus 18F-fluciclovine PET/CT (arm B) before radiotherapy. In arm B, positivity rates on CI and 18F-fluciclovine PET/CT for detection of recurrent PCa were determined. Final decisions on whether to offer radiotherapy and whether to include only the prostate bed or also the pelvis in the radiotherapy field were based on 18F-fluciclovine PET/CT findings. Radiotherapy decisions before and after 18F-fluciclovine PET/CT were compared. The statistical significance of decision changes was determined using the Clopper-Pearson (exact) binomial method. Prognostic factors were compared between patients with and without decision changes. Results: All 165 patients enrolled in the study had standard-of-care CI and were initially planned to receive radiotherapy. Sixty-three of 79 (79.7%) patients (median PSA, 0.33 ng/mL) who underwent 18F-fluciclovine PET/CT (arm B) had positive findings. 18F-Fluciclovine PET/CT had a significantly higher positivity rate than CI did for the whole body (79.7% vs. 13.9%; P < 0.001), prostate bed (69.6% vs. 5.1%; P < 0.001), and pelvic lymph nodes (38.0% vs. 10.1%; P < 0.001). Twenty-eight of 79 (35.4%) patients had the overall radiotherapy decision changed after 18F-fluciclovine PET/CT; in 4 of 79 (5.1%), the decision to use radiotherapy was withdrawn because of extrapelvic disease detected on 18F-fluciclovine PET/CT. In 24 of 75 (32.0%) patients with a final decision to undergo radiotherapy, the radiotherapy field was changed. Changes in overall radiotherapy decisions and radiotherapy fields were statistically significant (P < 0.001). Overall, the mean PSA at PET was significantly different between patients with and without radiotherapy decision changes (P = 0.033). Conclusion:18F-Fluciclovine PET/CT significantly altered salvage radiotherapy decisions in patients with recurrent PCa after prostatectomy. Further analysis to determine the impact of 18F-fluciclovine PET/CT guidance on clinical outcomes after radiotherapy is in progress.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Anciano , Ácidos Carboxílicos , Ciclobutanos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Focal boost to dominant intraprostatic lesions (DILs) has recently been proposed for prostate radiation therapy. Accurate and fast delineation of the prostate and DILs is thus required during treatment planning. In this paper, we develop a learning-based method using positron emission tomography (PET)/computed tomography (CT) images to automatically segment the prostate and its DILs. To enable end-to-end segmentation, a deep learning-based method, called cascaded regional-Net, is utilized. The first network, referred to as dual attention network, is used to segment the prostate via extracting comprehensive features from both PET and CT images. A second network, referred to as mask scoring regional convolutional neural network (MSR-CNN), is used to segment the DILs from the PET and CT within the prostate region. Scoring strategy is used to diminish the misclassification of the DILs. For DIL segmentation, the proposed cascaded regional-Net uses two steps to remove normal tissue regions, with the first step cropping images based on prostate segmentation and the second step using MSR-CNN to further locate the DILs. The binary masks of DILs and prostates of testing patients are generated on the PET/CT images by the trained model. For evaluation, we retrospectively investigated 49 prostate cancer patients with PET/CT images acquired. The prostate and DILs of each patient were contoured by radiation oncologists and set as the ground truths and targets. We used five-fold cross-validation and a hold-out test to train and evaluate our method. The mean surface distance and DSC values were 0.666 ± 0.696 mm and 0.932 ± 0.059 for the prostate and 0.814 ± 1.002 mm and 0.801 ± 0.178 for the DILs among all 49 patients. The proposed method has shown promise for facilitating prostate and DIL delineation for DIL focal boost prostate radiation therapy.
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Próstata , Neoplasias de la Próstata , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Pelvis/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Estudios RetrospectivosRESUMEN
F-fluciclovine is a PET radiotracer approved for detection of recurrent prostate cancer, with utility in other malignancies being investigated. We present the case of a 71-year-old man with high-risk primary prostate cancer (Gleason score 9, prostate-specific antigen 34 ng/mL) and newly diagnosed lung adenocarcinoma. As part of a clinical trial (NCT03081884), preoperative F-fluciclovine PET/CT showed localized abnormal uptake in the prostate gland with extracapsular extension. Additionally, an incidental anterior mediastinal mass measuring 2.2 × 1.8 cm demonstrated abnormal radiotracer uptake. Biopsy of the mediastinal mass confirmed invasive lung adenocarcinoma with solid and acinar patterns and high programmed death 1 ligand expression.
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Adenocarcinoma del Pulmón/diagnóstico por imagen , Ácidos Carboxílicos , Ciclobutanos , Hallazgos Incidentales , Mediastino/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Anciano , Biopsia , Humanos , MasculinoRESUMEN
We evaluated 18F-fluciclovine uptake parameters that correlate with true positivity for local recurrence in non-prostatectomy-treated patients. Methods: Twenty-one patients (prostate-specific antigen level, 7.4 ± 6.8 ng/mL) with biochemical recurrence after nonprostatectomy local therapy (radiotherapy and cryotherapy) underwent dual-time-point 18F-fluciclovine (364.1 ± 37.7 MBq) PET/CT from pelvis to diaphragm. Prostatic uptake over background was delineated and coregistered to a prostate-biopsy-planning ultrasound. Transrectal biopsies of 18F-fluciclovine-defined targets were completed using a 3-dimensional visualization and navigation platform. Histologic analyses of lesions were completed. Lesion characteristics including SUVmax, target-to-background ratio (TBR), uptake pattern, and subjective reader's suspicion level were compared between true-positive (malignant) and false-positive (benign) lesions. Univariate analysis was used to determine the association between PET and histologic findings. Receiver-operating-characteristic curves were plotted to determine discriminatory cutoffs for TBR. Statistical significance was set at a P value of less than 0.05. Results: Fifty lesions were identified in 21 patients on PET. Seventeen of 50 (34.0%) targeted lesions in 10 of 21 patients were positive for malignancy. True-positive lesions had a significantly higher SUVmax (6.62 ± 1.70 vs. 4.92 ± 1.27), marrow TBR (2.57 ± 0.81 vs. 1.69 ± 0.51), and blood-pool TBR (4.10 ± 1.17 vs. 2.99 ± 1.01) than false-positive lesions at the early time point (P < 0.01) and remained significant at the delayed time point, except for blood-pool TBR. Focal uptake (odds ratio, 12.07; 95% confidence interval, 2.98-48.80; P < 0.01) and subjective highest suspicion level (odds ratio, 10.91; 95% confidence interval, 1.19-99.69; P = 0.03) correlated with true positivity. Using the receiver-operating-characteristic curve, optimal cutoffs for marrow TBR were 1.9 (area under the curve, 0.82) and 1.8 (area under the curve, 0.85) at early and delayed imaging, respectively. With these cutoffs, 15 of 17 malignant lesions were identified at both time points; however, fewer false-positive lesions were detected at the delayed time point (5/33) than at the early time point (11/33). Conclusion: True positivity of 18F-fluciclovine-targeted prostate biopsy in non-prostatectomy-treated patients correlates with focal uptake, TBR (blood pool and marrow), and subjective highest suspicion level. A marrow TBR of 1.9 at the early time point and 1.8 at the delayed time point had optimal discriminating capabilities. Despite the relatively low intraprostate positive predictive value (34.0%) with 18F-fluciclovine, application of these parameters to interpretative criteria may improve true positivity in the treated prostate.
Asunto(s)
Ácidos Carboxílicos , Ciclobutanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Transporte Biológico , Biopsia , Ácidos Carboxílicos/metabolismo , Ciclobutanos/metabolismo , Humanos , Masculino , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Curva ROC , RecurrenciaRESUMEN
PROBLEM: Recently characterized interferon epsilon (IFNe) protects against sexually transmitted infections, including genital herpes simplex virus (HSV), in animal models. There are no reports of IFNe in genital tract secretions of pregnant women, and data on IFNe in non-pregnant women are limited. This pilot study is the first to measure concentrations of IFNe in vaginal and cervical secretions during pregnancy and compare values between healthy and genital HSV-infected women. METHOD OF STUDY: Vaginal or cervical specimens from 30 pregnant women were obtained from the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) repository. Cervical samples were collected during the first trimester and vaginal samples across pregnancy. Enzyme-linked immunosorbent assay determined concentrations of IFNe (pg/mL). Data for IFNe were log-transformed and compared by maternal demographics, clinical variables, and HSV status using t tests and linear regression. Repeated measures analysis explored trends across pregnancy. RESULTS: Among the entire cohort, first trimester concentrations of IFNe in vaginal or cervical secretions decreased as body mass index increased (ß = -0.14, P = .0466). Concentrations of vaginal IFNe increased across pregnancy in HSV-infected and healthy women (P = .009). Average vaginal IFNe across pregnancy was lower in women with HSV compared to healthy women (P = .0009). CONCLUSION: Interferon epsilon increased across pregnancy, but was less abundant in women with HSV. This pilot investigation cannot make any definitive conclusions. However, animal models suggest that IFNe may protect against STIs. Thus, larger studies are required to validate expression of IFNe in the reproductive tract of pregnant women with and without genital infections.