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Purpose: 18F-Flotufolastat (18F-rhPSMA-7.3) is a newly approved prostate-specific membrane antigen targeting radiopharmaceutical for diagnostic imaging of prostate cancer (PCa). SPOTLIGHT (National Clinical Trials 04186845) evaluated 18F-flotufolastat in men with suspected PCa recurrence. Here, we present results of predefined exploratory endpoints from SPOTLIGHT to evaluate the impact of clinical factors on 18F-flotufolastat detection rates (DR). Methods and Materials: The impact of baseline prostate-specific antigen (PSA), PSA doubling time (PSAdt), and International Society of Urologic Pathology Grade Group (GG) on 18F-flotufolastat DR was evaluated among all SPOTLIGHT patients with an evaluable scan, with DR stratified according to the patients' prior treatment (radical prostatectomy ± radiation therapy [RP] or radiation therapy only [RT]). The patients underwent positron emission tomography 50 to 70 minutes after receiving 18F-flotufolastat (296 MBq IV), and scans were read by 3 blinded central readers, with the majority read representing agreement between ≥2 readers. Results: In total, 389 men (median PSA: 1.10 ng/mL) were evaluable. By majority read, 18F-flotufolastat identified distant lesions in 39% and 43% of patients treated with prior RP or RT, respectively. The overall DR broadly increased with increasing PSA (<0.2 ng/mL: 33%; ≥10 ng/mL: 100%). Among patients with PSA <1 ng/mL, 68% had positive scans, and 27% had extrapelvic findings. PSAdt was available for 145/389 (37%) patients. PSAdt did not appear to influence 18F-flotufolastat DR (77%-90% across all PSAdt categories). Among patients with prior RP, DR ranged from 70% to 83% across PSAdt categories, and 100% DR was reported for all post-RT patients. In total, 362/389 (93%) patients had baseline GG data. Overall DRs were uniformly high (75%â95%) across all GG. When stratified by prior treatment, DRs across all GG were 69% to 89% in patients with prior RP and ≥96% in patients with prior RT. Conclusions: 18F-Flotufolastat-positron emission tomography enabled the accurate detection of recurrent PCa lesions across a wide range of PSA, PSAdt, and International Society of Urologic Pathology GG, thus supporting its clinical utility for a broad range of patients with recurrent PCa.
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PURPOSE: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT]. METHODS: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test. RESULTS: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021]. CONCLUSION: In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study. CLINICAL TRIAL REGISTRATION: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).
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PURPOSE: Whole-pelvis (WP) radiation therapy (radiation) improved biochemical relapse-free survival (bRFS) compared with prostate bed (PB)-only radiation in the Radiation Therapy Oncology Group 0534, but was performed in an era prior to positron emission tomography (PET) staging. Separately, 18F-fluciclovine PET/CT-guided postprostatectomy radiation improved 3-year bRFS versus radiation guided by conventional imaging alone. We hypothesized that patients who were changed from WP to PB-only radiation after PET would have bRFS that was: (a) no higher than patients initially planned for PB-only radiation; and (b) lower than patients planned for WP radiation without PET guidance. METHODS AND MATERIALS: We conducted a post hoc analysis of a prospective, randomized trial comparing conventional (arm 1) versus PET-guided (arm 2) postprostatectomy radiation. In arm 2, pre-PET treatment field decisions were recorded and post-PET fields were defined per protocol; pathologic node negative (pN0) without pelvic or extrapelvic PET uptake received PB-only radiation. Three-year bRFS was compared in patients planned for WP with change to PB-only radiation (arm 2 [WP:PB]) vs arm 2 patients planned for PB-only with final radiation to PB-only (arm 2 [PB:PB]) and arm 1 pN0 patients treated with WP radiation (arm 1 [WP]) using the Z test and log-rank test. Demographics were compared using the chi-square test, Fisher exact test, or analysis of variance, as appropriate. RESULTS: We identified 10 arm 2 (WP:PB), 31 arm 2 (PB:PB) and 11 arm 1 (WP) patients. Androgen deprivation was used in 50.0% of arm 2 (WP:PB) and 3.2% of arm 2 (PB:PB) patients, P < .01. Median preradiation prostate-specific antigen was higher in arm 2 (WP:PB) vs arm 2 (PB:PB) patients (0.4 vs 0.2 ng/mL, P = .03); however, there were no significant differences in T stage, Gleason score, or margin positivity. Three-year bRFS was 80% in arm 2 (WP:PB) vs 87.4% in arm 2 (PB:PB), P = .47, respectively. Arm 1(WP) patients had significantly worse 3-year (23%) bRFS vs arm 2 (WP:PB), P < .01. CONCLUSIONS: Patients initially planned for WP radiation with field decision change to PB-only radiation after PET showed (1) no significant difference in 3-year bRFS compared with patients initially planned for PB-only radiation; and (2) improved bRFS compared with patients receiving WP radiation without PET guidance. PET-guided volume de-escalation in selected patients may be 1 approach to mitigating toxicity without compromising outcomes.
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Interreader and intrareader reproducibility of 18F-flotufolastat PET/CT scans in newly diagnosed and recurrent prostate cancer patients was assessed from masked image evaluations from two phase 3 studies. Methods: 18F-flotufolastat PET/CT images of newly diagnosed (n = 352) or recurrent (n = 389) patients were evaluated by 3 masked readers. Cohen κ was used to assess pairwise patient- and region-level interreader agreement. Agreement among all readers was assessed using Fleiss κ. Intrareader agreement between the first and repeat read (20% of images, ≥4 wk later) was assessed using Cohen κ. Results: Pairwise interreader agreement was 95% or better (newly diagnosed) and 75% or better (recurrent). The κ coefficients were impacted by the high-agreement-low-κ paradox: Cohen κ ranged from not estimable to 0.55, whereas Fleiss κ was 0.50 (newly diagnosed) and 0.41 (recurrent). Agreement was highest in the prostate of newly diagnosed patients (≥95%) and in the pelvic lymph nodes in recurrent patients (≥87%). Intrareader agreement was 86% or better across both populations. Conclusion: 18F-flotufolastat PET/CT images can be reliably interpreted, with a high degree of inter- and intrareader agreement.
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Variações Dependentes do Observador , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Prospectivos , Idoso , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , RecidivaRESUMO
BACKGROUND: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization. PATIENTS AND METHODS: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival. FINDINGS: Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR. INTERPRETATION: For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Radioisótopos de Ítrio , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Masculino , Radioisótopos de Ítrio/uso terapêutico , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Dosagem Radioterapêutica , Resultado do Tratamento , Adulto , Idoso de 80 Anos ou maisRESUMO
18F-rhPSMA-7.3 (18F-flotufolastat) is a high-affinity prostate-specific membrane antigen-targeted diagnostic radiopharmaceutical for PET imaging in patients with prostate cancer. Here, we report findings from the SPOTLIGHT study (NCT04186845), assessing the performance of 18F-flotufolastat PET/CT for identifying prostate-specific membrane antigen-positive lesions confirmed by standard of truth (SoT) in men with biochemical recurrence of prostate cancer and negative conventional imaging at baseline. Methods: Men with biochemical recurrence received 296 MBq of 18F-flotufolastat intravenously and then underwent PET/CT 50-70 min later. 18F-flotufolastat PET/CT findings were evaluated by 3 masked central readers and verified using histopathology or follow-up confirmatory imaging (CT, MRI, bone scan, or 18F-fluciclovine PET/CT) as the SoT. The present analysis evaluated all patients who had negative conventional imaging at baseline, underwent 18F-flotufolastat PET/CT, and had SoT verification by histopathology or follow-up confirmatory imaging to report detection rate (DR), which is the number of patients with at least 1 PET-positive lesion, divided by the number of evaluable patients, and verified DR (VDR), which is the proportion of patients with at least 1 true-positive lesion as verified by SoT, of all patients scanned (PET-positive and PET-negative scans). DR and VDR were calculated and stratified according to prior therapy. Majority read data (agreement between ≥2 readers) are reported. Results: In total, 171 patients with negative baseline conventional imaging and SoT by histopathology or post-PET confirmatory imaging were evaluated. By majority read, the overall 18F-flotufolastat DR among these patients was 95% (163/171; 95% CI, 91.0%-98.0%), and 110 of 171 of these patients had at least 1 true-positive lesion identified (VDR, 64%; 95% CI, 56.7%-71.5%). In the postprostatectomy group (133/171), 8.3% of patients had at least 1 true-positive lesion in the prostate bed, 28% in pelvic lymph nodes, and 35% in other sites. Among those who had received radiotherapy (36/171), 50% of patients had true-positive detections in the prostate, 8.3% in pelvic lymph nodes, and 36% in other sites. Conclusion: 18F-flotufolastat frequently identified true-positive prostate cancer lesions in patients with negative conventional imaging. 18F-flotufolastat may help to better define sites of disease recurrence and inform salvage therapy decisions than does conventional imaging, potentially leading to improved outcomes.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Recidiva , Glutamato Carboxipeptidase II/metabolismo , Recidiva Local de Neoplasia/diagnóstico por imagem , Compostos Radiofarmacêuticos , Radioisótopos de FlúorRESUMO
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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Background and purpose: A novel radiotracer, 18F-fluciclovine (anti-3-18F-FACBC), has been demonstrated to be associated with significantly improved survival when it is used in PET/CT imaging to guide postprostatectomy salvage radiotherapy for prostate cancer. We aimed to investigate the feasibility of using a deep learning method to automatically detect and segment lesions on 18F-fluciclovine PET/CT images. Materials and methods: We retrospectively identified 84 patients who are enrolled in Arm B of the Emory Molecular Prostate Imaging for Radiotherapy Enhancement (EMPIRE-1) trial. All 84 patients had prostate adenocarcinoma and underwent prostatectomy and 18F-fluciclovine PET/CT imaging with lesions identified and delineated by physicians. Three different neural networks with increasing levels of complexity (U-net, Cascaded U-net, and a cascaded detection segmentation network) were trained and tested on the 84 patients with a fivefold cross-validation strategy and a hold-out test, using manual contours as the ground truth. We also investigated using both PET and CT or using PET only as input to the neural network. Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), center-of-mass distance (CMD), and volume difference (VD) were used to quantify the quality of segmentation results against ground truth contours provided by physicians. Results: All three deep learning methods were able to detect 144/155 lesions and 153/155 lesions successfully when PET+CT and PET only, respectively, served as input. Quantitative results demonstrated that the neural network with the best performance was able to segment lesions with an average DSC of 0.68 ± 0.15 and HD95 of 4 ± 2 mm. The center of mass of the segmented contours deviated from physician contours by approximately 2 mm on average, and the volume difference was less than 1 cc. The novel network proposed by us achieves the best performance compared to current networks. The addition of CT as input to the neural network contributed to more cases of failure (DSC = 0), and among those cases of DSC > 0, it was shown to produce no statistically significant difference with the use of only PET as input for our proposed method. Conclusion: Quantitative results demonstrated the feasibility of the deep learning methods in automatically segmenting lesions on 18F-fluciclovine PET/CT images. This indicates the great potential of 18F-fluciclovine PET/CT combined with deep learning for providing a second check in identifying lesions as well as saving time and effort for physicians in contouring.
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Skeletal metastases due to prostate cancer (PCa) are more commonly osteoblastic than osteolytic. In the rarer cases of osteolytic skeletal metastasis of PCa, transition to osteoblastic phenotype occurs following treatment, which indicates successful healing. In this report, we present a case of spontaneous osteolytic to osteoblastic evolution of PCa skeletal metastasis without treatment in a patient with recurrence of PCa. Our patient is a 59-year-old male who had a robotic radical prostatectomy in July 2014 for a T2c adenocarcinoma of the prostate gland (Gleason score = 4 + 3). He had adjuvant pelvic radiotherapy in January 2015 due to prostate-specific antigen (PSA) persistence. PSA began to rise in October 2015. An 18 F-fluciclovine positron emission tomography/computed tomography (PET/CT) scan obtained in June 2017 at a PSA of 0.5 ng/mL was negative. Repeat 18 F-fluciclovine PET/CT of February 2020 at PSA of 3.72 ng/mL showed prostate bed recurrence and a nonavid osteolytic left inferior pubic ramus lesion. 18F radiohybrid prostate-specific membrane antigen ( 18 F-rhPSMA) PET/CT scan of August 2020 performed as part of an ongoing clinical trial confirmed local prostate bed recurrence with a low-grade radiotracer uptake in the osteolytic left inferior pubic ramus bone lesion. Without salvage therapy, 18 F-fluciclovine PET/CT of October 2020 and March 2022 shows progressive sclerosis in the left pubic ramus lesion. An osteolytic to osteoblastic transition of a bone lesion as shown in this patient calls for a rethink in our understanding of untreated PCa skeletal metastasis progression. This case provides novel insight into the understanding of the temporal evolution of skeletal metastasis and calls for further research.
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BACKGROUND: Radiohybrid (rh) 18F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging. OBJECTIVE: To evaluate the diagnostic performance and safety of 18F-rhPSMA-7.3 in newly diagnosed PCa patients planned for prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Data on 18F-rhPSMA-7.3 were reported from the phase 3 prospective, multicentre LIGHTHOUSE study (NCT04186819). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients underwent positron emission tomography/computed tomography (PET/CT) 50-70 min after an injection of 296 MBq 18F-rhPSMA-7.3. Images were interpreted locally and by three blinded independent readers. The coprimary endpoints were patient-level sensitivity and specificity for the detection of pelvic lymph node (PLN) metastases, validated using histopathology at PLN dissection. Prespecified statistical thresholds (lower bounds of 95% confidence interval [CI]) were set at 22.5% for sensitivity and 82.5% for specificity. RESULTS AND LIMITATIONS: Of 372 patients screened, 352 had evaluable 18F-rhPSMA-7.3-PET/CT and 296 (99 [33%] with unfavourable intermediate-risk [UIR] and 197 [67%] with high-/very-high-risk [VHR] PCa) subsequently underwent surgery. As per the independent reads, 23-37 (7.8-13%) patients had 18F-rhPSMA-7.3-positive PLN. Seventy (24%) patients had one or more positive PLNs on histopathology. The sensitivity for PLN detection was 30% (95% CI, 19.6-42.1%) for reader 1, 27% (95% CI, 17.2-39.1%) for reader 2, and 23% (95% CI, 13.7-34.4%) for reader 3, not meeting the prespecified threshold. Specificity was 93% (95% CI, 88.8-95.9%), 94% (95% CI, 89.8-96.6%), and 97% (95% CI, 93.7-98.7%), respectively, exceeding the threshold for all readers. Specificity was high (≥92%) across both risk stratifications. Sensitivity was higher among high-risk/VHR (24-33%) than among UIR (16-21%) patients. Extrapelvic (M1) lesions were reported for 56-98/352 (16-28%) patients who underwent 18F-rhPSMA-7.3-PET/CT irrespective of surgery. Verification of these (predominantly by conventional imaging) gave a verified detection rate of 9.9-14% (positive predictive value, 51-63%). No serious adverse events were observed. CONCLUSIONS: Across all risk stratifications, 18F-rhPSMA-7.3-PET/CT had high specificity, meeting the specificity endpoint. The sensitivity endpoint was not met, although higher sensitivity was noted among high-risk/VHR than among UIR patients. Overall, 18F-rhPSMA-7.3-PET/CT was well tolerated, and identified N1 and M1 disease prior to surgery in newly diagnosed PCa patients. PATIENT SUMMARY: In order to select the most appropriate treatment for patients with prostate cancer, it is critical to diagnose the disease burden accurately at initial diagnosis. In this study, we investigated a new diagnostic imaging agent in a large population of men with primary prostate cancer. We found it to have an excellent safety profile and to provide clinically useful information regarding the presence of disease beyond the prostate.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/metabolismo , Próstata/patologia , Radioisótopos de GálioRESUMO
ABSTRACT: 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT is a valuable tool for staging and restaging of prostate cancer. Prostate-specific membrane antigen expression is not specific to prostate cancer, as it is expressed in normal tissues as well as in neoplastic and nonneoplastic processes. Awareness of the broad possibility of lesions with PSMA avidity is necessary to recognize normal variants and avoid potential pitfalls in image interpretation. We present a series of cases showing physiologic focal PSMA avidity in hepatic segment IVb. We correlate this uptake with aberrant hepatic vasculature. The awareness of this variant is important for accurate image interpretation to prevent additional invasive procedures, undue treatment escalation, and denial of curative treatment to patients.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Isótopos de Gálio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioisótopos de Gálio , Neoplasias da Próstata/patologia , Ácido Edético , Fígado/metabolismoAssuntos
Tomografia por Emissão de Pósitrons , Neoplasias da Próstata , Masculino , Humanos , Estudos Prospectivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagemRESUMO
Breast cancer (BC) remains one of the leading causes of death among women. The management and outcome in BC are strongly influenced by a multidisciplinary approach, which includes available treatment options and different imaging modalities for accurate response assessment. Among breast imaging modalities, MR imaging is the modality of choice in evaluating response to neoadjuvant therapy, whereas F-18 Fluorodeoxyglucose positron emission tomography, conventional computed tomography (CT), and bone scan play a vital role in assessing response to therapy in metastatic BC. There is an unmet need for a standardized patient-centric approach to use different imaging methods for response assessment.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Fluordesoxiglucose F18 , Tomografia por Emissão de PósitronsRESUMO
Prostate cancer has a wide spectrum ranging between low-grade localized disease and castrate-resistant metastatic disease. Although whole gland and systematic therapies result in cure in the majority of patients, recurrent and metastatic prostate cancer can still occur. Imaging approaches including anatomic, functional, and molecular modalities are continuously expanding. Currently, recurrent and metastatic prostate cancer is grouped in three major categories: 1) Clinical concern for residual or recurrent disease after radical prostatectomy, 2) Clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments, and 3) Metastatic prostate cancer treated by systemic therapy (androgen deprivation therapy, chemotherapy, immunotherapy). This document is a review of the current literature regarding imaging in these settings and the resulting recommendations for imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Neoplasias da Próstata , Masculino , Humanos , Estados Unidos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios , Seguimentos , Diagnóstico por Imagem/métodos , Sociedades MédicasRESUMO
PURPOSE: SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid 18F-rhPSMA-7.3, a novel high-affinity positron emission tomography radiopharmaceutical. MATERIALS AND METHODS: Men with prostate cancer recurrence underwent positron emission tomography/CT 50-70 minutes after intravenous administration of 296±20% MBq 18F-rhPSMA-7.3. To assess the coprimary end points (verified detection rate and combined region-level positive predictive value), 3 blinded, independent central readers evaluated the scans. Verified detection rate is equivalent to the overall detection rate × positive predictive value. Standard of truth was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for verified detection rate and combined region-level positive predictive value, respectively. Additional end points included detection rate, verified detection rate, and combined region-level positive predictive value in patients with histopathology standard of truth, and safety. RESULTS: The overall 18F-rhPSMA-7.3 detection rate among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median prostate-specific antigen 1.27 ng/mL) for whom a standard of truth (histopathology [n=69]/confirmatory imaging only [n=297]) was available, verified detection rate ranged from 51% (95% CI 46.1-56.6) to 54% (95% CI 48.8-59.3), exceeding the prespecified statistical threshold. Combined region-level positive predictive value ranged from 46% (95% CI 42.0-50.3) to 60% (95% CI 55.1-65.5) across the readers, not meeting the threshold. In the subset of patients with histopathology standard of truth, the verified detection rate and combined region-level positive predictive value were both above the prespecified thresholds (majority read, 81% [95% CI 69.9-89.6] and 72% [95% CI 62.5-80.7], respectively). No significant safety concerns were identified. CONCLUSIONS: 18F-rhPSMA-7.3 offers a clinically meaningful verified detection rate for localization of recurrent prostate cancer. Despite missing the coprimary end point of combined region-level positive predictive value, the totality of the data support the potential clinical utility of 18F-rhPSMA-7.3.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologiaRESUMO
ABSTRACT: A 62-year-old woman with right-sided invasive lobular breast carcinoma completed external beam radiotherapy 6 weeks before undergoing a 68 Ga-PSMA PET/CT and 18 F-fluciclovine PET/CT scan as part of an ongoing clinical trial (NCT04750473) assessing the performance of these molecular imaging modalities in invasive lobular breast carcinoma. The 68 Ga-PSMA PET/CT demonstrated a band-like area of increased radiotracer uptake in the dome of the right lobe of the liver anteriorly, whereas 18 F-fluciclovine PET/CT done a day later revealed photopenia in the corresponding area of the liver. The external beam radiotherapy plan confirmed that the radiotherapy field overlaid the region of the hepatic discordant radiotracer uptake on the PET/CT scans.
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Neoplasias da Mama , Hepatite , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioisótopos de Gálio , Neoplasias da Mama/patologiaRESUMO
ABSTRACT: 18 F-fluciclovine (Axumin; Blue Earth Diagnostics, Ltd, Oxford, United Kingdom) PET has shown value in detecting biochemical recurrent prostatic cancer. Lycopene, a plant-based carotenoid, is reported to have potential inhibitory effect on prostate cancer, as a complementary treatment. We report a case of biochemically recurrent prostate cancer showing treatment response to lycopene as seen on an 18 F-fluciclovine PET/CT correlating with serum prostate-specific antigen response.
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Ciclobutanos , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Licopeno , Recidiva Local de Neoplasia , Ácidos CarboxílicosRESUMO
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.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/cirurgia , Ácidos Carboxílicos , Falha de Tratamento , Terapia de Salvação , Recidiva Local de Neoplasia , Antígeno Prostático Específico , ProstatectomiaRESUMO
BACKGROUND: There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC). PURPOSE: To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization. MATERIALS AND METHODS: This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs. RESULTS: N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively. CONCLUSION: In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes. CLINICAL TRIAL NUMBER: NCT04172714.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Microesferas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversosRESUMO
ABSTRACT: A 41-year-old woman with invasive lobular carcinoma of the breast underwent sequential 68Ga-PSMA-11 PET/CT and 18F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18F-fluciclovine PET/CT showed increased radiotracer uptake in a leiomyomatous uterus. A clinical 18F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of 2 radiotracers approved for prostate cancer imaging but increasingly used in non-prostate malignancies imaging.