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We evaluated the incidence and potential etiology of tracheobronchial uptake in patients being evaluated by 18F-DCFPyL PET/CT for prostate cancer (PCa). Methods: The study included a consecutive 100 PCa patients referred for 18F-DCFPyL PET/CT. The PET/CT scans were retrospectively reviewed. The presence or absence of physiologic tracheobronchial uptake on PET/CT was recorded. To further evaluate tracheal prostate-specific membrane antigen (PSMA) expression, immunohistochemistry was performed on tracheal samples taken from 2 men who had surgical resection of lung cancer. Results: Tracheal uptake was present in 31 of 100 patients (31%). When tracheal uptake was present, the SUVmax was significantly higher in the left main bronchus (mean, 2.7) than in the right (mean, 2.3) (P < 0.001). Histopathologic testing of tracheobronchial samples showed PSMA expression in bronchial submucosal glands. Conclusion: In PCa patients undergoing 18F-DCFPyL PET/CT, tracheobronchial uptake occurred in 31% of patients. This is attributed to normal physiologic PSMA expression in bronchial submucosal glands.
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BACKGROUND: Lesion detection is one of the most important clinical tasks in positron emission tomography (PET) for oncology. An anthropomorphic model observer (MO) designed to replicate human observers (HOs) in a detection task is an important tool for assessing task-based image quality. The channelized Hotelling observer (CHO) has been the most popular anthropomorphic MO. Recently, deep learning MOs (DLMOs), mostly based on convolutional neural networks (CNNs), have been investigated for various imaging modalities. However, there have been few studies on DLMOs for PET. PURPOSE: The goal of the study is to investigate whether DLMOs can predict HOs better than conventional MOs such as CHO in a two-alternative forced-choice (2AFC) detection task using PET images with real anatomical variability. METHODS: Two types of DLMOs were implemented: (1) CNN DLMO, and (2) CNN-SwinT DLMO that combines CNN and Swin Transformer (SwinT) encoders. Lesion-absent PET images were reconstructed from clinical data, and lesion-present images were reconstructed with adding simulated lesion sinogram data. Lesion-present and lesion-absent PET image pairs were labeled by eight HOs consisting of four radiologists and four image scientists in a 2AFC detection task. In total, 2268 pairs of lesion-present and lesion-absent images were used for training, 324 pairs for validation, and 324 pairs for test. CNN DLMO, CNN-SwinT DLMO, CHO with internal noise, and non-prewhitening matched filter (NPWMF) were compared in the same train-test paradigm. For comparison, six quantitative metrics including prediction accuracy, mean squared errors (MSEs) and correlation coefficients, which measure how well a MO predicts HOs, were calculated in a 9-fold cross-validation experiment. RESULTS: In terms of the accuracy and MSE metrics, CNN DLMO and CNN-SwinT DLMO showed better performance than CHO and NPWMF, and CNN-SwinT DLMO showed the best performance among the MOs evaluated. CONCLUSIONS: DLMO can predict HOs more accurately than conventional MOs such as CHO in PET lesion detection. Combining SwinT and CNN encoders can improve the DLMO prediction performance compared to using CNN only.
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PURPOSE: While 177Lu-PSMA-617 (LuPSMA) is an effective therapy for many patients with metastatic castration-resistant prostate cancer (mCRPC), biomarkers associated with outcomes are not well defined. We hypothesized that prostate cancer mutational profile may associate with clinical activity of LuPSMA. We devised a study to evaluate associations between mCRPC mutational profile with LuPSMA clinical outcomes. METHODS: This was a multicenter retrospective analysis of patients with mCRPC with next-generation sequencing (NGS) who received LuPSMA. PSA50 response (ie, ≥50% decline in prostate-specific antigen [PSA]) rate, PSA progression free survival (PSA PFS), and overall survival (OS) were compared between genetically defined subgroups. RESULTS: One hundred twenty-six patients with NGS results who received at least one cycle of LuPSMA were identified. The median age was 73 (IQR, 68-78) years, 124 (98.4%) received ≥1 prior androgen receptor-signaling inhibitor, and 121 (96%) received ≥1 taxane-based chemotherapy regimen. Fifty-eight (46%) patients with a DNA damage repair gene mutation (DNA damage response group) and 59 (46.8%) with a mutation in TP53, RB1, or PTEN tumor suppressor genes (TSG group) were identified. After adjusting for relevant confounders, the presence of ≥1 TSG mutation was associated with shorter PSA PFS (hazard ratio [HR], 1.93 [95% CI, 1.05 to 3.54]; P = .034) and OS (HR, 2.65 [95% CI, 1.15 to 6.11]; P = .023). There was improved OS favoring the DNA damage response group (HR, 0.37 [95% CI, 0.14 to 0.97]; P = .044) on multivariable analysis. Univariate analysis of patients with ATM mutations had significantly higher rates of PSA50 response, PSA PFS, and OS. CONCLUSION: Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.
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Dipéptidos , Lutecio , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Estudios Retrospectivos , Anciano , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Lutecio/uso terapéutico , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Antígeno Prostático Específico/sangre , Antígenos de Superficie/genética , Estudios de Cohortes , Glutamato Carboxipeptidasa II/genéticaRESUMEN
BACKGROUND: Prognostic models have been developed using data from a multicentre noncomparative study to forecast the likelihood of a 50% reduction in prostate-specific antigen (PSA50), longer prostate-specific antigen (PSA) progression-free survival (PFS), and longer overall survival (OS) in patients with metastatic castration-resistant prostate cancer receiving [177Lu]Lu-PSMA radioligand therapy. The predictive utility of the models to identify patients likely to benefit most from [177Lu]Lu-PSMA compared with standard chemotherapy has not been established. OBJECTIVE: To determine the predictive value of the models using data from the randomised, open-label, phase 2, TheraP trial (primary objective) and to evaluate the clinical net benefit of the PSA50 model (secondary objective). DESIGN, SETTING, AND PARTICIPANTS: All 200 patients were randomised in the TheraP trial to receive [177Lu]Lu-PSMA-617 (n = 99) or cabazitaxel (n = 101) between February 2018 and September 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Predictive performance was investigated by testing whether the association between the modelled outcome classifications (favourable vs unfavourable outcome) was different for patients randomised to [177Lu]Lu-PSMA versus cabazitaxel. The clinical benefit of the PSA50 model was evaluated using a decision curve analysis. RESULTS AND LIMITATIONS: The probability of PSA50 in patients classified as having a favourable outcome was greater in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (odds ratio 6.36 [95% confidence interval {CI} 1.69-30.80] vs 0.96 [95% CI 0.32-3.05]; p = 0.038 for treatment-by-model interaction). The PSA50 rate in patients with a favourable outcome for [177Lu]Lu-PSMA-617 versus cabazitaxel was 62/88 (70%) versus 31/85 (36%). The decision curve analysis indicated that the use of the PSA50 model had a clinical net benefit when the probability of a PSA response was ≥30%. The predictive performance of the models for PSA PFS and OS was not established (treatment-by-model interaction: p = 0.36 and p = 0.41, respectively). CONCLUSIONS: A previously developed outcome classification model for PSA50 was demonstrated to be both predictive and prognostic for the outcome after [177Lu]Lu-PSMA-617 versus cabazitaxel, while the PSA PFS and OS models had purely prognostic value. The models may aid clinicians in defining strategies for patients with metastatic castration-resistant prostate cancer who failed first-line chemotherapy and are eligible for [177Lu]Lu-PSMA-617 and cabazitaxel. PATIENT SUMMARY: In this report, we validated previously developed statistical models that can predict a response to Lu-PSMA radioligand therapy in patients with advanced prostate cancer. We found that the statistical models can predict patient survival, and aid in determining whether Lu-PSMA therapy or cabazitaxel yields a higher probability to achieve a serum prostate-specific antigen response.
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Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) is transforming the management of patients with prostate cancer. In appropriately selected patients, PSMA-PET offers superior sensitivity and specificity compared to conventional imaging (e.g., computed tomography and bone scintigraphy) as well as choline and fluciclovine PET, with the added benefit of consolidating bone and soft tissue evaluation into a single study. Despite being a newly available imaging tool, PSMA-PET has established indications, interpretation guidelines, and reporting criteria, which will be reviewed. The prostate cancer care team, from imaging specialists to those delivering treatment, should have knowledge of physiologic PSMA radiotracer uptake, patterns of disease spread, and the strengths and limitations of PSMA-PET. In this review, current and emerging applications of PSMA-PET, including appropriateness use criteria as well as image interpretation and pitfalls, will be provided with an emphasis on clinical implications.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioisótopos de Galio , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/terapia , Tomografía de Emisión de PositronesRESUMEN
Immunotherapy approaches have changed the treatment landscape in a variety of malignancies with a high anti-tumor response. Immunotherapy may be associated with novel response and progression patterns that pose a substantial challenge to the conventional criteria for assessing treatment response, including response evaluation criteria in solid tumors (RECIST) 1.1. In addition to the morphologic details provided by computed tomography (CT) and MRI, hybrid molecular imaging emerges as a comprehensive imaging modality with the capacity to interrogate pathophysiological mechanisms like glucose metabolism. This review highlights the current status of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in prognostication, response monitoring, and identifying immune-related adverse events. Furthermore, it investigates the potential role of novel immuno-PET tracers that could complement the utilization of 18F-FDG PET/CT by imaging the specific pathways involved in immunotherapeutic strategies.
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Fluorodesoxiglucosa F18 , Neoplasias , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Tomografía Computarizada por Rayos X , Tomografía de Emisión de Positrones , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , InmunoterapiaRESUMEN
BACKGROUND: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [177Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [68Ga]Ga-PSMA-11 and 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET-CT. METHODS: TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [68Ga]Ga-PSMA-11 and 2-[18F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[18F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [177Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete. FINDINGS: 291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [177Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [177Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [177Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [177Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference -0·5 months [95% CI -3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [68Ga]Ga-PSMA-11 and 2-[18F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1). INTERPRETATION: These results support the use of [177Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[18F]FDG-discordant disease. FUNDING: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It's a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman's Ride.
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Radioisótopos de Galio , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Resultado del Tratamiento , Docetaxel/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Australia , Antígeno Prostático EspecíficoRESUMEN
Introduction: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. Methods: This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. Results: There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. Conclusion: Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.
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Hipofisitis , Neoplasias , Enfermedades de la Hipófisis , Humanos , Femenino , Persona de Mediana Edad , Masculino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Hipofisitis/diagnóstico por imagen , Hipofisitis/tratamiento farmacológicoRESUMEN
BACKGROUND: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. METHODS: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. RESULTS: At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3-32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%, p < 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4-98.0), kappa 0.83. CONCLUSION: Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction.
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Prostate cancer remains the commonest cancer diagnosed in males and a leading cause of cancer-related death. Men with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on chemotherapy and androgen receptor pathway inhibitors (ARPI) have limited treatment options, significant morbidity, and poor outcomes. Prostate-specific membrane antigen (PSMA)-directed radionuclide therapy (RNT) is emerging as an efficacious and well-tolerated therapy; however, disease progression is universal. Several ongoing RNT trials focus on combination strategies to improve efficacy and durability of treatment response, including combinations with ARPIs, chemotherapy, immunotherapy, and targeted therapies. Further, efforts are underway to expand the role of PSMA-directed RNT to earlier stages of disease including hormone-sensitive and localized prostate cancer. In this review, we discuss the rationale and ongoing RNT combination therapeutic trials in prostate cancer and summarize the efficacy and toxicity associated with RNT.
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Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Selección de Paciente , Radioisótopos/uso terapéutico , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Lutecio/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/radioterapiaRESUMEN
Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.
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Medicina Nuclear , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radiofármacos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Dipéptidos/uso terapéutico , Lutecio/uso terapéutico , Resultado del TratamientoRESUMEN
The clinical and imaging presentation of pancreatic neuroendocrine tumors (PanNETs) is variable and depends on tumor grade, stage, and functional status. This degree of variability combined with a multitude of treatment options and imaging modalities results in complexity when choosing the most appropriate imaging studies across various clinical scenarios. While various guidelines exist in the management and evaluation of PanNETs, there is an overall lack of consensus and detail regarding optimal imaging guidelines and protocols. This manuscript aims to fill gaps where current guidelines may lack specificity regarding the choice of the most appropriate imaging study in the diagnosis, treatment planning, monitoring, and surveillance of PanNETs under various clinical scenarios.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Diagnóstico por ImagenRESUMEN
Background Despite improved response to combined ipilimumab and nivolumab (hereafter, IpiNivo) treatment for advanced melanoma, many patients exhibit primary or acquired resistance. This, combined with high risk of immune-related adverse events, makes identifying markers predictive of outcomes desirable. Purpose To investigate the prognostic value of fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT parameters at baseline and as part of response monitoring in patients with advanced melanoma undergoing IpiNivo treatment. Materials and Methods This was a single-center retrospective study of adult patients with melanoma who received IpiNivo. Baseline FDG PET/CT parameters that included metabolic tumor volume (MTV), tumor stage, mutation status, Eastern Cooperative Oncology Group performance score, lactate dehydrogenase level, and treatment line were correlated with overall survival in univariable and multivariable Cox regression analyses. Treatment response as determined with FDG PET/CT was correlated with overall survival. Results In total, 122 patients (median age, 61 years [IQR, 51-69 years]; 89 men) were included; 78% (95 of 122) had an Eastern Cooperative Oncology Group score of 0, 52% (45 of 86) had an elevated lactate dehydrogenase level, 39% (48 of 122) had a metastatic stage of M1c and 45% (55 of 122) M1d, 45% (55 of 122) had BRAF V600E/K mutation, and the median MTV was 42 mL. Patients with a higher than median MTV at baseline FDG PET/CT had a lower 12-month survival rate compared with those with a lower than median MTV (43% [95% CI: 32, 58] vs 66% [95% CI: 55, 79], P < .001). In multivariable analysis, higher versus lower than median MTV, Eastern Cooperative Oncology Group performance scores of 1-2 versus 0, and subsequent versus first-line IpiNivo treatment were independently associated with overall survival (hazard ratio [HR]: 1.68 [95% CI: 1.02, 2.78], P = .04; 3.1 [95% CI: 1.8, 5.4], P < .001; and 11.2 [95% CI: 3.4, 37.1], P = .002, respectively). The 12-month overall survival rate was lower in patients with progressive disease than in those without progression (35% [95% CI: 24, 51] vs 90% [95% CI: 83, 99]; HR, 7.3 [95% CI: 3.9, 13.3]; P < .001). Conclusion Baseline fluorine 18 fluorodeoxyglucose PET/CT metabolic tumor volume was an independent prognostic marker in patients with advanced melanoma who received ipilimumab and nivolumab treatment. © RSNA, 2023 Supplemental material is available for this article.
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Melanoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Masculino , Adulto , Humanos , Persona de Mediana Edad , Ipilimumab , Fluorodesoxiglucosa F18 , Nivolumab , Pronóstico , Estudios Retrospectivos , Melanoma/patología , Lactato Deshidrogenasas , Carga TumoralRESUMEN
A 76-year-old man with metastatic castration-resistant prostate carcinoma progressing with antiandrogen and taxane therapy was treated with lutetium 177 prostate-specific membrane antigen (PSMA)-617 and showed marked biochemical and imaging response, with improvement in clinical status and osseous pain. A summary of nuclear medicine theranostics with emphasis on PSMA targeting agents is presented.
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Neoplasias de la Próstata Resistentes a la Castración , Anciano , Humanos , Masculino , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/inducido químicamente , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del TratamientoRESUMEN
Theranostics describes the coupling of a diagnostic biomarker and a therapeutic agent (i.e., a theranostic pair) that have a common target in tumor cells or their microenvironment. The term is increasingly associated with in vivo nuclear medicine oncologic applications that couple diagnostic imaging by means of gamma radiation with concomitant localized high-energy particulate radiation to a tissue expressing the common target. Several theranostic pairs have been translated into clinical practice in the United States and are poised to become a mainstay of cancer treatment. The purposes of this article are to review experience with theranostics for solid-organ malignancies and to address the practical integration into care pathways of ß-emitting therapies that include somatostatin analogue radioligands for neuroendocrine tumors, PSMA-directed therapy for prostate cancer, and 131I-MIBG therapy for tumors of neural crest origin. Toxicities related to theranostics administration and indications for cessation of therapy in patients who experience adverse events are also discussed. A multidisciplinary team-based approach for identifying patients most likely to respond to these agents, determining the optimal time for therapy delivery, and managing patient care throughout the therapeutic course is critical to the success of a radiotheranostic program.
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Medicina de Precisión , Neoplasias de la Próstata , Masculino , Humanos , Vías Clínicas , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Somatostatina , Atención al Paciente , Microambiente TumoralRESUMEN
BACKGROUND: Previously, results from the TheraP trial showed that treatment with lutetium-177 [177Lu]Lu-PSMA-617 improved frequency of prostate-specific antigen (PSA) response rate and progression-free survival compared with cabazitaxel in men with metastatic castration-resistant prostate cancer. In this study, we aimed to analyse gallium-68 [68Ga]Ga-PSMA-11 PET (PSMA-PET) and 2-[18F]fluoro-2-deoxy-D-glucose PET (FDG-PET) imaging parameters as predictive and prognostic biomarkers in this patient population. METHODS: TheraP was a multicentre, open-label, randomised phase 2 trial that recruited men with metastatic castration-resistant prostate cancer after treatment with docetaxel who were suitable for cabazitaxel from 11 hospitals in Australia. Participants were required to be 18 years old or older; have adequate haematological, renal, and liver function; and an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly assigned (1:1) using a centralised system using minimisation with a random component and that stratified patients by disease burden, previous treatment with enzalutamide or abiraterone, and study site. Patients were either given cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles) or [177Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles). The primary study endpoint, analysed previously, was PSA response rate. The prespecified tertiary study endpoint was association between total tumour quantitative parameters on PSMA-PET, FDG-PET, and baseline characteristics with clinical outcomes. A SUVmean of 10 or higher on PSMA-PET was evaluated as a predictive biomarker for response to [177Lu]Lu-PSMA-617 versus cabazitaxel. A metabolic tumour volume (MTV) of 200 mL or higher on FDG-PET was tested as a prognostic biomarker. Both cutoff points were prespecified. The analysis was intention-to-treat, using logistic regression. This trial is registered with ClinicalTrials.gov, NCT03392428. FINDINGS: 200 patients were randomly assigned between Feb 6, 2018, and Sept 3, 2019. 101 men were assigned to the cabazitaxel group and 99 were assigned to the [177Lu]Lu-PSMA-617 group. The median follow-up at data cutoff of July 20, 2020, was 18·4 months (IQR 12·8-21·8). 35 (35%) of 99 men who were assigned [177Lu]Lu-PSMA-617 and 30 (30%) of 101 men who were assigned cabazitaxel had high PSMA uptake (SUVmean of ≥10). Odds of PSA response to [177Lu]Lu-PSMA-617 versus cabazitaxel were significantly higher for men with SUVmean of 10 or higher compared with those with SUVmean of less than 10 (odds ratio [OR] 12·19 [95% CI 3·42-58·76] vs 2·22 [1·11-4·51]; padj=0·039 for treatment-by-SUVmean interaction). PSA response rate for [177Lu]Lu-PSMA-617 compared with cabazitaxel was 32 (91% [95% CI 76-98]) of 35 men versus 14 (47% [29-65]) of 30 men in patients with SUVmean of 10 or higher, and 33 (52% [39-64]) of 64 men versus 23 (32% [22-45]) of 71 men in those with SUVmean of less than 10. High-volume disease on FDG-PET (MTV ≥200 mL) was seen in 30 (30%) of 99 men who were assigned [177Lu]Lu-PSMA-617 and 30 (30%) of 101 men who were assigned cabazitaxel. PSA response rate for both treatment groups combined for FDG-PET MTV of 200 mL or higher versus FDG-PET MTV of less than 200 mL was 23 (38% [95% CI 26-52]) of 60 men versus 79 (56% [48-65]) of 140 men (OR 0·44, 95% CI 0·23-0·84; padj=0·035). INTERPRETATION: In men with metastatic castration-resistant prostate cancer, PSMA-PET SUVmean was predictive of higher likelihood of favourable response to [177Lu]Lu-PSMA-617 than cabazitaxel, which provides guidance for optimal [177Lu]Lu-PSMA-617 use. High FDG-PET MTV was associated with lower responses regardless of randomly assigned treatment, warranting further research for treatment intensification. A strength of this analysis is the validation of pre-specified cutpoints within a multicentre, randomised, controlled trial. Quantitative PET parameters used, however, require specialised software and are not yet routinely available in most clinics. FUNDING: Prostate Cancer Foundation of Australia, Endocyte (a Novartis Company), Australian Nuclear Science and Technology Organisation, Movember Foundation, It's a Bloke Thing, CAN4CANCER, The Distinguished Gentleman's Ride.
Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Adolescente , Adulto , Antígeno Prostático Específico/uso terapéutico , Fluorodesoxiglucosa F18 , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Pronóstico , Australia , Resultado del TratamientoRESUMEN
PURPOSE: Standardized reporting in radiology has an established role in numerous disease processes, with added benefits in oncology of reduced variability, and generation of a thorough and pertinent report with a focused and relevant conclusion. Many radiologists are not familiar with the imaging patterns of neuroendocrine neoplasm (NEN) spread and recurrence. This paper will present standardized CT, MRI, and PET templates for reporting gastroenteropancreatic (GEP) NENs and explain the rationale for including specific pertinent positive and negative findings, at various stages of disease management, based on site of origin. METHODS: Basic templates for initial and follow-up anatomic and molecular GEP NEN imaging were created with input from the multidisciplinary Society of Abdominal Radiology (SAR) Neuroendocrine Tumor Disease Focused Panel (NET-DFP). The templates were further modified and finalized after several iterations. RESULTS: Four main report templates were generated for (i) initial anatomic CT or MR imaging studies, (ii) follow-up anatomic CT or MR imaging studies, (iii) initial Somatostatin Receptor (SSTR) or FDG PET imaging studies, and (iv) follow-up SSTR or FDG PET imaging studies. Each study template was formatted to allow its integration into a dictation software directly and be modified as needed, with internalized instructions indicating where a drop-down menu or macro may be used to personalize the template as necessary. CONCLUSION: These templates were created through a combination of multidisciplinary expert opinion discussion supported by literature review and provide basic structured reporting standards for GEP NEN anatomic and molecular imaging studies.
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Neoplasias Gastrointestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Fluorodesoxiglucosa F18 , Neoplasias Pancreáticas/patología , Tumores Neuroendocrinos/patología , Receptores de SomatostatinaRESUMEN
With the relatively low incidence of neuroendocrine neoplasms (NEN), most radiologists are not familiar with their optimal imaging techniques. The imaging protocols for NENs should be tailored to the site of origin to accurately define local extension of NEN at time of staging. Patterns of spread and recurrence should be taken into consideration when choosing protocols for detection of recurrence and metastases. This paper will present the recommended CT and MRI imaging protocols for gastro-enteric and pancreatic NENs based on site of origin or predominant pattern of metastatic disease, and explain the rationale for MRI contrast type, contrast timing, as well as specific sequences in MRI. We will also briefly comment on PET/CT and PET/MRI imaging protocols.
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Tumores Neuroendocrinos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tumores Neuroendocrinos/patología , Tomografía de Emisión de Positrones , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: To determine the decision patterns of a neuroendocrine neoplasm (NEN) tumor board (TB) and the factors behind those. METHODS: We retrospectively reviewed all NEN-TB recommendations from 07/2018 to 12/2021 and recorded patient characteristics, TB outcomes and associations between them. RESULTS: A total of 652 patient entries were identified. Median age of participants was 61 years and an equal number of men and women were presented. Most patients (33.4%) had tumors originating in the small bowel with 16.8% of high grade and 25.9% of pancreatic origin. Imaging was reviewed 97.2% of the time, with most frequently reviewed modalities being PET (55.3%) and CT (44.3%). Imaging review determined that there was no disease progression 20.8% of the time and significant treatment changes were recommended in 36.1% of patients. Major pathology amendments occurred in 3.7% of cases and a clinical trial was identified in 2.6%. There was no association between patient or disease presentation with the tumor board outcomes. There was a slight decrease in number of patients discussed per session, from 10.0 to 8.2 (p < 0.001) when the TB transitioned to a virtual format during the COVID-19 pandemic but all other factors remained unchanged. CONCLUSION: NEN-TB relies heavily on image review, can impact significant treatment changes in patients with rare tumors like NENs, and was not affected by the switch to a virtual format. Finally, none of the examined factors were predictive of the tumor board recommendations.