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Candidates for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) frequently have "mismatch" lesions with pronounced 18-fluorodeoxyglucose ([18F]FDG) but attenuated PSMA ligand uptake on positron emission tomography (PET). However, no quantitative criteria yet exist to identify mismatch lesions and predict their response to RLT. To define such criteria, we retrospectively analyzed 267 randomly-selected glucometabolic mCRPC metastases from 22 patients. On baseline PET, we determined [18F]FDG and [68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax), and calculated the [18F]FDG SUVmax/[68Ga]Ga-PSMA-11 SUVmax quotient (FPQ). From follow-up [18F]FDG PET after two lutetium-177-PSMA-617 RLT cycles, we evaluated the treatment response and categorized the lesions into three subgroups (partial remission, stable disease, progression) based on change in [18F]FDG SUVmax. Lastly, we compared the baseline PET variables in progressing versus non-progressing lesions. Variables differing significantly, and a score incorporating them, were assessed via receiver operator characteristic (ROC) curve analysis, regarding ability to predict lesional progression, with area under the curve (AUC) as metric. Cut-offs with optimal sensitivity and specificity were determined using the maximum value of Youden's index. Fifty-one of 267 lesions (19.1%) progressed, 102/267 (38.2%) manifested stable disease, and 114/267 (42.7%) partially responded after two RLT cycles. At baseline, median [68Ga]Ga-PSMA-11 SUVmax was significantly lower (p < 0.001), median FPQ significantly higher (p < 0.001), and median [18F]FDG SUVmax similar in progressing versus non-progressing lesions. [68Ga]Ga-PSMA-11 SUVmax and FPQ showed predictive power regarding progression (AUCs: 0.89, 0.90). An introduced clinical score combining both further improved predictive performance (AUC: 0.94). Optimal cut-offs to foretell progression were: [68Ga]Ga-PSMA-11 SUVmax < 11.09 (88.2% sensitivity, 81.9% specificity), FPQ ≥ 0.92 (90.2% sensitivity, 78.7% specificity), clinical score ≥ 6/9 points (88.2% sensitivity, 87.5% specificity). At baseline, a low [68 Ga]Ga-PSMA-11 SUVmax and a high FPQ predict early lesional progression under RLT; [18F]FDG SUVmax does not. A score combining [68 Ga]Ga-PSMA-11 SUVmax and FPQ predicts early lesional progression even more effectively and might therefore be useful to quantitatively identify mismatch lesions.
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Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Anciano , Tomografía de Emisión de Positrones/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Radioisótopos de Galio , Radiofármacos , Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Anciano de 80 o más Años , LutecioRESUMEN
BACKGROUND: The state-of-the-art method for imaging men with biochemical recurrence of prostate cancer (BCR) is prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) with tracers containing short-lived radionuclides, e.g., gallium-68 (68Ga; half-life: â¼67.7 min). However, such imaging not infrequently yields indeterminate findings, which remain challenging to characterize. PSMA-targeted tracers labeled with zirconium-89 (89Zr; half-life: â¼78.41 h) permit later scanning, which may help in classifying the level of suspiciousness for prostate cancer of lesions previously indeterminate on conventional PSMA-targeted PET/CT. METHODS: To assess the ability of [89Zr]Zr-PSMA-617 PET/CT to characterize such lesions, we retrospectively analyzed altogether 20 lesions that were indeterminate on prior [68Ga]Ga-PSMA-11 PET/CT, in 15 men with BCR (median prostate-specific antigen: 0.70 ng/mL). The primary endpoint was the lesions' classifications, and secondary endpoints included [89Zr]Zr-PSMA-617 uptake (maximum standardized uptake value [SUVmax]), and lesion-to-background ratio (tumor-to-liver ratio of the SUVmax [TLR]). [89Zr]Zr-PSMA-617 scans were performed 1 h, 24 h, and 48 h post-injection of 123 ± 19 MBq of radiotracer, 35 ± 35 d post-[68Ga]Ga-PSMA-11 PET/CT. RESULTS: Altogether, 6/20 previously-indeterminate lesions (30%) were classified as suspicious (positive) for prostate cancer, 14/20 (70%), as non-suspicious (negative). In these two categories, [89Zr]Zr-PSMA-617 uptake and lesional contrast showed distinctly different patterns. In positive lesions, SUVmax and TLR markedly rose from 1 to 48 h, with SUVmax essentially plateauing at high levels, and TLR further steeply increasing, from 24 to 48 h. In negative lesions, uptake, when present, was very low, and decreasing, while contrast was minimal, from 1 to 48 h. No adverse events or clinically-relevant vital signs changes related to [89Zr]Zr-PSMA-617 PET/CT were noted during or ~ 4 weeks after the procedure. CONCLUSIONS: In men with BCR, [89Zr]Zr-PSMA-617 PET/CT may help characterize as suspicious or non-suspicious for prostate cancer lesions that were previously indeterminate on [68Ga]Ga-PSMA-11 PET/CT. TRIAL REGISTRATION: Not applicable.
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Dipéptidos , Compuestos Heterocíclicos con 1 Anillo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioisótopos de Galio , Estudios Retrospectivos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Oligopéptidos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Ácido EdéticoRESUMEN
"Tumor sink effects", decreased physiological uptake of radiopharmaceuticals due to sequestration by a tumor, may impact radioligand therapy (RLT) toxicity and dosing. We investigated these effects with prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals in the healthy organs-at-risk (the parotid glands, kidneys, liver, and spleen) of 33 patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively performed three intra-individual comparisons. First, we correlated changes from baseline to post-RLT (after two 177-lutetium (177Lu)-PSMA-617 cycles) in total lesional PSMA (∆TLP) and organ mean standardized uptake values (∆SUVmean). Second, in 25 RLT responders, we compared the organ SUVmean post-RLT versus that at baseline. Lastly, we correlated the baseline TLP and organ SUVmean. Data were acquired via 68-gallium-PSMA-11 positron emission tomography before the first and after the second 177Lu-PSMA-617 cycle. In the parotid glands and spleen, ∆TLP and ∆SUVmean showed a significant inverse correlation (r = -0.40, p = 0.023 and r = -0.36, p = 0.042, respectively). Additionally, in those tissues, the median organ SUVmean rose significantly from baseline after the response to RLT (p ≤ 0.022), and the baseline TLP and SUVmean were significantly negatively correlated (r = -0.44, p = 0.01 and r = -0.42, p = 0.016, respectively). These observations suggest tumor sink effects with PSMA-targeted radiopharmaceuticals in the salivary glands and spleen of patients with mCRPC.
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RATIONALE: In patients with biochemical recurrence of prostate cancer (BCR), preliminary data suggest that prostate-specific membrane antigen (PSMA) ligand radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h), which allow imaging ≥ 24 h post-injection, detect suspicious lesions that are missed when using tracers incorporating short-lived radionuclides. MATERIALS AND METHODS: To confirm [89Zr]Zr-PSMA-617 positron emission tomography/computed tomography (PET/CT) detection efficacy regarding such lesions, and compare quality of 1-h, 24-h, and 48-h [89Zr]Zr-PSMA-617 scans, we retrospectively analyzed visual findings and PET variables reflecting lesional [89Zr]Zr-PSMA-617 uptake and lesion-to-background ratio. The cohort comprised 23 men with BCR post-prostatectomy, median (minimum-maximum) prostate-specific antigen (PSA) 0.54 (0.11-2.50) ng/mL, and negative [68Ga]Ga-PSMA-11 scans 40 ± 28 d earlier. Primary endpoints were percentages of patients with, and classifications of, suspicious lesions. RESULTS: Altogether, 18/23 patients (78%) had 36 suspicious lesions (minimum-maximum per patient: 1-4) on both 24-h and 48-h scans (n = 33 lesions) or only 48-h scans (n = 3 lesions). Only one lesion appeared on a 1-h scan. Lesions putatively represented local recurrence in 11 cases, and nodal or bone metastasis in 21 or 4 cases, respectively; 1/1 lesion was histologically confirmed as a nodal metastasis. In all 15 patients given radiotherapy based on [89Zr]Zr-PSMA-617 PET/CT, PSA values decreased after this treatment. Comparison of PET variables in 24-h vs 48-h scans suggested no clear superiority of either regarding radiotracer uptake, but improved lesion-to-background ratio at 48 h. CONCLUSIONS: In men with BCR and low PSA, [89Zr]Zr-PSMA-617 PET/CT seems effective in finding prostate malignancy not seen on [68Ga]Ga-PSMA-11 PET/CT. The higher detection rates and lesion-to-background ratios of 48-h scans versus 24-h scans suggest that imaging at the later time may be preferable. Prospective study of [89Zr]Zr-PSMA-617 PET/CT is warranted.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioisótopos de Galio , Estudios Prospectivos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/patología , RecurrenciaRESUMEN
In biochemical recurrence of prostate cancer (BCR), prompt tumor localization guides early treatment, potentially improving patient outcomes. Gallium-68 prostate-specific membrane antigen-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) detection rates of lesions suspicious for prostate cancer are well known to rise along with prostate-specific antigen (PSA) concentration. However, published data are limited regarding very low values (≤0.2 ng/mL). We retrospectively analyzed ~7-year "real-world" experience in this setting in a large post-prostatectomy cohort (N = 115) from two academic clinics. Altogether 44 lesions were detected in 29/115 men (25.2%) (median [minimum-maximum] 1 [1-4]/positive scan). The apparent oligometastatic disease was found in nine patients (7.8%) at PSA as low as 0.03 ng/mL. Scan positivity rates were highest when PSA was >0.15 ng/mL, PSA doubling time was ≤12 months, or the Gleason score was ≥7b (in 83 and 107 patients, respectively, with available data); these findings were statistically significant (p ≤ 0.04), except regarding PSA level (p = 0.07). Given the benefits of promptly localizing recurrence, our observations suggest the potential value of 68Ga-PSMA-11 PET/CT in the very low PSA BCR setting, especially in cases with more rapid PSA doubling time or with high-risk histology.
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For patients undergoing radioiodine therapy (RIT) of differentiated thyroid carcinoma (DTC), thyroid-stimulating hormone (TSH) stimulation prior to RIT can be achieved using thyroid hormone withdrawal (THW) or administration of recombinant human TSH (rhTSH). As THW can lead to nausea, headaches, vomiting, fatigue, and dizziness secondary to transient acute hypothyroidism, rhTSH could be a good alternative. Recombinant human TSH has been administered in patients in order to stimulate TSH for RIT since 2005. According to the Martinique criteria formulated by the leading professional societies involved in care of patients with DTC, rhTSH can be applied in 3 settings: for remnant ablation, adjuvant treatment, and treatment of known disease. Numerous studies have investigated the effects of rhTSH as a method of TSH stimulation on the thyroid cell, the systemic effects, biokinetics, and clinical outcomes; however, no consensus has been reached about many aspects of its potential use. Recombinant human TSH is able to stimulate sufficient TSH levels (>30â mIU L-1) and is hypothesized to decrease risks of tumor cell proliferation. As rhTSH-use avoids the transiently impaired renal function associated with THW, radioiodine excretion is faster with the former, leading to a lower iodine-131 uptake and a difference in fractional remnant uptake, effective half-life, mean residence time, and dose to the blood. Differences between rhTSH and THW were observed in radioiodine genotoxic effects and endothelial-dependent vasodilation and inflammation. For thyroid remnant ablation, THW and rhTSH lead to similar remnant ablation rates. For adjuvant therapy and treatment of known disease, insufficient trials have been conducted and future prospective studies are recommended. The current review provides a state-of-the-science overview on the issues and debates surrounding TSH stimulation through either rhTSH adminsitration orendogenous TSH production after levothyroxin withdrawal.
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Hipotiroidismo , Neoplasias de la Tiroides , Tirotropina Alfa , Humanos , Neoplasias de la Tiroides/cirugía , Tirotropina/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Estudios Prospectivos , Hormonas Tiroideas , Hipotiroidismo/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a lethal fibrosing interstitial lung disease with a mean survival time of less than 5 years. Nonspecific presentation, a lack of effective early screening tools, unclear pathobiology of early-stage IPF and the need for invasive and expensive procedures for diagnostic confirmation hinder early diagnosis. In this study, we introduce a new screening tool for IPF in primary care settings that requires no new laboratory tests and does not require recognition of early symptoms. Using subtle comorbidity signatures identified from the history of medical encounters of individuals, we developed an algorithm, called the zero-burden comorbidity risk score for IPF (ZCoR-IPF), to predict the future risk of an IPF diagnosis. ZCoR-IPF was trained on a national insurance claims database and validated on three independent databases, comprising a total of 2,983,215 participants, with 54,247 positive cases. The algorithm achieved positive likelihood ratios greater than 30 at a specificity of 0.99 across different cohorts, for both sexes, and for participants with different risk states and history of confounding diseases. The area under the receiver-operating characteristic curve for ZCoR-IPF in predicting IPF exceeded 0.88 and was approximately 0.84 at 1 and 4 years before a conventional diagnosis, respectively. Thus, if adopted, ZCoR-IPF can potentially enable earlier diagnosis of IPF and improve outcomes of disease-modifying therapies and other interventions.
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Fibrosis Pulmonar Idiopática , Comorbilidad , Registros Electrónicos de Salud , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/epidemiología , Masculino , Curva ROC , Estudios RetrospectivosRESUMEN
PURPOSE: Concern is growing about long-term side effects of differentiated thyroid cancer treatment, most notably radioactive iodine (RAI) therapy. However, published studies on the subject have had heterogeneous cohorts and conflicting results. This review seeks to provide an updated evaluation of published evidence, and to elucidate the risk of second primary malignancies (SPMs), especially secondary hematologic malignancies (SHMs), attributable to RAI therapy. METHODS: An extensive literature search was performed in Ovid MEDLINE, Ovid MEDLINE and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Epub Ahead of Print, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed. Studies regarding RAI-induced SPMs or a dose-response relationship between RAI therapy and SPMs were identified, 10 of which were eligible for the analysis. We evaluated risk of bias in each study and judged quality of evidence (QOE) across all studies using the Grading of Recommendations, Assessment, Development and Evaluations approach. RESULTS: For the outcome "SPM", the relative effect (relative risk, hazard ratio, or odds ratio) of RAI vs. no RAI ranged from 1.14 to 1.84 across studies, but most results were not statistically significant. For the outcome "SHM", reported relative effects ranged from 1.30 to 2.50, with 2/3 of the studies presenting statistically significant results. In 7/8 of the studies, increased risk for SPM was shown with increasing cumulative RAI activity. QOE was "very low" regarding SPM after RAI and regarding a dose-response relationship, and "low" for SHM after RAI. CONCLUSION: Based on low quality evidence, an excess risk for the development of SPM cannot be excluded but is expected to be small.
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Adenocarcinoma , Neoplasias Inducidas por Radiación , Neoplasias Primarias Secundarias , Neoplasias de la Tiroides , Adenocarcinoma/complicaciones , Humanos , Radioisótopos de Yodo/efectos adversos , Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/etiología , Riesgo , Neoplasias de la Tiroides/radioterapiaRESUMEN
PURPOSE: Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety and efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples treated in everyday practice. METHODS: We analyzed prospectively collected registry data regarding lutetium-177 (177Lu)-PSMA-617 RLT of 254 consecutive men with mCRPC seen in everyday academic practice. Since 177Lu-PSMA-617 was experimental salvage treatment following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated (median age 70 years; prior taxanes 74.0%, 188/254), with late-end-stage disease (visceral metastasis in 32.7%, 83/254). Primary endpoints were response to RLT, defined by changes from baseline serum prostate-specific antigen (PSA) concentration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with Kaplan-Meier statistics, and caregiver-reported and patient-reported safety. Unless noted, median (minimum-maximum) values are given. RESULTS: Patients received 3 (1-13) 177Lu-PSMA-617 activities (6.5 [2.5-11.6] GBq/cycle) every 5.7 (3.0-11.0) weeks. Best response was ≥ 50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confidence interval [95%CI] 4.4-6.6) months and OS, 14.5 (95%CI 11.5-17.5) months. In multivariable Cox proportional-hazards modeling, response to the initial ≤ 2 RLT administrations was the strongest significant prognosticator related to OS (hazard ratio 3.7 [95%CI 2.5-5.5], p < 0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade 3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%). RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%). CONCLUSIONS: In a large, prospectively observed "real-world" cohort with late-stage/end-stage mCRPC and conventional treatment failure, 177Lu-PSMA-617 RLT was effective, safe, and well-tolerated. Early biochemical disease control by such therapy was associated with better OS. Prospective study earlier in the disease course may be warranted.
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Neoplasias de la Próstata Resistentes a la Castración , Anciano , Dipéptidos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Humanos , Lutecio/uso terapéutico , Masculino , Estudios Prospectivos , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radioisótopos , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Typically formulated by investigators from "world centres of excellence," differentiated thyroid carcinoma (DTC) management guidelines may have more limited applicability in settings of less expert care and fewer resources. Arguably the world's leading DTC guidelines are those of the American Thyroid Association, revised in 2009 ("ATA 2009") and 2015 ("ATA 2015"). To further explore the issue of "real-world applicability" of DTC guidelines, we retrospectively compared indications for ablation using ATA 2015 versus ATA 2009 in a two-centre cohort of ablated T1-2, M0 DTC patients (N = 336). Based on TNM status and histology, these patients were low-intermediate risk, but many ultimately had other characteristics suggesting elevated or uncertain risk. METHODS: Working by consensus, two experienced nuclear medicine physicians considered patient and treatment characteristics to classify each case as having "no indication," a "possible indication," or a "clear indication" for ablation according to ATA 2009 or ATA 2015. The physicians also identified reasons for classification changes between ATA 2015 versus ATA 2009. Classification was unblinded, but the physicians had cared for only 138/336 patients, and the charts encompassed September 2010-October 2013, several years before the classification was performed. RESULTS: One hundred of 336 patients (29.8 %) changed classification regarding indication for ablation using ATA 2015 versus ATA 2009. Most reclassified patients (70/100) moved from "no indication" or "clear indication" to "possible indication." Reflecting this phenomenon, "possible indication" became the largest category according to the ATA 2015 classification (141/336, 42.0 %, versus 96/336, 28.6 %, according to ATA 2009). Many reclassifications were attributable to multiple clinicopathological characteristics, most commonly, stimulated thyroglobulin or anti-thyroglobulin antibody levels, multifocality, bilateral involvement, or capsular/nodal invasion. CONCLUSIONS: Regarding indications for ablation, ATA 2015 appears to better "acknowledge grey areas," i.e., patients with ambiguous or unavailable data requiring individualised, nuanced decision-making, than does ATA 2009.
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Medicina Nuclear/normas , Guías de Práctica Clínica como Asunto , Radioterapia/normas , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Tiroidectomía/normas , Adulto , Terapia Combinada/métodos , Femenino , Grecia , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Factores de Riesgo , Neoplasias de la Tiroides/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Most publications to date compare outcomes after post-surgical thyroid remnant ablation stimulated by recombinant human thyrotropin (rhTSH) versus thyroid hormone withholding/withdrawal (THW) in low-recurrence risk differentiated thyroid carcinoma (DTC) patients. We sought to perform this comparison in high-risk patients. METHODS: We retrospectively analyzed ~9-year single-center experience in 70 consecutive adults with initial UICC (Union for International Cancer Control) stage III/IV, M0 DTC undergoing rhTSH-aided (N.=54) or THW-aided (N.=16) high-activity ablation. Endpoints included ablation success and DTC outcome. Assessed ≥1 year post-ablation, ablation success comprised a) no visible scintigraphic thyroid bed uptake or pathological extra-thyroidal uptake; b) undetectable stimulated serum thyroglobulin (Tg) without interfering autoantibodies; c) both criteria. DTC outcome, determined at the latest visit, comprised either 1) "no evidence of disease" (NED): undetectable Tg, negative Tg autoantibodies, negative most recent whole-body scan, no suspicious findings clinically, on neck ultrasonography, or on other imaging; 2) persistent disease: failure to attain NED; or 3) recurrence: loss of NED. RESULTS: After the first ablative activity, ablation success by scintigraphic plus biochemical criteria was 64.8% in rhTSH patients, 56.3% in THW patients (P=NS). After 3.5-year versus 6.2-year median follow-up (P<0.05), DTC outcomes were NED, 85.2%, persistent disease, 13.0%, recurrence, 1.9%, in the rhTSH group and NED, 87.5%, persistent or recurrent disease, 6.3% each, in the THW group (P=NS). CONCLUSION: In patients with initial stage III/IV, M0 DTC, rhTSH-aided and THW-assisted ablation were associated with comparable remnant eradication or DTC cure rates.
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Técnicas de Ablación/métodos , Proteínas Recombinantes/farmacología , Glándula Tiroides/efectos de los fármacos , Hormonas Tiroideas/metabolismo , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Tirotropina/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Determinación de Punto Final , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Neoplasias de la Tiroides/metabolismo , Tirotropina/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: We determined the reasons for radioiodine thyroid remnant ablation, and the procedure's necessity based on postsurgical remnant size, in patients with putatively "low-intermediate-risk" differentiated thyroid carcinoma (DTC). We identified key clinicopathological, treatment and remnant characteristics, and factors associated with remnant size in 336 patients with pT1/2, M0 DTC ablated during the period September 2010 to October 2013 at one Cypriot or one Greek referral centre. METHODS: Clinicopathological/treatment characteristics were compiled from charts. Experienced nuclear medicine physicians rated the numbers/intensities of uptake foci in the thyroid bed on postablation planar scintigrams using scales of 0-4 points and 0-3 points, respectively. The product of these scores was taken as the "remnant score" that ranged from 0 (no remnant) to 12 (multiple remnants, intense uptake). RESULTS: DTC was predominantly papillary. The median [25th-75th percentile] longest primary tumour diameter was 1.0 cm [0.7-1.5 cm]. Despite favourable histotypes and primary tumour classifications, patients often had preablation characteristics suggesting elevated or uncertain risk: 31.0% of patients (104 of 336) had primary tumour multifocality, 22.0% (74) had confirmed cervical lymph node metastases, 37.2% (125) had unknown nodal status, and 38.1% (128) had antithyroglobulin antibody seropositivity. The median [25th-75th percentile] remnant score was 4 [2-6]; 39.9% of patients (134 of 336) had scores ≥6. For the entire cohort, T or N stages (r ≤ 0.174, P ≤ 0.05) correlated positively with the remnant score in a univariate Spearman analysis. The numbers of patients referred by the surgeon, cervical lymph nodes excised and metastatic nodes excised correlated negatively (r ≤ 0.243, P ≤ 0.038) with the remnant score, and the first two factors independently predicted the remnant score (P ≤ 0.037) in a multivariate analysis. CONCLUSION: Patients with putatively "low-intermediate-risk" DTC frequently had disease characteristics denoting high or uncertain risk, suggesting that "selective" radioiodine ablation in such patients may seldom be applicable outside international centres of excellence. Proxies for surgeon experience and surgical completeness correlated with remnant number/uptake intensity and may aid ablation-related decision-making.
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Guías como Asunto , Radioisótopos de Yodo/uso terapéutico , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/radioterapia , Técnicas de Ablación/efectos adversos , Adulto , Toma de Decisiones , Femenino , Humanos , Radioisótopos de Yodo/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Garantía de la Calidad de Atención de Salud , Radiofármacos/efectos adversos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugíaRESUMEN
Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.
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Adrenomedulina/sangre , Precursores de Proteínas/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Animales , Biomarcadores/sangre , Humanos , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Medición de RiesgoRESUMEN
Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.
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Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Adrenomedulina/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Calcitonina/sangre , Disnea/clasificación , Disnea/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Precursores de Proteínas/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Medición de Riesgo , Fumar/epidemiología , Suiza/epidemiologíaRESUMEN
BACKGROUND/OBJECTIVES: We sought to determine whether exclusion of infection and antibiotic stewardship with the infection biomarker procalcitonin improves outcomes in congestive heart failure (CHF) patients presenting to emergency departments with respiratory symptoms and suspicion of respiratory infection. METHODS: We performed a secondary analysis of patients with a past medical history of CHF formerly included in a Swiss multicenter randomized-controlled trial. The trial compared antibiotic stewardship according to a procalcitonin algorithm or state-of-the-art guidelines (controls). The primary endpoint was a 30-day adverse outcome (death, intensive care unit admission); the secondary endpoints included a 30-day antibiotic exposure. RESULTS: In the 110/233 analyzed patients (47.2%) with low initial procalcitonin (<0.25 µg/L), suggesting the absence of systemic bacterial infection, those randomized to procalcitonin guidance (n=50) had a significantly lower adverse outcome rate compared to controls (n=60): 4% vs. 20% (absolute difference -16.0%, 95% confidence interval (CI) -28.4% to -3.6%, P=0.01), and significantly reduced antibiotic exposure [days] (mean 3.7 ± 4.0 vs. 6.5 ± 4.4, difference -2.8 [95% CI, -4.4 to -1.2], P<0.01). When initial procalcitonin was ≥0.25 µg/L, procalcitonin-guided patients had significantly reduced antibiotic exposure due to early stop of therapy without any difference in adverse outcomes (25.8% vs. 24.6%, difference [95% CI] 1.2% [-14.5% to 16.9%, P=0.88]). CONCLUSIONS: CHF patients presenting to the emergency department with respiratory symptoms and suspicion for respiratory infection had decreased antibiotic exposure and improved outcomes when procalcitonin measurement was used to exclude bacterial infection and guide antibiotic treatment. These data provide further evidence for the potential harmful effects of antibiotic / fluid treatment when used instead of diuretics and heart failure medication in clinically symptomatic CHF patients without underlying infection.
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Calcitonina/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/epidemiología , Precursores de Proteínas/sangre , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/epidemiología , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Biomarcadores/sangre , Péptido Relacionado con Gen de Calcitonina , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Suiza/epidemiología , Resultado del TratamientoAsunto(s)
Fluorodesoxiglucosa F18/farmacocinética , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/secundario , Octreótido/análogos & derivados , Compuestos Organometálicos/farmacocinética , Neoplasias Pancreáticas/patología , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Femenino , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Persona de Mediana Edad , Tumores Neuroendocrinos/irrigación sanguínea , Octreótido/farmacocinética , Valor Predictivo de las PruebasRESUMEN
PURPOSE OF THE REPORT: The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. PATIENTS AND METHODS: Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of "hot spots" with/without central photopenia and "cold spots" detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. RESULTS: 124I-PET detected significantly more "hot spots" with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more "cold spots" than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). CONCLUSIONS: 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.
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Pertecnetato de Sodio Tc 99m , Glándula Tiroides/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Adulto , Anciano , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Tomografía de Emisión de Positrones , Glándula Tiroides/patología , UltrasonografíaRESUMEN
CONTEXT: After severe reactor emergencies with release of radioactive iodine, elevated thyroid cancer risk in children and adolescents is considered the main health consequence for the population exposed. DESIGN: We studied thyroid cancer outcome after 11.3 years' median follow-up in a selected, very high-risk cohort, 234 Chernobyl-exposed Belarusian children and adolescents undergoing postsurgical radioiodine therapy (RIT) in Germany. INTERVENTIONS: Cumulatively 100 children with or (without; n = 134) distant metastasis received a median 4 (2) RITs and 16.9 (6.6) GBq, corresponding to 368 (141) MBq/kg iodine-131. MAIN OUTCOME MEASURES: Outcomes were response to therapy and disease status, mortality, and treatment toxicity. RESULTS: Of 229 patients evaluable for outcome, 147 (64.2%) attained complete remission [negative iodine-131 whole-body scan and TSH-stimulated serum thyroglobulin (Tg) < 1 µg /L], 69 (30.1%) showed nearly complete remission (complete response, except stimulated Tg 1-10 µg/L), and 11 (4.8%) had partial remission (Tg > 10 µg/L, decrease from baseline in radioiodine uptake intensity in ≥ 1 focus, in tumor volume or in Tg). Except for 2 recurrences (0.9%) after partial remission, no recurrences, progression, or disease-specific mortality were noted. One patient died of lung fibrosis 17.5 years after therapy, 2 of apparently thyroid cancer-unrelated causes. The only RIT side effect observed was pulmonary fibrosis in 5 of 69 patients (7.2%) with disseminated lung metastases undergoing intensive pulmonary surveillance. CONCLUSIONS: Experience of a large, very high-risk pediatric cohort with radiation-induced differentiated thyroid carcinoma suggests that even when such disease is advanced and initially suboptimally treated, response to subsequent RIT and final outcomes are mostly favorable.
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Carcinoma/radioterapia , Accidente Nuclear de Chernóbil , Radioisótopos de Yodo/uso terapéutico , Neoplasias Inducidas por Radiación/radioterapia , Radiofármacos/uso terapéutico , Glándula Tiroides/efectos de la radiación , Neoplasias de la Tiroides/radioterapia , Adolescente , Carcinoma/epidemiología , Carcinoma/cirugía , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Radioisótopos de Yodo/efectos adversos , Masculino , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/cirugía , Radiofármacos/efectos adversos , Inducción de Remisión , República de Belarús/epidemiología , Riesgo , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/cirugíaRESUMEN
UNLABELLED: In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. METHODS: Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. RESULTS: All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. CONCLUSION: This pilot study provided proof of principle that our simplified ED (18)F-FDG PET/CT protocol includes endpoints that effectively detect HCC hypervascularization; this finding suggests that the protocol can be used routinely.