Implications of the Harmonization of [18F]FDG-PET/CT Imaging for Response Assessment of Treatment in Radiotherapy Planning.

The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.

Central nervous system involvement in adult-onset relapsing hemophagocytic lymphohistiocytosis responsive to maintenance treatment with anakinra.

A 43 year-old male presented with a relapsing and progressive systemic inflammatory disorder with central nervous system (CNS) involvement. After a two years follow up, he was diagnosed with hemophagocytic lymphohistiocytosis (HLH), based on clinical, laboratory and radiological findings. Treatment was started with anakinra, a recombinant humanised interleukin-1 (IL-1) receptor antagonist. Clinical response was good. Laboratory and radiological findings showed no disease activity throughout a five years follow-up period. Several immunosuppressive agents have been used in HLH without any good outcomes. This is the first case report of HLH with CNS involvement responsive to chronic treatment with anakinra.

Thyroid Metastasis From Cutaneous Melanoma on an 18F-FDG PET/CT Study.

The thyroid gland is an uncommon location for metastasis. We report a 59-year-old woman with a history of cutaneous malignant melanoma. A unique hypermetabolic mass on the left thyroid lobe was identified by control F-FDG PET/CT scan, leading to dysphagia and stridor clinic. Total thyroidectomy and lymphadenectomy were performed with histopathological results concordant with metastasis from melanoma. Despite its rarity, finding focal thyroid lesions in patients with an oncological history should alert us, recommending that its metastatic etiology be ruled out.

Pneumonitis Related to Melanoma Immunotherapy.

Several regimens of immunotherapy have recently proven successful for multiple cancers, due to increased survival and quality of life. Rarely, immunotherapy with anti-programmed cell death protein 1 and programmed death-ligand 1 antibodies across cancer may cause immune-related pulmonary toxicity, with a low overall incidence, being particularly low among patients with melanoma and highest among individuals with lung cancer. In this vein, pulmonary toxicity is staged at 4 degrees according to the severity of the clinic and radiological findings, and its management is based on suppression of immunotherapy and administration of glucocorticoids. We report a case of pulmonary toxicity related to melanoma immunotherapy observed by F-FDG PET/CT.

Accurate, robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy.

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.

Association of 18F-FDG PET or PET/CT results with spontaneous remission in classic fever of unknown origin: A systematic review and meta-analysis.

BACKGROUND: Spontaneous remission is common in patients with undiagnosed classic fever of unknown origin (FUO). Although identifying reliable predictors of spontaneous remission in such diagnostically challenging cases could improve their management strategies, few studies have assessed such clinical factors. Recently, studies have reported that F-fluorodeoxyglucose positron emission tomography (F-FDG PET) alone and integrated with computed tomography (PET/CT) were useful in localizing the source of FUO. In this systematic review and meta-analysis, we assessed the association of results of these imaging modalities with spontaneous remission in patients with classic FUO. METHODS: We searched PubMed and Scopus from inception until June 30, 2018, and studies that evaluated the PET or PET/CT results of ≥10 adult or adolescent patients with classic FUO who were followed up for at least 3 months were included. At least 2 investigators extracted data and rated quality using the QUIPS-2 tool. We used a random-effects meta-analysis to calculate summary risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Nine studies of PET/CT results (418 patients) and 4 studies of standalone PET results (128 patients) were eligible. None explicitly specified the incidence of spontaneous remission as the primary or secondary outcomes of interest. The risk of bias was considered high in all studies because patients received subsequent diagnostic workup based on imaging results. Patients with negative PET/CT results were significantly more likely to present with spontaneous regression than those with positive results (summary RR = 5.6; 95% CI: 3.4-9.2; P < .001; I = 0%). In contrast, no significant association was found between standalone PET results and spontaneous remission. The random-effects study-level meta-regression found that PET/CT results [relative RR (rRR) = 7.4; 95% CI: 2.5-21.3; P = .002], compared with standalone PET results, and publication year (rRR = 1.2 per 1 year; 95% CI: 1.0-1.3; P = .013) were significantly associated with spontaneous remission. CONCLUSION: Limited data suggest that undiagnosed classic FUO patients with negative PET/CT results had a high likelihood of spontaneous remission after a series of unsuccessful investigations for fever workup. Prospective studies should validate these results.

Virchow Node From Prostate Carcinoma by 18F-Choline PET/CT.

F-choline PET/CT is increasingly being used during the follow-up of prostate cancer and is bringing us valuable information for the delineation of local and distant nodal recurrence in patients with hormone-resistant poorly differentiated cell types. Lymphatic spreading usually involves pelvic and retroperitoneal levels, being unusual at supraclavicular levels. We report a 75-year-old man with unsuspected involvement of Virchow node from prostate cancer observed using F-choline PET/CT.

Esophageal Cancer Diagnosed by Thyroid Scintigraphy.

We report a 34-year-old man referred because of increasing dysphagia secondary to goiter. Thyroid scintigraphy and SPECT/CT images helped to recognize an unsuspected esophageal dilation due to a poorly differentiated adenocarcinoma arising at the lower end of the esophagus. Further examinations are mandatory when abnormal activities are observed during thyroid scintigraphy.

Intrathoracic stomach mimicking bone metastasis from thyroid cancer in whole-body iodine-131 scan diagnosed by SPECT/CT.

The whole-body iodine-131 scintigraphy is an imaging technique in monitoring patients with a history of thyroid cancer. Although the rate of false positives is negligible, it is not nonexistent. We report the case of an intervened and treated patient for thyroid cancer with good clinical and biochemical response. Scintigraphic findings were consistent with unsuspected bone metastasis. Fused SPECT/CT data allowed accurate diagnosis of giant diaphragmatic hernia associated with intrathoracic stomach, a very rare pathology that can lead to false positive results.

Kummel's disease

Kummel's disease is a crush fracture of a vertebral body caused by a minor trauma, with the most accepted etiology being avascular necrosis. It is more frequent in individuals with risk factors such as osteoporosis or prolonged treatment with corticosteroids. Initially, it usually has normal radiological tests and an asymptomatic period, followed by a progressive onset of pain along with probable kyphosis and a sign of void or fluid abscess on radiological tests, which may create nerve/spinal involvement. The case is presented of a 76-year-old man, who was admitted to this center for the differential diagnosis of a single vertebral lesion. After imaging tests and biopsy, the definitive diagnosis of Kummel's disease was reached. The confirmatory diagnosis was reached by vertebral biopsy, but given its invasive nature, imaging techniques can play a significant role. As regards metabolic imaging tests, bone scintigraphy has shown to be one of the most sensitive tools to detect ischemia in earlier stages or to determine if it affects other locations. The whole body scan with diphosphonates shows an increase in activity in relation to bone remodeling activity in this condition. The 3-phase study makes it possible to differentiate whether it is an acute/subacute or chronic process, and can influence the therapeutic decision. Knowledge of this disease is important to make a differential diagnosis with tumour or infectious pathology, with emphasis on performing imaging tests in the event of persistent pain with a normal initial plaque.

La enfermedad de Kummel es una fractura-aplastamiento de un cuerpo vertebral precedida por un traumatismo menor, cuya etiología más aceptada es la necrosis avascular. Es más frecuente en individuos con factores de riesgo como osteoporosis o tratamiento prolongado con corticoides. Inicialmente, suele presentar pruebas radiológicas normales y un periodo asintomático, con aparición progresiva del dolor junto a probable cifosis y signo del vacío o absceso líquido en las pruebas radiológicas, pudiendo llegar a crear compromiso nervioso/medular. Presentamos el caso de un varón de 76 arios que ingresa en nuestro centro para el diagnóstico diferencial de una lesión única vertebral; tras la realización de las pruebas de imagen y biopsia se llega al diagnóstico definitivo de enfermedad de Kummel. El diagnóstico de confirmación de esta enfermedad se alcanza mediante la biopsia vertebral, pero dada su naturaleza invasiva, las técnicas de imagen toman un papel relevante. En relación con las pruebas de imagen metabólicas, la gammagrafía ósea ha demostrado ser una de las herramientas más sensibles para detectar isquemia en fases más tempranas o para conocer si afecta a otras localizaciones. El rastreo corporal de cuerpo completo con difosfonatos muestra un aumento de actividad en relación con la actividad ósea remodelativa en este cuadro. El estudio de tres fases permite diferenciar si se trata de un proceso agudo/subagudo o crónico, lo que influye en la decisión terapéutica. Es importante el conocimiento de esta enfermedad para realizar diagnóstico diferencial con patología tumoral o infecciosa e insistir en la realización de pruebas de imagen ante la persistencia del dolor con una placa inicial normal.

Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

Parkinson's disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease.

The dual syndrome hypothesis for cognitive impairment in Parkinson's disease (PD) establishes a dichotomy between a frontrostriatal dopamine-mediated syndrome, which leads to executive deficits, and a posterior cortical syndrome, which leads to dementia. Certain genes have been linked to these syndromes although the exact contribution is still controversial. The study's objective was to investigate the role of APOE, MAPT, COMT, SNCA and GBA genes in the dual syndromes. We genotyped APOE (rs429358 and rs7412), MAPT (rs9468), COMT (rs4680) and SNCA (rs356219) risk polymorphisms and sequenced GBA in a cohort of 298 PD patients. The degree of dopaminergic depletion was investigated with [123I]FP-CIT SPECTs and the presence of dementia was ascertained with a long-term review based on established criteria. The association between genetic and imaging parameters was studied with linear regression, and the relationship with dementia onset with Cox regression. We found that APOE2 allele (Pput = 0.002; Pcau = 0.01), the minor allele 'G' in SNCA polymorphism (Pput = 0.02; Pcau = 0.006) and GBA deleterious variants in (Pput = 0.01; Pcau = 0.001) had a detrimental effect on striatal [123I]FP-CIT uptake in PD. Conversely, Met/Met carriers in COMT polymorphism had increased caudate uptake (Pcau = 0.03). The development of dementia was influenced by APOE4 allele (HR = 1.90; P = 0.03) and GBA deleterious variants (HR = 2.44; P = 0.01). Finally, we observed no role of MAPT locus in any of the syndromes. As a conclusion, APOE2, SNCA, COMT and GBA influence frontostriatal dysfunction whereas APOE4 and GBA influence the development of dementia, suggesting a double-edged role of GBA. The dichotomy of the dual syndromes may be driven by a broad dichotomy in these genetic factors.

[Usefulness of (18)FDG PET-CT scan as a diagnostic tool of fever of unknown origin]. / Utilidad de la tomografía por emisión de positrones con (18)F-Fluorodesoxiglucosa combinada con tomografía computarizada en la orientación diagnóstica de la fiebre de origen desconocido.

BACKGROUND AND OBJECTIVE: Classic fever of unknown origin (FUO) is defined as the presence of fever greater than 38.3°C of at least 3 weeks with an uncertain diagnosis. Identification of the etiology is crucial in guiding further diagnostic procedures and subsequent patient management. The aim of this study was to evaluate the role of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography combined with computed tomography (PET/CT) in the diagnostic orientation of FUO. MATERIAL AND METHOD: An observational retrospective study was performed, including 30 consecutive patients who had been studied between March 2010 and September 2013. Twenty-six out of 30 patients (86.67%) had a definitive diagnosis after pathologic confirmation in 15 cases, microbiological findings in one patient and clinical and radiological follow-up in 10 patients (mean: 16.38 months). RESULTS: Among the positive scans, malignancy (n=10), inflammatory (n=8), infectious (n=4) and miscellaneous causes (n=1) were identified. (18)F-FDG PET/CT had a diagnostic accuracy of 90.00%, sensitivity of 88.46% (95% confidence interval [95% CI] 76-101), specificity of 100.00% (95% CI 100-100), positive predictive values of 100.00% (95% CI100-100) and negative predictive value of 57.14% (95% CI 20-91). CONCLUSIONS: (18)F-FDG PET/CT provided useful for the etiologic diagnosis of FUO, with high sensitivity and specificity. (18)F-FDG PET/CT has an incremental morphological and functional value, especially indicating the best biopsy site.