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In the workup of follicular lymphoma (FL), bone marrow biopsy (BMB) assessment is a key component of FLIPI and FLIPI2, the most widely used outcome scores. During the previous decade, several studies explored the role of FDG-PET/CT for detecting nodal and extranodal disease, with only one large study comparing both techniques.The aim of our study was to evaluate the diagnostic accuracy and the prognostic impact of both procedures in a retrospective cohort of 299 FL patients with both tests performed at diagnosis. In order to avoid a collinearity bias, FLIPI2 was deconstructed in its founding parameters, and the bone marrow involvement (BMI) parameter separately included as: a positive BMB, a positive PET/CT, the combined "PET/CT and BMB positive" or "PET/CT or BMB positive". These variables were also confronted independently with the POD24 in 233 patients treated with intensive regimens.In the total cohort, bone marrow was involved in 124 and 60 patients by BMB and PET/CT, respectively. In terms of overall survival, age 60 y.o. and the combined "PET/CT or BMB positive" achieved statistical independence as a prognostic factor. In patients treated with an intensive regimen, only the combined "PET/CT or BMB positive" added prognostic value for a shorter overall survival, when confronted with the POD24.Our results show that in FL both BMB and PET/CT should be considered at diagnosis, as their combined assessment provides independent prognostic value in the context of the most widely use clinical scores.

Purpose: Although metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have shown good prognostic value in head and neck cancer (HNC), there are still many issues to resolve before their potential application in standard clinical practice. The purpose of this study was to compare the discrimination ability of two relevant segmentation methods in HNC and to evaluate the potential benefit of adding lymph nodes’ metabolism (LNM) to the measurements. Methods: We retrospectively analyzed a recently published database of 62 patients with HNC treated with chemoradiotherapy. MTV and TLG were measured using an absolute threshold of SUV2.5. Comparison analysis with previously published background-level threshold (BLT) results was done through Concordance index (C-index) in eight prognostic models. Results: BLT obtained better C-index values in five out of the eight models. The addition of LNM improved C-index values in six of the prognostic models. Conclusion: We found a potential benefit in adding LNM to the main tumor measurements, as well as in using a BLT for MTV segmentation compared to the most commonly used SUV2.5 threshold. Despite its limitations, this study suggests a practical and simple manner to use these parameters in standard clinical practice, aiming to help elaborate a general consensus, Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

After recent observations that intrathecal administration of autologous bone marrow mesenchymal stromal cells (MSCs) increases cerebral metabolism in patients with severe traumatic brain injury (TBI), we examined this type of cell therapy in Alzheimer's type dementia. Three patients with clinical diagnosis of Alzheimer's disease received every 3 months 100million autologous MSCs by intrathecal route, until a total dose of 300million. During cell therapy the patients showed arrest in neurological deterioration and two of them manifested clear improvement of previous symptoms. A global increase in cerebral glucose metabolism, measured using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), was observed after every administration of cell therapy. Our present findings suggest that intrathecal administrations of autologous MSCs can be a new strategy for the treatment of Alzheimer's dementia, We thank the institutions supporting the development of our cell therapy program, in particular Mapfre and Rafael del Pino Foundations

Background: Validated biomarkers in head and neck squamous cell carcinoma (HNSCC) are scarce. Methods: We retrospectively analyzed 62 patients with HNSCC treated with radiotherapy +/− concurrent chemotherapy. Pretreatment metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured in a 18F-FDG positron emission tomography using a liver dependent standardized uptake value threshold. Cox regression analyses were performed to find associations with disease-free survival (DFS) and overall survival (OS). Results: High values of MTV (>37 ml) were independently associated with a worse DFS (hazard ratio [HR] = 3.45; 95% confidence interval [CI], 1.52–7.84) and OS (HR = 3.27; 95% CI, 1.41–7.57). Similar results were found for high values of TLG (>247 g) for DFS (HR = 3.32; 95% CI, 1.44–7.65) and OS (HR = 3.42; 95% CI, 1.45–8.07). Conclusions: MTV and TLG can be considered as independent prognostic factors for DFS and OS in patients with HNSCC. Considering how easily obtainable they are, they may be useful for predicting clinical outcomes in these patients

Background: We had previously reported that the administration of autologous stromal cells (ASCs) therapy to two patients with mild AD dementia led to a global increase in cerebral glucose metabolism which was accompanied by significant improvement of visual short-term memory binding (VSTMB), a function known to be a marker of AD. We suggested that intrathecal administration of autologous ASCs could be considered a new therapeutic strategy for AD dementia (Vaquero et al., 2019). We were interested in investigating the post-intervention durability of such cognitive improvements. Methods: We studied two AD patients with cerebral beta-amyloid neuritic plaques detected with 18FFDG-PET. The patients received every three months 100 million of ASCs by intrathecal route, until a total dose of 300 million. None received any other medication for its disease at the time of receiving cell therapy. Clinical and neuroimaging studies were performed previous and after the therapy, including brain glucose metabolism by 18F-FDG-PET and assessment with the visual short-term memory binding task (VSTMBT). This task has been proposed as a preclinical marker of AD. It requires subjects to detect whether or not two combinations of shape and colour change across two sequential arrays. Here we report on the assessment of these patients one year after the therapy. We compared them with 4 AD patients who did no undergo stem cell therapy. Results: Single case statistics revealed that benefits drawn by treated patients from the therapy remained a year after. Using a more taxing version of the VSTMB test (memory load of 3 items) we observed that, after the therapy, the chance that an untreated AD patient would show more impairment was 75.45% (p= 0.24) for Case 1 and 89.23% (p=0.11) for case 2. This chance remained after 1 year post-treatment for Case 1 (75.45%, p=0.24) and increased for Case 2 (96.89%, p=0.031). Conclusion: Improvements of memory functions known to be marker for AD in patients who underwent stem cell therapy remained stable after one year post-intervention. This offers a new therapeutic strategy for AD.

Introduction To evaluate the utility of positron emission tomography-computed tomography (PET/CT) as an imaging tool for the characterization of immune-mediated inner ear disease (IMIED), providing measurements of the inner ear region activity as well as detecting possible involvement of other organs. Material and methods The study included 28 patients with IMIED and 4 sex-matched and age-matched control subjects with no history of ear disease. Eighteen patients were considered to be suffering from primary IMIED and 10 patients from secondary. PET/CT scans with 18F-FDG were performed to assess systemic involvement as well as inner ear region activity. Interpretation of PET/CT scans was performed independently by two nuclear medicine physicians blinded to clinical history. In order to assess inter-rater agreement before performing the analysis of the inner ear, different Bland & Altman plots and the intraclass correlation coefficients were estimated. Results Different metabolically active foci findings were reported in 13 patients. Four patients diagnosed as primary IMIED showed thyroid and aorta activity. Regarding the inner-ear semiquantitative analysis, the inter-rater agreement was not sufficiently high. Comparisons between groups, performed using Mann–Whitney test or Kruskal–Wallis tests, showed no differences. Conclusions The study showed 18F-FDG PET/CT could be an important tool in the evaluation of IMIED as it can support the characterization of this entity providing the diagnosis of unknown or underestimated secondary IMIED. Nevertheless, we consider PET is not an adequate tool to approach the inner ear because of the small size and volume of the cochlea which makes the assessment very difficult.

The role of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in head and neck cancer (HNC) prognosis is not well established. We conducted a systematic review focusing on MTV and TLG measured by 18 F-FDG positron-emission tomography in HNC. Meta-analyses were developed, estimating hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Eighteen studies were found with a total of 1512 patients. MTV-adjusted analysis had an HR of 4.65 (95% CI = 2.04-10.6) for DFS and 3.89 (95% CI = 1.47-10.30) for OS. TLG-unadjusted analysis had an HR of 3.19 (95% CI = 2.33-4.37) for DFS and 2.48 (95% CI = 1.82-3.39) for OS. TLG-adjusted analysis for DFS obtained an HR of 2.05 (95% CI = 0.96-4.39). MTV and TLG are good prognostic factors in HNC, as high values predict a worse OS and DFS. Given the important information they provide, these parameters may be considered in clinical practice, as they are easily obtainable with current technology.

Therapy response assessment is one of the most challenging indications of imaging studies. In clinical trial patients is usually measured with standardized response criteria. However, in the clinical practice, many studies are carried out in which the clinical question is whether or not the treatment is being effective. Answering this question is one of the greatest challenges for diagnostic imaging physicians, especially when a new treatment modality is being introduced, whose effects on tumoral lesions are firstly poorly understood. We have an essential role in the introduction of new therapies, assessing their effects and benefits. The knowledge of these effects has led to the development of many response criteria that, despite being applicable only in clinical trials, offer us information on how to interpret the findings in clinical practice.

Background aims Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs). Methods Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 10 6 (one patient), 100 × 10 6 (one patient) and 300 × 10 6 (one patient). Results All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism. Conclusion Our present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias.

Background aims Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need. Methods We present a phase 2 clinical trial in patients with chronic SCI who received three intrathecal administrations of 100 x 106 MSCs and were followed for 10 months from the first administration. Efficacy analysis was performed on nine patients, and safety analysis was performed on 11 patients. Clinical scales, urodynamic, neurophysiological and neuroimaging studies were performed previous to treatment and at the end of the follow-up. Results The treatment was well-tolerated, without any adverse event related to MSC administration. Patients showed variable clinical improvement in sensitivity, motor power, spasms, spasticity, neuropathic pain, sexual function or sphincter dysfunction, regardless of the level or degree of injury, age or time elapsed from the SCI. In the course of follow-up three patients, initially classified as ASIA A, B and C, changed to ASIA B, C and D, respectively. In urodynamic studies, at the end of follow-up, 66.6% of the patients showed decrease in postmicturition residue and improvement in bladder compliance. At this time, neurophysiological studies showed that 55.5% of patients improved in somatosensory or motor-evoked potentials, and that 44.4% of patients improved in voluntary muscle contraction together with infralesional active muscle reinnervation. Conclusions The present guideline for cell therapy is safe and shows efficacy in patients with SCI, mainly in recovery of sphincter dysfunction, neuropathic pain and sensitivity.

Background: A decrease in brain glucose metabolism in Alzheimer’s disease (AD) patients is considered a critical driver of cognitive impairment, and medications used in AD target this metabolic dysfunction. Recent evidence has shown a significant increase in glucose metabolism associated with neurocognitive improvement after intrathecal administration of bone marrow mesenchymal stromal cells (MSCs) in patients suffering from severe TBI or haemorrhagic stroke. We hypothesise that this cell therapy could also be useful in AD patients. Methods: We studied two AD patients with cerebral beta-amyloid neuritic plaques detected with 18FFDG-PET. The patients received every three months 100 million of autologous MSCs by intrathecal route, until a total dose of 300 million. None received any other medication for its disease at the time of receiving cell therapy. Clinical and neuroimaging studies were performed previous and after the therapy, including brain glucose metabolism by 18F-FDG-PET and assessment with the visual short-term memory binding task (VSTMBT). This task has been proposed as a preclinical marker of AD. It requires subjects to detect whether or not two combinations of shape and colour change across two sequential arrays. Results: A global increase in cerebral glucose metabolism was observed after each administration of cell therapy. Single case statistics revealed that treated and untreated patients did not differ on their pre-treatment VSTMBT scores and both were significantly impaired relative to controls. The chance that an untreated AD patient would show more impairment than treated patients was 39.25% (p= 0.785) for case 1, and 50.00% (p=1.0) for case 2. This chance increased post-treatment to 97.40% (p=0.05) and 99.74% (p=0.005) respectively. Conclusion: These preliminary findings suggest that intrathecal administration of autologous MSCs should be considered as a new therapeutic strategy for Alzheimer’s dementia and deserves further studies.

Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B‐cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R‐CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow‐up of 25 months the estimated 3‐year progression‐free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB‐BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2‐microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first‐line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS.

Main ObjectivePatients with locally advanced cervical cancer (LACC) are usually treated with concurrent chemoradiotherapy. Extended-field chemoradiotherapy is indicated in cases of paraaortic nodal spread. Nowadays, 18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is considered to be the most accurate image method of detection of node or distant metastases. The goal of this study was to evaluate the accuracy of FDG-PET for detecting paraaortic lymph node (PALN) spread in patients with LACC.MethodsPatients with LACC from 2 tertiary university hospitals in Madrid, Spain, were submitted to a laparoscopic infrarenal PALN dissection after FDG-PET evaluation. Based on pathologic results as gold standard, sensitivity, specificity, and positive and negative predictive values of FDG-PET were calculated thereafter for PALN metastasis.ResultsA total of 52 patients with LACC fulfilled the inclusion criteria. All of them underwent a laparoscopic infrarenal paraaortic lymphadenectomy. Eighteen patients (34.6%) had pathologically proven PALN metastases. Among them, 4 (12.5%) had negative FDG-PET (false negatives). Furthermore, 2 positive FDG-PET patients were not affected after histologic analysis (11.1% false positives). No complications occurred in our series. Sensitivity, specificity, and positive and negative predictive value of the FDG-PET were 77.7, 94.1, 87.5, and 88.9, respectively, for the detection of PALN metastases.ConclusionsThe sensitivity and specificity of FDG-PET remains limited, so PALN dissection should be part of the pretherapeutic staging in every patient with LACC before definitive concurrent chemoradiotherapy.

La PET ha demostrado su utilidad en la toma de decisiones diagnóstico-terapéuticas en diversos tipos de tumores. En los tumores del tracto urinario y del cáncer de próstata su rendimiento diagnóstico ha sido menor debido a la eliminación urinaria del radiotrazador que puede enmascarar la presencia de lesiones. No obstante, deben aplicarse protocolos específicos que mejoran el rendimiento diagnóstico de la PET con 18F-FDG en la valoración de lesiones pélvicas. Además, el cáncer de próstata es un tumor de bajo grado con escasa avidez por la 18F-FDG. A pesar de estas limitaciones, con la PET se han planteado nuevas e interesantes posibilidades diagnósticas. La disponibilidad de equipos PET-TAC ha mejorado su rendimiento diagnóstico. Por otra parte, el desarrollo de nuevos radiotrazadores que permiten marcar otros procesos moleculares y que son metabolizados por vías diferentes de la urinaria, supone una ventaja importante respecto a la 18F-FDG y han proporcionado resultados interesantes. PET has demonstrated its utility in management decisions in several types of tumors. In urologic tract tumors and prostate cancer its diagnostic performance has been lower due to the urinary excretion of the radiotracer, which can mask the presence of lesions. However, specific protocols must be applied that improve the diagnostic performance of PET with 18F-FDG in the evaluation of pelvic lesions. Furthermore, prostate cancer is a low-grade tumor with low avidity for 18F-FDG. In spite of these limitations, with PET new and interesting possibilities have been presented. The availability of PET-CT systems has improved its diagnostic performance. On the other hand, the development of new radiotracers that allow targeting other molecular processes and that are metabolized by pathways different to the urinary tract signifies an important advantage compared to 18F-FDG and has evidenced interesting results.

Introduction The prognosis of patients with cutaneous melanoma is greatly influenced by the presence of lymph node metastases. One of the most innovative and fascinating concepts to emerge in the field of oncology in recent years is the use of sentinel lymph node biopsy (SLNB). Aim The aim of this study was to determine what SPECT-CT images contribute to the search for sentinel nodes in patients with melanoma. Methods From March 2007 to October 2008, 18 patients were examined for sentinel nodes using dynamic scintigraphy, planar images, and SPECT-CT in the Nuclear Medicine Department of San Carlos University Hospital. The group contained 10 women and 8 men, age range 14-83 years, mean age 57 years (57±20.1). Results The sentinel node was located by conventional imaging techniques (dynamic scintigraphy and planar images) in 16 of 18 patients (88.88%). SPECT-CT identified the sentinel node in 18 of 18 patients (100%) and detected clinically relevant findings in 6 of 18 patients (33.33%) Conclusions SPECT-CT imaging contributed clinically relevant information on sentinel nodes of melanoma, which is particularly important in patients with melanoma of the trunk or head and neck.