FOLFIRI in advanced platinum-resistant/refractory small-cell lung cancer: a retrospective study.

BACKGROUND: Small-cell lung cancer (SCLC) accounts for approximately 15% of lung cancer and is associated with poor prognosis. In platinum-refractory or -resistant SCLC patients, few treatment options are available. Topotecan is one of the standards of care for these patients, however, due to its high toxicity, several different approaches are employed. FOLFIRI (folinate, 5-fluorouracil and irinotecan) is a chemotherapy regimen used in digestive neuroendocrine carcinoma, which shares pathological similarities with SCLC. In this retrospective study, we evaluated the efficacy and safety of FOLFIRI in patients with platinum-resistant/refractory SCLC. METHODS: Medical records from all consecutive SCLC patients treated with FOLFIRI in a French University Hospital from 2013 to 2021 were analyzed retrospectively. The primary endpoint was the objective response rate according to RECIST v1.1 or EORTC criteria (ORR); secondary endpoints included duration of response, disease control rate, progression-free survival (PFS), overall survival (OS) and safety profile. RESULTS: Thirty-four patients with metastatic platinum-resistant (n = 14) or -refractory (n = 20) SCLC were included. Twenty-eight were evaluable for response, with a partial response observed in 5 patients for an overall ORR in the evaluable population of 17.9% (5/28) and 14.7% (5/34) in the overall population. The disease control rate was 50% (14/28) in the evaluable population. The median PFS and OS were 2.8 months (95%CI, 2.0-5.2 months) and 5.3 months (95%CI, 3.5-8.9 months), respectively. All patients were included in the safety analysis. Grade 3 or 4 adverse events occurred in 13 (38.2%) patients. The most common grade 3 or 4 adverse events were asthenia, neutropenia, thrombopenia and diarrhea. There was no adverse event leading to discontinuation or death. CONCLUSION: FOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response and had an acceptable safety profile. However, caution is needed in interpreting this result. FOLFIRI could represent a potential new treatment for platinum-resistant/refractory SCLC patients. Further prospective studies are needed to assess the benefits of this chemotherapy regimen.HIGHLIGHTSFOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response.FOLFIRI was well-tolerated in platinum resistant/refractory SLCL patients.FOLFIRI could represent a potential new treatment for SCLC, prospective studies are needed.

Brain Metabolic Alterations in Seropositive Autoimmune Encephalitis: An 18F-FDG PET Study.

INTRODUCTION: Autoimmune encephalitis (AE) diagnosis and follow-up remain challenging. Brain 18F-fluoro-deoxy-glucose positron emission tomography (FDG PET) has shown promising results in AE. Our aim was to investigate FDG PET alterations in AE, according to antibody subtype. METHODS: We retrospectively included patients with available FDG PET and seropositive AE diagnosed in our center between 2015 and 2020. Brain PET Z-score maps (relative to age matched controls) were analyzed, considering metabolic changes significant if |Z-score| ≥ 2. RESULTS: Forty-six patients were included (49.4 yrs [18; 81]): 13 with GAD autoantibodies, 11 with anti-LGI1, 9 with NMDAR, 5 with CASPR2, and 8 with other antibodies. Brain PET was abnormal in 98% of patients versus 53% for MRI. The most frequent abnormalities were medial temporal lobe (MTL) and/or striatum hypermetabolism (52% and 43% respectively), cortical hypometabolism (78%), and cerebellum abnormalities (70%). LGI1 AE tended to have more frequent MTL hypermetabolism. NMDAR AE was prone to widespread cortical hypometabolism. Fewer abnormalities were observed in GAD AE. Striatum hypermetabolism was more frequent in patients treated for less than 1 month (p = 0.014), suggesting a relation to disease activity. CONCLUSION: FDG PET could serve as an imaging biomarker for early diagnosis and follow-up in AE.

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort.

INTRODUCTION: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood. METHODS: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. RESULTS: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. DISCUSSION: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association. HIGHLIGHTS: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.

Ultra-low-dose in brain 18F-FDG PET/MRI in clinical settings.

We previously showed that the injected activity could be reduced to 1 MBq/kg without significantly degrading image quality for the exploration of neurocognitive disorders in 18F-FDG-PET/MRI. We now hypothesized that injected activity could be reduced ten-fold. We simulated a 18F-FDG-PET/MRI ultra-low-dose protocol (0.2 MBq/Kg, PETULD) and compared it to our reference protocol (2 MBq/Kg, PETSTD) in 50 patients with cognitive impairment. We tested the reproducibility between PETULD and PETSTD using SUVratios measurements. We also assessed the impact of PETULD for between-group comparisons and for visual analysis performed by three physicians. The intra-operator agreement between visual assessment of PETSTD and PETULD in patients with severe anomalies was substantial to almost perfect (kappa > 0.79). For patients with normal metabolism or moderate hypometabolism however, it was only moderate to substantial (kappa > 0.53). SUV ratios were strongly reproducible (SUVratio difference ± SD = 0.09 ± 0.08). Between-group comparisons yielded very similar results using either PETULD or PETSTD. 18F-FDG activity may be reduced to 0.2 MBq/Kg without compromising quantitative measurements. The visual interpretation was reproducible between ultra-low-dose and standard protocol for patients with severe hypometabolism, but less so for those with moderate hypometabolism. These results suggest that a low-dose protocol (1 MBq/Kg) should be preferred in the context of neurodegenerative disease diagnosis.

Radiation dose to nuclear medicine technologists when operating PET/MR compared with PET/CT.

Since 2010, positron emission tomography/magnetic resonance (PET/MR) has been increasingly used as clinical routine in nuclear medicine departments. One advantage of PET/MR over PET/computed tomography (CT) is the lower dose of ionising radiation delivered to patients. However, data on the radiation dose delivered to staff operating PET/MR compared with the new generation of PET/CT equipment are still lacking. Our aim was to compare the radiation dose to nuclear medicine technologists performing routine PET/MR and PET/CT in the same department. We retrospectively measured the daily radiation dose received by PET technologists over 13 months by collecting individual dosimetry measurements (from electronic personal dosimeters). Data were analysed taking into account the total number of studies performed with each PET modality (PET/MR with Signa 3T, General Electric Healthcare versus PET/CT with Biograph mCT flow, Siemens), the type of exploration (brain versus whole-body PET), the18F activity injected per day and per patient as well as the time spent in contact with patients after tracer injection. Our results show a significantly higher whole-body exposure to technologists for PET/MR compared with PET/CT (10.3 ± 3.5 nSv versus 4.7 ± 1.2 nSv per18F injected MBq, respectively;p< 0.05). This difference was related to prolonged contact with injected patients during patient positioning with the PET/MR device and MR coil placement, especially in whole-body studies. For an equal injected activity, radiation exposure to PET technologists for PET/MR was twice that of PET/CT. To minimise the radiation dose to staff, efforts should be made to optimise patient positioning, even in departments with extensive PET/CT experience.

Hybrid [18F]-F-DOPA PET/MRI Interpretation Criteria and Scores for Glioma Follow-up After Radiotherapy.

OBJECTIVE: 18F­fluoro-L­3,4­dihydroxyphenylalanine positron emission tomography (F­DOPA PET) is used in glioma follow-up after radiotherapy to discriminate treatment-related changes (TRC) from tumor progression (TP). We compared the performances of a combined PET and MRI analysis with F­DOPA current standard of interpretation. METHODS: We included 76 consecutive patients showing at least one gadolinium-enhanced lesion on the T1­w MRI sequence (T1G). Two nuclear medicine physicians blindly analyzed PET/MRI images. In addition to the conventional PET analysis, they looked for F­DOPA uptake(s) outside T1G-enhanced areas (T1G/PET), in the white matter (WM/PET), for T1G-enhanced lesion(s) without sufficiently concordant F­DOPA uptake (T1G+/PET), and F­DOPA uptake(s) away from hemorrhagic changes as shown with a susceptibility weighted imaging sequence (SWI/PET). We measured lesions' F­DOPA uptake ratio using healthy brain background (TBR) and striatum (T/S) as references, and lesions' perfusion with arterial spin labelling cerebral blood flow maps (rCBF). Scores were determined by logistic regression. RESULTS: 53 and 23 patients were diagnosed with TP and TRC, respectively. The accuracies were 74% for T/S, 76% for TBR, and 84% for rCBF, with best cut-off values of 1.3, 3.7 and 1.25, respectively. For hybrid variables, best accuracies were obtained with conventional analysis (82%), T1G+/PET (82%) and SWI/PET (81%). T1G+/PET, SWI/PET and rCBF ≥ 1.25 were selected to construct a 3-point score. It outperformed conventional analysis and rCBF with an AUC of 0.94 and an accuracy of 87%. CONCLUSIONS: Our scoring approach combining F­DOPA PET and MRI provided better accuracy than conventional PET analyses for distinguishing TP from TRC in our patients after radiation therapy.

Current and Future Tools for Diagnosis of Kaposi's Sarcoma.

Kaposi's sarcoma (KS) is a rare, atypical malignancy associated with immunosuppression and can be qualified as an opportunistic tumor, which responds to immune modulation or restoration. Four different epidemiological forms have been individualized (AIDS-related, iatrogenic, endemic or classic KS). Although clinical examination is sufficient to diagnose cutaneous lesions of KS, additional explorations are necessary in order to detect lesions involving other organs. New histological markers have been developed in recent years concerning the detection of HHV-8 latent or lytic proteins in the lesions, helping to confirm the diagnosis when it is clinically doubtful. More recently, the evaluation of the local immune response has also been shown to provide some guidance in choosing the appropriate therapeutic option when necessary. We also review the indication and the results of conventional radiological imaging and of non-invasive imaging tools such as 18F-fluoro-deoxy-glucose positron emission tomography, thermography and laser Doppler imaging for the diagnosis of KS and for the follow-up of therapeutic response in patients requiring systemic treatment.

Brain Glucose Metabolism in Cerebral Amyloid Angiopathy: An FDG-PET Study.

BACKGROUND AND PURPOSE: The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is currently based on the Boston criteria, which largely rely on hemorrhagic features on brain magnetic resonance imaging. Adding to these criteria 18F-fluoro-deoxy-D-glucose (FDG) positron emission tomography, a widely available imaging modality, might improve their accuracy. Here we tested the hypothesis that FDG uptake is reduced in posterior cortical areas, particularly the primary occipital cortex, which pathologically bear the brunt of vascular Aß deposition. METHODS: From a large memory clinic database, we retrospectively included all patients in whom both brain magnetic resonance imaging and FDG positron emission tomography had been obtained as part of routine clinical care and who fulfilled the Boston criteria for probable CAA. None had a history of symptomatic intracerebral hemorrhage. FDG data processing involved (1) spatial normalization to the Montreal Neurology Institute/International Consortium for Brain Mapping 152 space and (2) generation of standardized FDG uptake (relative standardized uptake value; relative to the pons). The relative standardized uptake value data obtained in 13 regions of interest sampling key cortical areas and the cerebellum were compared between the CAA and age-matched control groups using 2 separate healthy subject databases and image-processing pipelines. The presence of significant hypometabolism (2-tailed P<0.05) was assessed for the bilaterally averaged regions-of-interest relative standardized uptake values. RESULTS: Fourteen patients fulfilling the Boston criteria for probable CAA (≥2 exclusively lobar microbleeds) were identified. Significant hypometabolism (P range, 0.047 to <0.0001) consistently affected the posterior cortical areas, including the superior and inferior parietal, primary visual, lateral occipital, lateral temporal, precuneus, and posterior cingulate regions of interest. The anterior cortical areas were marginally or not significantly hypometabolic, and the cerebellum was spared. CONCLUSIONS: Supporting our hypothesis, significant glucose hypometabolism predominantly affected posterior cortical regions, including the visual cortex. These findings from a small sample may have diagnostic implications but require replication in larger prospective studies. In addition, whether they generalize to CAA-related symptomatic intracerebral hemorrhage warrants specific studies.

[18 F]FDG PET may differentiate cerebral amyloid angiopathy from Alzheimer's disease.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a frequent cause of both intracerebral hemorrhage (ICH) and cognitive impairment in the elderly. Diagnosis relies on the Boston criteria, which use magnetic resonance imaging markers including ≥2 exclusively lobar cerebral microbleeds (lCMBs). Although amyloid positron emission tomography (PET) may provide molecular diagnosis, its specificity relative to Alzheimer's disease (AD) is limited due to the prevalence of positive amyloid PET in cognitively normal elderly. Using early-phase 11 C-Pittsburgh compound B as surrogate for tissue perfusion, a significantly lower occipital/posterior cingulate (O/PC) tracer uptake ratio in probable CAA relative to AD was recently reported, consistent with histopathological lesion distribution. We tested whether this finding could be reproduced using [18 F]fluorodeoxyglucose (FDG)-PET, a widely available modality that correlates well with early-phase amyloid PET in both healthy subjects and AD. METHODS: From a large memory clinic database, we retrospectively included 14 patients with probable CAA (Boston criteria) and 21 patients with no lCMB fulfilling AD criteria including cerebrospinal fluid biomarkers. In all, [18 F]FDG-PET/computed tomography (CT) was available as part of routine care. No subject had a clinical history of ICH. Regional standardized [18 F]FDG uptake values normalized to the pons (standard uptake value ratio [SUVr]) were obtained, and the O/PC ratio was calculated. RESULTS: The SUVr O/PC ratio was significantly lower in CAA versus AD (1.02 ± 0.14 vs. 1.19 ± 0.18, respectively; p = 0.024). CONCLUSIONS: Despite the small sample, our findings are consistent with the previous early-phase amyloid PET study. Thus, [18 F]FDG-PET may help differentiate CAA from AD, particularly in cases of amyloid PET positivity. Larger prospective studies, including in CAA-related ICH, are however warranted.

Use of FDG-PET/CT for systemic assessment of suspected primary central nervous system lymphoma: a LOC study.

INTRODUCTION: Primary Central Nervous System Lymphoma (PCNSL) is a rare disease with different therapeutic implications than systemic lymphoma. In this study, we evaluated whole-body 18FDG-PET/CT for pre-chemotherapy imaging of suspected PCNSL. METHODS: One hundred and thirty consecutive immunocompetent patients were retrospectively included. The results of initial 18FDG-PET/CT, contrast-enhanced CT (CeCT) and bone marrow biopsy (BMB) when available were compared to a gold standard based on pathological diagnosis or follow-up. RESULTS: CNS lesion pathology showed large B-cell lymphoma in 95% of patients, including 11 patients with primary vitro-retinal lymphoma. Ten patients (8%) where ultimately diagnosed with systemic lymphoma involvement, including five pathologically confirmed cases, all of which were detected by 18FDG-PET/CT. 18FDG-PET/CT showed incidental systemic findings unrelated to lymphoma in 14% of patients. An SUVmax threshold of nine enabled good discrimination between systemic lymphoma and other lesions (sensitivity 92% and specificity 89%). CeCT and BMB performed in 108 and 77 patients respectively revealed systemic lesions in only three patients. CONCLUSION: 18FDG-PET/CT detected concomitant occult systemic involvement in a non-negligible proportion of suspected PCNSL cases (8%). In this setting its sensitivity is higher than that of CeCT. All of our patients ultimately diagnosed with concomitant systemic involvement had positive 18FDG-PET/CT. We believe it constitutes a safe one-stop shop evaluation for the systemic pre-treatment imaging of suspected PCNSL.

Novel PET tracers: added value for endocrine disorders.

Nuclear medicine has been implicated in the diagnosis and treatment of endocrine disorders for several decades. With recent development of PET tracers, functional imaging now plays a major role in endocrine tumors enabling with high performance to their localization, characterization, and staging. Besides 18F-FDG, which may be used in the management and follow-up of endocrine tumors, new tracers have emerged, such as 18F-DOPA for neuroendocrine tumors (NETs) (medullary thyroid carcinoma, pheochromocytomas and paragangliomas and well-differentiated NETs originating from the midgut) and 18F-Choline in the field of primary hyperparathyroidism. Moreover, some peptides such as somatostatin analogs can also be used for peptide receptor radionuclide therapy. In this context, Gallium-68 labeled somatostatin analogs (68Ga-SSA) can help to tailor therapeutic choices and follow the response to treatment in the so-called "theranostic" approach. This review emphasizes the usefulness of these three novel PET tracers (18F-Choline, 18F-FDOPA, and 68Ga-SSA) for primary hyperparathyroidism and neuroendocrine tumors.