Total Metabolic Tumor Volume on 18F-FDG PET/CT Is a Useful Prognostic Biomarker for Patients with Extensive Small-Cell Lung Cancer Undergoing First-Line Chemo-Immunotherapy.

Background: We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy. Methods: In this multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: chemo-immunotherapy (CIT) versus chemotherapy alone (CT). All patients underwent baseline 18-FDG PET/CT before therapy between June 2016 and September 2021. We evaluated clinical, biological, and PET parameters, and used cutoffs from previously published studies or predictiveness curves to assess the association with progression-free survival (PFS) or overall survival (OS) with Cox prediction models. Results: Sixty-eight patients were included (CIT: CT) (36: 32 patients). The median PFS was 5.9:6.5 months, while the median OS was 12.1:9.8 months. dNLR (the derived neutrophils/(leucocytes-neutrophils) ratio) was an independent predictor of short PFS and OS in the two cohorts (p < 0.05). High total metabolic tumor volume (TMTVhigh if > 241 cm3) correlated with outcomes, but only in the CIT cohort (PFS for TMTVhigh in multivariable analysis: HR 2.5; 95%CI 1.1-5.9). Conclusion: Baseline 18F-FDG PET/CT using TMTV could help to predict worse outcomes for ES-SCLC patients undergoing first-line CIT. This suggests that baseline TMTV may be used to identify patients that are unlikely to benefit from CIT.

Clinical and phantom validation of a deep learning based denoising algorithm for F-18-FDG PET images from lower detection counting in comparison with the standard acquisition.

BACKGROUND: PET/CT image quality is directly influenced by the F-18-FDG injected activity. The higher the injected activity, the less noise in the reconstructed images but the more radioactive staff exposition. A new FDA cleared software has been introduced to obtain clinical PET images, acquired at 25% of the count statistics considering US practices. Our aim is to determine the limits of a deep learning based denoising algorithm (SubtlePET) applied to statistically reduced PET raw data from 3 different last generation PET scanners in comparison to the regular acquisition in phantom and patients, considering the European guidelines for radiotracer injection activities. Images of low and high contrasted (SBR = 2 and 5) spheres of the IEC phantom and high contrast (SBR = 5) of micro-spheres of Jaszczak phantom were acquired on 3 different PET devices. 110 patients with different pathologies were included. The data was acquired in list-mode and retrospectively reconstructed with the regular acquisition count statistic (PET100), 50% reduction in counts (PET50) and 66% reduction in counts (PET33). These count reduced images were post-processed with SubtlePET to obtain PET50 + SP and PET33 + SP images. Patient image quality was scored by 2 senior nuclear physicians. Peak-signal-to-Noise and Structural similarity metrics were computed to compare the low count images to regular acquisition (PET100). RESULTS: SubtlePET reliably denoised the images and maintained the SUVmax values in PET50 + SP. SubtlePET enhanced images (PET33 + SP) had slightly increased noise compared to PET100 and could lead to a potential loss of information in terms of lesion detectability. Regarding the patient datasets, the PET100 and PET50 + SP were qualitatively comparable. The SubtlePET algorithm was able to correctly recover the SUVmax values of the lesions and maintain a noise level equivalent to full-time images. CONCLUSION: Based on our results, SubtlePET is adapted in clinical practice for half-time or half-dose acquisitions based on European recommended injected dose of 3 MBq/kg without diagnostic confidence loss.

Prognostic value of inflammatory response biomarkers using peripheral blood and [18F]-FDG PET/CT in advanced NSCLC patients treated with first-line chemo- or immunotherapy.

OBJECTIVES: We aimed to compare the prognostic value of inflammatory biomarkers extracted from pretreatment peripheral blood and [18F]-FDG PET for estimating outcomes in non-small cell lung cancer (NSCLC) patients treated with first-line immunotherapy (IT) or chemotherapy (CT). MATERIALS AND METHODS: In this retrospective multicenter study, we evaluated 111 patients with advanced NSCLC who underwent baseline [18F]-FDG PET/CT before IT or CT between 2016 and 2019. Several blood inflammatory indices were evaluated: derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP) and systemic immune-inflammation index (SII). FDG-PET inflammatory parameters were extracted from lymphoid tissues (BLR and SLR: bone marrow or spleen-to-Liver SUVmax ratios). Association with survival and relationships between parameters were evaluated using Cox prediction models and Spearman's correlation respectively. RESULTS: Overall, 90 patients were included (IT:CT) (51:39pts). Median PFS was 8.6:6.6 months and median OS was not reached:21.2 months. In the IT cohort, high dNLR (>3), high SII (≥1,270) and high SLR (0.77) were independent statistically significant prognostic factors for one-year progression-free survival (1y-PFS) and two-year overall survival (2y-OS) on multivariable analysis. In the CT cohort, high BLR (≥0.80) and high dNLR (>3) were associated with shorter 1y-PFS (HR 2.2, 95% CI 1.0-4.9) and 2y-OS (HR 3.4, 95CI 1.1-10.3) respectively, on multivariable analysis. Finally, BLR significantly but moderately correlated with most blood-based inflammatory indices (CRP, PLR and SII) while SLR was only associated with CRP (p < 0.01 for all). CONCLUSION: In advanced NSCLC patients undergoing first-line IT or CT, pretreatment blood and inflammatory factors evaluating the spleen or bone marrow on [18F]-FDG PET/CT provided prognostic information for 1y-PFS and 2y-OS. These biomarkers should be further evaluated for potential clinical application.

FDG-PET biomarkers associated with long-term benefit from first-line immunotherapy in patients with advanced non-small cell lung cancer.

OBJECTIVE: To determine FDG-PET biomarkers associated with long-term benefit (LTB) and survival in advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy. METHODS: In this multicenter study, we retrospectively analyzed advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥ 50%, who underwent FDG-PET/CT before first-line pembrolizumab, received from August 2017 to September 2019. Parameters extracted were SUVmax, SUVmean, TMTV (total metabolic tumor volume) and TLG (total lesion glycolysis). LTB was defined as objective (complete or partial) response or stable disease as best overall response, maintained for ≥ 12 months. A multivariate prediction model was developed using logistic regression for LTB and Cox models for progression-free survival (PFS) and overall survival (OS). RESULTS: On the 63 eligible patients, with a median follow-up of 13.4 (range, 1.5-29.1) months, 17 (27%) had LTB. Median PFS and OS were 7.7 months (95%CI 5.0-10.5) and 12.1 months (95%CI 8.6-15.6). In multivariate analyses, high TMTV (> 84cm3) and high tumor SUVmean (> 10.1) remained independent factors for predicting LTB (OR 0.2; p = 0.03 and OR 3.7; p = 0.04) and PFS (HR 2.2; p = 0.02 and HR 0.5; p = 0.045). High TMTV was significantly associated with poor OS (HR 3.1; p = 0.03). No association was observed between tumor SUVmax or TLG and clinical outcomes. CONCLUSIONS: In patients with advanced NSCLC and PD-L1 TPS ≥ 50%, baseline low TMTV and high tumor SUVmean correlate with survival and LTB from upfront pembrolizumab. Beyond the initial staging, FDG-PET/CT scan could provide relevant biomarkers associated with clinical outcomes that should be taken into account when considering first-line treatment options.

Images of COVID-19 Infection Cases in Asymptomatic or Paucisymptomatic Patients With Neoplastic Diseases on 18F-FDG PET/CT.

We describe the results of F-FDG PET/CT of 3 patients referred to our institution during the single day of Monday, March 23, 2020, for an initial assessment of cancer extension or for the therapeutic evaluation of chemotherapy of neoplastic pathology, with no obvious infectious or respiratory symptoms at the time of examination. A retrospective review of the recent clinical history of patients in association with the typical pulmonary images on CT scan suggested the diagnosis of COVID-19. The characteristic aspects of COVID-19 infection should be recognized on F-FDG PET/CT, even if patients are asymptomatic or minimally symptomatic.

Association of the Metabolic Score Using Baseline FDG-PET/CT and dNLR with Immunotherapy Outcomes in Advanced NSCLC Patients Treated with First-Line Pembrolizumab.

Background: We aimed to assess the clinical utility of a previously published score combining the total metabolic tumor volume (TMTV) on baseline FDG-PET/CT and pretreatment derived from the neutrophils to lymphocytes ratio (dNLR) for prognostication in NSCLC patients undergoing first-line immunotherapy (IT). Methods: In this multicenter retrospective study, 63 advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥50%, who underwent FDG-PET/CT before first-line IT, treated from January 2017 to September 2019, were enrolled. Associations between this score and the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and overall response rate (ORR) were evaluated. Results: The median (m) PFS and mOS were 7.7 (95% CI 4.9-10.6) and 12.1 (8.6-15.6) months, respectively, and DCR and ORR were 65% and 58%, respectively. mOS was 17.9 months (14.6 not reached) for the good group versus 13.8 (95%CI 8.4-18.9) and 6.6 (CI 2.0-11.2) months for the intermediate and poor groups, respectively. mPFS was 15.1 (95%CI 12.1-20.0) months for the good group versus 5.2 (1.9-8.5) and 1.9 (95%CI 1.3-2.5) months for the intermediate and poor groups, respectively. The poor prognosis group was associated with DCR and ORR (p < 0.05). Conclusions: The metabolic score combining TMTV on the baseline FDG-PET/CT scan and pretreatment dNLR was associated with the survival and response in a cohort of advanced NSCLC patients with ≥50% PD-L1 receiving frontline IT.

Ventilation/perfusion SPECT/CT findings in different lung lesions associated with COVID-19: a case series.

PURPOSE: The aim of this series of cases is to show the aspects of ventilation/perfusion single-photon emission computed tomography combined with computed tomography (V/Q SPECT/CT) in patients hospitalized for COVID-19 pneumonia, with the worsening of respiratory symptoms raising the suspicion of a pulmonary embolism. Patients did not benefit from CT angiography for various reasons: a contraindication, unavailability of the CT angiography, or a low clinical probability for pulmonary embolism. METHODS: We retrospectively describe the results of the V/Q SPECT/CT of five patients hospitalized for COVID-19 pneumonia in the nuclear medicine departments of the Centre Cardiologique du Nord and of the Delafontaine hospital in Saint-Denis (Ile-de-France, France) between April 2, 2020, and April 10, 2020. These patients had persistent dyspnea or chest pain suggesting pulmonary embolism. RESULTS: The V/Q SPECT/CT allowed to diagnose a pulmonary embolism in one of these five patients. We also noted several characteristics of the perfusion and ventilation depending on the lung lesions on the CT scan. The areas affected by COVID-19 were most often responsible for ventilatory anomalies with a relatively preserved perfusion. In more advanced cases of pneumonia, with alveolar fillings, the perfusion was also reduced or absent in accordance with large ventilation defects. In addition, the healthy parenchyma appeared to benefit from an uptake in ventilation and perfusion. CONCLUSION: V/Q SPECT/CT can play a role in the management of patients hospitalized for COVID-19 for the diagnosis of embolic complications with meticulous hygienic precautions. The different characteristics of the ventilatory and perfusion anomalies related to COVID-19 pneumonia will be confirmed with the next cases. In addition, in this pandemic context and facing a significant infectious risk, the utility of ventilation will also have to be specified.

Feasibility of simultaneous dual isotope acquisition for myocardial perfusion imaging with a cadmium zinc telluride camera.

BACKGROUND: We studied the impact of technetium-99m (99mTc) in the thallium-201 (201Tl) energy window (70 keV) to determine if CZT cardiac cameras allow us to perform simultaneous dual-isotope acquisition for myocardial perfusion imaging. METHODS: We included 117 consecutive patients. We injected 0.7 MBq/kg of 201Tl at stress, performed the first scan (image T1), then injected at rest 2 MBq/kg of 99mTc-tetrofosmin and immediately acquired a second scan with reconstruction in the energy window of thallium (image T2). A corrected thallium image was created by the subtraction of 99mTc downscattered photons (image TS). We compared spectra, image quality, and semiquantitative scores on T1, T2, and TS images. RESULTS: Though T2 images were of worse quality, TS images were of equal quality compared to T1 images in most cases. Scores show an underestimation of abnormalities in 20% of patients on T2 images and in 10% on TS images. CONCLUSIONS: Despite the improved energy resolution of CZT cameras, downscatter of technetium in the 201Tl window leads to an underestimation of the pathological territory in 10% to 20% of cases. It does not allow us to use simultaneous dual-isotope acquisition in clinical practice without additional tools for scatter correction.

Prognostic value of one millisievert exercise myocardial perfusion imaging in patients without known coronary artery disease.

The aim of this study was to assess the prognostic value of normal ultra-low-dose exercise MPI with a CZT camera. METHODS: 1901 consecutive patients without known CAD referred for exercise MPI with 1.8 MBq/kg (0.05 mCi) of Tc99m sestamibi or tetrofosmin and a CZT camera were included prospectively. Patients with an abnormal scan requiring an additional resting image (230) or a submaximal exercise test (271) were excluded. The 1400 remaining patients were followed for 39 months. The primary end-point was cardiac events (cardiac death, nonfatal myocardial infarction, and revascularization). The secondary end-point was noncardiac death. RESULTS: The mean injected activity was 145 ± 37 MBq (3.9 ± 1 mCi), the mean acquisition duration was 10 ± 0.7 minutes, and the mean effective dose was 0.91 ± 0.13 mSv. 1288 patients (92%) achieved full follow-up. We observed 22 cardiac events and 16 noncardiac deaths. The annualized rates were equivalent to 0.55% for cardiac events and 0.37% for noncardiac mortality. CONCLUSIONS: Normal ultra-low-dose exercise MPI with a CZT camera has a high negative predictive value. The effective dose was less than 1 mSv, and the study thus allays concerns about radiation burden.

The Use of FDG PET-CT Imaging for the Assessment of Early Antifungal Treatment Response in Disseminated Fusariosis.

Fusariosis is an opportunistic infection, caused by a filamentous fungus, found on plants and in soil. The treatment of disseminated pattern, seen in immunocompromised patients with severe neutropenia, is difficult because of antifungal therapy resistance. A 12-year-old girl, who was diagnosed with B-cell acute lymphoblastic leukemia, developed multiple widespread skin papules and subcutaneous nodules, at day 20 of consolidation therapy. Histological examination with cultures of skin tissue revealed Fusarium species. Treatment was started with intravenous liposomal amphotericin B and voriconazole. To assess treatment response, FDG PET/CT performed at baseline, at 2 and 4 months, showed a partial response.

IgG4-Related Tubulointerstitial Nephritis Pattern in 18F-FDG PET/CT.

A 17-year-old adolescent girl was admitted with chronic arthralgia, Raynaud phenomenon, pericarditis, and evidences of chronic diffuse inflammation. F-FDG PET/CT scan was performed to search systemic vasculitis and showed diffuse moderate uptake in the kidneys. We suggested the existence of a nephritis, but the ultrasonography result was normal, and no treatment was introduced. Another F-FDG PET/CT scan was performed 7 months later to explore abdominal pain. It showed again diffuse intense uptake in both kidneys. A proteinuria was highlighted, and renal biopsy allowed to diagnose IgG4-related disease.

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

BACKGROUND: The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. METHODS: Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. RESULTS: Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. CONCLUSION: In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

18F-FDG PET/CT imaging of Sister Mary Joseph's nodule.

An 82-year-old woman was followed up for an uterine cervical adenocarcinoma treated by surgery. A whole-body fluorodeoxyglucose positron emission tomography study revealed a pathologic fluorodeoxyglucose uptake located in the umbilicus associated to peritoneal carcinomatosis. Biopsy of the umbilical nodule demonstrated an umbilical metastasis from the uterine adenocarcinoma, the so-called "Sister Mary Joseph's nodule."

Place of modern imaging modalities for solitary plasmacytoma: toward improved primary staging and treatment monitoring.

Radiation therapy (RT) is the mainstay of treatment of solitary plasmacytoma. In most cases, doses ranging from 40 to 50 Gy yield in a local control more than 80%. However, the prognosis of patients with SP is marked by a high rate of transformation to multiple myeloma (MM), and there is no demonstrated benefit of adjuvant chemotherapy for decreasing this probability. However, clinical benefits could be reached from improving screening for other primary sites of plasmacytoma and earlier discovering signs suggestive of MM. Since such strategy could provide significant information regarding both prognosis and therapy, it has become first importance to improve initial staging of tumor widespread. Although conventional skeletal X-ray survey remains standard, usual sensitivity of radiographies does not permit diagnosing early myeloma lesions and a significant number of patients with supposed SP might be understaged and do not receive the appropriate treatment. The development of more sensitive and specific imaging modalities will make it feasible to earlier detect subclinical lesions, thus leading lead to new approaches in the treatment strategies. Here, we discuss the benefits and limitations of magnetic resonance imaging and positron emission tomography for primary staging of patients with solitary plasmacytoma. Both imaging modalities could also improve target volume delineation and assessment of tumor response after RT.

18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated patients.

CONTEXT: Most adrenal incidentalomas are nonfunctioning adrenocortical adenomas (ACAs). Adrenocortical carcinomas (ACCs) are rare but should be recognized at an early stage. OBJECTIVE: The objective of the study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) to predict malignancy in patients without a previous history of cancer. DESIGN: This was a prospective, multicenter study from 2001 to 2006. SETTING: The study was conducted at a network of seven university hospitals in Paris. PATIENTS: Seventy-seven patients were included. All underwent surgery because of hypersecretory and/or growing benign lesions (n = 18), obvious ACCs (n = 21), or radiologically indeterminate lesions (n = 38). MAIN OUTCOME MEASURE: The degree of (18)F-FDG PET uptake [maximum standardized uptake value (maxSUV)] was related to the pathological findings serving as a reference, and its diagnostic value was compared with that of computerized tomography (CT) scan. RESULTS: Pathology eventually diagnosed 43 ACAs, 22 ACCs, and 12 nonadrenocortical lesions. Using a cutoff value above 1.45 for adrenal to liver maxSUV ratio, the sensitivity and specificity to distinguish ACAs from ACCs were, respectively, 1.00 (95% confidence interval 0.85-1.00) and 0.88 (95% confidence interval 0.75-0.96). Among the 38 indeterminate lesions at CT scan, we could analyze a subgroup of 16 adrenocortical tumors with high unenhanced density (>10 HU) and an inappropriate washout: (18)F-FDG PET correctly predicted the benignity in 13 of 15 ACAs. CONCLUSIONS: In a multidisciplinary team approach, (18)F-FDG PET helps to manage suspicious CT scan lesions. An adrenal to liver maxSUV ratio less than 1.45 is highly predictive of a benign lesion.