Dataset Information

Early assessment with 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab.

ABSTRACT: BACKGROUND:We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. METHODS:Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter???30% or not). RESULTS:There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3?±?6.4, 115.5?±?14.9, respectively. Lesions whose diameter decreased ?30% at second assessment were defined as responding, and lesions whose diameter did not decrease ?30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P?=?0.025, OR: 13.087, 95%CI: 1.373-124.716). CONCLUSION:Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. TRIAL REGISTRATION:Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012.

SUBMITTER: Tabei T

PROVIDER: S-EPMC6446392 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Early assessment with <sup>18</sup>F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab.

Tabei Tadashi T Nakaigawa Noboru N Kaneta Tomohiro T Ikeda Ichiro I Kondo Keiichi K Makiyama Kazuhide K Hasumi Hisashi H Hayashi Narihiko N Kawahara Takashi T Izumi Koji K Osaka Kimito K Muraoka Kentaro K Teranishi Jun-Ichi JI Miyoshi Yasuhide Y Yumura Yasushi Y Uemura Hiroji H Kobayashi Kazuki K Inoue Tomio T Yao Masahiro M

BMC cancer 20190402 1

<h4>Background</h4>We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab.<h4>Methods</h4>Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study ...[more]

PMID: 30940117

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Project description:ImportanceNeoadjuvant immunotherapy is a novel approach with the potential to improve outcomes for patients with oral cavity squamous cell cancer (OCSCC). Adverse events of varying severity are reported with immunotherapy, and a biomarker to predict response would be clinically useful to avoid toxic effects in those unlikely to benefit.ObjectiveTo correlate changes on fluoro-[18F]-deoxy-2-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans with primary tumor pathologic response and immunologic biomarkers in patients with OCSCC receiving neoadjuvant immunotherapy.Design, setting, and participantsThis was a retrospective analysis of serial FDG-PET/CT scans obtained prospectively as part of a phase 2 open-label randomized clinical trial investigating neoadjuvant immunotherapy in patients with untreated OCSCC between 2016 and 2019. Included were a total of 29 patients from a single academic medical center with untreated OCSCC (≥T2, or clinically node positive) randomized 1:1 to receive neoadjuvant therapy with single agent nivolumab or combination nivolumab and ipilimumab followed by surgery and standard of care adjuvant therapy.InterventionsThe interventions in this study were FDG-PET/CT scans before (T0) and after (T1) preoperative immunotherapy.Main outcomes and measuresData collected from FDG-PET/CT scans included maximum standardized uptake value (SUVmax) of primary OCSCC and cervical lymph nodes (LNs) at T0 and T1 and new LN uptake and uptake consistent with radiologic immune-related adverse events (irAEs) at T1. Primary OCSCC pathologic response reported as percentages of viable vs nonviable tumor. The number of CD8+ cells/mm2 was determined in the primary tumor biopsy specimen and at surgery.ResultsThere was no correlation between pathologic response and change in SUVmax in the primary OCSCC between T0 and T1. Out of 27 total participants, 13 had newly FDG-avid ipsilateral LNs at T1, most negative on pathology. A total of 9 had radiologic irAEs, most commonly sarcoid-like LN (7 of 27). No correlations were found between primary OCSCC SUVmax at T0 and CD8+ T-cell number in the primary tumor biopsy, and no correlations were found between primary OCSCC SUVmax at T1 and CD8+ T-cell number in the primary tumor at surgery.Conclusions and relevanceThere were no correlations between changes in FDG uptake after neoadjuvant immunotherapy and pathologic primary tumor response. Importantly, newly FDG-avid ipsilateral LNs following neoadjuvant immunotherapy were commonly observed but did not represent progressive disease or indicate pathologically disease positive nodes in most cases. These findings argue against altering surgical plans in this setting and suggest that the role of FDG-PET/CT may be limited as an early imaging biomarker for predicting pathologic response to preoperative immunotherapy for OCSCC.Trial registrationClinicalTrials.gov Identifier: NCT02919683.

Project description:Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n?=?109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ?25?mm Hg (P?=?0.013, P?=?0.006, P?=?0.049, P?=?0.002, P?=?0.68, respectively) and with PVR ?480?dyn·s/cm (P?<?0.001, P?=?0.045, P?<?0.001, P?<?0.001, P?=?0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r?=?0.55, r?=?0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.

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Dataset Information

Early assessment with 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab.

Publications

Early assessment with <sup>18</sup>F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab.

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