Proliferation PET Image to Characterize Pathological Spatial Features in Patients With Non-Small Cell Lung Cancer: A Pilot Study

Chen, X.; Gao, Zhenhua; Gao, Yongsheng; Zhang, B.; Fu, Zheng; Mu, Dianbin; J, Yu; Meng, Xue

doi:10.1016/j.ijrobp.2015.07.1590

Cited by 3 publications

(4 citation statements)

References 19 publications

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“…In tumors with high intratumoral heterogeneity, the concordance between section and whole tumor might be low (42). In other words, the concordance of the Ki-67 index and SUVmax, which is the spatial co-localization between Ki-67 staining and FDG/FLT uptake in the same lesion, would be underestimated (21). In addition, a potential risk of bias exists that the Ki-67 results or other clinical data might have been known before assessing PET images in a retrospective study.…”

Section: Discussionmentioning

confidence: 99%

“…The accumulation of FLT serves as an indirect measurement of cell proliferation by reflecting thymidine kinase-1 expression (TK1), which is closely associated with cellular proliferation (16). In clinical studies, 18F-FLT uptake showed a significant correlation with the cell proliferation indicated by the Ki-67 index in pulmonary nodules (17–20), although this is not always the case (21,22). In addition, the sample sizes of these studies were small.…”

Section: Introductionmentioning

confidence: 97%

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Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis

Shen

Pang

et al. 2017

Acta Radiol

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Background Positron emission tomography (PET) imaging using the radiotracers 18F-fluorodeoxyglucose (FDG) or 18F-fluorothymidine (FLT) has been proposed as imaging biomarkers of cell proliferation. Purpose To explore the correlations of FDG and FLT uptake with the Ki-67 labeling index in patients with lung cancer. Material and Methods Major databases were systematically searched for all relevant literature published in English. The correlation coefficient (rho) and its 95% confidence interval (CI) of individual studies were meta-analyzed using a random-effects model. The sources of heterogeneity were explored by subgroup analyses. Results Twenty-seven articles involving 1213 patients were included in this meta-analysis, comprising 22 studies for FDG uptake/Ki-67 expression correlation and eight for FLT uptake/Ki-67 expression correlation. The pooled rho values for 18F-FDG/Ki-67 correlation and 18F-FLT/Ki-67 correlation were 0.45 (95% CI, 0.41-0.50) and 0.65 (95% CI, 0.56-0.73), respectively, which indicated a moderate correlation for the former and a significant one for the latter. Although the subgroup analyses based on study design, scanner, sample method, and Ki-67 labeling method did not significantly explain the heterogeneity, these factors were potential sources of heterogeneity. In lung cancer, the pooled SUVmax of FDG uptake was significantly higher than that of FLT uptake (7.59 versus 3.86, P < 0.05). In addition, compared to FDG, FLT showed higher specificity yet lower sensitivity for the diagnosis of pulmonary lesions. Conclusion Both 18F-FDG and 18F-FLT correlate significantly with the Ki-67 labeling index in pulmonary lesions, and the latter, with a stronger correlation, may be more reliable for assessing tumor cell proliferation in lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis

Shen

Pang

et al. 2017

Acta Radiol

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“…In this case, the Ki-67 proliferation index was less than 20%, whereas glycolytic hypermetabolism was detected on PET-CT imaging. It might be possible that the distribution of the 18 F-FDG uptake was not well co-localized with proliferating tumor cells, as indicated by Ki-67 labeling [22]. Moreover, the histopathological examination may be partial, Ki-67 labeling may suffer from sampling errors within the tissue of the biopsy and potential interobserver variations.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of refractory retroperitoneal Epstein-Barr virus-positive diffuse large B-cell lymphoma with secondary hemophagocytic syndrome by sequential combination regimen of PD-1 blockade and chimeric antigen receptor T cells: a case report

Zhang

et al. 2021

Anti-Cancer Drugs

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Epstein-Barr virus (EBV) is convincingly contributed to the development of several types of lymphomas such as NK/T cell lymphoma, Burkitt lymphoma, plasmablastic lymphoma, and diffuse large B cell lymphoma (DLBCL). Herein, we reported an atypical case of EBV-positive DLBCL in an immunocompetent young male patient who presented with epistaxis due to hypergammaglobulinemia. 2-Deoxy-2-[fluorine-8] fluoro-d-glucose PET/computed tomography showed multiple highly metabolic retroperitoneal tissue masses with the involvement of bilateral adrenal gland. Ultrasonography-guided biopsy revealed a significant number of lymphocytes and plasma-like cells that are immunopositive for plasmacell markers and partly positive for pan-B cell markers. The Ki-67 proliferation index was 20%. The extensive distribution of EBV-encoded small RNAs was confirmed by in-situ hybridization. Due to atypical/overlapping pathological characteristics, it was initially misdiagnosed as extramedullary plasmacytoma and treated with two cycles of bortezomib, lenalidomide, and dexamethasone. Disease progression occurred and pathology consultation for the retroperitoneal biopsies modified the diagnosis to EBV-positive DLBCL with plasma cell differentiation. The treatment was adjusted to etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab, and lenalidomide (R2-EPOCH), but no response was observed after three cycles of treatment and he developed hemophagocytic syndrome during treatment. A monotherapy of anti-programmed cell death-1 (PD-1) treatment with tiririzumab was administered, successfully controlling hemophagocytic syndrome and EBV infection. The response assessment was partial for EBV-positive DLBCL, subsequent anti-CD19 chimeric antigen receptor-T (CAR-T) cell therapy resulted in complete remission including lumps, immunoglobulins, and negative EBV-DNA 1.5 months later. The present case study proved the possibility of PD-1 blockade in controlling EBV infection and associated hemophagocytic syndrome and offered an example of the combination of CAR-T therapy and PD-1 blockade for refractory EBV-positive DLBCL in clinic. Anti-Cancer Drugs 33: e769-e775

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“…Several studies have evaluated [ 18 F]FLT as a proliferation biomarker [ 3 , 10 , 11 , 14 ]. However, most of these studies have not taken potential perfusion effects into account [ 10 , 11 , 14 ]. During this study, patients will undergo treatment with a TKI, which also intervenes with the vascular endothelial growth factor (VEGF) pathway.…”

Section: Methodsmentioning

confidence: 99%

Validation of [18F]FLT as a perfusion-independent imaging biomarker of tumour response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR tyrosine kinase inhibitor

et al. 2018

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Background3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) was proposed as an imaging biomarker for the assessment of in vivo cellular proliferation with positron emission tomography (PET). The current study aimed to validate [18F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [18F]FLT uptake and perfusion in non-small cell lung cancer (NSCLC) patients undergoing treatment with a tyrosine kinase inhibitor (TKI).Six patients with metastatic NSCLC, having an activating epidermal growth factor receptor (EGFR) mutation, were included in this study. Patients underwent [15O]H2O and [18F]FLT PET/CT scans at three time points: before treatment and 7 and 28 days after treatment with a TKI (erlotinib or gefitinib). Parametric analyses were performed to generate quantitative 3D images of both perfusion measured with [15O]H2O and proliferation measured with [18F]FLT volume of distribution (VT). A multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high [18F]FLT VT using a single global threshold for all scans and subjects. By combining these initial classifications, voxels were allocated to four categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT).ResultsA total of 17 perfusion and 18 [18F]FLT PET/CT scans were evaluated. The average tumour values across all lesions were 0.53 ± 0.26 mL cm− 3 min− 1 and 4.25 ± 1.71 mL cm− 3 for perfusion and [18F]FLT VT, respectively. Multiparametric analysis suggested a shift in voxel distribution, particularly regarding the VT: from an average of ≥ 77% voxels classified in the “high VT category” to ≥ 85% voxels classified in the “low VT category”. The shift was most prominent 7 days after treatment and remained relatively similar afterwards. Changes in perfusion and its spatial distribution were minimal.ConclusionThe present study suggests that [18F]FLT might be a perfusion-independent PET tracer for measuring tumour response as parametric changes in [18F]FLT uptake occurred independent from changes in perfusion.Trial registrationNederlands Trial Register (NTR), NTR3557. Registered 2 August 2012Electronic supplementary materialThe online version of this article (10.1186/s13550-018-0376-6) contains supplementary material, which is available to authorized users.

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Proliferation PET Image to Characterize Pathological Spatial Features in Patients With Non-Small Cell Lung Cancer: A Pilot Study

Cited by 3 publications

References 19 publications

Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis

Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis

Successful treatment of refractory retroperitoneal Epstein-Barr virus-positive diffuse large B-cell lymphoma with secondary hemophagocytic syndrome by sequential combination regimen of PD-1 blockade and chimeric antigen receptor T cells: a case report

Validation of [18F]FLT as a perfusion-independent imaging biomarker of tumour response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR tyrosine kinase inhibitor

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