Evolutionary dynamics at the tumor edge reveal metabolic imaging biomarkers

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET–computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non–small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.

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SUVmax of FDG PET-CT Can Be Used As An Identifier of Lesion for AI To Interpret Radiology Reports

10.21203/rs.3.rs-61799/v1 ◽

2020 ◽

Author(s):

Kenji Hirata ◽

Osamu Manabe ◽

Keiichi Magota ◽

Sho Furuya ◽

Tohru Shiga ◽

...

Keyword(s):

Fdg Pet ◽

Standardized Uptake Value ◽

Local Maximum ◽

Ct Images ◽

Whole Body ◽

Training Dataset ◽

Imaging Biomarkers ◽

Radiology Reports ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Background Radiology reports contribute not only to the particular patient, but also to constructing massive training dataset in the era of artificial intelligence (AI). The maximum standardized uptake value (SUVmax) is often described in daily radiology reports of FDG PET-CT. If SUVmax can be used as an identifier of lesion, that would greatly help AI interpret radiology reports. We aimed to clarify whether the lesion can be localized using SUVmax written in radiology reports.Methods The institutional review board approved this retrospective study. We investigated a total of 112 lesions from 30 FDG PET-CT images acquired with 3 different scanners. SUVmax was calculated from DICOM files based on the latest Quantitative Imaging Biomarkers Alliance (QIBA) publication. The voxels showing the given SUVmax were exhaustively searched in the whole-body images and counted. SUVmax was provided with 5 different degrees of precision: integer (e.g., 3), 1st decimal places (DP) (3.1), 2nd DP (3.14), 3rd DP (3.142), and 4th DP (3.1416). For instance, when SUVmax=3.14 was given, the voxels with 3.135≤SUVmax<3.145 were extracted. We also evaluated whether local maximum restriction could improve the identifying performance, where only the voxels showing the highest intensity within some neighborhood were considered. We defined that “identical detection” was achieved when only single voxel satisfied the criterion.Results A total of 112 lesions from 30 FDG PET-CT images were investigated. SUVmax ranged from 1.3 to 49.1 (median = 5.6, IQR = 5.2). Generally, when larger and more precise SUVmax values were given, fewer voxels satisfied the criterion. The local maximum restriction was very effective. When SUVmax was determined to 4 decimal places (e.g., 3.1416) and the local maximum restriction was applied, identical detection was achieved in 33.3% (lesions with SUVmax<2), 79.5% (2≤SUVmax<5), and 97.8% (5≤SUVmax) of lesions.Conclusions SUVmax of FDG PET-CT can be used as an identifier to localize the lesion if precise SUVmax is provided and local maximum restriction was applied, although the lesions showing SUVmax<2 were difficult to identify. The proposed method may have potential to make use of radiology reports retrospectively for constructing training datasets for AI.

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A Preliminary Study to Use SUVmax of FDG PET-CT as an Identifier of Lesion for Artificial Intelligence

Frontiers in Medicine ◽

10.3389/fmed.2021.647562 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kenji Hirata ◽

Osamu Manabe ◽

Keiichi Magota ◽

Sho Furuya ◽

Tohru Shiga ◽

...

Keyword(s):

Artificial Intelligence ◽

Fdg Pet ◽

Standardized Uptake Value ◽

Local Maximum ◽

Ct Images ◽

Whole Body ◽

Imaging Biomarkers ◽

Pet Ct ◽

Preliminary Study ◽

Fdg Pet Ct

Background: Diagnostic reports contribute not only to the particular patient, but also to constructing massive training dataset in the era of artificial intelligence (AI). The maximum standardized uptake value (SUVmax) is often described in daily diagnostic reports of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) – computed tomography (CT). If SUVmax can be used as an identifier of lesion, that would greatly help AI interpret diagnostic reports. We aimed to clarify whether the lesion can be localized using SUVmax strings.Methods: The institutional review board approved this retrospective study. We investigated a total of 112 lesions from 30 FDG PET-CT images acquired with 3 different scanners. SUVmax was calculated from DICOM files based on the latest Quantitative Imaging Biomarkers Alliance (QIBA) publication. The voxels showing the given SUVmax were exhaustively searched in the whole-body images and counted. SUVmax was provided with 5 different degrees of precision: integer (e.g., 3), 1st decimal places (DP) (3.1), 2nd DP (3.14), 3rd DP (3.142), and 4th DP (3.1416). For instance, when SUVmax = 3.14 was given, the voxels with 3.135 ≤ SUVmax < 3.145 were extracted. We also evaluated whether local maximum restriction could improve the identifying performance, where only the voxels showing the highest intensity within some neighborhood were considered. We defined that “identical detection” was achieved when only single voxel satisfied the criterion.Results: A total of 112 lesions from 30 FDG PET-CT images were investigated. SUVmax ranged from 1.3 to 49.1 (median = 5.6). Generally, when larger and more precise SUVmax values were given, fewer voxels satisfied the criterion. The local maximum restriction was very effective. When SUVmax was determined to 4 decimal places (e.g., 3.1416) and the local maximum restriction was applied, identical detection was achieved in 33.3% (lesions with SUVmax < 2), 79.5% (2 ≤ SUVmax < 5), and 97.8% (5 ≤ SUVmax) of lesions.Conclusion: In this preliminary study, SUVmax of FDG PET-CT could be used as an identifier to localize the lesion if precise SUVmax is provided and local maximum restriction was applied, although the lesions showing SUVmax < 2 were difficult to identify. The proposed method may have potential to make use of diagnostic reports retrospectively for constructing training datasets for AI.

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Prognostic Value of Sarcopenia in Patients Treated by Radiochemotherapy for Locally Advanced Oesophageal Cancer

10.21203/rs.2.23302/v1 ◽

2020 ◽

Author(s):

Romain Mallet ◽

Romain Modzelewski ◽

Justine Lequesne ◽

Pierre Decazes ◽

Hugues Auvray ◽

...

Keyword(s):

Skeletal Muscle ◽

Cancer Patients ◽

Oesophageal Cancer ◽

Fdg Pet ◽

Prognostic Value ◽

Locally Advanced ◽

Ct Images ◽

Pet Ct ◽

Nutritional Risk Index ◽

Fdg Pet Ct

Abstract Background Sarcopenia is defined by a loss of skeletal muscle mass with or without loss of fat mass. Sarcopenia has been associated to reduced tolerance to treatment and worse prognosis in cancer patients, including patients undergoing surgery for limited oesophageal cancer. Concomitant chemo-radiotherapy is the standard treatment for locally-advanced tumour, not accessible to surgical resection. Using automated delineation of the skeletal muscle, we have investigated the prognostic value of sarcopenia in locally advanced oesophageal cancer patients treated by curative-intent chemo-radiotherapy. Methods The clinical, nutritional, anthropometric, and functional-imaging ( 18 FDG-PET/CT) data were collected in 97 patients treated between 2006 and 2012 in our institution (RTEP3). The skeletal muscle area was automatically delineated on cross-sectional CT images acquired at the 3 rd . lumbar vertebra level and divided by the patient’s squared height (SML3/h 2 ) to obtain the Skeletal Muscle Index (SMI). The primary endpoint was overall survival probability. Results Seventy-six deaths were reported. The median survival time was 27 [95% Confidence Interval 23 – 40] months for the whole population. Univariate analyses (Cox Proportional Hazard Model) showed decreased survival probabilities in patients with reduced SMI, WHO >0, Body Mass Index ≤21, and Nutritional Risk Index ≤97.5. Multivariate analyses showed that reduced SMI (Hazard Ratio 0.948 [0.919 - 0.978] and male sex (2.977 [1.427 - 6.213] were significantly associated to decreased survival. Using Receiver Operating Characteristics curves, the Area Under the Curve (AUC) was 0.73 in males (p=0.0002], the optimal threshold being 51.5 cm 2 /m 2 . In women, the AUC was 0.65 (p=0.19). Conclusion Sarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality in patients treated exclusively by radiochemotherapy for a locally advanced oesophageal cancer. L3 CT images are easily gathered from 18 FDG-PET/CT acquisitions

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Evolutionary dynamics at the tumor edge reveals metabolic imaging biomarkers

10.1101/2020.10.06.20204461 ◽

2020 ◽

Author(s):

Juan Jiménez-Sánchez ◽

Jesús J. Bosque ◽

Germán A. Jiménez Londoño ◽

David Molina-García ◽

Álvaro Martínez ◽

...

Keyword(s):

Cancer Patients ◽

Metabolic Activity ◽

Fdg Pet ◽

Prognostic Value ◽

Small Cell ◽

Peak Activity ◽

Small Cell Lung ◽

Human Cancers ◽

Pet Ct ◽

Fdg Pet Ct

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatio-temporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models, and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, the NPAC, based on the distance from the location of peak activity (proliferation) to the tumor centroid. The NPAC metric can be computed for human patients using 18F-FDG PET/CT images where the voxel of maximum uptake (SUVmax) is taken as the point of peak activity. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NPAC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers new insights into the evolutionary mechanisms behind tumor progression and provides a PET/CT-based biomarker with clinical applicability.Significance StatementThrough the use of different in silico modeling approaches capturing tumor heterogeneity, we predicted that areas of high metabolic activity would shift towards the periphery as tumors become more malignant. To confirm the prediction and provide clinical value for the finding, we took 18F-FDG PET images of breast cancers and non-small-cell lung cancers, where we measured the distance from the point of maximum activity to the tumor centroid, and normalized it by a surrogate of the volume. We show that this metric has a high prognostic value for both malignancies and outperforms other classical PET-based metabolic biomarkers used in oncology.

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The Preoperative Maximum Standardized Uptake Value Measured by 18F-FDG PET/CT as an Independent Prognostic Factor of Overall Survival in Endometrial Cancer Patients

BioMed Research International ◽

10.1155/2014/234813 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 18

Author(s):

Malgorzata Walentowicz-Sadlecka ◽

Bogdan Malkowski ◽

Pawel Walentowicz ◽

Pawel Sadlecki ◽

Andrzej Marszalek ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Cancer Patients ◽

Fdg Pet ◽

Standardized Uptake Value ◽

Maximum Standardized Uptake Value ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Purpose. The aim of this study was to determine if the preoperative maximum standardized uptake value (SUVmax) measured by 18F-FDG PET/CT in the primary tumor has prognostic value in the group of patients with endometrial cancer.Patients, Materials, and Methods. A total of one hundred one consecutive endometrial cancer patients, age range 40–82 years (mean 62 years) and FIGO I–IV stage, who underwent 18-FDG-PET/CT within two weeks prior radical surgery, were enrolled to the study. The maximum SUV was measured and compared with the clinicopathologic features of surgical specimens. The relationship between SUVmax and overall survival was analyzed.Results. The mean preoperative SUVmax was 14.34; range (3.90–33.80) and was significantly lower for FIGO I than for higher stages (P=0.0012), as well as for grade 1 than for grade 2 and 3 (P=0.018), deep myometrial invasion (P=0.0016) and for high risk group (P=0.0004). The analysis of survival ROC curve revealed SUVmax cut-off value of 17.7 to predict high risk of recurrence. Endometrial cancer patients with SUVmax higher than 17.7 characterized by lower overall survival.Conclusion. The preoperative SUVmax measured by 18F-FDG PET/CT is considered as an important indicator reflecting tumor aggressiveness which may predict poor prognosis. High value of SUVmax would be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial cancer.

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Comparison of different images in gross target volume delineating on VX2 nasopharyngeal transplantation tumor models.

Journal of Global Oncology ◽

10.1200/jgo.2019.5.suppl.127 ◽

2019 ◽

Vol 5 (suppl) ◽

pp. 127-127

Author(s):

QingLian Wen ◽

ZhangQiang Xiang

Keyword(s):

Nasopharyngeal Carcinoma ◽

Fdg Pet ◽

Rabbit Model ◽

Standardized Uptake Value ◽

Target Volume ◽

Ct Images ◽

Pathological Examination ◽

Flt Pet ◽

Pet Ct ◽

Fdg Pet Ct

127 Background: To determine the optimum conditions for diagnosis of nasopharyngeal carcinoma, we established VX2 rabbit model to delineate gross target volume (GTV) in different imaging methods. Methods:The orthotopic nasopharyngeal carcinoma (NPC) was established in sixteen New Zealand rabbits. After 7-days inoculation, the rabbits were examined by CT scanning and then sacrificed for pathological examination. To achieve the best delineation, different GTVs of CT, MRI, 18F-FDG PET/CT, and 18F-FLT PET/CT images were correlated with pathological GTV (GTVp). Results: We found 45% and 60% of the maximum standardized uptake value (SUVmax) as the optimal SUV threshold for the target volume of NPC in 18F-FDG PET/CT and 18F-FLT PET/CT images, respectively (GTVFDG45% and GTVFLT60%). Moreover, the GTVMRI and GTVCT were significantly higher than the GTVp ( P ≤ 0.05), while the GTVFDG45% and especially GTVFLT60% were similar to the GTVp ( R = 0.892 and R = 0.902, respectively; P ≤ 0.001). Conclusions: Notably, the results suggested that 18F-FLT PET/CT could reflect the tumor boundaries more accurately than 18F-FDG PET/CT, MRI and CT, which makes 18F-FLT PET-CT more advantageous for the clinical delineation of the target volume in NPC. Keywords: Nasopharyngeal carcinoma; Gross tumor volume; Magnetic resonance imaging, Computed tomography; 18F-FLT PET/CT; 18F-FDG PET/CT

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The Search for New 2-18F-FDG PET/CT Imaging Biomarkers in Advanced Ovarian Cancer Patients

Clinical Nuclear Medicine ◽

10.1097/rlu.0000000000003784 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Roberto C. Delgado Bolton ◽

Adriana K. Calapaquí Terán ◽

Olivier Pellet ◽

Annamaria Ferrero ◽

Francesco Giammarile

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Fdg Pet ◽

Advanced Ovarian Cancer ◽

Ct Imaging ◽

Imaging Biomarkers ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

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Prognostic Value of Metabolic Imaging Data of 11C-choline PET/CT in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13030472 ◽

2021 ◽

Vol 13 (3) ◽

pp. 472

Author(s):

Matteo Donadon ◽

Egesta Lopci ◽

Jacopo Galvanin ◽

Simone Giudici ◽

Daniele Del Fabbro ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Imaging Modality ◽

Standardized Uptake Value ◽

Staging System ◽

Metabolic Imaging ◽

Imaging Data ◽

Operating Characteristics ◽

Choline Pet ◽

Pet Ct

11C-choline positron emission tomography/computed tomography (PET/CT) has been used for patients with some types of tumors, but few data are available for hepatocellular carcinoma (HCC). We queried our prospective database for patients with HCC staged with 11C-choline PET/CT to assess the clinical impact of this imaging modality. Seven parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), liver standardized uptake value (SUVliver), metabolic tumor volume (MTV), photopenic area, metabolic tumor burden (MTB = MTVxSUVmean), and SUVratio (SUVmax/SUVliver). Analysis was performed to identify parameters that could be predictors of overall survival (OS). Sixty patients were analyzed: fourteen (23%) were in stage 0-A, 37 (62%) in stage B, and 9 (15%) in stage C of the Barcelona classification. The Cox regression for OS showed that Barcelona stages (HR = 2.94; 95%CI = 1.41–4.51; p = 0.003) and MTV (HR = 2.11; 95%CI = 1.51–3.45; p = 0.026) were the only factors independently associated with OS. Receiver operating characteristics curve analysis revealed MTV ability in discriminating survival (area under the curve (AUC) = 0.77; 95%CI = 0.57–097; p < 0.001: patients with MTV ≥ 380 had worse OS (p = 0.015)). The use of 11C-choline PET/CT allows for better prognostic refinement in patients undergoing hepatectomy for HCC. Incorporation of such modality into HCC staging system should be considered.

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