Incorporation of tumor shape into an assessment of spatial heterogeneity for human sarcomas imaged with FDG-PET

O’Sullivan, Finbarr; Roy, Supratik; O’Sullivan, Janet; Vernon, Cheryl; Eary, Janet F.

doi:10.1093/biostatistics/kxi010

Cited by 62 publications

(45 citation statements)

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“…For head and neck cancer and non -small cell lung cancer, some preliminary data suggests radiation treatment outcome can be associated with kinetic behavior of 18F-MISO PET (38). O'Sullivan and colleagues noticed that FDG heterogeneity of malignant sarcoma was associated with time to patient death (37,39).…”

Section: Discussionmentioning

confidence: 99%

Intratumoral Metabolic Heterogeneity of Cervical Cancer

Kidd¹,

Grigsby

2008

Clinical Cancer Research

149

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Purpose: Previous research has shown that the intertumoral maximum standardized uptake value (SUV Max ) of F-18 fluorodeoxyglucose (FDG)^positron emission tomography (PET) for cervical cancer predicts disease outcome. The purpose of this study was to evaluate the pretreatment intratumoral metabolic heterogeneity of FDG. Experimental Design: This is a prospective cohort study of 72 patients with International Federation of Gynecology and Obstetrics stages Ib1 to IVa cervical cancer treated with chemoradiation. Three-dimensional FDG-PET threshold tumor volumes were calculated using image segmentation and an adaptive thresholding method for the primary cervix tumor from the pretreatment FDG-PET/computerized tomography. Intratumor heterogeneity was obtained for each patient's cervical tumor by taking the derivative (dV/dT) of the volume-threshold function from 40% to 80%. The association between intratumoral heterogeneity and tumorspecific factors and patient outcomes were determined. Results: The mean cervix tumor SUV Max was 12.4 (range, 3.0-38.4). The mean differential tumor heterogeneity was -1.074 (range, -0.107 to -5.623).There was no association between dV/dTand SUV Max (R 2 = 0.069), but there was a relationship with dV/dT and tumor volume (R 2 = 0.881). There was no correlation of dV/dT with tumor histology (P = 0.4905). Heterogeneity was significantly associated with the risk of lymph node metastasis at diagnosis (P = 0.0009), tumor response to radiation as evaluated by FDG-PET obtained 3 months after completing treatment (P = 0.0207), risk of pelvic recurrence (P = 0.0017), and progression-free survival (P = 0.03). Conclusions: Cervical intratumoral FDG metabolic heterogeneity on the pretreatment FDG-PET predicts risk of lymph node involvement at diagnosis, response to therapy, and risk of pelvic recurrence.It is understood that, on a microscopic level, tumors are heterogeneous (1 -3). Evaluation of tumor microenvironments has shown heterogeneity relating to variation in tumor responsiveness to treatment (4, 5), degree of vascularity (6, 7), hypoxia (1, 7, 8), proliferation rates (7), energy metabolites, and gene expression (9 -11). Although tumor heterogeneity has been shown within these tumor microenvironments, intratumoral heterogeneity across the entire volume of primary tumors in humans has not been quantified or analyzed for its association with outcome measures. F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging allows intratumoral heterogeneity to be assessed using objective criteria.Cervical cancer is an example of a tumor that shows heterogeneity relating to hypoxia, variation in response to treatment, risk of metastatic spread, and gene expression (4, 5, 10, 12 -15). Additionally, the response of the primary cervical cancer to treatment has been shown to be a much more complex issue than simply relating outcome to clinical stage, tumor volume, or tumor hypoxia. Specifically, our previous research has shown that the primary cervix tumor maximal standardized uptake...

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Section: Discussionmentioning

confidence: 99%

Intratumoral Metabolic Heterogeneity of Cervical Cancer

Kidd¹,

Grigsby

2008

Clinical Cancer Research

149

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“…Its many advantages for evaluation of patients with sarcomas include ability to provide quantitative, objective tumor metabolic information noninvasively, three-dimensional high-resolution images, and standardization in imaging techniques for tumor restaging and treatment response situations [18]. We used FDG-PET imaging uptake data for synovial sarcomas in a relatively large group.…”

Section: Discussionmentioning

confidence: 99%

Risk Assessment Based on FDG-PET Imaging in Patients with Synovial Sarcoma

Lisle

Eary

O’Sullivan

et al. 2008

Clin Orthop Relat Res

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Synovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent not all synovial sarcomas share the same tumor biology. 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We therefore assessed the clinical value of 18 F-FDG-PET-derived maximum standard uptake value (SUV max ) for predicting survival in patients with synovial sarcoma. 18 F-FDG-PET was performed in 44 patients with synovial sarcoma before therapy and resection. SUV max was calculated for each tumor and then evaluated for prognostic usefulness along with metastasis at presentation, tumor grade, histopathologic subtype, age, gender, postsurgical margins, anatomic location, and tumor size for overall survival and progression-free survival. SUV max ranged from 1.2 to 13.0 (median, 4.35). Pretherapy tumor SUV max predicted overall survival and progression-free survival. Patients presenting with a SUV max greater than 4.35 had a decreased diseasefree survival and were therefore at high risk for having local recurrences and metastatic disease.

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“…18 F-FDG, which correlates with cellular glucose metabolism, is the most widely used radioactive tracer in oncology and is often used in whole-body scanning to detect distant metastases (13). 18 F-FDG is considered a valuable adjunct to existing imaging methods in an increasing number of clinical oncologic applications, such as metastatic adenocarcinoma and musculoskeletal sarcomas (14)(15)(16). Although metastatic prostate cancer in humans traditionally exhibits relatively low uptake of 18 F-FDG, several studies have demonstrated its utility as a promising prognostic measure for patient survival (17,18).…”

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confidence: 99%

Characterization of Osteolytic, Osteoblastic, and Mixed Lesions in a Prostate Cancer Mouse Model Using ¹⁸F-FDG and ¹⁸F-Fluoride PET/CT

Hsu¹,

Virk²,

Stout³

et al. 2008

J Nucl Med

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The combination of small-animal PET/CT scans and conventional imaging methods may enhance the evaluation of in vivo biologic interactions of murine models in the study of prostate cancer metastasis to bone. Methods: Small-animal PET/CT scans using 18 F-fluoride ion and 18 F-FDG coregistered with high-resolution small-animal CT scans were used to longitudinally assess the formation of osteoblastic, osteolytic, and mixed lesions formed by human prostate cancer cell lines in a severe combined immunodeficient (SCID) mouse tibial injection model. These scans were correlated with plain radiographs, histomorphometry, and soft-tissue measurements. Results: Smallanimal PET/CT scans were able to detect biologic activity of cells that induced an osteoblastic lesion 2 wk earlier than on plain radiographs. Furthermore, both the size and the activity of the lesions detected on PET/CT images significantly increased at each successive time point (P , 0.05). 18 F-FDG lesions strongly correlated with soft-tissue measurements, whereas 18 F-fluoride ion activity correlated with bone volume measured on histomorphometric analysis (P , 0.005). Osteolytic lesions were successfully quantified using small-animal CT, whereas lesion sizes measured on 18 F-FDG PET scans also strongly correlated with soft-tissue tumor burden (P , 0.05). In contrast, for mixed lesions, 18 F-fluoride ion and 18 F-FDG PET/CT scans detected only minimal activity. Conclusion: 18 F-FDG and 18 F-fluoride ion PET/CT scans can be useful tools in characterizing pure osteolytic and osteoblastic lesions induced by human prostate cancer cell lines. The value of this technology needs further evaluation to determine whether these studies can be used effectively to detect more subtle responses to different treatment regimens in animal models.

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Incorporation of tumor shape into an assessment of spatial heterogeneity for human sarcomas imaged with FDG-PET

Cited by 62 publications

References 4 publications

Intratumoral Metabolic Heterogeneity of Cervical Cancer

Intratumoral Metabolic Heterogeneity of Cervical Cancer

Risk Assessment Based on FDG-PET Imaging in Patients with Synovial Sarcoma

Characterization of Osteolytic, Osteoblastic, and Mixed Lesions in a Prostate Cancer Mouse Model Using ¹⁸F-FDG and ¹⁸F-Fluoride PET/CT

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Incorporation of tumor shape into an assessment of spatial heterogeneity for human sarcomas imaged with FDG-PET

Cited by 62 publications

References 4 publications

Intratumoral Metabolic Heterogeneity of Cervical Cancer

Intratumoral Metabolic Heterogeneity of Cervical Cancer

Risk Assessment Based on FDG-PET Imaging in Patients with Synovial Sarcoma

Characterization of Osteolytic, Osteoblastic, and Mixed Lesions in a Prostate Cancer Mouse Model Using 18F-FDG and 18F-Fluoride PET/CT

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Characterization of Osteolytic, Osteoblastic, and Mixed Lesions in a Prostate Cancer Mouse Model Using ¹⁸F-FDG and ¹⁸F-Fluoride PET/CT