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Old 04-16-2009, 03:38 PM   #1
Rich66
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Researchers Can Tell in a Single Treatment if Chemotherapy is Working

PET and PET/CT: A clinical guide LINK
(Notably mentions glucose, G-CSF and "dual time point imaging" issues)



SUV in PET: Silly or Smart Uptake Values ?

2010 Presentation on variables influencing PET uptake values:
http://www.guillemet.org/irene/cours...A_Brussels.pdf

Suggests time from injection to scan needs to be over an hour and the same interval from scan to scan. Uptake values may vary between facilities, suggesting benefit of adequate, consistent timing and use of same facilty to allow meaningful scan comparisons.



Acta Radiol. 2010 Sep;51(7):782-8.
Interobserver variability among measurements of the maximum and mean standardized uptake values on (18)F-FDG PET/CT and measurements of tumor size on diagnostic CT in patients with pulmonary tumors.

Huang YE, Chen CF, Huang YJ, Konda SD, Appelbaum DE, Pu Y.
Department of Nuclear Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.


TEXT

Abstract

BACKGROUND: (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET) imaging has been shown to be an accurate method for diagnosing pulmonary lesions, and the standardized uptake value (SUV) has been shown to be useful in differentiating benign from malignant lesions.
PURPOSE: To survey the interobserver variability of SUV(max) and SUV(mean) measurements on (18)F-FDG PET/CT scans and compare them with tumor size measurements on diagnostic CT scans in the same group of patients with focal pulmonary lesions.
MATERIAL AND METHODS: Forty-three pulmonary nodules were measured on both (18)F-FDG PET/CT and diagnostic chest CT examinations. Four independent readers measured the SUV(max) and SUV(mean) of the (18)F-FDG PET images, and the unidimensional nodule size of the diagnostic CT scans (UD(CT)) in all nodules. The region of interest (ROI) for the SUV measurements was drawn manually around each tumor on all consecutive slices that contained the nodule. The interobserver reliability and variability, represented by the intraclass correlation coefficient (ICC) and coefficient of variation (COV), respectively, were compared among the three parameters. The correlation between the SUV(max) and SUV(mean) was also analyzed.
RESULTS: There was 100% agreement in the SUV(max) measurements among the 4 readers in the 43 pulmonary tumors. The ICCs for the SUV(max), SUV(mean), and UD(CT) by the four readers were 1.00, 0.97, and 0.97, respectively. The root-mean-square values of the COVs for the SUV(max), SUV(mean), and UD(CT) by the four readers were 0%, 13.56%, and 11.03%, respectively. There was a high correlation observed between the SUV(max) and SUV(mean) (Pearson's r=0.958; P <0.01).
CONCLUSION: This study has shown that the SUV(max) of lung nodules can be calculated without any interobserver variation. These findings indicate that SUV(max) is a more valuable parameter than the SUV(mean) or UD(CT) for the evaluation of therapeutic effects of chemotherapy or radiation therapy on serial studies.

PMID: 20707663 [PubMed - in process]


J Nucl Med. 2009 May;50 Suppl 1:122S-50S.
From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors.

Wahl RL, Jacene H, Kasamon Y, Lodge MA.
Division of Nuclear Medicine, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-0817, USA. rwahl@jhmi.edu


FREE TEXT

Abstract

The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with (18)F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0.
METHODS: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors' experience, draft criteria were formulated for PET tumor response to treatment.
RESULTS: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has limitations in response assessments. For example, despite effective treatment, changes in tumor size can be minimal in tumors such as lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor. CT tumor density, contrast enhancement, or MRI characteristics appear more informative than size but are not yet routinely applied. RECIST criteria may show progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher complete response rate than the original RECIST criteria, at least in lymph nodes. Variability appears greater in assessing progression than in assessing response. Qualitative and quantitative approaches to (18)F-FDG PET response assessment have been applied and require a consistent PET methodology to allow quantitative assessments. Statistically significant changes in tumor standardized uptake value (SUV) occur in careful test-retest studies of high-SUV tumors, with a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically relevant beneficial changes are often associated with a 30% or greater decline. The more extensive the therapy, the greater the decline in SUV with most effective treatments. Important components of the proposed PERCIST criteria include assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol, using a fixed small region of interest about 1 cm(3) in volume (1.2-cm diameter) in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, requiring a 30% decline in SUV for "response," and deferring to RECIST 1.1 in cases that do not have (18)F-FDG avidity or are technically unsuitable. Criteria to define progression of tumor-absent new lesions are uncertain but are proposed.
CONCLUSION: Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria have limitations, particularly in assessing the activity of newer cancer therapies that stabilize disease, whereas (18)F-FDG PET appears particularly valuable in such cases. The proposed PERCIST 1.0 criteria should serve as a starting point for use in clinical trials and in structured quantitative clinical reporting. Undoubtedly, subsequent revisions and enhancements will be required as validation studies are undertaken in varying diseases and treatments.

PMID: 19403881 [PubMed - indexed for MEDLINE]PMCID: PMC2755245Free PMC Article






Using PET/CT Imaging, Researchers Can Tell in a Single Treatment if Chemotherapy is Working

Posted Date: 4/15/2009
Faculty: Frederick (Fritz) Eilber, M.D.


Oncologists often have to wait months before they can determine whether a treatment is working. Now, using a non-invasive method, researchers at UCLA’s Jonsson Comprehensive Cancer Center have shown that they can determine after a single cycle of chemotherapy whether the toxic drugs are killing the cancer or not.

Using a combination Positron Emission Tomography (PET) and computed tomography (CT) scanner, researchers monitored 50 patients undergoing treatment for high-grade soft tissue sarcomas. The patients were receiving neoadjuvant chemotherapy treatments to shrink their tumors prior to surgery. The study found that response could be determined about a week after the first dose of chemotherapy drugs. Typically, patients are scanned at about three months into chemotherapy to determine whether the treatment is working.

“The question was, how early could we pick up a response? We wanted to see if we could determine response after a single administration of chemotherapy,” said Dr. Fritz Eilber, an assistant professor of surgical oncology, director of the Sarcoma Program at UCLA’s Jonsson Cancer Center and senior author of the study. “There’s no point in giving a patient a treatment that isn’t working. These treatments make patients very sick and have long-term serious side effects. ”

The study appears in the April 15 issue of the journal Clinical Cancer Research.

PET scanning shows biochemical functions in real time, acting as a sort of molecular camera. For this study, Eilber and his team monitored the tumor’s metabolic function, or how much sugar was being consumed by the cancer cells. Because they’re growing out of control, cancer cells use much more sugar than do normal cells, making them light up under PET scanning using a glucose uptake probe called FDG. In order to identify an effective response to treatment, researchers needed to see a 35 percent decrease in the tumor’s metabolic activity.

Of the 50 patients in the study, 28 did not respond and Eilber and his team knew within a week of their initial treatment. This allows the treatment course to be discontinued or changed
to another more effective treatment, getting the patient to surgery more quickly.

“The significance of this study was that it identified people – more than half of those in the study – who were not going to benefit from the treatment early in the course of their therapy,” Eilber said. “This information significantly helps guide patient care. Although this study was performed in patients scheduled for surgery, I think these findings will have an even greater impact on patients with inoperable tumors or metastatic disease as you get a much quicker evaluation of treatment effectiveness and can make decisions that will hugely impact quality of life.”

Eilber said he was surprised how soon response to therapy could be determined.

“We had an idea that patients either respond or do not respond to treatment, but we weren’t sure how early you could see that,” he said. “I really was not sure we would be able to see effectiveness this early.”

Eilber and his team will continue to follow the patients and a clinical trial currently is underway based on the results of this study. Eilber believes it will help personalize treatment for each patient and may one day become the standard of care.

Researchers also may use the non-invasive imaging method to gauge response to novel and targeted therapies. Eilber said that they are clinically testing new tracers as well. Instead of measuring glucose uptake, these probes look at cell growth. Response to therapy also may be tested using PET in other cancer types, he said.

The nearly two-year study represented a true multidisciplinary effort, Eilber said. Experts from surgery, medical oncology, molecular and medical pharmacology, radiology, pathology, orthopedics, nuclear medicine and biostatistics comprised the research team.

The study was funded by grants from the UCLA In Vivo Cellular and Molecular Imaging Centers and the Department of Energy.

UCLA's Jonsson Comprehensive Cancer Center has more than 350 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2008, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for nine consecutive years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.



Breast Cancer Res Treat. 2009 Feb;113(3):509-17. Epub 2008 Mar 9.
PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer.

Dehdashti F, Mortimer JE, Trinkaus K, Naughton MJ, Ellis M, Katzenellenbogen JA, Welch MJ, Siegel BA.
Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, St Louis, MO 63110, USA. dehdashtif@mir.wustl.edu
PURPOSE: To determine if response to endocrine therapy of breast cancer can be predicted by either a metabolic "flare reaction" detected by positron emission tomography (PET) with 2-[(18)F]-fluoro-2-deoxyglucose (FDG), induced by an estradiol challenge, or by estrogen-receptor (ER) status, determined by PET with the estrogen analog 16alpha-[(18)F]fluoroestradiol-17beta (FES). METHODS: Fifty-one post-menopausal women with advanced estrogen-receptor positive breast cancer were studied. Patients underwent FES-PET and FDG-PET at baseline and repeat FDG-PET after 30 mg estradiol. Tracer uptakes was measured as the standardized uptake value (SUV). Patients were subsequently treated with either an aromatase inhibitor or fulvestrant. A prospectively defined cut-off SUV >or= 2 for FES was considered positive for ER expression. A cutoff of >or=12% increase in SUV for FDG, determined by ROC analysis, represented metabolic flare. PET results were correlated with responsiveness to endocrine therapy. RESULTS: Seventeen patients responded and 34 patients did not respond to endocrine therapy. Four responders and one non-responder had a clinical flare reaction, while only the responders demonstrated metabolic flare. After estradiol challenge, a significantly higher mean (+/-SD) percent change in SUV for FDG was noted in responders (20.9 +/- 24.2) compared with non-responders (-4.3 +/- 11.0, P < 0.0001). On FES-PET, a higher tumor SUV was noted in responders (3.5 +/- 2.5) compared with non-responders (2.1 +/- 1.8, P = 0.0049). There was significantly longer overall survival in patients with metabolic flare than in those without flare regardless of type of endocrine therapy (P = 0.0062). CONCLUSION: Baseline tumor FES uptake and metabolic flare after an estradiol challenge are both predictive of responsiveness to endocrine therapy in ER+ breast cancer.

PMID: 18327670 [PubMed - indexed for MEDLINE]


Clin Cancer Res. 2010 May 11. [Epub ahead of print]
Tumor Metabolism and Blood Flow as Assessed by Positron Emission Tomography Varies by Tumor Subtype in Locally Advanced Breast Cancer.

Specht JM, Kurland BF, Montgomery SK, Dunnwald LK, Doot RK, Gralow JR, Ellis GK, Linden HM, Livingston RB, Allison KH, Schubert EK, Mankoff DA.
Authors' Affiliations: Medical Oncology and Nuclear Medicine, Departments of Medicine and Pathology, University of Washington, Seattle, Washington; Clinical Statistics, Fred Hutchinson Cancer Research Center, Seattle, Washington; and Medicine, Arizona Cancer Center, Tucson, Arizona.
Abstract

PURPOSE: Dynamic positron emission tomography (PET) imaging can identify patterns of breast cancer metabolism and perfusion in patients receiving neoadjuvant chemotherapy (NC) that are predictive of response. This analysis examines tumor metabolism and perfusion by tumor subtype. EXPERIMENTAL DESIGN: Tumor subtype was defined by immunohistochemistry in 71 patients with locally advanced breast cancer undergoing NC. Subtype was defined as luminal [estrogen receptor (ER)/progesterone receptor (PR) positive], triple negative [TN; ER/PR negative, human epidermal growth factor receptor 2 (HER2) negative], and HER2 (ER/PR negative, HER2 overexpressing). Metabolic rate (MRFDG) and blood flow (BF) were calculated from PET imaging before NC. Pathologic complete response (pCR) to NC was classified as pCR versus other. RESULTS: Twenty-five (35%) of 71 patients had TN tumors; 6 (8%) were HER2 and 40 (56%) were luminal. MRFDG for TN tumors was on average 67% greater than for luminal tumors (95% confidence interval, 9-156%) and average MRFDG/BF ratio was 53% greater in TN compared with luminal tumors (95% confidence interval, 9-114%; P < 0.05 for both). Average BF levels did not differ by subtype (P = 0.73). Most luminal tumors showed relatively low MRFDG and BF (and did not achieve pCR); high MRFDG was generally matched with high BF in luminal tumors and predicted pCR. This was not true in TN tumors. CONCLUSION: The relationship between breast tumor metabolism and perfusion differed by subtype. The high MRFDG/BF ratio that predicts poor response to NC was more common in TN tumors. Metabolism and perfusion measures may identify subsets of tumors susceptible and resistant to NC and may help direct targeted therapy. Clin Cancer Res; 16(10); 2803-10. (c)2010 AACR.

PMID: 20460489 [PubMed - as supplied by publisher]

My interpretation:
Higher uptake meant more probably triple negative and less response to chemo. Luminal (ER+/PR+) usually 67% lower uptake but..if high uptake occurred in a "luminal" tumor, likely to respond well to chemo.



Breast Cancer. 2010 Jul 9. [Epub ahead of print]
Early metabolic response to neoadjuvant letrozole, measured by FDG PET/CT, is correlated with a decrease in the Ki67 labeling index in patients with hormone receptor-positive primary breast cancer: a pilot study.

Ueda S, Tsuda H, Saeki T, Omata J, Osaki A, Shigekawa T, Ishida J, Tamura K, Abe Y, Moriya T, Yamamoto J.
Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan, syueda2000@yahoo.co.jp.
Abstract

PURPOSE: To assess whether the early metabolic response evaluated by (18)F-fluorodeoxy-glucose positron emission combined with computed tomography (FDG PET/CT) predicts the morphological, pathological, and cell-cycle responses to neoadjuvant endocrine therapy of hormone receptor-positive primary breast cancer. STUDY DESIGN: Eleven patients (12 tumors) with estrogen receptor-positive (Allred score 7 or 8) primary breast cancer were enrolled. All patients received a daily dose (2.5 mg) of letrozole for 12 weeks followed by surgery. Sequential FDG PET/CT scans were performed before treatment (baseline), at 4 weeks after the initiation of endocrine therapy (PET2), and prior to surgery (PET3). Tumors showing a 40% or more reduction and those showing a less than 40% reduction in the standardized uptake value maximum (SUV(max)) at PET2 compared with the baseline PET were defined as metabolic responders and metabolic nonresponders, respectively. Change in tumor size as measured by ultrasound (morphological response), pathological response, and change in the Ki67 labeling index in tumor tissue (cell-cycle response) during the neoadjuvant letrozole therapy were compared between the metabolic responders and nonresponders. RESULTS: The average decreases in SUV(max) at PET2 compared with the baseline PET in the metabolic responders (n = 6) and the metabolic nonresponders (n = 6) were 60.9% (+/-21.3 SD) and 14.2% (+/-12.0 SD), respectively. At PET3 compared with the baseline PET, the metabolic responders showed a significantly higher decrease of 64.5% (+/-18.7 SD) (p = 0.0004), whereas the nonresponders showed a nonsignificant decrease of 16.7% (+/-14.1 SD) (p = 0.06). The morphological and pathological responses after letrozole therapy did not differ between the metabolic responders and nonresponders. The metabolic responders showed a marked decrease in the Ki67 labeling index at 2 weeks after the initiation of treatment (62.9%, +/-35.9 SD, p = 0.04) and at surgery (91.7%, +/-10.7 SD, p = 0.03) compared with the baseline values. In contrast, metabolic nonresponders showed no significant change in the Ki67 index either after 2 weeks of therapy or at surgery. CONCLUSION: Cell-cycle response monitored by the Ki67 labeling index correlates with metabolic response monitored by tumor SUV(max). Monitoring of tumor SUV(max) using FDG PET/CT may be feasible to predict cell-cycle response to neoadjuvant endocrine therapy of primary breast cancer.

PMID: 20617404 [PubMed - as supplied by publisher]




Skeletal Radiol. 2010 Aug 2. [Epub ahead of print]
Recognition of fibrous dysplasia of bone mimicking skeletal metastasis on 18F-FDG PET/CT imaging.

Su MG, Tian R, Fan QP, Tian Y, Li FL, Li L, Kuang AR, Miller JH.
National Key Discipline of Medical Imaging and Nuclear Medicine, Department of Nuclear Medicine, West China Hospital, Sichuan University School of Medicine, 37 Guo Xue Xiang, 610041, Chengdu, Sichuan, People's Republic of China, suminggang@sina.com.
TEXT

AbstractPURPOSE: Fibrous dysplasia of bone (FDB) reveals intense 18F-FDG uptake mimicking metastases on 18F-FDG PET/CT. We reviewed sites of FDB revealed by 18F-FDG PET/CT imaging to allow identification of this abnormality.
MATERIALS AND METHODS: Eleven patients (7 male, 4 female, aged 16-78 years) were evaluated after 55 MBq (0.15 mCi)/kg 18F-FDG utilizing a 16-slice multiple detector CT (MDCT) whole-body PET scanner, with LOR algorithm 3D reconstruction. One- and 2-h imaging was performed in 9 patients. Standard uptake value (SUV) for each lesion, on early and delayed imaging, was calculated. Lesions were confirmed in 6 patients by biopsy. The PET images correlated with MDCT to establish the imaging characteristics.
RESULTS: Solitary lesions were found in 4 patients, two lesions in 1 patient, and in 6 patients there were multiple bone lesions. The SUV(early) ranged from 1.23 to 9.64 with an average of 3.76 +/- 2.40. The SUV(delayed) ranged from 1.76 to 11.42 with an average of 4.51 +/- 3.07. The SUV(delayed) decreased or increased slightly (-31% to 5%) in 6 of our patients, and increased significantly (11% to 39%) in 3. There was a negative correlation between SUVs and age, as well as the number of affected bones.
CONCLUSIONS: In our study, FDB had wide skeletal distribution with variability of 18F-FDG uptake and CT appearance. SUV in the delayed stage was seen to either decrease or increase on dual-time 18F-FDG PET scanning. It is very important to recognize the characteristics of this skeletal dysplasia to allow differentiation from skeletal metastasis.

PMID: 20680622 [PubMed - as supplied by publisher]



Suggestions for Management of Diabetic Patients for FDG PET-CT Scans
Edmonton, 2007
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Old 09-01-2010, 11:57 PM   #2
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Old 09-02-2010, 12:00 AM   #3
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