SUV Values Research Articles

Variations of the hepatic SUV in relation to the body mass index in whole body PET-CT studies

ObjectiveTo evaluate SUV changes in the liver in relation to body mass index (BMI) of patients who undergo whole body PET-CT scans. Material and methodsA retrospective study was performed. The variables studied were injected dose of 18FFDG (mCi), age (years), blood glucose level (mg/dL), height (cm) and weight (kg). BMI was calculated and the SUV mean value was expressed according to gender and BMI. A linear regression analysis was applied to identify the independent variables that best predict the SUV value. ResultsSix hundred and three patients were studied (305 women, 298 men; mean age: 54.9±15.2 years old). Mean SUV measurement was significantly higher in males than females and increased significantly both in male and female patients who were overweight and even more in obese patients. The independent variables that best predicted the SUV value were gender, age, and BMI. In those patients having similar characteristics related to the analyzed variables, the SUV value increased by 0.002 for each increase in one year, and by 0.066 per unit increase in the BMI value. ConclusionsHepatic uptake of 18FFDG increases according to the patient's BMI. The independent variables that best predict the hepatic SUV value are age and sex of patients. Our findings show that the practice of using the physiological hepatic metabolic activity level as a reference regarding questionable deposits elsewhere in the abdomen and pelvis is not useful, at least in male patients with overweightness and obesity.

Variaciones del SUV hepático con relación al índice de masa corporal en estudios PET/TC de cuerpo entero

To evaluate SUV changes in the liver in relation to body mass index (BMI) of patients who undergo whole body PET-CT scans.A retrospective study was performed. The variables studied were injected dose of (18F)FDG (mCi), age (years), blood glucose level (mg/dL), height (cm) and weight (kg). BMI was calculated and the SUV mean value was expressed according to gender and BMI. A linear regression analysis was applied to identify the independent variables that best predict the SUV value.Six hundred and three patients were studied (305 women, 298 men; mean age: 54.9±15.2 years old). Mean SUV measurement was significantly higher in males than females and increased significantly both in male and female patients who were overweight and even more in obese patients. The independent variables that best predicted the SUV value were gender, age, and BMI. In those patients having similar characteristics related to the analyzed variables, the SUV value increased by 0.002 for each increase in one year, and by 0.066 per unit increase in the BMI value.Hepatic uptake of (18F)FDG increases according to the patient's BMI. The independent variables that best predict the hepatic SUV value are age and sex of patients. Our findings show that the practice of using the physiological hepatic metabolic activity level as a reference regarding questionable deposits elsewhere in the abdomen and pelvis is not useful, at least in male patients with overweightness and obesity.

F18-FDG-PET/CT thyroid incidentalomas: a wide retrospective analysis in three Italian centres on the significance of focal uptake and SUV value

Thyroid incidental uptake is defined as a thyroid uptake incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for non-thyroid diseases. Aim of the study was to establish the prevalence and pathological nature of focal thyroid incidentalomas detected at F18-FDG-PET/CT in patients studied for oncological purposes and not for thyroid disease. Secondary end point was to establish a possible maximum standardised uptake value cut-off over which a malignant lesion should be suspected. We have retrospectively evaluated 49519 patients who underwent F18-FDG-PET/CT for oncologic purposes in three Nuclear Medicine Centres (N.1 = 11278, N.2 = 31076, N.3 = 7165). A focal incidental thyroid uptake was diagnosed in 729 (1.5 %) patients (287-39.4 % male and 442-60.6 % female; average age: 65.26). Of 729 thyroid incidentalomas 211 (28.9 %) underwent further investigation to determine the nature of the nodule; 124/211 (58.8 %) incidentalomas were benign, 72/211 (34.1 %) malignant, 4/211 (1.9 %) non-diagnostic at cytological examination in the absence of surgery and histological evaluation and 11/211 (5.2 %) were indeterminate at cytological examination. A centre-based receiver operating curve (ROC) analysis of the patients with a definitive diagnosis was performed to identify a SUVmax cut-off useful in differentiating benign from malignant incidentalomas. In the centre N.1 it was 4.8 (sensitivity = 95.7 %, specificity = 46.4 %, area under the curve = 0.758); 5.3 in the centre N.2 (sensitivity = 76.3 %, specificity = 72.5 %, area under the curve = 0.815); 7 in the centre N.3 (sensitivity = 57.1 %, specificity = 79.3 %, area under the curve = 0.627). F18-FDG-PET/CT thyroid incidentalomas are a relevant diagnostic reality which requires further investigations and clinical management especially considering that, despite mainly benign, approximately one third of focal thyroid uptakes are malignant.

Semi-Quantitative Evaluation of Pre-Transplant FDG-PET in Relapsed and Refractory Hodgkin Lymphoma

AbstractAbstract 2015▪▪This icon denotes a clinically relevant abstract Introduction:We previously reported the prognostic impact of pre-transplant functional imaging (FI) on outcome following autologous stem cell transplant (ASCT) for patients with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) (Moskowitz AJ, et al. Blood 2010). This analysis was based upon patients treated on 3 consecutive Memorial Sloan-Kettering Cancer Center (MSKCC) clinical trials from 1994 to 2003. The cohort included patients evaluated by gallium or FDG-PET and the 5 year event free survival (EFS) for patients with normal vs abnormal pre-transplant FI was 75% and 31% respectively. Based upon these results, our treatment program has focused on the use of FDG-PET to determine eligibility for ASCT. While determination of FI results in our series was based upon visual interpretation, we now aim to investigate whether semi-quantitative evaluation of pre-transplant FDG-PET could better distinguish favorable and less favorable cohorts. Methods:Patients with rel/ref HL treated on MSKCC clinical trials who underwent pre-salvage and pre-transplant evaluation with FDG-PET were included in this analysis. Pre-salvage and pre-transplant FDG-PET reports were reviewed and maximum SUV values for each scan were recorded. The delta-SUV was a calculation of the percent change in maximum SUV between pre-salvage and pre-transplant FDG-PET. EFS was calculated using the Kaplan-Meier method. The prognostic impact of FDG-PET results by visual interpretation and semi-quantitative interpretation was evaluated using the log-rank test. Results:One hundred and thirty nine patients with rel/ref HL treated on consecutive MSKCC clinical trials from October 2000 through August 2010 were evaluated. Of the 139 patients, 104 (75%) achieved FDG-PET normalization prior to ASCT. The median follow-up for survivors was 6 years. The 6 year EFS for FDG-PET negative and FDG-PET positive patients was 79% and 53% respectively (p<0.001, figure 1). Among the patients with abnormal pre-transplant FDG-PET, the median maximum SUV value was 4.3 and the median delta-SUV was 60%. We tested absolute pre-transplant maximum SUV values of 2, 3, 4, and 5 and we were unable to find a value of prognostic significance among FDG-PET positive patients. We tested delta-SUV values of 50%, 60%, 63%, 66%, and 72.9%. Patients with positive pre-transplant FDG-PET and ≥63% delta-SUV were found to have similar outcomes as patients with negative pre-transplant FDG-PET (p=.47, figure 2). The 6 year EFS for delta-SUV ≥63% patients was 77% compared to 44% for delta-SUV < 63% (p=0.12). Conclusion:For rel/ref HL patients undergoing ASCT, semi-quantitative evaluation of pre-transplant FDG-PET using delta-SUV of 63% identifies a favorable cohort among patients with positive pre-transplant FDG-PET. The difference in outcome for patients with ≥63% delta-SUV and < 63% delta-SUV was not statistically significant, however, likely due to the small number of FDG-PET positive patients in our series. Nevertheless, patients who achieve delta-SUV of at least 63% prior to ASCT achieved similar outcomes as those with negative pre-transplant FDG-PET. The prognostic significance of the 63% delta-SUV cutoff needs to be evaluated further in prospective studies. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

A tool for the extraction of new disease biomarkers from ex vivo and in vivo data

Motivation and Objectives Recent studies have demonstrated the correlation among features of diseases obtained from ex vivo and in vivo Molecular Imaging (MI) studies (e.g. Genomics and Positron Emission Tomography, PET, Strauss et al., 2008; Genomics and Computerized Tomography, CT, Segal et al., 2007), opening a new role to non invasive clinical MI technologies in the current approach of personalized medicine. At present, proper databases and statistical methodologies are on hand to deal with the different modalities of ex vivo and in vivo MI data but tools for the extraction of new disease biomarkers are still not available for the purpose of clinicians. The main interest of clinical specialists is in finding biomarkers of disease with diagnostic and prognostic values, and this can be performed with an interdisciplinary approach offered by ex vivo and in vivo MI and then translated into the clinical environment. Aim of this work was the development of a software tool (“cOuch” Correlative and Collaborative Touch System) (Castiglioni et al., 2011) designed to be used by clinicians to find new diagnostic/ prognostic biomarkers of disease from the comparison of ex vivo and in vivo data of patients. In this work, as representative example, “cOuch” has been applied to assess the prognostic and diagnostic value of the Standardized Uptake Value (SUV, Graham et al., 2000), a parameter of regional metabolic uptake measured by PET and 18F-labeled fluorodeoxiglucouse for breast cancer lesions.

18F-FDG semi-quantitative parameters and biological prognostic factors in locally advanced breast cancer

AimTo analyse the correlation between 18F-FDG uptake assessed by PET/CT in locally advanced breast tumours and histopathological and immunohistochemical prognostic factors. Material and methodsThirty-six women with breast cancer were prospectively evaluated. PET/CT was requested in the initial staging previous to adjuvant chemotherapy (multicentric study).All the patients underwent an 18F-FDG PET/CT with a dual-time-point acquisition. Both examinations were evaluated qualitatively and semiquantitatively with calculation of SUVmax values in PET-1 (SUV-1) and in PET-2 (SUV-2) and the percentage variation of the standard uptake values (retention index) between PET-1 and PET-2.Clinical and metabolic stages were assessed according to TNM classification. The biological prognostic parameters, such as the steroid receptor status, p53 and c-erbB-2 expression, proliferation rate (Ki-67), and grading were determined from tissue of the primary tumour. Metabolic and biological parameters were correlated. ResultsA positive relationship was found between semiquantitative metabolic parameters and biological parameters. SUV-1 and SUV-2 values did not show significant statistical correlation (p<.05) except for the clinical tumour size.About the biological parameters, retention index showed the best results with positive and significant relation (p<.05) with estrogen and progesterone receptor status and Ki-67. Isolated SUV values did not show significant relation to these parameters. ConclusionRetention index showed the best relation with biological parameters compared to isolated SUVmax values. These data suggest that SUV change over time is a prognostic marker.

Predicting the Risk of Secondary Malignancies Associated With Pelvic Nodal Irradiation in the Treatment of Prostate Cancer

superiority in prostate cancer detection including local recurrence and lymph node metastases over F-18 fluorodeoxyglucose (FDG) PET and a higher sensitivity and specificity compared with other imaging studies in prostate cancer. We report our experience. Materials/Methods: From January 2010 to December 2011, a total of 76 patients with prostate cancer were referred for evaluation. Of these, 32 patients underwent primary radiation therapy treatment, 23 patients were for adjuvant radiation therapy, and 10 patients received salvage radiation therapy as well as 11 patients were treated with palliative radiation therapy for painful bone metastases. High risk and patients with metastatic disease also received hormonal therapy. Patients with suspicious lymph nodes on CAT scan or MRI during staging work up underwent C11-acetate PET. The findings and changes to original treatment plan are reported. Results: A total of 19 patients had C11-acetate PET. Eleven patients (57%) had high risk prostate cancer. Nine patients (47%) underwent primary radiation therapy treatment. Seven patients (37%) had increased SUV values (Above 6). The involved areas on C11-acetate PET included external iliac lymph nodes in five patients as well as both, iliac external and inguinal lymph nodes in two patients; Modification of radiation therapy treatment volumes, dose or both was required in three , one and three patients respectively. The decision to add hormone therapy remained the same without any change. With a mean follow up of 18 months, all of these patients remained under biochemical control and C11-acetate PET showed decrease in SUV at the previously affected regions. There was no correlation between PSA level and lymph node involvement but most of the patients with positive C11-acetate PET were in high risk category. Conclusions: C11-acetate PET was useful in detecting lymph node metastases especially in high risk prostate cancer patients. The findings of C11-acetate PET resulted in the change of radiation therapy treatment field/ volume or dose in more than one third of the patients (37%), hopefully leading to better local regional control. SUV values may serve as a tool for monitoring radiation therapy response. Further studies including prospective clinical trials are needed. Author Disclosure: J. Hinojosa Gomez: None. M. Blake: None. J.O. Hernandez: None. J. Balam: None. B.S. Teh: None.

Metformin Use is Associated With Improved Response to Neoadjuvant Chemoradiation in Esophageal Adenocarcinoma

The vast majority of patients with esophageal carcinoma succumb to their disease, and there has been little improvement in outcomes in the past decade. The anti-diabetic agent metformin has been investigated both as a chemopreventative agent, as well as possible addition to current chemotherapeutics. However, little work has been done examining the role of metformin in radiosensitization. In the current study, the PET and pathologic response rate of esophageal cancer patients treated with neoadjuvant chemoradiation (CRT) were examined in patients taking metformin during therapy. Two hundred eighty-five patients treated with concurrent chemoradiation (CRT) followed by esophagectomy for esophageal adenocarcinoma from 1997 - 2012 were included in the study, including 29 diabetics taking metformin at the time of radiation, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post- treatment PET scans were available for 204 patients. Maximum SUV values of the tumor were recorded for both scans. Pathologic response was graded at the time of surgery. PET and pathologic CR rates were compared using both the chi-square statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT. The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and nondiabetic patients (19.6%, p = 0.05). Analysis of only patients taking metformin showed that daily doses ≥1,500 mg trended toward improved pathologic CR rates (p = 0.07). No significant difference was seen in pre-CRT tumor maximum SUV (p = 0.88); however, post-CRT tumor maximum SUV was significantly decreased in patients taking metformin (p = 0.02). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in-field loco-regional failure following radiation (p = 0.05). The use of metformin is associated with increased response to CRT in esophageal cancer in a dose-dependent manner and may be a sensitizer to this therapy.

442O - PI3K Kinase Inhibitor GSK2126458 (GSK458): Clinical Activity in Select Patient (PT) Populations Defined by Predictive Markers (STUDY P3K112826)

ABSTRACT Background GSK458 is an oral, potent inhibitor of PI3K (α, β, γ, δ), mTORC1, and mTORC2. Cell lines with activation of the PI3K pathway are more likely to be sensitive to GSK458. Methods Pts with advanced solid tumors received GSK458 until disease progression or intolerable toxicity. Dose escalation with once (QD) and twice daily dosing (BID) was explored. Pharmacodynamics (PD) (tumor biopsies and FDG–PET) in unselected populations, and clinical activity in specific populations (PIK3CA-mutant and wild-type [WT]) bladder cancer, renal cell carcinoma, PIK3CA-mutant metastatic breast cancer, and KRAS-WT metastatic endometrial cancer) were evaluated. Results 170 pts (49% female; mean age 57 [22-85] yrs) received doses ranging from 0.1 to 3 mg, the MTD for both QD and BID was 2.5 mg. The median (range) time above the target plasma concentration (20 ng/mL) was longer in BID versus QD dosing: 21hour (h) (14.8-24; n = 6) versus 8h (0-23.9; n = 18), respectively. Dose limiting toxicities were Grade 3 diarrhea. Most frequent (≥ 20%) drug related adverse events were diarrhea (28%), fatigue (24%) and nausea (23%). A dose response relationship between GSK458 plasma concentrations and increases in serum insulin levels was observed. 13 paired pre/post-dose tumor biopsies showed inconsistent changes in pAKT/total AKT, Ki67 and phospho-histone-H3. 9 pts had pre/post-dose FDG-PET; one pt had a mean SUV value decrease by ≥30% post-dose although none had responses per RECIST. Objective responses were seen in bladder cancer (1/3 PIK3CA mutant and 2/15 wild-type) and renal cell (2/23: 1 CR duration 25+ months, 1PR), but no responses were seen in PIK3CA-mutant breast cancer (1/10: stable for >6 months) or KRAS-WT endometrial cancer (1/12: stable disease for > 6 months). Conclusions Based on its superior pharmacokinetic profile, BID is the recommended schedule for GSK458 monotherapy. Surrogate PD markers (insulin) indicate on target activity. GSK458 showed promising activity in PIK3CA mutant bladder cancer and RCC. Disclosure P. Munster: Phase I Research: GSK J. Specht: Corporate-sponsored research: Pfizer, BMS, Genentech, BiPar Sciences, Boehringer Ingelheim E.C. Dees: Corporate-sponsored research: GSK, Novartis, Genentech/Roche, Millennium A. Tan: Corporate-sponsored research: GSK A. Daud: Membership on an advisory board or board of directors: Oncosec; Corporate-sponsored research: GSK, Pfizer, Merck, Oncosec, Exelixis G. Falchook: Corporate-sponsored research: GSK; GSK Travel reimbursement for ESMO 2010 J. F. Kleha: Stock ownership: GSK; GSK Employee M. Durante: Stock ownership: GSK; GSK Employee D.A. Smith: Stock ownership: GSK; GSK Employee L. Adams: Stock ownership: GSK; GSK Employee J. Greshock: Stock ownership: GSK; GSK Employee S.R. Morris: Stock ownership: GSK; GSK Employee All other authors have declared no conflicts of interest.

Positron Emission Tomography for Predicting Pathologic Response After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

To investigate whether before and after chemoradiotherapy (CRT) positron emission tomography (PET) predict for pathologic response after preoperative CRT in patients with locally advanced rectal adenocarcinoma. Thirty-five patients who underwent pre-CRT and post-CRT PET scans before surgery were included. All patients were staged with endoscopic ultrasound or high resolution CT. CRT was given with 50.4 Gy at 1.8 Gy per fraction and concurrent 5-fluorouracil-based chemotherapy. Surgery occurred at a median of 46 days (range, 27 to 112 d) after completing CRT. The maximum standardized uptake value (SUV(max)) and the metabolic tumor volume (MTV) using various minimum SUV thresholds (2, 2.5, 3) on the PET scans (MTV(2.0), MTV(2.5), MTV(3.0)) were determined. Post-CRT PET scans were done 3 to 5 weeks after completion of CRT. Pathologic response was assessed using the tumor regression grade (TRG) scale. Patients with complete or near-complete response (TRG=0 to 1) were considered pathologic responders. The pre-CRT and post-CRT PET scan SUV(max) and MTV values were correlated with TRG. The ΔSUV(max) and ΔMTV were correlated with TRG. No correlation was seen with SUV(max) (P=0.99), MTV(2.0) (P=0.73), MTV(2.5) (P=0.73), or MTV(3.0) (P=0.31) on the pre-CRT PET between pathologic responders versus nonresponders. No correlation was noted between SUV(max) (P=0.49), MTV(2.0) (P=0.73), MTV(2.5) (P=0.49), or MTV(3.0) (P=0.31) on the post-CRT PET scan and pathologic response. Finally, the ΔSUV(max) (P=0.32), ΔMTV(2.0) (P=0.99), ΔMTV(2.5) (P=0.31), ΔMTV(3.0) (P=0.31) did not correlate with pathologic response. Changes seen on PET have limited value in predicting for pathologic response of rectal cancer after preoperative neoadjuvant therapy.

Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: A PET study with the TSPO molecular imaging biomarker [11C]vinpocetine

Although there is increasing evidence for microglial activation after an ischaemic stroke in the infarct core and the peri-infarct region, the “evolution” of the process in stroke patients is poorly known. Using PET and [11C]vinpocetine, we measured the regional changes of TSPO in the brain of nine ischaemic stroke patients up to 14weeks after the insult. Already a week after stroke there was an increased radioligand uptake, indicating the up-regulation of TSPO and the presence of activated microglia, in both the ischaemic core and the peri-infarct zone. This increased activation showed a steady decrease with post stroke time. The proportion between %SUV values in the peri-infarct zone and the ischaemic core increased with time. There were no time-dependent TSPO activity changes in other regions, not affected directly by the stroke. The present observations demonstrate that increased regional microglia activation, as a consequence of stroke, can be visualised with PET, using the TSPO molecular imaging biomarker [11C]vinpocetine. The evolution of this microglial activation shows a time dependent decrease the gradient of which is different between the peri-infarct zone and the ischaemic core. The findings indicate an increased microglial activation in the peri-stroke region for several weeks after the insult.

18F-FDG PET/CT can predict nodal metastases but not recurrence in early stage uterine cervical cancer

ObjectivesTo evaluate the role of the metabolic characteristics of cervical tumor uptake as predictors of a) lymph node (LN) metastases, b) recurrence, in the preoperative staging of early-stage cervical cancer. Methods89 patients with FIGO stage IB1 and IIA <4cm cervical cancer were imaged with FDG-PET/CT before radical hysterectomy and pelvic lymphadenectomy. PET/CT images were analyzed and correlated to histological findings. Maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of cervical lesions were calculated by an iterative adaptive algorithm. These parameters were correlated to the presence of: a) LN metastases, b) relapse after primary treatment. ResultsOut of the 89 patients who underwent preoperative PET/CT scan for staging purpose, 16 were negative at cervical level: they were all pN0 and without recurrence during follow-up (mean 34.1±14.5months). In 69 patients MTV and TLG were significantly higher (p=0.0006 and p=0.03) in pN1 patients in comparison to pN0 patients, while SUV values did not show significant differences between the two groups. No significant correlations were found between SUVmax, SUVmean, MTV, TLG and the evidence of relapse (mean follow-up 29.2±15.5months). ConclusionsIn early-stage cervical cancer MTV and TLG correlate with the presence of nodal metastases, but their clinical impact on patients management has to be clarified. The absence of pathological cervical uptake could be a good prognostic factor, while SUVmax, SUVmean, MTV, TLG of the cervical uptake have not been found predictors of recurrence.

Spectroscopic Studies on the Interaction of Mefloquine with Phosphatidylcholine- Phosphatidylserine Bilayer Vesicle and Bovine Serum Albumin

To assess the interaction of mefloquine (MQ) with biomembranes and serum albumin, the partitioning of MQ into phosphatidylcholine-phosphatidylserine small unilamellar vesicles (PC-PS SUV) and its binding with bovine serum albumin (BSA) were examined using various spectroscopic methods. The partition coefficients (Kps) of MQ, determined by the second-derivative spectrophotometric method, increased in accordance with the PS content in PC-PS SUV: the Kp values for PC-PS SUV with PS contents of 10 mol% were about 2.5 times that for PC SUV. The zeta potential values of PC-PS SUV fell from -10 mV at a PS content of 0 mol% to -42 mV at PS contents of 10 mol%, and were found to depend to some extent on the Kp values. Meanwhile, the binding constant (logK) and the number of binding sites (n) for the binding of MQ to BSA were determined using a fluorescence quenching method. These values were significantly reduced by the presence of Cl– ions, from 5.55 to 4.66 for logK and from 1.30 to 1.11 for n. To examine the binding site of MQ on BSA, a 19F nuclear magnetic resonance (NMR) spectroscopic study was performed using typical competing ligands bound to BSA. The results revealed that whereas most of the MQ binds nonspecifically to BSA, MQ also partially binds to Site II. Finally, these results showed that the major interactions between MQ and PC-PS SUV or BSA were essentially different; the partitioning of MQ into PC-PS SUV was electrostatic and the binding of MQ to BSA was hydrophobic. Keywords: Binding constant, Bovine serum albumin, Fluorescence quenching, 19F nuclear magnetic resonance, Liposome, Mefloquine, Partition coefficient, Phosphatidylcholine, Phosphatidylserine, Second-derivative spectrophotometry, Zeta potential

SU-E-J-181: Explore the Value of 18F-FDG, PET and CT Scan for the Clinical Stage of Esophageal Carcinoma.

To evaluate the sensitivity, specificity and accuracy of 18F-FDG, PET and CT were used for T and N stage for esophageal carcinoma, and explore the SUV value evaluating prognosis of esophageal carcinoma. PET and CT scan as well as T and N stage were carried out for 29 cases of preoperative esophageal carcinoma patients, those results were analyzed and compared with postoperative pathological TNM stage. CT scan diagnosis the T stage was obviously higher than PET in term of determining T staging, while PET scan diagnosis the N stage was higher than CT, but there was no significantly difference. It was clear that only the Kappa value of preoperative PET scan in T stage was poor (Kappa value, 0.4), the Kappa values for PET scan in N stage, as well as preoperative CT scan in T and N stage were good (Kappa value.0.4). The SUV values were increasing with the lesion volume and length of PETsuv2.5 becoming bigger. The survival was better when patients with SUV value, 9.0 than those with SUV value=9.0. CT was better than PET in term of determining clinical T stage of esophageal carcinoma, while PET diagnosis the N stage was good the same as CT. SUV 9.0 may be regarded as a practical indexes to determine prognosis in esophageal carcinoma.

WE‐A‐217A‐07: Predicting Residual Disease for NSCLC Using Pre‐Radiotherapy 4D PET/CT

Purpose: To quantify PET treatment response using a novel image registration approach, and to investigate the impact of 4D PET/CT pre‐ radiotherapy scan for predicting residual high‐uptake areas toward dose‐ boosting in adaptive radiotherapy. Methods: 3D and 4D FDG‐PET/CT scans were obtained from ten patients with non‐small cell lung cancer (NSCLC) for approximately two weeks before radiotherapy (pre‐RT) and approximately one month after therapy (post‐RT). The 4D scan was taken immediately following a 3D PET scan. The areas of high uptake in the pre‐ RT scans were aligned with those in the post‐RT scans using a novel rigid‐ penalized deformable registration. The global lung bronchi and chest wall were non‐rigidly transformed to minimize the respiration effects while the target lesion is rigidly transformed to preserve the volume and SUV values. A region of interest (ROI) was defined by a threshold of 40% of the maximum SUV for both 3D and 4D PET scans. The maximal SUV within the ROI were measured. Volumetric overlap fraction (VOF) was calculated as the overlap volume of pre‐RT and post‐RT target volumes divided by the residual volume in the post‐RT scans. Results: The maximal SUVs for 4D pre and post PET have a 16.3% increase compared to those in 3D PET. The pre‐to‐post maximal SUV variations showed 57% lesions has nontrivial residual uptake (SUVmax&gt;2.5) for 3D PET, and 64% for 4D PET. The results of the VOFs showed that the residual metabolic‐active areas are mainly located within the primary tumor volume, 92% for 3D and 89% for 4D. Conclusions: Residual metabolic‐active areas have strong physiological and geometric correspondence to the primary tumor. With better signal recovery than standard 3D PET, high uptake areas of 4D PET pre‐RT can predict areas where residual metabolic activity will be found after radiotherapy.

SU-E-J-116: Investigation of Accuracy and Precision of ITV Delineation by PET SUV Threshold.

To determine PET SUV values in Pinnacle TPS and to assess the accuracy and precision of the ITV according to SUV thresholds. The goal is to minimize errors in target definition by using SUV showing enhanced metabolic activity of the tumor and fast CT imaging with less motion artifacts. Mean PET values in individual patients were obtained from statistics of body contours for whole body PET-CT scans. The SUVs were calculated by normalizing the PET values in any voxel by the mean body PET value. These clinically acquired SUVs were plotted against values reported at the time of the scan for verification. GTVs were contoured on petCT scans and the ITV's were contoured using three published methods of SUV thresholds at 2.5, at ratio of 40 percent of the maximum, and 30 percent of the maximum added to 60 percent of the mean body. GTV volumes were plotted against the 3 sets of ITVs to investigate their relationships. Examination of 11 patients showed a strong linear relationship between clinically determined SUVs and those reported; indicating the validity of our SUV definition. Plots of GTV volumes versus ITV volumes for each of the 3 thresholds revealed a less clear relationship. The effectiveness of each method to generate a reasonable ITV was highly patient dependent; in general the 2.5 threshold gave the best results, while the 40 percent maximum produced the worst. While more data is required to make a definitive statement about the value of PET SUV threshold defined ITVs, the findings do seem to reveal a pattern between GTV and ITV size. If an appropriate SUV threshold is chosen, the GTV-ITV volume relationship is nearly linear, which suggests extending the GTV in volume rather than the margin distance as is common in ITV delineation.

Optimum Contouring Method for Metabolic Tumor Volume Using PET/CT in Patients with Oral Cavity Squamous Cell Carcinoma

ABSTRACT:The metabolic tumor volume (MTV) is the volume of metabolically-active tumor on PET/CT. Although its potential clinical value has been investigated in many cancers, its routine use has been hampered by the delineation method used to calculate the tumor volume. This may be especially difficult for fuzzyPET images. Previous studies have used a lot of approaches for delineation of tumor volume; however, still there is no clear consensus on which method to be used, especially in the oral cavity region where the contouring may be difficult due to variable grades of physiological FDG uptake. Theaim of this study is to determine best contouring method for the metabolic tumor volume from PET/CT using different absolute and relative SUV values with correlation to the pathology. Materials and methods:We prospectively studied 126 patients with oral cavity squamous cell carcinoma (OCSCC) who underwent PET/CT before definitive treatment by radical surgery. The metabolic tumor volume (MTV) was calculated for the primary tumor according to absolute SUV figures (2.5, 3.0, 3.5 & 4.0) and fixed percentage of SUVmax (30%, 40%, 50%, 60% & 70%). Correlation between the axial diameters generated from these methods and the axial diameter from the fixed pathology specimens was used to determine the best of these methods. Results: Overall among the 9 contouring methods, absolute SUV 3.0 gave the best correlation (R = 0.723; P< 0.001). Among the methods based on fixed percentage of SUVmax, a threshold of30% gave the best correlation (R =0.701; P <0.001)Conclusion: Contouring the metabolic tumor volume based on absolute SUV 3.0 can be used to represent the best correlation with pathologic data in patients with OCSCC.

Evaluation of hepatic metabolic activity in non-alcoholic fatty livers on 18FDG PET/CT

The liver has been used as a reference organ for the assessment of abnormal (18)F-fluoro-2-deoxy-d-glucose ((18)FDG) in the body. Some researchers found that hepatosteatosis significantly changed the hepatic (18)FDG uptake, while others did not. This study investigated whether the liver's (18)FDG uptake was affected by the diffuse fatty infiltration of the liver. A total of 156 cases were included in this study. Different patient groups were defined according to the liver Hounsfield unit (HU). The HU was calculated from an unenhanced CT, for all patients, and we calculated the mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) on an (18)FDG PET scan. For this purpose, we placed regions of interest (ROIs) on the liver image. We statistically compared the SUVmean and SUVmax measured in the fatty liver patients and the control group. The average SUVmean and SUVmax values were calculated as 2.58±0.66 and 3.94±1, respectively, in the patient group and 2.54±0.57 and 3.7±0.88, respectively, in the control group. We found the average SUVmean and SUVmax values in the fatty liver group and its subsets were not significantly different from the values in the control group (p>0.05). We also did not find any statistically significant correlation between average liver density (HU) and the average SUV values (p>0.05). Fatty infiltration may not have a significant effect on the liver's (18)FDG uptake. Thus, the liver may be used as a reference or comparator on (18)FDG PET scans in patients with fatty liver disease.

A clinical and translational phase II trial of sequential axitinib and carboplatin/paclitaxel in advanced melanoma.

8580 Background: Several clinical trials adding VEGF signaling inhibitors to chemotherapy have not demonstrated any benefit over chemotherapy alone in advanced melanoma potentially due to decreased tumor cell proliferation induced by VEGF blockade. We tested the hypothesis that sequential administration of axitinib followed by carboplatin and paclitaxel may be more effective than chemotherapy alone in metastatic melanoma. Methods: We conducted a prospective phase II trial of this combination in previously treated metastatic melanoma patients. Patients had an ECOG PS 0-1, and normal organ function. Axitinib 5 mg PO bid was taken on days 1 through 14 of each 21-day treatment cycle, and carboplatin (AUC=5) with paclitaxel (175 mg/m2) was administered on day 1 starting with cycle 2. FLT-PET scans were performed on 6 patients to assess tumor cell proliferation on days 1, 14, 17, and 20 of cycle 1. Results: Treatment has been well tolerated. The most common grade 3 AEs have been neutropenia, hypertension, and gastrointestinal events. Grade 4 non-hematologic AEs have not been observed. 4 of 5 patients completing FLT-PET scans to date showed increases (23% to 92%) in SUV values during the axitinib holiday. The fifth patient had a single, minimally FLT avid lesion at baseline (SUV=1.9). In 30 evaluable patients, there have been 4 confirmed PRs, 2 unconfirmed PRs, and 3 patients with 28.6, 29.3, and 29.5% decreases in tumor size by RECIST. Overall, 19 patients have had SD and 5 have had PD as the best response. With a median follow-up of 8.3 months and 17 patients still active, the median PFS is 6.9 months, and 23 patients (77%) are still alive. 26 of 30 evaluable patients have been wild type for BRAF-V600E/K mutations. Conclusions: Axitinib followed by carboplatin and paclitaxel has been well tolerated and effective in a largely BRAF wild-type metastatic melanoma population. Given the urgent need for effective therapies in this population, this regimen warrants phase III testing.

18F-FDG Retention Index and Biologic Prognostic Parameters in Breast Cancer

To analyze the correlation between [(18)F]-fluoro-2-deoxy-D-glucose (F-FDG) uptake assessed by positron emission tomography/computed tomography (PET/CT) in breast tumors and histopathologic and immunohistochemical prognostic factors. Sixty-eight women with breast cancer were prospectively evaluated. PET/CT was requested in the initial staging previous to neoadjuvant chemotherapy (multicentric study).All the patients underwent a standard (18)F-FDG PET/CT followed by a delayed acquisition, 1 hour (PET-1) and 3 hours (PET-2) after FDG administration. Both examinations were evaluated qualitatively and semiquantitatively (SUV(max) values) in PET-1 (SUV-1) and in PET-2 (SUV-2). The percentage variation of the standard uptake values (retention index) between PET-1 and PET-2 was calculated.Clinical and metabolic stages were assessed according to TNM classification. All biologic prognostic parameters, such as the receptor status, p53 and c-erbB-2 expression, proliferation rate (Ki-67), and grading were determined from tissue of the primary tumor. Metabolic, clinical, and biologic parameters were correlated. A positive relationship was found between the SUV(max), tumor size, clinical, and metabolic stages. SUV-1 and SUV-2 values showed significant statistical correlation (P < 0.05) with PET stage and tumor size assessed by PET. On the contrary, the retention index showed relation with clinical stage (P < 0.05).When related to the biologic parameters, retention index showed the best results, with positive and significant relation (P < 0.05), with histologic grade, and Ki-67 and c-erbB-2 expression. Isolated SUV values only showed significant relation to Ki-67 expression. The retention index showed the best relation with biologic and clinical parameters compared with isolated SUVmax values for what could be a predictive marker of tumor biologic behavior.