Median Standardized Uptake Value Research Articles

Correlation between Biological Marker Expression and 18F-Fluorodeoxyglucose Uptake in Cervical Cancer Measured by Positron Emission Tomography

Background: This study aimed to determine whether several biologic markers were associated with ¹⁸fluorine-fluorodeoxyglucose (¹⁸F-FDG) uptake in patients with carcinoma of the cervix. Patients and Methods: 60 patients with International Federation of Gynecology and Obstetrics (FIGO) stages IA2 to IIB cervical cancer, who underwent ¹⁸FDG positron emission tomography/computed tomography (PET/CT), were included in the current study. All patients underwent radical hysterectomy. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), carbonic anhydrase-IX (CA-IX), vascular endothelial growth factor (VEGF), hexokinase type I (HK-I), hexokinase type II (HK-II), and cytoplasmic and nuclear hypoxia-inducible factor (HIF) 1α. Results: The expression of GLUT1 (p = 0.005), VEGF (p = 0.021), HK-II (p = 0.009), and cytoplasmic HIF1α (p = 0.024) was significantly associated with a higher median standardized uptake value (SUV_max). There was a positive correlation between ¹⁸F-FDG uptake and GLUT1 (p = 0.008), CA-IX (p = 0.030), HK-II (p < 0.001) as well as cytoplasmic HIF1α (p = 0.016), whereas this relationship was not observed among the VEGF, HK-I and nuclear HIF1α. Conclusion: The data presented in this study indicate that ¹⁸F-FDG uptake is associated with the presence of GLUT1, VEGF, nuclear HK-II, and cytoplasmic HIF1α. There was also a significant correlation among the rate of expression of GLUT1, HK-II, cytoplasmic HIF1α, and CAIX in carcinomas of the cervix.

18F‐FDG‐PET/CT for the Assessment of the Contralateral Neck in Patients with Head and Neck Squamous Cell Carcinoma

The aim was to compare the value of 18-Fluoro-Deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) regarding contralateral lymph node (LN) metastasis in the neck. Retrospective analysis of 61 patients staged by 18F-FDG-PET/CT. Cytology/histology served as a reference standard. Further, metabolic midline invasion (MI) of the primary tumor and the presence of bilateral LN metastases were assessed. A true positive rate in the ipsilateral neck of 80% versus 65% in the contralateral neck was found (P = 0.067). Median-standardized uptake value (SUV)-max for suspicious LN ipsilaterally was 7.6 versus 5.8 contralaterally (P = 0.038). There was no positive correlation between metabolic MI and bilateral metastasis (P = 0.82). The rate of true positive detected LN by 18F-FDG-PET/CT is less on the contralateral neck side; therefore, all suspicious LNs should be verified by cytology. A high SUV in the contralateral neck suggests metastatic disease regardless of nodal size. Metabolic MI needs to be addressed carefully as it was not predictive for bilateral LN involvement. 4.

4D-PET/CT with [11C]-PK11195 and [11C]-d-deprenyl Does not Identify the Chronic Inflammation in Asymptomatic Abdominal Aortic Aneurysms

The aim of this study was to investigate the relevance of inflammation in the pathogenesis of abdominal aortic aneurysm (AAA) in vivo with two novel positron emission tomography (PET) tracers: [(11)C]-PK11195 which targets the translocator protein (18kDa) expressed on macrophages and [(11)C]-d-deprenyl with a yet unknown target receptor expressed in chronic inflammation. Prospective clinical study. Five patients were examined with [(11)C]-PK11195-positron emission tomography/computed tomography (PET/CT) and 10 with [(11)C]-d-deprenyl-PET/CT. Nine large AAAs (54-66mm) scheduled for repair and six small AAA (35-44mm). All 15 patients were male and the AAAs were all asymptomatic. Regional activity was measured as standardised uptake values (SUVs) and retention index was calculated. Biopsies were taken from the aneurysm wall for histological examinations, in the nine patients operated on. No aortic uptake was recorded on the visual inspection, neither with [(11)C]-PK11195 nor with [(11)C]-d-deprenyl. For [(11)C]-PK11195 the median SUV of the AAA wall was 0.9 (range 0.8-1.0) and for [(11)C]-d-deprenyl, 0.7 (range 0.4-1.2). No increased uptake was seen in the aneurysmal infrarenal aorta compared with the non-aneurysmal suprarenal aorta. Histological examination of the aneurysm wall showed high inflammatory cell infiltration with lymphocytes and macrophages. The chronic inflammation observed in the vessel wall was not detectable with [(11)C]-PK11195 and [(11)C]-d-deprenyl. In order to study the relevance of the inflammation in the pathogenesis of AAA in vivo other PET tracers need to be investigated.

MIS3-5 - Fluorodeoxyglucose Positron Emission Tomography for Evaluating Early Response During Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma

ABSTRACT Background To determine whether fluorodeoxyglucose positron emission tomography (FDG-PET) could differentiate between responding and non-responding locally advanced esophageal squamous cell carcinoma (ESCC) early in the course of neoadjuvant chemoradiotherapy (CRT). Methods Patients with T3 or N1M0-1a (AJCC, 6th ed.) ESCC first received a 21-day cycle of induction CT with paclitaxel, cisplatin, 5-FU/leucovorin D 1, 8). This was followed by concurrent paclitaxel, cisplatin CRT (Lin CC et al. Ann Oncol 18: 93; 2007). When the accumulated RT dose reached 40 Gy, the feasibility of esophagectomy was evaluated. In patients for whom esophagectomy was not feasible, CCRT was continued to a dose of 60 Gy. Serial FDG-PETs were carried out before and 14 days after the start of induction CT. Pathologic response (PR) was defined as no or microscopic residual disease. PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic (ROC) analysis was used to evaluate the SUV ability in distinguishing between PR and non-PR. Results Of 65 patients (M:F = 60:5, median age 55, range 39–71) with locally advanced (M0:M1a = 58:7) ESCC enrolled from March 2008 to December 2011, 40 patients underwent esophagectomy and 26 patients were pathologic responders. The median SUV decrease 140 days after the start of therapy was 75.8% for pathologic responders and 30.1% for non-responders (P Conclusions A 35% SUV decrease 14 days after the start of induction CT is significantly associated with PR, but its accuracy in detecting non-responders is too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant CRT in patients with locally advanced ESCC.

1028P - Plasma EBV DNA Concentration Correlates with FDG Pet in Nasopharyngeal Carcinoma Treated with Induction Chemotherapy

ABSTRACT Background While local control rate in locally advanced NPC (LA-NPC) has improved with concurrent Cisplatin and IMRT, development of distant metastases remains common in these patients and limits survival. The role of induction chemotherapy in the treatment of LA- NPC is still a matter of debate. The aim of this retrospective review is to evaluate the effect of induction chemotherapy and to correlate between EBV-DNA concentration and tumor response by PET-CT. Methods Patients with stage III-IVB, WHO II/III received induction chemotherapy with 2 cycles of TPF : Docetaxel: 75 mg/m2, Cisplatin: 75 mg /m2, 5Fluorouracil: 750 mg / m2 CI for 96 hours followed 3-4 weeks later by concurrent weekly Cisplatin ( 40 mg /m2) and IMRT (GTV:70 Gy over 35 fractions). EBV-DNA quantification was performed at baseline and repeated before each cycle of TPF. PET scans were performed at baseline and repeated before IMRT. The max standard uptake values (SUV) were recorded in the primary tumors. Metabolic response was defined as a decrease in maximum SUV of 35% or more. Results 20 patients with LA-NPC (75%Stage IVA/IVB) were reviewed. All but one completed therapy. Objective response, according to RECIST criteria: CR: 4; PR: 14 NE: 2. Median concentration of EBV-DNA was 11,300 copies /ml (range: 1,184 - 43,000). Post TPF, reduction of EBV-DNA copies by >50% was observed in 83% pts and 66% achieved complete biochemical response. In the FDG-avid tumor pts, the median SUV at baseline was 12 (range 10.5 - 17.4); post TPF metabolic response was observed in 100% and was complete in 33%.All patients with complete biochemical response had also a complete metabolic response by PET. At 2-year loco-regional progression free rate is 95% and 2 year overall survival rate is 85%. No recurrence was seen in complete (biochemical / metabolic) responders. Conclusion A negative post induction FDG-PET and complete biochemical response after TPF are of significant value in LA-NPC and are useful determinant to predict outcome. Disclosure All authors have declared no conflicts of interest.

Stereotactic body radiotherapy (SBRT) for non- pathologically diagnosed lung cancer patients

Objective: Medically inoperable patients with primary or recurrent lung cancer are increasingly being diagnosed clinically without pathologic confirmation especially for patients with comorbidities that preclude biopsy. The objective of this study is to report the outcomes of medically inoperable patients with unbiopsied primary or recurrent lung carcinoma with SBRT. Methods: From 2008-2011, 22 patients with non-pathologically diagnosed primary or recurrent lung cancer were treated with SBRT. All patients had diagnostic imaging clinically consistent with primary or recurrent lung malignancy. Fifteen patients had primary lung cancer and 7 had recurrent disease previously treated with surgery or fractionated radiotherapy. Median SBRT dose was 50 Gy (Range 40-55 Gy) in a median of 5 fractions (Range 4-10 fractions). Median BED was 100 Gy (Range 72-151.2 Gy). Results: Median follow up is 15.3 months (Range 6.6-33.0 months). Primary tumors had a median longest dimension on the original CT of 1.6cm, which enlarged to 2.0cm ( P <0.001) on serial CT and decreased to 1.3cm ( P =0.003) after SBRT. Recurrent tumors had a median longest dimension of 1.6cm, which increased to 2.7cm ( P =0.33) on repeat CT and subsequently stabilized at 2.7cm after SBRT. On FDG-PET scan, median standard uptake value (SUV) for the entire population is 5.4 before SBRT which decreased to 2.3 ( P <0.001) after treatment. For the entire population, absolute local control was 90.9%. Kaplan-Meier curves estimates at 2 years show regional control 100%, distant control 75%, cancer specific survival 92%, and overall survival 75%. There were no grade 3/4 acute or chronic treatment-related toxicities. Conclusions: In medically inoperable patients, a diagnosis of lung cancer can be provisionally made radiographically without pathologic confirmation. Local control can be achieved with minimal toxicity with the use of SBRT.

Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

e14576 Background: To determine if fluorodeoxyglucose positron emission tomography (FDG-PET) could differentiate between responding and non-responding locally advanced esophageal squamous cell carcinoma (ESCC) early in the course of neoadjuvant chemoradiotherapy (CRT). Methods: Patients (pts) with T3 or N1M0-1a (AJCC, 6th Ed) ESCC first received a 21-D cycle of induction chemo (paclitaxel 70 mg/m2 D 1, 8; cisplatin 30 mg/m2 D 1, 8; fluorouracil 2000 and leucovorin 300 mg/m2 24-hr D 1, 8). This was followed by concurrent CRT (paclitaxel 35 mg/m2 1-hr D 1, 4 /wk, cisplatin 15 mg/m2 1-hr D 2, 5/wk, and radiotherapy 2 Gy D 1-5 /wk) (Lin CC, et al. Ann Oncol 18:93,2007). When the accumulated radiation dose reached 40 Gy, the feasibility of esophagectomy was evaluated. In pts for whom esophagectomy was not feasible, concurrent CRT was continued to a dose of ≥60 Gy. Serial FDG-PETs were performed before and 14 days after start of induction chemo. Pathologic response (PR) was defined as no or microscopic residual disease. PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of SUV in distinguishing between PR and non-PR. Results: Of 65 pts (M:F = 60:5, median age 55, range 39-71) with locally advanced (M0:M1a = 58:7) ESCC enrolled from March 2008 to December 2011, 40 pts underwent esophagectomy and 26 pts were pathologic responders. The median SUV decrease 14 days after the start of therapy was 75.8% for pathologic responders and 30.1% for non-responders (p &lt;0.05). In ROC analysis, the area under the curve was 0.70 (95% CI = 0.55-0.86). Using a 35% SUV decrease cutoff value, PET correctly identified 24 of 26 responders (sensitivity 92%) and 8 of 14 non-responders (specificity 57%). The corresponding positive and negative predictive values were 80% and 80%, respectively. Conclusions: A 35% SUV decrease 14 days after the start of induction chemo is significantly associated with PR, but its accuracy in detecting non-responders is too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant CRT in pts with locally advanced ESCC.

Fluorodeoxyglucose Positron Emission Tomography Response and Normal Tissue Regeneration After Stereotactic Body Radiotherapy to Liver Metastases

To characterize changes in standardized uptake value (SUV) in positron emission tomography (PET) scans and determine the pace of normal tissue regeneration after stereotactic body radiation therapy (SBRT) for solid tumor liver metastases. We reviewed records of patients with liver metastases treated with SBRT to ≥40 Gy in 3-5 fractions. Evaluable patients had pretreatment PET and ≥1 post-treatment PET. Each PET/CT scan was fused to the planning computed tomography (CT) scan. The maximum SUV (SUV(max)) for each lesion and the total liver volume were measured on each PET/CT scan. Maximum SUV levels before and after SBRT were recorded. Twenty-seven patients with 35 treated liver lesions were studied. The median follow-up was 15.7 months (range, 1.5-38.4 mo), with 5 PET scans per patient (range, 2-14). Exponential decay curve fitting (r=0.97) showed that SUV(max) declined to a plateau of 3.1 for controlled lesions at 5 months after SBRT. The estimated SUV(max) decay half-time was 2.0 months. The SUV(max) in controlled lesions fluctuated up to 4.2 during follow-up and later declined; this level is close to 2 standard deviations above the mean normal liver SUV(max) (4.01). A failure cutoff of SUV(max) ≥6 is twice the calculated plateau SUV(max) of controlled lesions. Parenchymal liver volume decreased by 20% at 3-6 months and regenerated to a new baseline level approximately 10% below the pretreatment level at 12 months. Maximum SUV decreases over the first months after SBRT to plateau at 3.1, similar to the median SUV(max) of normal livers. Transient moderate increases in SUV(max) may be observed after SBRT. We propose a cutoff SUV(max) ≥6, twice the baseline normal liver SUV(max), to score local failure by PET criteria. Post-SBRT values between 4 and 6 would be suspicious for local tumor persistence or recurrence. The volume of normal liver reached nadir 3-6 months after SBRT and regenerated within the next 6 months.

Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using 18FDG-PET/CT

Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15-30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC. This is a retrospective review of patients with EUS-staged T3-T4, N+rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002-2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan-Meier estimation evaluated significant predictors of survival. Seventy patients (age 62 years; 42M:28F) with preoperative stage T3 (n=61) and T4 (n=9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P=0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P=0.01). Median SUV decrease was 63% (7.5-95.5%) and predicted pCR (P=0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50 days) than those without (P=0.02). Patients with post-CRT SUV<4 had a lower recurrence compared with those without (P=0.03). Patients with SUV decrease≥63% had improved overall survival at median follow-up of 40 months than those without (P=0.006). PET/CT can predict response to CRT in patients with LARC. Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate with pCR. Post-CRT, SUV<4, and SUV decrease≥63% were predictive of recurrence-free and overall survival.

Low 18f-fluorodeoxyglucose uptake on positron emission tomography as a prognostic factor for stage I and II pancreatic cancer.

159 Background: Metabolic activity as defined by the uptake of 18F-fluorodeoxyglucose (FDG) on Positron Emission Tomography (PET) has proven beneficial as a prognostic marker for multiple malignancies; however, no study has examined the prognostic value of PET in stage I and II pancreatic cancer. We examined the value of PET FDG uptake in early pancreatic cancer. Methods: Using a comprehensive pancreatic adenocarcinoma database, we identified patients with early stage pancreatic cancer (I-II) who underwent pancreatectomy for cancer and had PET scan performed as part of their preoperative evaluation from 2004 to 2010. Patients were divided by the median primary tumor standard uptake value (SUVmax) into two groups: high and low FDG uptake. The primary outcomes were overall survival (OS) and disease free survival (DFS). Kaplan-Meier estimate was used for survival analysis. Pathologic data were compared using Fisher's exact and chi-square. Results: We identified 105 patients with resected stage I and II pancreatic cancer who had PET scans as part of their preoperative evaluation. 51 patients had low FDG uptake while 54 patients had high FDG uptake. The median age at diagnosis was 69 (24-89) years, 57% of the patients were male. 84 (81%) patients had PET avid tumors, while 20 (19%) patients did not. The median SUVmax was 5.1. High FDG uptake correlated with pathologic stage (p=0.012). Median follow-up was 12.3 (0-56) months. Patients with low FDG uptake had a significantly better median OS than patients with high FDG uptake (27 vs. 16 months; p=0.036). Recurrence occurred in 64 (60%) patients. Patients with low FDG uptake had significantly longer median DFS than patients with high FDG uptake (14 vs. 12 months; p=0.049). Conclusions: Low 18F-fluorodeoxyglucose uptake in PET scans for stage I and II pancreatic cancer correlates with improved overall survival and disease free survival. This observation supports the concept that glucose metabolic pathways are important in pancreatic cancer biology, and that PET scan activity can be used as a prognostic biomarker after pancreatectomy for pancreatic cancer.

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without 18F-choline PET-CT detected simultaneous integrated boost

BackgroundIn comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without 18F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study.MethodsWhole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq 18F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTVPET). A dose of 76Gy was prescribed to the prostate (PTVprostate) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite).ResultsWith a median cut-off standard uptake value (SUV) of 3, a median GTVPET of 4.0 cm3 and PTVboost (GTVPET with margins) of 17.3 cm3 was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D.ConclusionsTreatment planning with 18F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.

Detection of 18Fluoride Sodium Accumulation by Positron Emission Tomography in Calcified Stenotic Aortic Valves

Aortic valve stenosis progression rate is highly variable among patients and to date remains unpredictable. Evaluation of osteoblastic activity inside aortic valves may help identify patients with fast aortic stenosis progression rates and worse prognoses. Fluoride-18 sodium (FNa) is a clinically approved positron emission tomographic (PET) radiotracer with high and rapid bone uptake. The aim of this study was to test whether FNa accumulates in degenerative aortic valves and can be detected with PET imaging. Five patients with severe aortic stenosis and 10 patients free of aortic valvular calcium on computed tomography underwent PET imaging 40 minutes after the injection of 4 MBq/kg of FNa for oncologic or rheumatologic purposes. Maximal standard uptake values (SUVs) were measured retrospectively in aortic valves using PET imaging. Tissue-to-background ratios were calculated for each patient by dividing the maximal SUV measured in aortic valves by the mean SUV of blood. In patients with severe aortic stenosis, an intense accumulation of FNa was detected in aortic valve region on PET imaging, whereas only low activity was found in patients free of valvular calcification (median maximal SUV 2.6 g/ml/kg [interquartile range (IQR) 2.3 to 3.6] vs 2.0 g/ml/kg [IQR 1.7 to 2.2] and median tissue-to-background ratio 2.2 [IQR 2.0 to 2.7] vs 1.5 [IQR 1.5 to 1.7], respectively, p = 0.008 for both). Intraobserver variability for maximal SUV and tissue-to-background ratio in aortic valves was measured at 0.99 and interobserver variability at 0.98 and 0.97, respectively. In conclusion, in this pilot study, FNa accumulated in patients with severe aortic stenosis and could be quantified on PET imaging with good reproducibility. FNa PET imaging represents a promising imaging modality to evaluate osteoblastic activity inside calcified aortic valves.

Impact of F18‐fluorodeoxyglycose positron emission tomography/computed tomography on the management of resectable pancreatic tumours

Positron emission tomography/computed tomography (PET/CT) using F18-fluorodeoxyglucose has been shown to be valuable in the management of malignant disease. The aim of this study is to investigate the impact of this technique on the management of patients with resectable pancreatic tumours. Thirty-six patients with 37 potentially resectable pancreatic tumours on diagnostic CT imaging underwent PET/CT scans. Operative findings, histological reports and/or clinical follow-up served as standard of reference. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT. Pancreatic adenocarcinoma was diagnosed in 30 patients, neuroendocrine tumours in 3, mass-forming pancreatitis in 3 and serous cystadenoma in 1. The median standard uptake (max) value was 5.0 (range 2.2-12.0). Sensitivity and specificity of detecting extrapancreatic metastatic disease were 73% and 100%, respectively. Three occult liver metastases were detected at laparotomy following negative PET/CT. PET/CT findings influenced the management of 8 (22%) patients - 3 with liver metastases, 3 with bone metastases, 1 with lymph node metastases and 1 by identifying the benign appearance of the pancreatic tumour. PET/CT achieves a significant diagnostic impact in detecting extrapancreatic metastatic disease. F18-fluorodeoxyglucose PET/CT appears to be useful in assessing suspicious pancreatic masses.

Pharmacodynamic Study Using FLT PET/CT in Patients with Renal Cell Cancer and Other Solid Malignancies Treated with Sunitinib Malate

To characterize proliferative changes in tumors during the sunitinib malate exposure/withdrawal using 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging. Patients with advanced solid malignancies and no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amenable to FLT PET/CT imaging. Sunitinib was initiated at the standard dose of 50 mg p.o. daily either on a 4/2 or 2/1 schedule. FLT PET/CT scans were obtained at baseline, during sunitinib exposure, and after sunitinib withdrawal within cycle #1 of therapy. VEGF levels and sunitinib pharmacokinetic (PK) data were assessed at the same time points. Sixteen patients (8 patients on 4/2 schedule and 8 patients on 2/1 schedule) completed all three planned FLT PET/CT scans and were evaluable for pharmacodynamic imaging evaluation. During sunitinib withdrawal (change from scans 2 to 3), median FLT PET standardized uptake value (SUV(mean)) increased +15% (range: -14% to 277%; P = 0.047) for the 4/2 schedule and +19% (range: -5.3% to 200%; P = 0.047) for the 2/1 schedule. Sunitinib PK and VEGF ligand levels increased during sunitinib exposure and returned toward baseline during the treatment withdrawal. The increase of cellular proliferation during sunitinib withdrawal in patients with renal cell carcinoma and other solid malignancies is consistent with a VEGF receptor (VEGFR) tyrosine kinase inhibitor (TKI) withdrawal flare. Univariate and multivariate analysis suggest that plasma VEGF is associated with this flare, with an exploratory analysis implying that patients who experience less clinical benefit have a larger withdrawal flare. This might suggest that patients with a robust compensatory response to VEGFR TKI therapy experience early "angiogenic escape."

SU‐E‐J‐95: Evaluation of Repeat Respiratory Gated PET Scans for the Assessment of Treatment Effectiveness

Purpose: Gated (4D) PET/CT scans have been shown to be effective in recovering the signal lost due to respiratory motion. Ungated (3D) and 4D FDG‐PET scans obtained pre and post radiation therapy (RT) for lung cancer were compared to examine the role of 4D PET in assessing FDG uptake changes due to therapy. Methods: Sequential 3D and 4D FDG‐PET/CT scans were acquired approximately two weeks before (pre‐RT) and one month after (post‐RT) treatment for patients receiving definitive RT for lung cancer. Targeted lesions were identified for each patient, and a region of interest (ROI) was defined for each lesion on the 3D and each of the five phases of the 4D pre‐RT scans. The ROIs were generated using a 40% of the maximum standardized uptake value (SUV) threshold, and the maximum SUV for each lesion from the pre—RT scans was recorded. Pre‐RT ROIs were then used to locate the areas of the original FDG uptake on the post‐RT scans using rigid registration. A post‐RT ROI was generated, and the maximum post‐RT SUV was recorded. Results: Sixteen lesions were identified and analyzed for twelve patients. Comparison of pre‐RT to post‐RT 3D PET scans showed a median SUV decrease of 62% (range 36–89%), while comparison of pre‐RT to post‐RT 4D PET scans showed a median SUV decrease of 67% (range 30–89%). The mean difference between the SUV change on 3D versus 4D scans was 4.9% (range 0–15%, p=.07), and the highest quartile had an absolute difference greater than 9% in SUV change.Conclusion: When assessing SUV changes with PET scans done pre and post‐RT, a substantial proportion of lesions had showed differences of over 9% in measurement of SUV change when comparing 3D PET to 4D PET. Such differences could potentially influence classification of PET‐based response assessment.

Quantitative diffusion weighted MRI: A functional biomarker of nodal disease in Hodgkin lymphoma?

This study explores the relationship between MRI Apparent Diffusion Coefficient (ADC) and PET Standardized Uptake Value (SUV) measurements in pediatric Hodgkin lymphoma. Sixteen patients (mean age 15.4 yrs, 8 male) with proven Hodgkin lymphoma were recruited and staged using PET-CT, anatomical MRI and additional 1.5T diffusion weighted imaging (DWI) prior to and following chemotherapy. Pre-treatment lymph nodes and anatomically paired post-treatment residual tissue located on MRI were matched to the corresponding PET-CT. Region of interest (ROI) analysis was used to extract quantitative measurements. Mean ADC (ADC(mean)) and maximum SUV (SUV(max)) were recorded and correlation assessed using Spearman statistics. Fifty-three ROIs were sampled. Pre- and post-treatment ADC(mean) ranged from 0.77 × 10(−3) to 1.79 × 10(−3) (median 1.15 × 10(−3) mm(2)s(−1)) and 1.08 × 10(−3) to 3.18 ×10(−3) (median 1.88 × 10(−3) mm(2)s(−1)), and SUV(max) from 2.60 to 25.4 (median 8.85 mg/ml) and 1.00 to 3.50 mg/ml (median 1.90 mg/ml). Median post-treatment ADC(mean) was higher, and median SUV(max) lower than pretreatment values (p < 0.0001). There was an inverse correlation between pre-treatment ADC(mean) and SUV(max) (p = 0.005) and between fractional change ([post-treatment – pre-treatment]/pre-treatment)in ADC(mean) and SUV(max) (p =0.002). Our results confirm a strong reciprocal relationship between nodal ADC(mean) and SUV(max) in Hodgkin lymphoma;supporting the potential application of quantitative DWI as a functional biomarker of disease.

18F‐fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma

Metabolic activity assessed by (18)F-fluorodeoxyglocuse-positron emission tomography ((18)F-FDG-PET) reflects biological aggressiveness and prognoses in various tumors. The authors present a correlation between tumor metabolic activity and clinical outcomes in patients with hepatocellular carcinoma (HCC). Over a 3-year period (2005-2008), 135 locally advanced HCC patients were treated with localized concurrent chemoradiotherapy (CCRT; external beam radiotherapy at 45 grays for 5 weeks plus concurrent hepatic arterial infusion of 5-fluorouracil during the first and fifth week) followed by repetitive hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin. Among them, the authors studied 107 who received (18)F-FDG-PET before CCRT. Maximal standardized uptake values (SUVs) of tumors were calculated. The median maximal tumor SUV was 6.1 (range, 2.4-∼19.2). Patients with low maximal tumor SUVs (<6.1) had a higher disease control rate than those with high maximal tumor SUVs (≥6.1) (86.8% vs 68.5%, respectively, P = .023). Both median progression-free survival (PFS; 8.4 vs 5.2 months; P = .003) and overall survival (OS; 17.9 vs 11.3 months; P = .013) were significantly longer in the low maximal tumor SUV group than in the high maximal tumor SUV group, respectively. In multivariate analysis, low maximal tumor SUV and objective responses to CCRT remained significant for PFS and OS. The high maximal tumor SUV group was more likely to have extrahepatic metastasis within 6 months than the low maximal tumor SUV group (58.1% vs 26.8%, respectively; P < .001). Similar results were obtained for the maximal tumor SUV/normal liver maximal SUV ratio (<2 vs ≥2) concerning progression, death, and extrahepatic metastasis. Metabolic activity may be useful not only in predicting prognosis and treatment responses, but also in establishing optimal treatment plans in locally advanced HCC.

FDG-positron emission tomography/computed tomography and standardized uptake value in the primary diagnosis and staging of hilar cholangiocarcinoma

BackgroundThe diagnosis and staging of hilar cholangiocarcinoma (HCCA) remain challenging despite recent advances in imaging. Little is known about the use of positron emission tomography/computed tomography (PET/CT) in HCCA. ObjectivesThis study aimed to evaluate the additional value of FDG-PET/CT and standardized uptake value (SUV) in patients with highly suspected HCCA. MethodsBetween February 2006 and August 2009, PET/CT was performed in 30 patients with highly suspected HCCA, all of whom were deemed resectable by conventional staging methods, including laparoscopy. The results of PET-CT and SUV were compared with intraoperative and histopathological findings. ResultsThe primary tumour was 18F-FDG-positive in 88% of patients. Sensitivity and specificity for the detection of regional lymph node metastases and distant metastases were 67% and 68%, and 33% and 96%, respectively. The median SUV in the primary tumour was significantly (P < 0.05) higher in patients with (mean: 8.9) than without (mean: 6.1) distant metastases. The SUV in patients with benign disease (n= 4) showed a trend towards lower values than in patients with cholangiocarcinoma, although this was not significant. ConclusionsAfter conventional staging including diagnostic laparoscopy, the additional value of PET/CT is limited. This somewhat disappointing finding may reflect the fact that extensive staging studies were carried out prior to PET/CT. The SUV potentially predicts patients with distant metastases and may differentiate between HCCA and benign lesions that mimic malignancies.

Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy

Metabolic imaging is of interest in esophageal cancer; however, the usefulness of initial standardized uptake value (SUV) in positron emission tomography (PET) is unknown in patients with esophageal or gastroesophageal carcinoma treated with definitive chemoradiotherapy. The authors hypothesized that initial SUV would correlate with patient outcome. The authors retrospectively analyzed esophageal or gastroesophageal carcinoma patients who had baseline PET and endoscopic ultrasonography in addition to other routine staging. All patients received definitive chemoradiotherapy. Multiple statistical methods were used. The authors analyzed 209 consecutive esophageal or gastroesophageal carcinoma patients treated with definitive chemoradiation for outcome; of these, 180 had baseline PET for additional analyses. The median overall survival (OS) for all patients was 20.7 months (95% confidence interval, 18.8-26.3). Patients with clinical complete response (CR) lived longer than those with less than clinical CR (P < .0001). The median initial SUV was 12.7 (range, 0-51). Higher initial SUV was associated with longer tumors (P = .0001), higher T-stage status (P < .0001), positive N-stage status (P = .0001), higher overall stage (P < .0001), lack of clinical CR (P = .0002), and squamous cell histology (P < .0001). In the univariate analysis, initial SUV was associated with OS (Cox model, P = .016; log-rank test, P = .002). In the multivariate analysis, initial SUV dichotomized by the median value (P = .024) and tumor grade (P = .016) proved to be independent OS prognosticators. Median initial SUV for clinical CR patients was 10.2, compared with 15.3 for less than clinical CR patients (P = .0058). The data indicate that a higher initial SUV is associated with poorer OS in patients with esophageal or gastroesophageal carcinoma receiving definitive chemoradiation. Upon validation, baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy.

Predicting pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using FDG PET/CT.

505 Background: Pathologic complete response (pCR) after neoadjuvant chemoradiation has been observed in 15% to 30% of patients with locally advanced rectal cancer. The utility of FDG PET/CT scans in the management of patients with stage II or III rectal cancer is not well defined. The objective of this study is to determine if FDG PET/CT can be used to predict pCR and disease-free survival in patients receiving neoadjuvant chemoradiation with locally advanced rectal cancer. Methods: A retrospective chart review was conducted in patients with endorectal ultrasound-staged T3 to T4 rectal tumors who underwent preoperative and postoperative FGD PET/CT imaging. All patients were treated with neoadjuvant chemoradiotherapy (CRT). Maximum standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, % SUV change, and time between therapy and surgery in comparison to pathological complete response. Kaplan-Meier estimation was used to look for significant predictors of survival. Results: Seventy patients (mean age 62; 42M:28F) with preoperative stage T3Nx (n = 60) and T4Nx (n = 10) underwent pre-CRT and post-CRT FDG PET/CT scans between November 2002 and March 2009. All patients underwent definitive surgery after therapy with standard pathologic evaluation.The pCR rate was 26%. Median pre-CRT SUV was 10.5 while the median post-CRT SUV was 4.05. Patients with pCR had a lower mean post-CRT SUV compared to those without pCR (2.7 vs. 4.5, p = 0.02). Median SUV decrease was 61% (range 6% to 95%) and was significant in predicting pCR (p = 0.004). Patients with a pCR had a greater time interval between neoadjuvant therapy and surgery (median 57 days vs. 50 days) than those without (p = 0.05). Furthermore, patients with post-CRT SUV &lt; 4 had a lower local recurrence rate compared to those with post-CRT SUV &gt; 4 (p = 0.03). Patients with SUV decrease &gt; 61% had improved overall survival at mean follow-up of 39 months than those without (p = 0.01). Conclusions: PET/CT can predict response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Pre-CRT SUV was the only predictor of disease-free survival. No significant financial relationships to disclose.