Focal 18 F-FDG uptake predicts progression of pre-invasive squamous bronchial lesions to invasive cancers.

INTRODUCTION: Pre-invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high-risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) scans in predicting progression in patients with pre-invasive squamous endobronchial lesions. METHODS: In this retrospective study, patients with pre-invasive endobronchial lesions, who underwent an 18 F-FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow-up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time-to-progression and overall survival (OS). RESULTS: A total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18 F-FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow-up, with a median time to progression of 5.0 months (range, 3.0-25.0). In 23 (57.5%) patients with a negative 18 F-FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0-42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0-60.0 months) versus 49.0 months (range, 6.0-60.0 months) (p = 0.876) for the 18 F-FDG PET positive and negative groups, respectively. CONCLUSIONS: Patients with pre-invasive endobronchial squamous lesions and a positive baseline 18 F-FDG PET scan were at high-risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment.

Should vascular wall 18F-FDG uptake be adjusted for the extent of atherosclerotic burden?

Vascular wall 18F-FDG uptake is often used as a surrogate marker of atherosclerotic plaque inflammation. A potential caveat is that vascular wall 18F-FDG uptake is higher simply because more atherosclerosis is present. To determine if the degree of inflammation is high or low relative to the extent of atherosclerosis, vascular wall 18F-FDG uptake may require statistical adjustment for a non-inflammatory marker reflecting the extent of atherosclerosis, e.g. calcification. Adjustments is probably needed if (1) vascular wall 18F-FDG uptake correlates sufficiently strongly with arterial calcification and (2) adjustment for extent of calcification affects determinants of vascular 18F-FDG uptake. This study addresses these questions. 18F-FDG PET/low-dose-CT scans of 99 patients were used. Cardiovascular risk factors were assessed and PET/CT scans were analysed for standardized 18F-FDG uptake values and calcification. ANOVA was used to establish the association between vascular 18F-FDG uptake and calcification. Multiple linear regression (with and without calcification as independent variable) was used to show whether determinants of vascular 18F-FDG uptake were affected by the degree of calcification. 18F-FDG uptake was related to increased calcification in the aortic arch, descending and abdominal aorta. However, 18F-FDG uptake showed considerable overlap between categories of calcification. Age and body mass index were main determinants of vascular 18F-FDG uptake. In multiple regression analyses, most standardized beta coefficients of these determinants were not affected by adjustment for the degree of calcification. Although vascular 18F-FDG uptake is related to total atherosclerotic burden, as reflected by vascular calcification, the association is weak and unlikely to affect the identification of determinants of atherosclerotic inflammation implicating no need for adjustment in future studies.

Variability in quantitative analysis of atherosclerotic plaque inflammation using 18F-FDG PET/CT.

BACKGROUND: 18F-FDG-PET(/CT) is increasingly used in studies aiming at quantifying atherosclerotic plaque inflammation. Considerable methodological variability exists. The effect of data acquisition and image analysis parameters on quantitative uptake measures, such as standardized uptake value (SUV) and target-to-background ratio (TBR) has not been investigated extensively. OBJECTIVE: The goal of this study was to explore the effect of several data acquisition and image analysis parameters on quantification of vascular wall 18F-FDG uptake measures, in order to increase awareness of potential variability. METHODS: Three whole-body emission scans and a low-dose CT scan were acquired 38, 60 and 90 minutes after injection of 18F-FDG in six rheumatoid arthritis patients with high cardiovascular risk profiles.Data acquisition (1 and 2) and image analysis (3, 4 and 5) parameters comprised:1. 18F-FDG uptake time, 2. SUV normalisation, 3. drawing regions/volumes of interest (ROI's/VOI's) according to: a. hot-spot (HS), b. whole-segment (WS) and c. most-diseased segment (MDS), 4. Background activity, 5. Image matrix/voxel size.Intraclass correlation coefficients (ICC's) and Bland Altman plots were used to assess agreement between these techniques and between observers. A linear mixed model was used to determine the association between uptake time and continuous outcome variables. RESULTS: 1. Significantly higher TBRmax values were found at 90 minutes (1,57 95%CI 1,35-1,80) compared to 38 minutes (1,30 95%CI 1,21-1,39) (P = 0,024) 2. Normalising SUV for BW, LBM and BSA significantly influences average SUVmax (2,25 (±0,60) vs 1,67 (±0,37) vs 0,058 (±0,013)). 3. Intraclass correlation coefficients were high in all vascular segments when SUVmax HS was compared to SUVmax WS. SUVmax HS was consistently higher than SUVmax MDS in all vascular segments. 4. Blood pool activity significantly decreases in all (venous and arterial) segments over time, but does not differ between segments. 5. Image matrix/voxel size does not influence SUVmax. CONCLUSION: Quantitative measures of vascular wall 18F-FDG uptake are affected mainly by changes in data acquisition parameters. Standardization of methodology needs to be considered when studying atherosclerosis and/or vasculitis.

Effectiveness of an (18)F-FDG-PET based strategy to optimize the diagnostic trajectory of suspected recurrent laryngeal carcinoma after radiotherapy: The RELAPS multicenter randomized trial.

PURPOSE: The purpose of this study is to evaluate the efficacy of (18)F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy. PATIENTS AND METHODS: 150 patients suspected of recurrent T2-4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to (18)F-FDG-PET only followed by direct laryngoscopy if PET was assessed 'positive' or 'equivocal' (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy. RESULTS: Intention-to-treat analyses were performed on all randomized patients (CWU: n=74, PWU: n=76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60-81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19-40) (p<0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p=0·17, and 29%, 7%, respectively, p=0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference (p=0.32) in disease specific survival between both groups was found. CONCLUSION: In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment.

Colorectal liver metastatic disease: efficacy of irreversible electroporation--a single-arm phase II clinical trial (COLDFIRE-2 trial).

BACKGROUND: Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique that has shown promise for the ablation of lesions in proximity to vital structures such as blood vessels and bile ducts. The primary aim of the COLDFIRE-2 trial is to investigate the efficacy of IRE for unresectable, centrally located colorectal liver metastases (CRLM). Secondary outcomes are safety, technical success, and the accuracy of contrast-enhanced (ce)CT and (18)F-FDG PET-CT in the detection of local tumor progression (LTP). METHODS/DESIGN: In this single-arm, multicenter phase II clinical trial, twenty-nine patients with (18)F-FDG PET-avid CRLM ≤ 3,5 cm will be prospectively included to undergo IRE of the respective lesion. All lesions must be unresectable and unsuitable for thermal ablation due to vicinity of vital structures. Technical success is based on ceMRI one day post-IRE. All complications related to the IRE procedure are registered. Follow-up consists of (18)F-FDG PET-CT and 4-phase liver CT at 3-monthly intervals during the first year of follow-up. Treatment efficacy is defined as the percentage of tumors successfully eradicated 12 months after the initial IRE procedure based on clinical follow-up using both imaging modalities, tumor marker and (if available) histopathology. To determine the accuracy of (18)F-FDG PET-CT and ceCT, both imaging modalities will be individually scored by two reviewers that are blinded for the final oncologic outcome. DISCUSSION: To date, patients with a central CRLM unsuitable for resection or thermal ablation have no curative treatment option and are given palliative chemotherapy. For these patients, IRE may prove a life-saving treatment option. The results of the proposed trial may represent an important step towards the implementation of IRE for central liver tumors in the clinical setting. TRIAL REGISTRATION NUMBER: NCT02082782.

Response evaluation after chemoradiotherapy for advanced nodal disease in head and neck cancer using diffusion-weighted MRI and 18F-FDG-PET-CT.

OBJECTIVES: Evaluation of accuracy and interobserver variation of diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDGPET-CT) to detect residual lymph node metastases after chemoradiotherapy (CRT) in advanced staged head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Retrospectively, routinely performed DW-MRI (n=73) and 18F-FDG-PET-CT (n=58) 3months after CRT in HNSCC-patients with advanced nodal disease (N2-N3) were assessed by two radiologists and two nuclear medicine physicians (individually and in consensus). Imaging was scored dichotomously and on a five-point Likert scale. We also explored different scenarios for the potential added value of DW-MRI to PET-CT using the consensus Likert scale. Histopathology and a follow-up of 9months after CRT served as reference standard. RESULTS: Five patients (7%) had residual regional disease. DW-MRI showed a sensitivity of 60% and a specificity of 93%, vs. 100% and 84% for PET-CT, respectively. DW-MRI and PET-CT observers had 'moderate' and 'substantial' interobserver agreement (κ=0.58 and κ=0.64, respectively) with the dichotomous system. The combination of PET-CT and DW-MRI showed a sensitivity of 100% and a specificity of 95%. CONCLUSION: The high sensitivity of PET-CT authorizes a neck dissection in all patients with a positive test result and the high specificity of DW-MRI justifies avoidance of invasive neck dissections if the test is negative. Interobserver agreement varied as a function of test positivity criteria. Adding DW-MRI to PET-CT seemed to increase the specificity of PET-CT alone, thereby ensuring that less patients are exposed to unnecessary neck dissections.

Diffusion-weighted EPI- and HASTE-MRI and 18F-FDG-PET-CT early during chemoradiotherapy in advanced head and neck cancer.

MAIN PROBLEM: Diffusion-weighted MRI (DW-MRI) has potential to predict chemoradiotherapy (CRT) response in head and neck squamous cell carcinoma (HNSCC) and is generally performed using echo-planar imaging (EPI). However, EPI-DWI is susceptible to geometric distortions. Half-fourier acquisition single-shot turbo spin-echo (HASTE)-DWI may be an alternative. This prospective pilot study evaluates the potential predictive value of EPI- and HASTE-DWI and 18F-fluorodeoxyglucose PET-CT (18F-FDG-PET-CT) early during CRT for locoregional outcome in HNSCC. METHODS: Eight patients with advanced HNSCC (7 primary tumors and 25 nodal metastases) scheduled for CRT, underwent DW-MRI (using both EPI- and HASTE-DWI) and 18F-FDG-PET(-CT) pretreatment, early during treatment and three months after treatment. Median follow-up time was 38 months. RESULTS: No local recurrences were detected during follow-up. Median Apparent Diffusion Coefficient (ADC)EPI-values in primary tumors increased from 77×10(-5) mm(2)/s pretreatment, to 113×10(-5) mm(2)/s during treatment (P=0.02), whereas ADCHASTE did not increase (74 and 74 mm(2)/s, respectively). Two regional recurrences were diagnosed. During treatment, ADCEPI tended to be higher for patients with regional control [(117.3±12.1)×10(-5) mm(2)/s] than for patients with a recurrence [(98.0±4.2)×10(-5) mm(2)/s]. This difference was not seen with ADCHASTE. No correlations between ΔADCEPI and ΔSUV (Standardized Uptake Value) were found in the primary tumor or nodal metastases. CONCLUSIONS: HASTE-DWI seems to be inadequate in early CRT response prediction, compared to EPI-DWI which has potential to predict locoregional outcome. EPI-DWI and 18F-FDG-PET-CT potentially provide independent information in the early response to treatment, since no correlations were found between ΔADCEPI and ΔSUV.

The use of PET-MRI in the follow-up after radiofrequency- and microwave ablation of colorectal liver metastases.

BACKGROUND: Thermal ablation of colorectal liver metastases (CRLM) may result in local progression, which generally appear within a year of treatment. As the timely diagnosis of this progression allows potentially curative local treatment, an optimal follow-up imaging strategy is essential. PET-MRI is a one potential imaging modality, combining the advantages of PET and MRI. The aim of this study is evaluate fluorine-18 deoxyglucose positron emission tomography (FDG) PET-MRI as a modality for detection of local tumor progression during the first year following thermal ablation, as compared to the current standard, FDG PET-CT. The ability of FDG PET-MRI to detect new intrahepatic lesions, and the extent to which FDG PET-MRI alters clinical management, inter-observer variability and patient preference will also be included as secondary outcomes. METHODS/DESIGN: Twenty patients undergoing treatment with radiofrequency or microwave ablation for (recurrent) CRLM will be included in this prospective trial. During the first year of follow-up, patients will be scanned at the VU University Medical Center at 3-monthly intervals using a 4-phase liver CT, FDG PET-CT and FDG PET-MRI. Patients treated with chemotherapy <6 weeks prior to scanning or with a contra-indication for MRI will be excluded. MRI will be performed using both whole body imaging (mDixon) and dedicated liver sequences, including diffusion-weighted imaging, T1 in-phase and opposed-phase, T2 and dynamic contrast-enhanced imaging. The results of all modalities will be scored by 4 individual reviewers and inter-observer agreement will be determined. The reference standard will be histology or clinical follow-up. A questionnaire regarding patients' experience with both modalities will also be completed at the end of the follow-up year. DISCUSSION: Improved treatment options for local site recurrences following CRLM ablation mean that accurate post-ablation staging is becoming increasingly important. The combination of the sensitivity of MRI as a detection method for small intrahepatic lesions with the ability of FDG PET to visualize enhanced metabolism at the ablation site suggests that FDG PET-MRI could potentially improve the accuracy of (early) detection of progressive disease, and thus allow swifter and more effective decision-making regarding appropriate treatment. TRIAL REGISTRATION NUMBER: NCT01895673.

Can we increase the yield of FDG-PET in the preoperative work-up for epilepsy surgery?

PURPOSE: [(18)F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a semi-invasive, interictal method of localization of hypometabolic epileptic foci. FDG-PET can be useful in the clinical work-up prior to epilepsy surgery, especially in equivocal cases. We investigated whether we could increase the yield of presurgical FDG-PET in patients with difficult epilepsy requiring chronic subdural electrocorticography (ECoG). METHODS: We retrospectively studied patients with refractory focal epilepsy in whom there was uncertainty about the focus localization and who underwent FDG-PET and ECoG. Two experts (epileptologist and nuclear medicine radiologist) together systematically re-assessed the scans visually (PETRE), blinded to their initial reports. Scans were also re-analyzed by comparing them to a normal control dataset with Statistical Parametric Mapping (SPM), using a liberal (PETSPM1), and strict (PETSPM2) statistical threshold. Regions with hypometabolism and regions containing the seizure onset zone (SOZ) in ECoG were marked as positive anatomical regions (PARs). We compared the concordance of these PARs for the different PET re-assessments. We calculated the sensitivity, specificity and accuracy of the PET results for the SOZ. The added value of the re-assessments was evaluated with emphasis on scans initially reported as negative. RESULTS: 41 Patients (63% extra-temporal) were included. PETRE identified the SOZ best, with a sensitivity of 62% and specificity of 93%. PETSPM1 had a sensitivity of 62% and specificity 69%, for PETSPM2 this was 35% and 85% respectively. The overlap between PETRE vs. PETSPM1 and vs. PETSPM2 was 71% and 37%. Visual re-assessment and PETSPM1 identified the SOZ in four out of five scans that were initially reported as negative. CONCLUSIONS: Pre-surgical re-assessment of PET scans is worthwhile in epilepsy patients who undergo ECoG, especially when results were reported as negative before. Visual re-assessment itself has a higher combined specificity, sensitivity and accuracy than SPM analysis alone. SPM analysis could be used as a guide for visual (re-)assessment, because of its high sensitivity.

PET-CT after radiofrequency ablation of colorectal liver metastases: suggestions for timing and image interpretation.

INTRODUCTION: The main area of concern regarding radiofrequency ablation (RFA) of colorectal liver metastases is the risk of developing a local site recurrence (LSR). Reported accuracy of PET-CT in detecting LSR is high compared to morphological imaging alone, but no internationally accepted criteria for image interpretation have been defined. Our aim was to assess criteria for FDG PET-CT image interpretation following RFA, and to define a timetable for follow-up detection of LSR. METHODS: Patients who underwent RFA for colorectal liver metastases between 2005 and 2011, with FDG-PET follow-up within one year after treatment were included. Results of repeat FDG-PET scans were evaluated until a LSR was diagnosed. Results. One hundred-seventy scans were obtained for 79 patients (179 lesions), 57 scans (72%) were obtained within 6 months of treatment. Thirty patients developed local recurrence; 29 (97%) within 1 year. Only 2% of lesions of <1cm and 4% of <2 cm showed a LSR. CONCLUSION: The majority of local site recurrences are diagnosed within one year after RFA. Regular follow-up using FDG PET-CT within this period is advised, so repeated treatment can be initiated. Rim-shaped uptake may be present until 4-6 months, complicating evaluation. The benefit in the follow-up of lesions <2 cm may be limited.

Toward prediction of efficacy of chemotherapy: a proof of concept study in lung cancer patients using [¹¹C]docetaxel and positron emission tomography.

PURPOSE: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ([(11)C]docetaxel). The objective of this study was to investigate whether a [(11)C]docetaxel PET microdosing study could predict tumor uptake of therapeutic doses of docetaxel. EXPERIMENTAL DESIGN: Docetaxel-naïve lung cancer patients underwent 2 [(11)C]docetaxel PET scans; one after bolus injection of [(11)C]docetaxel and another during combined infusion of [(11)C]docetaxel and a therapeutic dose of docetaxel (75 mg·m(-2)). Compartmental and spectral analyses were used to quantify [(11)C]docetaxel tumor kinetics. [(11)C]docetaxel PET measurements were used to estimate the area under the curve (AUC) of docetaxel in tumors. Tumor response was evaluated using computed tomography scans. RESULTS: Net rates of influx (Ki) of [(11)C]docetaxel in tumors were comparable during microdosing and therapeutic scans. [(11)C]docetaxel AUCTumor during the therapeutic scan could be predicted reliably using an impulse response function derived from the microdosing scan together with the plasma curve of [(11)C]docetaxel during the therapeutic scan. At 90 minutes, the accumulated amount of docetaxel in tumors was less than 1% of the total infused dose of docetaxel. [(11)C]docetaxel Ki derived from the microdosing scan correlated with AUCTumor of docetaxel (Spearman ρ = 0.715; P = 0.004) during the therapeutic scan and with tumor response to docetaxel therapy (Spearman ρ = -0.800; P = 0.010). CONCLUSIONS: Microdosing data of [(11)C]docetaxel PET can be used to predict tumor uptake of docetaxel during chemotherapy. The present study provides a framework for investigating the PET microdosing concept for radiolabeled anticancer drugs in patients.

18F-fluorodeoxyglucose positron emission tomography in elderly patients with an elevated erythrocyte sedimentation rate of unknown origin.

Patients with an elevated erythrocyte sedimentation rate (ESR) and non-specific symptoms often pose a diagnostic dilemma. PET/CT visualises infection, inflammation and malignancy, all of which may cause elevated ESR. The objective of this study was to determine the contribution of 18F-fluorodeoxglucose positron emission tomography (PET/CT) in the diagnostic work-up of referred patients with an elevated ESR, in whom initial routine evaluation did not reveal a diagnosis. We conducted a combined retrospective (A) and prospective (B) study in elderly (>50 years) patients with a significantly elevated ESR of ≥ 50 mm/h and non-specific complaints. In study A, 30 patients were included. Malignancy (8 patients), auto-inflammatory disease (8 patients, including 5 with large-vessel vasculitis) and infection (3 patients) were suggested by PET/CT. Two scans showed non-specific abnormalities and 9 scans were normal. Of the 21 abnormal PET/CT results, 12 diagnoses were independently confirmed and two alternative diagnosis were made. Two diagnoses were established in patients with a normal scan. In study B, 58 patients in whom a prior protocolised work-up was non-diagnostic, were included. Of these, 25 PET/CT-scans showed suspected auto-inflammatory disease, particularly large-vessel vasculitis (14 cases). Infection and malignancy was suspected in 5 and 3 cases, respectively. Seven scans demonstrated non-specific abnormalities, 20 were normal. Of the 40 abnormal PET/CT results, 22 diagnoses were confirmed, 3 alternative diagnoses were established. Only one diagnosis was established in the 20 patients with a normal scan. In both studies, the final diagnosis was based on histology, clinical follow-up, response to therapy or additional imaging. In conclusion, PET/CT may be of potential value in the diagnostic work-up of patients with elevated ESR if routine evaluation reveals no diagnosis. In particular, large-vessel vasculitis appears to be a common finding. A normal PET/CT scan in these patients suggests that it is safe to follow a wait-and-see policy.

Incidence and treatment of local site recurrences following RFA of colorectal liver metastases.

BACKGROUND: Patients with colorectal liver metastases (CRLM) who are ineligible for curative surgery are potential candidates for radiofrequency ablation (RFA). Although RFA has emerged as a well accepted and documented treatment modality, there are still some reservations because of initially high rates of local site recurrences (LSR). The aim of the present study was to evaluate LSR levels following RFA treatment, with a specific focus on re-treatment and survival. PATIENTS AND METHODS: All patients ineligible for curative resection of CRLM and undergoing RFA alone or in combination with resection were prospectively included from July 2000 to December 2010 and retrospectively analyzed. Patients with untreatable extrahepatic disease were excluded. FDG PET-CT was conducted at 3-6 month intervals after RFA. Patients with LSR were evaluated for re-treatment. RESULTS: A total of 132 patients were treated with RFA, which was combined with resection in 64 patients. A total of 290 lesions were ablated, with a mean number of 2.19 per patient and a mean size of 2.2 cm. Median survival was 41 months, with a 3- and 5-year survival of, respectively, 60 and 30.8 %. Following initial RFA, 39 patients developed an LSR in 40 ablated lesions, and local recurrence was strongly related to lesion size. Re-treatment could be performed in 26/39 patients, of whom eight remained disease-free. CONCLUSIONS: Radiofrequency ablation can be applied to CRLM of less than 3 cm with curative intent. In the absence of extensive intrahepatic or extrahepatic disease, renewed treatment of local recurrences should be considered and is often successful.

Tumor cavitation in patients with stage III non-small-cell lung cancer undergoing concurrent chemoradiotherapy: incidence and outcomes.

INTRODUCTION: Commonly reported complications after concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC) include febrile neutropenia, radiation esophagitis, and pneumonitis. We studied the incidence of tumor cavitation and/or "tumor abscess" after CCRT in a single-institutional cohort. METHODS: Between 2003 and 2010, 87 patients with stage III NSCLC underwent cisplatin-based CCRT and all subsequent follow-up at the VU University Medical Center. Diagnostic and radiotherapy planning computed tomography scans were reviewed for tumor cavitation, which was defined as a nonbronchial air-containing cavity located within the primary tumor. Pulmonary toxicities scored as Common Toxicity Criteria v3.0 of grade III or more, occurring within 90 days after end of radiotherapy, were analyzed. RESULTS: In the entire cohort, tumor cavitation was observed on computed tomography scans of 16 patients (18%). The histology in cavitated tumors was squamous cell (n = 14), large cell (n = 1), or adenocarcinoma (n = 1). Twenty patients (23%) experienced pulmonary toxicity of grade III or more, other than radiation pneumonitis. Eight patients with a tumor cavitation (seven squamous cell carcinoma) developed severe pulmonary complications; tumor abscess (n = 5), fatal hemorrhage (n = 2), and fatal embolism (n = 1). Two patients with a tumor abscess required open-window thoracostomy post-CCRT. The median overall survival for patients with or without tumor cavitation were 9.9 and 16.3 months, respectively (p = 0.09). CONCLUSIONS: With CCRT, acute pulmonary toxicity of grade III or more developed in 50% of patients with stage III NSCLC, who also had radiological features of tumor cavitation. The optimal treatment of patients with this presentation is unclear given the high risk of a tumor abscess.

Blood-brain barrier P-glycoprotein function in Alzheimer's disease.

A major pathological hallmark of Alzheimer's disease is accumulation of amyloid-ß in senile plaques in the brain. Evidence is accumulating that decreased clearance of amyloid-ß from the brain may lead to these elevated amyloid-ß levels. One of the clearance pathways of amyloid-ß is transport across the blood-brain barrier via efflux transporters. P-glycoprotein, an efflux pump highly expressed at the endothelial cells of the blood-brain barrier, has been shown to transport amyloid-ß. P-glycoprotein function can be assessed in vivo using (R)-[(11)C]verapamil and positron emission tomography. The aim of this study was to assess blood-brain barrier P-glycoprotein function in patients with Alzheimer's disease compared with age-matched healthy controls using (R)-[(11)C]verapamil and positron emission tomography. In 13 patients with Alzheimer's disease (age 65 ± 7 years, Mini-Mental State Examination 23 ± 3), global (R)-[(11)C]verapamil binding potential values were increased significantly (P = 0.001) compared with 14 healthy controls (aged 62 ± 4 years, Mini-Mental State Examination 30 ± 1). Global (R)-[(11)C]verapamil binding potential values were 2.18 ± 0.25 for patients with Alzheimer's disease and 1.77 ± 0.41 for healthy controls. In patients with Alzheimer's disease, higher (R)-[(11)C]verapamil binding potential values were found for frontal, parietal, temporal and occipital cortices, and posterior and anterior cingulate. No significant differences between groups were found for medial temporal lobe and cerebellum. These data show altered kinetics of (R)-[(11)C]verapamil in Alzheimer's disease, similar to alterations seen in studies where P-glycoprotein is blocked by a pharmacological agent. As such, these data indicate that P-glycoprotein function is decreased in patients with Alzheimer's disease. This is the first direct evidence that the P-glycoprotein transporter at the blood-brain barrier is compromised in sporadic Alzheimer's disease and suggests that decreased P-glycoprotein function may be involved in the pathogenesis of Alzheimer's disease.

Absolute quantification of [(11)C]docetaxel kinetics in lung cancer patients using positron emission tomography.

PURPOSE: Tumor resistance to docetaxel may be associated with reduced drug concentrations in tumor tissue. Positron emission tomography (PET) allows for quantification of radiolabeled docetaxel ([(11)C]docetaxel) kinetics and might be useful for predicting response to therapy. The primary objective was to evaluate the feasibility of quantitative [(11)C]docetaxel PET scans in lung cancer patients. The secondary objective was to investigate whether [(11)C]docetaxel kinetics were associated with tumor perfusion, tumor size, and dexamethasone administration. EXPERIMENTAL DESIGN: Thirty-four lung cancer patients underwent dynamic PET-computed tomography (CT) scans using [(11)C]docetaxel. Blood flow was measured using oxygen-15 labeled water. The first 24 patients were premedicated with dexamethasone. For quantification of [(11)C]docetaxel kinetics, the optimal tracer kinetic model was developed and a noninvasive procedure was validated. RESULTS: Reproducible quantification of [(11)C]docetaxel kinetics in tumors was possible using a noninvasive approach (image derived input function). Thirty-two lesions (size ≥4 cm(3)) were identified, having a variable net influx rate of [(11)C]docetaxel (range, 0.0023-0.0229 mL·cm(-3)·min(-1)). [(11)C]docetaxel uptake was highly related to tumor perfusion (Spearman's ρ = 0.815;P < 0.001), but not to tumor size (Spearman's ρ = -0.140; P = 0.446). Patients pretreated with dexamethasone showed lower [(11)C]docetaxel uptake in tumors (P = 0.013). Finally, in a subgroup of patients who subsequently received docetaxel therapy, relative high [(11)C]docetaxel uptake was related with improved tumor response. CONCLUSIONS: Quantification of [(11)C]docetaxel kinetics in lung cancer was feasible in a clinical setting. Variable [(11)C]docetaxel kinetics in tumors may reflect differential sensitivity to docetaxel therapy. Our findings warrant further studies investigating the predictive value of [(11)C]docetaxel uptake and the effects of comedication on [(11)C]docetaxel kinetics in tumors.

Interobserver variability in chest CT and whole body FDG-PET screening for distant metastases in head and neck cancer patients.

PURPOSE: The aim of the study was to assess the interobserver variability in chest computed tomography (CT) and whole body 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) screening for distant metastases in head and neck squamous cell carcinoma (HNSCC) patients. PROCEDURE: Chest CT and whole body FDG-PET of 69 HNSCC patients with high-risk factors who underwent screening for distant metastases were analyzed. All scans were independently read by two experienced radiologists or nuclear physicians who were blinded to the other examinations and follow-up results. RESULTS: A kappa of 0.516 was found for assessment of size on CT. Kappa values for origin and susceptibility of 0.406 and 0.512 for CT and 0.834 and 0.939 for PET were found, respectively. The overall conclusions had a kappa of 0.517-0.634 for CT and 0.820-1.000 for PET. CONCLUSIONS: In screening for distant metastases in HNSCC patients with high-risk factors, chest CT readings had a reasonable to substantial agreement, while PET readings showed an almost perfect agreement. These findings suggest that for optimal assessment in clinical practice, PET most often can be scored by one observer, but CT should probably more often be scored by different observers in consensus or combined with PET.

18F-FDG PET as a tool to predict the clinical outcome of infliximab treatment of rheumatoid arthritis: an explorative study.

UNLABELLED: 18F-FDG PET is a sensitive, promising method for visualizing disease activity in rheumatoid arthritis. This study aimed to assess the association between changes in 18F-FDG joint uptake after 2 wk of infliximab treatment and clinical outcome. METHODS: Scans were obtained at the initiation of treatment and at 2 wk. Uptake in metacarpophalangeal and wrist joints was quantified using standardized uptake values. RESULTS: Changes in mean standardized uptake value at 0-2 wk significantly correlated with the disease activity score (DAS) at 14 and 22 wk and contributed significantly to the prediction of DAS at these time points. No significant correlation was found between changes in acute-phase reactants at 0-2 wk and the DAS at later time points. CONCLUSION: Early changes in 18F-FDG uptake in joints during infliximab treatment of rheumatoid arthritis patients, using PET, may predict clinical outcome.