[Show abstract][Hide abstract] ABSTRACT: In contemporary positron emission tomography (PET)/computed tomography (CT) scanners, PET attenuation correction is performed by means of a CT-based attenuation map. Respiratory motion can however induce offsets between the PET and CT data. Studies have demonstrated that these offsets can cause errors in quantitative PET measures. The purpose of this study is to quantify the effects of respiration-induced CT differences on the attenuation correction of pulmonary 18-fluordeoxyglucose (FDG) 3D PET/CT in a patient population and to investigate contributing factors.
For 32 lung cancer patients, 3D-CT, 4D-PET and 4D-CT data were acquired. The 4D FDG PET data were attenuation corrected (AC) using a free-breathing 3D-CT (3D-AC), the end-inspiration CT (EI-AC), the end-expiration CT (EE-AC) or phase-by-phase (P-AC). After reconstruction and AC, the 4D-PET data were averaged. In the 4Davg data, we measured maximum tumour standardised uptake value (SUV)max in the tumour, SUVmean in a lung volume of interest (VOI) and average SUV (SUVmean) in a muscle VOI. On the 4D-CT, we measured the lung volume differences and CT number changes between inhale and exhale in the lung VOI.
Compared to P-AC, we found −2.3% (range −9.7% to 1.2%) lower tumour SUVmax in EI-AC and 2.0% (range −0.9% to 9.5%) higher SUVmax in EE-AC. No differences in the muscle SUV were found. The use of 3D-AC led to respiration-induced SUVmax differences up to 20% compared to the use of P-AC.
SUVmean differences in the lung VOI between EI-AC and EE-AC correlated to average CT differences in this region (ρ = 0.83). SUVmax differences in the tumour correlated to the volume changes of the lungs (ρ = −0.55) and the motion amplitude of the tumour (ρ = 0.53), both as measured on the 4D-CT.
Respiration-induced CT variations in clinical data can in extreme cases lead to SUV effects larger than 10% on PET attenuation correction. These differences were case specific and correlated to differences in CT number in the lungs.
[Show abstract][Hide abstract] ABSTRACT: Patients and their peers need to be adequately informed to ensure proper treatment selection, and to facilitate optimal realisation and outcome of treatment. Written patient information can contribute, but only when brochures are of sufficient quality. An evaluation of patient brochures for radium-223 therapy in the Netherlands revealed significant differences in the information provided, as well as discrepancies between the brochures and national guidelines and product documentation. This potentially leads to confusion, false expectations, wrong treatment decisions, suboptimal realisation and outcome of treatment, and unnecessary toxicity and in radiation hygiene risks. Here we discuss the option of national patient information brochures that can be used by all centres in order to circumvent such issues. This would require collaboration between all medical professions, patient organisations and other groups involved, and responsibilities for medical information, distribution and updates must be properly defined. A national patient information brochure of this kind is currently under development for radium-223 therapy.
Nederlands tijdschrift voor geneeskunde 08/2015; 159:A8948.
[Show abstract][Hide abstract] ABSTRACT: Background:
After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.
In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.
This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.
Clinicaltrials.gov identifier: NCT01641679.
BMC Cancer 06/2014; 14(1):405. DOI:10.1186/1471-2407-14-405 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype.
We performed (18)F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in (18)F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses.
Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p = 0.033), breast cancer subtype (p < 0.001), relative change in SUVmax on PET/CT (p < 0.001) and relative change in largest tumour diameter on MRI (p < 0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95 % CI 0.68-0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95 % CI 0.70-0.89). The AUC increased to 0.90 (95 % CI 0.83-0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p = 0.012).
PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype.
European Journal of Nuclear Medicine 04/2014; 41(8). DOI:10.1007/s00259-014-2770-2 · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates the dependency of manual delineation on experience and qualification.
A total of 44 international interdisciplinary observers each defined a [(18)F]fluorodeoxyglucose (FDG)-PET based gross tumor volume (GTV) using the same PET/CT scan from a patient with lung cancer. The observers were "experts" (E; n = 3), "experienced interdisciplinary pairs" (EP; 9 teams of radiation oncologist (RO) + nuclear medicine physician (NP)), "single field specialists" (SFS; n = 13), and "students" (S; n = 10). Five automatic delineation methods (AM) were also included. Volume sizes and concordance indices within the groups (pCI) and relative to the experts (eCI) were calculated.
E (pCI = 0.67) and EP (pCI = 0.53) showed a significantly higher agreement within the groups as compared to SFS (pCI = 0.43, p = 0.03, and p = 0.006). In relation to the experts, EP (eCI = 0.55) showed better concordance compared to SFS (eCI = 0.49) or S (eCI = 0.47). The intermethod variability of the AM (pCI = 0.44) was similar to that of SFS and S, showing poorer agreement with the experts (eCI = 0.35).
The results suggest that interdisciplinary cooperation could be beneficial for consistent contouring. Joint delineation by a radiation oncologist and a nuclear medicine physician showed remarkable agreement and better concordance with the experts compared to other specialists. The relevant intermethod variability of the automatic algorithms underlines the need for further standardization and optimization in this field.
Strahlentherapie und Onkologie 03/2014; 190(6). DOI:10.1007/s00066-014-0644-y · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the association between extravesical (18)F-fluorodeoxyglucose (FDG) avid lesions on FDG-positron emission tomography/computed tomography (PET/CT) and mortality in patients with muscle-invasive bladder cancer.
An international, bi-institutional cohort study of 211 patients with muscle-invasive bladder cancer who underwent staging CT and FDG-PET/CT imaging. On the basis of the presence of extravesical FDG-avid lesions suspicious for malignancy on PET/CT images, patients were divided into a PET/CT-positive and PET/CT-negative group. Data on staging and mortality were retrospectively analyzed from prospective databases. Kaplan-Meier analyses were performed to compare overall (OS) and disease-specific survival (DSS) between the groups. Multivariable Cox regression models were used to investigate the association between extravesical PET/CT lesions and mortality. Extravesical lesions suspicious for malignancy on conventional CT were included in the models.
Of the 211 patients, 98 (46.4%) had 1 or more extravesical lesions on PET/CT, 113 (53.5%) had a negative PET/CT. Conventional CT revealed extravesical lesions in 51 patients (24.4%). Median follow-up was 18 months. Patients with a positive PET/CT had a significantly shorter OS and DSS (median OS: 14 vs 50 months, P = .001; DSS: 16 vs 50 months, P <.001). In multivariable analysis, the presence of extravesical lesions on PET/CT was an independent prognostic indicator of mortality (OS: hazard ratio = 3.0, confidence interval 95% 1.7-5.1). This association was not statistically significant for conventional CT (hazard ratio = 1.6 (95% confidence interval 0.9-2.7).
On the basis of our results, the presence of extravesical FDG-avid lesions on PET/CT might be considered an independent indicator of mortality.
[Show abstract][Hide abstract] ABSTRACT: Aim: Preoperative detection of extranodal spread (ENS) in head and neck cancer can have important consequences for patient management. The aim of this study was to determine whether 18-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) or a combination with Magnetic Resonance Imaging (MRI) could more accurately predict ENS, especially with the near availability of fully integrated [18F]FDG PET/MRI scanners. Methods: In retrospective cohort design a total of twelve patients, with 18 lymphnode metastases were studied with [18F]FDG PET and MRI. Presence of ENS was scored on MRI, and [18F]FDG PET images using a SUV max cut-off point of 12. Histopathology results were used as reference standard. Sensitivity, specificity and accuracy were calculated. Results: The sensitivity, specificity and accuracy of [18F]FDG PET for ENS reached 70%,100% and 83%, respectively. The mean SUVmax of ENS positive lymphnodes was 13.6 versus 8.7 for lymphnode metastases without ENS (P=0.03). The sensitivity, specificity and accuracy of MRI for ENS were 70%, 100% and 83%, respectively. When the [18F]FDG PET and MRI findings were combined sensitivity, specificity and accuracy were 80%, 100% and 89%, respectively. Thus, accuracy increased from 83% to 89%. Conclusion: When there is no ENS or doubt of ENS on MRI, [18F]FDG PET seems to have additional value since it improves sensitivity and resolves uncertainty in case of high FDG uptake. This benefit needs to be confirmed prospectively in a larger cohort.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.. 01/2014; · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In breast cancer patients treated with neoadjuvant chemotherapy (NAC) the number of tumor-positive nodes can no longer reliably be determined. Furthermore, ultrasound (US) seems suboptimal for the detection of N3-disease. Therefore we assessed the proportion of breast cancer patients treated with NAC in which pre-chemotherapy 18F-FDG PET/CT detected ≥4 axillary nodes or occult N3-disease, upstaging nodal status and changing risk estimation for locoregional recurrence (LRR). Conventional regional staging consisted of US with fine needle aspiration and/or sentinel lymph node biopsy. Patients were classified as low-risk (cT2N0), intermediate-risk (cT0N1, cT1N1, cT2N1, cT3N0), or high-risk (cT3N1, cT4, cN2-3) for LRR. The presence and number of FDG-avid nodes were evaluated and the proportion of patients that would be upstaged by PET/CT, based on detection of ≥4 FDG-avid axillary nodes defined as cN2(4+) or occult N3-disease, was calculated. In total, 87 of 278 patients were considered high-risk based on conventional staging. PET/CT detected occult N3-disease in 5 (11 %) of 47 low-risk patients. In 144 intermediate-risk patients, PET/CT detected ≥4 FDG-avid nodes in 24 (17 %) patients and occult N3-disease in 22 (15 %) patients, thereby finally upstaging 38 (26 %) of intermediate-risk patients. Of 43 (23 %) upstaged patients, 18 were ypN0, 12 were ypN1, and 13 were ypN2-3. Pre-chemotherapy PET/CT is valuable for selection of breast cancer patients at high risk for LRR. In our population, 23 % of patients treated with NAC were upstaged to the high-risk group based on PET/CT information, potentially benefiting from regional radiotherapy.
Breast Cancer Research and Treatment 09/2013; 141(2). DOI:10.1007/s10549-013-2678-8 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II-III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling.
A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥2cm and a relative difference in SUV ≥25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed.
Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p=0.028), diffuse (non-mass) and multifocal tumors on MRI (p=0.001), diffuse and multifocal tumors on PET/CT (p<0.001), tumors >3cm (p<0.001), and lobular carcinomas (p<0.001). No association was found with other features.
Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II-III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3cm, lobular carcinomas, and diffuse and multifocal tumors.
European journal of radiology 08/2013; 82(12). DOI:10.1016/j.ejrad.2013.08.011 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account.
In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis.
A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively.
In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR.
European Journal of Nuclear Medicine 08/2013; 41(1). DOI:10.1007/s00259-013-2515-7 · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the clinical impact of (18) F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) scanning, compared with conventional staging with contrast-enhanced CT imaging (CECT).
The FDG-PET/CT results of 96 consecutive patients with bladder cancer were analysed. Patients included in this study underwent standard CECT imaging of the chest and abdomen/pelvis <4 weeks before FDG-PET/CT. Based on the original imaging reports and recorded tumour stage before and after FDG-PET/CT imaging, the preferred treatment strategies before FDG-PET/CT and after FDG-PET/CT were determined for each patient using an institutional multidisciplinary guideline. One of the following treatment strategies was chosen: (i) local curative treatment; (ii) neoadjuvant/induction chemotherapy; or (iii) palliation. The changes in management decisions before and after FDG-PET/CT were assessed.
The median (range) interval between CECT and FDG-PET/CT was 0 (029) days. In 21.9% of the patients, stage on FDG-PET/CT and CECT were different. Upstaging by FDG-PET/CT was more frequent than downstaging (19.8 vs 2.1%). Clinical management changed for 13.5% of patients as a result of FDG-PET/CT upstaging. In eight patients, FDG-PET/CT detected second primary tumours. This led to changes of bladder cancer treatment in another four of 96 patients (4.2%). All the management changes were validated by tissue confirmation of the additional lesions.
FDG-PET/CT provides important additional staging information, which influences the treatment of carcinoma invading bladder muscle in almost 20% of cases. Patient selection for neoadjuvant/induction chemotherapy was improved and futile attempts at curative treatment in patients found to have metastases were avoided.
BJU International 06/2013; 112(6). DOI:10.1111/bju.12109 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of this study was to assess the accuracy of 18F-FDG PET/CT in T1 breast cancer regarding visualization of the primary tumor and the detection of locoregional and distant metastases.
Sixty-two women with invasive T1 breast cancer underwent a PET/CT. Image acquisition of the thorax was done in prone position with hanging breasts, followed by whole-body scanning in supine position. Primary tumor FDG uptake was evaluated and compared with clinical and histopathological characteristics. Presence of locoregional and distant metastases was assessed and compared with conventional imaging procedures.
The primary tumor was visible with PET/CT in 54 (87%) of 62 patients, increasing from 59% (10/17) in tumors ≤ 10 mm to 98% (44/45) in tumors over 10 mm. All triple negative and HER2-positive tumors and 40/48 (83%) ER-positive/HER2-negative tumors were visualized. Sensitivity and specificity of PET/CT in the detection of axillary metastases were 73% and 100%, respectively. PET/CT depicted periclavicular nodes in two patients. Of 12 distant lesions, one was confirmed to be a lung metastasis, three were false positive, and eight were new primary proliferative lesions.
Using optimal imaging acquisition, the majority of T1 breast carcinomas can be visualized with PET/CT. Specificity in the detection of axillary metastases is excellent, but sensitivity appears to be limited. Additional whole body imaging has a low yield in this specific patient group.
[Show abstract][Hide abstract] ABSTRACT: Purpose
We evaluated FDG-positron emission tomography/computerized tomography for monitoring the response of pelvic lymph node metastasis to neoadjuvant chemotherapy for bladder cancer. We compared this to contrast enhanced computerized tomography.
Materials and Methods
Included in study were 19 consecutive patients with lymph node positive bladder cancer who underwent FDG-positron emission tomography/computerized tomography and contrast enhanced computerized tomography before and after a median of 4 cycles (range 2 to 4) of neoadjuvant chemotherapy between September 2011 and April 2012. Metabolic response was assessed according to EORTC (European Organisation for Research and Treatment of Cancer) recommendations based on the change in FDG uptake on FDG-positron emission tomography/computerized tomography. Radiological response was assessed on contrast enhanced computerized tomography according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1. All patients underwent pelvic lymph node dissection. Histopathological evaluation served as the gold standard for the nodal response.
Before neoadjuvant chemotherapy, hypermetabolic FDG uptake was seen in all 19 patients, which matched the lymph node metastasis. Evaluating the nodal response with positron emission tomography/computerized tomography was feasible in all patients. On histopathology 16 patients were responders, including 14 with a complete pathological response of the lymph nodes. Positron emission tomography/computerized tomography and contrast enhanced computerized tomography correctly distinguished responders from nonresponders (18 of 19 patients or 94.7% and 15 of 19 or 78.9%) and complete responders from patients with residual disease (13 of 19 or 68.4% and 12 of 19 or 63.2%, respectively).
Although no definitive conclusions can be drawn from these preliminary data, positron emission tomography/computerized tomography appears feasible for evaluating the nodal response to neoadjuvant chemotherapy and distinguishing responders from nonresponders.
The Journal of urology 05/2013; 189(5):1687–1691. DOI:10.1016/j.juro.2012.11.009 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography-computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential (18)F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II-III breast cancer.
A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUVmax) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard.
A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUVmax was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68-0.92) and 0.65 (95 % confidence interval 0.52-0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %-that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy.
(18)F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.