Elske Quak

Prognostic Value of Microscopic Lymph Node Involvement in Patients With Papillary Thyroid Cancer

CONTEXT The impact of microscopic nodal involvement on the risk of persistent/recurrent disease (PRD) remains controversial in patients with papillary thyroid carcinoma (PTC). OBJECTIVE The goal of the study was to assess the risk of PRD and the 4-year outcome in PTC patients according to their initial nodal status [pNx, pN0, pN1 microscopic (cN0/pN1) or pN1 macroscopic (cN1/pN1)]. DESIGN We conducted a retrospective cohort study. PATIENTS The study included 305 consecutive PTC patients referred for radioiodine ablation from 2006 to 2011. MAIN OUTCOME MEASURE We evaluated the risk of structural PRD and the disease status at the last follow-up. At ablation, persistent disease was consistently assessed by using post-radioiodine ablation scintigraphy combining total body scan and neck and thorax single-photon computed tomography-computed tomography (SPECT-CT) acquisition. RESULTS Of 305 patients, 128 (42%) were pNx, 84 (28%) pN0, 44 (14%) pN1 microscopic, and 49 (16%) pN1 macroscopic. The 4-year cumulative risk of PRD was higher in pN1 macroscopic than in pN1 microscopic patients (49% vs 24%, P = .03), and higher in pN1 microscopic than in pN0 (12%, P = .01) or pNx patients (6%, P < .001). On multivariate analysis, tumor size of 20 mm or greater [relative risk (RR) 3.4; P = .0001], extrathyroid extension (RR 2.6; P < .003), pN1 macroscopic (RR 4.5; P < .0001), and pN1 microscopic (RR 2.5; P < .02) were independent risk factors for PRD. At the last visit, the proportion of patients with no evidence of disease decreased from pNx (98%), pN0 (93%), and pN1 microscopic (89%) to pN1 macroscopic patients (70%) (P < .0001, Cochran-Armitage trend test). Extrathyroid extension (odds ratio 9.7; P < .0001) and N1 macroscopic (OR 4.9; P < .001) independently predicted persistent disease at the last visit, but N1 microscopic did not. CONCLUSIONS PATIENTS with microscopic lymph node involvement present an intermediate outcome between that observed in pN0-pNx patients and pN1 macroscopic patients. These data may justify modifications to the risk recurrence staging systems.

F18-Choline, a Novel PET Tracer for Parathyroid Adenoma?

A 71-year-old man was referred for F18-fluorocholine (F18-choline) positron emission tomography (PET)/ computed tomography (CT) because of suspected prostate cancer recurrence after radical prostatectomy. The F18choline PET/CT was negative for recurrent prostate cancer. However, intense choline uptake was seen in a small lesion adjacent to the right lower pole of the thyroid (Figure 1). As we found out, the patient was analyzed for a primary hyperparathyroidism at the same time. Laboratory values were: calcium, 2.84 mmol/L (normal 2.15– 2.55); PTH, 91.8 pg/L (normal 80); and vitamin D, 31.4 ng/mL (normal 30–74). Thus, we evoked the hypothesis of a right-sided parathyroid adenoma (PTA). A few days later, parathyroid scintigraphy with Tc99m-sestamibi (MIBI) and ultrasonography were performed, and both were concordant with the PET/CT findings. The PTA was subsequently removed by minimally invasive surgery. Histology confirmed the diagnosis. After surgery, calcium levels normalized. To our knowledge, this is the first report of PTA localization with F18-choline PET/CT. We found one report of a C11-choline-positive PTA (1). The potential advantages of a PET tracer instead of MIBI for PTA localization are better spatial resolution allowing for smaller lesion detection and a shorter study protocol due to the rapid biokinetics of choline (2, 3). F18-choline is preferable over C11choline due to its much better availability worldwide and its favorable imaging characteristics. In conclusion, F18-choline PET/CT seems a promising new tool in PTA imaging. A prospective validation focusing on its usefulness as a second-line tracer in the one-third of MIBI negative patients (4) is required.

Clinical applications of positron emission tomography in sarcoma management.

Positron emission tomography (PET) with the fluorine-18-labeled glucose analog FDG is a technique that noninvasively visualizes glucose metabolism in the human body. In oncology, the addition of FDG-PET to the conventional anatomical imaging techniques provides very useful clinical information in diagnosis, staging, treatment response monitoring and follow-up. In the heterogeneous group of patients with sarcoma, FDG-PET has been shown to be of great value in improving patient care. In this article we will discuss the current role of FDG-PET in the management of patients with sarcoma and its value in assessing tumor grade, guiding biopsy, staging, monitoring treatment response, restaging and prognostication. Our future expectation is that the value of PET will only augment owing to the implementation of FDG-PET in clinical guidelines, the increasing availability worldwide, and the development of new tracers and new hybrid imaging techniques.

The importance of harmonizing interim positron emission tomography in non-Hodgkin lymphoma: focus on the Deauville criteria

We would like to draw the attention of the hematology and nuclear medicine communities to the importance of standardized uptake value (SUV) harmonization in response evaluation in non-Hodgkin lymphoma (NHL) patients. In NHL patients, the response evaluation during treatment (interim positron

Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: The impact of treatment preparation modalities and tumor burden

OBJECTIVE In patients with differentiated thyroid cancer (DTC), the stimulated serum thyroglobulin (Tg) level at radioiodine ablation is a known predictive factor of persistent disease. This prognostic value is based on data obtained after thyroid hormone withdrawal (THW), but little is known about this prognostic value after recombinant human TSH (rhTSH) stimulation and about the relationship between the stimulated Tg level and the burden of persistent tumor. We aimed to assess the impact of both radioiodine preparation modalities and persistent tumor burden on stimulated Tg levels. DESIGN AND METHODS The stimulated Tg level was measured at radioablation in 308 consecutive DTC patients without serum Tg antibodies. Of these, 123 (40%) were prepared with rhTSH and 185 with THW. Post-ablation scintigraphy included total-body scan and neck and thorax single photon emission computed tomography with computed tomography (SPECT-CT). During a mean follow-up of 43 months, persistent/recurrent disease (PRD) was found in 56 patients (18%). PRD was considered structural in the presence of lesions >1 cm and nonstructural otherwise. RESULTS Nonstructural PRD was more frequent in the rhTSH group than in the THW group (64 vs 26%, P=0.01). Stimulated Tg levels were lower after rhTSH than after THW in patients with (13.5 vs 99.5 ng/ml, P<0.01) and without (1.2 vs 3.2 ng/ml, P<0.001) PRD. Also, Tg levels were lower in nonstructural disease than in structural disease in both rhTSH (3.8 vs 127.0 ng/ml, P<0.01) and THW (13.0 vs 143.5 ng/ml, P<0.0001) patients. The best Tg cutoff to predict PRD was 2.8 in rhTSH and 28 ng/ml in THW patients. CONCLUSION Both radioiodine preparation modalities and the burden of persistent tumor affect the stimulated Tg level at ablation.

Does PET SUV Harmonization Affect PERCIST Response Classification

Pre- and posttreatment PET comparative scans should ideally be obtained with identical acquisition and processing, but this is often impractical. The degree to which differing protocols affect PERCIST classification is unclear. This study evaluates the consistency of PERCIST classification across different reconstruction algorithms and whether a proprietary software tool can harmonize SUV estimation sufficiently to provide consistent response classification. Methods: Eighty-six patients with non–small cell lung cancer, colorectal liver metastases, or metastatic melanoma who were scanned for therapy monitoring purposes were prospectively recruited in this multicenter trial. Pre- and posttreatment PET scans were acquired in protocols compliant with the Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine (EANM) acquisition guidelines and were reconstructed with a point spread function (PSF) or PSF + time-of-flight (TOF) for optimal tumor detection and also with standardized ordered-subset expectation maximization (OSEM) known to fulfill EANM harmonizing standards. After reconstruction, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs with the OSEM values. The impact of differing reconstructions on PERCIST classification was evaluated. Results: For the OSEMPET1/OSEMPET2 (OSEM reconstruction for pre- and posttherapeutic PET, respectively) scenario, which was taken as the reference standard, the change in SUL was −41% ± 25 and +56% ± 62 in the groups of tumors showing a decrease and an increase in 18F-FDG uptake, respectively. The use of PSF reconstruction affected classification of tumor response. For example, taking the PSF ± TOFPET1/OSEMPET2 scenario increased the apparent reduction in SUL in responding tumors (−48% ± 22) but reduced the apparent increase in SUL in progressing tumors (+37% ± 43), as compared with the OSEMPET1/OSEMPET2 scenario. As a result, variation in reconstruction methodology (PSF ± TOFPET1/OSEMPET2 or OSEM PET1/PSF ± TOFPET2) led to 13 of 86 (15%) and 17 of 86 (20%) PERCIST classification discordances, respectively. Agreement was better for these scenarios with application of the propriety filter, with κ values of 1 and 0.95 compared with 0.79 and 0.72, respectively. Conclusion: Reconstruction algorithm–dependent variability in PERCIST classification is a significant issue but can be overcome by harmonizing SULs using a proprietary software tool.

Lymphoscintigraphy and SPECT/CT using 99mTc filtered sulphur colloid in chylothorax

We present a rare case of a chylothorax in a 60-year-old patient after resection of the thymus (myasthenia gravis and thymus hyperplasia). A left-sided chylothorax developed 20 days after the resection with an estimated daily fluid loss of 1.7 l. Chest lymphoscintigraphy was performed in the anterior and posterior position 60 min after injection of 4×74 MBq Tc filtered sulphur colloid subcutaneously into the first interdigital space and the retromalleolar space of both feet. The images showed abnormal tracer accumulation in the left hemithorax, as seen on the posterior chest lymphoscintigraphic image. SPECT/CT (Symbia T2 Siemens Medical) of the thorax showed abnormal mediastinal tracer accumulation between the left common carotid artery and the left subclavian artery, suggesting rupture of a collateral thoracic lymph duct. Successful ligation of a ruptured ectopic thoracic duct, situated ventral to the left subclavian artery and the phrenic nerve, by video-assisted thoracoscopic surgery was performed and achieved control of the chylothorax. This case clearly illustrates the added value of SPECT/ CT in addition to lymphoscintigraphy for the anatomical location of a traumatic rupture of a thoracic lymph duct. To our knowledge only a few case reports have been published on this subject [1–4].

Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4–2008 image quality parameters

BackgroundThe use of iodinated contrast media in small-animal positron emission tomography (PET)/computed tomography (CT) could improve anatomic referencing and tumor delineation but may introduce inaccuracies in the attenuation correction of the PET images. This study evaluated the diagnostic performance and accuracy of quantitative values in contrast-enhanced small-animal PET/CT (CEPET/CT) as compared to unenhanced small animal PET/CT (UEPET/CT).MethodsFirstly, a NEMA NU 4–2008 phantom (filled with 18F-FDG or 18F-FDG plus contrast media) and a homemade phantom, mimicking an abdominal tumor surrounded by water or contrast media, were used to evaluate the impact of iodinated contrast media on the image quality parameters and accuracy of quantitative values for a pertinent-sized target. Secondly, two studies in 22 abdominal tumor-bearing mice and rats were performed. The first animal experiment studied the impact of a dual-contrast media protocol, comprising the intravenous injection of a long-lasting contrast agent mixed with 18F-FDG and the intraperitoneal injection of contrast media, on tumor delineation and the accuracy of quantitative values. The second animal experiment compared the diagnostic performance and quantitative values of CEPET/CT versus UEPET/CT by sacrificing the animals after the tracer uptake period and imaging them before and after intraperitoneal injection of contrast media.ResultsThere was minimal impact on IQ parameters (%SDunif and spillover ratios in air and water) when the NEMA NU 4–2008 phantom was filled with 18F-FDG plus contrast media. In the homemade phantom, measured activity was similar to true activity (−0.02%) and overestimated by 10.30% when vials were surrounded by water or by an iodine solution, respectively. The first animal experiment showed excellent tumor delineation and a good correlation between small-animal (SA)-PET and ex vivo quantification (r2 = 0.87, P < 0.0001). The second animal experiment showed a good correlation between CEPET/CT and UEPET/CT quantitative values (r2 = 0.99, P < 0.0001). Receiver operating characteristic analysis demonstrated better diagnostic accuracy of CEPET/CT versus UEPET/CT (senior researcher, area under the curve (AUC) 0.96 versus 0.77, P = 0.004; junior researcher, AUC 0.78 versus 0.58, P = 0.004).ConclusionsThe use of iodinated contrast media for small-animal PET imaging significantly improves tumor delineation and diagnostic performance, without significant alteration of SA-PET quantitative accuracy and NEMA NU 4–2008 IQ parameters.

EORTC PET response criteria are more influenced by reconstruction inconsistencies than PERCIST but both benefit from the EARL harmonization program

BackgroundThis study evaluates the consistency of PET evaluation response criteria in solid tumours (PERCIST) and European Organisation for Research and Treatment of Cancer (EORTC) classification across different reconstruction algorithms and whether aligning standardized uptake values (SUVs) to the European Association of Nuclear Medicine acquisition (EANM)/EARL standards provides more consistent response classification.Materials and methodsBaseline (PET1) and response assessment (PET2) scans in 61 patients with non-small cell lung cancer were acquired in protocols compliant with the EANM guidelines and were reconstructed with point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction for optimal tumour detection and with a standardized ordered subset expectation maximization (OSEM) reconstruction known to fulfil EANM harmonizing standards. Patients were recruited in three centres. Following reconstruction, EQ.PET, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs to the EANM standards. The impact of differing reconstructions on PERCIST and EORTC classification was evaluated using standardized uptake values corrected for lean body mass (SUL).ResultsUsing OSEMPET1/OSEMPET2 (standard scenario), responders displayed a reduction of −57.5% ± 23.4 and −63.9% ± 22.4 for SULmax and SULpeak, respectively, while progressing tumours had an increase of +63.4% ± 26.5 and +60.7% ± 19.6 for SULmax and SULpeak respectively. The use of PSF ± TOF reconstruction impacted the classification of tumour response. For example, taking the OSEMPET1/PSF ± TOFPET2 scenario reduced the apparent reduction in SUL in responding tumours (−39.7% ± 31.3 and −55.5% ± 26.3 for SULmax and SULpeak, respectively) but increased the apparent increase in SUL in progressing tumours (+130.0% ± 50.7 and +91.1% ± 39.6 for SULmax and SULpeak, respectively).Consequently, variation in reconstruction methodology (PSF ± TOFPET1/OSEMPET2 or OSEM PET1/PSF ± TOFPET2) led, respectively, to 11/61 (18.0%) and 10/61 (16.4%) PERCIST classification discordances and to 17/61 (28.9%) and 19/61 (31.1%) EORTC classification discordances. An agreement was better for these scenarios with application of the propriety filter, with kappa values of 1.00 and 0.95 compared to 0.75 and 0.77 for PERCIST and kappa values of 0.93 and 0.95 compared to 0.61 and 0.55 for EORTC, respectively.ConclusionPERCIST classification is less sensitive to reconstruction algorithm-dependent variability than EORTC classification but harmonizing SULs within the EARL program is equally effective with either.

FDG-PET/CT in a Patient with Poor-Risk Non-Seminoma Testis with Mature Teratoma and Secondary Gliosarcoma: Multimodality Imaging for Guiding Multimodality Treatment

The value of F-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in detecting viable tumours in patients with metastasised non-seminomatous testicular cancer and residual and new masses post chemotherapy remains to be determined. We describe the case of a 41-year-old patient with metastasised non-seminomatous testicular cancer, with both retroperitoneal and extra-retroperitoneal residual masses post chemotherapy, for whom FDG-PET/CT guided major treatment decisions. FDG-PET/CT correctly identified the locations of viable tumour, as was proved by histology, and successfully guided surgery. In conclusion, in selected cases surveillance of patients with non-seminomatous testicular cancer with FDG-PET/CT can guide major treatment decisions when considering surgery for metastatic disease.