OBJECTIVE. There is growing interest in using PET/CT for evaluating early response to therapy in cancer treatment. Although widely available and convenient to use, standardized uptake value (SUV) measurements can be influenced by a variety of biologic and technologic factors. Many of these factors can be addressed with close attention to detail and appropriate quality control. This article will review factors potentially affecting SUV measurements and provide recommendations on ways to minimize when using serial PET to assess early response to therapy.CONCLUSION. Scanner and reconstruction parameters can significantly affect SUV measurements. When using serial SUV measurements to assess early response to therapy, imaging should be performed on the same scanner using the same image acquisition and reconstruction protocols. In addition, attention to detail is required for accurate determination of the administered radiopharmaceutical dose.

https://www.ajronline.org/doi/pdfplus/10.2214/AJR.10.4923

A systematic review of the factors affecting accuracy of SUV measurements.

Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.

/pdf/european-society-of-endocrinology-clinical-practice-kp1v36e4y6.pdf

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

Radioiodine ((131)I) therapy of benign thyroid diseases was introduced 70 yr ago, and the patients treated since then are probably numbered in the millions. Fifty to 90% of hyperthyroid patients are cured within 1 yr after (131)I therapy. With longer follow-up, permanent hypothyroidism seems inevitable in Graves' disease, whereas this risk is much lower when treating toxic nodular goiter. The side effect causing most concern is the potential induction of ophthalmopathy in predisposed individuals. The response to (131)I therapy is to some extent related to the radiation dose. However, calculation of an exact thyroid dose is error-prone due to imprecise measurement of the (131)I biokinetics, and the importance of internal dosimetric factors, such as the thyroid follicle size, is probably underestimated. Besides these obstacles, several potential confounders interfere with the efficacy of (131)I therapy, and they may even interact mutually and counteract each other. Numerous studies have evaluated the effect of (131)I therapy, but results have been conflicting due to differences in design, sample size, patient selection, and dose calculation. It seems clear that no single factor reliably predicts the outcome from (131)I therapy. The individual radiosensitivity, still poorly defined and impossible to quantify, may be a major determinant of the outcome from (131)I therapy. Above all, the impact of (131)I therapy relies on the iodine-concentrating ability of the thyroid gland. The thyroid (131)I uptake (or retention) can be stimulated in several ways, including dietary iodine restriction and use of lithium. In particular, recombinant human thyrotropin has gained interest because this compound significantly amplifies the effect of (131)I therapy in patients with nontoxic nodular goiter.

Radioiodine Therapy in Benign Thyroid Diseases: Effects, Side Effects, and Factors Affecting Therapeutic Outcome

Quantitative positron emission tomography/computed tomography (PET/CT) can be used as diagnostic or prognostic tools (i.e. single measurement) or for therapy monitoring (i.e. longitudinal studies) in multicentre studies. Use of quantitative parameters, such as standardized uptake values (SUVs), metabolic active tumor volumes (MATVs) or total lesion glycolysis (TLG), in a multicenter setting requires that these parameters be comparable among patients and sites, regardless of the PET/CT system used. This review describes the motivations and the methodologies for quantitative PET/CT performance harmonization with emphasis on the EANM Research Ltd. (EARL) Fluorodeoxyglucose (FDG) PET/CT accreditation program, one of the international harmonization programs aiming at using FDG PET as a quantitative imaging biomarker. In addition, future accreditation initiatives will be discussed. The validation of the EARL accreditation program to harmonize SUVs and MATVs is described in a wide range of tumor types, with focus on therapy assessment using either the European Organization for Research and Treatment of Cancer (EORTC) criteria or PET Evaluation Response Criteria in Solid Tumors (PERCIST), as well as liver-based scales such as the Deauville score. Finally, also presented in this paper are the results from a survey across 51 EARL-accredited centers reporting how the program was implemented and its impact on daily routine and in clinical trials, harmonization of new metrics such as MATV and heterogeneity features.

/pdf/eanm-earl-harmonization-strategies-in-pet-quantification-cvtz2ybwmv.pdf

EANM/EARL harmonization strategies in PET quantification: From daily practice to multicentre oncological studies

https://www.cell.com/trends/molecular-medicine/pdf/S1471-4914(14)00204-4.pdf

Molecular mechanisms of maternal vascular dysfunction in preeclampsia

The standardized uptake value (SUV) has gained recognition in recent years as a semiquantitative evaluation parameter in positron emission tomography (PET) studies. However, there is as yet no consensus on the way in which this index should be determined. One of the confusing factors is the normalisation procedure. Among the proposed anthropometric parameters for normalisation is lean body mass (LBM); LBM has been determined by using a predictive equation in most if not all of the studies. In the present study, we assessed the degree of agreement of various LBM predictive equations with a reference method. Secondly, we evaluated the impact of predicted LBM values on a hypothetical value of 2.5 SUV, normalised to LBM (SUVLBM), by using various equations. The study population consisted of 153 women, aged 32.3±11.8 years (mean±SD), with a height of 1.61±0.06 m, a weight of 71.1±17.5 kg, a body surface area of 1.77±0.22 m2 and a body mass index of 27.6±6.9 kg/m2. LBM (44.2±6.6 kg) was measured by a dual-energy X-ray absorptiometry (DEXA) method. A total of nine equations from the literature were evaluated, four of them from recent PET studies. Although there was significant correlation between predicted and measured LBM values, 95% limits of agreement determined by the Bland and Altman method showed a wide range of variation in predicted LBM values as compared with DEXA, no matter which predictive equation was used. Moreover, only one predictive equation was not statistically different in the comparison of means (DEXA and predicted LBM values). It was also shown that the predictive equations used in this study yield a wide range of SUVLBM values from 1.78 to 5.16 (29% less or 107% more) for an SUV of 2.5. In conclusion, this study suggests that estimation of LBM by use of a predictive equation may cause substantial error for an individual, and that if LBM is chosen for the SUV normalisation procedure, it should be measured, not predicted.

Lean body mass-based standardized uptake value, derived from a predictive equation, might be misleading in PET studies.

Although radiosynovectomy (RS) applications have been carried out for many years, clinical indications of this non-invasive procedure is though to be limited probably due to the lack of information of clinicians. Clinicians’ preferential indication for RS is the treatment-resistant synovitis of individual joints, i.e. despite systemic pharmacotherapy and intra-articular steroid injections. We present here a case of “lipoma arborescens” treated by yttrium-90, which is a rare intra-articular lesion characterized by villous proliferation of the synovial membrane and hyperplasia of subsynovial fat. The results of clinical, biochemical and hematological examinations, magnetic resonance (MR) imaging, arthroscopy and histological analysis have shown that the etiology was lipoma arborescens in a female patient, aged 36 having swelling and sometimes associating pain at her right knee for 4 years. We have applied to our patient’s right knee RS with 185 MBq yttrium-90 colloid together with 40 mg of methylprednisolone acetate, although in our literature survey we have not met any similar case being treated with such indication. Even a year after the application, the patient has absolutely benefited from the treatment clinically, and this was also confirmed by comparative MR images (pre- and post-treatment). Consequently, we consider that Y-90 treatment might be applicable in suitable cases with lipoma arborescens.

Lipoma arborescens ; successfully treated by yttrium-90 radiosynovectomy

The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model.

Objective The aim of this study was to determine the change in volumetric and radiomics parameters of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) imaging in local/locally advanced cancer patients according to immunohistochemical findings. Patients and methods A total of 72 patients who were diagnosed with local/locally advanced breast cancer and then examined by F-FDG PET/CT for staging were included in this study. Immunohistochemical prognostic factors [estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), p53 mutation, Ki-67 proliferation index] and histological grades were determined. Standardized uptake value (SUV)-based, volume-based, and radiomics findings were obtained from F-FDG PET/CT images. Results In cases of ER and PR negativity, Her-2 positivity, presence of the p53 mutation, and Ki-67 index of at least 20% patients, total volumetric parameters were significantly higher in paired comparisons. The results of the ER-negative group were significantly higher than those of ER-positive patients in GLRLM_GLNU, GLRLM_RLNU, GLZLM_GLNU, and GLZLM_ZLNU comparisons. In grade 3 patients, mean SUV, maximum SUV, and GLRLM_LRHGE values were higher than those of grade 2 patients. SUV and volumetric parameters were significantly higher in patients with Ki-67 index of at least 20% than those with less than 20%. Maximum SUV, breast tumor lesion glycolysis values, and entropy in nuclear polymorphism in the 3+ patient group were found to be higher compared with the 2+ patient group. Moreover, patients with mitosis 3+ had significantly higher breast metabolic tumor volume, breast tumor lesion glycolysis, and kurtosis values than the 1+ group. Conclusion ER negativity, triple negativity, high tumor grade, and high nuclear polymorphism were associated with tumor heterogeneity. With respect to ER negativity, PR negativity, high tumor grade, high mitosis number, high Ki-67 index, Her-2 positivity, and the presence of p53 mutation, an increased tumor load were observed. In addition to immunohistochemical parameters, the use of radiomics data is believed to contribute to breast cancer management.

Comparison of the volumetric and radiomics findings of 18F-FDG PET/CT images with immunohistochemical prognostic factors in local/locally advanced breast cancer.

Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of (131)I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and 5.75+/-2.06, respectively, in the whole group, and these values differed significantly from each other ( P<0.001). In order to perform a quantitative evaluation of the present data and a comparative analysis with the results of previous studies reported in the literature, we defined acute and late effects using a "damage ratio" (DR) and a "recovery ratio" (RR), based on the basal, acute and late data for individual patients. No statistically significant difference was found in the DR between DTC and TTX patients (76.4%+/-11.5% vs 67.6%+/-9.0%), while the mean RR was higher in TTX patients than in the DTC group (75.2%+/-24.4% vs 36.8%+/-13.7%). The DR on the 3rd day was not related to the administered (131)I dose in the whole group, but a negative correlation was found between the (131)I dose and the RR at the 6th month (r=-0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x-28.4x(2)+38.1 ( R(2)=0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of (131)I and DR and RR were obtained with a linear-quadratic model (Y=alpha D+beta D(2)) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient beta to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following (131)I treatment. Further studies are therefore needed to clarify the effect of the negative beta value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of (131)I treatment.

Bülent Turgut

Papers

Lean body mass-based standardized uptake value, derived from a predictive equation, might be misleading in PET studies.

Lipoma arborescens ; successfully treated by yttrium-90 radiosynovectomy

The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model.

Comparison of the volumetric and radiomics findings of 18F-FDG PET/CT images with immunohistochemical prognostic factors in local/locally advanced breast cancer.

Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship