The utilization of positron emission tomography in the evaluation of renal health and disease

Purpose: Positron emission tomography (PET) is a nuclear imaging technique that uses radiotracers to visualize metabolic processes of interest across different organs, to diagnose and manage diseases, and monitor therapeutic response. This systematic review aimed to characterize the value of PET for the assessment of renal metabolism and function in subjects with non-oncological metabolic disorders. Methods: This review was conducted and reported in accordance with the PRISMA statement. Research articles reporting “kidney” or “renal” metabolism evaluated with PET imaging between 1980 and 2021 were systematically searched in Medline/PubMed, Science Direct, and the Cochrane Library. Search results were exported and stored in RefWorks, the duplicates were removed, and eligible studies were identified, evaluated, and summarized. Results: Thirty reports met the inclusion criteria. The majority of the studies were prospective (73.33%, n = 22) in nature. The most utilized PET radiotracers were 15O-labeled radio water (H215O, n = 14) and 18F-fluorodeoxyglucose (18F-FDG, n = 8). Other radiotracers used in at least one study were 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic acid (18F-FTHA), 18F-Sodium Fluoride (18F-NaF), 11C-acetate, 68-Gallium (68Ga), 13N-ammonia (13N-NH3), Rubidium-82 (82Rb), radiolabeled cationic ferritin (RadioCF), 11C‐para-aminobenzoic acid (11C-PABA), Gallium-68 pentixafor (68Ga-Pentixafor), 2-deoxy-2-F-fluoro-d-sorbitol (F-FDS) and 55Co-ethylene diamine tetra acetic acid (55Co-EDTA). Conclusion: PET imaging provides an effective modality for evaluating a range of metabolic functions including glucose and fatty acid uptake, oxygen consumption and renal perfusion. Multiple positron emitting radiolabeled racers can be used for renal imaging in clinical settings. PET imaging thus holds the potential to improve the diagnosis of renal disorders, and to monitor disease progression and treatment response

3D image guided adaptive brachytherapy in patients with locally advanced cervical cancer: experience and clinical results from a minimum of six years of follow-up

In 2005, individualized 3D image guided brachytherapy was implemented for cervical cancer patients, in accordance with the (GYN) GEC ESTRO recommendation, at St. Olav's Hospital, Trondheim, Norway. This study reports the clinical results of sixty-five consecutive patients treated from 2005 to 2010. The patients were treated with curative intent using external beam radiotherapy, brachytherapy and cisplatin. Results of this treatment are presented, including Kaplan-Meier estimates for overall survival (OS) and cancer specific survival (CSS), as well as biological effective dose normalized to equivalent 2 Gy fractions to tumor, defined as high-risk clinical target volume (CTVHR ), and to organs at risk (OARs, here bladder and rectum). Morbidity was prospectively assessed and scored in accordance with the CTCAE 3.0. 92% of the patients achieved treatment response. Local control (LC) remained in all but one patient during follow-up. Five-year OS and CSS were 71% and 80%, respectively. The mean minimum dose to CTVHR for all patients was 80.2 ± 7.3 Gy; 16% and 23% of the patients developed bladder and GI symptoms respectively, 14% of all symptoms were categorized as serious (CTCAE score ≥ 3). A dose-effect relationship was observed for adverse effects of the bladder, and the findings support the more recently recommended lower total dose limit for this OAR

Dosimetric evaluation of manually and inversely optimized treatment planning for high dose rate brachytherapy of cervical cancer

<div><p></p><p><b>Background.</b> To compare five inverse treatment planning methods with the conventional manually optimized planning approach for brachytherapy of cervical cancer with respect to dosimetric parameters.</p><p><b>Material and methods.</b> Eighteen cervical cancer patients treated with magnetic resonance imaging (MRI)-guided high dose rate (HDR) brachytherapy were included in this study. Six plans were created for each of the 4 HDR brachytherapy fractions for each patient: 1 manually optimized and 5 inversely planned. Three of these were based on inverse planning simulated annealing (IPSA) with and without extra constraints on maximum doses of the target volume, and different constraints on doses to the organs at risk (OARs). In addition there were two plans based on dose to target surface points. The resulting dose-volume histograms were analyzed and compared from the dosimetric point of view by quantifying specific dosimetric parameters, such as clinical target volume (CTV) D₉₀, CTV D₁₀₀, conformal index (COIN), and D_2cm3 for rectum, bladder and the sigmoid colon.</p><p><b>Results.</b> Manual optimization led to a mean target coverage of 78.3% compared to 87.5%, 91.7% and 82.5% with the three IPSA approaches (p < 0.001). Similar COIN values for manual and inverse optimization were found. The manual optimization led to better results with respect to the dose to the OARs expressed as D_2cm3. Overall, the best results were obtained with manual optimization and IPSA plans with volumetric constraints including maximum doses to the target volume.</p><p><b>Conclusions.</b> Dosimetric evaluation of manual and inverse optimization approaches is indicating the potential of IPSA for brachytherapy of cervical cancer. IPSA with constraints of maximum doses to the target volume is closer related to manual optimization than plans with constraints only to minimum dose to the target volume and maximum doses to OARs. IPSA plans with proper constraints performed better than those based on dose to target surface points and manually optimized plans.</p></div

Ring Versus Ovoids and Intracavitary Versus Intracavitary-Interstitial Applicators in Cervical Cancer Brachytherapy: Results From the EMBRACE I Study

Purpose: The aim of this study was to investigate the influence of brachytherapy technique and applicator type on target dose, isodose surface volumes, and organ-at-risk (OAR) dose. Methods and Materials: Nine hundred two patients treated with tandem/ovoids (T&O) (n = 299) and tandem/ring (T&R) (n = 603) applicators from 16 EMBRACE centers were analyzed. Patients received external beam radiation therapy and magnetic resonance imaging guided brachytherapy with dose prescription according to departmental practice. Centers were divided into 4 groups, according to applicator/technique: Ovoids and ring centers treating mainly with the intracavitary (IC) technique and ovoids and ring centers treating routinely with the intracavitary/interstitial (IC/IS) technique. V85Gy EQD2 10, CTV HR D 90% (EQD2 10), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD2 3) were evaluated among center groups. Differences between T&O and T&R were tested with multivariable analysis. Results: For similar point A doses, mean CTV HR D 90% was 3.3 Gy higher and V85Gy was 23% lower for ring-IC compared with ovoids-IC centers (at median target volumes). Mean bladder/rectum doses (D 2cm3 and ICRU-point) were 3.2 to 7.7 Gy smaller and vaginal 5-mm lateral-point was 19.6 Gy higher for ring-IC centers. Routine use of IC/IS technique resulted in increased target dose, whereas V85Gy was stable (T&R) or decreased (T&O); reduced bladder and rectum D 2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTV HR D 90% was 2.8 Gy higher, bladder D 2cm3 4.3 Gy lower, rectovaginal ICRU-point 4.8 Gy lower, and vagina 5-mm lateral-point 22.4 Gy higher for ring-IC/IS versus ovoids-IC/IS centers. The P values were <.002 for all comparisons. Equivalently, significant differences were derived from the multivariable analysis. Conclusions: T&R-IC applicators have better target dose and dose conformity than T&O-IC in this representative patient cohort. IC applicators fail to cover large target volumes, whereas routine application of IC/IS improves target and OAR dose considerably. Patients treated with T&R show a more favorable therapeutic ratio when evaluating target, bladder/rectum doses, and V85Gy. A comprehensive view on technique/applicators should furthermore include practical considerations and clinical outcome

MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study

Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems