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Purpose: To compare the predictive value of new immunotherapy-specific fluorine-18-labeled glucose Positron Emission Tomography/Computed Tomography ([18F]FDG PET/CT) response criteria to conventional PET/CT criteria for overall survival (OS) in melanoma and lung cancer patients treated with immunotherapy. Methods: MEDLINE (Ovid), Embase, Scopus, Web of Science and the Cochrane Library databases were searched until June 4, 2021, in line with the PRISMA statement. Two reviewers independently screened resulting records. Quality assessment was performed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and/or Quality in Prognostic Studies (QUIPS) criteria. PET/CT response assessment was divided in immunotherapy PET/CT response criteria, conventional PET/CT response criteria, and individual Δ[18F]FDG/PET CT metrics. The main outcome measure extracted was the univariate hazard ratio (HR) for OS. Results: Fifteen studies (n = 565) were included, with ten studies (225 NSCLC, 178 melanoma cases) reporting on PET/CT response criteria and five studies (126 NSCLC, 36 melanoma cases) on individual Δ[18F]FDG PET/CT metrics. Until 2016, conventional criteria: EORTC and PERCIST1.0 were applied; since then, several new, modified criteria emerged: imPERCIST, PERCIMT, PECRIT and iPERCIST. For both NSCLC and melanoma, univariate HRs did not show substantial differences between immunotherapy and conventional PET/CT response criteria, with overlapping confidence intervals. No individual Δ[18F]FDG PET/CT metric can yet be recommended. ΔTMTV in melanoma and ΔSUVmax in NSCLC showed the highest univariate HRs. Conclusion: There is insufficient evidence to decide whether the predictive value of immunotherapy PET/CT criteria is superior to conventional ones for OS, in melanoma and lung cancer treated with immunotherapy. A different research strategy is needed to reach the answer: PET/CT research should focus on directly comparing (modifications of) immunotherapy and conventional PET/CT criteria within a homogenous population with standardized PET timing, immunotherapy categories and OS definition. A consortium-based comprehensive database with individual patient data could be the solution.

The aim of this study was to investigate whether 18F-FDG PET/CT can predict histopathological response or recurrence in BRAF-mutated unresectable locally advanced stage III melanoma treated with neoadjuvant BRAF/MEK inhibition followed by resection and the value of PET in detecting early recurrence after resection.Twenty BRAF-mutated, unresectable stage III melanoma patients received BRAF/MEK inhibitors before surgery. 18F-FDG PET/CT was performed at baseline and 2 and 8 weeks after initiation of therapy. After resection, PET/CT was performed at specific time points during 5 years of follow-up. Pathological response was assessed on the dissection specimen. Response monitoring was measured with SUVmax, SUVpeak, MATV, and TLG and according to EORTC and PERCIST criteria.Pathological response was assessed in 18 patients. Nine patients (50%) had a pathologic complete or near-complete response, and 9 (50%) had a pathologic partial or no response. EORTC or PERCIST response measurements did not correspond with pathologic outcome. SUVmax, SUVpeak, MATV, and TLG at all time points and absolute or percentage change among the 3 initial time points did not differ between the groups.During follow-up, 8 of 17 patients with R0 resection developed a recurrence, 6 recurrences were detected with imaging only, 4 of which with PET/CT in less than 6 months after surgery. PET parameters before surgery did not predict recurrence.Baseline 18F-FDG PET or PET response in previous unresectable stage III melanoma patients seems not useful to predict pathologic response after neoadjuvant BRAF/MEK inhibitors treatment. However, PET/CT seems valuable in detecting recurrence early after R0 resection.

Objective: The number of radiomics studies in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is rapidly increasing. This systematic review aims to provide an overview of the available evidence of radiomics for clinical outcome measures in GEP-NETs, to understand which applications hold the most promise and which areas lack evidence. Methods: PubMed, Embase, and Wiley/Cochrane Library databases were searched and a forward and backward reference check of the identified studies was executed. Inclusion criteria were (1) patients with GEP-NETs and (2) radiomics analysis on CT, MRI or PET. Two reviewers independently agreed on eligibility and assessed methodological quality with the radiomics quality score (RQS) and extracted outcome data. Results: In total, 1364 unique studies were identified and 45 were included for analysis. Most studies focused on GEP-NET grade and differential diagnosis of GEP-NETs from other neoplasms, while only a minority analysed treatment response or long-term outcomes. Several studies were able to predict tumour grade or to differentiate GEP-NETs from other lesions with a good performance (AUCs 0.74–0.96 and AUCs 0.80–0.99, respectively). Only one study developed a model to predict recurrence in pancreas NETs (AUC 0.77). The included studies reached a mean RQS of 18%. Conclusion: Although radiomics for GEP-NETs is still a relatively new area, some promising models have been developed. Future research should focus on developing robust models for clinically relevant aims such as prediction of response or long-term outcome in GEP-NET, since evidence for these aims is still scarce. Key Points: • The majority of radiomics studies in gastroenteropancreatic neuroendocrine tumours is of low quality. • Most evidence for radiomics is available for the identification of tumour grade or differentiation of gastroenteropancreatic neuroendocrine tumours from other neoplasms. • Radiomics for the prediction of response or long-term outcome in gastroenteropancreatic neuroendocrine tumours warrants further research.

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According to IAEA/EANM/SNMMI guidelines, long-acting somatostatin analogues (LA-SSAs) should be discontinued 4-6 weeks prior to peptide receptor radionuclide therapy (PRRT) to prevent somatostatin receptor saturation. The aim of this study was to determine the effect of continued use of long-acting SSAs during PRRT on the uptake of [Consecutive patients with neuroendocrine tumours who were treated with PRRT receiving 7.4 GBq of [Forty-two patients with 135 cycles of PRRT were included: 28 with lanreotide, 50 with octreotide, and 57 cycles without LA-SSAs. Uptake of [Long-acting octreotide and lanreotide do not interfere with the uptake of [

The aim of this study was to estimate and subsequently measure the occupational radiation exposure for all personnel involved in producing, administering, or performing imaging or surgery with [99mTc]Tc-PSMA-I&S, which has been introduced for identification of tumor-positive lymph nodes during salvage prostate cancer surgery. Methods: The effective dose was estimated and subsequently measured with electronic personal dosimeters for the following procedures and personnel: labeling and quality control by the radiopharmacy technologist, syringe preparation by the nuclear medicine laboratory technologist, patient administration by the nuclear medicine physician, patient imaging by the nuclear medicine imaging technologist, and robot-assisted laparoscopic salvage lymph node dissection attended by an anesthesiology technologist, scrub nurse, surgical nurse, and surgeon. The dose rate of the patient was measured immediately after administration of [99mTc]Tc-PSMA-I&S, after imaging, and after surgery. Results: The estimated dose per procedure ranged from 1.59 × 10-10 μSv (imaging technologist) to 9.74 μSv (scrub nurse). The measured effective dose ranged from 0 to 5 μSv for all personnel during a single procedure with [99mTc]Tc-PSMA-I&S. The highest effective dose was received by the scrub nurse (3.2 ± 1.3 μSv), whereas the lowest dose was measured for the surgical nurse (0.2 ± 0.5 μSv). If a single scrub nurse were to perform as many as 100 procedures with [99mTc]Tc-PSMA-I&S in a year, the total effective dose would be 320 μSv/y. Immediately after administration, the dose rate at 50 cm from the patient was 18.5 ± 1.6 μSv/h, which dropped to 1.8 ± 0.3 μSv/h after imaging the following day, reducing even further to 0.56 ± 0.33 μSv/h after surgery. Conclusion: The effective dose for personnel involved in handling [99mTc]Tc-PSMA-I&S is comparable to that of other 99mTc-radiopharmaceuticals and therefore safe for imaging and radioguided surgery.

Item does not contain fulltext INTRODUCTION: The aim of this study was to identify subgroups of locally advanced NSCLC patients with a distinct treatment response during concurrent chemoradiotherapy (CCRT). Subsequently, we investigated the association of subgroup membership with treatment outcomes. METHODS: 394 NSCLC-patients treated with CCRT between 2007 and 2013 were included. Gross Tumor Volume (GTV) during treatment was determined and relative GTV-volume change from the planning-CT was subsequently calculated. Latent Class Mixed Modeling (LCMM) was used to identify subgroups with distinct volume changes during CCRT. The association of subgroup membership with overall survival (OS), progression free survival (PFS) and local regional control (LRC) was assessed using cox regression analyses. RESULTS: Three subgroups of GTV-volume change during treatment were identified, with each subsequent subgroup showing a more profound reduction of GTV during treatment. No associations between subgroup membership and OS, PFS nor LRC were observed. Nonetheless, baseline GTV (HR1.42; 95%CI 1.06-1.91) was significantly associated with OS. CONCLUSIONS: Three different subgroups of GTV-volume change during treatment were identified. Surprisingly, these subgroups did not differ in their risk of treatment outcomes. Only patients with a larger GTV at baseline had a significantly worse OS. Therefore, risk stratification at baseline might already be accurate in identifying the best treatment strategy for most patients.

The number of radiomics studies in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is rapidly increasing. This systematic review aims to provide an overview of the available evidence of radiomics for clinical outcome measures in GEP-NETs, to understand which applications hold the most promise and which areas lack evidence.PubMed, Embase, and Wiley/Cochrane Library databases were searched and a forward and backward reference check of the identified studies was executed. Inclusion criteria were (1) patients with GEP-NETs and (2) radiomics analysis on CT, MRI or PET. Two reviewers independently agreed on eligibility and assessed methodological quality with the radiomics quality score (RQS) and extracted outcome data.In total, 1364 unique studies were identified and 45 were included for analysis. Most studies focused on GEP-NET grade and differential diagnosis of GEP-NETs from other neoplasms, while only a minority analysed treatment response or long-term outcomes. Several studies were able to predict tumour grade or to differentiate GEP-NETs from other lesions with a good performance (AUCs 0.74-0.96 and AUCs 0.80-0.99, respectively). Only one study developed a model to predict recurrence in pancreas NETs (AUC 0.77). The included studies reached a mean RQS of 18%.Although radiomics for GEP-NETs is still a relatively new area, some promising models have been developed. Future research should focus on developing robust models for clinically relevant aims such as prediction of response or long-term outcome in GEP-NET, since evidence for these aims is still scarce.• The majority of radiomics studies in gastroenteropancreatic neuroendocrine tumours is of low quality. • Most evidence for radiomics is available for the identification of tumour grade or differentiation of gastroenteropancreatic neuroendocrine tumours from other neoplasms. • Radiomics for the prediction of response or long-term outcome in gastroenteropancreatic neuroendocrine tumours warrants further research.

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for patients with neuroendocrine neoplasms. The aim of this study was to identify clinical and treatment parameters associated with progression-free survival (PFS) and overall survival (OS). Methods: All patients treated from October 2002 until March 2016 at the Zentralklinik Bad Berka with at least 3 administrations of PRRT (maximal interval of 6 mo between consecutive administrations) were included. Data were collected in 5 categories: general patient characteristics, tumor characteristics, prior treatments, radioisotope used for PRRT, and blood chemistry. Survival was analyzed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to identify parameters associated with PFS and OS. Results: In total, 782 patients were included, with a median follow-up of 36 mo. The median PFS and OS were 22 and 53 mo, respectively. Parameters associated with lower PFS in the multivariate analysis were a Ki-67 of more than 5%, previous treatment with interferon-alpha and chemotherapy, presence of diabetes, and chromogranin-A (CgA) levels higher than 336 mu g/L. Parameters associated with lower OS were a Ki-67 of more than 10%, performance status of at least 1, previous chemotherapy and ablation, and CgA levels higher than 112 mu g/L. Conclusion: Higher Ki-67 values, as well as higher CgA levels and previous chemotherapy, had a negative outcome on both PFS and OS. Furthermore, PFS was negatively associated with previous interferon-alpha treatment and diabetes, whereas lower OS was related to prior ablation and higher performance status.

Patients with unresectable or metastasized neuroendocrine tumors are assumed eligible for PRRT (peptide receptor radionuclide therapy) with 177Lu-HA-DOTATATE if tumor uptake on somatostatin receptor imaging is higher than normal liver tissue. In our clinic, 2 patients presented with sufficient uptake of 68Ga-HA-DOTATATE in most metastases but with limited uptake in liver lesions. Posttherapy 177Lu imaging, however, showed good uptake in all neuroendocrine tumor lesions, including all liver metastases. Therefore, the presence of liver metastases in which the uptake of 68Ga-HA-DOTATATE is not or only slightly higher than in surrounding normal liver tissue should not be an absolute contraindication for PRRT.

The aim of this study was to estimate and subsequently measure the occupational radiation exposure for all personnel involved in producing, administering, or performing imaging or surgery with [

Neuroendocrine tumors are a rare form of cancer that arise from neuroendocrine cells and can be present at almost any location throughout the body. Although heterogeneous in presentation, a common denominator among these tumors is the overexpression of somatostatin receptors.

Neuroendocrine tumors are a rare form of cancer that arise from neuroendocrine cells and can be present at almost any location throughout the body. Although heterogeneous in presentation, a common denominator among these tumors is the overexpression of somatostatin receptors. 68Ga-DOTATATE is a somatostatin analog labeled with the positron emitter gallium-68 (68Ga). For well-differentiated neuroendocrine tumors, 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) imaging is used for diagnosis, determination of disease burden, and therapy selection. This protocol details the radiolabeling of 68Ga-DOTATATE, quality control, patient preparation, and subsequent PET/CT imaging. Radiolabeling of 68Ga-DOTATATE is performed with a fully automated labeling module coupled to a germanium-68 (68Ge)/68Ga generator. Quality control of the final product evaluates radiochemical purity with instant thin-layer chromatography and solid-phase chromatography, and pH prior to patient injection. Periodic quality control is performed to determine 68Ge breakthrough, sterility, and (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) content. Patient preparation includes patient instructions, a protocol for 68Ga-DOTATATE during treatment with somatostatin analogs, and intravenous administration of the radiopharmaceutical. For PET/CT imaging, the acquisition and reconstruction settings are described. For each step, radiation safety will be highlighted, as well as time constrictions due to the short half-life of 68Ga. Fully automated in-house production and quality control of 68Ga-DOTATATE leads to very high success rates (95%) and produces two to four patient dosages per batch, depending on the yield of the generator. In conclusion, 68Ga-DOTATATE PET/CT imaging is a noninvasive and fast method of providing information on the tumor burden of neuroendocrine tumors (NETs) while also assisting in diagnosis and therapy selection.

BACKGROUND Most neuroendocrine tumours (NETs) metastasize to the liver, lymph nodes and, although less frequently, to the bone. The heart is a rare localization for NET metastases. METHODS With the introduction of the Ga-DOTATATE PET/computed tomography (CT) in our hospital as a new diagnostic method for imaging neuroendocrine tumours, more rare metastatic localizations are being found. We present six cases of patients with cardiac NET metastases detected by Ga-DOTATATE PET/CT. Also, a review of literature is presented on case reports of cardiac NET metastases in patients detected by somatostatin receptor imaging, including In-Pentetreotide single photon emission computed tomography/CT, Ga-DOTATATE PET/CT, Ga-DOTANOC PET/CT or Ga-DOTATOC PET/CT. RESULTS AND CONCLUSION Most patients with cardiac NET metastases have extensive metastatic disease. The cardiac metastases are often asymptomatic.

Item does not contain fulltext AIMS: Pre-hydration is routinely applied to reduce nephrotoxicity in concurrent cisplatin-based chemo-radiotherapy (CCRT). However, pre-hydration may also have systemic effects, potentially leading to lower tumour cisplatin concentrations. We investigated the impact of pre-hydration on tumour cisplatin concentrations in mice, and on treatment outcomes in a clinical cohort study. MATERIALS AND METHODS: Four groups of 20 mice received either no pre-hydration prior to full-dose (6mg/kg) or half-dose cisplatin, overnight dehydration prior to full-dose cisplatin (dehydration), or NaCl intraperitoneally prior to full-dose cisplatin (pre-hydration). Kidney function and tumour platinum concentration were measured. In patients, a retrospective study compared 2 historical NSCLC cohorts which received CCRT with daily cisplatin, with and without standard pre-hydration. Overall survival (OS) and progression free survival (PFS) were compared using Kaplan-Meier and cox-regression. RESULTS: Pre-hydration significantly decreased cisplatin tumour concentrations in mice, comparable to mice receiving half the dose. In 419 patients (211 without and 208 with pre-hydration) with median follow-up 22months, there were no significant differences in PFS (18 vs. 15months) or OS (23 vs. 23months). CONCLUSION: Pre-hydration reduces cisplatin tumour concentrations in mice, but it does not compromise treatment outcomes in NSCLC patients treated with daily cisplatin and radiotherapy.

The aim of this study was to associate and predict B-rapidly accelerated fibrosarcoma valine 600 (BRAFV600) mutation status with both conventional and radiomics 18F-FDG PET/CT features, while exploring several methods of feature selection in melanoma radiomics. Methods: Seventy unresectable stage III–IV melanoma patients who underwent a baseline 18F-FDG PET/CT scan were identified. Patients were assigned to the BRAFV600 group or BRAF wild-type group according to mutational status. 18F-FDG uptake quantification was performed by semiautomatic lesion delineation. Four hundred eighty radiomics features and 4 conventional PET features (SUVmax, SUVmean, SUVpeak, and total lesion glycolysis) were extracted per lesion. Six different methods of feature selection were implemented, and 10-fold cross-validated predictive models were built for each. Model performances were evaluated with areas under the curve (AUCs) for the receiver operating characteristic curves. Results: Thirty-five BRAFV600 mutated patients (100 lesions) and 35 BRAF wild-type patients (79 lesions) were analyzed. AUCs predicting the BRAFV600 mutation varied from 0.54 to 0.62 and were susceptible to feature selection method. The best AUCs were achieved by feature selection based on literature, a penalized binary logistic regression model, and random forest model. No significant difference was found between the BRAFV600 and BRAF wild-type group in conventional PET features or predictive value. Conclusion: BRAFV600 mutation status is not associated with, nor can it be predicted with, conventional PET features, whereas radiomics features were of low predictive value (AUC 5 0.62). We showed feature selection methods to influence predictive model performance, describing and evaluating 6 unique methods. Detecting BRAFV600 status in melanoma based on 18F-FDG PET/CT alone does not yet provide clinically relevant knowledge.

Introduction: Somatostatin receptor imaging with PET is the standard of care for patients with a neuroendocrine tumour (NET). Since therapy and imaging with somatostatin analogues utilize the same receptor, current guidelines recommend withdrawing long-acting somatostatin analogues for 3-4 weeks prior to somatostatin receptor PET imaging. The aim of this study is to prospectively assess the effect of lanreotide use on the uptake of 68Ga-DOTATATE intra-individually 1 day prior to and 1 day post injection of lanreotide. Methods: Thirty-four patients with metastatic and/or unresectable NET and currently on lanreotide therapy for at least 4 months were included in the study. A 68Ga-DOTATATE PET/CT scan was performed on the day before and the day after lanreotide injection. In each patient 68Ga-DOTATATE uptake (SUVmax, mean, peak) was assessed in both tumour lesions and normal tissue. All scans were assessed by two blinded nuclear medicine physicians for visual analysis. Paired T-tests were performed to determine the differences between the scans. Results: Of the 34 patients included, 31 were available for analyses in which 190 tumour lesions were measured. Uptake of 68Ga-DOTATATE in tumour lesions was increased significantly after lanreotide, but decreased significantly in the liver, spleen, and thyroid gland resulting in a higher tumour-to-liver ratio. Conclusion: Lanreotide injection prior to 68Ga-DOTATATE PET/CT does not result in decreased tumour uptake. In contrast, tumour uptake was increased, whereas the uptake in normal organs is decreased, leading to an increased tumour-to-liver ratio. However, these differences were small and not deemed clinically relevant. These results strongly suggest that discontinuation of lanreotide injections in the weeks prior to 68Ga-DOTATATE PET examinations is unnecessary and does not compromise nuclear medicine imaging results.

In vivo biodistribution imaging of platinum-based compounds may allow better patient selection for treatment with chemo(radio)therapy. Radiolabeling with Platinum-195m (195mPt) allows SPECT imaging, without altering the chemical structure or biological activity of the compound. We have assessed the feasibility of 195mPt SPECT imaging in mice, with the aim to determine the image quality and accuracy of quantification for current preclinical imaging equipment. Enriched (>96%) 194Pt was irradiated in the High Flux Reactor (HFR) in Petten, The Netherlands (NRG). A 0.05 M HCl 195mPt-solution with a specific activity of 33 MBq/mg was obtained. Image quality was assessed for the NanoSPECT/CT (Bioscan Inc., Washington DC, USA) and U-SPECT+/CT (MILabs BV, Utrecht, the Netherlands) scanners. A radioactivity-filled rod phantom (rod diameter 0.85-1.7 mm) filled with 1 MBq 195mPt was scanned with different acquisition durations (10-120 min). Four healthy mice were injected intravenously with 3-4 MBq 195mPt. Mouse images were acquired with the NanoSPECT for 120 min at 0, 2, 4, or 24 h after injection. Organs were delineated to quantify 195mPt concentrations. Immediately after scanning, the mice were sacrificed, and the platinum concentration was determined in organs using a gamma counter and graphite furnace – atomic absorption spectroscopy (GF-AAS) as reference standards. A 30-min acquisition of the phantom provided visually adequate image quality for both scanners. The smallest visible rods were 0.95 mm in diameter on the NanoSPECT and 0.85 mm in diameter on the U-SPECT+. The image quality in mice was visually adequate. Uptake was seen in the kidneys with excretion to the bladder, and in the liver, blood, and intestine. No uptake was seen in the brain. The Spearman correlation between SPECT and gamma counter was 0.92, between SPECT and GF-AAS it was 0.84, and between GF-AAS and gamma counter it was0.97 (all p