Early CT and FDG-metabolic tumour volume changes show a significant correlation with survival in stage I-III small cell lung cancer: A hypothesis generating study

BACKGROUND: Many patients with stage I–III small cell lung cancer (SCLC) experience disease progression short after the completion of concurrent chemoradiotherapy (CRT). The purpose of the current study was to evaluate whether CT or FDG metabolic response early after the start of chemotherapy, but before the beginning of chest RT, is predictive for survival in SCLC. METHODS: Fifteen stage I–III SCLC patients treated with concurrent CRT with an FDG-PET and CT scan available before the start of chemotherapy and after or during the first cycle of chemotherapy, but before the start of radiotherapy, were selected. The metabolic volume (MV) was defined both within the primary tumour and in the involved nodal stations using the 40% (MV40) and 50% (MV50) threshold of the maximum SUV. Metabolic and CT response was assessed by the relative change in MV and CT volume, respectively, between both time points. The association between response and overall survival (OS) was analysed by univariate cox regression analysis. The minimum follow-up was 18 months. RESULTS: Reductions in MV40 and MV50 were −36 ± 38% (126.4 to 68.7 cm(3)) and −44 ± 38% (90.2 to 27.8 cm(3)), respectively. The median CT volume reduction was −40 ± 64% (190.6 to 113.8 cm(3)). MV40 and MV50 changes showed a significant association with survival (HR = 1.02, 95% CI: 1.00–1.04 (p = 0.042); HR = 1.02, 95% CI: 1.00–1.04 (p = 0.048), respectively), indicating a 2% increase in survival probability for 1% reduction in metabolic volume. The CT volume change was also significantly correlated with survival (HR = 1.01, 95% CI: 1.00–1.03, p = 0.007). CONCLUSIONS: This hypothesis generating study shows that both the early CT and the MV changes show a significant correlation with survival in SCLC. A prospective study is planned in a larger patient cohort to allow multivariate analysis, with the final aim to select patients early during treatment that could benefit from dose intensification or alternative treatment

Evaluation of the Implementation of FDG-PET/CT and Staging Laparoscopy for Gastric Cancer in The Netherlands

Background: The role of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) has increased in the preoperative staging of gastric cancer. Dutch national guidelines have recommended the use of FDG-PET/CT and SL for patients with locally advanced tumors since July 2016. Objective: The aim of this study was to evaluate the implementation of FDG-PET/CT and SL in The Netherlands. Methods: Between 2011 and 2018, all patients who underwent surgery for gastric cancer were included from the Dutch Upper GI Cancer Audit. The use of FDG-PET/CT and SL was evaluated before and after revision of the Dutch guidelines. Outcomes included the number of non-curative procedures (e.g. palliative and futile procedures) and the association of FDG-PET/CT and SL, with waiting times from diagnosis to the start of treatment. Results: A total of 3310 patients were analyzed. After July 2016, the use of FDG-PET/CT (23% vs. 61%; p < 0.001) and SL (21% vs. 58%; p < 0.001) increased. FDG-PET/CT was associated with additional waiting time to neoadjuvant therapy (4 days), as well as primary surgical treatment (20 days), and SL was associated with 8 additional days of waiting time to neoadjuvant therapy. Performing SL or both modalities consecutively in patients in whom it was indicated was not associated with the number of non-curative procedures. Conclusion

Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families. In the European HD-eHelp study, we aim to capture the needs and wishes of HDGECs, partners of HDGECs, and health care providers (HCPs) in order to develop a multinational eHealth platform targeting QoL of both HDGECs and partners at home.Methods: We will employ a participatory user-centered design (UCD) approach, which focusses on an in-depth understanding of the end-users' needs and their contexts. Premanifest and manifest adult HDGECs (n = 76), partners of HDGECs (n = 76), and HCPs (n = 76) will be involved as end-users in all three phases of the research and design process: (1) Exploration and mapping of the end-users' needs, experiences and wishes; (2) Development of concepts in collaboration with end-users to ensure desirability; (3) Detailing of final prototype with quick review rounds by end-users to create a positive user-experience. This study will be conducted in the Netherlands, Germany, Czech Republic, Italy, and Ireland to develop and test a multilingual platform that is suitable in different healthcare systems and cultural contexts.Discussion: Following the principles of UCD, an innovative European eHealth platform will be developed that addresses the needs and wishes of HDGECs, partners and HCPs. This allows for high-quality, tailored care to be moved partially into the participants' home, thereby circumventing some barriers in current HD care provision. By actively involving end-users in all design decisions, the platform will be tailored to the end-users' unique requirements, which can be considered pivotal in eHealth services for a disease as complex and rare as HD

Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT and biodistribution studies in megalin-deficient mice

Contains fulltext : 98302.pdf (publisher's version ) (Closed access)PURPOSE: Radiolabelled peptides used for peptide receptor radionuclide therapy are excreted mainly via the kidneys and are partly reabsorbed and retained in the proximal tubular cells. The resulting high renal radiation dose can cause nephrotoxicity, limiting the maximum activity dose and the effectiveness of peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of these peptides are incompletely understood, but the scavenger receptor megalin has been shown to play a role in the reabsorption of (111)In-octreotide. In this study, the role of megalin in the renal reabsorption of various relevant radiolabelled peptides was investigated. METHODS: Groups of kidney-specific megalin-deficient mice and wild-type mice were injected with (111)In-labelled somatostatin, exendin, neurotensin or minigastrin analogues. Single photon emission computed tomographic (SPECT) images of the kidneys were acquired and analysed quantitatively, or the animals were killed 3 h after injection and the activity concentration in the kidneys was measured. RESULTS: Megalin-deficient mice showed significantly lower uptake of all studied radiolabelled peptides in the kidneys, ranging from 22% ((111)In-octreotide) to 65% ((111)In-exendin) of uptake in wild-type kidneys. Quantitative analysis of renal uptake by SPECT and ex vivo measurements showed a very good correlation. CONCLUSION: Megalin is involved in the renal reabsorption of radiolabelled octreotide, octreotate, exendin, neurotensin and minigastrin. This knowledge may help in the design of strategies to reduce this reabsorption and the resulting nephrotoxicity in peptide receptor radionuclide therapy, enabling more effective therapy. Small-animal SPECT is an accurate tool, allowing in vivo quantification of renal uptake and serial measurements in individual mice

Analyzing the Estrogen Receptor Status of Liver Metastases with [F-18]-FES-PET in Patients with Breast Cancer

Background: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [18F]-FES uptake. We evaluated whether [18F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard. Methods: Patients with metastatic breast cancer (n = 23) were included if they had undergone a [18F]-FES-PET, liver metastasis biopsy, CT-scan, and [18F]-FDG-PET. [18F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined. Results: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER− metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive. Conclusion: In the majority of liver metastases, ER status can be determined with [18F]-FES-PET if background correction and separate thresholds are applied

Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

Contains fulltext : 88022.pdf (publisher's version ) (Closed access)PURPOSE: In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. METHODS: Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of (111)In-albumin, (111)In-minigastrin, (111)In-exendin and (111)In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of (111)In-minigastrin, (111)In-exendin and (111)In-octreotide was determined. RESULTS: FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of (111)In-albumin, (111)In-exendin and (111)In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide #6), was selected for in vivo testing. In rats, 5 mg of peptide #6 very efficiently inhibited the renal uptake of (111)In-minigastrin, by 88%. Uptake of (111)In-exendin and (111)In-octreotide was reduced by 26 and 33%, respectively. CONCLUSIONS: The albumin-derived peptide #6 efficiently inhibited the renal reabsorption of (111)In-minigastrin, (111)In-exendin and (111)In-octreotide and is a promising candidate for kidney protection in PRRT.1 februari 201

Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial

Background: Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potent

Prognostic Value of [¹⁸F]FDG PET Radiomics to Detect Peritoneal and Distant Metastases in Locally Advanced Gastric Cancer—A Side Study of the Prospective Multicentre PLASTIC Study

Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [18F]FDG-PET radiomics. Methods: [18F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [18F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis.</p

Clinical impact of PSMA PET/CT in primary prostate cancer compared to conventional nodal and distant staging: a retrospective single center study

BACKGROUND: To evaluate the impact of Gallium-68 [68Ga] labeled prostate specific membrane antigen (PSMA) positron emission tomography (PET)/X-ray computed tomography (CT) compared with conventional imaging on staging and clinical management of men evaluated for primary prostate cancer (PCa). METHODS: Men with newly diagnosed biopsy-proven PCa who had been staged with a conventional staging protocol including bone scintigraphy (BS) and additionally underwent [68Ga]PSMA PET/CT, were evaluated retrospectively. Imaging findings from BS, magnetic resonance imaging (MRI) and/or CT were categorized regarding locoregional nodal (N) and distant metastasis (M) status as negative, positive or equivocal before and after addition of the information of PET/CT. Also, the imaging-based level of confidence (LoC) in correct assessment of N and M status was scored. Impact of PET/CT on clinical management was evaluated by the percentage of treatment category changes after PET/CT as determined in the multidisciplinary tumour board. RESULTS: Sixty-four men with intermediate and high-risk PCa were evaluated. With additional information of PET/CT, N status was upstaged in 23%, and downstaged in 9%. M status was upstaged in 13%, and downstaged in 23%. A net increase in LoC of 20% was noted, mainly regarding M status. Treatment category changed from palliative to curative in 9%, and from curative to palliative in 3%. An undecided treatment plan changed to curative in 14%, as well as to palliative in another 9%. In total, a 36% treatment category change was noted. High negative predictive value of PET/CT for M status was indicated by 27 patients that underwent robot-assisted radical prostatectomy and reached postoperative biochemical disease-free status or had a likely other site of disease recurrence. CONCLUSIONS: PSMA PET/CT can cause considerable changes in N and M staging, as well as in management compared to conventional staging. Findings of this study support the replacement of BS and CT by PSMA PET/CT in staging primary PCa