Organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events in patients with high-risk melanoma treated with adjuvant immune checkpoint inhibitor.

PURPOSE: This study aimed to determine the organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events (irAEs) in patients with high-risk (stage III/IV) surgically resected melanoma treated with an adjuvant immune checkpoint inhibitor (ICI) and determine the incidence of irAEs within the first year after starting treatment. MATERIALS AND METHODS: This registry-based study included individuals who had undergone surgical removal of melanoma and were undergoing adjuvant ICI treatment (either nivolumab or pembrolizumab). The study specifically enrolled patients who had undergone both a baseline and at least one subsequent follow-up [18F]FDG-PET/CT scan. Follow-up scans were performed every third month in the first year after surgery to screen for disease recurrence. We retrospectively compared the follow-up scans with baseline scans to identify irAEs. Clinical information on irAEs was obtained from medical records and served as a reference standard for determining the accuracy of [18F]FDG-PET/CT. RESULTS: A total of 123 patients with 363 [18F]FDG-PET/CT scans were included, and 65 patients (52.8%) developed irAEs. In decreasing order, the organ-specific incidences of irAEs were: skin 26/65 (40%), muscle and joints 21/65 (32.3%), intestines 13/65 (20%), thyroid gland 12/65 (18.5%), lungs 4/65 (6.2%), and heart 2/65 (3.1%). The sensitivities and specificities of [18F]FDG-PET/CT for diagnosing irAEs were: skin 19% (95% CI: 7-39%) and 95% (88-98%), muscles and joints 71% (48-89%) and 83% (75-90%), intestines 100% (75-100%) and 85% (77-91%); thyroid gland 92% (62-99%) and 95% (89-98%), lungs 75% (19-99%) and 90% (83-95%), and heart 50% (13-99%) and 97% (92-99%), respectively. CONCLUSION: [18F]FDG-PET/CT generally had moderate to high sensitivities (except for skin and heart) and specificities in diagnosing irAEs in patients receiving adjuvant ICI; this could be suggested to be systematically assessed and reported in scan reports.

Identifying safe diagnostic algorithms for sentinel lymph node mapping in high-risk endometrial cancer: The SENTIREC-endo study.

INTRODUCTION: It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC. METHODS: We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET-positive lymph nodes. Accuracy analyses were performed for five algorithms. RESULTS: 170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74-100) and an NPV of 96% (95% CI 91-100). The sensitivity increased to 93% (95% CI 83-100) and the NPV to 98% (95% CI 94-100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83-100) and NPV 98% (95% CI 95-100). CONCLUSION: SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.

Gastrin-releasing peptide receptor as a theranostic target in breast cancer: a systematic scoping review.

The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a theranostic framework. Various radioligands targeting GRPR have undergone investigation in preclinical and clinical studies related to breast cancer. This systematic scoping review aimed to assess the current evidence on GRPR-targeted radioligands for diagnostic and therapeutic applications in breast cancer. The methodology followed the PRISMA-ScR protocol. The literature search was conducted in September 2023 and encompassed MEDLINE, Embase, Cochrane, and Scopus databases. We included original peer-reviewed studies focused on breast cancer patients or in vivo breast cancer models. Two reviewers performed the study selection process independently. Data were extracted, synthesized, and categorized into preclinical and clinical studies, further subdivided based on radioligand properties. A total of 35 original studies were included in the review, with three of them evaluating therapeutic outcomes. The results indicated that GRPR-radioantagonists are superior to GRPR-agonists, exhibiting preferable in vivo stability, rapid, specific tumor targeting, and enhanced retention. Both preclinical and clinical evaluations demonstrated renal excretion and high uptake in normal GRPR-expressing tissue, primarily the pancreas. A significant positive correlation was observed between GRPR and estrogen-receptor expression. In the clinical setting, GRPR-radioligands effectively detected primary tumors and, to a lesser extent, lymph node metastases. Moreover, GRPR-targeted radioantagonists successfully identified distant metastases originating from various sites in advanced metastatic disease, strongly correlated with positive estrogen receptor expression. Preclinical therapeutic evaluation of GRPR-radioligands labeled with lutetium-177 showed promising tumor responses, and none of the studies reported any observed or measured side effects, indicating a safe profile. In conclusion, the evidence presented in this review indicates a preference for GRPR-targeted antagonists over agonists, owing to their superior kinetics and promising diagnostic potential. Clinical assessments suggested diagnostic value for GRPR-targeted theranostics in breast cancer patients, particularly those with high estrogen receptor expression. Nevertheless, in the therapeutic clinical context, paying attention to the radiation dose administered to the pancreas and kidneys is crucial.

Preclinical evaluation of [58mCo]Co-DOTA-PSMA-617 for Auger electron therapy of prostate cancer.

Prostate-specific membrane antigen (PSMA), highly expressed in prostate cancer, is a promising target for radionuclide therapy. Auger electron-emitting radionuclides are well suited for targeted radionuclide therapy if they can be delivered close to the DNA of the targeted cells. This preclinical study evaluated the theranostic pair [55/58mCo]Co-DOTA-PSMA-617 for PET imaging and Auger electron therapy of prostate cancer. [58mCo]Co-DOTA-PSMA-617 was successfully prepared with > 99% radiochemical yield and purity. In vitro, uptake and subcellular distribution assays in PSMA-positive prostate cancer cells showed PSMA-specific uptake with high cell-associated activity in the nucleus. Incubation with [58mCo]Co-DOTA-PSMA-617 reduced cell viability and clonogenic survival in a significant dose-dependent manner (p < 0.05). Biodistribution of xenografted mice showed high specific tumor uptake of the cobalt-labeled PSMA ligand for all time points with rapid clearance from normal tissues, which PET imaging confirmed. In vivo, therapy with [58mCo]Co-DOTA-PSMA-617 in tumor-bearing mice demonstrated significantly increased median survival for treated mice compared to control animals (p = 0.0014). In conclusion, [55/58mCo]Co-DOTA-PSMA-617 displayed excellent in vitro and in vivo properties, offering significant survival benefits in mice with no observed toxicities.

The Pattern of Metastatic Breast Cancer: A Prospective Head-to-Head Comparison of [18F]FDG-PET/CT and CE-CT.

The study aimed to compare the metastatic pattern of breast cancer and the intermodality proportion of agreement between [18F]FDG-PET/CT and CE-CT. Women with metastatic breast cancer (MBC) were enrolled prospectively and underwent a combined [18F]FDG-PET/CT and CE-CT scan to diagnose MBC. Experienced nuclear medicine and radiology physicians evaluated the scans blinded to the opposite scan results. Descriptive statistics were applied, and the intermodality proportion of agreement was used to compare [18F]FDG-PET/CT and CE-CT. In total, 76 women with verified MBC were enrolled in the study. The reported number of site-specific metastases for [18F]FDG-PET/CT vs. CE-CT was 53 (69.7%) vs. 44 (57.9%) for bone lesions, 31 (40.8%) vs. 43 (56.6%) for lung lesions, and 16 (21.1%) vs. 23 (30.3%) for liver lesions, respectively. The proportion of agreement between imaging modalities was 76.3% (95% CI 65.2-85.3) for bone lesions; 82.9% (95% CI 72.5-90.6) for liver lesions; 57.9% (95% CI 46.0-69.1) for lung lesions; and 59.2% (95% CI 47.3-70.4) for lymph nodes. In conclusion, bone and distant lymph node metastases were reported more often by [18F]FDG-PET/CT than CE-CT, while liver and lung metastases were reported more often by CE-CT than [18F]FDG-PET/CT. Agreement between scans was highest for bone and liver lesions and lowest for lymph node metastases.

2-[18F]FDG-PET/CT in Cancer of Unknown Primary Tumor-A Retrospective Register-Based Cohort Study.

We investigated the impact of 2-[18F]FDG-PET/CT on detection rate (DR) of the primary tumor and survival in patients with suspected cancer of unknown primary tumor (CUP), comparing it to the conventional diagnostic imaging method, CT. Patients who received a tentative CUP diagnosis at Odense University Hospital from 2014-2017 were included. Patients receiving a 2-[18F]FDG-PET/CT were assigned to the 2-[18F]FDG-PET/CT group and patients receiving a CT only to the CT group. DR was calculated as the proportion of true positive findings of 2-[18F]FDG-PET/CT and CT scans, separately, using biopsy of the primary tumor, autopsy, or clinical decision as reference standard. Survival analyses included Kaplan-Meier estimates and Cox proportional hazards regression adjusted for age, sex, treatment, and propensity score. We included 193 patients. Of these, 159 were in the 2-[18F]FDG-PET/CT group and 34 were in the CT group. DR was 36.5% in the 2-[18F]FDG-PET/CT group and 17.6% in the CT group, respectively (p = 0.012). Median survival was 7.4 (95% CI 0.4-98.7) months in the 2-[18F]FDG-PET/CT group and 3.8 (95% CI 0.2-98.1) in the CT group. Survival analysis showed a crude hazard ratio of 0.63 (p = 0.024) and an adjusted hazard ratio of 0.68 (p = 0.087) for the 2-[18F]FDG-PET/CT group compared with CT. This study found a significantly higher DR of the primary tumor in suspected CUP patients using 2-[18F]FDG-PET/CT compared with patients receiving only CT, with possible immense clinical importance. No significant difference in survival was found, although a possible tendency towards longer survival in the 2-[18F]FDG-PET/CT group was observed.

Cost-effectiveness of 2-[18F]FDG-PET/CT versus CE-CT for response monitoring in patients with metastatic breast cancer: a register-based comparative study.

We evaluated the cost-effectiveness of 2-[18F]FDG-PET/CT compared to CE-CT for response monitoring in metastatic breast cancer (MBC) patients. The study included 300 biopsy-verified MBC patients treated at Odense University Hospital (Denmark). CE-CT was used in 144 patients, 83 patients underwent 2-[18F]FDG-PET/CT, and 73 patients received a combination of both. Hospital resource-based costs (2007-2019) were adjusted to the 2019 level. The incremental cost-effectiveness ratio (ICER) was calculated by comparing average costs per patient and gained survival with CE-CT. During a median follow-up of 33.0 months, patients in the 2-[18F]FDG-PET/CT group had more short admissions (median 6 vs. 2) and fewer overnight admissions (5 vs. 12) compared to the CE-CT group. The mean total cost per patient was €91,547 for CE-CT, €83,965 for 2-[18F]FDG-PET/CT, and €165,784 for the combined group. The ICER for 2-[18F]FDG-PET/CT compared to CE-CT was €-527/month, indicating gaining an extra month of survival at a lower cost (€527). 2-[18F]FDG-PET/CT was more cost-effective in patients with favorable prognostic factors (oligometastatic or estrogen receptor-positive disease), while CE-CT was more cost-effective in poor prognosis patients (liver/lung metastases or performance status ≥ 2 at baseline). In conclusion, our study suggests that 2-[18F]FDG-PET/CT is a cost-effective modality for response monitoring in metastatic breast cancer.

A randomised trial of [18F]PSMA-1007-PET/CT versus NaF-PET/CT for staging primary prostate cancer: A trial protocol.

Background: Prostate-specific membrane antigen (PSMA)-positron emission tomography/contrast-enhanced computed tomography (PET/CT) is a sensitive imaging modality for prostate cancer (PCa). Due to lack of knowledge of the patient benefit, PSMA-PET/CT is not yet recommended in the European guidelines for staging and treatment planning of patients with newly diagnosed PCa. We will investigate the potential difference in progression-free survival (PFS) and quality of life (QoL) of using PSMA-PET/CT versus sodium fluoride (NaF)-PET/CT for staging and treatment planning in patients with newly diagnosed PCa. Study Design: This is a prospective randomised controlled multicentre trial carried out at three centres in the Region of Southern Denmark. Endpoints: The primary endpoint is PFS. Secondary endpoints are residual disease, stage migration, impact on treatment strategies, stage distribution, QoL and diagnostic accuracy measures. Patients and Methods: Patients eligible for the study have newly diagnosed unfavourable intermediate- or high-risk PCa. A total of 448 patients will be randomised 1:1 into two groups: (A) a control group staged with Na[18F]F-PET/CT and (B) an intervention group staged with [18F]PSMA-1007-PET/CT. A subgroup in the intervention group will have a supplementary blinded Na[18F]F-PET/CT performed for the purpose of performing accuracy analyses. QoL will be assessed at baseline and with regular intervals (3-12 months) during the study period. Treatment decisions are achieved at multidisciplinary team conferences based on the results of the respective scans and according to current Danish guidelines. Trial Registration: The Regional Committees on Health Research Ethics for Southern Denmark (S-20190161) and the Danish Medicines Agency (EudraCT Number 2021-000123-12) approved the study, and it has been registered on clinicaltrials.gov (Record 2020110469).

2-[18F]FDG-PET/CT is a better predictor of survival than conventional CT: a prospective study of response monitoring in metastatic breast cancer.

This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities. TRIAL REGISTRATION: Clinical. TRIALS: gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www. CLINICALTRIALS: gov.

Comparison of Image Quality and Quantification Parameters between Q.Clear and OSEM Reconstruction Methods on FDG-PET/CT Images in Patients with Metastatic Breast Cancer.

We compared the image quality and quantification parameters through bayesian penalized likelihood reconstruction algorithm (Q.Clear) and ordered subset expectation maximization (OSEM) algorithm for 2-[18F]FDG-PET/CT scans performed for response monitoring in patients with metastatic breast cancer in prospective setting. We included 37 metastatic breast cancer patients diagnosed and monitored with 2-[18F]FDG-PET/CT at Odense University Hospital (Denmark). A total of 100 scans were analyzed blinded toward Q.Clear and OSEM reconstruction algorithms regarding image quality parameters (noise, sharpness, contrast, diagnostic confidence, artefacts, and blotchy appearance) using a five-point scale. The hottest lesion was selected in scans with measurable disease, considering the same volume of interest in both reconstruction methods. SULpeak (g/mL) and SUVmax (g/mL) were compared for the same hottest lesion. There was no significant difference regarding noise, diagnostic confidence, and artefacts within reconstruction methods; Q.Clear had significantly better sharpness (p < 0.001) and contrast (p = 0.001) than the OSEM reconstruction, while the OSEM reconstruction had significantly less blotchy appearance compared with Q.Clear reconstruction (p < 0.001). Quantitative analysis on 75/100 scans indicated that Q.Clear reconstruction had significantly higher SULpeak (5.33 ± 2.8 vs. 4.85 ± 2.5, p < 0.001) and SUVmax (8.27 ± 4.8 vs. 6.90 ± 3.8, p < 0.001) compared with OSEM reconstruction. In conclusion, Q.Clear reconstruction revealed better sharpness, better contrast, higher SUVmax, and higher SULpeak, while OSEM reconstruction had less blotchy appearance.

Value assessment of artificial intelligence in medical imaging: a scoping review.

BACKGROUND: Artificial intelligence (AI) is seen as one of the major disrupting forces in the future healthcare system. However, the assessment of the value of these new technologies is still unclear, and no agreed international health technology assessment-based guideline exists. This study provides an overview of the available literature in the value assessment of AI in the field of medical imaging. METHODS: We performed a systematic scoping review of published studies between January 2016 and September 2020 using 10 databases (Medline, Scopus, ProQuest, Google Scholar, and six related databases of grey literature). Information about the context (country, clinical area, and type of study) and mentioned domains with specific outcomes and items were extracted. An existing domain classification, from a European assessment framework, was used as a point of departure, and extracted data were grouped into domains and content analysis of data was performed covering predetermined themes. RESULTS: Seventy-nine studies were included out of 5890 identified articles. An additional seven studies were identified by searching reference lists, and the analysis was performed on 86 included studies. Eleven domains were identified: (1) health problem and current use of technology, (2) technology aspects, (3) safety assessment, (4) clinical effectiveness, (5) economics, (6) ethical analysis, (7) organisational aspects, (8) patients and social aspects, (9) legal aspects, (10) development of AI algorithm, performance metrics and validation, and (11) other aspects. The frequency of mentioning a domain varied from 20 to 78% within the included papers. Only 15/86 studies were actual assessments of AI technologies. The majority of data were statements from reviews or papers voicing future needs or challenges of AI research, i.e. not actual outcomes of evaluations. CONCLUSIONS: This review regarding value assessment of AI in medical imaging yielded 86 studies including 11 identified domains. The domain classification based on European assessment framework proved useful and current analysis added one new domain. Included studies had a broad range of essential domains about addressing AI technologies highlighting the importance of domains related to legal and ethical aspects.

Extramedullary Hematopoiesis Visualized on FDG-PET/CT in a Patient with Beta-Thalassemia.

Beta-thalassemia is an inherited blood disorder caused by reduced or absent synthesis of the beta chains of hemoglobin, resulting in decreased hemoglobin production. Symptoms depend on the type of beta-thalassemia ranging from no symptoms to severe illness. Ineffective erythropoiesis leads to a sequence of events responsible for bone marrow expansion, anemia, hemolysis, splenomegaly, increased iron absorption, and sometimes extramedullary hematopoiesis (EMH). We report an interesting case with EMH visualized on FDG-PET/CT and where FDG-PET/CT has also found the focus of a severe infection in a patient with beta-thalassemia.

Improved stratification of stage-specific survival for cervical uterine cancer by integrating FDG-PET/CT and MRI for lymph node staging in 2018 FIGO classification.

OBJECTIVE: Staging carcinoma of the uterine cervix (CCU) by FIGO-2018 suggests stage migration of FIGO-2009 stage I-III patients with lymph node metastasis into FIGO-2018 stage IIIC. We aimed to investigate the prognostic value of lymph node metastases identified by imaging. METHODS: We enrolled all patients with biopsy-verified CCU from 2007 to 2016 at Odense University Hospital, Denmark. FDG-PET/CT and MRI were performed before clinical examination in general anesthesia. Disease-specific mortality was compared between women with lymph node-positive and lymph node-negative imaging. RESULTS: In total, 488 patients underwent clinical staging according to FIGO-2009. Lymph node-positive imaging was identified in 146 (30%) patients: 0/36 (0%) in stage IA, 22/195 (11%) in IBI, 14/30 (47%) in IB2, 70/164 (43%) in II and 40/63 (63%) in III. The 5-year cumulative incidence of death due to CCU lymph node-negative vs. lymph node-positive patients was 0.8% vs. 7.1% (p = 0.034) in stage IBI, 0% vs. 34.5% (p = 0.003) in stage IB2, 15.1% vs. 41.4% (p < 0.0001) in stage II, and 33.3% vs. 46.6% (p = 0.28) in stage III by FIGO-2009. CONCLUSIONS: One of three women with FIGO-2009 stage I-III CCU had suspected lymph node metastasis on imaging and is upstaged to stage IIIC according to FIGO-2018. The cancer-specific mortality by CCU was significantly lower in the lymph node-negative women stages IBI-II, thus supporting stage migration due to suspected lymph node metastasis. However, the exact prognostic value within stage IIIC is challenged, and future revision of FIGO stages may include new sub-stages.

A role of FDG-PET/CT for response evaluation in metastatic breast cancer?

Breast cancer prognosis is steadily improving due to early detection of primary cancer in screening programs and revolutionizing treatment development. In the metastatic setting, therapy improvements render breast cancer a chronic disease. Although FDG-PET/CT has emerged as a highly accurate method for staging metastatic breast cancer, there has been no change in response evaluation methods for decades. FDG-PET/CT has proven high prognostic values in patients with metastatic breast cancer when using quantitative PET methods. It has also shown a higher predictive value than conventional CT when applying the respective response evaluation criteria, RECIST and PERCIST. Response categorization using FDG-PET/CT is more sensitive in detecting progressive and regressive disease, while conventional imaging such as CT and bone scintigraphy deem stable disease more often. These findings reflect the higher accuracy of FDG-PET/CT for response evaluation in this patient group. But does the higher accuracy of FDG-PET/CT translate into a patient benefit when implementing it for monitoring response to palliative treatment? We have evidence of survival benefit from a retrospective study indicating the superiority of using FDG-PET/CT compared with conventional imaging for response evaluation in metastatic breast cancer patients. The survival benefit seems to result from earlier detection of progression with FDG-PET/CT than conventional imaging, leading to an earlier change in treatment with potentially better efficacy of the subsequent treatment line. FDG-PET/CT can be used semiquantitatively as suggested in PERCIST. However, we still need to improve clinically applicable methods based on neural network modeling to better integrate the quantitative information in a smart and standardized way, enabling relevant comparability between scans, patients, and institutions. Such innovation is warranted to support imaging specialists in diagnostic response assessment. Prospective multicenter studies analyzing patients' survival, quality of life, societal and patient costs of replacing conventional imaging with FDG-PET/CT are needed before firm conclusions can be drawn on which type of scan to recommend in future clinical guidelines.

Response monitoring in metastatic breast cancer: a comparison of survival times between FDG-PET/CT and CE-CT.

BACKGROUND: We compared overall survival for metastatic breast cancer (MBC) patients monitored with CE-CT, FDG-PET/CT or a combination of them in an observational setting. METHODS: Patients with biopsy-verified (recurrent or de novo) MBC (n = 300) who were treated at Odense university hospital (Denmark) and response monitored with FDG-PET/CT (n = 83), CE-CT (n = 144), or a combination of these (n = 73) were followed until 2019. Survival was compared between the scan groups, and were adjusted for clinico-histopathological variables representing potential confounders in a Cox proportional-hazard regression model. RESULTS: The study groups were mostly comparable regarding baseline characteristics, but liver metastases were reported more frequently in CE-CT group (38.9%) than in FDG-PET/CT group (19.3%) and combined group (24.7%). Median survival was 30.0 months for CE-CT group, 44.3 months for FDG-PET/CT group and 54.0 months for Combined group. Five-year survival rates were significantly higher for FDG-PET/CT group (41.9%) and combined group (43.3%), than for CE-CT group (15.8%). Using the CE-CT group as reference, the hazard ratio was 0.44 (95% CI: 0.29-0.68, P = 0.001) for the FDG-PET/CT group after adjusting for baseline characteristics. FDG-PET/CT detected the first progression 4.7 months earlier than CE-CT, leading to earlier treatment change. CONCLUSIONS: In this single-center, observational study, patients with metastatic breast cancer who were response monitored with FDG-PET/CT alone or in combination with CE-CT had longer overall survival than patients monitored with CE-CT alone. Confirmation of these findings by further, preferably randomised clinical trials is warranted.

SENTIREC - The sentinel node mapping in women with cervical cancer study - Patient-reported early lymphedema and its impact on quality of life.

OBJECTIVE: To evaluate patient-reported incidence and severity of early lymphedema and its impact on quality of life (QoL) after sentinel lymph node (SLN) mapping only and after SLN and pelvic lymphadenectomy (PL) in women undergoing surgery for early-stage cervical cancer. METHODS: In a national prospective multicenter study, we included women with early-stage cervical cancer from March 2017-January 2021 to undergo radical surgery including SLN mapping. Women with tumors >20 mm underwent completion PL. The incidence and severity of early lymphedema and its influence on QoL were evaluated using validated patient-reported outcome measures before surgery and three months postoperative. We investigated changes over time using linear regression. RESULTS: Two hundred of 245 (81.6%) included women completed questionnaires at baseline and three months postoperatively. The incidence of early lymphedema was 5.6% (95% CI 2.1-11.8%) and 32.3% (95% CI 22.9-42.7%) in women who underwent SLN mapping only and SLN + PL, respectively. Lymphedema symptoms in the legs, genitals, and groins increased in both groups postoperatively but three times more in women who underwent PL. Lymphedema symptoms after SLN + PL significantly impaired physical performance (p = 0.001) and appearance (p = 0.007). Reporting lymphedema was significantly associated with impaired body image, physical-, role-, and social functioning, and a high level of fatigue. CONCLUSIONS: SLN mapping alone carries a low risk of lymphedema in women undergoing surgery for early-stage cervical cancer. In contrast, completion PL is associated with a high incidence of early lymphedema. Reporting lymphedema is associated with significant impairment of several physical, psychological, and social aspects of QoL.

How to increase value and reduce waste in research: initial experiences of applying Lean thinking and visual management in research leadership.

Waste in research has been well documented, but initiatives to reduce it are scarce. Here, we share our initial experiences of implementing Lean thinking and visual management into hospital research units in the Region of Southern Denmark. A Transformation Guiding Team (TGT) anchored in the top management was established with participation from leaders, researchers and patient representatives. The role of the TGT was to implement Lean methods, considering patients as primary end-users of the research results. This is in line with an explicit decision on setting patient values first in clinical settings at participating hospitals. The leaders of the research units were instructed in Lean thinking and Lean methods during a five-module course focusing on increasing value and reducing waste in research production. Initial experiences were that Lean tools could create a patient-centred vision that through visual management could identify waste in work processes. Concerns were lack of evidence for using Lean methods in research leadership and that the model itself could be a time consumer. Some lessons learnt were that adding Lean tools in research leadership should not just provide increased research productivity, but also improve other important key performance indicators such as quality of research and patient-relevant results. We intend to evaluate the value of the initiative by follow-up research and publish the outcome of key behavioural and key performance indicators.

Diagnosis of bone metastases in breast cancer: Lesion-based sensitivity of dual-time-point FDG-PET/CT compared to low-dose CT and bone scintigraphy.

We compared lesion-based sensitivity of dual-time-point FDG-PET/CT, bone scintigraphy (BS), and low-dose CT (LDCT) for detection of various types of bone metastases in patients with metastatic breast cancer. Prospectively, we included 18 patients with recurrent breast cancer who underwent dual-time-point FDG-PET/CT with LDCT and BS within a median time interval of three days. A total of 488 bone lesions were detected on any of the modalities and were categorized by the LDCT into osteolytic, osteosclerotic, mixed morphologic, and CT-negative lesions. Lesion-based sensitivity was 98.2% (95.4-99.3) and 98.8% (96.8-99.5) for early and delayed FDG-PET/CT, respectively, compared with 79.9% (51.1-93.8) for LDCT, 76.0% (36.3-94.6) for BS, and 98.6% (95.4-99.6) for the combined BS+LDCT. BS detected only 51.2% of osteolytic lesions which was significantly lower than other metastatic types. SUVs were significantly higher for all lesion types on delayed scans than on early scans (P<0.0001). Osteolytic and mixed-type lesions had higher SUVs than osteosclerotic and CT-negative metastases at both time-points. FDG-PET/CT had significantly higher lesion-based sensitivity than LDCT and BS, while a combination of the two yielded sensitivity comparable to that of FDG-PET/CT. Therefore, FDG-PET/CT could be considered as a sensitive one-stop-shop in case of clinical suspicion of bone metastases in breast cancer patients.

Benefits and harms of implementing [18F]FDG-PET/CT for diagnosing recurrent breast cancer: a prospective clinical study.

BACKGROUND: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. METHODS: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. RESULTS: [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively. CONCLUSION: [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017-Retrospectively registered, http://www.ClinicalTrials.gov.