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Silins, I., Sundin, A., Lubberink, M., O'Sullivan, L., Gurnell, M., Aigbirhio, F., . . . Antoni, G. (2023). First-in-human evaluation of [18F]CETO: a novel tracer for adrenocortical tumours. European Journal of Nuclear Medicine and Molecular Imaging, 50(2), 398-409
Open this publication in new window or tab >>First-in-human evaluation of [18F]CETO: a novel tracer for adrenocortical tumours
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2023 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 50, no 2, p. 398-409Article in journal (Refereed) Published
Abstract [en]

Purpose

[11C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [11C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[18F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[18F]fluoroethyletomidate positron emission computed tomography ([18F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers.

Methods

Fifteen patients underwent [18F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [15O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [18F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis.

Results

Uptake of [18F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [18F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K1. Both K1 and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K1, SUV65–70, and SUV120 were 25, 22, and 17%.

Conclusions

High adrenal uptake combined with a low unspecific liver uptake suggests that 18F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate Ki.

Trial registration

ClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
[18F]CETO, Adrenal tracer, Positron emission tomography
National Category
Surgery Radiology, Nuclear Medicine and Medical Imaging
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-487613 (URN)10.1007/s00259-022-05957-9 (DOI)000851349100002 ()36074157 (PubMedID)
Funder
Uppsala University
Available from: 2022-10-30 Created: 2022-10-30 Last updated: 2023-01-10Bibliographically approved
Jahn, U., Garske-Román, U., Sandström, M., Lubberink, M. & Sundin, A. (2023). Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression. EJNMMI Research, 13(1), 45
Open this publication in new window or tab >>Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression
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2023 (English)In: EJNMMI Research, E-ISSN 2191-219X, Vol. 13, no 1, p. 45-Article in journal (Refereed) Published
Abstract [en]

Background

The accumulation of 177Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients’ tumor load.

Method

Patients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation. All patients had received 7.4 GBq 177Lu-DOTATATE, and the amount of administered peptide in the preparation varied from 93 to 456 µg. The absorbed dose in tumors and normal tissue at the first PRRT cycle was calculated, based on SPECT-measurements at day 1, 4, and 7 post-infusion. The total tumor somatostatin receptor expression (tTSSTRE) was calculated on SPECT after 24 h by multiplying the functional tumor volume, delineated by 42% cut-off VOIs of the highest activity, with the SUVmean for the respective tumor VOIs. Spearman’s rank correlation analyzed any relationship between the administered amount of peptide and the absorbed dose in tumors and normal organs, in relation to the patients’ tTSSTRE.

Results

There was no correlation between the amount of peptide and any of the tested parameters in relation to tTSSTRE.

Conclusion

In this retrospective analysis, no correlation between the amount of administered peptide in the 177Lu-DOTATATE preparation and the absorbed radiation doses in tumors and normal tissues was demonstrated in relation to the total tumor SSTR expression.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Peptide, SUV, Small intestinal, Pancreatic, NET, Somatostatin receptor, PRRT
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-492865 (URN)10.1186/s13550-023-00997-0 (DOI)000990999800001 ()37204528 (PubMedID)
Funder
Uppsala University
Note

Authors in the list of papers of Ulrika Jahn's thesis: Jahn, U., Ilan, E., Garske-Román, U., Sandström, M., Lubberink, M., Sundin, A.

Available from: 2023-01-17 Created: 2023-01-17 Last updated: 2023-06-19Bibliographically approved
Dam, G., Grønbæk, H., Sundlöv, A., Botling, J., Sundin, A., Petersen, R. H., . . . Langer, S. W. (2023). Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms.. Acta Oncologica, 62(5), 431-437
Open this publication in new window or tab >>Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms.
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2023 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 62, no 5, p. 431-437Article in journal (Refereed) Published
Abstract [en]

Lung neuroendocrine neoplasms (NEN) are a heterogeneous population of neoplasms with different pathology, clinical behavior, and prognosis compared to the more common lung cancers. The diagnostic work-up and treatment of patients with lung- NEN has undergone major recent advances and new methods are currently being introduced into the clinic. These Nordic guidelines summarize and update the Nordic Neuroendocrine Tumor Group's current view on how to diagnose and treat lung NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. This review reflects our view of the current state of the art of diagnosis and treatment of patients with lung-NEN. Small cell lung carcinoma (SCLC) is not included in these guidelines.

Place, publisher, year, edition, pages
Informa UK Limited, 2023
Keywords
Lung, bronchopulmonary neoplasm, diagnosis, neuroendocrine carcinoma, neuroendocrine neoplasm, treatment
National Category
Cancer and Oncology Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-505319 (URN)10.1080/0284186X.2023.2212411 (DOI)000990174700001 ()37194281 (PubMedID)
Available from: 2023-06-19 Created: 2023-06-19 Last updated: 2023-10-13Bibliographically approved
Dogra, P., Sundin, A., Juhlin, C. C., Calissendorff, J., Falhammar, H. & Bancos, I. (2023). Rare benign adrenal lesions. European Journal of Endocrinology, 188(4), 407-420
Open this publication in new window or tab >>Rare benign adrenal lesions
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2023 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 188, no 4, p. 407-420Article in journal (Refereed) Published
Abstract [en]

While most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
adrenal cyst, calcification, ganglioneuroma, hemorrhage, schwannoma
National Category
Radiology, Nuclear Medicine and Medical Imaging Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-505317 (URN)10.1093/ejendo/lvad036 (DOI)001032683000001 ()36943310 (PubMedID)
Funder
Magnus Bergvall Foundation, 2021-04226NIH (National Institutes of Health), K23DK121888NIH (National Institutes of Health), R03DK132121NIH (National Institutes of Health), R03AG71934
Available from: 2023-06-19 Created: 2023-06-19 Last updated: 2023-08-15Bibliographically approved
Sundin, A. (2022). Commentary on Adrenal wash-out CT: moderate diagnostic value in distinguishing benign from malignant masses. European Journal of Endocrinology, 186(6), C9-C12
Open this publication in new window or tab >>Commentary on Adrenal wash-out CT: moderate diagnostic value in distinguishing benign from malignant masses
2022 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 186, no 6, p. C9-C12Article in journal (Refereed) Published
Abstract [en]

The increasing use of cross-sectional imaging, mainly CT, results in an accelerating number of incidental findings, for instance of adrenal tumours. Although most 'adrenal incidentalomas' are benign, it is important to identify the malignant and the hormone producing (functional) tumours. For a small fraction of adrenal incidentalomas, the diagnosis is apparent on imaging, but the large majority requires radiological characterisation. To this end, a previous joint European Society of Endocrinology and European Network for the Study of Adrenal Tumours publication in this jounal, recommends CT measurements of the native (non-contrast) tumour attenuation <= 10 Hounsfield units, consistent with a lipid-rich benign adrenocortical adenoma, and imaging at least 6 months apart, on which unchanged tumour size implies a benign tumour. Because of weak evidence, calculation of CT contrast medium washout was not recommended as a means for tumour characterisation, but this technique has nevertheless still been applied in several countries. The recent article by Schloetelburg et al. in this journal is important because, in the largest study to date, the authors confirm that calculation of CT contrast medium washout with established thresholds is insufficient to reliably characterise adrenal tumours. Their results are therefore expected to impact the management of these patients.

Place, publisher, year, edition, pages
Bioscientifica, 2022
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-482661 (URN)10.1530/EJE-21-1177 (DOI)000836569100002 ()35380985 (PubMedID)
Available from: 2022-09-22 Created: 2022-09-22 Last updated: 2022-10-31Bibliographically approved
Hicks, R. J., Dromain, C., de Herder, W. W., Costa, F. P., Deroose, C. M., Frilling, A., . . . Prasad, V. (2022). ENETS standardized (synoptic) reporting for molecular imaging studies in neuroendocrine tumours. Journal of neuroendocrinology, 34(3), Article ID e13040.
Open this publication in new window or tab >>ENETS standardized (synoptic) reporting for molecular imaging studies in neuroendocrine tumours
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2022 (English)In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 34, no 3, article id e13040Article in journal (Refereed) Published
Abstract [en]

The European Neuroendocrine Tumor Society (ENETS) promotes practices and procedures that aim to improve the standard of care delivered to patients diagnosed with or suspected of having neuroendocrine neoplasia (NEN). At its annual Scientific Advisory Board Meeting in 2018, experts in imaging, pathology and clinical care of patients with NEN drafted guidance for the standardised reporting of diagnostic studies critical to the diagnosis, grading, staging and treatment of NEN. These included pathology, radiology, endoscopy and molecular imaging procedures. In an iterative process, a synoptic reporting template for molecular imaging procedures was developed to guide personalised therapies. Following pilot implementation and refinement within the ENETS Center of Excellence network, harmonisation with specialist imaging societies including the Society of Nuclear Medicine, European Association of Nuclear Medicine and the International Cancer Imaging Society will be pursued.

Place, publisher, year, edition, pages
John Wiley & SonsWiley, 2022
Keywords
neuroendocrine neoplasia, PET, synoptic reporting
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-478336 (URN)10.1111/jne.13040 (DOI)000708852500001 ()34668262 (PubMedID)
Available from: 2022-06-23 Created: 2022-06-23 Last updated: 2024-01-15Bibliographically approved
Dromain, C., Vullierme, M.-P., Hicks, R. J., Prasad, V., O'Toole, D., de Herder, W. W., . . . Sundin, A. (2022). ENETS standardized (synoptic) reporting for radiological imaging in neuroendocrine tumours. Journal of neuroendocrinology, 34(3 SI), Article ID 13044.
Open this publication in new window or tab >>ENETS standardized (synoptic) reporting for radiological imaging in neuroendocrine tumours
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2022 (English)In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 34, no 3 SI, article id 13044Article in journal (Refereed) Published
Abstract [en]

This expert consensus document represents an initiative by the European Neuroendocrine Tumor Society (ENETS) to provide guidance for synoptic reporting of radiological examinations critical to the diagnosis, grading, staging and treatment of neuroendocrine neoplasms (NENs). Template drafts for initial tumor staging and follow-up by computed tomography (CT) and magnetic resonance imaging (MRI) were established, based on existing institutional and organisational reporting templates relevant for NEN imaging, and applying the RadLex lexicon of radiological information (Radiological Society of North America), for consistency regarding the radiological terms. During the ENETS Scientific Advisory Board meeting 2018, the template drafts were subject to iterative interdisciplinary discussions among experts in imaging, surgery, gastroenterology, oncology and pathology. Members of the imaging group stated a strong preference for a combination of limited and standardised options by way of drop-down menus. Separate templates were produced for the initial work-up and for follow-up, respectively. To provide a detailed description of the radiological findings of the primary tumor and its local extension and spread, different templates were developed for bronchial, pancreatic and gastrointestinal NENs for CT and MRI, respectively. Each template was structured in 10 sections: clinical details, comparative imaging modality, acquisition technique, primary tumor findings, regional lymph node metastases, distant metastases, TNM classification, reference lesions according to RECIST 1.1, additional findings and conclusion. Two templates were developed for follow-up, for CT and MRI, respectively, and were specifically focused on assessment of therapy response. These included a qualitative response assessment, such as decrease of vascularisation and presence of necrosis, and a quantitative assessment according to RECIST 1.1 and the modified RECIST (mRECIST) for assessing tumor response following transarterial chemoembolisation.

Place, publisher, year, edition, pages
John Wiley & SonsWiley, 2022
Keywords
CT, MRI, neuroendocrine neoplasia, synoptic reporting
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-478305 (URN)10.1111/jne.13044 (DOI)000710436700001 ()34693574 (PubMedID)
Available from: 2022-09-19 Created: 2022-09-19 Last updated: 2024-01-15Bibliographically approved
Mollazadegan, K., Skogseid, B., Botling, J., Åkerström, T., Eriksson, B., Welin, S., . . . Crona, J. (2022). Poor outcome after systemic therapy in secondary high-grade pancreatic neuroendocrine tumors. Endocrine Connections, 11(3), Article ID e210604.
Open this publication in new window or tab >>Poor outcome after systemic therapy in secondary high-grade pancreatic neuroendocrine tumors
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2022 (English)In: Endocrine Connections, E-ISSN 2049-3614, Vol. 11, no 3, article id e210604Article in journal (Refereed) Published
Abstract [en]

Longitudinal changes in pancreatic neuroendocrine tumor (panNET) cell proliferation correlate with fast disease progression and poor prognosis. The optimal treatment strategy for secondary panNET grade (G)3 that has progressed from a previous low- or intermediate-grade to high-grade panNET G3 is currently unknown. This was a single-center retrospective cohort study aimed to characterize treatment patterns and outcomes among patients with secondary panNET-G3. Radiological responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A total of 22 patients were included and received a median of 2 (range, 1–4) treatment lines in 14 different combinations. Median overall survival (OS) was 9 months (interquartile range (IQR): 4.25–17.5). For the 15 patients who received platinum–etoposide chemotherapy, median OS was 7.5 months (IQR: 3.75–10) and median progression-free survival (PFS) was 4 months (IQR: 2.5–5.5). The 15 patients who received conventional panNET therapies achieved a median OS of 8 months (IQR: 5–16.75) and median PFS was 5.5 months (IQR: 2.75–8.25). We observed one partial response on 177Lu DOTA-TATE therapy. In conclusion, this hypothesis-generating study failed to identify any promising treatment alternatives for patients with secondary panNET-G3. This demonstrates the need for both improved biological understanding of this particular NET entity and for designing prospective studies to further assess its treatment in larger patient cohorts.

Place, publisher, year, edition, pages
BioscientificaBioscientifica, 2022
Keywords
pancreatic neuroendocrine tumor, highgrade, systemic therapy, treatment outcomes
National Category
Surgery Endocrinology and Diabetes Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-475551 (URN)10.1530/EC-21-0604 (DOI)000793356700013 ()35148276 (PubMedID)
Funder
Swedish Cancer SocietyTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseÅke Wiberg Foundation
Available from: 2022-06-10 Created: 2022-06-10 Last updated: 2024-01-15Bibliographically approved
Sandqvist, P., Sundin, A., Nilsson, I.-L., Gryback, P. & Sanchez-Crespo, A. (2022). Primary hyperparathyroidism, a machine learning approach to identify multiglandular disease in patients with a single adenoma found at preoperative Sestamibi-SPECT/CT. European Journal of Endocrinology, 187(2), 257-263
Open this publication in new window or tab >>Primary hyperparathyroidism, a machine learning approach to identify multiglandular disease in patients with a single adenoma found at preoperative Sestamibi-SPECT/CT
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2022 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 187, no 2, p. 257-263Article in journal (Refereed) Published
Abstract [en]

Objective: Successful preoperative image localisation of all parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (pHPT) and multiglandular disease (MGD) remains challenging. We investigate whether a machine learning classifier (MLC) could predict the presence of overlooked PTA at preoperative localisation with Tc-99m-Sestamibi-SPECT/CT in MGD patients.

Design: This study is a retrospective study from a single tertiary referral hospital initially including 349 patients with biochemically confirmed pHPT and cured after surgical parathyroidectomy.

Methods: A classification ensemble of decision trees with Bayesian hyperparameter optimisation and five-fold cross-validation was trained with six predictor variables: the preoperative plasma concentrations of parathyroid hormone, total calcium and thyroid-stimulating hormone, the serum concentration of ionised calcium, the 24-h urine calcium and the histopathological weight of the localised PTA at imaging. Two response classes were defined: patients with single-gland disease (SGD) correctly localised at imaging and MGD patients in whom only one PTA was localised on imaging. The data set was split into 70% for training and 30% for testing. The MLC was also tested on a subset of the original data based on CT image-derived PTA weights.

Results: The MLC achieved an overall accuracy at validation of 90% with an area under the cross-validation receiver operating characteristic curve of 0.9. On test data, the MLC reached a 72% true-positive prediction rate for MGD patients and a misclassification rate of 6% for SGD patients. Similar results were obtained in the testing set with image-derived PTA weight.

Conclusions: Artificial intelligence can aid in identifying patients with MGD for whom Tc-99m-Sestamibi-SPECT/CT failed to visualise all PTAs.

Place, publisher, year, edition, pages
Bioscientifica, 2022
National Category
Radiology, Nuclear Medicine and Medical Imaging Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-487237 (URN)10.1530/EJE-22-0206 (DOI)000862631600008 ()35666799 (PubMedID)
Available from: 2022-11-14 Created: 2022-11-14 Last updated: 2022-11-14Bibliographically approved
Naeser, Y., Helgadottir, H., Hansson, J., Ingvar, C., Elander, N. O., Flygare, P., . . . Ullenhag, G. (2022). Quality of Life in the First Year of Follow-Up in a Randomized Multicenter Trial Assessing the Role of Imaging after Radical Surgery of Stage IIB-C and III Cutaneous Melanoma (TRIM Study). Cancers, 14(4), Article ID 1040.
Open this publication in new window or tab >>Quality of Life in the First Year of Follow-Up in a Randomized Multicenter Trial Assessing the Role of Imaging after Radical Surgery of Stage IIB-C and III Cutaneous Melanoma (TRIM Study)
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2022 (English)In: Cancers, ISSN 2072-6694, Vol. 14, no 4, article id 1040Article in journal (Refereed) Published
Abstract [en]

Simple Summary After surgery of high-risk melanoma, patients are usually followed up by physical examinations. Recommendations regarding imaging vary due to insufficient evidence of the benefit of regular scans. It might also be stressful for patients to undergo imaging. In an ongoing Swedish study, half of the patients are randomized to whole-body imaging in addition to physical examinations. Three imaging procedures are performed during the first year. The main aim of our study was to investigate if imaging during the first year of follow-up affected the patients' well-being. Validated self-reporting questionnaires regarding symptoms of anxiety and depression and quality of life were answered at study start and at 1 year. Questionnaires from 204 recurrence-free patients were analyzed. No differences in either level of anxiety/depression or quality of life were found at 1 year follow-up between the imaging and non-imaging group. These findings can be considered in the formulation of future follow-up programs. The benefit of imaging in the follow-up setting for high-risk melanoma patients is uncertain, and even less is known about the impact of intensive follow-up on the patient ' s quality of life. In 2017, a Swedish prospective randomized multicenter study started, in which high-risk melanoma patients are randomly assigned 1:1 to follow-up by physical examinations +/- whole-body imaging. The first-year examinations are scheduled at 0, 6 and 12 months. The aim of this study was to investigate whether the patients ' health-related quality of life (HRQoL) and levels of anxiety and depression were affected at 1 year by imaging. Anxiety/depression and HRQoL were assessed at 0 and 12 months by the questionnaires Hospital Anxiety and Depression (HAD) scale and EORTC QLQ-C30 version 3. Expected baseline QLQ-C30 values for the patients were calculated using data from the general population. In total, 204 patients were analyzed. Mean differences in subscale scores at 1 year were not statistically significant either for HRQoL or for anxiety/depression. Baseline HRQoL did not differ from expected values in the general Swedish population. In conclusion, the patients in general coped well with the situation, and adding whole-body imaging to physical examinations did not affect the melanoma patients' HRQoL or levels of anxiety or depression.

Place, publisher, year, edition, pages
MDPI AG, 2022
Keywords
melanoma, follow-up studies, positron emission tomography computed tomography, tomography, X-ray computed, quality of life, randomized controlled trial, prospective studies
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-470225 (URN)10.3390/cancers14041040 (DOI)000763756700001 ()35205786 (PubMedID)
Available from: 2022-03-22 Created: 2022-03-22 Last updated: 2024-03-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2214-6217

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