24 mei 2021: Bron: Diagnostics 2021, 11(4), 723

In een Deense retrospectieve studie hebben de onderzoekers de haalbaarheid en het eventuele voordeel van het toepassen van een regelmatige FDG-PET/CT-scan ook wel PERCIST (PET Response Criteria in Solide Tumoren) genoemd, voor monitoring van de effecten van behandelingen bij solide tumoren, ook bij 37 vrouwen met uitgezaaide borstkanker onderzocht. Basis standaard scans en nadirscans (meten van bloedwaarden, zoals witte bloedlichaampjes enz.) werden daarbij als referentie gebruikt.

Uit het onderzoek bij totaal 37 vrouwen bleek bij 94,7% van de patiënten uitgezaaide tumoren meetbaar volgens PERCIST. In 150 vervolgscans werd progressie vaker gerapporteerd met nadir-scans dan bij de standaard scans. Redenen voor progressie waren onder meer de detectie van nieuwe uitzaaiingen (63,6%), > 30% toename van SULpeak van de sterkst reagerende tumor (15,9%), of beide (20,5%).

Wel vraag ik me af of alleen een bloedtest als monitoring niet handiger, minder belastender voor de patiënt en veel goedkoper is. Zie o.a. deze search alleen al op onze site.
Bv deze bij borstkanker: https://kanker-actueel.nl/bloedtest-tardis-targeted-digitial-sequencing-op-in-bloed-circulerende-tumor-dna-meet-en-voorspelt-overgebleven-ziekte-voor-en-na-behandelingen-van-borstkanker.html

En deze: https://kanker-actueel.nl/ctdna-een-bloedtest-op-circulerend-dna-geeft-98-procent-betrouwbaarheid-bij-borstkankerpatienten-en-bewijst-effectiviteit-van-gebruik-in-de-klinische-praktijk-bij-studie-met-350-patienten.html

Een andere nieuwe studie biedt via zogeheten moleculaire profilering van circulerende extracellulaire blaasjes (EV's) een andere manier om de effecten van een behandeling te meten. De meting van 8 verschillende eiwitmarkers biedt 91 procent betrouwbaarheid. zie dit studieabstract: Protein analysis of extracellular vesicles to monitor and predict therapeutic response in metastatic breast cancer

De Deense studie is gratis in te zien. Klik op de titel van het abstract voor het uitgebreide studierapport.

FDG-PET/CT for Response Monitoring in Metastatic Breast Cancer: The Feasibility and Benefits of Applying PERCIST

Marianne Vogsen en collega's

1,2,3,4,5

Department of Nuclear Medicine, Odense University Hospital, DK-5000 Odense, Denmark

Department of Oncology, Odense University Hospital, DK-5000 Odense, Denmark

Department of Clinical Research, University of Southern Denmark, DK-5000 Odense, Denmark

Open Patient Data Explorative Network, Odense University Hospital, DK-5000 Odense, Denmark

Centre for Personalized Response Monitoring in Oncology, Odense University Hospital, DK-5000 Odense, Denmark

Centre for Innovative Medical Technology, Odense University Hospital, DK-5000 Odense, Denmark

Author to whom correspondence should be addressed.

Academic Editor: Hidehiko Okazawa

Diagnostics 2021, 11(4), 723; https://doi.org/10.3390/diagnostics11040723

Received: 15 March 2021 / Revised: 14 April 2021 / Accepted: 16 April 2021 / Published: 19 April 2021

(This article belongs to the Special Issue Advances in Multimodality Molecular Imaging)

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Abstract

Background:
We aimed to examine the feasibility and potential benefit of applying PET Response Criteria in Solid Tumors (PERCIST) for response monitoring in metastatic breast cancer (MBC). Further, we introduced the nadir scan as a reference. Methods: Response monitoring FDG-PET/CT scans in 37 women with MBC were retrospectively screened for PERCIST standardization and measurability criteria. One-lesion PERCIST based on changes in SULpeak measurements of the hottest metastatic lesion was used for response categorization. The baseline (PERCISTbaseline) and the nadir scan (PERCISTnadir) were used as references for PERCIST analyses.

Results: Metastatic lesions were measurable according to PERCIST in 35 of 37 (94.7%) patients. PERCIST was applied in 150 follow-up scans, with progression more frequently reported by PERCISTnadir (36%) than PERCISTbaseline (29.3%; p = 0.020). Reasons for progression were (a) more than 30% increase in SULpeak of the hottest lesion (n = 7, 15.9%), (b) detection of new metastatic lesions (n = 28, 63.6%), or both (a) and (b) (n = 9, 20.5%).

Conclusions: PERCIST, with the introduction of PERCISTnadir, allows a graphical interpretation of disease fluctuation that may be beneficial in clinical decision-making regarding potential earlier termination of non-effective toxic treatment. PERCIST seems feasible for response monitoring in MBC but prospective studies are needed to come this closer.

4. Discussion

In this feasibility study, we found high applicability for PERCIST for longitudinal response monitoring in metastatic breast cancer with 95% of patients having measurable disease according to PERCIST. A moderate proportion of agreement was observed when comparing PERCIST to visual assessment in daily clinical practice, with PERCIST suggesting non-response more often than visual assessment. When introducing PERCISTnadir, the number of non-response categories increased further. Earlier detection of progression translates into treatment change and has potential patient benefit.

The lack of consensus for response criteria in FDG-PET/CT is due to the absence of studies applying PERCIST (and other criteria) in clinical settings [18]. To our knowledge, only one retrospective study has applied PERCIST compared with RECIST 1.1. in MBC patients [15]. They found the predictive value between baseline and first follow-up scan in favor of PERCIST. In the present study, we chose to apply the PERCIST one-lesion, since no significant differences have been found between one-lesion PERCIST and five-lesion PERCIST [16]. Women with MBC have in general very widespread disease and, therefore, the total lesion glycolysis (TLG), also suggested by PERCIST [12] seems unfeasible for daily clinical practice.

We found a moderate agreement between PERCIST and visual assessment. PERCISTbaseline seems more sensitive for the detection of progression compared with visual assessment, and the same holds for PERCISTnadir compared with PERCISTbaseline. Identifying progression earlier has the potential to lead to earlier discontinuation of treatment and subsequent prevention of toxicity of an ineffective treatment. However, on the other hand, considering a state as progressive too early also has the risk of discarding a treatment too soon.

The PERCIST [12] criteria suggest subsequent follow-up scans to be compared with the pretreatment baseline scan. In daily clinical practice, the previous scan is also often used as a reference to allow detection of progression, if the disease has regressed since baseline. However, using the previous scan as a reference implies a risk of missing continuously small increases of FDG-uptake on successive scans. The potential clinical impact of using the nadir scan instead of the baseline as the reference in an individual patient is illustrated in Figure 3. When the SULpeak decreases in cases of metabolic regression, comparison to the baseline scan would be misleading. It seems relevant to introduce the nadir level of SULpeak for monitoring such cancer lesions in PERCIST in the same way as it suggested for the nadir of the tumor size in RECIST 1.1 [3].

Using SULpeak for monitoring has the advantage of providing continuous values that can visualize the disease fluctuations and hence identify the nadir level. However, visualizing the percentage change of SULpeak, as suggested in Figure 2 and Figure 3, gave rise to considerations of the response category CMR. It seems misleading to measure the SULpeak of a lesion being indistinguishable from background activity since the SULpeak depends on the organ of involvement. CMR in a lung metastasis is suspected to have low SULpeak values compared with bone or liver metastases, and we suggest cases of CMR to be visualized as minus 100%. The SULpeak of the first metastatic lesion detected thereafter is then considered PMD. This will be in line with the detection of new lesions, which then should be the new reference for measurement of the coming changes in SULpeak.

Standardization of response monitoring patients with MBC may have advantages such as facilitating evidence-based treatment decisions and increasing agreement between observers. Despite increased time spent performing PERCIST analysis compared with visual assessment at the moment, the time is considered well spend since PERCIST has shown a better inter-observer variability [20] in MBC patients compared with visual assessment and is also suggested to be more reproducible [21]. Future software and automated analysis will have the potential to be time-sparing when using PERCIST in clinical settings. Further, standardized response evaluation could be of potentially great value if FDG-PET/CT should be introduced for future clinical trials where quantitative measurements are demanded.

A strength of this study is the representation of daily clinical practice for longitudinal response monitoring in MBC without the strict acquisition of the PERCIST standardization protocol. Further, no other studies have, to our knowledge, applied PERCIST for longitudinal response monitoring in MBC. However, due to the retrospective design of this feasibility study, we excluded a large number of scans because of non-comparability. Future studies and clinical practice will assumingly not have to exclude the same amount of scans, since the improvement in scanner techniques has resulted in less fluctuation in the SUV. Further, the standardization protocol suggested by PERCIST could not be fully documented, which must be taken into account when interpreting data [22]. Nevertheless, in our daily clinical practice, FDG-PET/CT followed the EANM guideline which to a large extent fulfills suggested standardization requirements by PERCIST, and non-comparable scans were excluded. Since this is a retrospective study, we must account for potential selection bias in the study group. No specific reason was given for which patients being monitored by FDG-PET/CT as opposed to CE-CT, which was the main alternative for response monitoring of MBC at our institution. Choosing response monitoring by FDG-PET/CT could be related to substantial tumor burden, more aggressive subtype, or preference by the individual oncologist. The relatively short inclusion period of three months may have resulted in missed patients with longer intervals between response monitoring scans due to a better overall response to treatment. Finally, the lack of a reference standard in the evaluation of progressive and non-progressive disease limits the study for validation of the response categories. Despite the limitations, we still consider it of great importance to report on the clinical benefits and shortcomings of PERCIST for response monitoring MBC patients.

Prospective studies with sufficient follow-up are needed to validate PERCIST in longitudinal response monitoring of MBC, preferably in large prospective studies where the criteria can be compared between studies. Alongside, future studies should aim at comparing one-lesion PERCIST, five-lesion PERCIST, and total lesion glycolysis to clarify the most optimal PERCIST approach for patients with MBC, who in general have a very widespread disease.

In conclusion, PERCIST provides a semi-quantitative response categorization with a useful variable, SULpeak, allowing monitoring of disease fluctuation and enabling identification of a nadir level of SULpeak. PERCIST seemed feasible for response monitoring in patients with metastatic breast cancer and may be beneficial in clinical decision-making regarding potential earlier termination of non-effective toxic treatment. PERCISTnadir detected progression more frequently than visual assessment and PERCISTbaseline. Prospective studies are needed to validate PERCIST in longitudinal response monitoring of metastatic breast cancer and to assess the influence of PERCIST on clinical decision-making.

Author Contributions

Conceptualization, M.V. and M.G.H.; methodology, M.V., J.L.B., L.L., H.R.O., T.A.A., M.N.-B., P.-E.B. and M.G.H.; software, J.L.B., L.L., M.N.-B., P.-E.B. and M.G.H.; validation, M.V. and M.G.H.; formal analysis, M.V. and O.G.; investigation, M.V. and M.G.H.; resources, M.V., M.N.-B. and M.G.H.; data curation, M.V., M.N.-B. and O.G.; writing—original draft preparation, M.V.; writing—review and editing, M.V., O.G., M.N.-B. and M.G.H.; visualization, M.V.; supervision, O.G. and M.G.H.; project administration, M.G.H.; funding acquisition, M.V. and M.G.H. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Mrs. Astrid Thaysens grant, Qvesehls grant, The Independent Research Fund Denmark (DFF—7016-00359), the University of Southern Denmark (Ph.D. grant), Odense University Hospital (Ph.D. grant), and the Centre for Personalized Response Monitoring in Oncology (PREMIO), Odense University Hospital, Odense, Denmark.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board and the Data Protection Agency (Journal no. 17/29850).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to private and ethical reasons.

Acknowledgments

We want to acknowledge the two patient representatives, Marie Lykke Rasmussen and Susanne Geneser, who have served as co-researchers in this study for valuable discussions of the study.

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

Ferlay, J.; Steliarova-Foucher, E.; Lortet-Tieulent, J.; Rosso, S.; Coebergh, J.W.; Comber, H.; Forman, D.; Bray, F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur. J. Cancer 2013, 49, 1374–1403. [Google Scholar] [CrossRef] [PubMed]
Harbeck, N.; Penault-Llorca, F.; Cortes, J.; Gnant, M.; Houssami, N.; Poortmans, P.; Ruddy, K.; Tsang, J.; Cardoso, F. Breast cancer. Nat. Rev. Dis. Prim. 2019, 5, 66. [Google Scholar] [CrossRef]
Eisenhauer, E.A.; Therasse, P.; Bogaerts, J.; Schwartz, L.H.; Sargent, D.; Ford, R.; Dancey, J.; Arbuck, S.; Gwyther, S.; Mooney, M.; et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur. J. Cancer 2009, 45, 228–247. [Google Scholar] [CrossRef]
Semiglazov, V. RECIST for response (clinical and imaging) in neoadjuvant clinical trials in operable breast cancer. J. Natl. Cancer Inst. Monogr. 2015, 2015, 21–23. [Google Scholar] [CrossRef]
Schwartz, L.H.; Litiere, S.; de Vries, E.; Ford, R.; Gwyther, S.; Mandrekar, S.; Shankar, L.; Bogaerts, J.; Chen, A.; Dancey, J.; et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur. J. Cancer 2016, 62, 132–137. [Google Scholar] [CrossRef]
Cardoso, F.; Paluch-Shimon, S.; Senkus, E.; Curigliano, G.; Aapro, M.S.; André, F.; Barrios, C.H.; Bergh, J.; Bhattacharyya, G.S.; Biganzoli, L.; et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5)(†). Ann. Oncol. Off. J. Eur. Soc. Med Oncol. 2020. [CrossRef] [PubMed]
Yang, H.-L.; Liu, T.; Wang, X.-M.; Xu, Y.; Deng, S.-M. Diagnosis of bone metastases: A meta-analysis comparing 18 FDG PET, CT, MRI and bone scintigraphy. Eur. Radiol. 2011, 21, 2604–2617. [Google Scholar] [CrossRef] [PubMed]
Li, J.-N.; Zhong, R.; Zhou, X.-H. Prediction of Bone Metastasis in Breast Cancer Based on Minimal Driver Gene Set in Gene Dependency Network. Genes 2019, 10, 466. [Google Scholar] [CrossRef] [PubMed]
Hildebrandt, M.G.; Gerke, O.; Baun, C.; Falch, K.; Hansen, J.A.; Farahani, Z.A.; Petersen, H.; Larsen, L.B.; Duvnjak, S.; Buskevica, I.; et al. Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) in Suspected Recurrent Breast Cancer: A Prospective Comparative Study of Dual-Time-Point FDG-PET/CT, Contrast-Enhanced CT, and Bone Scintigraphy. J. Clin. Oncol. 2016, 34, 1889–1897. [Google Scholar] [CrossRef]
Ulaner, G.A. PET/CT for Patients with Breast Cancer: Where Is the Clinical Impact? AJR Am. J. Roentgenol. 2019, 213, 254–265. [Google Scholar] [CrossRef]
O, J.H.; Lodge, M.A.; Wahl, R.L. Practical PERCIST: A Simplified Guide to PET Response Criteria in Solid Tumors 1.0. Radiology 2016, 280, 576–584. [Google Scholar] [CrossRef]
Wahl, R.L.; Jacene, H.; Kasamon, Y.; Lodge, M.A. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J. Nucl. Med. Off. Publ. Soc. Nucl. Med. 2009, 50 (Suppl. 1), 122s–150s. [Google Scholar] [CrossRef]
Wahl, R.L. PERCIST in Perspective. Nucl. Med. Mol. Imaging 2018, 52, 1–4. [Google Scholar]
Helland, F.; Hallin Henriksen, M.; Gerke, O.; Vogsen, M.; Hoilund-Carlsen, P.F.; Hildebrandt, M.G. FDG-PET/CT Versus Contrast-Enhanced CT for Response Evaluation in Metastatic Breast Cancer: A Systematic Review. Diagnostics 2019, 9, 106. [Google Scholar] [CrossRef]
Riedl, C.C.; Pinker, K.; Ulaner, G.A.; Ong, L.T.; Baltzer, P.; Jochelson, M.S.; McArthur, H.L.; Gonen, M.; Dickler, M.; Weber, W.A. Comparison of FDG-PET/CT and contrast-enhanced CT for monitoring therapy response in patients with metastatic breast cancer. Eur. J. Nucl. Med. Mol. Imaging 2017, 44, 1428–1437. [Google Scholar] [CrossRef] [PubMed]
Pinker, K.; Riedl, C.C.; Ong, L.; Jochelson, M.; Ulaner, G.A.; McArthur, H.; Dickler, M.; Gönen, M.; Weber, W.A. The impact that number of analyzed metastatic breast cancer lesions has on response assessment by 18F-FDG PET/CT using PERCIST. J. Nucl. Med. Off. Publ. Soc. Nucl. Med. 2016, 57, 1102. [Google Scholar] [CrossRef]
Hildebrandt, M.G.; Lauridsen, J.F.; Vogsen, M.; Holm, J.; Vilstrup, M.H.; Braad, P.E.; Gerke, O.; Thomassen, M.; Ewertz, M.; Hoilund-Carlsen, P.F.; et al. FDG-PET/CT for Response Monitoring in Metastatic Breast Cancer: Today, Tomorrow, and Beyond. Cancers 2019, 11, 1190. [Google Scholar] [CrossRef] [PubMed]
Groheux, D. Role of Fludeoxyglucose in Breast Cancer: Treatment Response. PET Clin. 2018, 13, 395–414. [Google Scholar] [CrossRef]
Boellaard, R.; Delgado-Bolton, R.; Oyen, W.J.; Giammarile, F.; Tatsch, K.; Eschner, W.; Verzijlbergen, F.J.; Barrington, S.F.; Pike, L.C.; Weber, W.A.; et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: Version 2.0. Eur. J. Nucl. Med. Mol. Imaging 2015, 42, 328–354. [Google Scholar] [CrossRef]
Sørensen, J.S.; Vilstrup, M.H.; Holm, J.; Vogsen, M.; Bülow, J.L.; Ljungstrøm, L.; Braad, P.E.; Gerke, O.; Hildebrandt, M.G. Interrater Agreement and Reliability of PERCIST and Visual Assessment When Using 18F-FDG-PET/CT for Response Monitoring of Metastatic Breast Cancer. Diagnostics 2020, 10, 1001. [Google Scholar] [CrossRef]
Depardon, E.; Kanoun, S.; Humbert, O.; Bertaut, A.; Riedinger, J.-M.; Tal, I.; Vrigneaud, J.-M.; Lasserre, M.; Toubeau, M.; Berriolo-Riedinger, A. FDG PET/CT for prognostic stratification of patients with metastatic breast cancer treated with first line systemic therapy: Comparison of EORTC criteria and PERCIST. PLoS ONE 2018, 13, e0199529. [Google Scholar] [CrossRef] [PubMed]
Willemsen, A.E.; Vlenterie, M.; van Herpen, C.M.; van Erp, N.P.; van der Graaf, W.T.; de Geus-Oei, L.F.; Oyen, W.J. Positron emission tomography response criteria in solid tumours criteria for quantitative analysis of -fluorodeoxyglucose positron emission tomography with integrated computed tomography for treatment response assessment in metastasised solid tumours: All that glitters is not gold. Eur. J. Cancer 2016, 56, 54–58. [Google Scholar] [CrossRef] [PubMed]

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FDG-PET / CT scan, solide tumoren, borstkanker, PERCIST, PET-responscriteria, monitoring behandelingen