Short summary

The anatomy-based RECIST criteria are as of now considered to be the most widely applicable criteria, when assessing solid cancerous tumours over time. However, with the rapid improvement in PET technology, our study aims to shed light on whether the PERCIST-criteria, in which functional and molecular imaging is used to assess metabolic activity, may be better suited to evaluate treatment response over time in metastatic breast cancer (MBC). Our aim is to compare the more novel PERCIST criteria with the RECIST 1.1 criteria, as well as evaluating if there is concordance between the PERCIST criteria, and a pure visual assessment by a specialist in nuclear and molecular imaging, in the treatment response evaluation of patients with MBC.

Rationale

Guidelines recommend CT and the CT based criteria (RECIST 1.1) for response evaluation in MBC. However, the molecular method of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) / Computed Tomography (CT) may be superior for response evaluation in this patient group. FDG-PET/CT has been used sporadically and increasingly at our institution. It is our hypothesis that FDG-PET/CT will be more appropriate than CT in making the right choice in continuation or change of treatment, and for predicting relevant outcome measures.

We aim to compare CT versus FDG-PET/CT in regard to response evaluation of patients in treatment for MBC, and examine whether FDG-PET/CT leads to more frequent treatment transitions and to longer treatment periods - hence longer survival times - than does CT.

The project consists of parts A and B. In part A, histopathological and oncologic treatment data will be gathered, as well as information pertaining to the primary tumour. The metastatic burden will be evaluated at baseline (prior to treatment start), as will the length of intervals between treatment changes, type of treatment, and the number of treatment changes. The aim is to compare the courses for patients evaluated by CT to patients evaluated by FDG-PET/CT. We wish to register the pattern of metastasis before start of treatment, and to compare the length of treatment for patients evaluated by CT to those evaluated by FDG-PET/CT. "Length time bias" analyses will be used to estimate the potential differences in survival time between the groups.

Part B will include patients who have received at least 2 FDG-PET/CT scans in the treatment period. All scans will be studied retrospectively for visual assessment as suggested by journal entries (in RIS/PACS), suggested by the clinician. The scans will be categorised as either responders: "complete metabolic response" (CMR) and "partial metabolic response" (PMR) or non-responders: "stable metabolic disease" (SMD) and "progressive metabolic disease" (PMD). Furthermore, criteria based on quantitative analyses of FDG-PET/CT (PERCIST-criteria) will be applied and grouped according to the PERCIST-criteria.

A comparison of the categories applied by PERCIST criteria and the visual assessment will be examined, using Kappa-statistics to calculate the concordance between the two. The predictive clinical effect will be registered as "successful cases", in cases where PD is followed by a change of treatment, leading to RD or CR. We will also register less successful cases, where PD is not followed by a change of treatment, and leads to PD. Lastly, cases of SD will be registered.

Description of the cohort

We expect to include 500 women with MBC, who are receiving / or have received oncologic treatment for MBC at the Department of Oncology at Odense University Hospital. The distribution of patients evaluated by FDG-PET/CT and CT is expected to be 1:1.

Inclusion criteria:

• Women with MBC who have been followed in Department of Oncology at Odense University Hospital between 01.01.2007 - 01.01.2017
• Response evaluation with FDG-PET / CT scan or CT of thorax and abdomen.

• Written informed consent or approval from the Board of Patient Safety

Exclusion criteria:

• Pregnancy
• Treatment for other cancerous diseases, except carcinoma in situ cervicis uteri and common skin cancer within the last 5 years.

Data and biological material

We collect written consents from patients that allow us to gather data limited to their individual medical journals from the oncologic department, and their relevant scanning images. This will be done retrospectively, as well as a 1-year prospective follow-up period. Practical management of data is handled in SharePoint and OPEN (REDCap). Statistical analysis will be performed using STATA software.

Collaborating researchers and departments

Department of Nuclear Medicine, University of Southern Denmark, Odense University Hospital

• Consultant Malene Grubbe Hildebrandt, PhD
• PhD student Marianne Vogsen, MD
• Statistician Oke Gerke
• Medical student Tural A. Alamdari
• Medical student Hjalte Oltmann
• Medical student Lasse Ljungstrøm
• Medical student Jakob Lykke Bülow

Department of Oncology, Odense University Hospital

• PhD student Marianne Vogsen, Md

Publications associated with the project

Baun C, Vogsen M, Nielsen MK, Høilund-Carlsen PF, Hildebrandt MG. Perspective of Patients with Metastatic Breast Cancer on Electronic Access to Scan Results: Mixed-Methods Study. J Med Internet Res. 2020 Feb 10;22(2):e15723. doi: 10.2196/15723. PMID: 32039819; PMCID: PMC7055828.

Naghavi-Behzad M, Oltmann HR, Alamdari TA, Bülow JL, Ljungstrøm L, Braad PE, Asmussen JT, Vogsen M, Kodahl AR, Gerke O, Hildebrandt MG. Clinical Impact of FDG-PET/CT Compared with CE-CT in Response Monitoring of Metastatic Breast Cancer. Cancers (Basel). 2021 Aug 13;13(16):4080. doi: 10.3390/cancers13164080. PMID: 34439232; PMCID: PMC8392540.

Sørensen JS, Vilstrup MH, Holm J, Vogsen M, Bülow JL, Ljungstrøm L, Braad PE, Gerke O, Hildebrandt MG. Interrater Agreement and Reliability of PERCIST and Visual Assessment When Using 18F-FDG-PET/CT for Response Monitoring of Metastatic Breast Cancer. Diagnostics (Basel). 2020 Nov 24;10(12):1001. doi: 10.3390/diagnostics10121001. PMID: 33255442; PMCID: PMC7759893.

Vogsen M, Bülow JL, Ljungstrøm L, Oltmann HR, Alamdari TA, Naghavi-Behzad M, Braad PE, Gerke O, Hildebrandt MG. FDG-PET/CT for Response Monitoring in Metastatic Breast Cancer: The Feasibility and Benefits of Applying PERCIST. Diagnostics (Basel). 2021 Apr 19;11(4):723. doi: 10.3390/diagnostics11040723. PMID: 33921580; PMCID: PMC8073831.