Search

Background: Primary metastatic breast cancer (pMBC) accounts for 5–10% of annual breast cancers with a median survival of 3–4 years, varying among subtypes. In Denmark, the incidence of breast cancer increased until 2010, followed by a stabilisation. Several factors influencing pMBC incidence and survival, including screening prevalence, staging methods, and classification standards, remain pivotal but inadequately documented. Material and method: This retrospective observational study involving pMBC patients diagnosed between 2000 and 2020 encompassed all Danish oncology departments. Data from the Danish Breast Cancer Group database and the National Patient Register included diagnosis specifics, demographics, treatment, and follow-up. Results: Between 2000 and 2020, 3,272 patients were diagnosed with pMBC, a rise from 355 patients in 2000–2004 to 1,323 patients in 2015–2020. The increase was particularly observed in patients aged 70 years or older. Changes in tumour subtypes were observed, notably with a rise in human epidermal growth factor receptor 2 (HER2)-positive cases but a steady distribution of estrogen receptor (ER) status. Diagnostic practices changed over the two decades, with 6% evaluated with PET/CT (positron emission tomography–computed tomography) or CT (computed tomography) with a bone evaluation in 2000–2004 and 65% in 2015–2020. Overall survival (OS) improved from 23 months in 2000–2004 to 33 months in 2015–2020. In patients with ER-positive and HER2-positive disease, the multivariable model showed improved survival by year of diagnosis, and further, patients with ER-negative/HER2-negative disease fared worse the first 2 years after diagnosis. Interpretation: Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.

Abstract 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.

Abstract 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

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.

Abstract 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

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.

Abstract Background Despite increasing interest in patient involvement in health care research, researchers may be uncertain about the benefits of involving patients in the design and conduction of clinical studies. We aimed to evaluate the impact of patient involvement on patient recruitment and retention in a clinical study of PET/CT in women with advanced breast cancer. Further, we report our experience regarding the researchers’ attitudes towards involving patients as partners in the research process. Methods Two patient representatives from the Danish Breast Cancer Organization were invited as partners in the research team. These patient partners were asked to contribute in particular to participator information material and evaluation of ethical aspects of the study. The impact of patient involvement on patient recruitment was evaluated by comparing expected versus actual number of patients recruited, and then relating it to patient recruitment in a similar study at the same institution that did not involve patients as research partners. Results Having patients as partners in the research team led to a major revision of the participator information material and improved patient recruitment. The expected number of patients was 260, but 380 were actually enrolled within the planned study period, thus 146% of the expected patient recruitment. In the previous study, only 100 of the expected 150 patients were enrolled during a 10-month extended study period, i.e. 67% of the expected number. Patient retention in the current study was high, with 86% of eligible patients attending follow-up scans. We observed initial resistance amongst researchers against inviting patients as team partners. This resistance gradually lessened during the study, and the most reluctant researchers at the beginning of the study later applauded the collaboration and the ideas generated by the patient representatives. Conclusion Involving patients as partners in the research team resulted in major changes to the participator information material and contributed to higher than expected patient recruitment and retention. Furthermore, we observed a positive change of attitude amongst the researchers towards patient involvement in the research process. Trial registration Ongoing study: ClinicalTrials.gov (NCT03358589). Previous study: ClinicalTrials.gov (NCT01552655).

We compared response categories and impacts on treatment decisions for metastatic breast cancer (MBC) patients that are response-monitored with contrast-enhanced computed-tomography (CE-CT) or fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). A comparative diagnostic study was performed on MBC patients undergoing response monitoring by CE-CT (n = 34) or FDG-PET/CT (n = 31) at the Odense University Hospital (Denmark). The responses were assessed visually and allocated into categories of complete response (CR/CMR), partial response (PR/PMR), stable disease (SD/SMD), and progressive disease (PD/PMD). Response categories, clinical impact, and positive predictive values (PPV) were compared for follow-up scans. A total of 286 CE-CT and 189 FDG-PET/CT response monitoring scans were performed. Response categories were distributed into CR (3.8%), PR (8.4%), SD (70.6%), PD (15%), and others (2.1%) by CE-CT and into CMR (22.2%), PMR (23.8%), SMD (31.2%), PMD (18.5%), and others (4.4%) by FDG-PET/CT, revealing a significant difference between the groups (P < 0.001). PD and PMD caused changes of treatment in 79.1% and 60%, respectively (P = 0.083). PPV for CE-CT and FDG-PET/CT was 0.85 (95% CI: 0.72–0.97) and 0.70 (95% CI: 0.53–0.87), respectively (P = 0.17). FDG-PET/CT indicated regression of disease more frequently than CE-CT, while CE-CT indicated stable disease more often. FDG-PET/CT seems to be more sensitive than CE-CT for monitoring response in metastatic breast cancer.

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.

Response evaluation at regular intervals is indicated for treatment of metastatic breast cancer (MBC). FDG-PET/CT has the potential to monitor treatment response accurately. Our purpose was to: (a) compare the interrater agreement and reliability of the semi-quantitative PERCIST criteria to qualitative visual assessment in response evaluation of MBC and (b) investigate the intrarater agreement when comparing visual assessment of each rater to their respective PERCIST assessment. We performed a retrospective study on FDG-PET/CT in women who received treatment for MBC. Three specialists in nuclear medicine categorized response evaluation by qualitative assessment and standardized one-lesion PERCIST assessment. The scans were categorized into complete metabolic response, partial metabolic response, stable metabolic disease, and progressive metabolic disease. 37 patients with 179 scans were included. Visual assessment categorization yielded moderate agreement with an overall proportion of agreement (PoA) between raters of 0.52 (95% CI 0.44–0.66) and a Fleiss kappa estimate of 0.54 (95% CI 0.46–0.62). PERCIST response categorization yielded substantial agreement with an overall PoA of 0.65 (95% CI 0.57–0.73) and a Fleiss kappa estimate of 0.68 (95% CI 0.60–0.75). The difference in PoA between overall estimates for PERCIST and visual assessment was 0.13 (95% CI 0.06–0.21; p = 0.001), that of kappa was 0.14 (95% CI 0.06–0.21; p < 0.001). The overall intrarater PoA was 0.80 (95% CI 0.75–0.84) with substantial agreement by a Fleiss kappa of 0.74 (95% CI 0.69–0.79). Semi-quantitative PERCIST assessment achieved significantly higher level of overall agreement and reliability compared with qualitative assessment among three raters. The achieved high levels of intrarater agreement indicated no obvious conflicting elements between the two methods. PERCIST assessment may, therefore, give more consistent interpretations between raters when using FDG-PET/CT for response evaluation in MBC.

This study aimed to compare the prognostic value of quantitative measures of [18F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography (FDG-PET/CT) for the response monitoring of patients with metastatic breast cancer (MBC). In this prospective study, 22 patients with biopsy-verified MBC diagnosed between 2011 and 2014 at Odense University Hospital (Denmark) were followed up until 2019. A dual-time-point FDG-PET/CT scan protocol (1 and 3 h) was applied at baseline, when MBC was diagnosed. Baseline characteristics and quantitative measures of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), corrected SUVmean (cSUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and corrected TLG (cTLG) were collected. Survival time was analyzed using the Kaplan–Meier method and was regressed on MTV, TLG, and cTLG while adjusting for clinicopathological characteristics. Among the 22 patients included (median age: 59.5 years), 21 patients (95%) died within the follow-up period. Median survival time was 29.13 months (95% Confidence interval: 20.4–40 months). Multivariable Cox proportional hazards regression analyses of survival time showed no influence from the SUVmean, cSUVmean, or SUVmax, while increased values of MTV, TLG, and cTLG were significantly associated with slightly higher risk, with hazard ratios ranging between 1.0003 and 1.004 (p = 0.007 to p = 0.026). Changes from 1 to 3 h were insignificant for all PET measures in the regression model. In conclusion, MTV and TLG are potential prognostic markers for overall survival in MBC patients.

While current international guidelines include imaging of the target lesion for response monitoring in metastatic breast cancer, they do not provide specific recommendations for choice of imaging modality or response criteria. This is important as clinical decisions may vary depending on which imaging modality is used for monitoring metastatic breast cancer. FDG-PET/CT has shown high accuracy in diagnosing metastatic breast cancer, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) have shown higher predictive values than the CT-based Response Evaluation Criteria in Solid Tumors (RECIST) for prediction of progression-free survival. No studies have yet addressed the clinical impact of using different imaging modalities or response evaluation criteria for longitudinal response monitoring in metastatic breast cancer. We present a case study of a patient with metastatic breast cancer who was monitored first with conventional CT and then with FDG-PET/CT. We retrospectively applied PERCIST to evaluate the longitudinal response to treatment. We used the one-lesion PERCIST model measuring SULpeak in the hottest metastatic lesion on consecutive scans. This model provides a continuous variable that allows graphical illustration of disease fluctuation along with response categories. The one-lesion PERCIST approach seems able to reflect molecular changes and has the potential to support clinical decision-making. Prospective clinical studies addressing the clinical impact of PERCIST in metastatic breast cancer are needed to establish evidence-based recommendations for response monitoring in this disease.

18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (FDG-PET/CT) and contrast-enhanced computed tomography (CT) can be used for response evaluation in metastatic breast cancer (MBC). In this study, we aimed to review literature comparing the PET Response Criteria in Solid Tumors (PERCIST) with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with MBC. We made a systematic search in Embase, PubMed/Medline, and Cochrane Library using a modified PICO model. The population was MBC patients and the intervention was PERCIST or RECIST. Quality assessment was performed using the QUADAS-2 checklist. A total of 1975 articles were identified. After screening by title/abstract, 78 articles were selected for further analysis of which 2 duplicates and 33 abstracts/out of focus articles were excluded. The remaining 43 articles provided useful information, but only one met the inclusion and none of the exclusion criteria. This was a retrospective study of 65 patients with MBC showing one-year progression-free survival for responders versus non-responders to be 59% vs. 27% (p = 0.2) by RECIST compared to 64% vs. 0% (p = 0.0001) by PERCIST. This systematic literature review identified a lack of studies comparing the use of RECIST (with CE-CT) and PERCIST (with FDG-PET/CT) for response evaluation in metastatic breast cancer. The available sparse literature suggests that PERCIST might be more appropriate than RECIST for predicting prognosis in patients with MBC.

Background The aim was to investigate and challenge the belief that swimming immediately after eating is dangerous and also to investigate what potentially could happen when swimming immediately after a meal. We wanted to explore feasibility and get background data to perform sample size calculations and choose outcome parameters for a full-scale randomized trial. Methods The trial was performed during lunch breaks at a medical writing course in Turkey in June 2022. Participants were randomised on the first trial day to swim 14 meters breaststroke immediately after lunch or wait 30 minutes after eating, with crossover on the second trial day. Main outcomes measures were mortality, and mood, discomfort, and adverse events were assessed in participant-reported questionnaires. Participants completed a Profile of Mood States-Adolescents questionnaire, a visual analogue scale for discomfort, and a questionnaire of adverse events after each swim. Results A total of 26 participants completed the trial. No cases of mortality, drowning, resuscitation, side stitch, or muscle cramps were reported. The participants reported no significant difference in their mood states after each swim and no significant difference was found regarding the participants’ swimming time (P = 0.53). However, more discomfort was reported when swimming immediately instead of 30 minutes after eating (P = 0.05). Conclusions It seems that swimming after eating is safe since no mortality or cramps were registered. However, a significant level of discomfort was found when swimming immediately after eating lunch. This feasibility trial provides background data for a future full-scale randomised trial. Clinicaltrials.gov registration NCT05401396 (25/05/2022).