Detecting Metastatic Patterns of Oligometastatic Breast Cancer: A Comparative Analysis of 18F-FDG PET/CT and Conventional CT Imaging.

Metastasis-directed therapy has the potential to improve progression-free and overall survival in oligometastatic disease (OMD). For breast cancer, however, randomized trials have failed so far to confirm this finding. Because the concept of metastasis-directed therapy in OMD is highly dependent on the accuracy of the imaging modality, we aimed to assess the impact of 18F-FDG PET/CT on the definition of OMD in breast cancer patients. Methods: Eighty patients with a total of 150 18F-FDG PET/CT images (between October 2006 and January 2022) were enrolled in this retrospective study at the Technical University of Munich. The inclusion criteria were OMD, defined as 1-5 distant metastases, at the time of 18F-FDG PET/CT. For the current study, we systemically compared the metastatic pattern on 18F-FDG PET/CT with conventional CT. Results: At the time of 18F-FDG PET/CT, 21.3% of patients (n = 32) had a first-time diagnosis of metastatic disease, 40.7% (n = 61) had a previous history of OMD, and 38% (n = 57) had a previous history of polymetastatic disease. In 45.3% of cases, the imaging modality (18F-FDG PET/CT vs. conventional CT) had an impact on the assessment of whether OMD was present. An identical metastatic pattern was observed in only 32% of cases.18F-FDG PET/CT detected additional metastases in 33.3% of cases, mostly in the nonregional lymph node system. Conclusion: The use of 18F-FDG PET/CT had a substantial impact on the definition of OMD and detection of metastatic pattern in breast cancer. Our results emphasize the importance of establishing a standardized definition for imaging modalities in future trials and clinical practices related to metastasis-directed therapy in breast cancer patients.

Long-Term Nephrotoxicity of 177Lu-PSMA Radioligand Therapy.

ß-emitting 177Lu targeting prostate-specific membrane antigen (PSMA) is an approved treatment option for metastatic castration-resistant prostate cancer. Data on its long-term nephrotoxicity are sparse. This study aimed to retrospectively evaluate post-177Lu-PSMA estimated glomerular filtration rate (eGFR) dynamics for at least 12 mo in a cohort of metastatic castration-resistant prostate cancer patients. Methods: The institutional databases of 3 German tertiary referral centers identified 106 patients who underwent at least 4 cycles of 177Lu-PSMA and had at least 12 mo of eGFR follow-up data. eGFR (by the Chronic Kidney Disease Epidemiology Collaboration formula) at 3, 6, and 12 mo after 177Lu-PSMA radioligand therapy was estimated using monoexponentially fitted curves through available eGFR data. eGFR changes were grouped (≥15%-<30%, moderate; ≥30%-<40%, severe; and ≥40%, very severe). Associations between eGFR changes (%) and nephrotoxic risk factors, prior treatment lines, and number of 177Lu-PSMA cycles were analyzed using multivariable linear regression. Results: At least moderate eGFR decreases were present in 45% (48/106) of patients; of those, nearly half (23/48) had a severe or very severe eGFR decrease. A higher number of risk factors at baseline (-4.51, P = 0.03) was associated with a greater eGFR decrease. Limitations of the study were the retrospective design, lack of a control group, and limited number of patients with a follow-up longer than 1 y. Conclusion: A considerable proportion of patients may experience moderate or severe decreases in eGFR 1 y from initiation of 177Lu-PSMA. A higher number of risk factors at baseline seems to aggravate loss of renal function. Further prospective trials are warranted to estimate the nephrotoxic potential of 177Lu-PSMA.

Early Prostate-Specific Antigen Changes and Clinical Outcome After 177Lu-PSMA Radionuclide Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer.

Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer. However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes after 177Lu-labeled prostate-specific membrane antigen (177Lu-PSMA) radionuclide treatment in metastatic castration-resistant prostate cancer patients. Methods: Men who were treated with 177Lu-PSMA under a compassionate-access program at our institution and had available PSA values at baseline and at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to 3 groups on the basis of PSA changes: response (≥30% decline), progression (≥25% increase), and stable (<30% decline and <25% increase). The coprimary endpoints were overall survival and imaging-based progression-free survival. The secondary endpoints were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A greater than or equal to 30% decline in PSA at 6 wk was associated with longer overall survival (median, 16.7 mo; 95% CI, 14.4-19.0) than stable PSA (median, 11.8 mo; 95% CI, 8.6-15.1) (P = 0.007) or PSA progression (median, 6.5 mo; 95% CI, 5.2-7.8) (P < 0.001). Patients with a greater than or equal to 30% decline in PSA at 6 wk also had a lower risk of imaging-based progression than patients with stable PSA (hazard ratio, 0.60; 95% CI, 0.38-0.94) (P = 0.02), whereas patients with PSA progression had a higher risk of imaging-based progression than patients with stable PSA (hazard ratio, 3.18; 95% CI, 1.95-5.21) (P < 0.001). The percentage changes in PSA at 6 and 12 wk were highly associated (r = 0.90; P < 0.001). Of 31 patients who experienced early PSA progression at 6 wk, 29 (94%) showed biochemical progression at 12 wk. Overall, only 1 (3%) of 36 patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). The limitations of the study included its retrospective nature and the single-center experience. Conclusion: PSA changes at 6 wk after 177Lu-PSMA initiation are an early indicator of long-term clinical outcome. Patients with PSA progression after 6 wk of treatment could benefit from a very early decision to switch treatment. PSA flare-up during 177Lu-PSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of 177Lu-PSMA.

Aspirin treatment and outcomes after percutaneous coronary intervention: results of the ISAR-ASPI registry.

BACKGROUND: Aspirin administration, as part of a dual antiplatelet treatment regimen, is essential for patients undergoing percutaneous coronary intervention (PCI). Although the correlation between high on-clopidogrel treatment platelet reactivity (HCPR) and clinical outcome is well established, data for high on-aspirin treatment platelet reactivity (HAPR) are conflicting. OBJECTIVES: The aim of the ISAR-ASPI (Intracoronary Stenting and Antithrombotic Regimen-ASpirin and Platelet Inhibition) registry was to assess the value of HAPR as a possible prognostic biomarker in PCI-treated patients with regard to clinical outcome. METHODS: From February 2007 to May 2013, we identified 7,090 consecutive PCI-treated patients with measured on-aspirin treatment platelet aggregation values directly before PCI. Platelet function was assessed with a Multiplate analyzer. The primary endpoint was death or stent thrombosis (ST) at 1 year. RESULTS: The upper quintile of patients (n = 1,414), according to Multiplate measurements, was defined as the HAPR cohort. Compared with non-HAPR patients (n = 5,676), HAPR patients showed a significantly higher risk of death or ST at 1 year (6.2% vs. 3.7%, respectively; odds ratio [OR]: 1.78; 95% confidence interval [CI]: 1.39 to 2.27; p < 0.0001). HAPR was found to be an independent predictor of the primary outcome (adjusted hazard ratio [HRadj]: 1.46; 95% CI: 1.12 to 1.89; p = 0.005). CONCLUSIONS: HAPR, measured at the time point of the PCI, is associated with a higher risk for death or ST during the first year after PCI. Present data are in support of the addition of HAPR to a panel of prognostic biomarkers in PCI-treated patients.