A 69-year-old Mexican female with end stage renal disease on haemodialysis secondary to biopsy-confirmed leucocyte cell-derived chemotaxin 2 (ALECT2) amyloidosis underwent a positron emission tomography (PET) computed tomography (CT) scan with florbetapir 18F, a US Food and Drug Administration-approved radiotracer for detection of β-amyloid in the brain. Green arrows highlight diffuse intense activity above normal background in the lungs (maximum standardized uptake value [SUVmax] 10·0), spleen (SUVmax 40·6), adrenal glands (SUVmax 12·3), kidneys (SUVmax 16·3) and bone marrow (images). These organs normally have low activity on florbetapir PET/CT. The activity pattern is consistent with pathological data on the distribution of amyloidosis in this disease. Unlike transthyretin-related (ATTR) and light chain-related (AL) amyloidosis, there is normal background activity in the heart of this patient, which is consistent with autopsy data showing cardiac sparing in ALECT2 amyloidosis. The most remarkable finding in this patient is the uptake in the kidney because she makes little urine and is on chronic haemodialysis. ALECT2 amyloidosis is now recognized as the third most common type of renal amyloidosis in the United States, predominately in patients of Mexican or Native American descent. Cases have also been described in patients of Egyptian, Indian and Arab descent. The lack of cardiac or nerve involvement makes ALECT2 amyloidosis difficult to recognize and no laboratory test currently exists for screening. The use of florbetapir PET/CT could serve as a screening test for this at-risk population.
Introduction: As interest in metastasis-directed therapy (MDT) for prostate cancer (PCa) grows, exploring indications and patient selection is increasingly more important. Thus far, few studies have described long-term outcomes after surgical MDT in those with disease recurrence involving the lung. The objective of our study was to compare the cumulative incidence of cancer-related death by treatment modality in men with metachronous pulmonary metastases from PCa. Methods: In a single-institution retrospective study, we identified 75 men from the prospectively maintained Mayo Clinic C-11 Positron Emission Tomography Choline PCa registry with recurrent prostate cancer involving the lung but no other visceral organs. Patients were categorized into 3 groups based on treatment modalities: wedge resection ± hormonal therapy, chemohormonal therapy, and hormonal therapy alone. The risk of cancer-related death after treatment at the time of lung metastases was reported as cumulative incidence estimates. Non–cancer-related deaths were treated as a competing risk of death. A univariate Cox regression model was conducted to assess the impact of treatment modality on the risk of cancer-related death. Results: At the time of lung metastasis, the median age was 69.5 years, and the median (IQR) prostate-specific antigen was 4 (1.3-8.6) ng/ml. Forty-seven patients (62.7%) had hormone-sensitive disease, and 28 patients (37.3%) had hormone-resistant disease. A total of 26 patients (34.7%) were treated with wedge resection ± hormonal therapy, 27 (36%) with chemohormonal therapy, and 22 (29.3%) with hormonal therapy alone. The median (IQR) follow-up time was 50.3 (31.1-78.4) months, and 21 patients (28%) died. Patients who were treated with wedge resection ± hormonal therapy had lower rated of cancer-related death compared with those who received chemohormonal therapy (Hazard Ratio [HR]: 4.14, 95% CI: 1.01-16.96, P = .048) or hormonal therapy alone (HR: 6.37, 95% CI: 1.72-23.54, P = .005). Conclusion: This exploratory analysis supports the safety and feasibility of surgical metastasis-directed therapy in select patients with recurrent prostate cancer involving the lung. Favorable long-term survival provides justification for further evaluation of this approach.
SABR has demonstrated clinical benefit in oligometastatic prostate cancer. However, the risk of developing new distant metastatic lesions remains high, and only a minority of patients experience durable progression-free response. Therefore, there is a critical need to identify which patients will benefit from SABR alone versus combination SABR and systemic agents. Herein we provide, to our knowledge, the first proof-of-concept of circulating prostate cancer-specific extracellular vesicles (PCEVs) as a noninvasive predictor of outcomes in oligometastatic castration-resistant prostate cancer (omCRPC) treated with SABR.We analyzed the levels and kinetics of PCEVs in the peripheral blood of 79 patients with omCRPC at baseline and days 1, 7, and 14 after SABR using nanoscale flow cytometry and compared with baseline values from cohorts with localized and widely metastatic prostate cancer. The association of omCRPC PCEV levels with oncological outcomes was determined with Cox regression models.Levels of PCEVs were highest in mCRPC followed by omCRPC and were lowest in localized prostate cancer. High PCEV levels at baseline predicted a shorter median time to distant recurrence (3.5 vs 6.6 months; P = .0087). After SABR, PCEV levels peaked on day 7, and median overall survival was significantly longer in patients with elevated PCEV levels (32.7 vs 27.6 months; P = .003). This suggests that pretreatment PCEV levels reflect tumor burden, whereas early changes in PCEV levels after treatment predict response to SABR. In contrast, radiomic features of 11C-choline positron emission tomography and computed tomography before and after SABR were not predictive of clinical outcomes. Interestingly, PCEV levels and peripheral tumor-reactive CD8 T cells (TTR; CD8+ CD11ahigh) were correlated.This original study demonstrates that circulating PCEVs can serve as prognostic and predictive markers to SABR to identify patients with "true" omCRPC. In addition, it provides novel insights into the global crosstalk, mediated by PCEVs, between tumors and immune cells that leads to systemic suppression of immunity against CRPC. This work lays the foundation for future studies to investigate the underpinnings of metastatic progression and provide new therapeutic targets (eg, PCEVs) to improve SABR efficacy and clinical outcomes in treatment-resistant CRPC.
