Introduction: Breast cancer is one of the most common cancers among women. Its incidence is increasing in many countries and a higher number of older women are now being diagnosed with the disease. Immune parameters are implicated in disease progression, and the frequencies of both myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), associated with tumour burden, have been suggested to be indicators of poor prognosis in cases of metastatic breast cancer. Methods: Here, we have assessed the frequency of peripheral Tregs and MDSCs in relation to in vitro T cell responses to Her2 antigen in 40 untreated breast cancer patients 65 to 87 years of age at diagnosis. Results: The five-year survival rate of patients who mounted a CD8+ T cell response to Her2 peptides and had a lower frequency of Lin−CD14+HLA-DR−MDSCs was 100% compared to only 38% in patients without Her2-reactive CD8+ T cells and with higher frequencies of MDSCs (P = 0.03). Patients who lacked a CD8 response to Her2 tended to have higher frequencies of MDSCs. Similarly, patients who lacked a CD8 response to Her2 and had higher frequencies of CD4+Foxp3+CD127lowCD25+ Tregs had only 50% survival compared to the 100% survival of patients who did mount a CD8 response and had lower frequencies of Tregs (P = 0.03). A similar trend was observed for activated (CD4+CD45RA−Foxp3hi) but not resting Tregs (CD4+CD45RA+FoxP3+). This survival advantage was observed in both metastatic and non-metastatic patients. Conclusions: Our data demonstrate a negative role of both MDSCs and Tregs in the prognosis of breast cancer patients, the mechanism of which might be through dampening favourable CD8+ T cell immune responses to tumour-associated antigens.
Identifying immune markers in blood that are informative for breast cancer patient survival would not only be useful for prognosis but might also provide mechanistic insights into processes facilitating survival. We phenotyped circulating plasmacytoid dendritic cells (pDCs), myeloid-derived suppressor cells (MDSCs) and regulatory T-cells in relation to T-cell responses to Her-2 in vitro in 75 untreated breast cancer patients 28–87 years of age at diagnosis. Patients with later stage tumors had lower levels of circulating pDCs (p = 0.008). There was a positive association between 5-year survival and higher than median levels of circulating pDCs (p = 0.03). We confirmed that 5-year survival correlated with CD8+ but not CD4+ T-cell responsiveness to Her-2 peptides in this cohort of younger and older patients (p = 0.04). Including pDCs in the analysis of previously-established parameters revealed that patients who had a CD8+ T-cell response to Her-2 together with a low ratio of MDSCs:pDCs had 100 % 5-year survival. High levels of pDCs and the presence of a CD8+ T-cell response to Her-2 were independent positive survival indicators according to multivariate Cox analysis. Our new results suggest that circulating pDCs could be a positive prognostic indicator in breast cancer patients of all ages, together with the previously established CD8+ T-cell reactivity to Her-2 antigens in older patients only. These two prognostic indicators were independent and emphasize the important role of immunity in ensuring breast cancer patient survival, even in those not undergoing immunotherapy.
18 March 2017 in European Journal of Nuclear Medicine and Molecular Imaging
Objectives The aims of this study were to investigate subjective perceptions and sensory side effects during whole-body positron emission tomography (PET)/magnetic resonance (MR) examinations and to evaluate differences between PET/MR and standard PET/computed tomography (CT) examinations. Material and Methods During prospective clinical trials using a PET/MR hybrid system after a standard PET/CT examination, 266 patients (including 19 juveniles) were asked to complete questionnaires on causes of discomfort and side effects after both examinations (self-assessment). In case of complaints regarding causes of discomfort, physicians were also asked to complete the questionnaires to provide an external assessment. Visual analog scales were used for the ratings. Results Seventy-four percent (183/247) of all adult patients and 68% (13/19) of all teenage patients completed the questionnaires. In most of the cases, patient compliance was good and allowed for the acquisition of diagnostic images. Most patients did not report side effects or discomfort at all. Only 11 of 247 PET/MR scans of adult patients (4.4%) and 4 of 19 scans of juvenile patients (21%) were aborted prematurely by the patients' requests; however, this did not influence the final PET/MR diagnoses in most cases (12/15). In terms of noise levels and examination times, patients rated the PET/MR significantly lower than the PET/CT. With the exception of male patients not tolerating the examination time as well as female patients, no significant influences of sex, age, body mass index, and real scan times were observed. The attending physicians tended to underestimate their patient's discomfort, particularly when the discomfort was because of time (in the case of children) or noise exposure (all patients). Conclusions Patient comfort should drive the design and development of optimized scanner types, workflow processes, and scan protocols. For PET/MR, the most important aim should be to shorten the scan time. However, patient-centered management may be the best instrument to improve patient compliance.
To investigate imaging features of osteomyelitis of the jaw (OMJ) using [18F]fluoride positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG)-PET compared with computed tomography (CT) and magnetic resonance imaging (MRI) to assess extent and disease activity. Six female patients (55.3 ± 10.0 years) were enrolled for assessment of symptomatic OMJ. 4/6 patients underwent [18F]FDG-PET/MRI and [18F]fluoride-PET/CT, one patient MRI and [18F]fluoride-PET/CT and another patient only [18F]FDG-PET/MRI. Image analysis was performed by two radiologists, an oral and maxillofacial surgeon, and a nuclear medicine specialist. The extent of affected jawbone was analyzed both qualitatively and quantitatively, including the PET tracer uptake, CT-Hounsfield-Units (HU) and MRI parameters in affected and healthy jawbone. All patients had trabecular sclerosis in the affected jawbone compared to healthy jawbone (560 ± 328 HU vs. 282 ± 211 HU; p > 0.05), while 3/6 patients had cortical erosions. Bone marrow edema and gadolinium enhancement were documented in 5/6 patients. In affected jawbone, [18F]fluoride-uptake was increased in all patients compared to healthy jawbone (SUVmean 15.4 ± 4.2 vs. 2.1 ± 0.6; p < 0.05), and [18F]FDG-uptake was moderately higher (SUVmean 1.9 ± 0.7 vs. 0.7 ± 0.2; p > 0.05). The extent of regions with increased metabolic activity was less than the extent of morphologic changes in all patients. Information on jawbone metabolism and inflammation is different from morphologic changes and therefore has the potential to provide a more accurate and objective assessment of the extent and activity of OMJ.
Objective: To determine the impact of 18F-FDG-PET/CT on clinical management of patients with cholangiocellular carcinoma (CCA). Methods: Patients with CCA undergoing clinically indicated 18F-FDG-PET/CT between 04/2013 and 08/2018 were prospectively included in a local PET/CT registry study. Intended clinical management (“non-treatment” such as watchful-waiting or additional diagnostic tests, and “palliative” or “curative treatment”) was recorded before and after PET/CT. Changes in intended management after PET/CT were analyzed. Results: 27 patients (mean age: 60 years, IQR: 51.5–67.5 years, 56% males) with 43 PET/CT examinations were included. Intended management changed in 35/43 cases (81.4%) following PET/CT. Major changes (i.e., between “non-treatment” and “treatment” strategies or between a “curative” and “palliative” treatment goal) occurred in 27/43 (62.8%) cases. Before PET/CT, additional imaging and/or biopsy were intended in 21/43 (48.8%) and 9/43 (20.9%) cases, respectively. After PET/CT, further imaging was carried out in one case and imaging-targeted biopsy in eight cases. Although the absolute number of biopsies after PET/CT did not decrease, in only one of these eight cases biopsy had already been planned before PET/CT, whereas in the other eight cases, the originally planned biopsies were dispensable after PET/CT. Conclusions: 18F-FDG-PET/CT significantly impacts clinical management of patients with CCA. It guides decisions on treatment strategy (especially curative vs palliative treatment goal) and on additional tests, particularly by helping referring clinicians to avoid unnecessary imaging and by guiding targeted biopsy. Advances in knowledge: Systematic implementation of 18F-FDG-PET/CT may enable a more appropriate and tailored treatment of patients with CCA, especially in cases of suspected recurrence.