Fixed-dose pembrolizumab (200 mg absolute, day 1, every 3 wk) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared with ...second-line chemotherapy. Because of lack of validated imaging response criteria, responder subgroups with potential survival benefit have not yet been identified. Here, we administered high-dose pembrolizumab (10 mg/kg, day 1, every 2 wk) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum.
Data from 27 patients with baseline and follow-up
F-FDG PET/CT imaging were retrospectively analyzed. RECIST, version 1.1; modified RECIST; and PERCIST using both tumor lesion metabolic activity in a 1 cm
spheric region of interest of up to 5 target lesions (PERCIST
) and metabolic tumor volume PERCIST (PERCIST
) were applied separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) were compared between responders and nonresponders using Kaplan-Meier and log-rank analyses. Programmed cell death protein 1 ligand expression status was assessed, and its association with outcome was investigated.
Twenty-seven patients had
F-FDG PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 mo, respectively. Response rates were 7%, 7%, 30%, and 30% based on RECIST, modified RECIST, PERCIST
, and PERCIST
response criteria, respectively. Response according to PERCIST
predicted prolonged OS or PFS (
< 0.01), whereas all other imaging criteria and programmed cell death protein 1 ligand expression did not.
F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials.
Biliary-tract-carcinomas (BTC), pancreatic-ductal-adenocarcinomas (PDAC) and adenoidcystic-carcinomas (AC) have in common that they are traditionally treated with large clinical-target-volumes (CTV). ...The aim of this study is to examine the impact of pretreatment-
GaFAPI-PET/CT on target-volume-definition and posttreatment-
GaFAPI-PET/CT-response-assessment for BTC-, PDAC- and AC-patients referred to radiation-therapy. All consecutive BTC-, PDAC-, and AC-patients who received pretreatment-
GaFAPI-PET/CT±
FFDG-PET/CT were included from 01.01.2020 to 01.03.2022. MTV and SUV
were separately generated based on
GaFAPI- and
FFDG-PET/CT-images. A
GaFAPI- and
FFDG-based-CTV was defined. Treatment-plans were compared. Treatment-response was reassessed by a second
GaFAPI-PET/CT and
FFDG-PET/CT after treatment-completion. Intermodality comparison of lesion-to-background-ratios SUV
/SUV
for individual timepoints t
and t
revealed significant higher values for
GaFAPI compared to
FFDG (t
, p = 0.008; t
, p = 0.005). Intermodality comparison of radiation-therapy-plans showed that
GaFAPI-based planning resulted in D100% = 97.2% and V95% = 98.8% for the
FFDG-MTV.
FFDG-based-planning resulted in D100% = 35.9% and V95% = 78.1% for
GaFAPI-MTV.
FFDG-based-planning resulted only in 2 patients in V95% > 95% for
GaFAPI-MTV, and in 1 patient in D100% > 97% for
GaFAPI-MTV. GTV-coverage in terms of V95% was 76.4% by
FFDG-based-planning and 99.5% by
GaFAPI-based-planning. Pretreatment
GaFAPI-PET/CT enhances radiation-treatment-planning in this particular group of patients. While perilesional and tumoral follow-up
FFDG-uptake behaved uniformly, perilesional and tumoral reaction may differ in follow-up
GaFAPI-imaging. Complementary
GaFAPI- and
FFDG-imaging enhance treatment-response-assessment.
Background Neuroendocrine tumors (NETs) frequently overexpress somatostatin receptors (SSTRs), which is the molecular basis for .sup.68Ga-DOTATOC positron-emission tomography (PET) and radiopeptide ...therapy (PRRT). However, SSTR expression fluctuates and can be subject to treatment-related changes. The aim of this retrospective study was to assess, which changes in PET and apparent diffusion coefficient (ADC) occur for different treatments and if pre-therapeutic .sup.68Ga-DOTATOC-PET/MRI was able to predict treatment response to PRRT. Methods Patients with histopathologically confirmed NET, at least one liver metastasis > 1 cm and at least two .sup.68Ga-DOTATOC-PET/MRI including ADC maps were eligible. .sup.68Ga-DOTATOC-PET/MRI of up to 5 liver lesions per patients was subsequently analyzed. Extracted features comprise conventional PET parameters, such as maximum and mean standardized uptake value (SUVmax and SUVmean) and ADC values. Furthermore, textural features (TFs) from both modalities were extracted. In patients with multiple .sup.68Ga-DOTATOC-PET/MRI a pair of 2 scans each was analyzed separately and the parameter changes between both scans calculated. The same image analysis was performed in patients with .sup.68Ga-DOTATOC-PET/MRI before PRRT. Differences in PET and ADC maps parameters between PRRT-responders and non-responders were compared using Mann-Whitney test to test differences among groups for statistical significance. Results 29 pairs of .sup.68Ga-DOTATOC-PET/MRI scans of 18 patients were eligible for the assessment of treatment-related changes. In 12 cases patients were treated with somatostatin analogues between scans, in 9 cases with PRRT and in 2 cases each patients received local treatment, chemotherapy and sunitinib. Treatment responders showed a statistically significant decrease in lesion volume and a borderline significant decrease in entropy on ADC maps when compared to non-responders. Patients treated with standalone SSA showed a borderline significant decrease in mean and maximum ADC, compared to patients treated with PRRT. No parameters were able to predict treatment response to PRRT on pre-therapeutic .sup.68Ga-DOTATOC-PET/MRI. Conclusions Patients responding to current treatment showed a statistically significant decrease in lesion volume on ADC maps and a borderline significant decrease in entropy. No statistically significant changes in PET parameters were observed. No PET or ADC maps parameters predicted treatment response to PRRT. However, the sample size of this preliminary study is small and further research needed. Keywords: DOTATOC, PET/MRI, Textural features, Radiomics, NET, Radiopeptide therapy
Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to ...implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring.
136 patients received 99mTc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest.
Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%.
We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.
Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous and phenotypically variable systemic disease characterized by deposition of misfolded transthyretin fibrils in ...various tissues. ATTRv cardiomyopathy and progressive axonal polyneuropathy are the most common manifestations, leading to severe disability and ultimately death within approximately ten years. As disease-modifying treatment options evolve, timely diagnosis and treatment initiation are crucial to prevent rapid disease progression.
Here, we report on a 73-year old patient initially diagnosed with cardiac wild-type ATTR (ATTRwt) amyloidosis by endomyocardial biopsy. Molecular genetic analysis revealed a novel TTR sequence variant (p.Ala65Val) that is highly likely to be amyloidogenic in light of previously reported TTR mutations and the patient's clinical presentation and family history.
Our findings expand the spectrum of known pathogenic TTR mutations and underline the importance of a thorough diagnostic workup in amyloidosis patients including careful genetic testing to avoid misdiagnosis and missing of treatment opportunities and to enable cascade testing and tracking of carriers.
The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. ...However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and management of inflammation. Imaging can provide insights into individual and temporospatial biology and grade of inflammation which can be of diagnostic, therapeutic, and prognostic value. There is therefore an urgent need to evaluate and understand current approaches and potential applications for imaging of inflammation. This review discusses radiotracers for positron emission tomography (PET) that have been used to image inflammation in cardiovascular diseases and other inflammatory conditions with a special emphasis on radiotracers that have already been successfully applied in clinical settings.
Purpose
FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this ...study is the head-to-head intra-individual comparison of
68
Ga-FAPI versus standard-of-care
18
F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers.
Material and Methods
This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both
68
Ga-FAPI and
18
F-FDG PET/CT within a median time interval of 10 days (range 1–89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ).
Results
A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions.
68
Ga-FAPI uptake in primary tumors and metastases was comparable to
18
F-FDG in most cases. The SUVmax was significantly lower for
68
Ga-FAPI than
18
F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus,
68
Ga-FAPI TBRs were significantly higher than
18
F-FDG TBRs in some sites, including liver and bone metastases.
Conclusion
Quantitative tumor uptake is comparable between
68
Ga-FAPI and
18
F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for
68
Ga-FAPI. Thus,
68
Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological
18
F-FDG uptake.
The clinical phenotype of poorly differentiated thyroid cancer (PDTC) can vary substantially. We aim to evaluate risk factors for radioiodine refractory (RAI-R) disease and reduced overall survival ...(OS).
We retrospectively screened our institutional database for PDTC patients. For the assessment of RAI-R disease, we included patients who underwent dual imaging with
F-FDG-PET and
I-PET/
I scintigraphy that met the internal standard of care. We tested primary size, extrathyroidal extension (ETE), and age >55 years as risk factors for RAI-R disease at initial diagnosis and during the disease course using uni- and multivariate analyses. We tested metabolic tumor volume (MTV), total lesion glycolysis (TLG) on
F-FDG-PET, and the progression of stimulated thyroglobulin within 4-6 months of initial radioiodine therapy as prognostic markers for OS.
Size of primary >40 mm and ETE were significant predictors of RAI-R disease in the course of disease in univariate (81% vs. 27%,
= 0.001; 89% vs. 33%,
< 0.001) and multivariate analyses. Primary tumor size was an excellent predictor of RAI-R disease (AUC = 0.90). TLG/MTV > upper quartile and early thyroglobulin progression were significantly associated with shorter median OS (29.0 months vs. 56.9 months,
< 0.05; 57.8 months vs. not reached
< 0.005, respectively).
PDTC patients, especially those with additional risk factors, should be assessed for RAI-R disease at initial diagnosis and in the course of disease, allowing for early implementation of multimodal treatment. Primary tumor size >40 mm, ETE, and age >55 are significant risk factors for RAI-R disease. High MTV/TLG is a significant risk factor for premature death and can help identify patients requiring intervention.
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