Background To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. Methods A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). Results A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25–34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47–24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16–30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over − 39.8% or Δ%SUV02 over − 54.1% showed worse EFS rates than others (p < 0.05). Conclusions PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.
The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a Ca2+-free solution and thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by GDP-beta-S, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external Ca2+ influx, phospholipase C activation, and Ca2+ release from internal storage in a G protein-independent and protein kinase C-independent manner.
This study aimed to investigate the predictive efficacy of positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the pathological response of advanced breast cancer to neoadjuvant chemotherapy (NAC). The breast PET/MRI image deep learning model was introduced and compared with the conventional methods. PET/CT and MRI parameters were evaluated before and after the first NAC cycle in patients with advanced breast cancer [n = 56; all women; median age, 49 (range 26–66) years]. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained with the corresponding baseline values (SUV0, MTV0, and TLG0, respectively) and interim PET images (SUV1, MTV1, and TLG1, respectively). Mean apparent diffusion coefficients were obtained from baseline and interim diffusion MR images (ADC0 and ADC1, respectively). The differences between the baseline and interim parameters were measured (ΔSUV, ΔMTV, ΔTLG, and ΔADC). Subgroup analysis was performed for the HER2-negative and triple-negative groups. Datasets for convolutional neural network (CNN), assigned as training (80%) and test datasets (20%), were cropped from the baseline (PET0, MRI0) and interim (PET1, MRI1) images. Histopathologic responses were assessed using the Miller and Payne system, after three cycles of chemotherapy. Receiver operating characteristic curve analysis was used to assess the performance of the differentiating responders and non-responders. There were six responders (11%) and 50 non-responders (89%). The area under the curve (AUC) was the highest for ΔSUV at 0.805 (95% CI 0.677–0.899). The AUC was the highest for ΔSUV at 0.879 (95% CI 0.722–0.965) for the HER2-negative subtype. AUC improved following CNN application (SUV0:PET0 = 0.652:0.886, SUV1:PET1 = 0.687:0.980, and ADC1:MRI1 = 0.537:0.701), except for ADC0 (ADC0:MRI0 = 0.703:0.602). PET/MRI image deep learning model can predict pathological responses to NAC in patients with advanced breast cancer.
Purpose For pediatric lymphoma, quantitative FDG PET/CT imaging features such as metabolic tumor volume (MTV) are important for prognosis and risk stratification strategies. However, feature extraction is difficult and time-consuming in cases of high disease burden. The purpose of this study was to fully automate the measurement of PET imaging features in PET/CT images of pediatric lymphoma. Methods 18F-FDG PET/CT baseline images of 100 pediatric Hodgkin lymphoma patients were retrospectively analyzed. Two nuclear medicine physicians identified and segmented FDG avid disease using PET thresholding methods. Both PET and CT images were used as inputs to a three-dimensional patch-based, multi-resolution pathway convolutional neural network architecture, DeepMedic. The model was trained to replicate physician segmentations using an ensemble of three networks trained with 5-fold cross-validation. The maximum SUV (SUVmax), MTV, total lesion glycolysis (TLG), surface-area-to-volume ratio (SA/MTV), and a measure of disease spread (Dmaxpatient) were extracted from the model output. Pearson’s correlation coefficient and relative percent differences were calculated between automated and physician-extracted features. Results Median Dice similarity coefficient of patient contours between automated and physician contours was 0.86 (IQR 0.78–0.91). Automated SUVmax values matched exactly the physician determined values in 81/100 cases, with Pearson’s correlation coefficient (R) of 0.95. Automated MTV was strongly correlated with physician MTV (R = 0.88), though it was slightly underestimated with a median (IQR) relative difference of − 4.3% (− 10.0–5.7%). Agreement of TLG was excellent (R = 0.94), with median (IQR) relative difference of − 0.4% (− 5.2–7.0%). Median relative percent differences were 6.8% (R = 0.91; IQR 1.6–4.3%) for SA/MTV, and 4.5% (R = 0.51; IQR − 7.5–40.9%) for Dmaxpatient, which was the most difficult feature to quantify automatically. Conclusions An automated method using an ensemble of multi-resolution pathway 3D CNNs was able to quantify PET imaging features of lymphoma on baseline FDG PET/CT images with excellent agreement to reference physician PET segmentation. Automated methods with faster throughput for PET quantitation, such as MTV and TLG, show promise in more accessible clinical and research applications.
Ga-DOTATOC PET/CT has a higher diagnostic sensitivity than (111)In-pentetreotide scans with SPECT/CT. The TNR on PET/CT is higher than that of SPECT/CT, which also suggests the higher sensitivity of PET/CT. (111)In-pentetreotide SPECT/CT should be used carefully if it is used instead of (68)Ga-DOTATOC PET/CT.
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