Acute hematologic toxicity prediction using dosimetric and radiomics features in patients with cervical cancer: does the treatment regimen matter?

BackgroundAcute hematologic toxicity (HT) is a prevalent adverse tissue reaction observed in cervical cancer patients undergoing chemoradiotherapy (CRT), which may lead to various negative effects such as compromised therapeutic efficacy and prolonged treatment duration. Accurate prediction of HT occurrence prior to CRT remains challenging.MethodsA discovery dataset comprising 478 continuous cervical cancer patients (140 HT patients) and a validation dataset consisting of 205 patients (52 HT patients) were retrospectively enrolled. Both datasets were categorized into the CRT group and radiotherapy (RT)-alone group based on the treatment regimen, i.e., whether chemotherapy was administered within the focused RT duration. Radiomics features were derived by contouring three regions of interest (ROIs)—bone marrow (BM), femoral head (FH), and clinical target volume (CTV)—on the treatment planning CT images before RT. A comprehensive model combining the radiomics features as well as the demographic, clinical, and dosimetric features was constructed to classify patients exhibiting acute HT symptoms in the CRT group, RT group, and combination group. Furthermore, the time-to-event analysis of the discriminative ROI was performed on all patients with acute HT to understand the HT temporal progression.ResultsAmong three ROIs, BM exhibited the best performance in classifying acute HT, which was verified across all patient groups in both discovery and validation datasets. Among different patient groups in the discovery dataset, acute HT was more precisely predicted in the CRT group [area under the curve (AUC) = 0.779, 95% CI: 0.657–0.874] than that in the RT-alone (AUC = 0.686, 95% CI: 0.529–0.817) or combination group (AUC = 0.748, 95% CI: 0.655–0.827). The predictive results in the validation dataset similarly coincided with those in the discovery dataset: CRT group (AUC = 0.802, 95% CI: 0.669–0.914), RT-alone group (AUC = 0.737, 95% CI: 0.612–0.862), and combination group (AUC = 0.793, 95% CI: 0.713–0.874). In addition, distinct feature sets were adopted for different patient groups. Moreover, the predicted HT risk of BM was also indicative of the HT temporal progression.ConclusionsHT prediction in cervical patients is dependent on both the treatment regimen and ROI selection, and BM is closely related to the occurrence and progression of HT, especially for CRT patients

Curcumin-Induced Apoptosis in Human Hepatocellular Carcinoma J5 Cells: Critical Role of Ca+2-Dependent Pathway

The antitumor effects of curcumin, a natural biologically active compound extracted from rhizomes of Curcuma longa, have been studied in many cancer cell types including human hepatocellular carcinoma (HCC). Here, we investigated the effects of Ca2+ on curcumin-induced apoptosis in human HCC J5 cells. The abrogation of mitochondrial membrane potential (ΔΨm), the increase of reactive oxygen species (ROS) production, and calcium release were demonstrated with flow cytometry as early as 15 minutes after curcumin treatment. In addition, an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation was observed. To verify the role of Ca2+ in curcumin-induced apoptosis, 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), an intracellular calcium chelator, was applied. Cell viability was increased, but ΔΨm, ROS production, activation of caspase 3, and cell death were decreased in J5 cells pretreated with BAPTA for 2 h followed by the treatment of 25 μM curcumin. These results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via mitochondria-dependent pathway and is closely related to the level of intracellular accumulation of calcium