Analysis of the Parotid Glands on an Energy Spectrum CT Iodine Map to Evaluate Irradiation-Induced Acute Xerostomia in Patients With Nasopharyngeal Carcinoma.

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance (P < .001). There was a noticeable attenuation in NIC as the RTOG dry mouth grade increased. Particularly, at the 20 fraction, the NIC experienced the most substantial attenuation (P < .001), a significant negative correlation was observed between the NIC of the left, right, and both parotid glands, and the RTOG evaluation grade of acute irradiation-induced xerostomia (P < .001, r = -0.46; P < .001, r = -0.45; P < .001, r = -0.47). The critical NIC values for the left, right, and both parotid glands when acute xerostomia occurred were 0.175, 0.185, and 0.345 mg/ml, respectively, with AUC = 0.73, AUC = 0.75, and AUC = 0.75. Conclusion: The NIC may be used to evaluate changes in parotid gland function during radiotherapy and acute irradiation-induced xerostomia.

Dual-Responsive Turn-On T1 Imaging-Guided Mild Photothermia for Precise Apoptotic Cancer Therapy.

Apoptosis has gained increasing attention in cancer therapy as an intrinsic signaling pathway, which leads to minimal leakage of waste products from a dying cell to neighboring normal cells. Among various stimuli to trigger apoptosis, mild hyperthermia is attractive but confronts limitations of non-specific heating and acquired resistance from elevated expression of heat shock proteins. Here, a dual-stimulation activated turn-on T1 imaging-based nanoparticulate system (DAS) is developed for mild photothermia (≈43 °C)-mediated precise apoptotic cancer therapy. In the DAS, a superparamagnetic quencher (ferroferric oxide nanoparticles, Fe3 O4 NPs) and a paramagnetic enhancer (Gd-DOTA complexes) are connected via the N6-methyladenine (m6 A)-caged, Zn2+ -dependent DNAzyme molecular device. The substrate strand of the DNAzyme contains one segment of Gd-DOTA complex-labeled sequence and another one of HSP70 antisense oligonucleotide. When the DAS is taken up by cancer cells, overexpressed fat mass and obesity-associated protein (FTO) specifically demethylates the m6 A group, thereby activating DNAzymes to cleave the substrate strand and simultaneously releasing Gd-DOTA complex-labeled oligonucleotides. The restored T1 signal from the liberated Gd-DOTA complexes lights up the tumor to guide the location and time of deploying 808 nm laser irradiation. Afterward, locally generated mild photothermia works in concert with HSP70 antisense oligonucleotides to promote apoptosis of tumor cells. This highly integrated design provides an alternative strategy for mild hyperthermia-mediated precise apoptotic cancer therapy.

Novel CT based clinical nomogram comparable to radiomics model for identification of occult peritoneal metastasis in advanced gastric cancer.

BACKGROUND: Occult peritoneal metastasis (OPM) in advanced gastric cancer (AGC) patients remains a major diagnostic challenge. The aim of this study was to develop novel predictive models for identification of OPM in AGCs. METHOD: A total of 810 patients with primary AGCs from two hospitals were retrospectively selected and divided into training (n = 393), internal validation (n = 215) and external validation cohorts (n = 202). CT based machine learning models were built and tested to predict the OPM status in AGCs., which are 1) Radiomic signatures: using venous CT imaging features, 2) Clinical models: integrating tumor location, differentiation and extent of serosal exposure, and 3) Radiomics models: combining of radiomic signature, tumor location and tumor differentiation. RESULT: Total incidence of OPM was 8.27% (67/810). Clinical models yielded comparable classification accuracy with the corresponding radiomics models with similar AUCs (0.902-0.969 vs. 0.896-0.975) while the radiomic signatures showed relatively low AUCs of 0.863-0.976. In the case where the specificity is higher than 90%, the overall sensitivity of clinical model and radiomics model for OPM positive cases was 76.1% (51/67) and 82.1% (55/67). A nomogram based on the logistic clinical model was drawn to facilitate the usage and verification of the clinical model. CONCLUSION: Both the novel CT based clinical nomogram and radiomics model provide promising method to yield high accuracy in identification of OPM in AGC patients.

Preoperative Muscle-Adipose Index: A New Prognostic Factor for Gastric Cancer.

BACKGROUND: Studies have shown that traditional nutrition indicators and body composition indicators are closely related to prognosis after radical gastric cancer (GC) surgery. However, the effect of the combined muscle and adipose composite on the prognosis of GC has not been reported. METHODS: The clinicopathological data of 514 patients with GC were retrospectively analyzed. The skeletal muscle adipose tissue were measured by preoperative CT images to obtain the muscle index and adipose index. X-tile software was used to determine the diagnostic threshold of muscle-adipose imbalance. RESULTS: The 5-year OS and RFS of the muscle-adipose imbalanced group were significantly worse than those of the balanced group. Multivariate analysis showed that muscle-adipose imbalance and the CONUT score were independent prognostic factors of OS and RFS (p < 0.05). The nuclear density curve showed that the recurrence risk of the muscle-adipose imbalanced group was higher than that of the balanced group, whereas the nuclear density curve of the CONUT score was confounded. Incorporating the muscle-adipose index into cTNM has the same prognostic performance as the pTNM staging system. Chemotherapy-benefit analysis showed that stage II/III patients in the muscle-adipose balanced group could benefit from adjuvant chemotherapy. CONCLUSIONS: The preoperative muscle-adipose index discovered for the first time is a new independent prognostic factor that affects the prognosis with GC. In addition, the preoperative muscle-adipose index is better than traditional nutrition and body composition indicators in terms of the prognostic evaluation of GC patients and the predictive value of recurrence risk.

Magnetothermally Triggered Free-Radical Generation for Deep-Seated Tumor Treatment.

Tumor hypoxia and the tissue penetration limitation of excitation light hamper the widespread clinical use of photodynamic therapy. The development of new therapeutic strategies that can generate oxygen-independent free radicals without penetration depth limitation is of great demand. Herein, a novel magnetothermodynamic strategy for deep-seated tumor therapy is reported. In this system, a radical initiator (AIPH) was loaded into porous hollow iron oxide nanoparticles (PHIONs). Under the induction of an alternating magnetic field (AMF), PHIONs can generate heat to trigger the release and decomposition of AIPH, resulting in the generation of oxygen-independent alkyl radicals. The resulting alkyl radicals can effectively kill cancer cells under hypoxic conditions. More importantly, this magnetothermally triggered free-radical generator exhibits significant therapeutic efficacy for orthotopic liver tumors in a rat model. This magnetothermodynamic therapy strategy with the advantages of oxygen independence and no limitation of penetration depth holds great promise in deep-seated solid tumor treatment.

CT-based radiomics nomogram for preoperative prediction of No.10 lymph nodes metastasis in advanced proximal gastric cancer.

INTRODUCTION: Preoperative diagnosis of No.10 lymph nodes (LNs) metastases in advanced proximal gastric cancer (APGC) patients remains a challenge. The aim of this study was to develop a CT-based radiomics nomogram for identification of No.10 LNs status in APGCs. MATERIALS AND METHODS: A total of 515 patients with primary APGCs were retrospectively selected and divided into a training cohort (n = 340) and a validation cohort (n = 175). Total incidence of No.10 LNM was 12.4% (64/515). CT based radiomics nomogram combining with radiomic signature calculated from venous CT imaging features and CT-defined No.10 LNs status evaluated by radiologists was built and tested to predict the No.10 LNs status in APGCs. RESULTS: CT based radiomics nomogram yielded classification accuracy with areas under ROC curves, AUC = 0.896 and 0.814 in training and validation cohort, respectively, while radiomic signature and radiologist' diagnosis based on contrast-enhanced CT images yielded lower AUCs ranging in 0.742-0.866 and 0.619-0.685, respectively. In the specificity higher than 80%, the sensitivity of using radiomics nomogram, radiomic signature and radiologists' evaluation to detect No.10 LNs positive cases was 82.8% (53/64), 67.2% (43/64) and 39.1% (25/64), respectively. CONCLUSIONS: The CT-based radiomics nomogram provides a promising and more effective method to yield high accuracy in identification of No.10 LNs metastases in APGC patients.

Evaluation of the Therapeutic Effect of Magneto-Nanomicelles Based on Magneto-Thermal and Photo-Thermal Therapy.

In this study, we investigated the hyperthermia efficiency of magnetic hyperthermia therapy (MHT), photo-thermal therapy (PTT), and the combination of both techniques by employing SPIO-based magneto-nanomicelles as the heating agents. Magneto-nanomicelles in aqueous suspension were exposed to 808-nm laser irradiation (PTT mode), alternating magnetic field (MHT mode), and both modalities (DUAL mode). All the three methods can offer effective temperature increases (above 20 °C). DUAL-mode resulted in an approximately 2-fold increase in heating efficiency (36 °C) compared with PTT or MHT alone. For in vivo experiments, a total of 24 Lewis carcinoma-bearing mice were randomly divided into four groups: the control group (no therapy), PTT, MHT, and DUAL group. In the three therapy groups, magneto-nanomicelles were injected into the tumor and the corresponding treatment measures were performed every other day for a total of three times each. MRI scans were used to calculate tumor volume after each treatment. One-way analysis of variance (ANOVA) was employed to compare the curative effect of different treatment groups. Compared with the control group, PTT, MHT, and DUAL groups all showed a significant inhibitory effect on tumor volume (P < 0.05). In the DUAL group, the mean tumor volume was smaller than that of the PTT or the MHT group. Our work demonstrated that hyperthermia using SPIO-based magnetonanomicelles has a remarkable suppressive effect in anticancer therapy. Moreover, the combined model of hyperthermia in vivo can achieve synthetic effects with shorter healing time by using the same magneto-nanomicelles.

Iron phosphide nanoparticles as a pH-responsive T 1 contrast agent for magnetic resonance tumor imaging.

In this work, the potential of FeP nanoparticles as a pH-responsive T 1 contrast agent was investigated. The FeP nanoparticles have good biocompatibility and can significantly amplify T 1 magnetic resonance signals in response to the acidic microenvironment of solid tumors, holding great promise in serving as an acid-activatable T 1 contrast agent for tumor imaging.