Search

Abstract Activating cGAS‐STING pathway has great potential to achieve effective antitumor immunotherapy. However, mutant p53 (mutp53), a commonly observed genetic alteration in over 50% of human cancer, will impede the therapeutic performance of the cGAS‐STING pathway. Herein, multifunctional ZIF‐8@MnO2 nanoparticles are constructed to degrade mutp53 and facilitate the cGAS‐STING pathway. The synthesized ZIF‐8@MnO2 can release Zn2+ and Mn2+ in cancer cells to induce oxidative stress and cytoplasmic leakage of fragmented mitochondrial double‐stranded DNAs (dsDNAs). Importantly, the released Zn2+ induces variable degradation of multifarious p53 mutants through proteasome ubiquitination, which can alleviate the inhibitory effects of mutp53 on the cGAS‐STING pathway. In addition, the released Mn2+ further increases the sensitivity of cGAS to dsDNAs as immunostimulatory signals. Both in vitro and in vivo results demonstrate that ZIF‐8@MnO2 effectively promotes the cGAS‐STING pathway and synergizes with PD‐L1 checkpoint blockades, leading to remarkable regression of local tumors as well as distant metastases of breast cancer. This study proposes an inorganic metal ion‐based nanoplatform to enhance the cGAS‐STING‐mediated antitumor immunotherapy, especially to those tumors with mutp53 expression.

Abstract In the process of radiation therapy (RT), the cytotoxic effects of excited electrons generated from water radiolysis tend to be underestimated due to multiple biochemical factors, particularly the recombination between electrons and hydroxyl radicals (·OH). To take better advantage of radiolytic electrons, we constructed WO3 nanocapacitors that reversibly charge and discharge electrons to regulate electron transportation and utilization. During radiolysis, WO3 nanocapacitors could contain the generated electrons that block electron-·OH recombination and contribute to the yield of ·OH at a high level. These contained electrons could be discharged from WO3 nanocapacitors after radiolysis, resulting in the consumption of cytosolic NAD+ and impairment of NAD+-dependent DNA repair. Overall, this strategy of nanocapacitor-based radiosensitization improves the radiotherapeutic effects by increasing the utilization of radiolytic electrons and ·OH, warranting further validation in multiple tumour models and preclinical experiments.

Abstract Introduction Definitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50–50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation. Methods and analysis The ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization. Ethics and dissemination This trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations. Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.

PurposeThe purpose of this study was to evaluate the accuracy of a lung stereotactic body radiotherapy (SBRT) treatment plan with the target of a newly predicted internal target volume (ITVpredict) and the feasibility of its clinical application. ITVpredict was automatically generated by our in-house deep learning model according to the cone-beam CT (CBCT) image database.MethodA retrospective study of 45 patients who underwent SBRT was involved, and Mask R-CNN based algorithm model helped to predict the internal target volume (ITV) using the CBCT image database. The geometric accuracy of ITVpredict was verified by the Dice Similarity Coefficient (DSC), 3D Motion Range (R3D), Relative Volume Index (RVI), and Hausdorff Distance (HD). The PTVpredict was generated by ITVpredict, which was registered and then projected on free-breath CT (FBCT) images. The PTVFBCT was margined from the GTV on FBCT images gross tumor volume on free-breath CT (GTVFBCT). Treatment plans with the target of Predict planning target volume on CBCT images (PTVpredict) and planning target volume on free-breath CT (PTVFBCT) were respectively re-established, and the dosimetric parameters included the ratio of the volume of patients receiving at least the prescribed dose to the volume of PTV (R100%), the ratio of the volume of patients receiving at least 50% of the prescribed dose to the volume of PTV in the Radiation Therapy Oncology Group (RTOG) 0813 Trial (R50%), Gradient Index (GI), and the maximum dose 2 cm from the PTV (D2cm), which were evaluated via Plan4DCT, plan which based on PTVpredict (Planpredict), and plan which based on PTVFBCT (PlanFBCT).ResultThe geometric results showed that there existed a good correlation between ITVpredict and ITV on the 4-dimensional CT [ITV4DCT; DSC= 0.83 ±0.18]. However, the average volume of ITVpredict was 10% less than that of ITV4DCT (p = 0.333). No significant difference in dose coverage was found in V100% for the ITV with 99.98 ± 0.04% in the ITV4DCT vs. 97.56 ± 4.71% in the ITVpredict (p = 0.162). Dosimetry parameters of PTV, including R100%, R50%, GI and D2cm showed no statistically significant difference between each plan (p > 0.05).ConclusionDosimetric parameters of Planpredict are clinically comparable to those of the original Plan4DCT. This study confirmed that the treatment plan based on ITVpredict produced by our model could automatically meet clinical requirements. Thus, for patients undergoing lung SBRT, the model has great potential for using CBCT images for ITV contouring which can be used in treatment planning.

Purpose: This study aims to develop a deep learning (DL)-based (Mask R-CNN) method to predict the internal target volume (ITV) in cone beam computed tomography (CBCT) images for lung stereotactic body radiotherapy (SBRT) patients and to evaluate the prediction accuracy of the model using 4DCT as ground truth. Methods and Materials: This study enrolled 78 phantom cases and 156 patient cases who received SBRT treatment. We used a novel DL model (Mask R-CNN) to identify and delineate lung tumor ITV in CBCT images. The results of the DL-based method were compared quantitatively with the ground truth (4DCT) using 4 metrics, including Dice Similarity Coefficient (DSC), Relative Volume Index (RVI), 3D Motion Range (R 3D ), and Hausdorff Surface Distance (HD). Paired t -tests were used to determine the differences between the DL-based method and manual contouring. Results: The DSC value for 4DCT MIP versus CBCT is 0.86 ± 0.16 and for 4DCT AVG versus CBCT is 0.83 ± 0.18, indicating a high similarity of tumor delineation in CBCT and 4DCT. The mean Accuracy Precision (mAP), R 3D , RVI, and HD values for phantom evaluation are 0.94 ± 0.04, 1.37 ± 0.36, 0.79 ± 0.02, and 6.79 ± 0.68, respectively. For patient evaluation, the mAP, R 3D , RVI, and HD achieved averaged values of 0.74 ± 0.23, 2.39 ± 1.59, 1.27 ± 0.47, and 17.00 ± 19.89, respectively. These results showed a good correlation between predicted ITV and manually contoured ITV. The phantom p -value for RVI, R 3D , and HD are 0.75, 0.08, 0.86, and patient p -value are 0.53, 0.07, 0.28, respectively. These p -values for phantom and patient showed no significant difference between the predicted ITV and physician's manual contouring. Conclusion: The current improved method (Mask R-CNN) yielded a good similarity between predicted ITV in CBCT and the manual contouring in 4DCT, thus indicating great potential for using CBCT for patient ITV contouring.

Purpose: A novel in-house technology “Non-Uniform VMAT (NU-VMAT)” was developed for automated cardiac dose reduction and treatment planning optimization in the left breast radiotherapy. Methods: The NU-VMAT model based on I GM (gantry MLC Movement coefficient index) was established to optimize the volumetric modulated arc therapy (VMAT) MLC movement and modulation intensity in certain gantry angles. The ESAPI embedded in Eclipse® was employed to connect TPS and the optimization program via I/O relevant DICOM RT files. The adjuvant whole-breast radiotherapy of 14 patients with left breast cancer was replanned using our NU-VMAT technology in comparison with VMAT and IMRT technology. Dosimetric parameters including D 1% , D 99% , and D mean of PTV, V 5 , V 10 , and V 20 of ipisilateral lung, V 5 , D 20 , D 30 , and D mean of heart, monitor units (MUs), and delivery time derived from IMRT, VMAT, and NU-VMAT plans were evaluated for plan quality and delivery efficiency. The quality assurance (QA) was conducted using both point-dose and planar-dose measurements for all treatment plans. Results: The I GM−NU−VMAT curves with plan optimization (range from 50% to 147%) were converged more significantly than I GM - VMAT curves (range from 0% to 297%). The dose distribution requirements of the target and normal tissues could be met using IMRT, VMAT, or NU-VMAT; the lowest D mean was achieved in NU-VMAT plans (5.38 ± 0.46 Gy vs 5.63 ± 0.61 Gy in IMRT and 7.95 ± 0.52 Gy in VMAT plans). Statistically significant differences were found in terms of delivery time and MU when comparing IMRT with VMAT and NU-VMAT plans ( P

Background: This study aims to establish lung biologically effective dose (BED)–based uniform dosimetric constraints for minimizing the risk of symptomatic radiation pneumonitis (SRP) from stereotactic body radiation therapy (SBRT) using variable fractionations in patients with lung tumors.Materials and Methods: A total of 102 patients with primary or oligometastatic lung tumors treated with SBRT in our institution were enrolled into this study. The associations between the clinical and dosimetric parameters and the incidences of SRP were analyzed using univariate and multivariate Cox regression hazard models. The receiver operating characteristic (ROC) curve was generated to evaluate the predictive performance of lung BED on the SRP risk compared with the physical dose.Results: SRP occurred in 11 patients (10.8%). In univariate analysis, the mean lung dose (p = 0.002), V5 (p = 0.005), V20 (p < 0.001), and the percentage of non-target normal lung volume receiving more than a BED of 5–170 Gy (VBED5−170, p < 0.05) were associated with SRP. Multivariate logistic regression analysis showed that there existed a significant statistical correlation between SRP and VBED70 (p < 0.001), which performed better than V5 or V20 on the ROC curves, resulting in an optimal cut-off value of lung VBED70 of 2.22%.Conclusions: This retrospective study indicated that non-target lung BED may better predict SRP from patients with SBRT-treated lung cancer. Limiting the lung VBED70 below 2.22% may be favorable to reduce the incidence of SRP, which warranted further prospective validation.

Background and objective Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice. Methods The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. Results Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. Conclusion A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.

Precision medicine demands accurate assessment of tumor response to therapies with the purpose of timely optimization or adjustment of the given treatment regimens. Chemoradiation remains the standard of care in advanced lung cancers and imaging-based noninvasive response evaluation could improve therapeutic efficacy and reduce treatment-related severe side effects. In this review, we overviewed the applications and pitfalls of major imaging modalities in response evaluation in lung cancer from a quantitative perspective. The development of radiomics will provide more precise information for treatment predicting, evaluation and prognosis.

PURPOSEWe aimed to explore the value of localizing small ground-glass nodules (GGNs;

Introduction Concurrent chemoradiation is the standard therapy for patients with local advanced oesophageal carcinoma unsuitable for surgery. Paclitaxel is an active agent against oesophageal cancer and it has been proved as a potent radiation sensitiser. There have been multiple studies evaluating paclitaxel-based chemoradiation in oesophageal cancer, of which the results are inspiring. However, which regimen, among cisplatin (TP), carboplatin (TC) or fluorouracil (TF) in combination with paclitaxel concurrent with radiotherapy, provides best prognosis with minimum adverse events is still unknown and very few studies focus on this field. The purpose of this study is to confirm the priority of TF to TP or TF to TC concurrent with radiotherapy in terms of overall survival and propose a feasible and effective plan for patients with local advanced oesophageal cancer. Methods and analysis ESO-Shanghai 2 is a three-arm, multicenter, open-labelled, randomised phase III clinical trial. The study was initiated in July 2015 and the duration of inclusion is expected to be 4 years. The study compares two pairs of regimen: TF versus TP and TF versus TC concurrent with definitive radiotherapy for patients with oesophageal squamous cell carcinoma (OSCC). Patients with histologically confirmed OSCC (clinical stage II, III or IVa based on the sixth Union for International Cancer Control-tumour, node, metastasis classification) and without any prior treatment of chemotherapy, radiotherapy or surgery against oesophageal cancer will be eligible. A total of 321 patients will be randomised and allocated in a 1:1:1 ratio to the three treatment groups. Patients are stratified by lymph node status (N0, N1, M1a). The primary endpoint is overall survival and the secondary endpoint is progression-free survival and adverse events. [ABSTRACT FROM AUTHOR]

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance. [ABSTRACT FROM AUTHOR]