Deep-learning-driven dose prediction and verification for stereotactic radiosurgical treatment of isolated brain metastases.

Purpose: While deep learning has shown promise for automated radiotherapy planning, its application to the specific scenario of stereotactic radiosurgery (SRS) for brain metastases using fixed-field intensity modulated radiation therapy (IMRT) on a linear accelerator remains limited. This work aimed to develop and verify a deep learning-guided automated planning protocol tailored for this scenario. Methods: We collected 70 SRS plans for solitary brain metastases, of which 36 cases were for training and 34 for testing. Test cases were derived from two distinct clinical institutions. The envisioned automated planning process comprised (1): clinical dose prediction facilitated by deep-learning algorithms (2); transformation of the forecasted dose into executable plans via voxel-centric dose emulation (3); validation of the envisaged plan employing a precise dosimeter in conjunction with a linear accelerator. Dose prediction paradigms were established by engineering and refining two three-dimensional UNet architectures (UNet and AttUNet). Input parameters encompassed computed tomography scans from clinical plans and demarcations of the focal point alongside organs at potential risk (OARs); the ensuing output manifested as a 3D dose matrix tailored for each case under scrutiny. Results: Dose estimations rendered by both models mirrored the manual plans and adhered to clinical stipulations. As projected by the dual models, the apex and average doses for OARs did not deviate appreciably from those delineated in the manual plan (P-value≥0.05). AttUNet showed promising results compared to the foundational UNet. Predicted doses showcased a pronounced dose gradient, with peak concentrations localized within the target vicinity. The executable plans conformed to clinical dosimetric benchmarks and aligned with their associated verification assessments (100% gamma approval rate at 3 mm/3%). Conclusion: This study demonstrates an automated planning technique for fixed-field IMRT-based SRS for brain metastases. The envisaged plans met clinical requirements, were reproducible across centers, and achievable in deliveries. This represents progress toward automated paradigms for this specific scenario.

Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma.

Importance: The optimal treatment for and potential benefit populations of synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC) remain unclear. Objectives: To evaluate outcomes of concurrent chemoradiotherapy (CCRT) and to construct decision tree models for predicting the risk of progression and mortality in patients with SOESCC. Design, Setting, and Participants: This prognostic study included 532 patients with SOESCC who were treated at 2 cancer centers in China from January 2012 to December 2018 and consisted of a development cohort (n = 381) and a validation cohort (n = 151). Data were analyzed from March 2019 to December 2021. Exposures: All patients received chemotherapy alone or CCRT. Main Outcomes and Measures: The primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were locoregional control and treatment-related toxic effects. Propensity score matching was performed to control potential confounding factors. Cox regression was used to screen important explanatory variables. Decision trees for optimally partitioning patients were established using recursive partitioning analysis and were then subjected to internal and independent external validation. Results: Among the 532 patients (median [range] age, 63 [32-82] years; 367 men [69.0%]), 292 patients received chemotherapy alone and 240 patients underwent CCRT. With a median (IQR) follow-up time of 37.0 (21.6-55.8) months, CCRT was associated with improved objective response rate (139 of 240 [57.9%] vs 123 of 292 [42.1%]; P < .001), median (IQR) PFS (9.7 [8.5-10.9] months vs 7.6 [6.6-8.6] months; P < .001), and median (IQR) OS (18.5 [16.1-20.9] months vs 15.2 [13.6-16.8] months; P < .001) compared with chemotherapy alone. Propensity score matching analysis verified the results. Cox multivariate analysis indicated that treatment modality (CCRT vs chemotherapy alone) was an independent prognostic factor related to PFS (hazard ratio, 0.69; 95% CI, 0.57-0.83; P < .001) and OS (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008). The final decision trees divided patients with SOESCC into low-, intermediate-, and high-risk groups in both the internal and external validations, and the corresponding cumulative risk function curves had significant differences (all P < .001). Time-dependent maximum areas under receiver operating curves of decision trees for progression risk at 3 years and mortality risk at 5 years were 0.820 (95% CI, 0.693-0.948) and 0.894 (95% CI, 0.822-0.966), respectively. Calibration curves also demonstrated that the decision trees had favorable performance of risk stratification. Conclusions and Relevance: In this study, CCRT vs chemotherapy alone as a first-line treatment for patients with SOESCC had superior survival. Patients with low risk had promising long-term survival based on the current treatment modality. The predictive information of the decision tree could provide accurate decision-making for the management of patients with SOESCC.

Notoginsenoside R1 induces oxidative stress and modulates LPS induced immune microenvironment of nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor with high incidence. Notoginsenoside R1 (NGR1) is the main active compound of total Panax notoginseng saponin, and has multiple anti-tumor effects. This study aimed to investigate the effect and mechanism of NGR1 in NPC. MATERIALS: NPC cells were treated with different doses of NGR1. The NGR1 function in NPC was evaluated using Cell Counting Kit-8, Transwell, Western blot, flow cytometry, immunofluorescence assay, and quantitative real-time PCR. Meanwhile, the NGR1 mechanism in NPC was assessed by rescue experiments. Furthermore, the NGR1 function in vivo was determined by constructing an NPC xenotransplantation model, TUNEL, and immunohistochemistry assays. RESULTS: NGR1 repressed NPC cell growth and invasion but facilitated NPC cell apoptosis and oxidative stress. Also, NGR1 alleviated inflammation in NPC cells. Mechanistically, NGR1 restrained NPC cell growth and induced oxidative stress in NPC cells, while these effects were abolished after lipopolysaccharide (an activator of the TRAF6/NF-κB pathway) treatment, implying that NGR1 reduced NPC cell growth and induced oxidative stress in NPC cells by the inactivation of TRAF6/NF-κB axis. Moreover, in vivo studies further proved the palliative effect of NGR1 on NPC. CONCLUSION: NGR1 inhibited NPC cell growth and induced oxidative stress in NPC cells by inactivating TRAF6/NF-κB axis.

Anticancer effects of Lanostane against human gastric cancer cells involves autophagy, apoptosis and modulation of m-TOR/PI3K/AKT signalling pathway.

PURPOSE: Gastric carcinoma is the fourth leading cause of cancer-related morbidity throughout the globe. There are limited clinical therapies for gastric cancer due to lack of effective drugs and ambiguity in molecular mechanisms. As such there is a pressing need for novel and effective anticancer drugs for gastric cancer. The main aim of the current research work was to investigate the anticancer effects of Lanostane natural product in MKN-45 human gastric cancer cells along with evaluating its effects on cell autophagy, apoptosis, and m-TOR/PI3K/AKT signalling pathway. METHODS: MTT cytotoxicity assay was used to evaluate cell viability of MKN-45 human gastric cancer cells. Apoptosis was evaluated by fluorescence microscopy using Hoechst 33258 and Annexin-V/propidium iodide (PI) assay using flow cytometry. Autophagy was evaluated by transmission electron microscopy (TEM) and western blot method. Effects on m-TOR/PI3K/AKT related protein expression were evaluated by western blot method. RESULTS: Lanostane molecule led to substantial and dose-dependent growth inhibitory effects onMKN-45 human gastric cancer cells. Clonogenic assay showed significant decrease in MKN-45 cell colonies. Hoechst 33258 and annexin V/PI revealed that lanostane induced dominant apoptotic effects in these cells and exhibited dose-dependence. TEM revealed that lanostane induced autophagy in MKN-45 cells by forming autophagosomes and autophagic vacuoles. Lanostane also targeted m-TOR/PI3K/AKT signalling pathway by altering the expression of some key proteins. CONCLUSION: Lanostane displayed strong anticancer effects in MKN-45 human gastric cancer cells by triggering apoptosis and autophagy and targeting m-TOR/PI3K/AKT signalling pathway.

Dosimetric Comparison of Three Radiotherapy Techniques in Irradiation of Left-Sided Breast Cancer Patients after Radical Mastectomy.

RESULTS: The VMAT plans showed superior to PTV dose conformity index (CI), homogeneity index (HI), protection of the ipsilateral lung, monitor units (MUs), and maximum dose (Dmax) to the contralateral breast compared with TSP and 9FIMRT plans. The TSP provided better protection for Dmean of the heart and left ventricle (p < 0.05). A dose for left anterior descending artery from the three techniques had no significant difference. Compared with the 9FIMRT plans, the V5Gy (%) and V10Gy (%) for the ipsilateral lung were significantly reduced with TSP and VMAT (p < 0.05). The V5Gy (%) and V10Gy (%) for the ipsilateral lung turned out to be similar between VMAT and TSP techniques. CONCLUSIONS: Our study indicates that VMAT should be a better choice of radiotherapy for left-sided breast cancer patients after radical mastectomy. If VMAT is unavailable, 9FIMRT can achieve better CI and HI values and be more MU-efficient compared with TSP; however, TSP can effectively reduce the low dose volume of the ipsilateral lungs and heart.

Comparison of geometrical uncertainties in the radiotherapy for various treatment sites with two different immobilization marking methods.

OBJECTIVE: The skin marking method (SMM) and bow-form-ruler marking method (BFRM) are two commonly used patient marking methods in mainland China. This study aims to evaluate SMM and BFRM by comparing the inter-fraction setup errors from using these two methods together with vacuum cushion immobilization in patients underwent radiotherapy for different treatment sites. MATERIALS AND METHODS: Eighteen patients diagnosed with pelvic, abdominal and thoracic malignant tumors (with 6 patients per treatment site) were enrolled in this prospective study. All patients were immobilized with vacuum cushion. Each patient was marked by both SMM and BFRM before computed tomography (CT) simulation. Target location was verified by cone beam CT images with displacements assessed prior to each sampled treatment session. The localization errors in three translational and three rotational directions were recorded and analyzed. RESULTS: Images from 108 fractions in 18 patients produced 324 translational and 324 rotational comparisons for SMM and BFRM. The setup errors of all treatment sites showed no difference in two marking methods in any directions (p > 0.05). In subgroups of treatment site analysis, SMM significantly lessened the lateral and yaw setup errors compared to BFRM in the pelvic sites (0.39±1.85 mm vs -1.28±1.13 mm, p < 0.01 and -0.19±0.59° vs -0.61±0.59°, p < 0.05). However, in the abdominal subgroup, BFRM was superior to SMM for reduced vertical errors (0.17±2.73 mm vs 2.28±3.16 mm, p < 0.05). For the underweight or obese patients (with Body Mass Index, BMI < 18.5 or BMI≥24), SMM resulted in less yaw errors compared to BFRM (-0.05±0.38° vs -0.43±0.48°, p < 0.05). No significant difference between SMM and BFRM in setup errors of normal weighted patients (18.5≤BMI < 24) was observed for all three studied treatment sites. CONCLUSIONS: This study shows no significant difference in patient setup errors for various treatment sites between SMM and BFRM in general. SMM may be suitable for the pelvic tumor and patients with BMI < 18.5 or BMI≥24, while BFRM is recommended for the abdominal tumor sites.

[Application of Imaging-Guided Radiation Therapy in Pelvic Tumor Radiotherapy].

OBJECTIVE: To discuss the influence of setup errors on the accuracy of pelvic cancer in IGRT, analysis setup errors and determine the CTV-to-PTV margins. METHODS: 60 pelvic cancer patients treated with Varian 23IX, all of them were performed by CBCT before and after-correction three times in the first week and after that once a week. Then, to measure the setup errors at X(left-right), Y(superior-inferior), Z(anterior-posterior) axis and E(coronal), F(sagittal), G(axial) rotation directions. RESULTS: 530 scans obtained in all, the setup errors in X, Y, Z, E, F, G were (-0.52 ± 4.18) mm, (0.73 ± 4.86) mm, (-0.36 ± 3.62) mm, (0.14 ± 1.20)degrees, (0.13 ± 1.34)degrees, (0.21 ± 1.73)degrees respectively and were much lower after correction at X, Y, Z axis, besides, CTV-to-PTV margins decrease a lot. CONCLUSION: The accuracy of radiotherapy can be highly increased with the use of IGRT in pelvic cancer.