CT-based radiomics combined with hematologic parameters for survival prediction in locally advanced esophageal cancer patients receiving definitive chemoradiotherapy.

OBJECTIVES: The purpose of this study was to investigate the prognostic significance of radiomics in conjunction with hematological parameters in relation to the overall survival (OS) of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy (dCRT). METHODS: In this retrospective analysis, a total of 122 patients with locally advanced ESCC were included. These patients were randomly assigned to either the training cohort (n = 85) or the validation cohort (n = 37). In the training group, the least absolute shrinkage and selection operator (LASSO) regression was utilized to choose the best radiomic features for calculating the Rad-score. To develop a nomogram model, both univariate and multivariate analyses were conducted to identify the clinical factors and hematologic parameters that could predict the OS. The performance of the predictive model was evaluated using the C-index, while the accuracy was assessed through the calibration curve. RESULTS: The Rad-score was calculated by selecting 10 radiomic features through LASSO regression. OS was predicted independently by neutrophil-to-monocyte ratio (NMR) and Rad-score according to the results of multivariate analysis. Patients who had a Rad-score > 0.47 and an NMR > 9.76 were at a significant risk of mortality. A nomogram was constructed using the findings from the multivariate analysis. In the training cohort, the nomogram had a C-index of 0.619, while in the validation cohort, it was 0.573. The model's accuracy was demonstrated by the calibration curve, which was excellent. CONCLUSION: A prognostic model utilizing radiomics and hematologic parameters was developed, enabling the prediction of OS in patients with ESCC following dCRT. CRITICAL RELEVANCE STATEMENT: Patients with esophageal cancer who underwent definitive chemoradiotherapy may benefit from including CT radiomics in the nomogram model. KEY POINTS: • Predicting the prognosis of ESCC patients before treatment is particularly important. • Patients with a Rad-score > 0.47 and neutrophil-to-monocyte ratio > 9.76 had a high risk of mortality. • CT-based radiomics nomogram model could be used to predict the survival of patients.

Recurrence/prognosis estimation using a molecularly positive surgical margin-based model calls for alternative curative strategies in pIIIA/N2 NSCLC.

Stage pIIIA/N2 non-small cell lung cancer (NSCLC) is primarily treated by complete surgical resection combined with neoadjuvant/adjuvant therapies. However, up to 40% of patients experience tumor recurrence. Here, we studied 119 stage pIIIA/N2 NSCLC patients who received complete surgery plus adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). The paired tumor and resection margin samples were analyzed using next-generation sequencing (NGS). Although all patients were classified as negative resection margins by histologic methods, NGS revealed that 47.1% of them had molecularly positive surgical margins. Patients who tested positive for NGS-detected residual tumors had significantly shorter disease-free survival (DFS) (P = 0.002). Additionally, metastatic lymph node ratio, erb-b2 receptor tyrosine kinase 2 (ERBB2) mutations, and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations were also independently associated with DFS. We used these four features to construct a COX model that could effectively estimate recurrence risk and prognosis. Notably, mutational profiling through broad-panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.

Novel model integrating computed tomography-based image markers with genetic markers for discriminating radiation pneumonitis in patients with unresectable stage III non-small cell lung cancer receiving radiotherapy: a retrospective multi-center radiogenomics study.

BACKGROUND: Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC. METHODS: In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively. RESULTS: The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram. CONCLUSION: Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.

Association of antibiotic exposure with survival in patients with extensive-stage small cell lung cancer receiving immune checkpoint inhibitor therapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically shifted the therapeutic paradigm of extensive-stage small cell lung cancer (ES-SCLC). Antibiotic (ATB) exposure before or during ICI therapy can harm the integrity of the gut microbiome and lead to intestinal dysbiosis, which has a profoundly negative impact on the treatment response for various malignancies. Whether this is applicable to ES-SCLC remains unclear. METHODS: We retrospectively reviewed the electronic medical records of all patients diagnosed with ES-SCLC who were treated with ICI-based immunotherapies from July 2019 to December 2020 at Shandong Cancer Hospital and Institute, China. Outcomes with the use of ATBs before or after the first infusion of ICI, including progression-free survival (PFS) and overall survival (OS), were investigated using the Kaplan-Meier method. Multivariate analyses were also conducted using a Cox proportional hazards model. RESULTS: A total of 214 patients were included, among whom 41 (19.2%) received ATBs within 2 months before or after the first initiation of ICI therapy and were assigned to the ATB group. The ATB group showed a shorter median PFS (4.3 vs. 6.3 months; HR = 1.43, 95% CI: 0.97-2.11; p = 0.043) and a significantly shorter median OS (6.9 vs. 13 months; HR = 1.47, 95% CI: 0.98-2.20; p = 0.033) than the non-ATB group. In the multivariate analysis, ATB exposure was markedly associated with worse PFS (HR = 1.47, 95% CI: 1.03-2.09, p = 0.035) and OS (HR = 1.46, 95% CI: 1.01-2.11, p = 0.043). CONCLUSIONS: Our results demonstrate that ATB exposure was significantly associated with worse survival in ES-SCLC patients who received ICI therapy.

Tertiary lymphoid structures combined with biomarkers of inflammation are associated with the efficacy of neoadjuvant immunochemotherapy in resectable non-small cell lung cancer: A retrospective study.

BACKGROUND: Neoadjuvant immunochemotherapy can effectively downstage tumors and reduce the risk of postoperative recurrence and distant metastasis in patients with non-small cell lung cancer (NSCLC). In this study, we investigated the correlation between inflammatory biomarkers and tertiary lymphoid structure (TLS) expression. We also compared the predictive values of these inflammatory parameters, TLSs, and a combination of inflammatory parameters and TLSs for neoadjuvant efficacy in patients with NSCLC. METHODS: We retrospectively analyzed the clinical information of 106 patients with NSCLC who underwent neoadjuvant immunochemotherapy and radical surgery at Shandong Cancer Hospital between June 2020 and June 2022. RESULTS: TLS was evaluated using hematoxylin-eosin staining and immunohistochemically-stained tissue sections. Logistic analysis was performed to determine the correlation between inflammatory parameters, TLSs, and the factors affecting major pathological response (MPR). Receiver operating characteristic curves and the C-index were used to evaluate the predictive value of the nomogram models for MPR. The systemic immune-inflammatory index (SII) was an independent predictor of high TLS abundance and maturity. Platelet-to-lymphocyte ratio (PLR) ≤201.8, TLS abundance, and TLS maturity were independent predictors of MPR. The PLR-TLS combined model performed better in assessing the MPR in patients with NSCLC than models using single indicators. CONCLUSION: Our study demonstrated that the SII is an independent predictor of both TLS abundance and maturity. Both TLSs and PLR can predict MPR rates in patients with NSCLC receiving neoadjuvant immunochemotherapy. However, assessing the MPR in patients with NSCLC using a combination of PLR and TLSs is more accurate than using either indicator alone.

Value of [18F]AlF-NOTA-FAPI-04 PET/CT for differential diagnosis of malignant and various inflammatory lung lesions: comparison with [18F]FDG PET/CT.

OBJECTIVE: Uptake of the imaging tracers [18F]AlF-NOTA-FAPI-04 and [18F]FDG varies in some inflammatory lesions, which may result in false-positive findings for malignancy on PET/CT. Our aim was to compare the [18F]AlF-NOTA-FAPI-04 and [18F]FDG PET/CT imaging features of malignant and various inflammatory lung lesions and to analyze their value for differential diagnosis. METHODS: We retrospectively analyzed [18F]AlF-NOTA-FAPI-04 PET/CT scans from 67 cancer patients taken between December 2020 and January 2022, as well as the scans of 32 patients who also underwent [18F]FDG PET/CT imaging. The maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) and lesion-to-background ratio (LBR) were calculated. The predictive capabilities of semiquantitative PET/CT parameters were analyzed by receiver operating characteristic curve analysis. RESULTS: A total of 70 inflammatory and 37 malignant lung lesions were evaluated by [18F]AlF­NOTA­FAPI­04 PET/CT, and 33 inflammatory and 26 malignant lung lesions also were evaluated by [18F]FDG PET/CT. Inflammatory lesions exhibited lower [18F]AlF-NOTA-FAPI-04 and [18F]FDG uptake compared to malignant lesions, with statistically significant differences in SUVmax, SUVmean, and LBR (all p < 0.001). [18F]AlF-NOTA-FAPI-04 uptake also varied among different types of inflammatory lesions (SUVmax, p = 0.005; SUVmean, p = 0.008; LBR, p < 0.001), with the highest uptake observed in bronchiectasis with infection, followed by postobstructive pneumonia, and the lowest in pneumonia. [18F]FDG uptake was higher in postobstructive pneumonia than in pneumonia (SUVmax, p = 0.009; SUVmean, p = 0.016; LBR, p = 0.004). CONCLUSION: [18F]AlF-NOTA-FAPI-04/[18F]FDG PET/CT showed significantly lower uptake in inflammatory lesions than malignancies as well as variation in different types of inflammatory lesions, and thus, may be valuable for distinguishing malignant and various inflammatory findings. CLINICAL RELEVANCE STATEMENT: Our study confirmed that the uptake of [18F]AlF-NOTA-FAPI-04/[18F]FDG PET/CT in inflammatory and malignant lung lesions is different, which is beneficial to distinguish inflammatory and malignant lung lesions in clinic. KEY POINTS: • Malignant and different inflammatory lung lesions showed varying degrees of uptake of [18F]AlF-NOTA-FAPI-04 and [18F]FDG. • Inflammatory lung lesions showed significantly less uptake than malignancies, and uptake varied among different types of inflammatory lesions. • Both types of PET/CT could differentiate malignant and various inflammatory lung findings.

Effects of Radiotherapy and Chemotherapy on Platelet in Patients with Lung Cancer.

BACKGROUND: An animal study has shown that platelets form are formed in the lungs. Therefore, we wanted to study the relationship between lung radiation dose and platelet count in lung cancer patients receiving radiation therapy. METHODS: This retrospective study included 93 patients with lung cancer who received radical thoracic radiation therapy. The correlation between pulmonary dose-volume histogram (DVH) parameters and thrombocytopenia during radiotherapy (RT) was evaluated by chi-square test, logistic regression analysis, Spearman and Pearson correlation analysis, etc. Results: Thrombocytopenia occurred in 17 of 93 patients (18.3%). Chi-square test and logistic regression analysis showed that chemotherapy (p = 0.038), MLD (mean lung dose, p = 0.001), V5 (p = 0.008), V10 (p = 0.004), AND V20 (p = 0.003) were important independent predictors of thrombocytopenia. Using the chi-square test, increased MLD (p = 0.002), V5 (p = 0.021), V10 (p = 0.008), and V20 (p = 0.006) were associated with increased risk of thrombocytopenia. Receiver operating characteristic (ROC) curve was used to analyze the thresholds of MLD, V5, V10, and V20, which showed high sensitivity and specificity for distinguishing between non-thrombocytopenia and thrombocytopenia. CONCLUSIONS: Higher doses of radiation to the lung are associated with an increased risk of thrombocytopenia. Moreover, optimization of treatment plans via the control of DVH parameters may reduce treatment interruptions and improve outcomes in lung cancer patients treated with RT.

Combined inflammatory parameters and tertiary lymphoid structure predict prognosis in patients with resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy.

Introduction: Neoadjuvant chemoimmunotherapy shows great potential for patients with non-small cell lung cancer (NSCLC), but no clear prognostic markers have been identified. This study investigates the correlation between inflammatory parameters and the expression of tertiary lymphoid structures (TLS) and the predictive ability of inflammatory parameters combined with TLS for disease-free survival (DFS) in patients with resectable NSCLC receiving neoadjuvant chemotherapy. Materials and methods: We retrospectively analyzed the clinical data and hematological parameters of 117 patients with NSCLC who underwent neoadjuvant chemoimmunotherapy and radical surgery. TLS were evaluated by observing H&E stained and immunohistochemically stained tissue sections. Univariate chi-square and multifactor logistic analyses were used to determine the correlation between hematological parameters and TLS. The Kaplan-Meier method, univariate and multivariate Cox regression analysis and constructed nomogram models were used to assess the prognostic value of the investigated parameters on DFS. Receiver operating characteristic (ROC) curves analyses were used to compare the performances of the three models. Results: After logistic analysis, it was found that platelet-to-lymphocyte ratio (PLR) ≤288.78 (odds ratio OR=0.122, P=0.009) was an independent predictor of high TLS expression. The Cox regression analyses showed that Histology (HR=0.205, P=0.002), systemic immune inflammation index (SII) (HR=2.758, P=0.042) and TLS (HR=0.057, P<0.05) were independent prognostic factors in patients with NSCLC. The combined SII-TLS model was better than the single-indicator model in assessing the 1-year and 18-months DFS rates in patients with NSCLC. Conclusion: Our study showed that PLR was an independent predictor of TLS and that both TLS and SII predicted prognosis in patients with neoadjuvant chemoimmunotherapy-resectable NSCLC; however, combining SII and TLS to assess DFS was more accurate than using either parameter alone.

FAPI Compared with FDG PET/CT for Diagnosis of Primary and Metastatic Lung Cancer.

Background The radiotracer fluorine 18 (18F)-labeled fibroblast activation protein inhibitor (FAPI) has shown promise for visualizing several types of cancer, but the accuracy of 18F-FAPI compared with 18F-fluorodeoxyglucose (FDG) for the detection of lung cancer remains uncertain. Purpose To evaluate the effectiveness of 18F-FAPI-based PET/CT imaging for the diagnosis of primary and metastatic lung cancer lesions as compared with 18F-FDG PET/CT. Materials and Methods In this secondary analysis of a prospective trial, consecutively recruited patients from a single center with pathologically confirmed lung cancer were prospectively enrolled from December 2020 to April 2022 and underwent paired 18F-FAPI and 18F-FDG PET/CT examinations at intervals of more than 20 hours and within 7 days of each other. Histopathologic and clinical follow-up results were used as reference standards for final diagnoses. 18F-FAPI and 18F-FDG uptake were compared using the McNemar test or paired Student t test. Diagnostic accuracy was compared between the two techniques by using the McNemar χ2 test. Results Sixty-eight participants (median age, 63 years [IQR, 58-68 years; range, 42-79 years]; 46 male [68%]) were evaluated. Compared with the mean tumor-to-background ratio (TBR) for FDG uptake, TBR for FAPI uptake was lower in primary lung tumors (25.3 ± 14.0 [SD] vs 32.1 ± 21.1; P < .001) but higher in metastatic lymph nodes (7.5 ± 6.6 vs 5.9 ± 8.6; P < .001) and bone metastases (8.6 ± 5.4 vs 4.3 ± 2.3; P < .001). For diagnostic accuracy in a total of 548 lesions in 68 participants, compared with 18F-FDG PET/CT, 18F-FAPI PET/CT demonstrated a higher sensitivity (99% [392 of 397 lesions] vs 87% [346 of 397]; P < .001), specificity (93% [141 of 151 lesions] vs 79% [120 of 151]; P = .004), accuracy (97% [533 of 548 lesions] vs 85% [466 of 548]; P < .001), and negative predictive value (97% [141 of 146 lesions] vs 70% [120 of 171 lesions]; P < .001), but there was no evidence of a difference for positive predictive value (98% [392 of 402 lesions] vs 92% [346 of 377 lesions]; P = .57). Conclusion 18F-FAPI PET/CT may be superior to 18F-FDG PET/CT for detecting lung cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zukotynski and Gerbaudo in this issue.

Compound Kushen Injection Reduces Severe Toxicity and Symptom Burden Associated With Curative Radiotherapy in Patients With Lung Cancer.

BACKGROUND: Radiotherapy (RT) causes adverse events for which there are no effective treatments. This study investigated the clinical benefits of compound Kushen injection (CKI) in managing radiation injury in patients with lung cancer. METHODS: A multicenter, open-label, randomized clinical trial randomly assigned patients with lung cancer to receive either CKI (20 mL/d for at least 4 weeks) integrated with curative RT (RT + CKI group; n=130) or RT alone (control group; n=130). The primary outcome was the incidence of grade ≥2 radiation-induced lung injury (RILI) in the lungs, esophagus, or heart. Secondary outcomes included patient-reported symptoms, quality of life, objective response rate (ORR), and toxic effects. RESULTS: During the 16-week trial, the RT + CKI group had a significantly lower incidence of grade ≥2 RT-related injury than the control group (12.3% [n=16] vs 23.1% [n=30]; P=.02). Compared with the control group, the RT + CKI group experienced a significant decrease in moderate-to-severe symptoms of fatigue, cough, and pain (P<.001 for the treatment and time interaction term); significantly less physical symptom interference (P=.01); and significantly better quality of life by the end of the trial (P<.05). No statistically significant difference in ORR was found. Adverse reactions associated with CKI were rare. CONCLUSIONS: This study demonstrated low toxicity of CKI and its effectiveness in patients with lung cancer in reducing the incidence of grade ≥2 RILI and symptom burden, improving patients' quality of life.

Early and Accurate Detection of Radiation-induced Heart Damage by Cardiodynamicsgram.

Cardiodynamicsgram (CDG) has emerged recently as a noninvasive spatiotemporal electrocardiographic method for subtle cardiac dynamics information analysis within electrocardiogram (ECG). This study explored the feasibility of CDG for detecting radiation-induced heart damage (RIHD) in a rat model. A single radiation dose of 40 Gy was delivered to the cardiac apex of female Wistar rats. First, CDG was generated through dynamic modeling of ECG signals using the deterministic learning algorithm. Furthermore, CDG indexes were calculated using the wavelet transform and entropy. In this model, CDG entropy indexes decreased significantly after radiotherapy. The shape of CDG changed significantly after radiotherapy (irregular shape) compared with controls (regular shape). Macrophage and fibrosis in myocardium of rats increased significantly after radiotherapy. CDG changes after radiotherapy were significantly correlated with histopathological changes and occurred significantly earlier than histopathological changes. This study provides an experimental basis for the clinical application of CDG for the early detection of RIHD.

Recurrence patterns are significantly associated with the 18F­FDG PET/CT radiomic features of patients with locally advanced non­small cell lung cancer treated with chemoradiotherapy.

A model for predicting the recurrence pattern of patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy is of great importance for precision treatment. The present study analyzed whether the comprehensive quantitative values (CVs) of the fluorine-18(18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) radiomic features and metastasis tumor volume (MTV) combined with clinical characteristics could predict the recurrence pattern of patients with LA-NSCLC treated with chemoradiotherapy. Patients with LA-NSCLC treated with chemoradiotherapy were divided into training and validation sets. The recurrence profile of each patient, including locoregional recurrence (LR), distant metastasis (DM) and both LR/DM were recorded. In the training set of patients, the primary tumor prior radiotherapy with 18F-FDG PET/CT and both primary tumors and lymph node metastasis were considered as the regions of interest (ROIs). The CVs of ROIs were calculated using principal component analysis. Additionally, MTVs were obtained from ROIs. The CVs, MTVs and the clinical characteristics of patients were subjected to aforementioned analysis. Furthermore, for the validation set of patients, the CVs and clinical characteristics of patients with LA-NSCLC were also subjected to logistic regression analysis and the area under the curve (AUC) values calculated. A total of 86 patients with LA-NSCLC were included in the analysis, including 59 and 27 patients in the training and validation sets of patients, respectively. The analysis revealed 22 and 12 cases with LR, 24 and 6 cases with DM and 13 and 9 cases with LR/DM in the training and validation sets of patients, respectively. Histological subtype, CV2-5 and CV3-4 were identified as independent variables in the logistic regression analysis (P<0.05). In addition, the AUC values for diagnosing LR, DM and LR/DM were 0.873, 0.711 and 0.826, and 0.675, 0.772 and 0.708 in the training and validation sets of patients, respectively. Overall, the results demonstrated that the spatial and metabolic heterogeneity quantitative values from the primary tumor combined with the histological subtype could predict the recurrence pattern of patients with LA-NSCLC treated with chemoradiotherapy.

Research for accurate auxiliary diagnosis of lung cancer based on intracellular fluorescent fingerprint information.

The distinctions in pathological types and genetic subtypes of lung cancer have a direct impact on the choice of treatment choices and clinical prognosis in clinical practice. This study used pathological histological sections of surgically removed or biopsied tumor tissue from 36 patients. Based on a small sample size, millions of spectral data points were extracted to investigate the feasibility of employing intracellular fluorescent fingerprint information to diagnose the pathological types and mutational status of lung cancer. The intracellular fluorescent fingerprint information revealed the EGFR gene mutation characteristics in lung cancer, and the area under the curve (AUC) value for the optimal model was 0.98. For the classification of lung cancer pathological types, the macro average AUC value for the ensemble-learning model was 0.97. Our research contributes new idea for pathological diagnosis of lung cancer and offers a quick, easy, and accurate auxiliary diagnostic approach.

Increased 18F-FAPI uptake in bones and joints of lung cancer patients: characteristics and distributions.

OBJECTIVE: This study investigated the distribution and characteristics of various bone and joint lesions on 18F-FAPI PET/CT in lung cancer patients. METHODS: Seventy-four lung cancer patients who underwent 18F-FAPI PET/CT were reviewed. Bone and joint lesions with elevated 18F-FAPI uptake were recorded and analyzed. The distribution and maximum uptake value (SUVmax) of different benign lesions or bone metastases were presented. In addition, the SUVmax of bone metastases on 18F-FDG and 18F-FAPI-04 PET/CT were also compared. RESULTS: In 53 patients, a total of 262 lesions presented 18F-FAPI accumulation. Bone metastases were mainly in vertebrae, pelvis, and ribs, while benign lesions were in vertebral margins, alveolar bone, and shoulder joints. The SUVmax of bone metastases was significantly higher than that of benign lesions ([Formula: see text] vs. [Formula: see text], [Formula: see text]), with NSCLC cases having higher SUVmax values than SCLC cases ([Formula: see text] vs. [Formula: see text], [Formula: see text]). Among benign lesions, arthritis and periodontitis demonstrated higher SUVmax than degenerative lesions (arthritis: [Formula: see text]; periodontitis: [Formula: see text]; degenerative diseases: [Formula: see text]; [Formula: see text] and [Formula: see text], respectively). The SUVmax of bone metastases was comparable between 18F-FDG and 18F-FAPI PET/CT. However, 18F-FAPI PET/CT was found to be superior in identifying cranial metastases compared to 18F-FDG PET/CT (TBRmet/brain: [Formula: see text] vs. [Formula: see text], [Formula: see text]). CONCLUSION: This study demonstrated that 18F-FAPI PET/CT is a valuable imaging modality for detecting bone and joint lesions in lung cancer patients. The SUVmax of malignant lesions was higher than that of benign lesions, but cannot accurately distinguish benign and malignant lesions. The uptake of FAPI differs among lesions with different pathological types.

Plasma Markers for Early Prediction of Radiation-Induced Myocardial Damage.

There is no sensitive and effective method to predict radiation-induced myocardial damage (RIMD). The aim of this study was to explore effective plasma biomarkers for early prediction of RIMD after radiotherapy (RT) in lung cancer patients and in a rat model. Biomarker levels were measured in plasma samples collected before and after thoracic RT from 17 lung cancer patients. For the animal model, a single radiation dose of 40 Gy was delivered to the cardiac apex of female Wistar rats. Control rats received sham irradiation (0 Gy). Dynamic plasma biomarker detection and histopathological analysis to confirm RIMD were performed in rats up to 6 months after RT. In lung cancer patients, the plasma caspase-3 concentration was significantly increased after thoracic RT (P = 0.0479), with increasing but nonsignificant trends observed for caspase-1, CCL2, vascular endothelial growth factor (VEGF), interleukin-1ß, and IL-6 (P > 0.05). Changes in caspase-3, VEGF, and IL-6 correlated significantly with mean heart dose (P < 0.05). In the RIMD rat model, caspase-1, caspase-3, CCl-2, VEGF, CCl-5, and TGF-ß1 levels were significantly elevated in the first week post-RT (P < 0.05), which was earlier than pathological changes. Myocardial tissue of the RIMD rats also showed significant macrophage infiltration at 1 month (P < 0.01) and fibrosis at 6 months postradiation (P < 0.0001). Macrophage infiltration correlated significantly with plasma caspase-3, CCL2, CCL5, VEGF, and TGF-ß1 levels from 3 weeks to 2 months post-RT. Increased plasma caspase-1, caspase-3, CCl-2, and VEGF levels were detected before RIMD-related pathological changes, indicating their clinical potential as biomarkers for early prediction of RIMD.

Model integrating CT-based radiomics and genomics for survival prediction in esophageal cancer patients receiving definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy (dCRT) is a standard treatment option for locally advanced stage inoperable esophageal squamous cell carcinoma (ESCC). Evaluating clinical outcome prior to dCRT remains challenging. This study aimed to investigate the predictive power of computed tomography (CT)-based radiomics combined with genomics for the treatment efficacy of dCRT in ESCC patients. METHODS: This retrospective study included 118 ESCC patients who received dCRT. These patients were randomly divided into training (n = 82) and validation (n = 36) groups. Radiomic features were derived from the region of the primary tumor on CT images. Least absolute shrinkage and selection operator (LASSO) regression was conducted to select optimal radiomic features, and Rad-score was calculated to predict progression-free survival (PFS) in training group. Genomic DNA was extracted from formalin-fixed and paraffin-embedded pre-treatment biopsy tissue. Univariate and multivariate Cox analyses were undertaken to identify predictors of survival for model development. The area under the receiver operating characteristic curve (AUC) and C-index were used to evaluate the predictive performance and discriminatory ability of the prediction models, respectively. RESULTS: The Rad-score was constructed from six radiomic features to predict PFS. Multivariate analysis demonstrated that the Rad-score and homologous recombination repair (HRR) pathway alterations were independent prognostic factors correlating with PFS. The C-index for the integrated model combining radiomics and genomics was better than that of the radiomics or genomics models in the training group (0.616 vs. 0.587 or 0.557) and the validation group (0.649 vs. 0.625 or 0.586). CONCLUSION: The Rad-score and HRR pathway alterations could predict PFS after dCRT for patients with ESCC, with the combined radiomics and genomics model demonstrating the best predictive efficacy.

Application of nanomedicine in radiotherapy sensitization.

Radiation therapy is an important component of cancer treatment. As research in radiotherapy techniques advances, new methods to enhance tumor response to radiation need to be on the agenda to enable enhanced radiation therapy at low radiation doses. With the rapid development of nanotechnology and nanomedicine, the use of nanomaterials as radiosensitizers to enhance radiation response and overcome radiation resistance has attracted great interest. The rapid development and application of emerging nanomaterials in the biomedical field offers good opportunities to improve the efficacy of radiotherapy, which helps to promote the development of radiation therapy and will be applied in clinical practice in the near future. In this paper, we discuss the main types of nano-radiosensitizers and explore their sensitization mechanisms at the tissue level, cellular level and even molecular biology and genetic level, and analyze the current status of promising nano-radiosensitizers and provide an outlook on their future development and applications.

SLC27A4-mediated selective uptake of mono-unsaturated fatty acids promotes ferroptosis defense in hepatocellular carcinoma.

Aberrant lipid metabolism mediated by the selective transport of fatty acids plays vital roles in cancer initiation, progression, and therapeutic failure. However, the biological function and clinical significance of abnormal fatty acid transporters in human cancer remain unclear. In the present study, we reported that solute carrier family 27 member 4 (SLC27A4) is significantly overexpressed in 21 types of human cancer, especially in the fatty acids-enriched microenvironment surrounding hepatocellular carcinoma (HCC), breast cancer, and ovarian cancer. Upregulated SLC27A4 expression correlated with shorter overall and relapse-free survival of patients with HCC, breast cancer, or ovarian cancer. Lipidomic analysis revealed that overexpression of SLC27A4 significantly promoted the selective uptake of mono-unsaturated fatty acids (MUFAs), which induced a high level of MUFA-containing phosphatidylcholine and phosphatidylethanolamine in HCC cells, consequently resulting in resistance to lipid peroxidation and ferroptosis. Importantly, silencing SLC27A4 significantly promoted the sensitivity of HCC to sorafenib treatment, both in vitro and in vivo. Our findings revealed a plausible role for SLC27A4 in ferroptosis defense via lipid remodeling, which might represent an attractive therapeutic target to increase the effectiveness of sorafenib treatment in HCC.