Application of nano-radiosensitizers in non-small cell lung cancer.

Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.

Artemis as Predictive Biomarker of Responsiveness to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer.

The aim of this study was to identify Artemis as a predictive biomarker for guiding preoperative chemoradiotherapy in locally advanced rectal cancer. The resection specimens were collected from 50 patients with rectal cancer who underwent preoperative chemoradiotherapy. Artemis expression in biopsy tissues was evaluated using immunohistochemical staining according to the percentage of positively stained cells combined with staining intensity. Among the 50 patients, 36 (72%) had a weakly positive Artemis protein expression, 10 (20%) had a moderately positive expression, and 4 (8%) showed a strongly positive expression. The criteria of magnetic resonance imaging tumor regression grade (mrTRG) and pathological rectal cancer regression grade (RCRG) were used to assess the tumor response to chemoradiotherapy. Correlation analysis shows that there is a significant negative correlation between high Artemis immunoscore and treatment response (r = -0.532, p < 0.001). The results imply that high Artemis expression was associated with poor treatment response. Our study suggested a potential role of Artemis as a predictive biomarker of the tumor response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

Inflammation index predicts radiation-induced lung injury and prognosis in lung tumors treated with stereotactic body radiation therapy.

PURPOSE: To investigate the effect of inflammation-based indexes in predicting radiation pneumonitis (RP) and prognosis in lung tumor patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: The data of one hundred and seventy-two patients with 272 lung lesions from November 2015 to December 2020 were retrospectively analyzed. Pretreatment hematological indexes including platelet count, neutrophil count, and lymphocyte count were collected before treatment. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated. The receiver operating characteristic (ROC) curve was established to predict the RP and overall survival of patients, and the Youden index was calculated to determine the cutoff values of SII, NLR, and PLR before radiotherapy. RESULTS: Pretreatment SII, NLR, and PLR could predict RP in lung tumor patients treated with SBRT, the optimal cutoff values of SII, NLR, and PLR were 355.38, 2.04, and 141.09, respectively. Pretreatment PLR could predict survival and the optimal cutoff value of PLR was 166.83, patients with a PLR > 166.83 predict worse overall survival (OS) (P < 0.001). The 1-year and 2-year OS for patients with a PLR ≤ 166.83 were 96.3% and 82.4%, while for those with a PLR > 166.83 were 82.0% and 58.5%, respectively. CONCLUSION: In lung tumor patients treated with SBRT, pretreatment SII, NLR, and PLR can effectively predict RP and a higher PLR predicts poor OS. These inflammation-based indexes could serve as reliable and convenient predictors to guide treatment for physicians in clinical practice.

Relationship Between Microstructural Alterations and Cognitive Decline After Whole-Brain Radiation Therapy for Brain Metastases: An Exploratory Whole-Brain MR Analysis Based on Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT. PURPOSE: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (seven female; mean age, 60.9 years). FIELD STRENGTH/SEQUENCE: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence. ASSESSMENT: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated. STATISTICAL TESTS: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05. RESULTS: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT. DATA CONCLUSION: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Whole brain atlas-based diffusion kurtosis imaging parameters for the evaluation of multiple cognitive-related brain microstructure injuries after radiotherapy in lung cancer patients with brain metastasis.

Background: Whole brain radiation therapy (WBRT) can cause cognitive dysfunctions in lung cancer patients with brain metastasis (BM). Diffusion kurtosis imaging (DKI) can detect brain microstructural alterations sensitivly. We aimed to identify the potential of DKI parameters for early radiation-induced brain injury and investigate the association between microstructure changes and neurocognitive function (NCF) decline. Methods: Lung cancer patients with BM (n=35) who underwent WBRT in a single center in Zhejiang, China, were consecutively and prospectively enrolled between June 24th, 2020 and December 22nd, 2021, and the median follow-up time was 6.0 months (3.6-6.6 months). DKI and T1-weighted (T1W) MRI scans were acquired prior to and following WBRT. Diffusivity-based (mean diffusivity, MD; fractional anisotropy, FA) and kurtosis-based (mean kurtosis, MK; axial kurtosis, AK) parameters were calculated within the automated anatomical labeling (AAL) atlas-based regions. Reliable change indices practice effects (RCI-PE) scores of the Mini-Mental State Examination (MMSE) were calculated to determine significant neurocognitive decline by a one-sample t-test from baseline to 2-6 months post-WBRT. To assess the subacute induced effects within the whole brain, percentage changes of DKI parameters were evaluated at 170 atlas-based regions by a one-sample t-test. Linear regression analyses were used to evaluate the association between DKI parameter changes and RCI-PE scores. Results: Finally, the study included 19 patients in the longitudinal follow-up. RCI-PE scores declined at 2-6 months post-WBRT (mean RCI-PE =-0.842, 95% CI, -0.376 to -1.310; P=0.002). With the atlas-based analysis of subacute effects after post-WBRT, a total of 28 regions changed in at least one diffusion parameter, revealing region-wise microstructural alterations in the brain. Significant correlations of at least one diffusion parameters with RCI-PEs were observed in 9 regions, such as the right orbital part of the inferior frontal gyrus [right IFGorb, r(AK) =0.47, P=0.03] and left middle temporal gyrus [left MTG, r(MK) =-0.49, P=0.03]. Conclusions: DKI parameters can be used to detect early microstructure changes and represent important imaging predictors for cognitive decline. The reported 9 regions are more particularly vulnerable to neurocognitive radiation-induced impairment for lung cancer patients with BM, representing potential dose-avoidance targets for cognitive function preservation.

The emerging potential of quantitative MRI biomarkers for the early prediction of brain metastasis response after stereotactic radiosurgery: a scoping review.

Background: At present, the simple prognostic models based on clinical information for predicting the treatment outcomes of brain metastases (BMs) are subjective and delayed. Thus, we performed this systematic review of multiple studies to assess the potential of quantitative magnetic resonance imaging (MRI) biomarkers for the early prediction of treatment outcomes of brain metastases with stereotactic radiosurgery (SRS). Methods: We systematically searched the PubMed, Embase, Cochrane, Web of Science, and Clinical Trials.gov databases for articles published between February 1, 1991, and April 11, 2022, with no language restrictions. We included studies involving patients with BMs receiving SRS; the included patients were required to have definite pathology of a primary tumor and complete imaging data (pre- and post-SRS). We excluded the articles that included patients who had undergone previous surgery and those that did not include regular follow-up or corresponding MRI scans. Results: We identified 2,162 studies, of which 26 were included in our analysis, involving a total of 1,362 participants. All 26 studies explored the relevant MRI parameters to predict the prognosis of patients with BMs who received SRS. The outcomes were generalized according to the relationships between the anatomical/morphological, microstructural, vascular, and metabolic changes and SRS. Generally, with traditional MRI, there are several quantitative prognostic models based on preradiosurgical radiomics that predict the outcome of SRS treatment in local BM control. With the implementation of advanced MRI, the relative apparent diffusion coefficient (ADC), perfusion fraction (f), relative cerebral blood volume (rCBV), relative regional cerebral blood flow (rrCBF), interstitial fluid pressure (IFP), quadratic of time-dependent leakage (Ktrans 2), extracellular extravascular volume (ve), choline/creatine (Cho/Cr), nuclear Overhauser effect (NOE) peak, and intraextracellular water exchange rate constant (kIE ) were confirmed to be indicative of the therapeutic effect of SRS for BMs. Conclusions: Quantitative MRI biomarkers extracted from traditional or advanced MRI at different time points, which can represent the anatomical/morphological, microstructural, vascular, and metabolic changes, respectively, have been proposed as promising markers for the early prediction of SRS response in those with BMs. There are some limitations in this review, including the risk of selection bias, the limited number of study objects, the incomparability of the total data, and the subjectivity of the review process.

Neutrophil-lymphocyte ratio as a prognostic factor for stereotactic body radiotherapy treatment of metastatic liver tumors.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may be able to predict clinical outcomes in patients with malignant solid tumors. However, the relationship between NLR and the prognosis of liver metastasis after stereotactic body radiotherapy (SBRT) is not well established. METHODS: Patients with liver metastatic tumors who underwent SBRT in our center between 2015 and 2018 were enrolled, and their data were retrospectively analyzed. The patient' baseline total white blood cell (WBC), neutrophil, lymphocyte, and platelet counts were recorded, along with their mean platelet volume (MPV) and red blood cell distribution width (RDW). The cut-off values for NLR and platelet-lymphocyte ratio (PLR) were determined by receiver operating characteristic (ROC) curves. Local control (LC) and overall survival (OS) were calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to study significant variable line and factors associated with OS. RESULTS: A total of 65 patients with 82 lesions were enrolled. The median duration follow-up was 21 months. The local control (LC) rate was 76.8%, and the 1- and 2-year OS rates were 70.7% and 46.1%, respectively. The cut-off values of NLR and PLR were 3.16 and 201.33, respectively. Multivariate analysis identified the NLR cut-off value as a potential independent indicator of inferior OS [P=0.005, HR =3.317 (95% CI, 1.433-7.678)]. Biological effective dose (BED) was also associated with OS (P=0.035, HR =0.984 (95% CI, 0.969-0.999)]. CONCLUSIONS: NLR showed a strong association with LC and OS, which could serve as a predictive guide in the treatment of liver metastasis with SRBT. BED is also an independent factor affecting OS.