Could nutrition status predict fatigue one week before in patients with nasopharynx cancer undergoing radiotherapy?

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy experience significant fatigue, which is frequently underestimated due to the lack of objective indicators for its evaluation. This study aimed to explore the longitudinal association between fatigue and nutrition status 1 week in advance. METHODS: From January 2021 to June 2022, a total of 105 NPC patients who received intensity-modulated radiation therapy were enrolled in the observational longitudinal study. The significant outcomes, including the Piper Fatigue Scale-12 (PFS-12), the Scored Patient-Generated Subjective Global Assessment (PG-SGA), four body composition indices, and the Hospital Anxiety and Depression Scale (HADS), were assessed weekly from pre-treatment until the completion of radiotherapy (T0-T7) to explore their relationship. RESULTS: The trajectories of PFS-12 and all dimensions for 105 participants reached a peak during the fifth week. Sensory fatigue consistently received the highest scores (T0 = 1.60 ± 2.20, T5 = 6.15 ± 1.57), whereas behavior fatigue exhibited the fastest increase over time (T0 = 1.11 ± 1.86, T5 = 5.47 ± 1.70). Higher PG-SGA scores were found to be weakly explainable for aggravating fatigue (ß = 0.02 ~ 0.04). Unlike generalized additive mixed models, marginal structural models (MSM) produced larger effect values (ß = 0.12 ~ 0.21). Additionally, body composition indices showed weakly negative relationships with fatigue in MSMs one week in advance. CONCLUSIONS: The PG-SGA may be a more accurate predictor of future-week fatigue than individual body composition indicators, particularly when HADS is controlled for as a time-dependent confounder.

Glycyrrhetinic Acid Mitigates Radiation-Induced Pulmonary Fibrosis via Inhibiting the Secretion of TGF-ß1 by Treg Cells.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a common side effect of radiation therapy for thoracic tumors without effective prevention and treatment methods at present. The aim of this study was to explore whether glycyrrhetinic acid (GA) has a protective effect on RIPF and the underlying mechanism. METHODS AND MATERIALS: A RIPF mouse model administered GA was used to determine the effect of GA on RIPF. The cocultivation of regulatory T (Treg) cells with mouse lung epithelial-12 cells or mouse embryonic fibroblasts and intervention with GA or transforming growth factor-ß1 (TGF-ß1) inhibitor to block TGF-ß1 was conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-ß1 levels was performed to verify the roles of TGF-ß1 and Treg cells. RESULTS: GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltration, TGF-ß1 levels, epithelial mesenchymal transition (EMT), and myofibroblast (MFB) transformation in mice after irradiation. Treg cell-induced EMT and MFB transformation in vitro were prevented by GA, as well as a TGF-ß1 inhibitor, by decreasing TGF-ß1. Furthermore, reinfusion of Treg cells upregulated TGF-ß1 levels and exacerbated RIPF in GA-treated RIPF mice. CONCLUSIONS: GA can improve RIPF in mice, and the corresponding mechanisms may be related to the inhibition of TGF-ß1 secreted by Treg cells to induce EMT and MFB transformation. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF.

Paclitaxel aggravating radiation-induced pulmonary fibrosis is associated with the down-regulation of the negative regulatory function of Spry2.

Paclitaxel (PTX) is capable of aggravating radiation-induced pulmonary fibrosis (RIPF), but the mechanism is unknown. Spry2 is a negative regulator of receptor tyrosine kinase-related Ras/Raf/ERK pathway. This experiment was aimed at exploring whether the aggravation of RIPF by PTX is related to Spry2. The RIPF model was established with C57BL/6 mice by thoracic irradiation, and PTX was administered concurrently. Western blot was used to detect the expression level of ERK signaling molecules and the distribution of Spry2 in the plasma membrane/cytoplasm. Co-IP and immunofluorescence were used to observe the co-localization of Spry2 with the plasma membrane and tubulin. The results showed that PTX-concurrent radiotherapy could aggravate fibrotic lesions in RIPF, down-regulate the content of membrane Spry2 and up-regulate the levels of p-c-Raf and p-ERK in lung tissue. It was found that knockdown of Spry2 in fibroblast abolished the up-regulation of p-c-Raf and p-ERK by PTX. Both Co-IP results and immunofluorescence staining showed that PTX increased the binding of Spry2 to tubulin and that microtubule depolymerizing agents could abolish PTX's inhibition of Spry2 membrane distribution and inhibit PTX's up-regulation of Raf/ERK signaling. Both Nintedanib and ERK inhibitor were effective in relieving PTX-exacerbated RIPF. Taken together, the mechanism of PTX's aggravating RIPF was related to its ability to enhance Spry2's binding to tubulin, thus attenuating Spry2's negative regulation on Raf/ERK pathway. Significance Statement The obtained mechanism of paclitaxel aggravating RIPF by restraining Spry2 provides targets such as Raf/ERK for reducing radiation-induced damage to normal tissues caused by paclitaxel combined with radiation therapy.

Correlation between hippocampal radiation doses and psychological condition for patients with stage T1-2 nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: The study aimed to investigate the correlation between radiation doses to the hippocampi and the psychological status of patients with stage T1-2 nasopharyngeal carcinoma (NPC) undergoing intensity modulated radiotherapy (IMRT) and recommend proper hippocampal dose limits for preserving patients' psychological well-being. MATERIALS AND METHODS: A retrospective study was conducted involving 152 newly diagnosed NPC patients. The patients' psychological status was assessed using the Hospital Anxiety and Depression Scale (HADS) before and after radiotherapy. The hippocampi were manually delineated on treatment planning images, and dosimetric parameters were obtained from dose-volume histograms. Logistic regression analysis was performed to identify influential dosimetric factors associated with anxiety and depression. RESULTS: The results showed that several dosimetric parameters to the hippocampi were significantly associated with anxiety but not depression. The optimal cut-off value for the independent predictor of anxiety was determined as D40 to hippocampi > 1500 cGy. Patients with D40 to hippocampi > 1500 cGy showed a higher probability for anxiety after radiotherapy. CONCLUSION: This study provides insights into the relationship between radiation doses to the hippocampi and the psychological status of stage T1-2 NPC patients undergoing IMRT. It suggests the importance of hippocampal protection for preserving patients' psychological well-being. Further studies are needed to validate these results.

The effect of early oral nutritional supplements on improving nutritional outcomes and radiation-induced oral mucositis for nasopharyngeal carcinoma patients undergoing concurrent chemoradiotherapy.

BACKGROUND: To explore the value of early oral nutritional supplements (ONS) in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). METHODS: Patients with newly diagnosed II-IVA stage NPC were analyzed and divided into Early and Routine ONS groups according to whether they received early ONS at the beginning of CCRT. Changes in nutritional indicators, incidence of treatment-related toxicity, radiation interruption, and completion of CCRT were compared. RESULTS: In total, 161 patients with NPC were analyzed, including 72 in the Early ONS group and 89 in the Routine ONS group. Multivariate analysis showed that early ONS was an independent protective factor for concurrent chemotherapy ≥2 cycles, and a protective factor against ≥grade 3 radiation-induced oral mucositis (RIOM) and weight loss >5%. In stage III-IVA patients, early ONS was beneficial in decreasing the risk of severe malnutrition. CONCLUSIONS: Early ONS can improve nutritional outcomes, reduce RIOM, and enhance treatment adherence.

Nomogram for prognosis of elderly patients with cervical cancer who receive combined radiotherapy.

This retrospective study identified prognostic factors to help guide the clinical treatment of elderly patients (≥ 65 years) with cervical cancer who had undergone radiotherapy. A personalized model to predict 3- and 5-years survival was developed. A review was conducted of 367 elderly women with cervical cancer (staged II-III) who had undergone radiotherapy in our hospital between January 2012 and December 2016. The Cox proportional hazards regression model was used for survival analysis that considered age, hemoglobin, squamous cell carcinoma antigen, pathologic type, stage, pelvic lymph node metastasis status, and others. A nomogram was constructed to predict the survival rates. The median follow-up time was 71 months (4-118 months). The 3- (5-) years overall, progression-free, local recurrence-free, and distant metastasis-free survival rates were, respectively, 91.0% (84.4%), 92.3% (85.9%), 99.18% (99.01%), and 99.18% (97.82%). The following were significant independent prognostic factors for overall survival: tumor size, pre-treatment hemoglobin, chemotherapy, and pelvic lymph node metastasis. The C-index of the line chart was 0.699 (95% CI 0.652-0.746). The areas under the receiver operating characteristic curves for 3- and 5-years survival were 0.751 and 0.724. The nomogram was in good concordance with the actual survival rates. The independent prognostic factors for overall survival in elderly patients with cervical cancer after radiotherapy were: tumor size, pre-treatment hemoglobin, chemotherapy, and pelvic lymph node metastasis. The novel prognostic nomogram based on these factors showed good concordance with the actual survival rates and can be used to guide personalized clinical treatment.

MiR-223-3p attenuates radiation-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages.

Macrophage pyroptosis plays an important role in the development of radiation-induced cell and tissue damage, leading to acute lung injury. However, the underlying mechanisms of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)-mediated macrophage pyroptosis and the regulatory factors involved in radiation-induced pyroptosis are unclear. In this study, the expression of the NLRP3 inflammasome and pyroptosis-associated factors in murine macrophage cell lines was investigated after ionizing radiation. High-throughput RNA sequencing was performed to identify and characterize miRNAs and mRNA transcripts associated with NLRP3-mediated cell death. Our results demonstrated that cleaved-caspase-1 (p10) and N-terminal domain of gasdermin-D (GSDMD-N) were upregulated, and the number of NLRP3 inflammasomes and pyroptotic cells increased in murine macrophage cell lines after irradiation (8 Gy). Comparativeprofiling of 300miRNAs revealed that 41 miRNAsexhibited significantly different expression after 8 Gy of irradiation. Granulocyte-specific microRNA-223-3p (miR-223-3p) is a negative regulator of NLRP3. In vitro experiments revealed that the expression of miR-223-3p was significantly altered by irradiation. Moreover, miR-223-3p decreased the expression of NLRP3 and proinflammatory factors, resulting in reduced pyroptosis in irradiated murine macrophages. Subsequently, in vivo experiments revealed the efficacy of miR-223-3p supplementation in ameliorating alveolar macrophage (AM) pyroptosis, attenuating the infiltration of inflammatory monocytes, and significantly alleviating the severity of acute radiation-induced lung injury (ARILI). Our findings suggest that the miR-223-3p/NLRP3/caspase-1 axis is involved in radiation-induced AM pyroptosis and ARILI.

Effects of Multimodal Exercise on Health-related Physical Fitness and Quality of Life in Patients with Nasopharyngeal Carcinoma during Radiotherapy.

BACKGROUND: The health-related physical fitness of patients with nasopharyngeal carcinoma can decrease significantly during radiotherapy, which can adversely affect their quality of life. AIM: This study was designed to evaluate the potential influence of a multimodal exercise program on the health-related physical fitness and quality of life of patients with nasopharyngeal carcinoma during radiotherapy. METHODS: Forty patients with nasopharyngeal carcinoma undergoing radiotherapy in the First Affiliated Hospital of Fujian Medical University from May to November 2019 were included. The participants in the control group (N=20) received routine nursing, while those in the intervention group (N=20) were also subjected to the multimodal exercise program during radiotherapy. RESULTS: The multimodal exercise program had a positive effect on participants. The step test index in the intervention group was significantly higher as compared to the control group (p < .05). The participants were subjected to 5 times slow speed (60°/s) and 10 times fast (180°/s) speed, and function of some extensor and flexor muscles of the elbow, shoulder, and knee joints in the intervention group was markedly improved (p < .05). In the intervention group, the grip strength of the right hand was observed to be significantly improved (p < .01). Furthermore, the upper limb scratch dorsal test of intervention group was significantly better than that of the control group (p < .05). The scores of physical, emotional, and social functions in the intervention group were found to be significantly higher as compared to the control group (p < .05). CONCLUSIONS: The multimodal exercise program significantly improved the health-related physical fitness and life quality of the patients with nasopharyngeal carcinoma during radiotherapy, though its long-term effects remain to be further analyzed.

Risk of cardiac-related death in astrocytoma patients treated with chemotherapy: A competing risk analysis using the SEER database.

Purpose: To explore the impact of chemotherapy on the risk of cardiac-related death in astrocytoma patients. Methods: We retrospectively evaluated astrocytoma patients diagnosed between 1,975 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Using Cox proportional hazards models, we compared the risks of cardiac-related death between a chemotherapy group and non-chemotherapy group. Competing-risks regression analyses were used to evaluate the difference in cardiac-related death. Also, propensity score matching (PSM) was employed to reduce confounding bias. The robustness of these findings was evaluated by sensitivity analysis, and E values were calculated. Results: A total of 14,834 patients diagnosed with astrocytoma were included. Chemotherapy (HR = 0.625, 95%CI: 0.444-0.881) was associated with cardiac-related death in univariate Cox regression analysis. Chemotherapy was an independent prognostic factor for a lower risk of cardiac-related death before (HR = 0.579, 95%CI: 0.409-0.82, P = 0.002) and after PSM (HR = 0.550, 95%CI: 0.367-0.823 P = 0.004). Sensitivity analysis determined that the E-value of chemotherapy was 2.848 and 3.038 before and after PSM. Conclusions: Chemotherapy did not increase the risk of cardiac-related death in astrocytoma patients. This study highlights that cardio-oncology teams should provide comprehensive care and long-term monitoring for cancer patients, especially those with an increased risk of cardiovascular disease.

Serum lipids concentration on prognosis of high-grade glioma.

OBJECTIVE: To investigate the effect of serum lipids concentration on the prognosis of high-grade glioma patients undergoing postoperative radiotherapy. METHODS: Retrospective analysis of the patients with high-grade glioma who received postoperative Intensity Modulated Radiotherapy between 13 May 2013 and 12 September 2018 was performed. The patients were grouped according to the average values of serum total cholesterol, LDL, and HDL concentration in peripheral blood (before surgery, 6 months after therapy). Cox proportional hazards model was performed to determine whether the total cholesterol concentration, LDL concentration, and HDL concentration in peripheral blood before therapy and their changes after therapy were factors influencing the prognosis. RESULTS: The results of COX regression analysis showed that the independent prognostic factors of high-grade glioma patients were pathological grade, the extent of resection, serum cholesterol concentration pre-surgery, and the change of LDL concentration from pre-surgery to post-therapy. The prognosis of patients with high serum total cholesterol concentration before therapy was worse than those of patients with low total cholesterol concentration. The 5-year survival rate and the median survival time of patients with high serum total cholesterol concentration before therapy were 4.9% and 23.6 months, but the low cholesterol concentration group were 19.6% and 24.5 months, respectively. Besides, the average serum LDL concentration in high-grade glioma patients gradually increased after therapy. The 5-year survival rate of patients and the median survival time with elevated LDL concentration after therapy is 11.8% and 20.4 months, but the reduced LDL concentration group was 16.7% and 28.4 months, respectively. The total cholesterol and LDL concentration increased significantly after therapy in Grade IV patients while Grade III patients did not. CONCLUSIONS: The cholesterol concentration before therapy and LDL concentration change from pre-surgery to post-therapy are the factors that affect the prognosis of high-grade glioma patients who have undergone postoperative radiotherapy. In the final analysis, the high serum cholesterol pre-surgery and the increased in serum LDL concentration from pre-surgery to post-therapy were associated with worse survival of patients.

Log odds of negative lymph nodes/T stage ratio (LONT): A new prognostic tool for differentiated thyroid cancer without metastases in patients aged 55 and older.

Background: The optimal approach to assess the postoperative status of lymph nodes in differentiated thyroid cancer (DTC) remains controversial. Our aim was to determine if the log odds of negative lymph nodes/T stage ratio (LONT) could serve as a new prognostic and predictive tool for DTC without metastases in patients aged ≥ 55 years. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to study the role of LONT in patients aged ≥55 years diagnosed with DTC without metastases. The primary outcome was overall survival (OS). The Kaplan-Meier method and the Cox proportional hazard regression model were used to calculate the outcome. Moreover, the robustness of research findings was evaluated using sensitivity analyses. Results: A total of 21,172 DTC patients aged ≥55 years without distant metastasis were enrolled. Multivariate Cox regression analyses and a "floating absolute risk" analysis showed that a LONT ≥0.920 (vs. -0.56 to 0.92) was a protective factor for OS in DTC patients. Sensitivity analyses revealed an E-value of 1.98 for the obtained LONT value. In subgroup analyses, LONT was correlated significantly with OS in different subgroups of negative lymph nodes, stage-I-II subgroups and the N0 subgroup. The conditional probability of survival of DTC improved with prolonged survival time in the LONT ≥0.920 group. Conclusion: A high LONT was associated with longer OS compared with low LONT in patients aged ≥55 years with non-metastatic DTC. LONT could provide valuable information for undertaking postoperative evaluations.

A Subset of Breg Cells, B10, Contributes to the Development of Radiation-Induced Pulmonary Fibrosis.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a serious side effect of radiation therapy, but the underlying mechanisms are unknown. B10 cells, as negative B regulatory cells, play important roles in regulating inflammation and autoimmunity. However, the role of B10 cells in RIPF progression is unclear. The aim of this study was to determine the role of B10 cells in aggravating RIPF and the underlying mechanism. METHODS AND MATERIALS: The role of B10 cells in RIPF was studied by constructing mouse models of RIPF and depleting B10 cells with an anti-CD22 antibody. The mechanism of B10 cells in RIPF was further explored through cocultivation of B10 cells and MLE-12 or NIH3T3 cells and administration of an interleukin (IL)-10 antibody to block IL-10. RESULTS: B10 cell numbers increased significantly during the early stage in the RIPF mouse models compared with the controls. In addition, depleting B10 cells with the anti-CD22 antibody attenuated the development of lung fibrosis in mice. Subsequently, we confirmed that B10 cells induced epithelial-mesenchymal transition and the transformation of myofibroblasts via activation of STAT3 signaling in vitro. After blockade of IL-10, it was verified that IL-10 secreted by B10 cells mediates the epithelial-mesenchymal transition of myofibroblasts, thereby promoting RIPF. CONCLUSIONS: Our study uncovers a novel role for IL-10-secreting B10 cells that could be a new target of research for relieving RIPF.

Prognostic Value of Serum Transferrin Level before Radiotherapy on Radio-Sensitivity and Survival in Patients with Nasopharyngeal Carcinoma.

PURPOSE: To investigate the prognostic value of serum transferrin (TRF) level before intensity-modulated radiation therapy (IMRT) on radio-sensitivity and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). METHODS: From October 2012 to October 2016, a total of 348 patients with NPC in the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed in our study. The concentration of serum TRF was detected by the method of enzyme-linked immunosorbent assay (ELISA). In the whole group, 46 patients received IMRT, and 302 patients received IMRT plus chemotherapy. The radio-sensitive tumor was defined when the local tumor lesions disappeared completely in the nasopharyngeal MRI scan and no tumor residues were found under the electronic nasopharyngoscope one month after the end of radiotherapy. RESULTS: The serum TRF level before IMRT was (1.34-3.89) g/L, with a median of 2.16 g/L and a mean of (2.20 ± 0.42) g/L. In the whole group, 242 cases (69.5%) were radiosensitive, and 106 cases (30.5%) were insensitive. The number of radiosensitive patients in the group of HTRF (transferrin > 2.16 g/L) and LTRF (transferrin ≤ 2.16 g/L) before radiotherapy was 129 (74.6%) and 113 (64.6%), respectively. The difference in radio-sensitivity between the two groups was statistically significant (χ2 = 4.103, p = 0.043). Logistic regression analysis showed that the level of TRF before radiotherapy (OR = 1.702; 95% CI 1.044~2.775; p = 0.033) was an independent factor for radio-sensitivity. The log-rank test showed that patients in the LTRF group achieved a significantly worse OS (χ2 = 5.388, p = 0.02) than those in the HTRF group. Cox regression analysis showed that baseline TRF level (HR = 1.706; 95% CI 1.065~2.731; p = 0.026) was an independent prognostic factor for overall survival. CONCLUSIONS: The low level of TRF before IMRT is a risk factor for radio-sensitivity and a prognostic factor for poor OS in NPC patients. It may be a promising marker to predict radio-sensitivity and OS in NPC patients who accept IMRT.

Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study.

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologically confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1. Findings: Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade ≥3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported. Conclusion: In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167. Funding: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015).

The prognostic significance of tumor-associated neutrophils and circulating neutrophils in glioblastoma (WHO CNS5 classification).

BACKGROUND: Tumor-associated neutrophils (TANs) in the tumor microenvironment are prognostic biomarkers in many malignancies. However, it is unclear whether TANs can serve as a prognostic marker for clinical outcomes in patients with glioblastoma (GBM), as classified according to World Health Organization Classification of Tumors of the Central Nervous System, fifth edition (CNS5). In the present study, we analyzed correlations of TANs and peripheral blood neutrophils prior to radiotherapy with overall survival (OS) in GBM (CNS5). METHODS: RNA-seq expression profiles of patients with newly diagnosed GBM (CNS5) were extracted from The Cancer Genome Atlas (TCGA), and The Chinese Glioma Genome Atlas (CGGA). TAN infiltration was inferred using CIBERSORTx algorithm. Neutrophil counts prior to radiotherapy in newly diagnosed GBM (CNS5) were obtained from the First Affiliated Hospital of Fujian Medical University. The prognostic value of TANs and peripheral blood neutrophils before radiotherapy was investigated using Kaplan-Meier analysis and Cox proportional hazards models. The robustness of these findings was evaluated by sensitivity analysis, and E values were calculated. RESULTS: A total of 146 and 173 individuals with GBM (CNS5) were identified from the TCGA and CGGA cohorts, respectively. High infiltration of TANs was of prognostic of poor OS in TCGA (HR = 1.621, 95% CI: 1.004-2.619) and CGGA (HR = 1.546, 95% CI: 1.029-2.323). Levels of peripheral blood neutrophils before radiotherapy (HR = 2.073, 95% CI: 1.077-3.990) were independently associated with poor prognosis. Sensitivity analysis determined that the E-value of high TANs infiltration was 2.140 and 2.465 in the TCGA and CGGA cohorts. CONCLUSIONS: TANs and peripheral blood neutrophil levels before radiotherapy are prognostic of poor outcomes in GBM (CNS5).

Effect of nutritional status before radiotherapy on radiation-induced acute toxicities in patients with nasopharyngeal carcinoma.

BACKGROUND: To investigate the effect of nutritional status on radiation-induced acute toxicities in nasopharyngeal carcinoma (NPC) patients before radiotherapy. METHODS: Nutritional status of 228 patients with NPC who received intensity-modulated radiotherapy was retrospectively analyzed by modified nutrition index (m-NI). Cumulative grading score of six common acute toxicities were defined as total score for acute toxicities. RESULTS: M-NI ≤6 is a risk factor for xerostomia (p = 0.016, OR = 0.208, 95% CI 0.058-0.743), oral mucositis (p = 0.016, OR = 0.287, 95% CI 0.104-0.793), dysgeusia (p = 0.001, OR = 0.028, 95% CI 0.004-0.217), and dysphagia (p = 0.015, OR = 0.251, 95% CI 0.083-0.764) as well in patients with NPC. Total score of radiation-induced acute toxicities of patients with malnutrition (13.6 ± 1.7) was significantly higher than that of patients with normal nutrition (12.0 ± 2.4) (t = -5.464, p < 0.001). CONCLUSIONS: NPC patients with malnutrition before radiotherapy develop more serious dysgeusia, oral mucositis, dysphagia, and xerostomia after intensity-modulated radiotherapy.

A deficient MIF-CD74 signaling pathway may play an important role in immunotherapy-induced hyper-progressive disease.

BACKGROUND: With the advent of immune checkpoint inhibitors (ICIs) therapies, a major breakthrough has been made in cancer treatment. However, instead of good results, some patients experienced a deterioration of their disease. This unexpected result is termed as hyper-progressive disease (HPD). The biology of HPD is currently not fully understood. METHODS: Isolation of CD3+ cells from peripheral blood mononuclear cells (PBMC) in healthy control, tumor patients receiving immunotherapy with or without immunotherapy-induced HPD, then conducted single-cell RNA sequencing (scRNA-seq). RESULTS: By analyzing scRNA-seq data, we identified 15 cell clusters. We observed developed-exhausted CD4+ T cells and regulatory T cells (Tregs) increasingly enriched in HPD group. Meanwhile, some effector T cells were decreased in HPD. The imbalance potentially contributes to the occurrence of HPD and poor clinical prognosis. In addition, we analyzed ligand-receptor interactions between subsets. The ligand-receptor interaction "CD74-MIF" was absent in HPD. However, in vitro experiment, we found that CD74 regulated effector function of effector CD8+ T cells. Overall, the article provides a primary study of immune profile in HPD.

Timing of radiotherapy in glioblastoma based on IMRT and STUPP chemo-radiation: may be no need to rush

To investigate the effect of surgery to radiotherapy interval (SRI) on the prognosis of patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma.MethodsRetrospective analysis of the relationship between SRI and prognosis of patients with IDH wild-type glioblastoma who received postoperative intensity modulated radiotherapy (IMRT) in our center from July 2013 to July 2019. The patients were divided into SRI ≤ 42 days (regular group) and SRI > 42 days (delay group). Kaplan–Meier univariate analysis and Cox proportional hazard model were used to analyze whether SRI was an independent factor influencing the prognosis.ResultsA total of 102 IDH wild-type glioblastoma were enrolled. Median follow-up was 35.9 months. The 1-, 2- and 3-year OS of “regular group” were 69.5%, 34.8%, 19.1%, and “delay group” were 69.8%, 26.1% and 13.4% respectively. Multivariate analysis showed that extent of resection (p = 0.041) was an independent prognostic factor for OS. SRI (p = 0.347), gender (p = 0.159), age (p = 0. 921), maximum diameter (p = 0.637) MGMT promoter methylation status (P = 0.630) and ki-67 expression (P = 0.974) had no effect on OS. Univariate analysis (p = 0.483) and multivariate analysis (p = 0.373) also showed that SRI had no effect on OS in glioblastoma who received gross total resection.ConclusionAppropriate extension in SRI has no negative effect on the OS of IDH wild-type glioblastoma. It is suggested that radiotherapy should be started after a good recovery from surgery. This conclusion needs further confirmed by long-term follow-up of a large sample. (AU)

Radiomic model to predict the expression of PD-1 and overall survival of patients with ovarian cancer.

BACKGROUND: Programmed cell death 1 (PD-1), encoded by programmed cell death protein 1 (PDCD1), is widely investigated in clinical trials. We aimed to develop a radiomic model to discriminate its expression levels patients with ovarian cancer (OC) and explore its prognostic value. METHODS: Computed tomography (CT) images with the corresponding sequencing data and clinicopathological features were used. The volumes of interest were manually delineated. After extraction and normalization, the radiomic features were screened using repeat least absolute shrinkage and selection operator. A radiomic model for PD-1 prediction, radiomic score (rad_score), was developed using logistic regression and validated via internal 5-fold cross-validation. The Kaplan-Meier curves, COX proportional hazards model, and landmark analysis were used for survival analysis. RESULTS: The mRNA level of PDCD1 significantly affects the overall survival (OS) of OC patients. The rad_score for PDCD1 prediction was based on four features and was significantly correlated with other genes involved in T-cell exhaustion and immune checkpoint molecules. The areas under the receiver operating characteristic curves reached 0.810 and 0.772 in the training and validation datasets, respectively. The calibration curves and decision curve analysis proved the model's fitness and clinical benefits. Patients with higher rad_score had poorer OS (P < 0.001, 0.031, 0.014, 0.01, and < 0.001, after landmark of 12 months, before and after landmark of 36 months, and before and after landmark of 60 months, respectively). CONCLUSIONS: The radiomic signature from CT images can discriminate the PD-1 expression status and OC prognosis, which is correlated with T-cell exhaustion.

Extracellular matrix of early pulmonary fibrosis modifies the polarization of alveolar macrophage.

Macrophage polarization is modulated by many different stimuli. However, the effect of fibrotic extracellular matrix (ECM) on macrophage polarization remains unclear. In this study, a mouse model of radiation induced pulmonary fibrosis (RIPF) was established. Alveolar macrophages (AMs) were seeded on separated decellularized ECM respectively derived from early RIPF lung tissue (dECM-RIPF) and normal lung tissue (dECM-Nor), on which the polarization of AMs was examined. By way of bio-AFM analysis, a significant difference in surface roughness, but no difference in stiffness, was found between dECM-RIPF and dECM-Nor. Compared with dECM-Nor, dECM-RIPF induced a higher M1 activation and increased the levels of TNF-α, IL-6 and IL-1ß, while it showed no significant effect M2 density. Nevertheless, such effects induced by dECM-RIPF could be abrogated by the integrin pan-inhibitor. Furthermore, dECM-RIPF caused integrin-dependent activation of NFκB, and NFκB inhibitor was capable of inhibiting dECM-RIPF-induced AMs proliferation and M1 activation. Animal experiments showed that NFκB inhibitor alleviated RIPF mainly through inhibiting M1 activation and down-regulating the levels of inflammatory cytokines. Our results showed that differential biophysical signaling from the fibrotic ECM of early RIPF promoted AMs polarization towards a M1 phenotype via integrin-NFκB. Inhibition of M1 activation may be an attractive approach for treating RIPF.