Gy Group Research Articles

Radioprotective Effect of Piperine, as a Major Component of Black Pepper, Against Radiation-induced Colon Injury: Biochemical and Histological Studies.

Patients undergoing radiotherapy are prone to radiation-induced gastrointestinal injury. Piperine is an alkaloid component in black pepper with a unique chemopreventive activity against oxidative stress-related damage in healthy tissues. The purpose of this study was to investigate the effects of piperine on intestinal damage. In this study, mice were divided into eight groups: including the control, piperine (10, 25, and 50 mg/kg), radiation (6 Gy), and piperine+radiation (10, 25 and 50 mg/kg + 6 Gy) groups. The radioprotective effects of piperine were evaluated by biochemical (MDA, GSH, and PC) and histopathological assessments in colon tissues. The 10 mg/kg dose of piperine significantly reduced the levels of oxidative stress biomarkers compared to the group that received only radiation. In addition, pre-treatment with 10 mg/kg piperine diminished the histopathological changes like vascular congestion in the submucosa, while the dose of 50 mg/kg led to the infiltration of inflammatory cells. Based on this study, it is concluded that piperine, at low dose, with its antioxidant properties, could reduce the colon damage caused by radiation.

Dual-energy computed tomography in the early evaluation of acute radiation pneumonia

ObjectiveTo investigate the value of dual-energy dual-source computed tomography (DSCT) in evaluating pulmonary perfusion changes before and after radiotherapy for esophageal cancer, and its clinical use in the early diagnosis of acute radiation pneumonia (ARP).MethodsWe selected 45 patients with pathologically confirmed esophageal cancer who received radiotherapy (total irradiation dose of 60 Gy). Dual-energy DSCT scans were performed before and after radiotherapy and the normalized iodine concentrations (NIC) in the lung fields of the areas irradiated with doses of > 20 Gy, 10–20 Gy, 5–10 Gy, and < 5 Gy were measured. We also checked for the occurrence of ARP in the patients, and the differences in NIC values and NIC reduction rates before and after radiotherapy were calculated and statistically analyzed.ResultsA total of 16 of the 45 patients developed ARP. The NIC values in the lung fields of all patients decreased at different degrees after radiotherapy, and the NIC values in the area where ARP developed, decreased significantly. The rate of NIC reduction and incidence rate of ARP increased gradually with the increasing irradiation dose, and the inter-group difference in NIC reduction rate was statistically significant (P < 0.05). Based on the receiver operating characteristic (ROC) curve analysis, the areas under the curves of NIC reduction rate versus ARP occurrence in the V5-10 Gy, V10-20 Gy, and V> 20 Gy groups were 0.780, 0.808, and 0.772, respectively. Sensitivity of diagnosis was 81.3%, 75.0%, and 68.8% and the specificity was 65.5%, 82.8%, and 79.3%, when taking 12.50%, 16.50%, and 26.0% as the diagnostic thresholds, respectively. The difference in NIC values in the lung fields of V<5 Gy before and after radiotherapy was not statistically significant (P > 0.05).ConclusionThe dual-energy DSCT could effectively evaluate pulmonary perfusion changes after radiotherapy for esophageal cancer, and the NIC reduction rate was useful as a reference index to predict ARP and provide further reference for decisions in clinical practice.

Efficacy and Mechanism of Hypofractionation Radiotherapy Combined with PD-1 Inhibitors in a Model of Head and Neck Melanoma

Head and neck mucosal melanoma is one of the most common types of melanoma in China, but the prognosis is worse than other types, and there is no effective treatment plan to improve patient survival. This study analyzes the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitor in the treatment of head and neck mucosal melanoma, as well as its impact on the tumor immune microenvironment. NPSG mice were used to construct a humanized bilateral lesion tumor model of the humanized immune system. The models were divided into an RT (8 Gy)+anti PD-1 group, an RT (2 GyX4)+anti PD-1 group, an Anti PD-1 group, an RT (8 Gy) group, and a blank group. Differences in efficacy and immune cells in blood, lymph nodes, and tumor tissues were compared between different treatment groups. The treatment effect of RT (8 Gy)+anti PD-1 was better than the other groups with a tumor growth inhibition value (TGI) over 60%. Significant recruitment and activation of CD8+T cells were found in the blood, lymph nodes, and tumor tissues and significantly inhibited the level of PD-1+CD8+T cells in the group of RT (8 Gy)+anti PD-1. This study confirmed the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitors, which can inhibit tumor growth and produce distant effects. The appearance of a distant effect is related to the enhancement in the number and activity of CD8+T cells in the local tumor and peripheral blood and lymph nodes. This study confirms the therapeutic and immune regulatory effect of hypofractionation radiotherapy combined with PD-1 inhibitors.

Reactive oxygen species may be involved in the distinctive biological effects of different doses of 12C6+ ion beams on Arabidopsis.

Heavy ion beam is a novel approach for crop mutagenesis with the advantage of high energy transfer line density and low repair effect after injury, however, little investigation on the biological effect on plant was performed. 50 Gy irradiation significantly stimulated the growth of Arabidopsis seedlings, as indicated by an increase in root and biomass, while 200 Gy irradiation significantly inhibited the growth of seedlings, causing a visible decrease in plant growth. The Arabidopsis seeds were irradiated by 12C6+. Monte Carlo simulations were used to calculate the damage to seeds and particle trajectories by ion implantation. The seed epidermis received SEM detection and changes in its organic composition were detected using FTIR. Evidence of ROS and antioxidant systems were analyzed. RNA-seq and qPCR were used to detect changes in seedling transcript levels. Monte Carlo simulations revealed that high-dose irradiation causes various damage. Evidence of ROS and antioxidant systems implies that the emergence of phenotypes in plant cells may be associated with oxidative stress. Transcriptomic analysis of the seedlings demonstrated that 170 DEGs were present in the 50 Gy and 200 Gy groups and GO enrichment indicated that they were mainly associated with stress resistance and cell wall homeostasis. Further GO enrichment of DEGs unique to 50 Gy and 200 Gy revealed 58 50Gy-exclusive DEGs were enriched in response to oxidative stress and jasmonic acid entries, while 435 200 Gy-exclusive DEGs were enriched in relation to oxidative stress, organic cyclic compounds, and salicylic acid. This investigation advances our insight into the biological effects of heavy ion irradiation and the underlying mechanisms.

Proton-FLASH: effects of ultra-high dose rate irradiation on an in-vivo mouse ear model

FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-β1, TNF-α, IL1α, and IL1β were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.

Effects of Surface Textures Created Using Additive Manufacturing on Shear Bond Strength Between Resin and Zirconia.

This investigation aimed to assess the impact of additive manufacturing-generated surface textures on zirconia bond strength. Zirconia samples (n = 144) fabricated using digital light-processing (DLP) technology were categorized into 6 groups according to the type of surface conditioning (group NN: no designs, no air abrasion; group NY: no designs, with air abrasion; group GN: groove designs, no air abrasion; group GY: groove designs with air abrasion; group HN: hexagon grid, no air abrasion; group HY: hexagon grid, with air abrasion). Composite resin cylinders were cemented to the treated zirconia surfaces with dual-curing, self-adhesive resin cement (Clearfil SA Luting). The shear bond strength (SBS) was tested after water storage for 3 days or 3 days with an additional 10,000 thermocycles. The zirconia samples fabricated using DLP technology have high accuracy. The SBS of the NY, GY, and HY groups did not significantly differ after 3 days, and neither did the SBS of the NN, GN, and HN groups. The NN, NY, and HY groups exhibited reduced SBS compared to their initial values following artificial aging, while the SBS of the remaining three groups were not diminished. The GY group obtained the highest SBS value after aging. Printing grooves with air abrasion can improve the bond strength.

Low-Dose Radiation Yields Lower Rates of Pathologic Response in Esophageal Cancer Patients

BackgroundAlthough neoadjuvant chemoradiation (nCRT) followed by surgery is standard treatment for locally advanced esophageal or gastroesophageal junction (E/GEJ) cancer, the optimal radiation dose is still under debate.ObjectiveThe aim of this study was to assess the impact of different preoperative radiation doses (41.4 Gy, 45 Gy or 50.4 Gy) on pathologic response and survival in E/GEJ cancer patients.MethodsAll consecutive patients with E/GEJ tumors, treated with curative intent between January 2009 and December 2016 in two referral centers were divided into three groups (41.4 Gy, 45 Gy and 50.4 Gy) according to the dose of preoperative radiotherapy. Pathologic complete response (pCR) rates, postoperative morbidity, overall survival (OS) and disease-free survival (DFS) were compared among the three groups, with separate analyses for adenocarcinoma (AC) and squamous cell carcinoma (SCC).ResultsFrom the 326 patients analyzed, 48 were included in the 41.4 Gy group (14.7%), 171 in the 45 Gy group (52.5%) and 107 in the 50.4 Gy group (32.8%). Postoperative complication rates were comparable (p = 0.399). A pCR was observed in 15%, 30%, and 34% of patients in the 41.4 Gy, 45 Gy and 50.4 Gy groups, respectively (p = 0.047). A 50.4 Gy dose was independently associated with pCR (odds ratio 2.78, 95% confidence interval 1.10–7.99) in multivariate analysis. Within AC patients, pCR was observed in 6.2% of patients in the 41.4 Gy group, 29.2% of patients in the 45 Gy group, and 22.7% of patients in the 50.4 Gy group (p = 0.035). No OS or DFS differences were observed.ConclusionsA pCR was less common after a preoperative radiation dose of 41.4 Gy in AC patients. Radiation dose had no impact on postoperative morbidity, long-term survival, and recurrence.

CT texture features and lung shunt fraction measured using 99mTc-macroaggregated albumin SPECT/CT before trans-arterial radioembolization for hepatocellular carcinoma patients

The aim of this study is to determine whether contrast-enhanced computed tomography (CECT)-based texture parameters can predict high (> 30 Gy) expected lung dose (ELD) calculated using 99mTc macroaggregated albumin single-photon emission computed tomography/computed tomography (SPECT/CT) for pre-trans-arterial radioembolization (TARE) dosimetry. 35 patients were analyzed, with a treatable planned dose of ≥ 200 Gy for unresectable hepatocellular carcinoma (HCC). Lung shunt fraction (LSF) was obtained from planar and SPECT/CT scans. Texture features of the tumor lesion on CECT before TARE were analyzed. Univariate and multivariate linear regression analyses were performed to determine potential ELD > 30 Gy predictors. Among the 35 patients, nine (25.7%) had ELD > 30 Gy, and had a higher LSF than the ELD ≤ 30 Gy group using the planar (20.7 ± 8.0% vs. 6.3 ± 3.3%; P < 0.001) and SPECT/CT (12.4 ± 5.1% vs. 3.5 ± 2.0%; P < 0.001) scans. The tumor integral total (HU × L) value was a predictor for high LSF using SPECT/CT, with an area under the curve, sensitivity, and specificity of 0.983 (95% confidence interval: 0.869–1.000, P < 0.001), 100%, and 88.5%, respectively. The tumor integral total value is an imaging marker for predicting ELD > 30 Gy. Applying CECT texture analysis may assist in reducing time and cost in patient selection and modifying TARE treatment plans.

Predicting Teeth Extraction after Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Cancer Patients Using the Novel GLUCAR Index

To evaluate the value of the newly created GLUCAR index in predicting tooth extraction rates after concurrent chemoradiotherapy (C-CRT) in locally advanced nasopharyngeal carcinomas (LA-NPCs). Methods: A total of 187 LA-NPC patients who received C-CRT were retrospectively analyzed. The GLUCAR index was defined as ′GLUCAR = (Fasting Glucose × CRP/Albumin Ratio) by utilizing measures of glucose, C-reactive protein (CRP), and albumin obtained on the first day of C-CRT. Results: The optimal GLUCAR cutoff was 31.8 (area under the curve: 78.1%; sensitivity: 70.5%; specificity: 70.7%, Youden: 0.412), dividing the study cohort into two groups: GLUCAR ˂ 1.8 (N = 78) and GLUCAR ≥ 31.8 (N = 109) groups. A comparison between the two groups found that the tooth extraction rate was significantly higher in the group with a GLUCAR ≥ 31.8 (84.4% vs. 47.4% for GLUCAR ˂ 31.8; odds ratio (OR):1.82; p &lt; 0.001). In the univariate analysis, the mean mandibular dose ≥ 38.5 Gy group (76.5% vs. 54.9% for &lt;38.5 Gy; OR: 1.45; p = 0.008), mandibular V55.2 Gy group ≥ 40.5% (80.3 vs. 63.5 for &lt;40.5%, p = 0.004, OR; 1.30), and being diabetic (71.8% vs. 57.9% for nondiabetics; OR: 1.23; p = 0.007) appeared as the additional factors significantly associated with higher tooth extraction rates. All four characteristics remained independent predictors of higher tooth extraction rates after C-CRT in the multivariate analysis (p &lt; 0.05 for each). Conclusions: The GLUCAR index, first introduced here, may serve as a robust new biomarker for predicting post-C-CRT tooth extraction rates and stratifying patients according to their tooth loss risk after treatment.

Evaluation of the shear bond strength of various adhesives on the surface of enamel irradiated with various doses of radiotherapy

We aimed to compare the shear bond strength (SBS) forces on the enamel surface with 2 adhesives after treatment with various radiation doses. A total of 120 premolars were included in the study. The teeth were randomly divided into 5 main groups (n= 24): negative control (without aging), positive control (with aging), 40 Gy, 60 Gy, and 70 Gy radiation. The 40 Gy, 60 Gy, and 70 Gy groups underwent conventional radiotherapy 5 days a week with a dose of 2 Gy each day. After the radiotherapy, all samples except the negative control group were subjected to thermal cycle aging. In all 5 groups, the specimens were divided into 2 subgroups, and half were bonded using 2 adhesives. After bonding, the universal Shimadzu test device was used to analyze the SBS. After the test, the tooth surfaces were examined under a stereomicroscope to determine the adhesive remnant index. When adhesives were compared, Biofix adhesive's bond strength value was statistically higher in the 40 Gy group than in the Transbond XT group (P= 0.001). The SBS value was higher in all irradiated groups than in nonirradiated groups (P= 0.001). When the adhesive remnant index score was analyzed, no significant difference was found among the groups. The SBS increased in irradiated teeth compared with unirradiated teeth, and the SBS values of both adhesives were within the acceptable limits in all radiation groups.

Hsa_circ_0000392 affects the radiation sensitivity of cervical cancer by targeting the miR-145-5p/CRKL/MAPK pathway

Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.

Effects of Radiation Doses on Clinical Recurrence in Patients with Biochemically Recurrent Prostate Cancer after Prostatectomy.

Salvage radiotherapy (SRT) to the prostate bed is the only curative treatment for patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Although several systematic reviews indicated that a dose escalation in the range of 60-70 Gy improved biochemical control, the effects of radiation doses on clinical relapse after SRT remain unclear. Our aim was to investigate the relationship between radiation doses and clinical relapse-free survival (cRFS) after SRT. We identified 295 eligible patients receiving SRT for biochemically recurrent prostate cancer after RP between 2005 and 2018 at 15 institutions. Sixteen patients (5%) received short-term (< 6 months) androgen deprivation therapy (ADT) following RP and/or concurrently with SRT. SRT was delivered to the prostate and seminal vesicle bed using photon beams at a median (range) dose of 66 Gy (61-85) in 1.8-3.0 Gy fractions. The primary outcome was cRFS. Clinical relapse was identified on radiological imaging and/or biopsy and included local recurrence, lymph node metastasis, and distant metastasis. In all analyses, doses were recalculated as an equivalent dose in 2-Gy fractions (EQD2) with α/β = 1.5 Gy. Clinical RFS between the EQD2 ≥ 66 Gy (n = 229) and EQD2 < 66 Gy (n = 66) groups were compared using the Log-rank test, followed by univariate and multivariate Cox regression analyses and a subgroup analysis. The median follow-up duration was 73 months. Among patients with BCR (n = 119), 79 of 96 (82%) in the EQD2 ≥ 66 Gy group and 21 of 23 (91%) in the EQD2 < 66 Gy group received second salvage ADT (p = 0.36). Among all patients (n = 295), clinical relapse was identified in 22 (7%) patients after SRT. Six-year biochemical relapse-free survival (bRFS), cRFS, cancer-specific survival (CSS), and overall survival (OS) rates were 58%, 93%, 98%, and 94%, respectively. Six-year cRFS rates were 94% (95% confidence interval [CI], 90-97) in the EQD2 ≥ 66 Gy group and 87% (95% CI, 75-93) in the EQD2 < 66 Gy group (p = 0.020). The multivariate analysis revealed that EQD2 < 66 Gy, Gleason score ≥ 8, seminal vesicle involvement, and PSA at BCR ≥ 0.5 ng/ml correlated with clinical relapse (p = 0.0016, 0.014, 0.011, and 0.027, respectively). The subgroup analysis showed the consistent benefit of EQD2 ≥ 66 Gy in patients across most subgroups including PSA at BCR after RP, extracapsular extension, and age at SRT. This large multi-institutional observational study demonstrated that a higher SRT dose (EQD2 ≥ 66 Gy) resulted in superior cRFS. The present result supports the dose recommendations in the 2023 National Comprehensive Cancer Network guidelines (64-72 Gy) even in terms of clinical relapse. Prospective trial is warranted to investigate an upper threshold for optimal SRT dose.

High Dose Hyperfractionated Thoracic Radiotherapy vs. Standard Dose for Limited Stage Small-Cell Lung Cancer: A Multicenter, Open-Label Randomized, Phase 3 Trial

Limited stage small-cell lung cancer (LS-SCLC) is associated with poor prognosis. We aimed to assess the efficacy and safety of high-dose, hyperfractionated thoracic radiotherapy of 54 Gy in 30 fractions compared with standard dose (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC. The study was an open-label, randomized, phase 3 trial, done at 16 public hospitals in China. Key inclusion criteria were patients aged 18-70 years, with previously histologically or cytologically confirmed LS-SCLC, previously untreated or received 1-2 courses of intravenous cisplatin (75 mg/m²of body-surface area, on day 1 or divided into two days of each cycle) or carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle)and intravenous etoposide (100 mg/m²of body-surface area, on days 1-3 of each cycle), and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions or the simultaneous integrated boost VMAT (SIB-VMAT) of 54 Gy in 30 fractions to the primary lung tumor and lymph node metastases starting 0-42 days after the first chemotherapy course. Both groups of patients received thoracic radiotherapy twice per day and 10 fractions per week. Prophylactic cranial radiation (PCI, 25 Gy in 10 fractions) was implemented to patients with responsive disease. The primary endpoint was overall survival. Safety was analyzed in the as-treated population. Between June 30, 2017, and April 6, 2021, 224 eligible patients were enrolled and randomly assigned to 54 Gy (n = 108) or 45 Gy (n = 116). Median follow-up for the primary analysis was 45 months (IQR 41-48). Median overall survival was significantly improved in the 54 Gy group (62.4 months) compared with the 45 Gy group (43.1 months; p = 0.001). Median progression-free survival was significantly improved in the 54 Gy group (30.5 months) compared with the 45 Gy group (16.7 months; p = 0.044). The most common grade 3-4 adverse events were neutropenia (30 [28%] of 108 patients in the 54 Gy group vs 27 [23%] of 116 patients in the 45 Gy group), neutropenic infections (6 [6%] vs 2 [2%]), thrombocytopenia (13 [12%] vs 12 [10%]), anemia (6 [6%] vs 4 [3%]), and esophagitis (1 [1%] vs 3 [3%]). Treatment-related serious adverse events occurred in 9 [8%] patients in the 54 Gy group and 16 [14%] patients in the 45 Gy group. There were one treatment-related deaths in 54 Gy group (myocardial infarction). Compared with standard thoracic radiotherapy dose of 45 Gy, the high dose of 54 Gy improved overall survival and progression-free survival without increasing toxicities in patients with LS-SCLC, supporting twice-daily hyperfractionated thoracic radiotherapy of 54 Gy with concurrent chemotherapy is an alternative treatment option for LS-SCLC. This study is complete and registered with ClinicalTrials.gov, NCT03214003.

The Early and Late Effects of High-Dose Irradiation on Cardiac Injury in a Rat Model

Radiation-induced heart disease is a critical concern after radiotherapy (RT) for thoracic and chest wall tumors; however, the biological effects and mechanisms are still unknown. In this study, we investigated dose-responsive functional and pathological changes in rat hearts at 1, 3, and 5 months after high-dose irradiation. Then, we sought to elucidate the underlying mechanisms of myocardial changes induced by high-dose irradiation. Whole hearts of rats (N = 72) were irradiated with a single fraction of 0 (control), 10, 20, or 30 Gy and allocated into three groups according to the follow-up period after RT: baseline, one, three, and five months. During follow-up periods, rats underwent functional evaluation by electrocardiogram and echocardiography at 4-week intervals. If a rat's body weight decreased by 20% or more, it was considered premature death, and the heart was explanted immediately. Otherwise, all hearts were explanted when each group's follow-up period was completed. Pathological changes of cardiac structures were evaluated using a light microscope after staining with hematoxylin-eosin, Masson's trichrome, α-smooth muscle actin, desmin, and connexin-43. All rats irradiated with 0 or 10 Gy completed their follow-up periods with continuously increasing body weight. However, among rats irradiated with 20 or 30 Gy, half of the rats died prematurely at 8-10 weeks after RT, and the remainder survived until 20 weeks. In echocardiography, increased wall thickness and E/E' ratio, and decreased end-diastolic volume were observed in 20-30 Gy groups compared to 0-10 Gy groups from 8 weeks after RT. Ejection fraction was preserved in all groups. In pathological review, 20-30 Gy groups demonstrated diffuse inflammation and vacuolization at 4 weeks. Then, at 8 weeks, prominent fibrotic changes and intercalated disc disruptions were observed. Notably, fibrotic changes were somewhat resolved at 20 weeks, but intercalated disc disruptions were not repaired until 20 weeks. The 0 and 10 Gy groups showed no significant changes in both functional and pathological analyses. Rats irradiated with 20 or 30 Gy showed diastolic dysfunction in functional analysis and time-dependent myocardial changes in pathological analysis. Radiation-induced fibrosis might be a "reactive" fibrosis, which could proceed to either a profibrotic course (progressive fibrosis) or an anti-fibrotic course (recovery phase). Further studies are needed to identify whether high-dose irradiation-induced cardiac fibrosis could be reversible.

30 Gy vs. 45 Gy Consolidative Thoracic Radiation (cTRT) for Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Multicenter, Randomized, Phase 3 Trial

Consolidative thoracic radiotherapy (cTRT) showed potential benefit to extensive stage small cell lung cancer (ES-SCLC). However, the optimum dose of cTRT is unknown. The purpose of this randomized trial was to compare the effect of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC. This phase III, randomized trial was conducted in 12 public hospitals in China. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions or 45 Gy in 15 fractions cTRT. The primary outcome was 2-year overall survival (OS). Secondary outcomes included 2-year progression-free survival (PFS), 2-year local control (LC) and radiation treatment related toxicity. The primary objective was to detect an OS improvement in 45 Gy cTRT group at 2 years from 13% to 26% assuming a two-sided a = 0.05 and power of 85%, with a planned sample size of 186 patients. This trial was registered with Clinical Trials.gov, number NCT02675088. Between January 15, 2016, and September 20, 2022, 90 patients were randomly assigned either 30 Gy in 10 fractions (n = 50) or 45 Gy in 15 fractions (n = 40) cTRT group. Recruitment to the trial closed early due to slow accrual since first-line chemoimmunotherapy has become the new standard of care for ES-SCLC. The median age of patients was 58 years, 87.8% were male, 76.7% had a smoking history, 95.6% received IMRT, and 58.9% received prophylactic cranial irradiation. At a median follow-up of 39.9 months (IQR 27.2-59.2), there was no significant difference in the 2-year OS between the 45 Gy group and the 30 Gy group, at 43.4% (95% CI 29.3%-64.3%) and 40.0% (95% CI 27.9%-59.1%), respectively (log-rank p = 0.62; HR 1.13 [95% CI 0.69-1.84]). The 2-year PFS was 12.1% (95% CI 4.3%-33.8%) in the 45 Gy group and 9.0% (95% CI 3.2%-25.2%) in the 30 Gy group (log-rank p = 0.25, HR 0.76(95% CI [0.478-1.22]). There were also no significant differences in locoregional recurrence free survival (log-rank p = 0.75; HR 0.888 [95% CI 0.423-1.863]) and distant metastasis free survival (log-rank p = 0.95; HR 1.015 [95% CI 0.624-1.651]) between two groups. No grade 5 toxicity was observed in both groups. Patients treated with higher cTRT dose presented with increased incidence of grade 3+ radiation pneumonitis (10% vs 2%) and hematological toxicity (20% vs 12.5%). This randomized trial did not find a higher probability of survival improvement in patients with ES-SCLC receiving cTRT of 45 Gy in 15 fractions compared with 30 Gy in 10 fractions. In contrast, there was an increase in toxicity, especially radiation pneumonitis. Additional randomized studies investigating the role of cTRT in ES-SCLC after a response to chemoimmunotherapy are warranted.

Comparing Acute Oral Mucosa Toxicity Associated with Minibeam and Conventional Radiotherapy

Acute oral mucosa toxicity is associated with ulceration, severe pain, and nutritional deficiencies that may lead to treatment interruptions and a decreased quality of life for head and neck cancer patients. Minibeam radiotherapy (MRT) is a type of spatially fractionated radiotherapy that delivers an alternating pattern of sub-millimeter wide peaks of high dose immediately adjacent to much lower valley doses. By delivering a non-uniform dose distribution, MRT allows for elevated peak doses while maintaining extraordinary normal tissue tolerance. In this study, we used an acute oral mucosa toxicity mouse model to test the hypothesis that MRT provides superior tissue sparing compared to conventional radiotherapy (CRT). A total of 33 female C57BLJ6 mice were randomized by body weight (BW) across two CRT groups (n = 4/group) receiving open field radiation of 16 and 20 Gy and five MRT groups (n = 5/group) receiving peak:valley doses of 48:8, 72:12, 96:16, 96:8, and 152:8 Gy. All radiation was given in one fraction. The CRT groups were irradiated with a 10 mm circular field using a 225 kVp PA x-ray beam encompassing the oral cavity and oropharynx. The MRT groups were irradiated with the same arrangement, but the beam was collimated into 0.5 mm wide minibeams spaced 1.1 mm center-to-center using tungsten collimators of 0.5, 1, and 2.5 mm thickness to deliver peak-to-valley ratios (PVRs) of 6:1, 12:1, and 19:1. Acute effects in the oral mucosa were studied using changes in BW as a surrogate for clinically significant oral mucositis. BWs were measured daily starting on the day of treatment, and BW changes were computed relative to the day of treatment. The toxicity endpoint was defined such that mice losing >20% BW were humanely euthanized. Doses of 20 Gy CRT and 96:16 Gy MRT were highly toxic, with all animals in these groups reaching the toxicity endpoint between 9-11 days post-RT, compared to only one animal in the 16 Gy CRT group, and no animals in the other MRT groups. The BWs of all surviving animals returned to baseline within 15 days post-RT. The groups 48:8, 96:8, and 152:8 Gy showed similar BW loss and full recovery patterns. Additionally, the groups 48:8, 72:12, and 96:16 Gy showed that, for the same PVR, increasing the valley dose resulted in increased BW loss. Lastly, animals did not tolerate 96:16 Gy, but those in the 96:8 Gy group fully recovered. Despite the extreme toxicity caused by 20 Gy CRT, animals in the MRT groups tolerated peak doses up to 152 Gy when the valley dose was 8 Gy. These results confirm the superior normal tissue sparing capacity of MRT compared to CRT in an oral mucosa mouse model. We delivered tolerable MRT peak doses an order of magnitude larger than toxic CRT doses. Importantly, our results suggest that valley dose is the most useful parameter to assess acute toxicity when using MRT. Our data may prove useful for eventual clinical applications of MRT in head and neck cancers.

Effect of X-ray irradiation on quality, cell ultrastructure and electrical parameters of postharvest kiwifruit

In this research, kiwifruit was irradiated with different doses (0, 200, 400 Gy) of X-ray and stored in cold storage for 120 days (0– 1 °C, 90– 95% relative humidity) to investigate the postharvest preservation effect of X-ray. The results indicated that 400 Gy X-ray reduced the decay rate and respiration rate, delayed the rise in soluble solids content (SSC), and inhibited chlorophyll decomposition, maintained higher peroxidase and phenylalanine deaminase activities and lower polyphenol oxidase activity compared to the control group. Microscopically, the 400 Gy group displayed a clear and well-integrated cell structure at the end of storage. Based on the electrical parameters, Rs was screened as a characteristic electrical parameter common in all groups, and decay rate and SSC as characteristic qualities. The study proved that X-ray irradiation has a positive effect on kiwifruit preservation and the electrical parameter Rs can be used to predict the quality of kiwifruit after X-ray irradiation.

The role of single‐walled carbon nanotubes functionalized with gold to increase radiosensitivity of cancer cells to X‐ray radiation

The improvement of high‐Z‐based metallic nanostructures as radiosensitizers with high monolithicity and versatility by superadditive therapeutic track and the good protective effect is considerable, but they are limited by some problems such as nonideal selectivity for the target tissue. In this study, nanosystems were developed to enhance the efficacy of radiotherapy and reduce cancer cell survival based on innovative gold (Au) functionalized oxygen‐single‐walled carbon nanotubes (O‐SWCNTs). We illustrate the use of folic acid (FA) as a targeting agent and bovine serum albumin (BSA) to stabilize the physiological environment and increase durability. The physical and chemical properties of the nanosystems were evaluated using transmission electron microscopy (TEM), selected area electron diffraction (SAED), dynamic light scattering (DLS), zeta potential, X‐ray diffraction (XRD), ultraviolet–visible (UV–Visible), and Fourier transform infrared (FTIR) techniques. Finally, the MTT assay was used to investigate the therapeutic effects of nanoparticles in the 4 T1 mouse breast cancer model in the presence and absence of X‐rays. So, the cancer cells experienced a more effective reduction in survival after receiving O‐SWCNTs‐Au‐BSA‐FA + 8 Gy than O‐SWCNTs‐BSA, Au‐BSA‐FA, and O‐SWCNTs‐Au‐BSA + 8 Gy groups.

Screening of lipids for long-term brain irradiation effect based on non-targeted lipidomics

Irradiation and weightlessness are the main causes of neurological damage in astronauts on long-duration manned flights. Ionizing radiation induces the proliferation of microglia and astrocytes and the production of pro-inflammatory and chemokines, leading to neuroinflammatory responses. Peripheral blood sampling is convenient and serum lipidomic analysis allows the characterisation of the lipid profile of biological fluids in serum after whole brain irradiation (WBI) and the assessment of the long-term effects of radiation-induced brain damage. Therefore, a systematic study of neurological damage after whole brain irradiation using a lipidomic approach can help to elucidate the dose- and time-dependent nature of radiation damage and the associated molecular mechanisms of damage, and provide a corresponding theoretical basis for the selection of targets for space radiation bio-protection. In this study the dose dependence of WBI injury was evaluated by monitoring different factors as, hair removal, body weight, and organ index. Data collected after one month after the WBI upon 10 Gy, 10 Gy × 3, and 30 Gy. Non-targeted lipidomics was used to analyze the differential lipids in serum, one-month after the WBIinduced by different radiation doses. The results indicated that the degree of injury in the 10 Gy × 3 group was between 10 Gy, and 30 Gy groups. The proliferation of microglia (Iba-1+), and astrocytes (GFAP+) in different brain regions (prefrontal cortex, striatum, hippocampus, midbrain, and cerebellum) was also analyzed. When parameters are used in combination that prominently effect long-term inflammatory damage to the hippocampus. Our study showed significant difference in the expression of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine lipids in the serum of rats one month after WBI. A total of 191 differential lipids were found common in the 10 Gy, 10 Gy × 3, and 30 Gy groups relative to the non-irradiated group. The lipids belonging to the subclasses, sphingomyelin, monoacylglycerol, lysophosphatidylethanolamine, ceramide nonhydroxyfatty acidsphingosines, and anacardic acid (Acar) were down-regulated. Lipids that belonged to sulfoquinovosyl diacylglycerol, phosphatidylglycerol, monogalaktos diacylglycerol, lysodiacylglyceryltrimethyl homoserines, and cholesterol ester were up-regulated according to our study. Among these lipids, ω-6 20:4 fatty acids, lysophosphatidylcholines (LPCs), and triglycerides (TAGs) showed a promoting effect on inflammation; however, others such as ceramide (Cer), sphingomyelin (SM) showed an inhibitory effect on inflammation. Overall, our study shows a comprehensive long-term inflammatory response after WBI.

Optimized Conformal Total Body Irradiation with VMAT Using a Linear-Accelerator-Based Radiosurgery Treatment System in Comparison to the Golden Standard Helical TomoTherapy.

Modern irradiation techniques for optimized conformal TBI can be realized by Helical Tomotherapy (HT) or Volumetric Modulated Arc Therapy (VMAT), depending on the availability of suitable specialized equipment. In this dosimetric planning study, we compared both modalities and addressed the question of whether VMAT with small field sizes is also suitable as a backup in case of HT equipment malfunctions. For this purpose, we retrospectively used planning computed tomography (CT) data from 10 patients treated with HT with a total dose of 8 Gy (n = 5) or 12 Gy (n = 5) for treatment planning for VMAT with a small field size (36 × 22 cm). The target volume coverage, dose homogeneity at target volume, and dose reduction in organs at risk (OAR) (lungs, kidneys, lenses) were analyzed and compared. One patient was irradiated with both modalities due to a device failure of the HT equipment during the study, which facilitated a comparison in a real clinical setting. The findings indicate that in addition to a higher mean dose to the lenses in the 12 Gy group for VMAT and a better dose homogeneity in the target volume for HT, comparably good and adequate target dose coverage and dose reduction in the other OAR could be achieved for both modalities, with significantly longer treatment times for VMAT. In conclusion, after appropriate optimization of the treatment times, VMAT using linear accelerator radiosurgery technology can be used both as a backup in addition to HT and in clinical routines to perform optimized conformal TBI.