Radiotherapy In Cancer Patients Research Articles

Description of sleep disorders in radiotherapy patients of head and neck cancer

ObjectiveTo depict the picture of sleep disorders of head and neck cancer radiotherapy patients. MethodThis research was a descriptive study, using total sampling in head and neck cancer radiotherapy patients in April 2019 at Hasanuddin University Hospital as many as 16 samples using PSQI questionnaire, Snoring score, Epworth Sleepness Scale, and Insomnia Severity Index. Result14 people experienced sleep disorders of 16 patients. They are at risk for suffering from obstructive sleep apnea, and two people are easily sleepy, nine people have insomnia. ConclusionHead and neck cancer radiotherapy patients suffer more insomnia sleep disorders and have a risk of suffering from obstructive sleep apnea (OSA).

Reducing 4DCBCT scan time and dose through motion compensated acquisition and reconstruction

Conventional 4DCBCT captures 1320 projections across 4 min. Adaptive 4DCBCT has been developed to reduce imaging dose and scan time. This study investigated reconstruction algorithms that best complement adaptive 4DCBCT acquisition for reducing imaging dose and scan time whilst maintaining or improving image quality compared to conventional 4DCBCT acquisition using real patient data from the first 10 adaptive 4DCBCT patients. Adaptive 4DCBCT was implemented in the ADaptive CT Acquisition for Personalized Thoracic imaging clinical trial. Adaptive 4DCBCT modulates gantry rotation speed and kV acquisition rate in response to the patient’s real-time respiratory signal, ensuring even angular spacing between projections at each respiratory phase. We examined the first 10 lung cancer radiotherapy patients that received adaptive 4DCBCT. Fast, 200-projection scans over 60–80 s, and slower, 600-projection scans over ∼240 s, were obtained after routine patient treatment and compared against conventional 4DCBCT acquisition. Adaptive 4DCBCT acquisitions were reconstructed using Feldkamp−Davis−Kress (FDK), McKinnon–Bates (MKB), Motion Compensated FDK (MCFDK) and Motion Compensated MKB (MCMKB) algorithms. Reconstructions were assessed via, Structural SIMilarity (SSIM), Signal-to-Noise-Ratio (SNR), Contrast-to-Noise-Ratio (CNR), Tissue Interface Sharpness of Diaphragm (TIS-D) and Tumor (TIS-T). The 200- and 600-projection adaptive 4DCBCT acquisition corresponded to 85% and 55% reduction in imaging dose, shorter and similar scan times of approximately 90 s and 236 s respectively, compared to conventional 4DCBCT acquisition. 200- and 600-projection adaptive 4DCBCT reconstructions achieved more than 0.900 SSIM relative to conventional 4DCBCT acquisition. Compared to conventional 4DCBCT acquisition, 200-projection adaptive 4DCBCT reconstructions achieved higher SNR, CNR, TIS-T, TIS-D with motion compensated algorithms, MCFDK (208%, 159%, 174%, 247%) and MCMKB (214%, 173%, 266%, 245%) respectively. The 200-projection adaptive 4DCBCT MCFDK- and MCMKB-reconstruction results show image quality improvements are possible even with 85% fewer projections acquired. We established acquisition-reconstruction protocols that provide substantial reductions in imaging time and dose whilst improving image quality.

Preparation and Effect of Selenium Nanoparticles/Oligochitosan on the White Blood Cell Recovery of Mice Exposed to Gamma-Ray Radiation

Owing to their excellent bioavailability, high bioactivity, and low toxicity, selenium nanoparticles (SeNPs) are emerging nanomaterials. In this study, SeNPs with a size of ∼41.8 nm were synthesised by γ-irradiation using oligochitosan (OCS) as the stabiliser. As-synthesized SeNPs/OCS were characterised by UV-Vis spectroscopy, transmission electron microscopy, and energy-dispersive X-ray (EDX) analysis. Results revealed that the as-obtained SeNP/OCS powder exhibits high purity. The SeNP/OCS solution’s stability test results indicated that the SeNP/OCS solution stored at 4°C exhibits good stability for 60 days. The SeNP/OCS solution was unstable at ambient temperature, and SeNP/OCS exhibited agglomeration after about 15 days. SeNP/OCS products recovered the total white blood cells of γ-ray irradiated mice. The SeNP/OCS product, which was synthesised by a green approach, with high purity and efficient recuperation of white blood cells, can be used potentially as a functional supplement to assist cancer radiotherapy patients.

Can SARS-CoV-2 change individual radiation sensitivity of the patients recovered from COVID-19? (experimental and theoretical background).

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Science of Ukraine has been studying the mechanisms and specificities of individual radiation sensitivity (IRS) formation in professionals who work in the field of ionizing radiation, cancer patients and representatives of other population groups. Our data based on the use of G2-test in in vitro irradiated blood lymphocytes in late G2-period of cell cycle indicated an increased carcinogenic risk in professionals with high IRS. We suggest that the COVID-19pandemic could make significant adjustments in the formation of IRS in professionals who have survived the disease and continue to work with ionizing radiation (IR). Increased systemic inflammatory activity, which persists for a long time in COVID-19patients, in combination with low-dose range irradiation (professionals who continue to work with IR) and with local irradiation in the high-dose range (radiation therapy for cancer patients) may affect IRS. Repeated determination of IRS in professionals who have had COVID-19infection, using chromosomal G2-radiation sensitivity assay will answer the question: can SARS-CoV-2coronavirus affect the IRS? The proposed hypothesis of the radiosensitivity evolution needs further experimental validation using a set of radiobiological indices to clarify the mechanism of IRS formation following COVID-19infection. The detected changes (increase) of human IRS after COVID-19must be taken into account for personalized planning of radiotherapy of COVID-19cancer patients.

Traditional chinese medicine diet paratherapy for alleviating toxicity in chemotherapy and radiotherapy in cancer patients: a meta-analysis

The aim of this meta-analysis was to evaluate the efficacy of Traditional Chinese Medicine (TCM) diet therapy in alleviating the toxicity of chemotherapy and radiotherapy in patients with cancer. Searches were conducted in seven databases for relevant studies published from 1, January 2000 to 1 March, 2020. Randomized controlled trials (RCTs) comparing TCM diet with ordinary diet of cancer patients undergoing chemotherapy and(or) radiotherapy were included. The study has been registered on the “PROSPERO” website with registration number of CRD42019131232. A total of sixteen RCTs included 2336 cases were included. TCM diet therapy is superior to ordinary diet in terms of reducing incidence of leukopenia [RR= 0.57; 95% CI (0.47, 0.69); P<0.0001], and nausea and vomiting [RR=0.54, 95% CI= (0.43, 0.70), P= 0.004], increasing hemoglobin [MD=10.04; 95% CI (7.66, 12.41); P<0.0001], improving Karnofsky Performance Status (KPS) [RR= 1.28; 95% CI (1.15, 1.42); P<0.0001], and gaining weight [RR=1.53, 95%CI= (1.38, 1.68), P < 0.0001] in patients with cancer undergoing chemotherapy and(or) radiotherapy. This meta-analysis demonstrated that TCM diet may reduce the toxicity of chemotherapy (and/or radiotherapy).

Therapeutic challenges in radiation-induced salivary gland cancers.

To give an overview of recent advances in therapeutic approaches of radiation-induced salivary gland cancers (ri-SGCs). Reirradiation with protons and carbon ions demonstrated to be feasible, safe and to offer good local control rates, with the possibility of overcoming radioresistance and dosimetric issues in previously irradiated cancer patients. Chromosomal rearrangements, gene fusions and expression profiles are important to identify specific cancer subtypes and can guide tailored systemic therapy. Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival.

The effect of individual nutritional support and nurse follow-up on weight loss during radiotherapy in cancer patients

Purpose:The aim of this study was to evaluate the nutritional status of patients receiving definitive or adjuvant radiotherapy with head and neck, pelvic, thorax and intraabdominal tumors and to determine their weight loss. Patients and Methods:40 patients admitted to the radiation oncology outpatient clinic since 01.11.2015 and planned head, thoracic, abdominal and pelvic radiotherapy were included in the study. The patients were evaluated before the treatment and in addition to the daily nutrition of the patients, special nutritional support was provided as 35 kcal/kg energy, 2gr/kg protein and 15 mg glutamine daily. The weight loss of the patients evaluated by radiation oncologist and nurse was recorded. Results:The mean age was 61 years (range, 39-86 years). 9 patients with lung cancer were over 70 years old and had definitive radiotherapy. All patients underwent radiotherapy treatment without interrupting treatment, except for a 86-year-old patient scheduled for adjuvant therapy with gastric cancer and two patients with lung cancer receiving chemoradiotherapy. 72% of the patients continued their nutritional support during the entire treatment. When weight loss was evaluated, only 8% of patients had more than 10% weight loss. According to the nutritional support, weight loss rates were found to be significantly lower in patients who fully applied nutritional support (p: 0.003). Conclusion:Early and intense nutritional support of cancer patients with risk of malnutrition may lead to less weight loss during radiotherapy.

PD-0428: Large scale evaluation of sarcopenia as prognostic factor in lung cancer radiotherapy patients

PD-0428: Large scale evaluation of sarcopenia as prognostic factor in lung cancer radiotherapy patients

Monitoring DNA Damage and Repair in Peripheral Blood Mononuclear Cells of Lung Cancer Radiotherapy Patients

Simple SummaryEvery patient responds to radiotherapy in individual manner. Some suffer severe side-effects because of normal tissue toxicity. Their radiosensitivity can be caused by inability of DNA repair system to fix radiation-induced damage. The γ-H2AX assay can detect such deficiency in untransformed primary cells (e.g., peripheral blood mononuclear cells, PBMC), over a period of only hours post ex-vivo irradiation. Earlier we have shown that the level and kinetics of decline (repair) of radiation-induced DNA damage detected by the assay is a measure of the cellular radiosensitivity. In this study, we applied the γ-H2AX assay to judge the radiosensitivity of lung cancer radiotherapy patients as normal or abnormal, based on kinetics of DNA damage repair. Considering the potential of the assay as a clinical biodosimeter, we also monitored DNA damage in serial samples of PBMC during the course of radiotherapy. This study opens an opportunity to monitor individual response to radiotherapy treatment.Thoracic radiotherapy (RT) is required for the curative management of inoperable lung cancer, however, treatment delivery is limited by normal tissue toxicity. Prior studies suggest that using radiation-induced DNA damage response (DDR) in peripheral blood mononuclear cells (PBMC) has potential to predict RT-associated toxicities. We collected PBMC from 38 patients enrolled on a prospective clinical trial who received definitive fractionated RT for non-small cell lung cancer. DDR was measured by automated counting of nuclear γ-H2AX foci in immunofluorescence images. Analysis of samples collected before, during and after RT demonstrated the induction of DNA damage in PBMC collected shortly after RT commenced, however, this damage repaired later. Radiation dose to the tumour and lung contributed to the in vivo induction of γ-H2AX foci. Aliquots of PBMC collected before treatment were also irradiated ex vivo, and γ-H2AX kinetics were analyzed. A trend for increasing of fraction of irreparable DNA damage in patients with higher toxicity grades was revealed. Slow DNA repair in three patients was associated with a combined dysphagia/cough toxicity and was confirmed by elevated in vivo RT-generated irreparable DNA damage. These results warrant inclusion of an assessment of DDR in PBMC in a panel of predictive biomarkers that would identify patients at a higher risk of toxicity.

Nutrition during radiotherapy of cancer patients

Nutrition during radiotherapy of cancer patients

Abstract 2413: Ferroptosis plays an important role in the radiotherapy-induced tumor suppression and radioresistance

Abstract Introduction: Radiotherapy (RT) is widely used to treat cancers, but radioresistance remains a major factor in the failure of RT. RT generates reactive oxygen species (ROS) through the radiolysis of cellular water and the stimulation of oxidase, causing cellular damage. Ferroptosis is a regulated cell death induced by iron-dependent peroxidation of phospholipids containing polyunsaturated fatty acids (PUFA-PLs), which is morphologically and mechanistically distinct from apoptosis. There are several core regulators in ferroptosis pathway. SLC7A11 and GPX4 play a role in inhibiting ferroptosis, whereas ACSL4, as an essential lipid metabolism enzyme, promotes ferroptosis by regulating the biosynthesis of PUFA-PLs. Ferroptosis can be induced by either class 1 ferroptosis inducers (FINs) that inhibit SLC7A11 or class 2/3 FINs that inhibit or deplete GPX4. Our study aims to determine the role and mechanisms by which ferroptosis contributes to RT-induced cell death and tumor suppression and to evaluate therapeutic potential of FINs as robust radiosensitizers. Methods: Ferroptosis markers such as lipid peroxidation or PTGS2 expression was evaluated by flow cytometry, q-PCR or transmission electron microscopy (TEM). Mechanisms were analyzed by western blot and CRISPR-Cas9. Patient derived xenografts (PDX) co-treated with RT and FINs were employed to access the combination effectiveness. Samples were collected from patients before and after RT and ferroptosis marker 4-HNE was correlated with prognosis of patients. Results: RT induced lipid peroxidation and PTGS2 expression in a variety of cancer types and TEM revealed that cancer cells after RT exhibited shrunken mitochondria with enhanced membrane density, a morphologic feature of ferroptosis. Treatment with ferroptosis inhibitor ferrostatin-1 significantly restored cell survival that had been reduced by exposure to RT, suggesting ferroptosis represents an important part of the RT-induced cell death response. Mechanistically, RT up-regulated the expression of ACSL4, together with RT-generated ROS, to promote lipid peroxidation and ferroptosis. RT also induced the expression of ferroptosis negative regulators, including SLC7A11 and GPX4, leading to radioresistance. In preclinical model, ferroptosis inhibitor liproxstatin-1 partially abolished the RT-induced tumor suppression in H460 xenografts, and FINs (e.g. sulfasalazine) treatment exhibited a significant radiosensitization in A549 xenografts or radioresistant lung cancer patient-derived xenografts (PDXs). In clinical analysis, we revealed very weak 4-HNE levels in all tumor samples before RT, but RT increased 4-HNE levels moderately or strongly in all tumor samples. Importantly, the 4-HNE levels were positively correlated with RT response and disease-free survival in cancer patients. Conclusions: Our study reveals a previously unrecognized link between RT and ferroptosis, and demonstrates that FINs as a radiosensitizer reverse ferroptosis-mediated radioresistance, and proposes a novel combination therapeutic strategy for cancers, providing an effective approach to overcome radioresistance and facilitating us to initiate follow-up clinical trials to further explore the therapeutic potential of FINs combined with RT in cancer patients. Citation Format: Guang Lei, Yilei Zhang, Pranavi Koppula, Xiaoguang Liu, Steven Hsesheng Lin, Zhongxing Liao, Hui Wang, Boyi Gan. Ferroptosis plays an important role in the radiotherapy-induced tumor suppression and radioresistance [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2413.

Impact of non-adherence to radiotherapy on 1-year survival in cancer patients in Catalonia, Spain

BackgroundThis study aims to assess the effects of non-adherence to external beam radiation therapy in cancer patients receiving treatment with a curative. MethodsThis retrospective cohort study collected health records data for all cancer patients treated with external beam radiotherapy with curative intent in 2016 in Catalonia, Spain. Adherence was defined as having received at least 90% of the total dose prescribed. A logistic regression model was used to assess factors related to non-adherence, and its association with one-year survival was evaluated using Cox regression. ResultsThe final sample included 8721 patients (mean age 63.6 years): breast cancer was the most common tumour site (38.1%), followed by prostate and colon/rectum. Treatment interruptions prolonged the total duration of therapy in 70.7% of the patients, and 1.0% were non-adherent. Non-adherence was associated with advanced age, female gender, and some localization of primary tumour (head and neck, urinary bladder, and haematological cancers). The risk of death in non-adherent patients was higher than in adherent patients (hazard ratio [HR] 1.63, 95% confidence interval 0.97–2.74), after adjusting for the potential confounding effect of age, gender, tumour site and comorbidity. ConclusionNon-adherence to radiotherapy, as measured by the received dose, is very low in our setting, and it may have an impact on one-year survival.

Palliative Lung Radiotherapy: Higher Dose Leads to Improved Survival?

AimsChoosing the optimal palliative lung radiotherapy regimen is challenging. Guidance from The Royal College of Radiologists recommends treatment stratification based on performance status, but evidence suggests that higher radiotherapy doses may be associated with survival benefits. The aim of this study was to investigate the effects of fractionation regimen and additional factors on the survival of palliative lung cancer radiotherapy patients. Materials and methodsA retrospective univariable (n = 925) and multivariable (n = 422) survival analysis of the prognostic significance of baseline patient characteristics and treatment prescription was carried out on patients with non-small cell and small cell lung cancer treated with palliative lung radiotherapy. The covariates investigated included: gender, age, performance status, histology, comorbidities, stage, tumour location, tumour side, smoking status, pack year history, primary radiotherapy technique and fractionation scheme. The overall mortality rate at 30 and 90 days of treatment was calculated. ResultsUnivariable analysis revealed that performance status (P < 0.001), fractionation scheme (P < 0.001), comorbidities (P = 0.02), small cell histology (P = 0.02), ‘lifelong never’ smoking status (P = 0.01) and gender (P = 0.06) were associated with survival. Upon multivariable analysis, only better performance status (P = 0.01) and increased dose/fractionation regimens of up to 30 Gy/10 fractions (P < 0.001) were associated with increased survival. Eighty-five (9.2%) and 316 patients (34%) died within 30 and 90 days of treatment, respectively. ConclusionIn this retrospective single-centre analysis of palliative lung radiotherapy, increased total dose (up to and including 30 Gy/10 fractions) was associated with better survival regardless of performance status.

Does a ketogenic diet as an adjuvant therapy for drug treatment enhance chemotherapy sensitivity and reduce target lesions in patients with locally recurrent or metastatic Her-2-negative breast cancer? Study protocol for a randomized controlled trial

BackgroundRecent studies have indicated that a ketogenic diet can be used as an adjuvant therapy to enhance sensitivity to chemotherapy and radiotherapy in cancer patients. However, there are no sufficient data and no consistent international treatment guidelines supporting a ketogenic diet as an adjuvant therapy for metastatic breast cancer. Therefore, this trial was designed to observe whether irinotecan with a ketogenic diet can promote sensitivity to chemotherapy and remit target lesions in locally recurrent or metastatic Her-2-negative breast cancer patients.Methods/designThis trial aims to recruit 518 women with locally recurrent or metastatic breast cancer admitted to the Liaoning Cancer Hospital and Institute (Shenyang, China) in northeast China. All patients will be randomly assigned into the combined intervention group (n = 259) or the control group (n = 259), followed by treatment with irinotecan + ketogenic diet or irinotecan + normal diet, respectively. The primary endpoints are sensitivity to irinotecan and the objective response rate of target lesions; the secondary endpoints include quality of life scores (EORTC QLQ-C30), progression-free survival, overall survival time, incidence of adverse events, and cost-effectiveness. The endpoints will be evaluated at baseline (before drug administration), during treatment, 4 weeks after treatment completion, and every 3months (beginning 2 months after treatment completion).DiscussionThis trial attempts to investigate whether irinotecan treatment with a ketogenic diet for locally recurrent or metastatic breast cancer among women in northeast China can enhance the disease’s sensitivity to chemotherapy and reduce target lesions.Trial registrationChinese Clinical Trial Registry, ID: ChiCTR1900024597. Registered on 18 July 2019. Protocol Version: 1.1, 24 February 2017.

Radiation-induced augmentation in dendritic cell function is mediated by apoptotic bodies/STAT5/Zbtb46 signaling

Purpose: To evaluate the effect of ionizing radiation (IR) exposure on differentiation and maturation of dendritic cells (DC).Materials and methods: Bone marrow progenitor cells irradiated in vitro or isolated from mice exposed to whole body or localized tumor irradiation were differentiated into DC. Phenotypic maturation of DC was characterized by labeling with specific antibodies and flow cytometry analysis. Cytokines were estimated by ELISA.Results: Splenic and bone marrow-derived DC (BMDC) from tumor-bearing mice exposed to localized irradiation showed abrogation of tumor-induced immunosuppression. This was not due to the effect of radiation on tumor cells as DC derived from normal mice exposed to whole-body irradiation (WBI) also showed increase in immune-activating potential of DC. This was observed in terms of increased phenotypic and functional activation of DCs. This phenomenon was also recapitulated if DC were differentiated from in vitro irradiated progenitor cells and was found to be due to STAT5/Zbtb46 signaling mediated by the irradiation-induced apoptotic bodies (ABs). When these ABs were depleted using annexin-beads, these effects were reversed confirming the involvement of this pathway. The role of ABs was further validated in DC derived from mice exposed to WBI in adaptive response experiments with 0.1 Gy priming dose prior to 2 Gy challenge dose. A corresponding reduction in DC maturation markers was observed with decrease in apoptosis in vivo. Further, these DCs derived from irradiated progenitors (IP) could resist the suppressive effects of tumor conditioned medium (TCM) and had increased immune-activating potential as seen in the tumor-bearing mice.Conclusions: Though radiation is the most commonly used therapeutic modality for cancer, its effects on dendritic cell differentiation is not completely understood. We demonstrate here for the first time that exposure to select doses of IR can increase immune-activating potential of DC through ABs. This can have implications in selection of appropriate doses of IR during radiotherapy of cancer patients.

Efficacy of the plantago major L. syrup on radiation induced oral mucositis in head and neck cancer patients: A randomized, double blind, placebo-controlled clinical trial

IntroductionOral mucositis is a complication of radiation therapy in cancer patients. We designed a trial to evaluate efficacy of plantago major on symptoms of radiation induced mucositis in cancer patients. MethodsIn this randomized double blind, placebo-controlled trial 23 patients received plantago major syrup as intervention group and 23 patients received placebo syrup as control group for 7 weeks. Outcome measures were severity of mucositis according to WHO scale and severity of patients' pain assessed by visual analogue scale. ResultsSeverity of mucositis were significantly lower in intervention group compared to placebo group (p value<0.05). Also patients in intervention group experienced significantly less pain compared to placebo group during radiotherapy period (p value<0.05) ConclusionPlantago major L syrup was effective on the reduction of the symptoms of radiation induced mucositis in patients with head and neck cancers.

Hubungan Tingkat Pengetahuan dengan Tingkat Kepatuhan Radioterapi pada Pasien Kanker di Instalasi Radioterapi RSUD Abdul Wahab Sjahranie Samarinda

Cancer is a disease characterized by abnormal cell growth outside the usual boundary then attacks the adjacent body and can spreads to other organs. Cancer treatment can be done with several therapies according to indications, one of them is radiotherapy. One of succession factor in the radiotherapy treatment for cancer is having good knowledge. Treatment adherence is very important to get optimal results such as healing or improving quality of life. The aim of this research was to determine the relationship between radiotherapy knowledge with radiotherapy adherence in undergoing radiotherapy cancer patients at General Hospital of Abdul Wahab Sjahranie Samarinda . This research was an observational analytic design with cross-sectional approach. Data retrieval was done at the Radiotherapy Installation at General Hospital of Abdul Wahab Sjahranie Samarinda from March to April 2019 by using a purposive sampling technique. The results showed that there were 50 samples who met the inclusion and exclusion criteria with details of patients who had good knowledge was 33 people, sufficient knowledge was 15 people, bad knowledge was 2 people and obey patients was 46 people and disobey patients was 4 people. Data analysis using Fisher's test obtained the value of p = 0.157 so it can be concluded that there was no relationship between radiotherapy knowledge and radiotherapy adherence in cancer patients at Radiotherapy Installation at General

Quantitation of Urinary Acylcarnitines by DMS-MS/MS Uncovers the Effects of Total Body Irradiation in Cancer Patients.

Acylcarnitines have been identified in human and animal metabolomic-profiling studies as urinary markers of radiation exposure, a result which is consistent with their cytoprotective effects and roles in energy metabolism. In the present work, a rapid method for quantitation of the more abundant acylcarnitines in human urine is developed using a valuable set of samples from cancer patients who received total body irradiation (TBI) at Memorial Sloan Kettering Cancer Center. The method uses solid-phase extraction (SPE) processing followed by differential mobility spectrometry (DMS with ethyl acetate modifier) tandem mass spectrometry (ESI-DMS-MS/MS) with deuterated internal standards. The analyzed human urine samples were collected from 38 individual patients at three time points over 24 h during and after the course of radiation treatment, a design allowing each patient to act as their own control and creatinine normalization. Creatinine-normalized concentrations for nine urinary acylcarnitine (acyl-CN) species are reported. Six acyl-CN species were reduced at the 6 h point. Acetylcarnitine (C2:0-CN) and valerylcarnitine (C5:0-CN) showed recovery at 24 h, but none of the other acyl-CN species showed recovery at that point. Levels of three acyl-CN species were not significantly altered by radiation. This rapid quantitative method for clinical samples covers the short- and medium-chain acylcarnitines and has the flexibility to be expanded to cover additional radiation-linked metabolites. The human data presented here indicates the utility of the current approach as a rapid, quantitative technique with potential applications by the medical community, by space research laboratories concerned with radiation exposure, and by disaster response groups.

The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression.

Ferroptosis, a form of regulated cell death caused by lipid peroxidation, was recently identified as a natural tumor suppression mechanism. Here, we show that ionizing radiation (IR) induces ferroptosis in cancer cells. Mechanistically, IR induces not only reactive oxygen species (ROS) but also the expression of ACSL4, a lipid metabolism enzyme required for ferroptosis, resulting in elevated lipid peroxidation and ferroptosis. ACSL4 ablation largely abolishes IR-induced ferroptosis and promotes radioresistance. IR also induces the expression of ferroptosis inhibitors, including SLC7A11 and GPX4, as an adaptive response. IR- or KEAP1 deficiency-induced SLC7A11 expression promotes radioresistance through inhibiting ferroptosis. Inactivating SLC7A11 or GPX4 with ferroptosis inducers (FINs) sensitizes radioresistant cancer cells and xenograft tumors to IR. Furthermore, radiotherapy induces ferroptosis in cancer patients, and increased ferroptosis correlates with better response and longer survival to radiotherapy in cancer patients. Our study reveals a previously unrecognized link between IR and ferroptosis and indicates that further exploration of the combination of radiotherapy and FINs in cancer treatment is warranted.

Effect of changes in lung physical properties on microwave ablation zone during respiration.

Microwave ablation is a promising minimally invasive treatment for cancer. However, due to the respiratory movement of the lungs, it is very difficult to accurately predict and control the microwave ablation zone. Therefore, the influence of the changes of the physical parameters of the respiratory process on the microwave ablation zone is studied. Firstly, based on the 4D-CT describing the respiratory process of the lungs, all the image data are from 100 non-small cell lung cancer radiotherapy patients (50 males and 50 females, average 58years, range 55-61years). According to the theory of porous media, the change of the effective thermal conductivity of the lung tissue during the breathing process is obtained. The effective thermal conductivity of the lung parenchyma during respiration varies from 0.16 to 0.20W/m°C, with the lowest vale at the end of inspiration and the highest at the end of expiration. The transient problems during microwave ablation of pulmonary tissue are analyzed by finite element method. The changes of relative permittivity, conductivity and density changes during the breathing process are also considered. The results show that the microwave ablation zone is significantly larger under dynamic physical parameters. At the end of expiration, when the tissue parameter is set to constant, the ablation lesion area is more concentrated around the tip and slot of the antenna, and the backward heating effect is smaller, Ablation volume was superior in nonventilated lungs. Therefore, single-lung ventilation can be considered during pulmonary ablation to reduce the impact of breathing on the ablation area. These findings can be useful to further our understanding the MWA and hold promise towards achieving successful treatment objective as well as enhanced therapeutic output via improved treatment planning and strategy. This study provides the basis for clinical pulmonary ablation and can also be used as a preoperative plan to provide guidance to physicians.