Potential of ferroptosis and ferritinophagy in migraine pathogenesis.

Objective: To assess the potential of ferroptosis and ferritinophagy in migraine pathogenesis. Background: Ferroptosis and ferritinophagy are related to increased cellular iron concentration and have been associated with the pathogenesis of several neurological disorders, but their potential in migraine pathogenesis has not been explored. Increased iron deposits in some deep brain areas, mainly periaqueductal gray (PAG), are reported in migraine and they have been associated with the disease severity and chronification as well as poor response to antimigraine drugs. Results: Iron deposits may interfere with antinociceptive signaling in the neuronal network in the brain areas affected by migraine, but their mechanistic role is unclear. Independently of the location, increased iron concentration may be related to ferroptosis and ferritinophagy in the cell. Therefore, both phenomena may be related to increased iron deposits in migraine. It is unclear whether these deposits are the reason, consequence, or just a correlate of migraine. Still, due to migraine-related elevated levels of iron, which is a prerequisite of ferroptosis and ferritinophagy, the potential of both phenomena in migraine should be explored. If the iron deposits matter in migraine pathogenesis, they should be mechanically linked with the clinical picture of the disease. As iron is an exogenous essential trace element, it is provided to the human body solely with diet or supplements. Therefore, exploring the role of iron in migraine pathogenesis may help to determine the potential role of iron-rich/poor dietary products as migraine triggers or relievers. Conclusion: Ferroptosis and ferritinophagy may be related to migraine pathogenesis through iron deposits in the deep areas of the brain.

Retrospective analysis of the effectiveness of volumetric modulated arc therapy half­body irradiation in palliation of pain in patients with multiple bone metastases.

Bone metastases are the most common cause of cancer-related pain. It has been reported that radiotherapy is efficient in the palliation of pain caused by bone metastases. Half-body irradiation (HBI) is a method of palliative treatment in patients with multiple metastases to bones. The present study aimed to evaluate the efficiency of upper and lower HBI in reducing pain in patients with multiple bone metastases treated with volumetric modulated arc therapy (VMAT) HBI. A total of 22 patients received HBI based on the VMAT technique between July 2018 and July 2020. Treatment plans were subject to a dosimetric analysis. The absorbed doses ranged from 6 to 8 Gy in a single fraction. The patients rated pain on the 11-point (0-10) verbal numeric pain score (VNPS) before irradiation and after 1 month of follow-up. To assess the analgesic effect of HBI radiotherapy, data from 19 patients who attended the follow-up visit were analyzed. Before the treatment, the median VNPS of pain was 5 (IQR, 3-8); after the follow-up period, it was 3 (IQR, 1-4) (P=0.003). The median VNPS of the maximum pain within the last month before treatment was 8 (IQR, 7-10) and after irradiation it was 5 (IQR, 4-7) (P<0.001). The median VNPS of the average pain within the last month before the treatment was 5 (IQR, 4-7); after the treatment, it was 3 (IQR, 2-5) (P=0.003). In conclusion, conformal VMAT-intensity-modulated radiation therapy HBI is an effective method for reducing pain in patients with painful multiple bone metastases. Conformal techniques of radiation allow for the reduction of doses to organs at risk thus potentially reducing the toxicity of treatment.

The impact of adjuvant treatment with external beam radiotherapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma - initial results of a prospective study.

OBJECTIVES: Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high-dose-rate brachytherapy (HDR BT) on health-related quality of life (HRQL) in patients with early-stage endometrioid endometrial carcinoma. MATERIAL AND METHODS: We assessed HRQL of patients based on the EORTC QLQ-C30 questionnaire, with endometrial cancer specific HRQL module - EORTC QLQ-EN24. From March 2019 to April 2020 we enrolled 20 patients with early-stage endometrioid endometrial carcinoma, qualified for adjuvant treatment after hysterectomy. We compared the scores measured with the questionnaires at the beginning and at the end of the treatment. RESULTS: There was a statistically significant decrease in the mean of global health status/quality of life assessed according to the EORTC QLQ-C30 scale, from 62.25 ± 13.12 at the beginning of the adjuvant radiotherapy to 55.85 ± 14.68 at the end of the treatment (p = 0.047). The mean appetite loss score was higher at the onset of the treatment as compared to its value after EBRT, 19.9 ± 27.33 vs 11.6 ± 19.52 (p = 0.043). Similarly to the mean constipation score, which was 29.85 ± 30.40 vs 11.6 ± 19.52 (p = 0.013). The mean diarrhoea symptom scale increased from 16.55 ± 20.16 to 56.75 ± 36.10 (p = 0.001). In the EORTC QLQ-EN24 scales, gastrointestinal symptoms scores were higher at the end of the treatment, (with the mean of 26.45 ± 22.76) as compared to 14.30 ± 16.52 at the beginning of EBRT (p = 0.003). CONCLUSIONS: Patients who receive adjuvant radiotherapy have decreased quality of life during the treatment reporting more serious gastrointestinal symptoms. The potential risk of treatment-related toxicity should be taken into account during the treatment planning process in order to minimize the deterioration of HRQL.

Lipopolysaccharide-binding protein is efficient in biodosimetry during radiotherapy of lung cancer.

The aim of the present study was to determine if the serum levels of early markers of inflammation, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and lipopolysaccharide-binding protein (LBP) were correlated with the radiation dose received by the pulmonary and mediastinal structures of patients with non-small cell lung cancer (NSCLC). This pilot study included 26 patients with NSCLC who received total radiation doses ranging from 54 to 74 Gy (2.0 Gy/fraction). Cytokines were measured at baseline by enzyme-linked immunosorbant assay, and following administration of total doses of 20 and 40 Gy. A control group of 26 participants was sampled for comparisons with patient baseline cytokine levels. Only data from the 40-Gy cytokine blood levels of patients with NSCLC were identified to be correlated with histograms of the parameters of each patient's radiotherapy protocol. The IL-6, TNF-α and CRP median baseline levels of the patients with NSCLC were significantly higher than those of the controls (all P≤0.01). No differences were observed between the LBP levels of the patients and controls [median, 36.34 (25-75%; 31.35-39.27) vs. 36.92 (30.20-44.05) µg/ml, respectively; P=0.42]. No significant differences in the levels of the four cytokines between baseline, and at 20 and 40 Gy were observed [IL-6 (P=0.19); TNF-α (P=0.68); CRP (P=0.44) and LBP (P=0.29)]. LBP was significantly and positively correlated with the mean radiation dose to the lung (r=0.409; P=0.038), and showed a positive correlation with the percentage of lung volume exposed to at least 20 Gy of the planned radiation dose (r=0.3536; P=0.0764). CRP levels were positively correlated with the mean radiation dose to the esophagus (r=0.404; P=0.041); however, IL-6, TNF-α and CRP were not significantly associated with other lung dosimetry parameters. Thus, LBP levels were correlated with radiation exposure of pulmonary tissues, and LBP may be a marker that warrants further investigation on radiotoxicity in NSCLC patients.

Highly conformal CT based surface mould brachytherapy for non-melanoma skin cancers of earlobe and nose.

PURPOSE: Brachytherapy (BT), due to rapid dose fall off and minor set-up errors, should be superior to external beam radiotherapy (EBRT) for treatment of lesions in difficult locations like nose and earlobe. Evidences in this field are scarce. We describe computed tomography (CT) based surface mould BT for non-melanoma skin cancers (NMSC), and compare its conformity, dose coverage, and tissue sparing ability to EBRT. MATERIAL AND METHODS: We describe procedure of preparation of surface mould applicator and dosimetry parameters of BT plans, which were implemented in 10 individuals with NMSC of nose and earlobe. We evaluated dose coverage by minimal dose to 90% of planning target volume (PTV) (D90), volumes of PTV receiving 90-150% of prescribed dose (PD) (VPTV90-150), conformal index for 90 and 100% of PD (COIN90, COIN100), dose homogeneity index (DHI), dose nonuniformity ratio (DNR), exposure of organs. Prospectively, we created CT-based photons and electrons plans. We compared conformity (COIN90, COIN100), dose coverage of PTV (D90, VPTV90, VPTV100), volumes of body receiving 10-90% of PD (V10-V90) of EBRT and BT plans. RESULTS: We obtained mean BT-DHI = 0.76, BT-DNR = 0.23, EBRT-DHI = 1.26. We observed no significant differences in VPTV90 and D90 between BT and EBRT. Mean BT-VPTV100 (89.4%) was higher than EBRT-VPTV100 (71.2%). Both COIN90 (BT-COIN90 = 0.46 vs. EBRT-COIN90 = 0.21) and COIN100 (BT-COIN100 = 0.52 vs. EBRT-COIN100 = 0.26) were superior for BT plans. We observed more exposure of normal tissues for small doses in BT plans (V10, V20), for high doses in EBRT plans (V70, V90). CONCLUSIONS: Computed tmography-based surface mould brachytherapy for superficial lesions on irregular surfaces is a highly conformal method with good homogeneity. Brachytherapy is superior to EBRT in those locations in terms of conformity and normal tissue sparing ability in high doses.

Availability and outcomes of radiotherapy in Central Poland during the 2005-2012 period - an observational study.

BACKGROUND: Using a cross-database integrative approach, we performed an epidemiological analysis in a representative region of central Poland to evaluate the availability of radiotherapy (RTx) and overall survival of adult patients undergoing RTx for cancer. METHODS: Epidemiological data on cancer incidence in the 2005-2012 period were obtained from the Nationwide Cancer Registry. Using data from the Ministry of Internal Affairs, we collected survival information of all patients treated in the only centre providing RTx for a region inhabited by approximately 2.6 million people. RESULTS: After filtering out individuals on the basis of exclusion criteria, the final dataset covered 17,736 patients. Availability of RTx increased marginally, from 23.5% (2005) to 24.4% (2011, R = 0.39, p = 0.38), with the highest values noted in patients with cervical (78.5%), prostate (70.6%) and breast cancer (62.7%). However, due to the decreasing population of the region, we noted increasing disparity in the likelihood of receiving RTx depending on the patient's area of residence, with rural areas becoming progressively more neglected. The best prognosis was noted among patients with breast or prostate cancer with 5-year OS rates reaching 81.2% and 83.3%, respectively. Multivariate analysis controlling for type of diagnosis and patient age showed a time-dependent improvement in outcomes (HR(95% CI): 0.96(0.94-0.98); p < 0.0001). CONCLUSIONS: Availability of RTx in Poland is still below that reported by developed European centres. Survival of patients undergoing radical RTx has gradually improved, although it is still below that of leading RTx departments, potentially due to delayed diagnosis or organisational barriers, necessitating further investigations.