Radiation-induced Side Effects Research Articles

MR Image Changes of Normal-Appearing Brain Tissue after Radiotherapy.

Simple SummaryRadiotherapy is one of the most important treatment options against cancer. Irradiation of cancerous tissue either directly destroys the cancer cells or damages them such that they cannot reproduce. One side-effect of radiotherapy is that tumor-surrounding normal tissue is inevitably also irradiated, albeit at a lower dose. The resulting long-term damage can significantly affect cognitive performance and quality of life. Many studies investigated the effect of irradiation on normal-appearing brain tissues and some of these correlated imaging findings with functional outcome. This article provides an overview of the examination of radiation-induced injuries using conventional and enhanced MRI methods and summarizes conclusions about the underlying tissue changes. Radiation-induced morphologic, microstructural, vascular, and metabolic tissue changes have been observed, in which the effect of irradiation was evident in terms of decreased perfusion and neuronal health as well as increased diffusion and atrophy.Radiotherapy is part of the standard treatment of most primary brain tumors. Large clinical target volumes and physical characteristics of photon beams inevitably lead to irradiation of surrounding normal brain tissue. This can cause radiation-induced brain injury. In particular, late brain injury, such as cognitive dysfunction, is often irreversible and progressive over time, resulting in a significant reduction in quality of life. Since 50% of patients have survival times greater than six months, radiation-induced side effects become more relevant and need to be balanced against radiation treatment given with curative intent. To develop adequate treatment and prevention strategies, the underlying cause of radiation-induced side-effects needs to be understood. This paper provides an overview of radiation-induced changes observed in normal-appearing brains measured with conventional and advanced MRI techniques and summarizes the current findings and conclusions. Brain atrophy was observed with anatomical MRI. Changes in tissue microstructure were seen on diffusion imaging. Vascular changes were examined with perfusion-weighted imaging and susceptibility-weighted imaging. MR spectroscopy revealed decreasing N-acetyl aspartate, indicating decreased neuronal health or neuronal loss. Based on these findings, multicenter prospective studies incorporating advanced MR techniques as well as neurocognitive function tests should be designed in order to gain more evidence on radiation-induced sequelae.

Radiomic and radiogenomic modeling for radiotherapy: strategies, pitfalls, and challenges.

.The power of predictive modeling for radiotherapy outcomes has historically been limited by an inability to adequately capture patient-specific variabilities; however, next-generation platforms together with imaging technologies and powerful bioinformatic tools have facilitated strategies and provided optimism. Integrating clinical, biological, imaging, and treatment-specific data for more accurate prediction of tumor control probabilities or risk of radiation-induced side effects are high-dimensional problems whose solutions could have widespread benefits to a diverse patient population—we discuss technical approaches toward this objective. Increasing interest in the above is specifically reflected by the emergence of two nascent fields, which are distinct but complementary: radiogenomics, which broadly seeks to integrate biological risk factors together with treatment and diagnostic information to generate individualized patient risk profiles, and radiomics, which further leverages large-scale imaging correlates and extracted features for the same purpose. We review classical analytical and data-driven approaches for outcomes prediction that serve as antecedents to both radiomic and radiogenomic strategies. Discussion then focuses on uses of conventional and deep machine learning in radiomics. We further consider promising strategies for the harmonization of high-dimensional, heterogeneous multiomics datasets (panomics) and techniques for nonparametric validation of best-fit models. Strategies to overcome common pitfalls that are unique to data-intensive radiomics are also discussed.

<p><strong>Effect of edaravone on lungs and small intestine in rats with induced radiotherapy</strong></p>

Radiotherapy is a frequently used method for treatment of cancer which is regarded as one of the top two diseases causing premature death worldwide. However, radiotherapy is known to have many side effects. In this study, we evaluated biologically and histologically the possible protective effects of edaravone, the free radical scavenger and neuroprotective agent used to treat amyotrophic lateral sclerosis, on lung and small intestine against radiation-induced early side effects of 15 Gy total body irradiation in single fraction. Thirty-two rats were divided randomly into four equal groups. Groups were administered 15 Gy of external ionizing radiation to the whole body after 30 minutes of EDA administration (a dose of 500 and 50 mg/kg). Rats were sacrified at 72 h of the experiment. Tissues were separated to investigate levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPX) and malondialdehyde (MDA); and evealuate histopathological changings. The protective effect of EDA showed statistically significant in MDA, SOD and GSHPX values of lungs except CAT and statistically significant effect was observed in MDA in small intestine. Also, we showed statistically significant values with histopathological changings. Pediatric cancer patients who have a longer life expectancy are as important as their recovery from their normal life. We are expecting that EDA as a modulator of free radical scavenging pathways in many organs can reduce the side effects of radiation damage on lungs and small intestine.

Single institutional outcomes of whole brain radiotherapy for metastatic melanoma brain metastases

BackgroundThe management of melanoma with brain metastases (MBM) is increasingly complex, especially given recent improvements in targeted agents, immunotherapy, and radiotherapy. Whole brain radiation therapy (WBRT) is a longstanding radiotherapy technique for which reported patient outcomes and experiences are limited. We sought to report our institutional outcomes for MBM patients receiving WBRT and assess whether other clinical factors impact prognosis.MethodsA retrospective review of a single institution database was performed. Patients diagnosed with MBM from 2000 to 2018 treated with WBRT, with or without other systemic treatments, were included. Post-WBRT brain MRI scans were assessed at timed intervals for radiographic response. Clinical and treatment variables associated with overall survival (OS), distant failure-free survival (DFFS), local failure-free survival (LFFS), and progression-free survival (PFS) were assessed. Data on radiation-induced side effects, including radionecrosis, hemorrhage, and memory deficits, was also captured.Results63 patients with MBM were ultimately included in our study. 69% of patients had 5 or more brain metastases at the time of WBRT, and 68% had extracranial disease. The median dose of WBRT was 30 Gy over 10 fractions. Median follow-up was 4.0 months. Patients receiving WBRT had a median OS of 7.0 months, median PFS of 2.2 months, median DFFS of 6.1 months, and median LFFS of 4.9 months. Performance status correlated with OS on both univariate and multivariable analysis. BRAF inhibitor was the only systemic therapy to significantly impact OS on univariate analysis (HR 0.24, 95% CI 0.07–0.79, p = 0.019), and this effect extended to multivariable analysis as well. Post-WBRT intralesional hemorrhage decreased DFFS on both univariate and multivariable analysis. Of patients with post-treatment brain scans available, there was a 16% rate of radionecrosis, 32% rate of hemorrhage, and 19% rate of memory deficits.ConclusionsOutcomes for MBM patients receiving WBRT indicate that WBRT remains an effective treatment strategy to control intracranial disease. Treatment-related toxicities such as intralesional hemorrhage, necrosis, or neurocognitive side effects are limited. With continued innovations in WBRT technique and systemic therapy development, MBM outcomes may continue to improve. Further trials should evaluate the role of WBRT in the modern context.

Late Side Effects in Normal Mouse Brain Tissue After Proton Irradiation

Radiation-induced late side effects such as cognitive decline and normal tissue complications can severely affect quality of life and outcome in long-term survivors of brain tumors. Proton therapy offers a favorable depth-dose deposition with the potential to spare tumor-surrounding normal tissue, thus potentially reducing such side effects. In this study, we describe a preclinical model to reveal underlying biological mechanisms caused by precise high-dose proton irradiation of a brain subvolume. We studied the dose- and time-dependent radiation response of mouse brain tissue, using a high-precision image-guided proton irradiation setup for small animals established at the University Proton Therapy Dresden (UPTD). The right hippocampal area of ten C57BL/6 and ten C3H/He mice was irradiated. Both strains contained four groups (nirradiated = 3, ncontrol = 1) treated with increasing doses (0 Gy, 45 Gy, 65 Gy or 85 Gy and 0 Gy, 40 Gy, 60 Gy or 80 Gy, respectively). Follow-up examinations were performed for up to six months, including longitudinal monitoring of general health status and regular contrast-enhanced magnetic resonance imaging (MRI) of mouse brains. These findings were related to comprehensive histological analysis. In all mice of the highest dose group, first symptoms of blood-brain barrier (BBB) damage appeared one week after irradiation, while a dose-dependent delay in onset was observed for lower doses. MRI contrast agent leakage occurred in the irradiated brain areas and was progressive in the higher dose groups. Mouse health status and survival corresponded to the extent of contrast agent leakage. Histological analysis revealed tissue changes such as vessel abnormalities, gliosis, and granule cell dispersion, which also partly affected the non-irradiated contralateral hippocampus in the higher dose groups. All observed effects depended strongly on the prescribed radiation dose and the outcome, i.e. survival, image changes, and tissue alterations, were very consistent within an experimental dose cohort. The derived dose–response model will determine endpoint-specific dose levels for future experiments and may support generating clinical hypotheses on brain toxicity after proton therapy.

Usefulness of Honey as an Adjunct in the Radiation Treatment for Head and Neck Cancer: Emphasis on Pharmacological and Mechanism/s of Actions.

In the treatment of head and neck cancer (HNC), ionizing radiation is an important modality in achieving curative objectives. However, the effective use of radiation is compromised by the side effects resulting from the damage to the adjacent normal tissue. Preclinical studies carried out in the recent past have shown that the age-old dietary agent honey, which also possesses myriad medicinal use, is beneficial for mitigating diverse radiation-induced side effects like mucositis, xerostomia, fatigue, weight loss and promoting healing of refractory wounds. The objective of this memoir is to review the beneficial effects of honey in mitigating radiation-induced side effects in HNC and to emphasize on the underlying mechanisms of action for inducing the beneficial effects. Two authors searched Google Scholar, PubMed, Embase, and the Cochrane Library for publications up to December 2019 to assess the capability of honey for reducing the severity of radiation-induced ill effects in the treatment of HNC. Subsequently, the adjunct pharmacological effects and mechanism/s responsible were also searched for and appropriately used to substantiate the underlying mechanism/s of action for the beneficial effects. The existing data is suggestive that honey is beneficial in mitigating the radiation-induced mucositis, xerostomia, amd healing of recalcitrant wounds in radiation-exposed regions, and that the multiple pathways mediate the beneficial effects, especially free radical scavenging, antioxidant, wound healing, anticancer, analgesic, anti-inflammatory, anabolic, anti-fatigue and anti-anaemic effects that add additional value to the use of honey as an adjunct in cancer therapy. For the first time, this review addresses the underlying pharmacological related to the beneficial effects of honey in radiation-induced damage, and attempts at emphasizing the lacunae that need further studies for optimizing the use of honey as an adjunct in radiotherapy of HNC. The authors suggest that future studies should be directed at understanding the detailed molecular mechanisms responsible for the beneficial effects using validated cell culture and animal models of study. Large multicentric clinical trials with standardised honey also needed to understand the clinical use of honey.

Профилактическое облучение лимфатических узлов малого таза у больных раком предстательной железы высокого риска прогрессирования. Обзор

One way to enhance the effectiveness of treatment for high-risk prostate cancer is to use com-bined hormonal/radiation therapy. The effectiveness of this approach has already been demon-strated and confirmed. The study results show that application of the hormonal therapy potenti-ates the total radiation effect and makes 5-year local control is more effective compared with the control achieved after application of EBRT modality. At the same time, if high dose radiation ther-apy is applied or large volume to be exposed to radiation, in both cases there is increased risk of radiation-induced side effects development. The radiation-related complications affect patients’ quality of life significantly. A natural question arises in such a case, whether inclusion of lesion free pelvic lymph nodes (N0) in patients with high risk of prostate cancer progression in the area of radiation exposure is necessary, if no data on their lesion (N0) are available and thus to in-crease the irradiated volume significantly. The considered published studies devoted to the prob-lem were considered, the most part of the studies a retrospective, results of some studies contra-dicted conclusions. This does not allow us to find definitive answer to the “natural” question. Until now, it is also unknown what criteria are to be used for deciding whether radiotherapy to the area of regional metastasis zones is necessary. In this connection, it would be reasonable to conduct a prospective randomized study, its results will possibly allow us to assess the need for prophylac-tic irradiation of the pelvic lymph nodes during combined modality radiotherapy for high risk pros-tate cancer patients.

Indian Indigenous Fruits as Radioprotective Agents: Past, Present and Future

Dietary agents with beneficial effects like free radical scavenging, antioxidant and immunomodulatory effects are being recognized as useful and have been investigated for their radioprotective properties. Studies in these lines have shown that the fruits of Aegle marmelos (stone apple or bael), Emblica officinalis or Phyllanthus emblica (Indian gooseberry/amla), Eugenia jambolana or Syzygium jambolana (black plum/jamun), Mangifera indica (mango) and Grewia asiatica (phalsa or falsa) that are originally reported to be indigenous to India have been investigated for their usefulness as radioprotective agents. The objective of this review is to summarize the beneficial effects of the Indian indigenous fruits, stone apple, mango, Indian gooseberry, black plum, and phalsa, in mitigating radiation-induced side effects, emphasize the underlying mechanism of action for the beneficial effects and address aspects that merit detail investigations for these fruits to move towards clinical application in the near future. The authors data-mined Google Scholar, PubMed, Embase, and the Cochrane Library for publications in the field from 1981 up to July 2020. The focus was on the radioprotection and the mechanism responsible for the beneficial effects, and accordingly, the articles were collated and analyzed. This article emphasizes the usefulness of stone apple, mango, Indian gooseberry, black plum, and phalsa as radioprotective agents. From a mechanistic view, reports are suggestive that the beneficial effects are mediated by triggering free radical scavenging, antioxidant, anti-mutagenic and anti-inflammatory effects. For the first time, this review addresses the beneficial effects of mango, Indian gooseberry, black plum, stone apple and phalsa as radioprotective agents. The authors suggest that future studies should be directed at understanding the selective radioprotective effects with tumor-bearing laboratory animals to understand their usefulness as radioprotective drug/s during radiotherapy and as a food supplement to protect people from getting exposed to low doses of radiation in occupational settings. Phase I clinical trial studies are also required to ascertain the optimal dose and the schedule to be followed with the standardized extract of these fruits. The most important aspect is that these fruits, being a part of the diet, have been consumed since the beginning of mankind, are non-toxic, possess diverse medicinal properties, have easy acceptability, all of which will help take research forward and be of benefit to patients, occupational workers, agro-based sectors and pharma industries.

Radioprotective Effect of Flavonoids on Ionizing Radiation-Induced Brain Damage.

Patients receiving brain radiotherapy may suffer acute or chronic side effects. Ionizing radiation induces the production of intracellular reactive oxygen species and pro-inflammatory cytokines in the central nervous system, leading to brain damage. Complementary Chinese herbal medicine therapy may reduce radiotherapy-induced side effects. Flavonoids are a class of natural products which can be extracted from Chinese herbal medicine and have been shown to have neuroprotective and radioprotective properties. Flavonoids are effective antioxidants and can also inhibit regulatory enzymes or transcription factors important for controlling inflammatory mediators, affect oxidative stress through interaction with DNA and enhance genomic stability. In this paper, radiation-induced brain damage and the relevant molecular mechanism were summarized. The radio-neuro-protective effect of flavonoids, i.e., antioxidant, anti-inflammatory and maintaining genomic stability, were then reviewed. We concluded that flavonoids treatment may be a promising complementary therapy to prevent radiotherapy-induced brain pathophysiological changes and cognitive impairment.

Harnessing genome-wide association studies to minimize adverse radiation-induced side effects.

Radiotherapy is used as definitive treatment in approximately two-thirds of all cancers. However, like any treatment, radiation has significant acute and long-term side effects including secondary malignancies. Even when similar radiation parameters are used, 5%–10% of patients will experience adverse radiation side effects. Genomic susceptibility is thought to be responsible for approximately 40% of the clinical variability observed. In the era of precision medicine, the link between genetic susceptibility and radiation-induced side effects is further strengthening. Genome-wide association studies (GWAS) have begun to identify single-nucleotide polymorphisms (SNPs) attributed to overall and tissue-specific toxicity following radiation for treatment of breast cancer, prostate cancer, and other cancers. Here, we review the use of GWAS in identifying polymorphisms that are predictive of acute and long-term radiation-induced side effects with a focus on chest, pelvic, and head-and-neck irradiation. Integration of GWAS with “omic” data, patient characteristics, and clinical correlates into predictive models could decrease radiation-induced side effects while increasing therapeutic efficacy.

Yap activation in irradiated parotid salivary glands is regulated by ROCK activity.

Radiotherapy plays a major role in the curative treatment of head and neck cancer, either as a single modality therapy, or in combination with surgery or chemotherapy, or both. Despite advances to limit radiation-induced side-effects, the major salivary glands are often affected. This frequently leads to hyposalivation which causes an increased risk for xerostomia, dental caries, mucositis, and malnutrition culminating in a significant impact on patients’ quality of life. Previous research demonstrated that loss of salivary function is associated with a decrease in polarity regulators and an increase in nuclear Yap localization in a putative stem and progenitor cell (SPC) population. Yap activation has been shown to be essential for regeneration in intestinal injury models; however, the highest levels of nuclear Yap are observed in irradiated salivary SPCs that do not regenerate the gland. Thus, elucidating the inputs that regulate nuclear Yap localization and determining the role that Yap plays within the entire tissue following radiation damage and during regeneration is critical. In this study, we demonstrate that radiation treatment increases nuclear Yap localization in acinar cells and Yap-regulated genes in parotid salivary tissues. Conversely, administration of insulin-like growth factor 1 (IGF1), known to restore salivary function in mouse models, reduces nuclear Yap localization and Yap transcriptional targets to levels similar to untreated tissues. Activation of Rho-associated protein kinase (ROCK) using calpeptin results in increased Yap-regulated genes in primary acinar cells while inhibition of ROCK activity (Y-27632) leads to decreased Yap transcriptional targets. These results suggest that Yap activity is dependent on ROCK activity and provides new mechanistic insights into the regulation of radiation-induced hyposalivation.

Surgical aspects in craniopharyngioma treatment.

ObjectivesTotal surgical resection is the gold standard in the treatment of craniopharyngioma. However, there is concern that aggressive surgical resection might result in high rates of endocrinologic, metabolic, and behavioral morbidities. Subtotal resection (SR) with subsequent radiation therapy (RT) may reduce surgical complications, but it may also increase the risk of tumor recurrence and radiation-induced side effects. Therefore, the optimal surgical strategy remains debatable.MethodsTo determine the optimal surgical strategy, we assessed the clinical courses of 39 patients (19 male patients and 20 female patients) with newly diagnosed craniopharyngioma who were treated at our institute. The median age at diagnosis was 34 years (range: 0–76 years). The median follow-up period was 8.5 years (range: 3–160 months). Our treatment strategy comprised gross total resection (GTR) for craniopharyngioma in patients that were not at surgical risk. Conversely, after adequate tumor decompression, we used RT, mainly Gamma Knife radiosurgery, in patients at risk. We divided the patients into the following three groups depending on the treatment course: GTR, SR with RT, and SR with staged surgery. We compared tumor characteristics, as well as patients’ conditions at the preoperative stage and last follow-up, among the three groups.ResultsThere were 8, 21, and 10 patients in the GTR, SR with RT, and SR with staged surgery groups, respectively. There were no differences in the maximum tumor diameter, tumor volume, composition, and presence of calcification among the groups. Among the 39 patients, 24 underwent transcranial microsurgery and 15 underwent trans-sphenoidal surgery as the initial treatment. No cases involving surgical mortality, cerebrospinal fluid leakage, severely deteriorated visual function, or severe hypothalamic damage were observed. No tumor recurrence was noted in the GTR group. One patient required additional RT, and one patient underwent second surgery for tumor recurrence in the SR with RT group. In the SR with staged surgery group, 8 of the 10 patients eventually underwent RT, but tumor control was achieved in all patients at the latest follow-up. In this group, the third trans-sphenoidal surgery caused a severe vascular injury in one patient. At the final follow-up, 33 (85%) patients were undergoing anterior pituitary hormone replacement, and the rate of diabetes insipidus was 51%. There was no significant difference in the pituitary dysfunction rate among the groups.ConclusionsWe observed a low rate of surgical complications and a sufficient tumor control rate in response to our treatment strategy. Despite attempting preservation of the pituitary stalk, we found it difficult to rescue anterior pituitary function.

CN43 Effect of self-care teaching module on radiation- induced acute side effects and clinical outcomes for head and neck cancer patients

The major concern of health care professionals regarding the value of teaching self-care for management of acute side effects of radiation therapy of head and neck cancer (HNC) patients is the improvement of their clinical outcomes. Aim: This quasi-experimental randomized controlled study design aimed to evaluate the effect of self-care teaching module on radiation-induced acute side effects and clinical outcomes in HNC patient. A random sample of (50) adult patients with HNC undergoing recent radiation therapy were selected. All subjects of the current study were meeting all inclusion criteria. Subjects were divided into two groups; each group consisted of 25 patients. Group I; control group did not receive self-care teaching module about acute side effect whereas the self-care teaching module was provided by the researcher to Group II. Three tools were utilized to collect data pertinent to the study. These tools were structured patient assessment interview questionnaire. Tool (II) included Modified Eastern Cooperative Oncology Group performance scale (ECOG). Tool (III) was Self-care questionnaire. There was improvement of mean scores regarding change of quality grade of functional ability of the study group II one and three months after receiving self-care teaching module with very high statistical significance difference. Also, the occurrence and severity of acute side effects was improved in the study group II compared to control group I. Self-care teaching module on radiation induced acute side effects had an effect on decreasing the occurrence, the severity and the distressing of these side effects in head and neck cancer patients.

Topical Application of Phlorotannins from Brown Seaweed Mitigates Radiation Dermatitis in a Mouse Model.

Radiation dermatitis (RD) is one of the most common side effects of radiotherapy; its symptoms progress from erythema to dry and moist desquamation, leading to the deterioration of the patients’ quality of life. Active metabolites in brown seaweed, including phlorotannins (PTNs), show anti-inflammatory activities; however, their medical use is limited. Here, we investigated the effects of PTNs in a mouse model of RD in vivo. X-rays (36 Gy) were delivered in three fractions to the hind legs of BALB/c mice. Macroscopic RD scoring revealed that PTNs significantly mitigated RD compared with the vehicle control. Histopathological analyses of skin tissues revealed that PTNs decreased epidermal and dermal thickness compared with the vehicle control. Western blotting indicated that PTNs augmented nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway activation but attenuated radiation-induced NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and inflammasome activation, suggesting the mitigation of acute inflammation in irradiated mouse skin. PTNs also facilitated fast recovery, as indicated by increased aquaporin 3 expression and decreased γH2AX (histone family member X) expression. Our results indicate that topical PTN application may alleviate RD symptoms by suppressing oxidative stress and inflammatory signaling and by promoting the healing process. Therefore, PTNs may show great potential as cosmeceuticals for patients with cancer suffering from radiation-induced inflammatory side effects such as RD.

Radiation-induced side effects in breast cancer patients and factors affecting them

Breast cancer is the most frequent malignancy and the leading cause of cancer morbidity and mortality in women worldwide. Radiation therapy (RT) is a widely used approach for its treatment. About 50% of patients with malignant breast tumors receive radiation therapy and most of them appear to tolerate it, but some experience severe side effects induced by this therapy. This variability of response may be caused by several factors, like age, inflammatory responses, body weight and variation in genes involved in the response to radiation-induced DNA damage. To limit radiotherapy side effects in breast cancer patients it is therefore important to have a good knowledge of these associated factors. This review discussed about the radiotherapy-related side effects in breast cancer patients and the factors affecting them.
 Asian J. Med. Biol. Res. June 2020, 6(2): 138-148

Institutional outcomes of whole brain radiotherapy for metastatic melanoma brain metastases.

e14504 Background: The management of melanoma with multiple brain metastases (MBM) is complex given improvements in targeted agents, immunotherapy, and radiotherapy. Whole brain radiation therapy (WBRT) is a radiotherapy technique with limited outcomes data. We report our institutional outcomes for MBM patients receiving WBRT and assess whether certain clinical factors impact prognosis. Methods: A retrospective review of a single institution database was performed. Patients diagnosed with MBM from 2000-2018 treated with WBRT, with or without systemic treatments, were included. Post-WBRT brain MRI scans were assessed at timed intervals for radiographic response. Clinical and treatment variables associated with overall survival (OS), progression free survival (PFS), intracranial failure-free survival (IFFS), and local failure-free survival (LFFS) were assessed. Data was collected on radiation-induced side effects, including radionecrosis, hemorrhage, and memory deficits. Results: Of 1347 patients treated with WBRT from 2000-2018, 63 patients had melanoma. 69% of patients had ≥5 brain metastases at the time of WBRT, 68% had extracranial disease, and 71% received steroids during their overall treatment course. Most had received previous therapies and had WBRT as a last resort. Median WBRT dose was 30 Gray over 10 fractions. Median follow-up was 4.0 months. Six-month OS, PFS, IFFS, and LFFS were 52.7%, 20.4%, 52.3%, and 43%. Median OS, PFS, IFFS, and LFFS were 7.0 months, 2.2 months, 6.1 months, and 4.9 months. Performance status correlated with OS on univariate and multivariate analysis. BRAFi was the only systemic therapy to significantly impact OS on univariate analysis (HR 0.24, 95% CI 0.07-0.79, p = 0.019), although this was not seen on multivariate analysis. There was a 19% rate of memory deficits. Among the 46 patients with post-WBRT brain scans, 17% had radionecrosis and 28% had intralesional hemorrhage. Not all radiographically noted radiotoxicities were clinically significant, although hemorrhage decreased IFFS on both univariate and multivariate analysis. Conclusions: Outcomes for MBM patients receiving WBRT indicate that WBRT remains a worthy option to control intracranial disease. Treatment-related effects such as hemorrhage, necrosis, or cognitive changes are considerations. Median PFS and IFFS suggest that systemic disease control continues to be the greater issue. The role of WBRT should be re-evaluated in the modern era, which features advanced imaging detection ability, newer systemic agents, and improved steroid avoidance strategies.

Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation.

SummaryThe effectiveness of cancer radiotherapy is frequently hindered by the hypoxia of the tumor microenvironment. Direct delivery of oxygen to hypoxic tumor tissues is an attractive strategy to overcome this hypoxia-associated radioresistance. Herein, we report the generation of submicron-sized particles comprising myoglobin fused to the crystal-forming domain of Cry3Aa protein for the targeted delivery of oxygen to cancer cells. We demonstrate that myoglobin-containing particles were successfully produced in Bacillus thuringiensis with the assistance of the Cry3Aa domain I. Furthermore, these particles could be genetically modified to incorporate the cell penetrating peptide TAT and cell targeting peptide A549.1, resulting in particles that exhibited improved cellular uptake and targeting toward A549 cells. Notably, these myoglobin-containing particles increased the intracellular oxygen levels of A549 cells and thereby sensitized them to radiation. These findings suggest that the targeted delivery of O2-bound myoglobin could be an effective approach to enhance the efficacy of radiotherapy.

Cardiovascular Damage Associated With Chest Irradiation.

The improvement of anticancer-therapies results in a greater amount of long-term survivors after radiotherapy. Therefore, the understanding of cardiotoxicity after irradiation is of increasing importance. Cardiovascular adverse events after chest irradiation have been acknowledged for a long time but remain difficult to diagnose. Long-term cardiovascular adverse events may become evident years or decades after radiotherapy and the spectrum of potential cardiovascular side effects is large. Recent experimental and clinical data indicate that cardiovascular symptoms may be caused especially by heart failure with preserved ejection fraction, which remains incompletely understood in patients after radiation therapy. Heart radiation dose and co-existing cardiovascular risk factors represent some of the most important contributors for incidence and severity of radiation-induced cardiovascular side effects. In this review, we aim to elucidate the underlying patho-mechanisms and to characterize the development of radiation-induced cardiovascular damage. Additionally, approaches for clinical management and treatment options are presented.

Management of breast cancer: an overview for therapeutic radiographers

AbstractIntroduction:The management of breast cancer patients from diagnosis to treatment and beyond can be variable depending on factors including tumour extent and location, histology, genetics, health and wellbeing of the patient as well as personal patient preferences. The therapeutic radiographer’s role is not only vital to ensure safe and accurate radiotherapy delivery but also crucially, as the regular patient interface, they must be fully empowered to engage effectively with all aspects of the patient care pathway. They must be knowledgeable and up to date with evidence-based practices relating to the patient experience including surgery, chemotherapy, endocrine therapy and radiotherapy.Aim:The aim of this paper is to outline the breast cancer management pathway, highlighting the potential side effects that occur as a result of breast radiotherapy treatment and concomitant treatment in order to inform therapeutic radiographers and best practice.Discussion:The treatment pathway for breast cancer patients varies greatly depending on a wide range of factors and is very much individualised for each patient. Each treatment modality has its advantages and disadvantages, and all come with a number of side effects that can affect a patient’s daily living. Toxicities can arise during radiotherapy treatment or months after treatment, and education regarding the management of these is essential for effective patient care. Many technological advances in radiotherapy treatment techniques and regimes have the potential to decrease radiation-induced side effects. Despite attempts to standardise clinical guidelines on the use of topical agents and dressings, historical opinions and ideas are still evident in clinical practice. The use of grading systems in radiotherapy tends to only record patients’ physical symptoms and not their holistic wellbeing and emotional needs.Conclusion:Therapeutic radiographers must ensure that they remain equipped with the skills and knowledge to correctly manage and/or signpost services effectively. This overall outline of the management of patients with breast cancer is designed to help therapeutic radiographers reflect on the current practices and to inspire them, where evidence dictates, to seize opportunities, to explore improvement and to enhance best practice.

Role of Oxycodone Hydrochloride in Treating Radiotherapy-Related Pain.

Radiotherapy is commonly used to treat cancer patients. Besides the curable effect, radiotherapy also could relieve the pain of cancer patients. However, cancer pain is gradually alleviated about two weeks after radiotherapy. In addition, cancer patients who receive radiotherapy may also suffer from pain flare or radiotherapy-induced side effects such as radiation esophagitis, enteritis, and mucositis. Pain control is reported to be inadequate during the whole course of radiotherapy (before, during, and after radiotherapy), and quality of life is seriously affected. Hence, radiotherapy is suggested to be combined with analgesic drugs in clinical guidelines. Previous studies have shown that radiotherapy combined with oxycodone hydrochloride can effectively alleviate cancer pain. In this review, we firstly presented the necessity of analgesia during the whole course of radiotherapy. We also sketched the role of oxycodone hydrochloride in radiotherapy of bone metastases and radiotherapy-induced oral mucositis. Finally, we concluded that oxycodone hydrochloride shows good efficacy and tolerance and could be used for pain management before, during, and after radiotherapy.