Academic literature on the topic 'Radiation-induced tissue toxicity'

Radiation-induced toxicity to healthy/normal intestinal tissues, especially during radiotherapy, limits the radiation dose necessary to effectively eradicate tumors of the abdomen and pelvis. Although the pathogenesis of intestinal radiation toxicity is highly complex, understanding post-irradiation alterations in protein profiles can provide crucial insights that make radiotherapy safer and more efficient and allow for increasing the radiation dose during cancer treatment. Recent preclinical and clinical studies have advanced our current understanding of the molecular changes associated with radiation-induced intestinal damage by assessing changes in protein expression with mass spectrometry-based approaches and 2-dimensional difference gel electrophoresis. Studies by various groups have demonstrated that proteins that are involved in the inflammatory response, the apoptotic pathway, reactive oxygen species scavenging, and cell proliferation can be targeted to develop effective radiation countermeasures. Moreover, altered protein profiles serve as a crucial biomarkers for intestinal radiation damage. In this review, we present alterations in protein signatures following intestinal radiation damage as detected by proteomics approaches in preclinical and clinical models with the aim of providing a better understanding of how to accomplish intestinal protection against radiation damage.

Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.

Preoperative radiotherapy ? chemotherapy became the standard treatment for locally advanced rectal cancer. Despite better local control with this approach, there was not seen a significant improvement in overall survival and disease free survival, yet. The main disadvantage is toxicity that can be developed, especially concomitantly with chemotherapy. Toxicity can be acute and late. Acute complications are transitory, but late might lead to permanent damage and consequently are more significant for patients. Today, there are technical opportunities in reduction of acute and late radiation toxicity in the treatment of rectal cancer. With the implementation of 3D conformal radiotherapy (3D CRT) and intensity modulated radiation therapy (IMRT) techniques in clinical practice significant accuracy, better dose distribution and safety in the treatment of rectal cancer patients is achieved, with maximal sparing of surrounding normal tissue. Utilization of advanced techniques and new software solutions can keep adverse effects on satisfactory levels with excellent local control.

Exaggerated acute and late toxicities following radiotherapy have been reported in patients with pre-existing connective tissue diseases, such as systemic lupus and scleroderma. Behcet’s disease (BD) is a relapsing multisystem connective tissue disease characterized by vasculitis in the mucocutaneous, ocular, gastrointestinal, respiratory, neurologic, urogenital, articular, and cardiovascular systems. Data concerning the relationship between radiotherapy toxicity and BD are limited in the literature. Here, we report a case of lung cancer treated with radiotherapy (60 Gy) in a patient with BD. No severe radiation-induced toxicity was observed. Radiation-induced toxicity in patients with BD has also been discussed.

Background and Objectives: Reducing time of treatment during COVID-19 outbreaks has been recommended by the leading Radiation Oncology societies. Still minimizing radiation induced tissue toxicity is one of the most important issues in breast cancer patients. The study aimed to investigate compliance, clinical and dosimetry normal tissue toxicity, and cosmetic results between moderated and ultra-fractionated regimes for breast cancer patients during COVID-19 pandemic. Materials and Methods: This pilot prospective randomized study included 60 patients with early breast cancer after preserving surgery, 27 patients advocated to ultra-hypofractionated whole-breast three dimensional (3D) conformal radiotherapy of 26 Gy in 5 fractions over 1 week and 33 patients with moderate fractionated breast 3D conformal radiotherapy patients between March 2020 and July 2020, during the COVID pandemic outbreak. The compliance to treatment, dosimetric parameters, acute and late skin toxicity, subcutaneous tissue toxicity, cosmetic results and clinical follow up for 18 months for the two regimes were analyzed and compared. Results: When two regimes were compared 5 fraction group had significantly lower prevalence of newly infected cases of SARS-CoV-2 and thus delayed/interrupted treatment (p = 0.05), comparable grade 1 CTCAE v5, acute skin toxicity (p = 0.18), Grade 1 Radiation Morbidity Scoring Scheme (RESS) subcutaneous tissue toxicity (p = 0.18), Grade 1 RESS late skin toxicity (p = 0.88) and cosmetic results (p = 0.46). Dosimetric results reveled that patients in 5 fraction group received significantly lower median ipsilateral lung doses (p < 0.01) in addition to left breast cancer patients that received significantly lower median heart dose (p < 0.01) and median left anterior descending artery (LAD) dose (p < 0.01). Conclusion: Ultra-hypofractionated radiotherapy for breast cancer is comparable to moderate hypofractionation regimen regarding grade 1 acute skin toxicity, grade 1 subcutaneous tissue toxicity, late skin toxicity and cosmetic results. Application of ultra-hypofractionated radiotherapy with significantly lower radiation doses for lung and heart could be crucial in reducing the risk of acute/late pulmonary and heart radiation-induced toxicity.

Radiotherapy is one of the most effective methods for the treatment of cancer, but occurrence of adverse reactions developing in the co-irradiated normal tissue can be a threat for patients. Identification of individuals at risk of severe reaction is very difficult and considerable efforts have been made to correlate normal tissue toxicity with cellular responses to ionizing radiation. Genetic markers enabling to identify hyper-sensitive patients prior to treatment would considerably improve its outcome. Gene association studies should help to identify such markers. Expression levels of specific transcripts could be putative markers; in fact different studies found associations between gene expression profiles in normal cells and the reaction of normal tissues to radiation therapy. The finding that ionizing radiation induces the deregulation of a high number of genes suggests that also microRNAs that affect the expression of a large number of target genes may be involved. This review briefly introduces the mechanisms of radiation-induced normal tissue toxicity and summarizes clinical research focused on the evaluation of molecular biomarkers for predicting risk of injury to normal tissue, mainly describing gene transcripts alterations.

Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. We conducted a morphological analysis of MRT-irradiated normal liver, lung and skin tissues as well as lung and melanoma tumours. MRT induced distinct patterns of DNA damage, reflecting the geometry of the microbeam array. Macrophages infiltrated these regions of peak dose deposition at variable timepoints post-irradiation depending on the tissue type. In normal liver and lung tissue, macrophages clearly demarcated the beam path by 48 h and 7 days post-irradiation, respectively. This was not reflected, however, in normal skin tissue, despite clear DNA damage marking the beam path. Persistent DNA damage was observed in MRT-irradiated lung carcinoma, with an accompanying geometry-specific influx of mixed M1/M2-like macrophage populations. These data indicate the unique potential of MRT as a tool to induce a remarkable accumulation of macrophages in an organ/tissue-specific manner. Further characterization of these macrophage populations is warranted to identify their organ-specific roles in normal tissue sparing and anti-tumour responses.

Liver was always considered to be ‘highly sensitive’ to radiation therapy (RT) and was not considered ‘safe’ for radiation therapy treatment. The most significant radiation induced liver toxicity was described by Ingold et al. as “Radiation hepatitis.” Historically, radiation to liver lesions with curative intent or incidental exposure during adjacent organ treatment or total body irradiation implied whole organ irradiation due to lack of high precision technology. Whole organ irradiation led to classic clinical picture termed as “Radiation Induced Liver Disease (RILD).” In conventional fractionation, the whole liver could be treated only to the doses of 30–35Gy safely, which mostly serves as palliation rather than cure. With the advent of technological advancements like IMRT, especially stereotactic radiation therapy (SBRT), the notion of highly precise and accurate treatment has been made practically possible. The toxicity profile for this kind of focused radiation was certainly different from that of whole organ irradiation. There have been attempts made to characterize the effects caused by the high precision radiation. Thus, the QUANTEC liver paper distinguished RILD to ‘classic’ and ‘non-classic’ types. Classic RILD is defined as ‘anicteric hepatomegaly and ascites’, and also can also have elevated alkaline phosphatase (more than twice the upper limit of normal or baseline value). This is the type of clinical picture encountered following irradiation of whole or greater part of the organ. Non-classic RILD is defined by elevated liver transaminases more than five times the upper limit of normal or a decline in liver function (measured by a worsening of Child-Pugh score by 2 or more), in the absence of classic RILD. In patients with baseline values more than five times the upper limit of normal, CTCAE Grade 4 levels are within 3 months after completion of RT. This is the type of RILD that is encountered typically after high-dose radiation to a smaller part of liver. It is commonly associated with infective etiology. Emami et al. reported the liver tolerance doses or TD 5/5 (5% complication rate in 5 years) as 50 Gy for one-third (33%) of the liver, 35 Gy for two-thirds (67%) of the liver, and 30 Gy for the whole liver (100%). Liver function (Child Pugh Score), infective etiology, performance status and co-morbidities influence the radiation induced toxicity. Lyman–Kutcher–Burman (LKB)-NTCP model was used to assess dose-volume risk of RILD. Lausch et al. at London Regional Cancer Program (LRCP), developed a logistic TCP model. Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reported recommendations that mean normal liver dose should be <18 Gy for baseline CP-A patients and < 6 Gy for those with CP-B, for a 6-fraction SBRT regimen. The University of Colorado phase 1 clinical trial of SBRT for liver metastases described the importance of the liver volume spared, that is, ‘critical volume model.’ It is estimated that a typical normal liver volume is approximately 2000 mL and specified that a minimum volume of 700 mL or 35% of normal liver should remain uninjured by SBRT i.e. at least 700 mL of normal liver (entire liver minus cumulative GTV) had to receive at total dose less than 15 Gy. In treatment regimen of 48 Gy in 3 fractions, CP-A patients were required to either limit the dose to 33% of the uninvolved liver (D33%) < 10 Gy and maintain the liver volume receiving <7 Gy to <500 cc. In more conservative treatment regimen, such as in 40 Gy in 5 fractions schedule, CP-B7 patients had to meet constraints of D33% < 18 Gy and/or > 500 cc receiving <12 Gy. The concept of body surface area (BSA) and Basal Metabolic Index (BMI) guided estimation of optimal liver volume is required to estimate the liver volume need to be spared during SBRT treatment. Radiation induced liver injury is potentially hazardous complication. There is no definitive treatment and a proportion of patient may land up in gross decompensation. Usually supportive care, diuretics, albumin supplement, and vitamin K replacement may be useful. Better case selection will avert incidence of RILD. Precise imaging, contouring, planning and respecting normal tissue constraints are critical. Radiation delivery with motion management and image guidance will allow delivery of higher dose and spare normal liver and hence will improve response to treatment and reduce RILD.

Although radiation therapy (RT) planning and execution techniques have evolved to minimize radiotoxicity to a considerable extent, adjacent tissues still receive a substantial dose of ionizing radiation, resulting in radiotoxicities that may limit patients’ quality of life. Depending on the location of tissue injury and the severity of the cellular response, there may also be a need to interrupt RT, thus interfering with the prognosis of the disease. There is a hypothesis that genetic factors may be associated with individual radiosensitivity. Recent studies have shown that genetic susceptibility accounts for approximately 80% of the differences in toxicity. The evolution of genomic sequencing techniques has enabled the study of radiogenomics, which is emerging as a fertile field to evaluate the role of genetic biomarkers. Radiogenomics focuses on the analysis of genetic variations and radiation responses, including tumor responses to RT and susceptibility to toxicity in adjacent tissues. Several studies involving polymorphisms have been conducted to assess the ability to predict RT-related acute and chronic skin toxicities, particularly in patients with breast and head and neck cancers. The purpose of this chapter is to discuss how radiogenomics can help in the management of radiotoxicities, particularly radiodermatitis.

Introduction: Carcinoma cervix is the fourth (GLOBACON 2012) most common cancer among women worldwide, and the main cancer affecting women in Sub-Saharan Africa, Central America and south-central Asia. In India, approx. 1,23,000 (GLOBACON 2012) new cases of carcinoma cervix are diagnosed each year. Brachytherapy is an integral part of treatment of cancer cervix. In the context of a developing country like us where maximum utilization of the resource is of prime importance to provide treatment to the large patient cohort, shortening the treatment duration and number of fractions always increases efficiency. In order to maximize the logistic benefits of HDR-BT while improving patient compliance and resource sparing, various fractionation regimens are used. Fractionation and dose adjustments of the total dose are radiobiologically important factors in lowering the incidence of complications without compromising the treatment results. Aim: To compare patient outcomes and complications using two linear-quadratic model-based fractionation schemes of high-dose-rate intracavitary brachytherapy (HDR-IC) used to treat cervical cancer. Materials and Methods: A prospective randomized study on 318 patients, with histologically proven advanced carcinoma cervix (stages IIB-IIIB) was enrolled in the study. All patients received External Beam Radio Therapy (EBRT) 50 Gy in 25 fractions with concurrent chemotherapy (cisplatin 35 mg/m2) followed by IntraCavitary brachytherapy using high dose rate equipment. Patients were randomised after completion of EBRT into two arms: (1) Arm 1: HDR ICRT 6.5 Gy per fraction for 3 fractions, a week apart. (2) Arm 2: HDR ICRT, 9 Gy per fraction for 2 fractions, 1 week apart. On completion of treatment, patients were assessed monthly for 3 months followed by 3 monthly thereafter. Treatment response was assessed according to WHO criteria after one month of completion of radiotherapy. The RTOG criteria were used for radiation induced toxicities. We analyzed late toxicities in terms of Rectal, Bladder, Small Bowel toxicity and Vaginal Stenosis. Results: Acute reactions in both the groups were comparable. None of the patient developed Grade 4 toxicity in our study and no toxicity related mortality was encountered. A slightly high frequency of late toxicity was observed in 9Gy Arm patients but was not statistically significant. Conclusion: In our setup, HDR brachytherapy at 9 Gy per fraction in two fractions is safe, effective and resource saving method with good local control, survival, and manageable normal tissue toxicity.