A suprapubic refractory skin ulcer following keloid radiotherapy: from hyper-proliferation to hypo-proliferation.

Radiation-induced skin ulcer following cancer and/or tumour is well-documented in the literature. However, radiation-induced skin ulcer following the excision of keloid is yet to be reported. Here, we report the case of a 33-year-old female patient with a suprapubic skin ulcer of five months' duration following keloid treatment with electron beam therapy at recommended dosage. Various examinations, including a skin biopsy, metagenomic sequencing, magnetic resonance imaging and immunochemistry, indicated that the skin ulcer was induced by radiotherapy. While postoperative radiotherapy has been recommended immediately following keloid excision to reduce the risk of recurrence, the present case highlights the risk of skin refractory ulcer following keloid radiotherapy.

Probiotics in the management of radiation-induced oral mucositis.

Oral mucositis is a common and debilitating oral complication in head and neck cancer patients undergoing radiotherapy, resulting in diminished quality of life and potential treatment disruptions. Oral microbiota has long been recognized as a contributing factor in the initiation and progression of radiation-induced oral mucositis (RIOM). Numerous studies have indicated that the radiation-induced oral microbial dysbiosis promotes the occurrence and severity of oral mucositis. Therefore, approaches that modulate oral microbial ecology are promising for the management of RIOM. Probiotics as a relatively predicable and safe measure that modulates microecology have garnered significant interest. In this review, we discussed the correlation between RIOM and oral microbiota, with a particular focus on the efficacy of probiotics in the control of RIOM, in order to provide novel paradigm for the management of this disease.

Cancer therapy-related salivary dysfunction.

Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described.

A Basis for Strengthening Coping Strategies and Treatment Expectations in Patients Undergoing Emetogenic Pelvic-Abdominal Radiotherapy: A Longitudinal Study.

Objectives: To study the relationship between coping strategies and nausea during emetogenic pelvic-abdominal radiotherapy, and to describe the patients' rationales for their expectations regarding nausea. Methods: Patients (n = 200: 84% women, mean age 64 years, 69% had gynecological, 27% colorectal, and 4% had other malignances) longitudinally participated during pelvic-abdominal radiotherapy. We measured adopted coping strategies using the Mental Adjustment to Cancer scale and the patients' rationales for their expectations regarding nausea at baseline. The patients registered nausea and vomiting daily during the radiotherapy period (mean 36 + Standard Deviation 10 days). Results: Patients who experienced nausea (n = 128, 64%) during the radiotherapy period graded a lower score on "Fighting Spirit" (median, md, score 51, P = .031) and a higher score on "anxious preoccupation" (md 18, P = .040) compared to patients who did not experience nausea (n = 72, 36%), md 54 and md 17. More of the patients for whom "Helpless-Hopeless" represented the most predominant response experienced nausea (100%) or vomited (56%) compared to patients adopting "Fighting Spirit": 62% experienced nausea (P = .011) and 20% vomited (P = .014). Only four (6%) of the nausea-free patients had expected themselves to be at increased risk for nausea. Of the patients who became nauseous, 22 (17%) patients had expected themselves to be at increased risk for nausea (P = .017), based on previous experience. Conclusion: Patients adopting maladaptive coping strategies or patients expecting nausea based on previous experiences, were more likely to experience nausea than other patients when undergoing emetogenic pelvic-abdominal radiotherapy. Cancer care professionals may identify patients adopting maladaptive coping strategies or having high nausea expectations by applying the MAC scale and self-assessment of expected nausea risk and guide these patients to adopt adaptive coping strategies and strengthen their expectations on successful prevention of nausea.Trial registration number: Clinicaltrials.gov: NCT00621660.

Constitutional Factors and Irradiation as Risk Factors for Thymoma: A European Case-Control Study.

Little is known about the aetiology of thymoma. This study aims to identify medical risk factors for thymoma as a systematic approach to new hypotheses on the aetiology of this disease. A European multi-centre case-control study was conducted from 1995 to 1997, including incident cases aged 35-69 years with thymoma. Altogether, we accepted 85 cases and 3350 controls, of which we interviewed 77 cases and 2071 population controls about constitutional factors, medical examinations, and former diseases. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Medical examinations with X-ray or radiotherapy performed >20 times at least one year before the thymoma diagnosis indicated a possible risk factor for thymoma (OR 1.58, 95% CI 0.93-2.69). Having the first radiotherapy treatment at least one year before the thymoma diagnosis yielded an OR for thymoma of 2.39; 95% CI (0.96-5.99), and if it was at least five years before, the OR for thymoma was 2.81; 95% CI (1.03-7.72). Having a red/auburn hair colour was associated with thymoma, (OR 3.6, 95% CI 1.4-9.5) whereas having pigmented skin was slightly associated with thymoma (OR 1.8, 95% CI 0.8-3.8). Over twenty instances of X-ray examinations or radiotherapy were identified as potential risk factors for thymoma, along with certain constitutional factors. The observed correlations between benign tumours and thymoma could stem from an inherent predisposition to tumour development or result from detection bias. Given that this is the initial analytical study examining medical risk factors for thymoma, all of the results should be approached with caution, acknowledging the possibility that some findings might be incidental.

Radiation-associated cardiovascular disease in patients with cancer: current insights from a cardio-oncologist.

Radiation-associated cardiovascular disease (RACD), a complex disease characterized with pericarditis, myocardial damage, valvular heart diseases, heart failure, vasculopathy and ischemic heart disease, has a generally poor prognosis. While RACD may be acute, it often manifests in the late years or even decades following radiation exposure to the chest. With an increasing number of cancer survivors, RACD is likely to become an important issue in cardio-oncology. This review discusses pre-radiation therapy (RT) preparation, peri-RT patient management and long follow-up planning post-RT from a cardiology perspective. Additionally, a novel technique of stereotactic radiotherapy, which has been applied for the treatment of intractable cardiac arrhythmias, is presented. Appropriate patient examination and management during and after RT are essential to support patients undergoing cancer treatment to improve long life expectancy. A multidisciplinary team is needed to determine how to manage patients who receive RT to reduce RACD, to detect early phases of RACD and to provide the best treatment for RACD. Recent studies increasingly report advances in diagnosis using new equipment that has the potential to detect early phases of RACD, along with growing evidence for the optimal treatment for RACD. This review provides an overview of recent studies and guidelines to report on the latest findings, and to identify unresolved issues surrounding RACD that require validation in future studies.

Advancements in Understanding and Managing Radiation Cystitis: A Comprehensive Review.

PURPOSE OF REVIEW: This manuscript aims to provide a comprehensive overview of the pathophysiology, risk factors, prevention strategies, and management options for radiation cystitis. RECENT FINDINGS: Recent studies have shed light on the pathophysiology of radiation cystitis, highlighting the role of inflammation, fibrosis, and vascular damage. Emerging preventive measures like stem cell therapy offer promise, alongside novel treatments such as amniotic bladder therapy and hyperbaric oxygen therapy. This review outlines the latest research on radiation cystitis, covering its pathophysiology, risk factors, prevention, and management. Major findings include insights into the mechanisms of RC development, promising preventive and therapeutic approaches, and the importance of standardized treatment pathways. Future research should focus on identifying genetic risk factors, improving treatment efficacy, and enhancing patient outcomes. This review offers valuable insights for clinicians and researchers, guiding future investigations into radiation cystitis management.

Pelvic Radiation Therapy Increases Risk of Pouch Failure in Patients with Inflammatory Bowel Disease and Ileal Pouch.

BACKGROUND: The effect of radiation on the ileal pouch is less well studied in patients with inflammatory bowel disease (IBD) and ileal pouch-anal anastomosis. AIMS: This retrospective study investigates the impact of external radiation therapy on the outcomes of ileal pouches. METHODS: The study included 82 patients with IBD and ileal pouches, of whom 12 received pelvic radiation, 16 abdominal radiation, 14 radiation in other fields, and 40 served as controls with no radiation. Pouch-related outcomes, including pouch failure, worsening of symptoms, pouchitis, and development of strictures, along with changes in Pouch Disease Activity Index (PDAI) scores pre- and post-radiation were assessed. RESULTS: The pelvic radiation group exhibited a significantly higher rate of pouch failure (25%, p < 0.004) and worsening pouch-related symptoms (75%, p = 0.012) compared to other groups. Although not statistically significant, a higher incidence of pouchitis was observed in the pelvic radiation group (45.5%, p = 0.071). Strictures were more common in the pelvic radiation group (25%, p = 0.043). Logistic regression analysis revealed that pelvic radiation significantly increased the odds of pouch-related adverse outcomes (OR 5.66; 95% confidence interval: 1.61-21.5). CONCLUSION: Pelvic radiation significantly impacts the outcomes of ileal pouches in patients with IBD, increasing the risk of pouch failure, symptom exacerbation, and structural complications. These findings underscore the need for careful consideration of radiation therapy in this patient population and highlight the importance of closely monitoring and managing radiation-induced pouch dysfunction.

Definitive radiotherapy and trismus in HNC patients: A critical review.

INTRODUCTION: Trismus is a potentially critical morbidity following curative-intended radiotherapy in head and neck cancer patients. However, in this setting, evidence regarding this side effect remains to be fully defined, particularly in terms of dosimetric parameters. MATERIALS AND METHODS: Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. RESULTS: This paper contains a narrative report and a critical discussion of the evidence on radiation-induced trismus in the literature, particularly the dosimetric concerns. CONCLUSIONS: The treatment goal should be to maintain high cure rates and limit the onset of complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring.

Single Nucleotide Polymorphisms in APE1, hOGG1, RAD51 Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients.

BACKGROUND: Radiotherapy (RT) is a crucial treatment for head and neck cancer however, it causes adverse reactions to the normal tissue and organs adjacent to target tumor. The present study was carried out to investigate possible association of single nucleotide polymorphism in DNA repair genes with toxicity effects of radiotherapy on normal tissue. METHODS: Three hundred and fifty head and neck cancer patients receiving radiotherapy treatment were enrolled in this study. The adverse after effects of radiotherapy on the normal tissue in the form of skin reactions were recorded. Single nucleotide polymorphisms of APE1 (rs1130409), hOGG1 (rs1052133) and Rad51 (rs1801320, rs1801321) genes were studied by polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing methods and their association with development of severe radio-toxicity effects was evaluated logistic regression analysis. RESULTS: The 172G/T polymorphism of Rad51 was 2.85 times higher and significantly associated with skin reactions (OR=2.85, 95% CI: 1.50-5.41; p=0.001) and severe oral mucositis (OR=4.96, 95% CI: 2.40-10.25; p<0.0001). These results suggested that the polymorphic nature of Rad51 is responsible for risk of radiotherapy adverse effects in HNC patients. The variant 326Cys and heterozygous 326Ser/Cys genotype of hOGG1 was significantly associated with high tumor grade (OR=3.16 95% CI: 1.66-5.99; p=0.0004, and OR=3.97 95% CI: 2.15-7.34; p=<0.0001 respectively). The homozygous variant 172TT genotype of Rad51 showed positive association with poor response of both tumor and nodes towards radiotherapy treatment (p=0.007 and p=0.022). CONCLUSIONS: Interpretation of our results revealed significant association of rs1801321 SNP of Rad51 with development of adverse toxicity reactions in normal tissue of head and neck cancer patients treated with radiotherapy.

The effect of probiotics on severe oral mucositis in cancer patients undergoing chemotherapy and/or radiotherapy: A meta-analysis.

PURPOSE: Oral mucositis is a frequent adverse reaction in cancer treatment. Probiotics exhibit anti-inflammatory and immunomodulatory properties that could prevent the occurrence of severe oral mucositis (SOM) induced by chemotherapy or radiation therapy in patients. This meta-analysis aimed to investigate the influence of probiotics on the incidence of SOM in cancer patients undergoing chemotherapy and/or radiotherapy. METHODS: We conducted a comprehensive search in PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) from their inception to September 2023. Dichotomous variables are analyzed with odds ratios (ORs) with 95% CIs, and statistical significance was set at a two-tailed P <0 .05. The primary outcome indicator was the effect of probiotics on SOM. Secondary outcome indicators included the effect of probiotics on oral mucositis and the ratio of diarrhoea. Statistical analysis was conducted using RevMan (5.4) and Stata 17.0 software. RESULTS: The study included a total of 12 articles and involved 1055 patients. All patients had undergone either radiotherapy or chemotherapy. Our findings revealed that the experimental group, which received probiotics for treatment, exhibited a lower ratio of SOM compared to the control group that received traditional placebo treatment (OR=0.37, 95%CI [0.28, 0.50], P<0.01). Subgroup analysis revealed variations in the ratio of SOM based on therapeutic regimen, tumor type, and region. The overall ratio of oral mucositis was significantly lower in the experimental group compared to the control group (OR=0.19, 95%CI [0.09-0.39], P<0.01). The ratio of diarrhea in the two patient groups showed no significant difference (OR=0.85, 95%CI [0.24, 3.01], P>0.05). CONCLUSION: The results of this meta-analysis suggest that probiotics could decrease the occurrence of SOM.

Pubic bone osteomyelitis and fistulas after radiation therapy of the pelvic region: patient-reported outcomes and urological management of a rare but serious complication.

PURPOSE: This study investigated late urinary adverse events (UAEs) in patients who underwent pelvic radiation therapy, with a focus on occurrence, diagnostic characteristics and the impact of subsequent extirpative surgery with the need of urinary diversion on quality of life. METHODS: A retrospective analysis of 20 patients after pelvic radiotherapy (2016-2022) was conducted. Data included demographics, perioperative details, oncological parameters, and patient-reported outcomes. Imaging (CT, MRI) was examined for early manifestations of late UAEs. RESULTS: In the study cohort, prostate cancer was the primary malignancy in 85% with a mean radiation dose of 84 Gray over 35 days. Time to diagnosis of late UAEs was 4.0 years post-radiation. Radiological assessment demonstrated a progressive increase in typical CT and MRI features of pubic bone osteomyelitis over time. Surgical interventions, mainly cystectomy, were required with variable outcomes in patient-reported post-surgery quality of life. CONCLUSION: Diagnosing and managing late UAEs after pelvic radiation necessitate an understanding of their occurrence, diagnostic features and appropriate management strategies. Early imaging, particularly MRI, is crucial for timely diagnosis and treatment planning. Variable post-surgery quality of life underscores the importance of a multidisciplinary approach in managing late UAEs. The study contributes to understanding these complications and emphasizes their consideration in post-radiation follow-up care.

Radiation Induced Skin Fibrosis (RISF): Opportunity for Angiotensin II-Dependent Intervention.

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. The primary goal is to offer essential insights in order to better care for and improve the quality of life of cancer survivors who face the risk of developing RISF.

Prevention and management of radiotherapy-related toxicities in gynecological malignancies. Position paper on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology).

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.

Cardiovascular toxicity in antitumor therapy: biological and therapeutic insights.

The evolution of antitumor therapies has significantly improved cancer prognosis but has concurrently resulted in cardiovascular toxicities. Understanding the biological mechanisms behind these toxicities is crucial for effective management. Immunotherapy-related cardiovascular toxicities are primarily mediated by immune cells and secreted cytokines. Chemotherapy may cause cardiovascular damage through autophagy disruption and mitochondrial dysfunction. Targeted therapies can induce toxicity through endothelin-1 (ET-1) production and cardiac signaling disruption. Radiotherapy may lead to cardiomyopathy and myocardial fibrosis by affecting endothelial cells, triggering inflammatory responses and accelerating atherosclerosis. This review provides insights into these mechanisms and strategies, aiming to enhance the clinical prevention and treatment of cardiovascular toxicities.

Cardiac conduction system as a new organ at risk in radiotherapy.

BACKGROUND: Cardiovascular diseases represent the most common non-oncologic cause of death in patients following radiotherapy (RT) in the thoracic region. Radiation-induced heart disease (RIHD) can manifest as various heterogeneous clinical entities. However, the influence of RT on the cardiac conduction system has only recently gained more attention. Arrhythmogenic toxicity, i.e., conduction disorders and arrhythmias, constitutes a significant part of these adverse effects. The cardiac conduction system is not routinely monitored as an organ at risk (OaR). Its specific histological nature and function suggest different sensitivity and response to radiation. The heart is a highly heterogeneous organ, and the routinely monitored dose to the whole heart may not adequately characterize the risk of increased arrhythmogenic toxicity from RT. Cardiac structures, including the conduction system, appear to be additional OaRs for which dose distribution should be monitored. MATERIAL AND METHODS: For the systematic selection of studies, we utilized the PubMed database with keywords derived from the analysis of existing literature. The search was limited to English-language publications, and the selection criteria included relevance to the topic and the quality of methodology. PURPOSE: This article summarizes the impact of RT on the cardiac conduction system. CONCLUSION: Radiotherapy-induced cardiotoxicity significantly affects morbidity and mortality. The heart exhibits heterogeneity in terms of radiosensitivity. Certain cardiac subregions in the dose distribution show a higher correlation with poorer overall survival than routinely monitored doses to the whole heart and derived parameters (the volumes irradiated with the doses of 5 or 30 Gy - V5 or V30, respectively). The most radiosensitive subregions appear to be the base of the heart, including the beginning of the conduction system. Higher doses to the conduction system, especially the sinoatrial (SA) node, are associated with a higher incidence of a wide range of arrhythmias and poorer overall survival. However, dose limits (Dmean and Dmax) for the conduction system have not yet been established. Dosimetric studies have identified cutoff doses to the SA node, exceeding which there is a significant increase in mortality and the occurrence of arrhythmias.