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Purpose Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. Methods Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). Results Twenty participants were 26–71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. Conclusions According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial.

Many head and neck cancer (HNC) survivors experience reduced quality of life due to radiotherapy (RT)-related dysphagia. The aim of this prospective randomized trial was to evaluate the impact of prophylactic swallowing exercises on swallowing-related outcomes in HNC patients treated with curative RT. Patients treated with primary RT for HNC were candidates for this randomized protocol. Participants in the exercise group were instructed to perform swallowing exercises at home. Participants in the control group were given standard care. Patients were evaluated with modified barium swallow and several other secondary outcome measures at four and nine different time points, respectively. Data were analyzed according to intention-to-treat analyses. A total of 44 consecutive patients were included; 22 in each group. In general, there was no difference between the two groups regarding any of the dysphagia outcomes during and after treatment. Adherence to exercises was poor and dropouts due to especially fatigue were very frequent in both groups. Systematic swallowing exercises had no impact on swallowing outcomes within the first year after RT. Despite repeated supervised sessions, adherence to exercises was a major issue and dropouts were frequent in both the intervention and control group.

Objective This study aimed to detect early changes in left ventricular systolic function in Beagle dogs after radiotherapy using two-dimensional speckle tracking echocardiography and to explore its potential value in evaluating radiation-induced heart disease. Methods Thirty-six Beagle dogs were randomized into a control group ( n  = 18) and an irradiation group ( n  = 18). The irradiation group received a single dose of 20 Gy to the left ventricular anterior wall, while controls underwent sham irradiation. Conventional echocardiography and 2D speckle tracking echocardiography were performed at baseline and 3, 6, and 12 months post-procedure. Additionally, six dogs were randomly selected from each group and euthanized at 3-, 6-, and 12-month post-irradiation, and their hearts were collected for histopathological testing. Results In the irradiation group, the global longitudinal strain of the left ventricle and regional strain in the irradiated area were significantly reduced versus baseline and controls by 3 months, with progressive decline at 6 and 12 months. Strain reduction correlated spatially with pathological injury. Conversely, there were no substantial differences in conventional echocardiographic parameters between the groups after 3 months. Conventional parameters (e.g., LVEF) showed differences only at later timepoints. Histopathology revealed progressive cardiomyocyte damage, fibrosis, and microvascular injury in irradiated regions, extending to the posterior wall by 12 months. Conclusion Two-dimensional speckle tracking echocardiography-derived strain parameters spatially correlate with radiation-induced pathological changes and detect subtle systolic dysfunction prior to irreversible remodeling. Speckle tracking may localize regions of peak radiation dose delivery.

ABSTRACT Objective: to evaluate the effect of physical therapy on the range of motion of the shoulders and perimetry of the upper limbs in women treated with radiotherapy for breast cancer. Methods: a total of 35 participants were randomized into two groups, with 18 in the control group (CG) and 17 in the study group (SG). Both of the groups underwent three evaluations to assess the range of motion of the shoulders and perimetry of the upper limbs, and the study group underwent supervised physical therapy for the upper limbs. Results: the CG had deficits in external rotation in evaluations 1, 2, and 3, whereas the SG had deficits in flexion, abduction, and external rotation in evaluation 1. The deficit in abduction was recovered in evaluation 2, whereas the deficits in all movements were recovered in evaluation 3. No significant differences in perimetry were observed between the groups. Conclusion: the applied supervised physical therapy was effective in recovering the deficit in abduction after radiotherapy, and the deficits in flexion and external rotation were recovered within two months after the end of radiotherapy. Registration number of the clinical trial: NCT02198118. RESUMEN Objetivo: evaluar el efecto de la terapia física en el rango de movimiento de los hombros y la perimetría de las extremidades superiores en mujeres tratadas con radioterapia debido a cáncer de mama. Métodos: un total de 35 participantes fueron aleatorizadas en dos grupos, 18 en el grupo control y 17 en el grupo de estudio. Ambos grupos fueron sometidos a tres evaluaciones para evaluar el rango de movimiento de los hombros y la perimetría de las extremidades superiores, y el grupo de estudio fue sometido a terapia física supervisada de las extremidades superiores. Resultados: el grupo de control tuvo déficits en la rotación externa en la evaluación 1, 2, y 3, mientras que el grupo de estudio tuvo déficits en la flexión, abducción y rotación externa en la evaluación 1. El déficit en la abducción fue recuperado en la evaluación 2, mientras que los déficits en todos los movimientos fueron recuperados en la evaluación 3. No se observaron diferencias significativas en la perimetría. Conclusión: la terapia física supervisada aplicada fue efectiva en la recuperación del déficit en la abducción después de la radioterapia y los déficits en flexión y rotación externa fueron recuperados dos meses después de terminada la radioterapia. Número de registro del ensayo clínico: NCT02198118. RESUMO Objetivo: avaliar o efeito da fisioterapia na amplitude de movimento do ombro e na perimetria do membro superior, aplicada durante o período da radioterapia nas mulheres em tratamento para o câncer de mama. Métodos: 35 voluntárias foram randomizadas em dois grupos, 18 para o grupo controle e 17 para o grupo de estudo. Os dois grupos foram submetidos a três avaliações da amplitude de movimento do ombro e perimetria do membro superior, sendo o grupo de estudo também submetido à fisioterapia supervisionada para os membros superiores. Resultados: o grupo controle apresentou déficit entre os membros para o movimento de rotação externa nas avaliações 1, 2 e 3. O grupo de estudo apresentou déficit entre os membros para os movimentos de flexão, abdução e rotação externa na avaliação 1. Houve recuperação do déficit de movimento de abdução na avaliação 2 e, na avaliação 3, os déficits de todos os movimentos estavam recuperados. Na análise da perimetria não foi observada diferença significativa. Conclusão: o protocolo fisioterapêutico supervisionado aplicado foi efetivo na recuperação do déficit de abdução pós-radioterapia e de flexão e rotação externa quando avaliados até 2 meses após o término da radioterapia. Número do registro do ensaio clínico: NCT02198118.

The endothelium, a tissue that forms a single layer of cells lining various organs and cavities of the body, especially the heart and blood as well as lymphatic vessels, plays a complex role in vascular biology. It contributes to key aspects of vascular homeostasis and is also involved in pathophysiological processes, such as thrombosis, inflammation, and hypertension. Epidemiological data show that high doses of ionizing radiation lead to cardiovascular disease over time. The aim of this review is to summarize the current knowledge on endothelial cell activation and dysfunction after ionizing radiation exposure as a central feature preceding the development of cardiovascular diseases.

Purpose Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer. It results in a multitude of symptoms that significantly impact quality of life. Understanding the mechanisms of RIF-induced changes is essential to developing effective strategies to prevent long-term disability and discomfort following radiation therapy. In this review, we describe the current understanding of the etiology, clinical presentation, pathogenesis, treatment, and directions of future therapy for this condition. Methods A literature review of publications describing mechanisms or treatments of RIF was performed. Specific databases utilized included PubMed and clinicaltrials.gov, using keywords “Radiation-Induced Fibrosis,” “Radiotherapy Complications,” “Fibrosis Therapy,” and other closely related terms. Results RIF is the result of a misguided wound healing response. In addition to causing direct DNA damage, ionizing radiation generates reactive oxygen and nitrogen species that lead to localized inflammation. This inflammatory process ultimately evolves into a fibrotic one characterized by increased collagen deposition, poor vascularity, and scarring. Tumor growth factor beta serves as the primary mediator in this response along with a host of other cytokines and growth factors. Current therapies have largely been directed toward these molecular targets and their associated signaling pathways. Conclusion Although RIF is widely prevalent among patients undergoing radiation therapy and significantly impacts quality of life, there is still much to learn about its pathogenesis and mechanisms. Current treatments have stemmed from this understanding, and it is anticipated that further elucidation will be essential for the development of more effective therapies.

Radiotherapy is used in >50% of patients with cancer, both for curative and palliative purposes. Radiotherapy uses ionizing radiation to target and kill tumour tissue, but normal tissue can also be damaged, leading to toxicity. Modern and precise radiotherapy techniques, such as intensity-modulated radiotherapy, may prevent toxicity, but some patients still experience adverse effects. The physiopathology of toxicity is dependent on many parameters, such as the location of irradiation or the functional status of organs at risk. Knowledge of the mechanisms leads to a more rational approach for controlling radiotherapy toxicity, which may result in improved symptom control and quality of life for patients. This improved quality of life is particularly important in paediatric patients, who may live for many years with the long-term effects of radiotherapy. Notably, signs and symptoms occurring after radiotherapy may not be due to the treatment but to an exacerbation of existing conditions or to the development of new diseases. Although differential diagnosis may be difficult, it has important consequences for patients. Radiotherapy is used in >50% of patients with cancer but may be associated with short-term toxicity and long-term consequences. This Primer summarizes the mechanisms by which normal tissues are affected by irradiation, the techniques to mitigate such damage and how to treat the symptoms of radiotherapy toxicity.

Key Points Intracranial radiotherapy leads to permanent and substantial cognitive disability in 50–90% of patients The pathophysiology of radiotherapy-associated cognitive disability remains poorly understood and there are no effective preventive measures or long-term treatments Historically, most research has addressed markers of damage and the cognitive decline that appears 6 months to 1 year or more after irradiation More-sensitive imaging techniques have revealed subtle evidence of CNS damage much sooner than 6 months after radiation These early forms of CNS damage can persist and synergize over time to cause long-term, irreversible deficits in neurons and supporting cell lineages that are vital to cognition Consideration of early forms of radiation-induced CNS damage could help to identify early treatments that can reverse degenerative processes before they cause permanent disability The majority of patients who receive radiotherapy for brain tumours go on to develop disability, but the pathophysiological mechanisms of radiation-associated cognitive decline remains poorly understood. Here, Makale and colleagues review animal model and patient data on the mechanisms of radiotherapy-associated CNS damage and posit that early damage — occurring before 6 months after irradiation — contributes to long-term cognitive disability. Standard treatment of primary and metastatic brain tumours includes high-dose megavoltage-range radiation to the cranial vault. About half of patients survive >6 months, and many attain long-term control or cure. However, 50–90% of survivors exhibit disabling cognitive dysfunction. The radiation-associated cognitive syndrome is poorly understood and has no effective prevention or long-term treatment. Attention has primarily focused on mechanisms of disability that appear at 6 months to 1 year after radiotherapy. However, recent studies show that CNS alterations and dysfunction develop much earlier following radiation exposure. This finding has prompted the hypothesis that subtle early forms of radiation-induced CNS damage could drive chronic pathophysiological processes that lead to permanent cognitive decline. This Review presents evidence of acute radiation-triggered CNS inflammation, injury to neuronal lineages, accessory cells and their progenitors, and loss of supporting structure integrity. Moreover, injury-related processes initiated soon after irradiation could synergistically alter the signalling microenvironment in progenitor cell niches in the brain and the hippocampus, which is a structure critical to memory and cognition. Progenitor cell niche degradation could cause progressive neuronal loss and cognitive disability. The concluding discussion addresses future directions and potential early treatments that might reverse degenerative processes before they can cause permanent cognitive disability.

Despite the monumental advances in the diagnoses and therapeutics of malignancy, several cancer patients have presented with pericardial involvement, including acute pericarditis, constrictive pericarditis, and pericardial effusion. Multiple factors can contribute to acute pericarditis, including direct metastasis to the heart, pericardial hemorrhage, infections due to immunosuppression, and cancer therapies that include chemotherapy, immunotherapy, and radiation. Pericardial effusion, either due to cancer invasion or cancer treatment, is one of the most common incidental findings in cancer patients, which significantly worsens morbidity and mortality. If left untreated, pericardial effusion is known to cause complications such as pericardial tamponade. Constrictive pericarditis can be due to radiation exposure, chemotherapy, or is a sequela of a previous episode of acute pericarditis. In conclusion, early detection, prompt treatment, and understanding of pericardial diseases are necessary to help improve the quality of life of cancer patients, and we aim to summarize the knowledge of pericardial involvement in patients with cancer.

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co‐morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2 + stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve‐dependent mechanism. Synopsis Salivary glands regenerate after radiation injury through SOX2‐mediated secretory acinar cell replacement as shown using genetic lineage tracing and ablation methods, in combination with in vivo and ex vivo gamma radiation‐induced damage models. SOX2 + stem cells are essential to acinar cell replacement in the sublingual gland (SLG) during homeostasis and after radiation‐induced damage. SOX2‐mediated acinar cell replacement is contingent on neuronal muscarinic signalling. In the absence of nerves, a muscarinic mimetic can drive SOX2‐mediated regeneration. SOX2 function is essential for SLG regeneration following radiation‐induced injury. SOX2 along with parasympathetic nerves are diminished in human salivary gland biopsies following irradiation therapy and SOX2 and the acinar lineage are upregulated in response to muscarinic activation. Graphical Abstract Salivary glands regenerate after radiation injury through SOX2‐mediated secretory acinar cell replacement as shown using genetic lineage tracing and ablation methods, in combination with in vivo and ex vivo gamma radiation‐induced damage models.