Radiation therapy-associated toxicity: Etiology, management, and prevention.

Radiation therapy (RT) is a curative treatment for many malignancies and provides effective palliation in patients with tumor-related symptoms. However, the biophysical effects of RT are not specific to tumor cells and may produce toxicity due to exposure of surrounding organs and tissues. In this article, the authors review the clinical context, pathophysiology, risk factors, presentation, and management of RT side effects in each human organ system. Ionizing radiation works by producing DNA damage leading to tumor death, but effects on normal tissue may result in acute and/or late toxicity. The manifestation of toxicity depends on both cellular characteristics and affected organs' anatomy and physiology. There is usually a direct relationship between the radiation dose and volume to normal tissues and the risk of toxicity, which has led to guidelines and recommended dose limits for most tissues. Side effects are multifactorial, with contributions from baseline patient characteristics and other oncologic treatments. Technological advances in recent decades have decreased RT toxicity by dramatically improving the ability to deliver RT that maximizes tumor dose and minimizes organ dose. Thus the study of RT-associated toxicity is a complex, core component of radiation oncology training that continues to evolve alongside advances in cancer management. Because RT is used in up to one-half of all patients with cancer, an understanding of its acute and late effects in different organ systems is clinically pertinent to both oncologists and nononcologists.

Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.

BACKGROUND: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology. METHODS: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline. RESULTS: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart. CONCLUSIONS: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.

Update on lacrimal apparatus dysfunction associated with differentiated thyroid cancer after I-131 therapy.

PURPOSE: The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC. METHODS: A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were "Thyroid cancer", "I-131", "Complications", "Dry eye", "Epiphora", "Tear", "Nasolacrimal duct" and "NLDO". RESULTS: The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131. CONCLUSION: It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease.

Quantitative analysis of myokymic discharges in radiation versus nonradiation cases.

INTRODUCTION: Myokymic discharges are classically associated with nerve injury from prior radiation but may occur in other neuromuscular disorders. Using quantitative analysis we aimed to identify the spectrum of conditions in which myokymic discharges are present and determine if there are electrophysiological features that distinguish postradiation from nonradiation causes of myokymia. METHODS: We reviewed the clinical history of all patients examined in our electromyography labs with myokymic discharges recorded from June 2017 to February 2020. Quantitative analysis of each myokymic discharge was performed using a custom MATLAB script, assessing features such as burst frequency, spikes per burst, and burst regularity. RESULTS: Eighty-eight distinct myokymic discharges (70 patients) were analyzed: 51 postradiation recordings from 35 patients and 37 recordings from 35 nonradiation patients. The diagnostic spectrum of nonradiation cases was diverse, with common causes being median neuropathy (n = 8), cervical (n = 7), and lumbar (n = 5) radiculopathy, and motor neuron disease (n = 5). On quantitative analysis, postradiation myokymia had an increased burst-to-silence ratio (median, 0.29; nonradiation, 0.08) and greater peak number (median, 15; nonradiation, 7). Except for one patient with hereditary peripheral nerve hyperexcitability, all patients who had two or more muscles demonstrating myokymic discharges belonged to postradiation group. CONCLUSIONS: Myokymic discharges can be seen in diverse neuromuscular conditions; most common in our cohort was chronic median neuropathy. Postradiation myokymia appears to have distinguishing morphological features when quantitatively analyzed compared with nonradiation cases.

Single Center Outcomes of Carotid Artery Stenting in Veterans with Prior Head and Neck Cancer.

BACKGROUND: Patients meeting criteria for intervention of carotid stenosis with a history of prior cervical radiation or neck dissection are considered "high risk" for carotid endarterectomy. This is a well-established indication for carotid artery stenting (CAS). The long-term outcomes of CAS in this population are less frequently published in the literature but are poor. The purpose of this study was to review long-term results of CAS in veteran patients with a prior history of treatment for head and/or neck cancer. METHODS: This is a retrospective review of a veteran patient population from 1998 to 2016. All patients at our institution with a prior history of treatment for head and/or neck cancer who underwent CAS were included in the analysis. During this time period, 44 patients met inclusion criteria and were treated with 57 carotid stenting interventions. The Kaplan-Meier analysis was used to determine survival and primary patency. The secondary aims were to analyze early outcomes and to identify predictive risk factors for mortality and reintervention. RESULTS: The mean follow-up was 42.9 ± 36.6 months. The cumulative survival at 1, 5, and 10 years was 91%, 67%, and 48%, respectively. The primary patency at 1, 5, and 10 years was 95%, 86%, and 86%, respectively. The reintervention rate was 11% (n = 6) with an assisted primary patency rate of 100%. No neurologic events occurred within 30 days. There were 3 strokes in late follow-up and no stroke-related deaths. Eighteen patients (41%) died during the follow-up period, 15 of whom died during the first 5 years of follow-up. Ten (66%) of those patients died of recurrent or active index cancer. On univariate analysis, tumor, node, metastasis stage IV was significantly associated with death (P = 0.02). Multivariate models were not statistically significant for predicting mortality or reintervention CONCLUSIONS: On the basis of the results in this series, CAS can be performed in these patients with low long-term rates of neurologic events and need for reintervention. However, the survival of patients with head and neck cancer undergoing CAS in this cohort is poor, which is consistent with other published series of patients undergoing CAS for head/neck cancer with at least 5-year follow-up. In this specific patient population, a more critical analysis of the patient's overall prognosis, especially as related to cancer, should be undertaken before offering CAS.

RETINAL MICROVASCULAR CHANGES IN UVEAL MELANOMA FOLLOWING CONBERCEPT INJECTION AFTER PLAQUE RADIOTHERAPY AS DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To investigate macular microvascular characteristics imaged by optical coherence tomography angiography in patients with uveal melanoma following conbercept injections after plaque radiotherapy. METHODS: Prospective comparative analysis comprising 15 patients with uveal melanoma with conbercept injections and 30 patients without conbercept injections after plaque radiotherapy by optical coherence tomography angiography. The conbercept group received intravitreal conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal conbercept injection. RESULTS: After initiation of conbercept injections, superficial retinal vascular density in the whole image and parafoveal region were significantly higher at 6 months, whereas there was no significant difference at 9 months and 12 months. In analysis of variance analysis, superficial retinal vascular density in the whole image remained stable after conbercept injections (P = 0.069), whereas the superficial retinal vascular density decreased significantly after plaque radiotherapy in the control group (P = 0.011). In multivariable linear regression, a higher superficial retinal vascular density in the whole image region at 6 months was significantly associated with intravitreal conbercept injection (P = 0.018), wider tumor base (P = 0.026), and thinner tumor thickness (P = 0.04). CONCLUSION: Optical coherence tomography angiography can provide a quantitative evaluation of early retinal microvascular changes after radiotherapy. Intravitreal conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma; however, it may not be able to provide long-term positive functional outcomes.

Radiation-induced lung injury: current evidence.

Chemo-radiotherapy and systemic therapies have proven satisfactory outcomes as standard treatments for various thoracic malignancies; however, adverse pulmonary effects, like pneumonitis, can be life-threatening. Pneumonitis is caused by direct cytotoxic effect, oxidative stress, and immune-mediated injury. Radiotherapy Induced Lung Injury (RILI) encompasses two phases: an early phase known as Radiation Pneumonitis (RP), characterized by acute lung tissue inflammation as a result of exposure to radiation; and a late phase called Radiation Fibrosis (RF), a clinical syndrome that results from chronic pulmonary tissue damage. Currently, diagnoses are made by exclusion using clinical assessment and radiological findings. Pulmonary function tests have constituted a significant step in evaluating lung function status during radiotherapy and useful predictive tools to avoid complications or limit toxicity. Systemic corticosteroids are widely used to treat pneumonitis complications, but its use must be standardized, and consider in the prophylaxis setting given the fatal outcome of this adverse event. This review aims to discuss the clinicopathological features of pneumonitis and provide practical clinical recommendations for prevention, diagnosis, and management.

ß-Arrestin1-mediated decrease in endoplasmic reticulum stress impairs intestinal stem cell proliferation following radiation.

Gastrointestinal toxicity limits the clinical application of abdominal and pelvic radiotherapy and currently has no effective treatment. Intestinal leucine-rich-repeat-containing GPCR 5 (Lgr5)-positive stem cell depletion and loss of proliferative ability due to radiation may be the primary factors causing intestinal injury following radiation. Here, we report the critical role of ß-arrestin1 (ßarr1) in radiation-induced intestinal injury. Intestinal ßarr1 was highly expressed in radiation enteritis and in a radiation model. ßarr1 knockout (KO) or knockdown mice exhibited increased proliferation in intestinal Lgr5+ stem cell, crypt reproduction, and survival following radiation. Unexpectedly, the beneficial effects of ßarr1 deficiency on intestinal stem cells in response to radiation were compromised when the endoplasmic reticulum stress-related protein kinase RNA-like ER kinase (PERK)/eukaryotic initiation factor-2α (eIF2α) pathway was inhibited, and this result was further supported in vitro. Furthermore, we found that ßarr1 knockdown with small interfering RNA significantly enhanced intestinal Lgr5+ stem cell proliferation after radiation via directly targeting PERK. ßarr1 offers a promising target for mitigating radiation-induced intestinal injury.-Liu, Z., Jiang, J., He, Q., Liu, Z., Yang, Z., Xu, J., Huang, Z., Wu, B. ß-Arrestin1-mediated decrease in endoplasmic reticulum stress impairs intestinal stem cell proliferation following radiation.

Stiff left atrial syndrome after low-dose radiotherapy for right breast cancer: The need for invasive hemodynamics at exercise.

Stiff left atrial (LA) syndrome is a distinct phenotype of heart failure with preserved ejection fraction, characterized by predominant high LA pressure. We describe the case of a middle-aged woman who developed exertional breathlessness during low-dose radiotherapy for right breast cancer and who was eventually found to be affected by stiff LA syndrome. Invasive hemodynamics allowed the recognition of pathognomonic tall V waves in the wedge position during exercise, in spite of inconclusive noninvasive investigations.

Primary cancer location predicts predominant level of brachial plexopathy.

BACKGROUND: Changes in radiation therapy practice and cancer incidence bring into question prior evidence suggesting that radiation therapy predominantly injures the brachial plexus upper trunk, while tumor invasion typically injures the lower trunk. METHODS: We reviewed electrodiagnostic brachial plexopathy reports in cancer survivors for predominant trunk involvement, injury mechanism (tumor invasion vs radiation), and primary cancer location. RESULTS: Fifty-six cases of cancer-associated brachial plexopathy were identified. There was no relationship between injury mechanism and brachial plexus injury level. However, primary cancer location superior/inferior to the clavicle increased the odds of predominantly upper/lower trunk involvement by a factor of 60.0 (95% confidence interval: 7.9, 1401, respectively). CONCLUSIONS: Cancers superior/inferior to the clavicle increase the likelihood of predominantly upper/lower trunk plexopathy, respectively, regardless plexus injury mechanism. These findings contrast with older work, possibly due to more precise radiation therapy techniques and increased incidence of radiosensitive head and neck cancers.

Exercise cardiovascular magnetic resonance reveals reduced cardiac reserve in pediatric cancer survivors with impaired cardiopulmonary fitness.

BACKGROUND: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO2) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise. METHODS: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO2, with a value < 85% of predicted defined as impaired peak VO2. Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR). RESULTS: Twelve of 20 survivors (60%) had reduced peak VO2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO2. However, those with reduced peak VO2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71). CONCLUSIONS: Whilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.

Pathological effects of ionizing radiation: endothelial activation and dysfunction.

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.

Sarcopenia and myosteatosis in patients undergoing curative radiotherapy for head and neck cancer: Impact on survival, treatment completion, hospital admission and cost.

BACKGROUND: Computed tomography (CT) is the gold standard of body composition analysis at the tissue-organ level. The present study aimed to determine the impact of CT-defined sarcopenia and myosteatosis on outcomes, including overall survival, unplanned hospital admissions and related costs, in patients who had completed treatment of curative intent for head and neck cancer (HNC). METHODS: Retrospective observational study of patients undergoing radiotherapy of curative intent ± other treatment modalities for HNC. Tissue density data derived at the third lumbar vertebra (L3) were evaluated with sarcopenia defined per sex-specific published threshold values for skeletal muscle index, stratified by body mass index and mean skeletal muscle attenuation in HU (Hounsfield units). RESULTS: Pre- or post-treatment images were available for 79/98 patients (80.6%) and 61/98 patients (62.2%), respectively. Sarcopenia was present in 42/79 patients pre-treatment and 36/61 patients post-treatment, whereas myosteatosis was present in 63/79 patients pre-treatment and 48/61 patients post-treatment. In patients with pre- and post-treatment images (n = 60), the median (range) percentage weight change was -8.5% (-29.9 to +11.7). On multivariable analysis, a post-treatment sarcopenia hazard ratio of 3.87 (95% confidence interval = 1.22-12.24, P = 0.021) and a pre-treatment myosteatosis hazard ratio of 8.86 (95% confidence interval = 1.12-69.88, P = 0.038) were independent predictors of reduced overall survival. There was no difference in radiotherapy or chemotherapy treatment completion based on pre-treatment sarcopenia status. The mean (SD) difference unplanned hospital admission cost was $15 846 ($17 707) for patients without sarcopenia versus $47 945 ($82 688) for patients with sarcopenia at any time point (P = 0.077). CONCLUSIONS: As CT-defined sarcopenia and myosteatosis hold clinically meaningful prognostic value, muscle status evaluation is recommended in routine clinical practice.

Pregnancy and symptomatic relief following ultrasound-guided transvaginal radiofrequency ablation in patients with adenomyosis.

AIM: To report the reproductive results and symptomatic relief of patients with adenomyosis who attempted to conceive after ultrasound-guided radiofrequency ablation (RFA). METHODS: Of 182 consecutive patients with adenomyosis who had undergone RFA, only 81 patients were eligible for this study. Pregnancy outcomes, postoperative complications, preoperative and postoperative pictorial blood loss assessment chart scores, and pain scores were evaluated. RESULTS: Of these 81 patients, 74 were infertile and seven were single at the time of RFA. The mean age at the time of operation was 35.8 years. The mean duration from the time of RFA to conception was 18.9 months (range, 2-72 months). Fifty-nine patients tried natural conception, while 22 patients attempted conception with assisted reproductive techniques. Twenty-nine (35.8%) patients achieved 39 pregnancies. Except for the 23 patients who did not actively try to conceive and who inevitably or arbitrarily discontinued pregnancy attempts, the pregnancy success rate reached 50%. Twenty-two (84.6%) of the 29 patients delivered 24 (66.7%) live babies (nine vaginal deliveries and 15 cesarean sections). Twelve (33.3%) pregnancies ended in spontaneous abortions. No uterine ruptures occurred. Paired sample t-tests revealed that preoperative pictorial blood loss assessment chart and pain scores were significantly (P < 0.05) different from the postoperative scores at 1-, 3- and 6-months. CONCLUSION: RFA could be considered a minimally-invasive treatment option for patients with adenomyosis who desire to maintain fertility and alleviate symptoms.

Association of Neck Range of Motion and Skin Caliper Measures on Dysphagia Outcomes in Head and Neck Cancer and Effects of Neck Stretches and Swallowing Exercises.

To date, there is a paucity of information in the literature regarding the association between cervical range of motion (CROM) and skin caliper measures (SCM) and swallowing outcomes in post-RT individuals with head and neck cancer. Also lacking in the literature are reports of the effect of swallowing exercises and neck stretches on changes in CROM and SCM and their associations with swallowing outcomes. The aim of this study was to assess the associations between CROM and SCM before initiation of a neck stretching and swallowing exercise program and to determine if 12 weeks of twice daily practice changes in CROM and SCM were associated with changes in swallowing outcomes in a cohort of 119 head and neck cancer survivors. Primary results revealed that at baseline, greater right and left CROM were associated with lower penetration aspiration scale (PAS) scores (r = - 0.321, p = < 0.001; r = - 0.203, p = 0.026, respectively). Improved skin pliability revealed lower PAS scores (r = - 0.210, p = 0.022). After 12 weeks, there were no significant correlations between changes in CROM and SCM and PAS scores. Changes in left CROM and CROM extension had positive associations with the Head and Neck Cancer Inventory eating score (r = 0.210, p = 0.026; r = 0.245, p = 0.009, respectively). Findings appear to indicate that any improvement was not associated with changes in swallowing outcomes. Head and neck cancer survivors may perceive improved diet and swallowing skills through exercise, with respect to improved CROM extension.

Erythema of the skin after breast radiotherapy: It is not always recurrence.

Recurrence of breast cancer is a predominant fear for patients who were treated for breast cancer. Acute and late dermatologic effects of radiotherapy are not uncommon and could have similar characteristics to breast cancer recurrence. Thus, it is important to highlight key differences between the clinical and histologic presentations of radiation effects and recurrence. Herein, we present two patients who presented with late dermatologic effects of radiotherapy months to years after treatment, neither of whom had workup consistent with cancer recurrence. We provide clinical and microscopic descriptions of each case and provide a review to differentiate various dermatologic conditions. This report aims to outline potential late dermatologic effects of radiation treatment and emphasise that changes in the breast do not always signal breast cancer recurrence.

Evaluation of Stromal Vascular Fraction Properties and Histological Changes of Regenerating Tissue during Healing of Radiation-Induced Lesions in the Rectum.

We analyzed the main properties of autologous adipose-derived stromal vascular fraction (SVF) used for the treatment of radiation-induced lesions in the rectum. No statistically significant correlation between the main characteristics of the cell product (cell number, viability) and patient's age or donor area were revealed. The stages and peculiarities of histological changes in the regenerating tissue after injection of autologous adipose tissue cells were analyzed. Morphological changes at the stages of granulation, early and complete epithelialization, and tissue maturation were described.

P2X7 receptor deletion suppresses γ-radiation-induced hyposalivation.

Head and neck cancer treatments typically involve a combination of surgery and radiotherapy, often leading to collateral damage to nearby tissues causing unwanted side effects. Radiation damage to salivary glands frequently leads to irreversible dysfunction by poorly understood mechanisms. The P2X7 receptor (P2X7R) is a ligand-gated ion channel activated by extracellular ATP released from damaged cells as "danger signals." P2X7R activation initiates apoptosis and is involved in numerous inflammatory disorders. In this study, we utilized P2X7R knockout (P2X7R-/-) mice to determine the role of the receptor in radiation-induced salivary gland damage. Results indicate a dose-dependent increase in γ-radiation-induced ATP release from primary parotid gland cells of wild-type but not P2X7R-/- mice. Despite these differences, apoptosis levels are similar in parotid glands of wild-type and P2X7R-/- mice 24-72 h after radiation. However, γ-radiation caused elevated prostaglandin E2 (PGE2) release from primary parotid cells of wild-type but not P2X7R-/- mice. To attempt to uncover the mechanism underlying differential PGE2 release, we evaluated the expression and activities of cyclooxygenase and PGE synthase isoforms. There were no consistent trends in these mediators following radiation that could explain the reduction in PGE2 release in P2X7R-/- mice. Irradiated P2X7R-/- mice have stimulated salivary flow rates similar to unirradiated controls, whereas irradiated wild-type mice have significantly decreased salivary flow rates compared with unirradiated controls. Notably, treatment with the P2X7R antagonist A438079 preserves stimulated salivary flow rates in wild-type mice following γ-radiation. These data suggest that P2X7R antagonism is a promising approach for preventing γ-radiation-induced hyposalivation.

Evaluation of early changes of macular function and morphology by multifocal electroretinograms in patients with nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: To assess the role of multifocal electroretinograms (mfERGs) and optical coherence tomography (OCT) for detecting early changes in macular functions of patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: mfERGs and OCT were used to examine a NPC group (36 NPC patients after radiotherapy without clinically visible radiation retinopathy, 36 eyes) and a normal control group (25 healthy individuals, 25 eyes) with the same procedure and parameters. The two groups of mfERG were summarized by calculating ring averages, response density, N1 amplitude and P1 and N1 latencies were analysed. OCT scan thickness was summarized into ETDRS regions for comparison. RESULTS: Compared with controls, the NPC group had significantly decreased P1 response densities in 1-4 ring regions and N1 amplitudes in 1-3 rings (P < 0.01). P1 latencies were obviously prolonged in rings 1 (P < 0.01). In four quadrants (inferonasal, superonasal, inferotemporal and superotemporal) of the mfERG response waveforms, the NPC group had significantly decreased P1 response densities and N1 amplitudes mainly in the inferonasal and inferotemporal quadrants, showing statistically significant differences from the control group (P < 0.0125). But for the OCT results, there is no statistically significant difference between the NPC group and the control group. CONCLUSIONS: In NPC patients after radiotherapy, there may be changes in the mfERGs before any visible fundus lesions appeared as radiation macular oedema. Since the global OCT macular thickness analysis cannot reveal early changes, the mfERGs can objectively and quantitatively assess the earlier changes in macular function in NPC patients.