Effect of total body irradiation on late lung effects: Hidden dangers

Purpose:?In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge.

Materials and methods:?C57BL/6J mice received total body irradiation (0.5–10 Gy) and were followed for 6–18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]).

Results:?Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL]6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls.

Conclusions:?We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.     

Radiographic and function changes after partial lung irradiation in the rat.

The early and late changes in the right rat lung following single dose X-irradiation were studied using computerised axial tomography (CT) and noninvasive lung function tests. The biphasic response of the lung, i.e., the early pneumonitis phase, from six to ten weeks and later fibrosis starting at 18 weeks after irradiation, were both detectable by increased lung density. Whereas functional changes were prominent during the pneumonitis phase, these were only minor in the late phase.     

微波辐射对大鼠海马线粒体形态及能量代谢的影响

目的探讨微波辐射对大鼠海马线粒体形态及能量代谢的影响。方法采用30mW／cm^2微波辐射30只雄性Wiser大鼠，于辐射后6h、1d、3d和7d活杀取海马，采用电镜观察线粒体超微结构改变，酶活性染色显示线粒体ATP酶活性改变，分光光度计测定线粒体琥珀酸脱氢酶（succino denhydrogenase,SDH）、单胺氧化酶（monoamine oxidase，MAO）活性，高效液相色谱测量线粒体腺苷酸含量的变化。结果30mW／cm^2微波辐射后6h，海马线粒体大小、形状不规则，辐射后1和3d线粒体损伤加重，出现肿胀、空化、嵴紊乱、短小、数量减少等改变。SDH活性和ATP含量在辐射后6h降低，3d降至最低（P〈0．01），7d呈恢复趋势。ATP酶和MAO活性变化一致，于辐射后1和3d活性升高最为显著（P〈0．01）。结论微波辐射可损伤大鼠海马线粒体结构与功能，使线粒体能量代谢酶异常。     

Volume and dose-response effects for severe symptomatic pneumonitis after fractionated irradiation of canine lung

PURPOSE: To study the dose-related incidence of severe symptomatic pneumonitis following fractionated irradiation applied to three different volumes of lung in normal beagle dogs. MATERIALS AND METHODS: A three-dimensional treatment planning system was used to design mediastinal fields of increasing width to irradiate 33%, 67% or 100% of both lungs combined in 128 normal beagle dogs. Total doses, ranging from 27 to 72 Gy, were delivered in 1.5 Gy fractions over 6 weeks. RESULTS: No dogs irradiated to 33% of their total lung volume developed severe symptomatic pneumonitis. In the 67% volume group, logistic fit of the data showed a dose-response curve with a 50% probability of developing severe symptomatic pneumonitis (ED50) after a total dose of 56.0 Gy (52.2-66.0 Gy, 95% confidence interval, CI). The more clinically relevant ED5 for the first 6 months after irradiation of 67% of the lung was 48.1 Gy (18.5-52.0 Gy, 95% CI). The ED50 and ED5 values after irradiation of the whole lung (100%) were 44.1 Gy (41.2-53.5Gy, 95% CI) and 39.1 Gy (8.8-41.8 Gy, 95% CI) respectively. CONCLUSION: Severe symptomatic pneumonitis proved to be a very informative volume-effect endpoint, clearly demonstrating that irradiated lung volume is a critical parameter to be considered in assigning thoracic radiotherapy treatment parameters. Volume effects in lung are dependent on the compensatory capacity of the nonirradiated lung. Underlying pathophysiology of irradiated tissue, as well as decreased compensatory capacity of nonirradiated tissue may have a strong effect on the dose-volume response.     

Early and late bone-marrow changes after irradiation: MR evaluation

Knowledge of the chronologic evolution of bone-marrow changes during and after radiation therapy is essential in differentiating normal postradiation changes from other marrow abnormalities. The appearance of the lumbar vertebral bone marrow was studied on 55 serial spin-echo and short-T1 inversion-recovery (STIR) MR images obtained in 14 patients receiving radiation therapy for Hodgkin disease, seminoma, or prostate carcinoma. Images were obtained before, at weekly intervals during, and at various monthly intervals up to 14 months after a 3- to 6-week course of fractionated paravertebral lymph-node irradiation of 1500-5000 rad (15-50 Gy). During the first 2 weeks of therapy, there was no definite change in the appearance of the marrow on spin-echo images; however, there was an increase in signal intensity on the STIR images, apparently reflecting early marrow edema and necrosis. Between weeks 3 and 6, the marrow showed an increasingly heterogenous signal and prominence of the signal from central marrow fat, shown best on T1-weighted images. Late marrow patterns (6 weeks to 14 months after therapy) varied and consisted of either homogenous fatty replacement or a band pattern of peripheral intermediate signal intensity, possibly representing hematopoietic marrow surrounding the central marrow fat. No focal marrow lesions or soft-tissue edema were identified during the course of radiation therapy; their presence should raise the possibility of the presence of a pathologic process other than radiation change. These data suggest that MR can detect radiation-induced marrow changes as early as 2 weeks after starting therapy, and that there are at least two distinct types of late marrow MR patterns.     

Early versus late prophylactic cranial irradiation in patients with extensive small cell lung cancer

Objective

Previous studies demonstrated that prophylactic cranial irradiation (PCI) significantly reduced the incidence of brain metastases in patients with extensive disease small cell lung cancer (ED-SCLC). However, the appropriate timing for PCI in treating ED-SCLC is still unclear. This study aimed to compare the effect and safety of early versus late PCI.

Methods

Between November 2011 and July 2016, 103 patients with ED-SCLC were reviewed, receiving appropriate imaging tests to exclude brain metastases prior to cranial irradiation. Of these 103 patients, early PCI was performed in 47 patients and the other 56 patients received late PCI. The primary endpoint was the incidence of brain metastases. The progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also assessed.

Results

Early PCI significantly lowered the risk of brain metastases, as compared to late PCI (p?=?0.024). Additionally, multivariate analyses demonstrated that early PCI was a favorable independent predictor of the incidence of brain metastases. The PFS and OS of patients in the early and late PCI groups were comparable (PFS: 8.4 months vs. 7.5 months, p?=?0.234; OS: 16.1 months vs. 15.2 months, p?=?0.753). The AEs were generally acceptable in both groups.

Conclusion

To reduce the incidence of brain metastases, early PCI is more effective than late PCI for ED-SCLC patients.

     

Late follow-up of lung function after whole lung irradiation for Wilms' tumour.

Radiotherapy is known to have acute and long term deleterious effects on lung tissue. However, pulmonary irradiation is an established treatment in advanced childhood tumours with pulmonary metastases not responsive to chemotherapy. In this study eight patients with Wilms' tumours and lung metastases treated with whole lung irradiation (1200-1837 cGy) and chemotherapy were reassessed clinically, radiologically and with lung function tests 6-26 years after radiotherapy. One patient was breathless after mild exertion, four after strenuous exercise and three were asymptomatic. Clinically all had small chests and four of five females had underdeveloped breasts. A chest radiograph showed clear lung fields in all cases. Lung volumes, especially total lung capacity (TLC) and vital capacity (VC), were decreased when compared with predicted values for age and height. However, gas transfer per unit lung volume (KCO) was normal. This study suggests that pulmonary irradiation in childhood results primarily in underdevelopment of the thorax and that diffuse interstitial lung fibrosis is not a significant feature at this dose level.     

Early effects in kidney enzyme activities after irradiation.

Brush border enzymes of proximal tubules, lysosomal activities and protein content of rat kidney were analysed after whole-body irradiation using two different experimental schedules. Maltase, alkaline phosphatase and beta-glucuronidase activities increased moderately during the first days after irradiation, whereas LAP, cathespsin D activities and protein content were not modified. No evident morphologic alterations were observed.     

Endothelial cell population dynamics in rat brain after local irradiation

The dynamics of the endothelial cell population was investigated in the rat brain after local irradiation with different doses of X rays. A fluorescent-histochemical technique was used for the visualization of the cells. A decrease in endothelial cell number was observed within 1 day of irradiation with doses of 5-200 Gy. At this time the endothelial cell number had decreased by up to 15% compared with the pre-treatment values. This early dose-independent loss in cell number was maintained for up to 1 month after irradiation. This was then followed by a slow dose-independent decrease in cell density up to 6 months after exposure. Subsequently the depletion of the endothelial cell population exposed to 40 and 60 Gy continued. After a dose of 25 Gy an abortive recovery of cell numbers occurred followed by an abrupt depletion of the endothelial cell population. The possible mechanisms of such changes are discussed.     

Examination for the late physical after effects of torture

This paper describes the experience of doctors at the Medical Foundation for the Care of Victims of Torture, London, in documenting torture as recounted by survivors, mostly refugees from one of 63 countries, and in writing medico-legal reports to support their asylum claims. More than 2000 new patients are seen each year and 500 reports written. Few patients are seen in the acute phase; many not until 10 years following their torture. Patterns of torture practised in different countries are described, with the resulting physical signs. Methods of history-taking and examination are discussed, with emphasis on the detection of subtle forms of torture, recognition of deception and encouragement of full disclosure.