[en] Purpose: The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Methods and Materials: Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations through 2014 (median follow-up time: 48 months). Results: A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Conclusions: Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy.

[en] Purpose: To study in detail the temporal and spatial release of the pro-inflammatory cytokines tumor necrosis factor α, interleukin (IL)-1α, and IL-6 in the lung tissue of C57BL/6 mice after thoracic irradiation with 12 Gy. Methods and Materials: C57BL/6J mice were exposed to either sham irradiation or a single fraction of 12 Gy delivered to the thorax. Treated and sham-irradiated control mice were killed at 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 4 weeks, 8 weeks, 16 weeks, and 24 weeks post-irradiation (p.i.). Real-time multiplex reverse transcriptase polymerase chain reaction was established to evaluate the relative messenger RNA (mRNA) expression of TNF-α, IL-1α, and IL-6 in the lung tissue of the mice (compared with nonirradiated lung tissue). Immunohistochemical detection methods (alkaline phosphatase anti-alkaline phosphatase, avidin-biotin-complex [ABC]) and automated image analysis were used to quantify the protein expression of TNF-α, IL-1α, and IL-6 in the lung tissue (percentage of the positively stained area). Results: Radiation-induced release of the pro-inflammatory cytokines TNF-α, IL-1α, and IL-6 in the lung tissue was detectable within the first hours after thoracic irradiation. We observed statistically significant up-regulations for TNF-α at 1 h p.i. on mRNA (4.99 ± 1.60) and at 6 h p.i. on protein level (7.23% ± 1.67%), for IL-1α at 6 h p.i. on mRNA (11.03 ± 0.77) and at 12 h p.i. on protein level (27.58% ± 11.06%), for IL-6 at 6 h p.i. on mRNA (6.0 ± 3.76) and at 12 h p.i. on protein level (7.12% ± 1.93%). With immunohistochemistry, we could clearly demonstrate that the bronchiolar epithelium is the most prominent source of these inflammatory cytokines in the first hours after lung irradiation. During the stage of acute pneumonitis, the bronchiolar epithelium, as well as inflammatory cells in the lung interstitium, produced high amounts of TNF-α (with the maximal value at 4 weeks p.i.: 9.47% ± 1.78%), IL-1α (with the peak value at 8 weeks p.i.: 14.76% ± 7.77%), and IL-6 (with the peak value at 8 weeks p.i.: 4.28% ± 1.33%). Conclusions: In the present study we have clearly demonstrated the immediate expression of the pro-inflammatory cytokines TNF-α, IL-1α, and IL-6 in the bronchiolar epithelium in the first hours after lung irradiation. A second, long-lasting release of these cytokines by the bronchiolar and alveolar epithelium, as well as by inflammatory cells, was observed at the onset of acute pneumonitis. Therefore, we postulate that lung irradiation causes immediate epithelial reaction, with the bronchiolar epithelium becoming a significant source of pro-inflammatory cytokines capable of promoting inflammation through recruitment and activation of inflammatory cells

[en] To evaluate the quality of life (QoL) of patients with inoperable non-small cell lung cancer treated with conventionally fractionated radiotherapy (CF) vs. continuous hyperfractionated accelerated radiotherapy weekend-less (CHARTWEL).