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MeSH Review:

Radiation Pneumonitis

Arpin, D. et al., Vozenin-Brotons, M.C. et al., Tee, P.G. et al., Chen, Y. et al., Pui, M.H. et al., et al.

Vozenin-Brotons, Milliat, Sabourin, de Gouville, François, Lasser, Morice, Haie-Meder, Lusinchi, Antoun, Bourhis, Mathé, Girinsky, Aigueperse, Choy, Nabid, Stea, Scott, Roa, Kleinberg, Ayoub, Smith, Souhami, Hamburg, Spanos, Kreisman, Boyd, Cagnoni, Curran, Arpin, Perol, Blay, Falchero, Claude, Vuillermoz-Blas, Martel-Lafay, Ginestet, Alberti, Nosov, Etienne-Mastroianni, Cottin, Perol, Guerin, Cordier, Carrie, Burstein, Bellon, Galper, Lu, Kuter, Taghian, Wong, Gelman, Bunnell, Parker, Garber, Winer, Harris, Powell,

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Disease relevance of Radiation Pneumonitis

PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis [1].
Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%) [2].
Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy [3].
In vivo, IL-2 secretion by post-radiation fibrosis fibroblasts and the subsequent up-regulation of ICAM-1 and CD44 may represent key events during the process that leads to radiation fibrosis [4].
CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis [5].

High impact information on Radiation Pneumonitis

These data confirm the putative role of TGF-beta in intestinal radiation fibrosis [6].
IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis [1].
Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis [1].
Contrary to previous results in the literature, we found that basic fibroblast growth factor did not protect against radiation pneumonitis in either C3Hf/Kam or NCR/Sed-nu/+ mice [7].
In our laboratory, the LD50 for radiation pneumonitis between 12 and 28 weeks after irradiation, the standard assay time for this phase of radiation-induced lung damage, is 12.5 Gy in the C3Hf/Kam and 8.5 Gy in the NCR/Sed-nu/+ strain [7].

Chemical compound and disease context of Radiation Pneumonitis

Deaths from radiation pneumonitis occurred as early as 6 weeks in mice given cyclophosphamide before irradiation; few deaths occurred after 26 weeks [8].
Nine patients with radiation pneumonitis were given chemotherapy (actinomycin D) together with irradiation, and in this group the incidence of radiation pneumonitis was 25% [9].
Positive 111In-pentetreotide scans delineated areas of radiation pneumonitis that adequately correlated with areas of decreased ventilation/perfusion and x-ray abnormalities [10].
However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion [11].
These data are the first to demonstrate that the ACE inhibitor captopril might provide a novel intervention in the pathogenesis of radiation fibrosis [12].

Biological context of Radiation Pneumonitis

Early alterations in extracellular matrix and transforming growth factor beta gene expression in mouse lung indicative of late radiation fibrosis [13].

Anatomical context of Radiation Pneumonitis

CONCLUSION: This study is the first showing involvement of the Rho/Rho kinase pathway in radiation fibrosis and intestinal smooth muscle cell fibrogenic differentiation [14].
CONCLUSION: The increased level of CTGF protein and mRNA associated with the accumulation of fibroblasts/myofibroblasts and collagen deposition were parts of the fibrogenic signals involved in the persistence of late intestinal radiation fibrosis [15].
Alveolar macrophages from both lungs during unilateral radiation pneumonitis exhibited impaired generation of superoxide after phorbol myristate (only a 30% increase) [16].
RESULTS: There was significantly higher uptake of Tc-99m MIBI by NPC than normal nasopharynx and radiation fibrosis (P < .05) [17].

Gene context of Radiation Pneumonitis

PURPOSE: To investigate the expression of a new fibrogenic cytokine the connective tissue growth factor (CTGF) in intestinal radiation fibrosis and to characterize the mesenchymal cell subtypes involved in CTGF synthesis and collagen deposition [15].
Analysis of a panel of circulating cytokines with different putative functions in radiation pulmonary injury identified IL-1alpha and IL-6 as early circulating cytokine markers for radiation pneumonitis [18].
The pattern of changes of MCP-1, E-selectin, L-selectin, TGF-beta1, and bFGF varied, but none of these cytokines correlated with radiation pneumonitis [18].
Then, in striking contrast to the other two cytokines, an increase in TGF-beta2 mRNA occurred at around 120 days and correlated with the detection of organizing alveolitis/radiation fibrosis and mortality [19].
CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis [1].

Analytical, diagnostic and therapeutic context of Radiation Pneumonitis

Fluorine-18 FDG dual-head gamma camera coincidence imaging of radiation pneumonitis [20].
CONCLUSION: This study suggests that Tc-99m MIBI SPECT is useful for detecting primary NPC and for differentiating residual or recurrent tumor from radiation fibrosis [17].

References

Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis. Arpin, D., Perol, D., Blay, J.Y., Falchero, L., Claude, L., Vuillermoz-Blas, S., Martel-Lafay, I., Ginestet, C., Alberti, L., Nosov, D., Etienne-Mastroianni, B., Cottin, V., Perol, M., Guerin, J.C., Cordier, J.F., Carrie, C. J. Clin. Oncol. (2005) [Pubmed]
Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer. Choy, H., Nabid, A., Stea, B., Scott, C., Roa, W., Kleinberg, L., Ayoub, J., Smith, C., Souhami, L., Hamburg, S., Spanos, W., Kreisman, H., Boyd, A.P., Cagnoni, P.J., Curran, W.J. J. Clin. Oncol. (2005) [Pubmed]
Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist. Swenson, E.R. Arch. Intern. Med. (1986) [Pubmed]
IL-2 production by myofibroblasts from post-radiation fibrosis in breast cancer patients. Alileche, A., Han, D., Plaisance, S., Assier, E., Sahraoui, Y., Clemanceau, C., Metivier, D., Brouty-Boyer, D., Jasmin, C., Azzarone, B. Int. Immunol. (1994) [Pubmed]
CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis. Inoue, T., Fujishima, S., Ikeda, E., Yoshie, O., Tsukamoto, N., Aiso, S., Aikawa, N., Kubo, A., Matsushima, K., Yamaguchi, K. Eur. Respir. J. (2004) [Pubmed]
Recombinant soluble transforming growth factor beta type II receptor ameliorates radiation enteropathy in mice. Zheng, H., Wang, J., Koteliansky, V.E., Gotwals, P.J., Hauer-Jensen, M. Gastroenterology (2000) [Pubmed]
Basic fibroblast growth factor does not protect against classical radiation pneumonitis in two strains of mice. Tee, P.G., Travis, E.L. Cancer Res. (1995) [Pubmed]
Residual damage in mouse lungs at long intervals after cyclophosphamide treatment. Travis, E.L., Bucci, L., Fang, M.Z. Cancer Res. (1990) [Pubmed]
Total-lung irradiation in the treatment of pulmonary metastases. Baeza, M.R., Barkley, H.T., Fernandez, C.H. Radiology. (1975) [Pubmed]
Radiation pneumonitis imaged with indium-111-pentetreotide. Valdés Olmos, R.A., van Zandwijk, N., Boersma, L.J., Hoefnagel, C.A., Baas, P., Baars, J.B., Muller, S.H., Lebesque, J.V. J. Nucl. Med. (1996) [Pubmed]
Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer. Burstein, H.J., Bellon, J.R., Galper, S., Lu, H.M., Kuter, I., Taghian, A.G., Wong, J., Gelman, R., Bunnell, C.A., Parker, L.M., Garber, J.E., Winer, E.P., Harris, J.R., Powell, S.N. Int. J. Radiat. Oncol. Biol. Phys. (2006) [Pubmed]
Captopril reduces collagen and mast cell accumulation in irradiated rat lung. Ward, W.F., Molteni, A., Ts'ao, C.H., Hinz, J.M. Int. J. Radiat. Oncol. Biol. Phys. (1990) [Pubmed]
Early alterations in extracellular matrix and transforming growth factor beta gene expression in mouse lung indicative of late radiation fibrosis. Finkelstein, J.N., Johnston, C.J., Baggs, R., Rubin, P. Int. J. Radiat. Oncol. Biol. Phys. (1994) [Pubmed]
Inhibition of Rho kinase modulates radiation induced fibrogenic phenotype in intestinal smooth muscle cells through alteration of the cytoskeleton and connective tissue growth factor expression. Bourgier, C., Haydont, V., Milliat, F., François, A., Holler, V., Lasser, P., Bourhis, J., Mathé, D., Vozenin-Brotons, M.C. Gut (2005) [Pubmed]
Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression. Vozenin-Brotons, M.C., Milliat, F., Sabourin, J.C., de Gouville, A.C., François, A., Lasser, P., Morice, P., Haie-Meder, C., Lusinchi, A., Antoun, S., Bourhis, J., Mathé, D., Girinsky, T., Aigueperse, J. Int. J. Radiat. Oncol. Biol. Phys. (2003) [Pubmed]
Unilateral radiation pneumonitis in sheep: physiological changes and bronchoalveolar lavage. Tillman, B.F., Loyd, J.E., Malcolm, A.W., Holm, B.A., Brigham, K.L. J. Appl. Physiol. (1989) [Pubmed]
Imaging of nasopharyngeal carcinoma with Tc-99m MIBI. Pui, M.H., Du, J.Q., Yueh, T.C., Zeng, S.Q. Clinical nuclear medicine. (1998) [Pubmed]
Radiation pneumonitis and early circulatory cytokine markers. Chen, Y., Williams, J., Ding, I., Hernady, E., Liu, W., Smudzin, T., Finkelstein, J.N., Rubin, P., Okunieff, P. Seminars in radiation oncology. (2002) [Pubmed]
Manganese [correction of Magnesium] superoxide dismutase (MnSOD) plasmid/liposome pulmonary radioprotective gene therapy: modulation of irradiation-induced mRNA for IL-I, TNF-alpha, and TGF-beta correlates with delay of organizing alveolitis/fibrosis. Epperly, M.W., Travis, E.L., Sikora, C., Greenberger, J.S. Biol. Blood Marrow Transplant. (1999) [Pubmed]
Fluorine-18 FDG dual-head gamma camera coincidence imaging of radiation pneumonitis. Lin, P., Delaney, G., Chu, J., Kiat, H., Pocock, N. Clinical nuclear medicine. (2000) [Pubmed]

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