Translational Research in Radiation Oncology of Lung Cancer

  • Yuhchyau Chen
Part of the Medical Radiology Radiation Oncology book series (MEDRAD)


Clin Oncol Radiat Oncol Biol Phys Radiation Therapy Oncology Group Interstitial Pneumonitis Radiation Pneumonitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anscher MS, Kong F-M, Andrews K, et al. (1998) Plasma transforming growth factor β1 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 41:1029–1035CrossRefPubMedGoogle Scholar
  2. Arriagada R, le Chevalier T, Quoix E, et al. (1991) ASTRO Plenary: effect of chemotherapy on locally advanced non-small cell lung carcinoma: a randomized study of 353 patients. Int J Radiat Oncol Biol Phys 20:1183–1190PubMedGoogle Scholar
  3. Ash-Bernal R, Browner I, Erlich R (2002) Early detection and successful treatment of drug-induced pneumonitis with corticosteroids. Cancer Invest 20:876–879CrossRefPubMedGoogle Scholar
  4. Barcelloss-Hoff M-H (1998) How do tissues respond to damage at the cellular level? The role of cytokines in irradiated tissues. Radiat Res 150:109–120Google Scholar
  5. Boehm T, Folkman J, Browder T, et al. (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390:404–407CrossRefPubMedGoogle Scholar
  6. Brodin O, Wagenius G, Helsing M (2000) Daily paclitaxel (P) and radiotherapy (RT) in patients (PTS) with locally advanced non-small cell lung cancer (NSCLC). A phase I study. [abstract 2022]. In: Program/proceedings of the American Society of Clinical Oncology, 36th annual meeting, New Orleans. ASCO, Virginia, p 516aGoogle Scholar
  7. Browder T, Butterfield CE, Kraling BM, et al. (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60:1878–1886PubMedGoogle Scholar
  8. Burger A, Löffler H, Bamberg M, et al. (1998) Molecular and cellular basis of radiation fiborsis. Int J Radiat Biol 73:401–408CrossRefPubMedGoogle Scholar
  9. Burton C, Kaczmarski R, Jan-Mohamed R (2003) Interstitial pneumonitis related to rituximab therapy. N Engl J Med 348:2690–2691CrossRefPubMedGoogle Scholar
  10. Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272:60–66PubMedGoogle Scholar
  11. Chen Y, Okunieff P (2004) Radiation and third generation chemotherapy. Hematol Oncol Clin N Am 18:55–80CrossRefGoogle Scholar
  12. Chen Y, Okunieff P, Ahrendt SA (2003) Translational research in lung cancer. Semin Surg Oncol 21:205–219CrossRefPubMedGoogle Scholar
  13. Chen Y, Pandya K, Keng PC, et al. (2001) Schedule dependent pulsed low-dose paclitaxel radiosensitization for thoracic malignancy. Am J Clin Oncol 24:432–437CrossRefPubMedGoogle Scholar
  14. Chen Y, Pandya K, Keng PC, et al. (2003a) Phase I/II clinical trial using pulsed low-dose paclitaxel radiosensitization for thoracic malignancies: a therapeutic approach based on pre-clinical research of human lung cancer cells. Clin Cancer Res 9:969–975PubMedGoogle Scholar
  15. Chen Y, Rubin P, Williams J, et al. (2001a) Circulating IL-6 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 49:641–648CrossRefPubMedGoogle Scholar
  16. Chen Y, Williams J, Ding I, et al. (2002) Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol 12:26–33CrossRefPubMedGoogle Scholar
  17. Choy H, Akerly W, Safran H, et al. (1994) Phase I trial of out-patient weekly paclitaxel and concurrent radiation therapy for advanced non-small cell lung cancer. J Clin Oncol 12:2682–2686PubMedGoogle Scholar
  18. Choy H, Rodriguez FF, Koester S, et al. (1993) Investigation of taxol as a potential radiation sensitizer. Cancer 71:3774–3778PubMedGoogle Scholar
  19. Cromwell O, Hamid O, Corrigan CJ, et al. (1992) Expression and generation of interleukin-8, IL-6, and granulocyte macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1β and tumor necrosis factor α. Immunology 77:330–337PubMedGoogle Scholar
  20. Crestani B, Cornillet P, Dehoux M, et al. (1994) Alveolar type II epithelial cells produce interleukin-6 in vitro and in vivo. J Clin Invest 94:731–740PubMedGoogle Scholar
  21. Curran WJ Jr, Scott C, Langer C, et al. (2000) Phase III comparison of sequential vs. concurrent chemoradiation for PTS with unresected stage III non-small cell lung cancer (NSCLC): initial report of Radiation Therapy Oncology Group (RTOG) 9410. Proc ASCO 19:484a abstr 1891Google Scholar
  22. Dillman RO, Seagren SL, Propert KJ, et al. (1990) A randomized trial of induction chemotherapy plus high dose radiation versus radiation alone in stage III non-small cell lung cancer. N Engl J Med 323:940–945Google Scholar
  23. Ding Z, Xiong K, Issekutz TB (2000) Regulation of chemokine-induced transendothelial migration of T lymphocytes by endothelial activation: differential effects on naive and memory T cells. J Leukoc Biol 67:825–833PubMedGoogle Scholar
  24. Elias JA, Lentz V (1990) IL-1 and tumor necrosis factor synergistically stimulate fibroblast IL-6 production and stabilize IL-6 messenger RNA. J Immunol 145:161–166PubMedGoogle Scholar
  25. Elias JA, Schreiber AD, Gustilo K, et al. (1985) Differential interleukin-1 elaboration by unfractionated and density fractionated human alveolar macrophages and blood monocytes: relationship to cell maturity. J Immunol 135:3198–3204PubMedGoogle Scholar
  26. Elomaa L, Joensuu H, Kulmala J, et al. (1995) Squamous cell carcinoma is highly sensitive to taxol, a possible new radiation sensitizer. Acta Otolaryngol 115:340–344PubMedGoogle Scholar
  27. Fine A, Goldstein RH (1987) The effect of transforming growth factor beta on cell proliferation and collagen formation by lung fibroblasts. J Biol Chem 262:3897–3902PubMedGoogle Scholar
  28. Finkelstein JN, Johnston CJ, Baggs R, et al. (1994) Early alterations in extracellular matrix and transforming growth factor β gene expression in mouse lung indicative of late radiation fibrosis. Int J Radiat Oncol Biol Phys 28:621–631PubMedGoogle Scholar
  29. Fletcher GH (1973) Clinical dose-response curves of human malignant epithelial tumours. Br J Radiol 46:1–12PubMedGoogle Scholar
  30. Franko AJ, Sharplin J, Ghahary A, et al. (1997) Immunihistochemical localization of transforming growth factor beta and tumor necrosis alpha in the lungs of fibrosis-prone and “non-fibrosing” mice during the latent period and early phase after irradiation. Radiat Res 147:245–256PubMedGoogle Scholar
  31. Fryer CJH, Fitzpatrick PJ, Rider WD, et al. (1978) Radiation pneumonitis: experience following a large single dose of radiation. Int J Radiat Oncol Biol Phys 4:931–936PubMedGoogle Scholar
  32. Furuse K, Fukuoka M, Kawahara M, et al. (1999) Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 17:2692–2699PubMedGoogle Scholar
  33. Geard CR, Jones JM, Schiff PB (1993) Taxol and radiation. J Natl Cancer Inst Monographs 15:89–94PubMedGoogle Scholar
  34. Gianni L, Kearns CM, Giani A, et al. (1995) Nonlinear pharmacokinetics and metqabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 13:180–190PubMedGoogle Scholar
  35. Graham MV, Burdy JA, Emami B, et al. (1999) Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer. Int J Radiat Oncol Biol Phys 45:323–329CrossRefPubMedGoogle Scholar
  36. Grant D, Williams TL, Zahaczewsky M, et al. (2003) Comparison of antiangiogenic activities using paclitaxel (Taxol) and docetaxel (Taxotere). Int J Cancer 104:121–129PubMedGoogle Scholar
  37. Hallahan DE, Geng L, Shyr Y (2002) Effects of intercellular adhesion molecule 1 (ICAM-1) null mutation on radiation-induced pulmonary fibrosis and respiratory insufficiency in mice. J Natl Cancer Inst 94:733–741PubMedGoogle Scholar
  38. Hallahan DE, Virudachalam S (1997) Ionizing radiation mediates expression of cell adhesion molecules in distinct histological patterns within the lung. Cancer Res 57:2096–2099PubMedGoogle Scholar
  39. Hallahan DE, Virudachalam S (1997a) Intercellular adhesion molecule-1 knockout abrogates radiation induced pulmonary inflammation. Proc Natl Acad Sci USA 94:6432–6437PubMedGoogle Scholar
  40. Havemann K, Wolf M, George C, et al. (1995) Paclitaxel and simultaneous radiation in the treatment of stage III A/B non-small cell lung cancer. Semin Oncol 22:19–22Google Scholar
  41. Helle M, Brakenhoff JPJ, De Groot ER, et al. (1988) Interleukin 6 is involved in interleukin 1-induced activities. Eur J Immunol 18:957–959PubMedGoogle Scholar
  42. Hernando ML, Marks LB, Bentel GC, et al. (2001) Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Int I Radiat Oncol Biol Phys 51:650–659CrossRefGoogle Scholar
  43. Hornback NB, Shen R-N, Sutton GP, et al. (1994) Synergistic cytotoxic and antitumor effects of irradiation and Taxol on human Hela cervix carcinoma and mouse B16 melanoma cells. In Vivo 8:819–824PubMedGoogle Scholar
  44. Inoue A, Kunitoh H, Sekine I, et al. (2001) Radiation pneumonitis in lung cancer patients: a retrospective study of risk factors and the long-term prognosis. Int J Radiat Oncol Biol Phys 49:649–655CrossRefPubMedGoogle Scholar
  45. Ishii Y, Kitamura S (1999) Soluble intercellular adhesion molecule-1 as an early detection marker for radiation pneumonitis. Eur Respir J 13:733–738CrossRefPubMedGoogle Scholar
  46. Jenkins P, D'Amico K, Benstead K, et al. (2003) Radiation pneumonitis following treatment of non-small-cell lung cancer with continuous hyperfractionated accelerated radiotherapy (CHART). Int J Radiat Oncol Biol Phys 56:360–366CrossRefPubMedGoogle Scholar
  47. Johnston CJ, Wright TW, Rubin P, et al. (1998) Alterations in the expression of chemokine mRNA levels in fibrosis-resistant and-sensitive mice after thoracic irradiation. Exp Lung Res 24:321–337PubMedGoogle Scholar
  48. Jordan MA, Wendell K, Gardiner S, et al. (1996) Mitotic block induced in HeLa cells by low concentrations of paclitaxel results in abnormal mitotic exit and apoptotic cell death. Cancer Res 56:816–825PubMedGoogle Scholar
  49. Kaseda M, Kadota J, Mukae H, et al. (2000) Possible role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. Clin Exp Immunol 121:146–150CrossRefPubMedGoogle Scholar
  50. Kelley J (1990) Cytokines of the lung. Am Rev Respir Dis 141:765–788PubMedGoogle Scholar
  51. Keng PC, Okunieff P, Chen Y (2000) Low dose taxol/taxotere radiosensitization for human lung cancer cells is schedule dependent. Proceedings of the 42nd annual ASTRO meeting. Int J Radiat Oncol Biol Phys 48:272CrossRefGoogle Scholar
  52. Kirkbride P, Gelmon K, Eisenhauer E (1999) Paclitaxel and concurrent radiotherapy in locally advanced non-small cell lung cancer: the Canadian experience. Semin Radiat Oncol 9(suppl 1):102–107PubMedGoogle Scholar
  53. Kovacs EJ (1991) Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today 12:17–23CrossRefPubMedGoogle Scholar
  54. Kumar N (1981) Taxol-induced polymerization of purified tubulin. Mechanism of action. J Biol Chem 256:10435–10441PubMedGoogle Scholar
  55. Kwa SLS, Lebesque JV, Theuws JCM, et al. (1998) Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys 42:1–9CrossRefPubMedGoogle Scholar
  56. Lau DH, Ryu JK, Gandara DR, et al. (1997) Twice weekly paclitaxel and radiation for stage III non-small-cell lung cancer. Semin Oncol 24(suppl 12):106–109Google Scholar
  57. Lokeshwar BL, Ferrell SM, Block NL (1995) Enhancement of radiation response of prostatic carcinoma by taxol: therapeutic potential for late-stage malignancy. Anticancer Res 15:93–98PubMedGoogle Scholar
  58. Lynch T, Bell D, Sordella R, et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gemfitinib. N Engl J Med 350:2129–2139PubMedGoogle Scholar
  59. Maasilta P, Hallman M, Taskinen E, et al. (1993) Bronchoal-veolar lavage fluid findings following radiotherapy for non-small cell lung cancer. Int J Radiat Oncol Biol Phys 26:117–123PubMedGoogle Scholar
  60. Manfredi JJ, Parness J, Horwitz SB (1982) Taxol binds to cellular microtubules. J Cell Biol 94:688–696CrossRefPubMedGoogle Scholar
  61. Milas L, Hunter NR, Kurdoglu B, et al. (1995) Kinetics of mitotic arrest and apoptosis in murine mammary and ovarian tumors treated with taxol. Cancer Chemother Pharmacol 35:297–303PubMedGoogle Scholar
  62. Milas L, Hunter NR, Mason KA, et al. (1995a) Tumor re-oxygenation as a mechanism of taxol-induced enhancement of tumor radioresponse. Acta Oncologica 34:409–412PubMedGoogle Scholar
  63. Million RR, Cassisi NJ, Mancuso AA, et al (1994). Chapter 6: Management of the neck for squamous cell carcinoma. In: Million RR, Cassisi NJ (eds) Management of head and neck cancer, a multidisciplinary approach, 2nd edn. Lippincott, Philadelphia, pp 75–142Google Scholar
  64. Milross CG, Mason KA, Hunter NR, et al. (1996) Relationship of mitotic arrest and apoptosis to antitumor effect of paclitaxel. J Natl Cancer Inst 88:1308–1314PubMedGoogle Scholar
  65. Morton RF, Jett JR, McGinnis WL, et al. (1991) Thoracic radiation therapy alone compared with combined chemotherapy for locally unresectable non-small cell lung cancer. Ann Int Med 115:681–686PubMedGoogle Scholar
  66. Murphy WK, Fossella FV, Winn RJ, et al. (1993) Phase II study of Taxol in patients with untreated non-small cell lung cancer. J Natl Cancer Inst 85:384–388PubMedGoogle Scholar
  67. Nakayama Y, Makino S, Fukuda Y, et al. (1996) Activation of lavage lymphocytes in lung injuries caused by radiotherapy for lung cancer. Int J Radiat Oncol Biol Phys 34:459–467CrossRefPubMedGoogle Scholar
  68. O'Brien-Lander A, Nelson ME, Kimler BF, et al. (1993) Release of interleukin-1 by human alveolar macrophages after in vitro irradiation. Radiat Res 136:37–41PubMedGoogle Scholar
  69. Parness J, Horwitz SB (1981) Taxol binds to polymerized tubulin in vitro. J Cell Biol 91:479–487CrossRefPubMedGoogle Scholar
  70. Paez JG, Janne PA, Lee JC, et al. (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500CrossRefPubMedGoogle Scholar
  71. Pukkinen JO, Elomaa L, Joensuu H, et al. (1996) Paclitaxel-induced apoptotic changes followed by time-lapse video microscopy in cell lines established from head and neck cancer. J Cancer Res Clin Oncol 122:214–218CrossRefPubMedGoogle Scholar
  72. Randall K, Coggle JE (1995) Expression of transforming growth factor β1 in mouse skin during the acute phase of radiation damage. Int J Radiat Biol 68:301–309PubMedGoogle Scholar
  73. Rathmann J, Leopold KA, Rigas JR (1999) Daily paclitaxel and thoracic radiation therapy for non-small-cell lung cancer: preliminary results. Semin Radiat Oncol 9(suppl 1):130–135PubMedGoogle Scholar
  74. Reckzeh B, Merte H, Pfluger KH, et al. (1996) Severe lymphocy-topenia and interstitial pneumonia in patients treated with paclitaxel and simultaneous radiotherapy for non-small cell lung cancer. J Clin Oncol 14:1071–1076PubMedGoogle Scholar
  75. Roach M, Gandara D, You H-S, et al. (1995) Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors. J Clin Oncol 13:2606–2612PubMedGoogle Scholar
  76. Roberts CM, Foulcher E, Zaunders JJ, et al. (1993) Radiation pneumonitis: a possible lymphocyte-mediated hypersensitivity reaction. Ann Intern Med 118:696–700PubMedGoogle Scholar
  77. Robnett TJ, Machtay M, Vines EF, et al. (2000) Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys 48:89–94CrossRefPubMedGoogle Scholar
  78. Rodemann HP, Bamberg M (1995) Cellular basis of radiation induced fibrosis. Radiother Oncol 35:83–90CrossRefPubMedGoogle Scholar
  79. Rodriguez M, Sevin BU, Perras J, et al. (1995) Paclitaxel: a radiation sensitizer of human cervical cancer cells. Gynecol Oncol 57:165–169CrossRefPubMedGoogle Scholar
  80. Rosado MF, Donna E, Ahn YS (2003) Challenging problems in advanced malignancy: case 3. Imatinib mesylate-induced interstitial pneumonitis. J Clin Oncol 21:3171–3173CrossRefPubMedGoogle Scholar
  81. Rosenthal DI, Algazy K, Dowell J, et al. (2000) Seven-week continuous infusion paclitaxel concurrent with radiation therapy for locally advanced non-small cell lung cancer: a phase I study [abstract 2164]. In: Program/proceedings of the American Society of Clinical Oncology, 36th annual meeting, New Orleans. ASCO, Virginia, p 549aGoogle Scholar
  82. Rowinsky EK, Donehower RC, Jones RJ, et al. (1988) Microtubule changes and cytotoxicity in leukemia cell lines treated with taxol. Cancer Res 48:4093–4100PubMedGoogle Scholar
  83. Rubin P, Finkelstein J, Shapiro D (1992) Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys 24:93–101PubMedGoogle Scholar
  84. Rubin P, Johnston CJ, Williams JP, et al. (1995) A perpetual cascade of cytokines post-irradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys 33:99–109CrossRefPubMedGoogle Scholar
  85. Sause W, Kolesar P, Taylor S IV, et al. (2000) Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer. Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 117:358–364CrossRefPubMedGoogle Scholar
  86. Schaake-Koning C, van den Bogaert W, Dalesio O, et al. (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N Engl J Med 326:524–530PubMedGoogle Scholar
  87. Schiff PB, Horwitz SB (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77:1561–1565PubMedGoogle Scholar
  88. Segawa Y, Takigawa N, Kataoka M, et al. (1997) Risk factors for development of radiation pneumonitis following radiation therapy with or without chemotherapy for lung cancer. Int J Radiat Oncol Biol Phys 39:91–98CrossRefPubMedGoogle Scholar
  89. Sigel AV, Centrella M, Eghbali-Webb M (1996) Regulation of proliferative response of cardiac fibroblasts by transforming growth factor-beta 1. J Mol Cell Cardiol 28:1921–1929CrossRefPubMedGoogle Scholar
  90. Sinclair WK, Morton RA (1966) X-ray sensitivity during the cell generation cycle of cultured Chinese hamster cells. Radiat Res 29:450–474PubMedGoogle Scholar
  91. Sleijfer S (2001) Bleomycin-induced pneumonitis. Chest 120:617–624CrossRefPubMedGoogle Scholar
  92. Steren A, Sevin B-U, Perras J, et al. (1993) Taxol sensitizes human ovarian cancer cells to radiation. Gynecol Oncol 48:252–258CrossRefPubMedGoogle Scholar
  93. Thomas AL, Cox G, Sharma RA, et al. (2000) Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose escalating study. Eur J Cancer 36: 2329–2334CrossRefPubMedGoogle Scholar
  94. Tishler RB, Geard CR, Hall EJ, et al. (1992) Taxol sensitizes human astrocytoma cells to radiation. Cancer Res 52:3495–3497PubMedGoogle Scholar
  95. Wang GS, Yang KY, Perng RP (2001) Life-threatening hypersensitivity pneumonitis induced by docetaxel (Taxotere). Br J Cancer 85:1247–1250CrossRefPubMedGoogle Scholar
  96. Yorke ED, Jackson A, Rosenzweig KE, et al. (2002) Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys 54:329–339CrossRefPubMedGoogle Scholar
  97. Zhang D, Jacobberger JW (1996) TGF-β1 perturbation of the fibroblasts cell cycle during exponential growth: switching between negative and positive regulation. Cell Proliferation 29:289–307PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Yuhchyau Chen
    • 1
  1. 1.Department of Radiation OncologyRochesterUSA

Personalised recommendations