Abstract
During the 1990s, thoracic radiotherapy (RT) combined with chemotherapy was accepted as a “new” gold standard for patients with good performance status locally advanced/inoperable non-small cell lung cancer (NSCLC). This paradigm shift away from RT alone has raised several fundamental questions: What is the optimal sequencing of chemotherapy and radiotherapy? Should standard (once-daily) RT continue to be employed? What about altered fractionation schema? Is there a role for three-dimensional conformal RT? How can the toxicity of combined modality strategies be reduced?
Keywords
- Advanced NSCLC
- Radiation Pneumonitis
- Concurrent Chemoradiation
- Molecular Staging
- Tumor Cell Repopulation
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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Perez, C. A., Pajak, T. F., Rubin, P., Simpson, J. R., Mohiuddin, M., Brady, L. W., et al. (1987) Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Cancer 59, 1874–1881.
Dillman, R. O., Seagren, S. L., Propert, K. J., Guerra, J., Eaton, W. L., Perry, M. C., 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, 940–945.
Dillman, R. O., Herndon, J., Seagren, S. L., Eaton, W., and Green, M. R. (1996) Improved survival in stage III non-small cell lung cancer: Seven-year followup of Cancer and Leukemia Group B (CALGB) 8433 trial. J. Natl. Cancer Inst. 88, 1210–1215.
Jeremic, B., Shibamoto, Y., Acimovic, L., and Djuric, L. (1995) Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small cell lung cancer. J. Clin. Oncol. 13, 452–458.
Jeremic, B., Shibamoto, Y., Acimovic, L., and Milisavljevic, S. (1996) Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small cell lung cancer: A randomized study. J. Clin. Oncol. 14, 1065–1070.
Le Chevalier, T., Arriagada, R., Tarayre, M., Lacombe-Terrier, M. J., LaPlanche, A., Quoix, E., et al. (1992) Significant effect of adjuvant chemotherapy on survival in locally advanced non-small cell lung carcinoma (Letter). J. Natl. Cancer Inst. 84, 58.
Sause, W. T., Scott, C., Taylor, S., Johnson, D., Livingston, R., Komaki, R., et al. (1995) Radiation therapy oncology group (RTOG) 88-08 and eastern cooperative oncology group (ECOG) 4588: Preliminary results of a phase III trial in regionally advanced unresectable non-small cell lung cancer. J. Natl. Cancer Inst. 87, 198–205.
Schaake-Koning, C., vanden Bogaert, W., Dalesio, O., Festen, J., Hoogenhout, J., van Houtte, P., et al. (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N. Engl. J. Med. 326, 524–530.
Marino, P., Preatoni, A., and Cantoni, A. (1995) Randomized trials of radiotherapy alone vs. combined chemotherapy and radiotherapy in stages IIIa and IIIb non-small cell lung cancer: a meta-analysis. Cancer 76, 593–601.
Non-Small Cell Lung Cancer Collaborative Group (1995) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. BMJ 311, 899–909.
Pritchard, R. S. and Anthony, S. P. (1996) Chemotherapy plus radiotherapy compared with radiotherapy alone in the treatment of locally advanced, unresectable non-small cell lung cancer: A meta-analysis. Ann. Intern. Med. 125, 723–729.
Sause, W. T., Kolesar, P., Taylor, S., Johnson, D., Livingston, R., Komaki, R., et al. (1997) Five-year results: Phase III trial of regionally advanced unresectable non-small cell lung cancer, RTOG 8808, ECOG 4588, SWOG 8892 Abstract A-1743. Proc. Am. Soc. Clin. Oncol. 17, 453.
Clamon, G., Herndon, J., Cooper, R., Chang, A. Y., Rosenman, J., and Green, M. R. (1999) Radiosensitization with carboplatin for patients with unresectable stage III non-small cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J. Clin. Oncol. 17, 4–11.
Arriagada, R., Le Chevalier, T., Rekacewicz, C., Quoix, E., De Cremoux, H., Douillard, J., and Tarayre, M. (1997) Cisplatin-based chemotherapy (CT) in patients with locally advanced non-small cell lung cancer (NSCLC): late analysis of a French randomized trial Abstract. Proc. Ann. Meet. Am. Soc. Clin. Oncol. 16, 1601.
Furuse, K., Hosoe, S., Msuda, N., Sugiura, T., Yokota, S., Ohbayashi, K., Okazaki, M., et.al. (2000) Impact of tumor control on survival in unresectable stage III non-small cell lung cancer (NSCLC) treated with concurrent thoracic radiotherapy (TRT) and chemotherapy (CT). Proc. ASCO 19, 484a.
Komaki, R., Seiferheld, W., Curran, W., Langer, C., Lee, J., Hauser, S., et al. (2000) Sequential vs. concurrent chemotherapy and radiation therapy for inoperable non-small cell lung cancer (NSCLC): Analysis of failures in a phase III study (RTOG 9410) Abstract 5. Int. J. Radiat. Oncol. Biol. Phys. 48, 113.
Movsas, B. (2000) Innovative treatment strategies in locally advanced and/or unresectable non-small cell lung cancer. Cancer Control 7, 25–34.
Gaspar, L., Gandara, D., Chansky, K., Albain K. S., Lara, P. N. Jr., Crowley, J., Livingston, R. B. (2001) Consolidation Docetaxel following concurrent chemoradiotherapy in pathologic stage IIIB non-small cell lung cancer (NSCLC) (SWOG 9504): Patterns of Failure and Updated Survival. Proceedings ASCO 20, 315a. Abstract 1255.
Kerr, K. M. and Lamb, D. (1984) Actual growth rate and tumour cell proliferation in human pulmonary neoplasms. Br. J. Cancer 50, 343–349.
Thames, H. D., Peters, L. J., Withers, H. R., et al. (1983) Accelerated fractionation vs hyperfractionation: rationale for several treatments per day. Int. J. Radiat. Oncol. Biol. Phys. 9, 127–139.
Cox, J. D., Azarnia, N., Byhardt, R. W., Shin, K. H., Emami, B., and Pajak, T. F. (1990) A randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60 Gy to 79.2 Gy: possible survival benefit with >=69.6 Gy in favorable patients with radiation therapy oncology group stage III non-small cell lung carcinoma: report of RTOG 83-11. J. Clin. Oncol. 8, 1543–1553.
Jeremic, B., Shibamoto, Y., Radosavljevic-Asic, G., Nikolic, N., Dagovic, A., Aleksandrovic, J., et al. (2000) Hyperfractionated radiation therapy (HFXRT) and concurrent low-dose, daily carboplatin/etoposide (CE) with or without weekend CE in stage III non small cell lung cancer (NSCLC). A randomized trial. Proc. ASCO 19, 504a.
Saunders, M. I., Dische, S., Barrett, A., et al. (1997) Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: A randomized multicentre trial. Lancet 350, 161–165.
Perez, C. A., Stanley, K., Rubin, P., Kramer, S., Brady, L., Perez-Tamayo, R., et al. (1980) A prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat cell carcinoma of the lung. Cancer 45, 2744–2753.
Hazuka, M. B., Turrisi, A. T., Lutz, S. T., Martel, M. K., Ten Haken, R. K., Strawderman, M., et al. (1993) Results of high-dose thoracic irradiation incorporating beam’s eye view display in non-small cell lung cancer: A retrospective multivariate analysis. Int. J. Radiat. Oncol. Biol. Phys. 27, 273–284.
Perez, C. A., Stanley, K., Grundy, G., Hanson, W., Rubin, P., Kramer, S., et al. (1982) Impact of irradiation technique and tumor extent in tumor control and survival of patients with unresectable non-oat cell carcinoma of the lung. Cancer 50, 1091–1099.
Robinow, J. S., Shaw, E. G., Eagan, R. T., Lee, R. L., Creagan, E. T., Frytak, S., et al. (1989) Results of combination chemotherapy and thoracic radiation therapy for unresectable non-small cell carcinoma of the lung. Int. J. Radiat. Oncol. Biol. Phys. 17, 1203–1210.
Hayman, J., Martel, M., Ten Haken, R., Normolle, D., Todd III, R., Littles, F., et al. (2001) Dose escalation in non-small cell lung cancer using three-dimensional conformal radiation therapy: update of a Phase I trial. J. Clin. Oncol. 19, 127–136.
Mitra, R., Mah, D., Das, I., Movsas, B., and Schultheiss, T. (2000) Effect of inhomogeneity in small fields: Dosimetric implications for complex IMRT of lung 37. Int. J. Radiat. Oncol. Biol. Phys. 48, 129.
Socinski, M., Halle, J., Schell, M., Clark, J., Limentani, S., Mitchell, W., et al. (2000) Induction (I) and concurrent (C) carboplatin/paclitaxel (C/P) with dose-escalated thoracic conformal radiotherapy )TCRT) in stage IIIA/B non-small cell lung cancer (NSCLC): A Phase I/II trial. Proc. ASCO 19, 496a.
Cox, J. D., Pajak, T. F., Asbell, S., Russell, A. H., Pederson, J., Byhardt, R. W., et al. (1993) Interruptions of high-dose radiation therapy decrease long-term survival of favorable patients with unresectable non-small cell carcinoma of the lung: analysis of 1244 cases from three RTOG trials. Int. J. Radiat. Oncol. Biol. Phys. 27, 493–498.
Movsas, B., Scott, C., Sause, W., Byhardt, R., Komaki, R., Cox, J., Johnson, D., Lawton, C., Dar, A. R., Wasserman, T., Roach, M., Lee, J. S., Andras, E. (1999) The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): A quality-adjusted survival analysis of Radiation Therapy Oncology Group (RTOG) chemo-radiation studies. Int. J. Radiat. Oncol. Biol. Phys. 45(5), 1143–1149.
Treskes, M., Holwerda, U., Nijtmans, L., Fichtinger-Schepman, A. M. J., Pinedo, H. M., and van der Vijgh, W. J. F. (1994) Modulation of cisplatin and carboplatin with WR-2721, molecular aspects. Chem. Mod. Cancer Treat 322–323.
Washburn, L. C., Rafter, J. J., and Hayes, R. L. (1976) Prediction of the effective radioprotective dose of WR-2721 in humans through an interspecies tissue distribution study. Radiat. Res. 55, 100–105.
Yuhas, J., Spellman, J. M., and Culo, F. (1980) The role of WR-2721 in radiotherapy and/or chemotherapy. Cancer Clin. Trials 3, 211–216.
Tannehill, S. P. and Mehta, M. P. (1996) Amifostine and radiation therapy: past, present, and future. Semin. Oncol. 23, 69–77.
Buntzel, J., Glatzel, M., Kuttner, K., Schuth, J., Oster, J., and Frohlich, F. (1996) Selective cytoprotection with amifostine in simultaneous radiochemotherapy of head and neck cancer. Ann. Oncol. 7, 81.
Brizel, D. M., Wasserman, T. H., Henke, M., Strnad, V., Rudat, V., Monnier, A., Eschwege, F., et al. (2000) Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J. Clin. Oncol. 18, 3339–3345.
Antonadou, D., Coliarakis, N., Synodinou, M., Athanassiou, H., Kouveli, A., Verigos, C., Georgakopoulos, G., Panoussaki, K., Karageorgis, P., Throuvalas, N. (2001) Randomized Phase III trial of radiation treatment +/− amifostine in patients with advanced-stage lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 51, 915–922.
Antonadou, D., Synodinou, M., Bougi, M., Sagriotis, A., Paloudis, S., and Throuvalas, N. (2000) Amifostine reduces acute toxicity during radiochemotherapy in patients with localized advanced stage non small cell lung cancer. Proc. ASCO 19, 501a.
Epperly, M. W., Bray, J. A., Krager, R. S., et al. (1999) Intratracheal injection of adenovirus containing the human MnSOD transgene protects athymic nude mice from irradiation induced organizing alveolitis. Int. J. Radiat. Oncol. Biol. Phys. 22, 623–625.
Kim, Y.-C., Park, K.-O., Kern, J., et al. (1998) The interactive effects of Ras, HER2, p53 and Bcl2 expression in predicting the survival of non-small cell lung cancer patients. Lung Cancer 22, 181–190.
Komaki, R., Milas, L., Ro, J., Fujii, T., Perkins, P., Allen, P., et al. (1998) Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 40, 787–796.
Kwiatkowski, D. J., Harpole, D. H. J., Godleski, J., et.al. (1998) Molecular pathologic substaging in 244 stage I non-small cell lung cancer patients: clinical implications. J. Clin. Oncol. 16, 2468–2477.
Cox, G., Jones, L., Andi, A., et.al. (2000) Molecular staging for operable non-small cell lung cancer Abstract 1884. Proc. Am. Soc. Clin. Oncol. 19, 482a.
Perou, C., Sorlie, T., Elsen, M., et al. (2000) Molecular portraits of human breast tumors. Nature 406, 747–752.
Pieterman, R., van Putten, J., Meuzelaar, J., Mooyaart, E., Vaalburg, W., Koeter, G., et al. (2000) Preoperative staging of non-small cell lung cancer with positron-emission tomography. N. Engl. J. Med. 343, 254–61.
Van Tinteren, H., Hoekstra, O., Smit, E., et al. (2000) Randomized controlled trial (RCT) to evaluate the cost-effectiveness of positron emission tomography (PET) added to conventional diagnosis in non-small cell lung cancer (NSCLC) Abstract 1885. Proc. Am. Soc. Clin. Oncol. 19, 482a.
Balogh, J., Caldwell, C., Ung, Y., Mah, K., Danjoux, E., Ganguli, S., and Ehrlich, L. (2000) Interobserver variation in contouring gross tumour volume in carcinoma of the lung associated with pneumonitis and atelectasis: The impact of 18 FDG-hybrid PET fusion Abstract 36. Int. J. Radiat. Oncol. Biol. Phys. 48, 128.
Erdi, Y., Yorke, E., Erdi, A., Braban, L., Hu, Y., Macapinlac, H., et al. (2000) Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET) 33. Int. J. Radiat. Oncol. Biol. Phys. 48, 127.
Schmuecking, M., Plichta, K., Lopatta, E., Przetak, C., Leonhardi, J., Gottschild, D., et al. (2000) Image fusion of F-18 FDG PET and CT: Is there a role in 3D radiation treatment planning of non-small cell lung cancer? (abstract) Int. J. Radiat. Oncol. Biol. Phys. 48, 130.
MacManus, M., Hicks, R., Wada, M., Hogg, A., Matthews, J., Wirth, A., et al. (2000) Early F-18 FDG-PET response to radical chemoradiotherapy correlates strongly with survival in unresectable non-small cell lung cancer 1888. Am. Soc. Clin. Oncol. 19, 483a.
Roth, J. A., Dguyen, D., Lawrence, D. D., et al. (1996) Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nat. Med. 2, 985–991.
Volm, M., Koomagi, R., and Mattern, J. (1997) Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer. Int. J. Cancer 74, 64–68.
De Vore, R., Fehrenbachter, L., Herbst, R., et.al. (2000) A randomized phase III trial comparing RHUMAB VEG (Recombinant humainized monoclonal antibody to vascular endothelial cell growth factor) plus carboplatin/paclitaxel (CP) to CP alone in patients with stage IIIB/IV NSCLC. Proc. Am. Soc. Clin. Oncol. 19, 485a.
Baselga, J. (2000) New therapeutic agents targeting the epidermal growth factor receptor. J. Clin. Oncol. 18, 54s–59s.
Hanna, N., Seetharam, S., Mauceri, H., Beckett, M., Jaskowiak, N., Salloum, R., et.al. (2000) Antitumor interaction of short-course endostatin and ionizing radiation. Cancer J. 6, 287–293.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Movsas, B. (2003). Recent Advances and Dilemmas in the Radiotherapeutic Management of Locally Advanced Non-Small Cell Lung Cancer. In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicine™, vol 75. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-324-0:489
Download citation
DOI: https://doi.org/10.1385/1-59259-324-0:489
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-0-89603-920-9
Online ISBN: 978-1-59259-324-8
eBook Packages: Springer Protocols