Innovative Treatment Strategies in Locally Advanced and/or Unresectable Non-Small Cell Lung Cancer

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Abstract
Background: While small improvements in outcome have occurred for patients with locally advanced non-small cell lung cancer (NSCLC), 5-year survival results remain low, ranging from 5% to 20%. Distant metastases and local-regional progression remain significant patterns of failure. Methods: Trials investigating innovative treatment strategies for patients with locally advanced and/or unresectable NSCLC are reviewed, including altered radiation fractionation schema, conformal 3-dimensional radiotherapy, and combined chemoradiotherapy regimens. Results: Whereas hyperfractionated radiation therapy (HFRT) alone does not appear to be beneficial, combined HFRT and chemotherapy appears promising in several trials. Patients treated with accelerated RT compared with standard RT have an improved survival. As higher radiation doses appear to enhance local tumor control, strategies involving 3-dimensional conformal radiotherapy merit further investigation. RT plus chemotherapy is superior to RT alone, albeit with greater toxicity. Amifostine is currently being investigated as a radioprotector. The optimal chemotherapy agents and their integration with radiotherapy are the subject of randomized trials. Conclusions: Ongoing investigations are warranted to combat both local-regional and systemic failures for patients with locally advanced NSCLC. Treatment strategies need to consider not only the traditional endpoints of survival and local control, but also quality of life.