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Lung cancer is the leading cause of cancer deaths, having caused an estimated 1.18 million deaths worldwide in 2002.1 In the US alone, lung cancer resulted in an estimated 159,300 deaths in 2009.2 Most deaths are from non-small-cell lung cancer (NSCLC), which accounts for more than 80% of lung cancers diagnosed in the US. Sadly, most patients present with advanced, inoperable disease. While stage IV patients remain incurable, there is now potentially curative therapy that can be offered to most patients with stage III NSCLC.3
Over 40 years ago, Wolf et al. established the role of RT in the treatment of lung cancer. Their randomized phase III trial compared radiotherapy (RT) versus placebo for clinically inoperable lung cancer (including both small-cell and NSCLC). RT was delivered with 200–250kV X-rays and included the delivery of 40–50Gy in 1.5–2.0Gy daily fractions. The median survival of patients given RT was 142 days compared with 112 days for those who received the placebo (p=0.05).4 A phase III Radiation Therapy Oncology Group (RTOG) trial evaluated the effect of dose on outcome by randomly assigning patients to receive 40Gy in 20 daily fractions, 50Gy in 25 daily fractions, or 60Gy in 30 daily fractions. The local failure rates determined with serial chest X-rays were 48% with 40Gy, 38% with 50Gy, and 27% with 60Gy. Although the differences in survival were not significant, this study defined the standard RT dose as 60Gy in 30 daily fractions.5 This dose fractionation pattern remained the standard of care for decades. Conventional RT alone resulted in a median survival of 10 months and a five-year survival of 5%. Until the 1990s, the standard treatment for locally advanced inoperable lung cancer was RT alone.5
In order to improve the outcome of treatment, chemotherapy was added to RT. Phase III trials demonstrated a survival advantage following the addition of chemotherapy to RT for NSCLC.6,7 The Cancer and Leukemia Group B reported that induction chemotherapy (cisplatin plus vinblastine) followed by conventional RT (60Gy/30 fractions) resulted in significantly better survival than conventional RT alone.6 The median and five-year survivals were 13.7 months and 17% for the combined therapy versus 9.6 months and 6% for RT alone (p=0.012).6