Lung cancer

Non-small-cell lung cancer (NSCLC), the most common cause of cancer death worldwide, is amenable to surgery in patients with early or localized disease (approximately 15–20% of cases) (Shields 1993). Surgical resection of stage I (T1–2, N0) NSCLC yields satisfying outcome results with 5-year survival rates of 60–70%, and remains at present the golden standard in this population. Nevertheless its use is restricted to compliant, medically fit patients (Naruke et al. 1988; Mountain 1997; Adebonojo et al. 1999). Patients refusing surgery or deemed medically inoperable due to comorbidities, who despite impaired life expectancy would ultimately die of cancer progression in more than half of cases if no specific cancer treatment is performed (McGarry et al. 2002), have been treated with nonsurgical therapies such as standard fractionated radiotherapy, with disappointing results (Dosoretz et al. 1992). Optimal tumor control might be obtained by adequate dose escalation, though at the expense of increased toxicity with traditional radiotherapy techniques and schedules (Rosenzweig et al. 2005). Moreover, irradiation of lung lesions must also take into account tumor motion during the breathing cycle that can result, during expiration and deep inspiration, in excursions up to 3 cm as a function of tumor location and respiratory pattern (Seppenwoolde et al. 2002). Since wide margins would be needed to cover the presumed range of motion, detection of tumor position during the treatment course may contribute to maintain acceptable treatment volumes, thus reducing exposure of healthy lung to radiation damage. Therefore improvement in dose delivery and in target recognition became of primary interest in radiation research during the last decade, pushing toward development of stereotactic body radiotherapy (SBRT) as a valuable option in this setting. In a pivotal work comparing four-dimensional SBRT with three-dimensional conformal radiotherapy, an increase up to 75% in mean biological dose was possible without significant additional dose to the organs at risk, in particular lung (Prevost et al. 2008). Data from retrospective series of unresectable patients showed promising local control rates of 80–100% (Onishi et al. 2004; van der Voort et al. 2009; Lagerwaard et al. 2008) and overall survival rates of 40–80% at 3 years (Simone et al. 2013), in particular when biologically effective dose (BED) superior to 100 Gy is delivered (Onishi et al. 2004). It is also noteworthy that overall survival was comparable to surgery in SBRT patients when treatment groups were adjusted for variables (age, comorbidities, etc.) that might lead to a selection bias (Palma et al. 2011; Soldà et al. 2013). However, no direct comparison is available at present since the two phase III trials; STARS (StereoTActic Radiotherapy vs. Surgery) and ROSEL (Radiosurgery Or Surgery for operable Early stage non-small-cell Lung cancer) comparing SBRT to surgical resection were prematurely closed due to low accrual (Chang et al. 2015). These favorable results are achieved by modern image-guided radiotherapy systems that combine high-dose delivery with accurate treatment guidance by integration of linear accelerators with medical imaging devices like Cone-Beam CT, MegaVoltage CT (Tomotherapy®: Accuray Inc., Sunnyvale, California, USA) or X-ray tubes (CyberKnife®; Accuray Inc., Sunnyvale, California, USA). In this chapter, a summary of methods to minimize the impact of tumor motion and clinical aspects of SBRT in the treatment of primary lung tumors is discussed.

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