Similarly the use of SBRT for larger primary tumors
Similarly, the use of SBRT for larger primary tumors or organ invasion may be limited by concerns of increased normal tissue toxicity. A few small series using SBRT for Stage II disease have been published and demonstrated safe toxicity profiles, including a report of 13 patients with chest wall invasive NSCLC . SBRT was delivered with median dose of 50 Gy in 5 fractions with 1-year local control rate of 89%, and only 2 patients developed grade 1–2 new or worsening chest wall pain. The same group also reported outcomes in 40 patients with node-negative NSCLC and primary tumor > 5 cm (median size 5.6 cm), who received hypofractionated Thymoquinone to 50 Gy in 5 or 10 fractions, or 60 Gy in 8 fractions. With a local control rate of 91.2% at 18 months, there was a 7.5% rate of grade 3–4 and 0% grade 5 pulmonary toxicity . In another single institution retrospective report including patients with primary tumors > 5 cm (24% of patients) treated with 3–5 fractions of SBRT, rates of radiation-related toxicity were low, with 2.1% of patient having high-grade radiation pneumonitis, 1.6% having non-malignant pleural effusion, 2.6% having chronic chest wall pain, and 1.6% having rib fracture . Although these studies describe promising efficacy and low rates of significant toxicity with SBRT treatment for larger primary tumors, our analysis indicates the use of SBRT in this setting is not common practice. For patients with Stage II NSCLC who received SBRT, our report provides an update on the dose fractionations employed in the United States within the last decade, with the two most common regimens being 50 Gy in 5 fractions followed by 48 Gy in 4 fractions. Published SBRT regimens for early stage NSCLC range from single dose fractions in 30–34 Gy [27,28] to 15–20 Gy x 3 fractions [4,, , ,29], 12 Gy x 4 fractions , to 10–12 Gy x 5 fractions [8,30]. A survey of American radiation oncologists conducted in 2010 reported that the most common SBRT prescriptions were 20 Gy x 3 (22%), 18 Gy x 3 (21%), and 12 Gy x 4 (17%), with 95% of reported prescriptions having BED10 ≥ 100 Gy . An NCDB analysis of Stage I NSCLC treated with SBRT identified the most commonly used dose fractionation schemes as 20 Gy x 3, 12 Gy x 4, and 18 Gy x 3 . The overall mean and median calculated BEDs of these regimens were 134.5 and 132 Gy, respectively. Corso et al. found that use of the 3-fraction regimens (20 Gy x 3 and 18 Gy x 3) declined from 47.9% in 2006 to 27.9% in 2011, whereas the use of 10 Gy x 5 increased and became the most commonly prescribed regimen in 2011. The authors also found that smaller tumors tended to be treated with significantly higher BED10. Therefore, it was postulated that the trend toward a 5-fraction, lower-BED regimen was partly due to an increase in the treatment of centrally-located tumors. Similar to Corso et al., we identified a weak negative correlation between BED10 and tumor size. Timmerman et al. had identified excessive high-grade toxicity when centrally-located tumors were treated with 60–66 Gy in 3 fractions . This led to RTOG 0813, which investigated doses of 10–12 Gy x 5 fractions for central T 1-2 N0 NSCLC up to 5 cm, within or touching the proximal bronchial tree or adjacent to mediastinal or pericardial pleura . In our study, we could not assess the relationship between dose and peripheral versus central tumor location as this distinction was not captured in NCDB. Our results indicate that dose prescriptions used for Stage II NSCLC were similar to those used for Stage I NSCLC. The more frequent use of 10 Gy x 5 (BED10 100 Gy) and 12 Gy x 4 (BED10 105.6 Gy) as opposed to 20 Gy x 3 (BED10 180 Gy) or 18 Gy x 3 (BED10 151.2 Gy) may reflect the preferential use of lower dose per fraction for larger tumors or those invading adjacent structures, likely to reduce dose to OARs.