Tumor motion may be 2–3 cm in peri-diaphragmatic regions of the lower lung. Motion management strategies include respiratory gating , coaching with audio-visual feedback, breath-hold techniques, abdominal compression , and intrafraction tumor tracking real-time imaging techniques with dynamic beam and/or couch compensation.

Thin-cut CT (≤1.5 mm) thickness recommended. 4DCT or maximal inspiratory and expiratory phase CTs or slow CT recommended to assess target and critical structure internal motion. Free-breathing helical or mean intensity projection CT should be used for dose calculation.

iGTV contoured from Maximum Intensity Projection (MIP) generated from 4DCT. MIP should be used judiciously in tumors adjacent to diaphragm or chest wall , with additional imaging as needed to fully discriminate the target from surrounding normal tissue with similar CT tissue density.

GTV /iGTV  = tumor visible on CT lung window.

CTV /ITV  = GTV /iGTV  + 0–10 mm (in RTOG protocols , GTV and CTV have been considered identical on CT planning with zero expansion margin added).

PTV  = CTV /ITV  + 3–10 mm (dependent upon available center-specific IGRT and motion management capabilities). Current RTOG guidelines are:

Dose to proximal OARs attributed to compact intermediate dose region outside of the CTV /ITV region, generally reduced with increased beams and angles, as well as minimization of margins on target.

Treatment planning guidelines (adapted from RTOG 0618).

Heterogeneity correction algorithms are increasingly routinely used for planning (anisotropic analytical algorithm, collapsed cone convolution, Monte Carlo , etc.). Pencil-beam algorithms that overestimate dose in heterogeneous tissue are generally not recommended.

Phantom-based QA on treatment plans.

Dose and fractionation directed by adjacent normal tissue RT toxicity constraints with goal tumor BED₁₀ > 100. Adaptive dosimetry for histology -, volume-, location-, and context-based lesions (primary vs. metastatic) are under investigation.

Current dose fractionation schema largely employs 1–5 fractions.

Peripheral Lung Tumors

Central Lung Tumors

Dose typically prescribed 60–90 % IDL , with ≥95 % PTV coverage by prescription dose.

Composite planning should be employed in cases of regional lung re-irradiation with appropriate BED conversion for dose summation.

See Table 7.2, assuming no prior regional radiotherapy (TG101, Benedict et al., 2010; RTOG 0618).

Dose delivered in consecutive daily or every other day fractions as per current NRG protocols.

Setup may be isocentric or non-isocentric depending upon SBRT delivery system.

Verification by kV XR or CBCT , aligned to visualized tumor or surrogate.

Intrafraction dose delivery adjustment by motion management and IGRT systems as discussed above.

Evidence widely supports efficacy and safety of SBRT in early-stage NSCLC, with optimal patient selection criteria and dose schema emerging as studies mature.

CALGB 39904 (Bogart et al. 2010). Phase I dose-escalation study of 39 stage I (≤4 cm) NSCLC patients. 70 Gy in 29 decreased to 17 fractions. 92.3 % actuarial control, 82.1 % actuarial distant control. No late grade 3 or 4 toxicity.

Onishi et al. (2004). Initial report of retrospective Japanese multi-institutional series of 245 patients with stage I NSCLC treated with SBRT 18–75 Gy in 1–22 fractions with a median follow-up of 24 months. Grade ≥3 toxicity 2.4 %. LR at 3 years for BED  ≥ 100 vs. BED < 100 was 8.1 % vs. 26.4 %, p < 0.05 and OS was 88.4 % vs. 69.4 %, p < 0.05, establishing BED ≥ 100 as prescribing criterion.

Nordic Study Group (Baumann et al. 2009). Phase II study of SBRT in 57 patients with medically inoperable early-stage peripheral tumors (40 stage IA, 17 stage IB), treated with 45–66 Gy in 3 fractions. Estimated 3 year LC and OS were 88.4 % and 59.5 %, respectively. Distant metastatic rate 16 %. Risk of any failure increased in T2 vs. T1 tumors (41 % vs. 18 %, p = 0.027).

RTOG 0236 (Timmerman et al. 2010, Stanic et al. 2014). Phase II multicenter trial of 55 patients with medically inoperable early-stage (<5 cm) peripheral NSCLC (44 stage IA, 11 stage IB), treated with 54 Gy in 3 fractions SBRT . Three year primary tumor and involved lobe control was 98 %. Rate of distant failure 22 % at 3 years. OS 56 % at 3 years. Grade 3 and 4 toxicities were 12.7 % and 3.5 %, respectively. Poor baseline PFT not predictive of SBRT-related toxicity.

Timmerman et al. (2006), Farikis et al. (2009). Phase II study of SBRT at Indiana University for T1-2N0 medically inoperable NSCLC patients (n = 70), 60–66 Gy in 3 fractions. LC and OS at 3 years were 88.1 % and 42.7 %, respectively. Grade ≥3 toxicity rates of 10.4 % peripheral vs. 27.3 % central over a median follow-up of 50.2 months (p = 0.088).

JCOG 0403 (Nagata et al. 2012). Phase II trial of SBRT in early-stage NSCLC, stratified by medically operable/inoperable. In medically inoperable arm, 100 patients with stage IA disease received 48 Gy in 4 fractions. LC and OS at 3 years were 88 % and 59.9 %, respectively. For 64 medically operable patients, LC and OS at 3 years were 86.0 % and 76.0 %, respectively. Grade 3 pneumonitis 7 %, overall grade 4 toxicity 2 %.

RTOG 0618 (Timmerman et al. 2013). Phase II trial of 33 patients with medically operable early-stage peripheral NSCLC (<5 cm), treated with 60 Gy in 3 fractions. Completed accrual in 2010 with results presented at ASCO 2013 showing estimated 2 years primary tumor failure rate of 7.8 %, with a median follow-up of 25 months. Local failure , including ipsilateral lobe, was 19.2 %. PFS and OS at 2 years were estimated at 65.4 % and 84.4 %. Grade 3 toxicity was 16 %.

RTOG 0813. Phase I/II dose-escalation trial of medically inoperable centrally located (<2 cm of proximal bronchial tree) early-stage NSCLC (<5 cm). At the time of accrual completion, dose escalated to 60 Gy in 5 fractions. Closed to accrual at 120 patients in 2013. Results are pending.

RTOG 0915 (Videtic et al. 2013). Phase II randomized trial of 34 Gy in 1 fraction vs. 48 Gy in 4 fractions for medially inoperable early-stage peripheral NSCLC (<5 cm). Study completed accrual in 2011 with 94 patients. At 1 year, LC 97.1 % vs. 97.6 %; OS 85.4 % vs. 91.1 %, and PFS 78.0 % vs. 84.4 %. Adverse events were 9.8 % vs. 13.3 %. Based on the favorable toxicity, the 34 Gy in 1 fraction arm will be compared to the 54 Gy in 3 fractions arm of RTOG 0236 in a phase III setting.

Hoppe et al. (2008). Study of 50 stage I NSCLC patients treated with SBRT 60 Gy in 3 fractions or 44–48 Gy in 4 fractions with a median follow-up of 6 months. Skin toxicity was 38 % grade 1, 8 % grade 2, 4 % grade 3, and 2 % grade 4. Reduced number of beams, proximal distance to chest wall , and skin dose ≥50 % prescription dose were associated with increased risk of skin toxicity.

Mutter et al. (2012). Retrospective study of 128 early-stage NSCLC patients receiving SBRT 40–60 Gy in 3–5 fractions. With a median follow-up of 16 months, grade ≥2 chest wall toxicity was 39 % estimated at 2 years. On dosimetric analysis, grade ≥2 chest wall pain was associated with a V30Gy >70 cm³ within a 2 cm 2D-ipsilateral chest wall expansion.

ACOSOG Z4099/RTOG 1021. Phase III trial of SBRT vs. sublobar resection for high-risk operable, early-stage peripheral NSCLC (<3 cm). Terminated for poor accrual.

ROSEL Trial (VUMC, NCT00687986). Phase III trial of SBRT (60 Gy in 3 or 5 fractions) vs. surgery for stage IA peripheral NSCLC. Terminated for poor accrual.

STARS Trial (MDACC, NCT00840749). Phase III trial of SBRT 60 Gy in 3–4 fractions based on lesion location vs. surgery for stage I NSCLC. Terminated for poor accrual.

Grills et al. (2010). Retrospective comparison of 124 patients (95 % medically inoperable) T1-2 N0 NSCLC receiving wedge resection (n = 69) vs. SBRT (n = 58), 48–60 Gy in 4–5 fractions. No statistically significant differences in LRR (27 % wedge vs. 9 % SBRT, p > 0.16) or CSS (94 % wedge vs. 93 % SBRT, p = 0.53) noted at a median follow-up of 30 months. OS favored wedge resection (87 % wedge vs. 72 % SBRT, p = 0.01).

Crabtree et al. (2010). Retrospective comparison of stage I NSCLC patients receiving either surgery (n = 462) or SBRT (n = 76) for definitive care. Surgical candidates had fewer medical comorbidities . Thirty-five percent of surgical patients were upstaged on final pathology. OS 5 years 55 % surgery and OS 3 years 32 % with SBRT. In propensity matched analysis, no statistically significant difference in LC (88 % vs. 90 %) and OS (54 % vs. 38 %) at 3 years in surgery vs. SBRT groups.

SEER -Medicare analysis (Shirvani et al. 2012). Comparative outcomes of stage I NSCLC patients ≥60 years old, which demonstrated overall ranked outcomes as lobectomy > sublobar resection  > SBRT  > conventional EBRT  > observation. However, as treatment outcomes were likely influenced by patient selection and comorbidities , there was no difference in OS between SBRT and surgical modalities on propensity matched analysis, and EBRT remained inferior to SBRT.

Shah et al. (2013a, b). Cost-effectiveness comparison of surgical resection vs. SBRT for stage I NSCLC patients >65 years. For marginally operable patients, SBRT was most cost effective with a mean cost and quality-adjusted life expectancy of $42 k/8.0 years vs. lobectomy at $49 k/8.9 years. However, for completely operable candidates, lobectomy was found more cost effective, having an incremental cost-effectiveness ratio of $13 K/quality-adjusted life year .

Table 7.3 summarizes several multiple primarily retrospective series indicating local control rate s of 85–95 % at 3–5 years, and overall survival rates of 50–95 % at 3–5 years for early-stage NSCLC managed with SBRT . Some series include limited numbers of recurrent and metastatic patients.

Studies have suggested a role for dose escalation as part of conventional chemoradiation in locally advanced lung cancer , with current focus on reduced volume boost , to minimize normal lung toxicity, for which SBRT may be of utility.