Efficacy
For medically inoperable peripheral lung tumours with a maximum diameter less than 5 cm, stereotactic ablative body radiation therapy (SABR) with BED >100 Gy should be considered as standard therapy, and achieves 5-year local control rates of >90% and 3-year overall survival (OS) rates of 60%-70%.
SABR versus conventional RT
The phase III multicentre Australian TROG/ALTG randomised trial (CHISEL) involved 101 patients receiving 54 Gy in 3 fractions or 48 Gy in 4 fractions if the tumour was within 2 cm from the chest wall, compared to 66 Gy in 33 fractions or 50 Gy in 20 fractions in inoperable patients or patients refusing surgery with stage 1 (T1-T2a) NSCLC.r The primary endpoint was time to local failure with secondary endpoints of OS, lung cancer specific survival, toxicity and quality of life. After a median follow up of approximately two years, time to local failure was improved with SABR (HR 0.29, 95% CI 0.13-0.66) as was OS (HR 0.51, 95% CI 0.29-0.91). Toxicity was low with only 1 grade 4 toxicity.
Figure 1. Freedom from local failure and OS
© Lancet Oncol 2019r
The phase II multicentre Scandinavian randomised trial (SPACE) involved 102 patients comparing 66 Gy in 3 fractions prescribed to the isocentre over one week with 70 Gy in 35 fractions over 7 weeks in medically inoperable patients with stage 1 non central NSCLC.r The primary end point was progression-free survival (PFS) at 3 years with secondary endpoints of OS, local control, acute toxicity, late toxicity and quality of life. After a median follow up of 37 months, the 3-year PFS was 42% in both arms (HR 0.85, 95% CI 0.52-1.36), with no difference in OS (HR 0.75, 95% CI 0.43-1.30). Local control for SABR versus conventional radiation therapy was 86.4% versus 85.7%. Any grade pneumonitis was 19% versus 34%, with oesophagitis 8% versus 30%. Quality of life evaluation showed worse dyspnoea, chest pain and cough with 3D conformal radiation therapy compared to SABR which lasted over time.
A systematic review and meta-analysis of 87 SABR and 24 non-SABR articles showed improved 2-year (70.9% versus 47.0%) and 3-year (60.1% versus 37.3%) OS with SABR, with similar incidence of pneumonitis (11% versus 13.8%) and less oesophagitis (<1% versus 15.1%).r
Inoperable patients
The phase II multicentre RTOG 0236 trial of SABR with 54 Gy in 3 fractions in 55 inoperable patients with T1-3 N0 non central lung cancer <5 cm showed 5 year primary failure of 7%, locoregional failure of 25%, distant recurrence in 25% and OS of 40% with 27% grade 3 and 3% grade 4 adverse events.r
Figure 2. Overall survival and disease free survival
© JAMA Oncol 2018 r
The phase II trial by Videtic et al. evaluated 34 Gy in 1 fraction versus 48 Gy in 4 fractions in inoperable patients.r The median survival times for 34 Gy and 48 Gy were 4.1 years versus 4.6 years respectively. Five-year outcomes for primary tumour failure rate were 10.6% (95% CI: 3.3%-23.1%) versus 6.8% (95% CI: 1.7%-16.9%) for 34 Gy and 48 Gy respectively. Overall survival was 29.6% (95% CI: 16.2%-44.4%) for 34 Gy versus 41.1% (95% CI: 26.6%-55.1%) for 48 Gy. Progression-free survival was 19.1% (95% CI: 8.5%-33.0%) versus 33.3% (95% CI: 20.2%-47.0%) for 34 Gy and 48 Gy respectively.
The phase II MD Anderson Cancer Centre trial of SABR with 50 Gy in 4 fractions in inoperable patients showed a 7-year local recurrence of 8% and OS of 47% with 4% grade 3 adverse events.r
A National Cancer Database analysis of 3147 patients with T1-3N0 NSCLC aged 70 or older managed with SABR (258 patients) compared to no treatment (2889 patients) showed improved median survival with SABR compared to observation (29 months versus 10 months, HR 0.64, p <0.001).r
Figure 3. Survival probability
© Cancer 2015r