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 OS rates of 60%-70%.
SABR versus conventional RT
The phase 3 multicentre Australian TROG/ALTG randomised trial (CHISEL) involved 101 patients comparing 54Gy in 3 fractions or 48Gy in 4 fractions if the tumour was within 2 cm from the chest wall with 66Gy in 33 fractions or 50Gy 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 2 multicentre Scandinavian randomised trial (SPACE) involved 102 patients comparing 66Gy in 3 fractions prescribed to the isocentre over one week with 70Gy 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 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 vs conventional RT was 86.4% vs 85.7%. Any grade pneumonitis was 19% vs 34%, with oesophagitis 8% vs 30%. Quality of life evaluation showed worse dyspnoea, chest pain and cough with 3DCRT compared to SBRT which lasted over time.
A systematic review and meta-analysis of 87 SABR and 24 non-SABR articles showed improved 2-year (70.9% vs 47.0%) and 3-year (60.1% vs 37.3%) OS with SABR, with similar incidence of pneumonitis (11% vs 13.8%) and less oesophagitis (<1% vs 15.1%).r
The phase 2 multicentre RTOG 0236 trial of SABR with 54Gy in 3# 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 2 MD Anderson Cancer Centre trial of SABR with 50Gy 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 vs 10 months, HR 0.64, p-value <0.001).r
Figure 3. Survival probability
© Cancer 2015r