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survival even though its toxicity rate is well below that of morbidity rates after surgery. Outcomes of 772
early stage NSCLC patients treated with 50 Gy/4 fractions (12.5 Gy per fraction) of SBRT, or in cases
of central lesions, 70 Gy/10 fractions (7 Gy per fraction), were analyzed to verify safety in the elderly
population. It was found that the elderly group had no significant difference in PFS, OS and toxicity
compared to the patients younger than 75. After a median follow-up of 55 months, the cumulative
incidence of loco-regional failure was 17.3%. The 1-, 3- and 5-year OS rates for patients ≥ 75 years were
86%, 57.5% and 39.5%, respectively. No Grade 4-5 toxicity was registered, and Grade 3 toxicity rate was
[25]
comparable (ranging around 1-2%): the group of patients older than 75 did not differ from others . SBRT
can thus be very safely and effectively utilized in patients older than 80 for Stage I tumors at a median
ablative dose (BED ≥ 100 Gy) of 54 Gy/3 fractions (18 Gy per fraction) with 1- and 2-year LC rate of 100%
[26]
and 92.3%, and no reported toxicity Grade 2-5 . An observational study reviewed 58 consecutive patients
≥ 80 years who received SBRT for early-stage NSCLC. Overall, the 3-year OS rate was 56.4%, suggesting the
efficacy of SBRT; patients with Karnofsky performance status ≥ 75 had improved 3-year CSS and OS rates
[27]
(99.4% and 91.9%, compared to 47.8% and 23.6% in patients with KPS < 75, respectively) .

Oncological outcomes and toxicity rates were analyzed in NSCLC Stage I patients older than 90 years
and treated with SBRT at a dose of 50 Gy/5 fractions daily (10 Gy per fraction). Nineteen patients were
identified: the median age was 91.6 years, the median tumor size was 2.1 cm, and 31.6% were central
[28]
lesions. Two-year rates of local failure and OS were 5.6%, and 47.8%; no Grade 3 toxicity was registered .
SBRT vs. surgery
SBRT is a noninvasive, well-tolerated ablative treatment perceived as an attractive option even for patients
who are potentially fit for surgery. For this reason, three randomized clinical trials (ROSEL, STARS,
ACOSOG Z4099) have been launched to compare SBRT with lobectomy in patients deemed medically
operable. Each of this trial has been closed prematurely because of scarce accrual of results, although a
pooled analysis of the ROSEL and STARS trials reported reduced morbidity and no inferior OS and PFS
of SBRT compared to lobectomy. The estimated 3-year OS rate was 95% for SBRT vs. 79% in the surgical
group (HR = 0.14, 95%CI: 0.017-1.19). It must be emphasized that the small sample size is such that this
[29]
data not reliable . Retrospective studies reported comparisons amongst similar groups of patients treated
with surgery or SBRT, even though most authors reported unmatched baseline characteristics. Patients
treated with surgery were more likely to be fit, younger, healthier, and have more favorable lung function;
on the other hand, the SBRT group proportionally had more T1 tumors.

[30]
According to the American Society of Clinical Oncologists , for patients with standard operative risk
(1.5% mortality rate) and Stage I NSCLC, SBRT is not recommended as an alternative to surgery outside
clinical trials. The standard operative risk reached 4.4% in patients aged 81 years or more, even though age,
sex, cardiovascular and pulmonary comorbidities, and patients’ functional status are factors influencing
peri-operative risk.

SBRT vs. lobar resection
Lobectomy represents the standard of care for early stage lung cancer with 3- and 5-years OS rate of
approximately 82% and 66%, respectively. The minimally invasive approach (video-assisted thoracoscopic
surgery) has showed non-inferior results in survival and fewer peri-operative complications and morbidity
[31]
compared to open lobectomy . In the absence of clinical trials, more reliable data has come from a meta-
analysis of propensity score-matched analysis comparing lobectomy to SBRT. OS rate at 1 year was similar
among groups, but data favored surgery at 3 years. Nevertheless, CSS rates were comparable in both arms,
[32]
which indicates that SBRT patients may be less healthy and die of non-cancer causes . A systematic
review investigated the efficacy of both SBRT and lobectomy for Stage I-II disease and found no difference
in 1-year survival rate. However,, long-term results indicate a benefit of lobectomy over SBRT: lobectomy