Introduction
Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide [1]. The lung is one of the most commonly involved sites of distant metastasis, with 5–25% of patients presenting lung metastases at diagnosis [2]. In selected patients with a limited burden of disease, considered oligometastatic disease [3, 4], local ablative treatment is a valid option, where surgical resection is the mainstay therapy. Patients submitted to lung metastasectomy have a survival rate of around 26% at 10 years [5]. For patients with medically inoperable metastases or those that refuse surgery, alternative treatment options include radiofrequency, microwave ablation or stereotactic body radiotherapy (SBRT).
SBRT delivers high ablative doses of radiation in a few fractions. SBRT has been used in the treatment of lung metastases based on good clinical results, limited toxicity and experience obtained from treatment of stage I non-small cell lung cancer [6]. A prospective phase I/II study demonstrated that SBRT is a safe and effective treatment for these patients [7]. Other studies conducted with this group of patients also showed low toxicity and high local control rate [8–11]. There are no defined recommendations regarding selection criteria (patient and disease characteristics) and dose-fractionation schedule.
We intended to evaluate the local control of pulmonary oligometastases from CRC treated with SBRT. Additionally, we expect to study prognostic factors that may influence survival and local control.
Materials and methods
We performed a retrospective review of 109 consecutive patients (173 lesions) with lung metastases from CRC treated with SBRT between January 2013 and December 2020 at our Radiation Oncology Department. Sixteen patients were lost during follow-up, therefore were excluded from this study.
The treatment of each patient was discussed in a multidisciplinary board. SBRT was the treatment of choice for patients: i) not candidate for surgery or refusing surgery; ii) with oligorecurrence/ oligometastatic lung disease (≤ 5 synchronous or metachronous metastases at the time of treatment)4; iii) absence or controlled extrathoracic disease at least in the last 3 months; iv) performance status Eastern Cooperative Oncology Group Criteria (ECOG) ≤ 2 (3, in selected cases). The Institutional Ethics Committee approved this study. The ethical standards displayed in the Declaration of Helsinki (1964) and its later amendments were followed.
All patients underwent a 4-dimensional (4D) pre-treatment planning CT, with a slice thickness of 1.25 mm. Patient was in supine position, with immobilization devices (vacuum cushion and abdominal compression when appropriated). The maximum intensity projection (MIP) was reconstructed from the 10-phase 4D-CT (Ge Advantage 4D, version 4.1). The reconstructed 4D-CT was used to delineate the internal target volume (ITV). Planning treatment volume (PTV) was determined by adding 5 mm in all directions to the ITV. Ninety-five percent of the volume (PTV) was covered by the prescribed dose. Patients were initially treated with image guided 3-dimensional conformal radiation therapy-3DCRT (2014 to 2016 using a Varian Trilogy®) and, more recently, with image-guided volumetric modulated arc therapy (VMAT, using a Varian TrueBeam® STX). 3DCRT was delivered using 6-MV FF photons (10-MV FF in selected lesions), using multiple non-opposing coplanar fields, shaped with a multileaf collimator. VMAT was delivered using 6-MV FFF (10-MV FFF in selected lesions). Position before treatment was verified using an in-room cone-beam CT scan and fluoroscopy with real-time respiratory gating.
The prescribed total dose was 30–34 Gy in a single fraction, 45–50 Gy in 4 fractions or 40–50 Gy in 5 fractions. The dose-fractionation scheme was chosen by a radiation oncologist according to tumor size, location and organs at risk (OARs) dose constraints. Biological effective dose (BED) was calculated using the linear quadratic formula: BED10 = nd[1 + d/(α/β)], where n is the number of fractions, d is the dose/fraction, and α/β ratio = 10 Gy.
After SBRT treatment, patients underwent periodic follow-up, every 3 to 6 months for the first two years and every 6 to 12 months up to five years or until progression. Patients underwent clinical and analytical examination and radiological evaluation.
Treatment response was evaluated mainly by Response Evaluation Criteria in Solid Tumours (RECIST) criteria in computed tomography (CT) scan with contrast. Disease progression was assumed when increase of the dimension of one or more of the treated lesions was observed, or new metastases appeared outside the treatment field (in the lung out-of-field or other organs) [12, 13]. When there was significant uncertainty in CT evaluations due to the confounding effect of radiation pneumonitis, cases were discussed with trained radiologists and, if needed, positron emission tomography (PET)/CT and/or biopsy were requested. Toxicity was evaluated during treatment and follow-up, being classified according to Radiation Therapy Oncology Group (RTOG) toxicity grade [14].
The primary end-point was local control (LC). For secondary end-points, we determined overall survival (OS), progression-free survival (PFS) and analyzed prognostic factors that could influence survival and LC. Local progression-free survival (LPFS) was defined as the time to recurrence in the field (within the initial PTV) or marginal regrowth (radiation field wedge ≥ 50% of dose) after SBRT treatment, regional progression-free survival (RPFS) as the time to occurrence of pulmonary progression out of field (intrathoracic recurrence not contiguous with irradiated area in the same lobe) and distance progression-free survival (DPFS) as the time to occurrence of extra-pulmonary progression [15–17]. Overall survival (OS) was defined as the time from SBRT to death from any cause.
Various possible prognostic factors were analyzed, namely age, sex, primary and metastatic tumor characteristics, RAS status, previous treatments to SBRT, state of oligometastatic disease (synchronous/metachronous), extrapulmonary disease, number of lung metastases, lesion diameter and volume, location of the lesion (central lesion was defined as tumors within 2 cm of the proximal bronchial tree) and biologically effective dose (BED10).
The volume of each individual lesion was calculated using the formula: V = (lengthxwidth2)/2. The total volume of pulmonary metastases for each patient was calculated, through the sum of the volume of all pulmonary metastases treated with SBRT simultaneously.
Survival outcomes were estimated by the Kaplan-Meier method and the differences in survival outcomes were assessed using the log-rank test. Univariate and multivariate Cox proportional hazard analyses were performed to evaluate the effect of different variables on LC, PFS and OS. For multivariate analysis (MVA), we included age, lesion volume, systemic treatment before or after SBRT and any additional variable statistically significant on univariate analysis (UVA). An independent analysis by lesion was also performed. Statistical analysis and data output were conducted using R (R Core Team, 2021), version 4.0.5, with the following packages: “Relsurv”, ”Survival” and “Survminer” [18–20].
Results
A total of 109 patients with 173 metastatic lesions met the inclusion criteria. The patient and tumor characteristics are shown in Table 1. Two-thirds of the patients were male and the median age was 66 years. Sixty-eight patients (62%) presented rectal cancer and 41 patients (38%) had colon cancer as a primary cancer. Systemic treatment was administered previously to SBRT in 87.2% of patients. Thirty-four percent of patients received systemic treatment after SBRT. Thirty-one patients (28.4%) previously developed pulmonary metastasis, having performed other local treatments (metastasectomy or thermoablation) prior to current treatment with SBRT.
|
Characteristics |
Patients, n (% total) |
|
Median age, years [min–max] |
66 [38–87] |
|
≥ 70 years |
43 (39.4%) |
|
Sex |
|
|
Female |
37 (33.9%) |
|
Male |
72 (66.1%) |
|
Primary tumor |
|
|
Rectal |
68 (62.4%) |
|
Colon |
41 (37.6%) |
|
Active primary tumor |
2 (1.83%) |
|
State of oligometastatic disease |
|
|
Synchronous |
17 (15.6%) |
|
Metachronous |
92 (84.4%) |
|
Average nr. of metastases [min–max] |
1.6 [1–5] |
|
1 |
66 (60.5%) |
|
2–3 |
38 (34.9%) |
|
> 3 |
5 (4.6%) |
|
Median of total volume of disease [min–max] |
1.99 [0.11–99.2] |
|
< 1 cc |
33 (30.3%) |
|
1–5 cc |
52 (47.7%) |
|
5–10 cc |
13 (11.9%) |
|
≥ 10 cc |
11 (10.1%) |
|
Nr. of ChT lines before SBRT |
|
|
0 |
14 (12.8%) |
|
1–2 |
69 (63.3%) |
|
≥ 3 |
26 (23.9%) |
|
ChT after SBRT Yes No |
37 (33.9%) 72 (66.1%) |
|
Extrapulmonary disease |
35 (32.1%) |
|
RAS Mutation |
35 (32.1%) |
|
Characteristics |
Lesions, n (% total) |
|
Location of lung metastases |
|
|
Central |
30 (17.3%) |
|
Peripheral |
143 (82.7%) |
|
Median of lesion volume [min-max] |
0.847 [0.080-99.2] |
|
< 1 cc |
93 (53.8%) |
|
1–5 cc |
57 (32.9%) |
|
5–10 cc |
14 (8.1%) |
|
≥ 10 cc |
9 (5.2%) |
|
Median of lesion diameter [min–max] |
14.0 [1.00-59.0] |
|
< 15 mm |
93 (53.8%) |
|
15–25 mm |
55 (31.8%) |
|
≥ 25 mm |
25 (14.4%) |
|
SBRT scheme |
|
|
30 Gy/1 fraction |
96 (55.5%) |
|
50 Gy/4 fractions |
19 (11.0%) |
|
50 Gy/5 fractions |
30 (17.3%) |
|
Others schemes |
28 (16.2%) |
|
BED10 |
|
|
< 100 |
25 (14.5%) |
|
> 100 |
148 (85.5%) |
Sixty-six patients (60.5%) were treated for a single metastasis, 38 patients (35%) for 2 to 3 metastases and 5 patients (4.6%) for > 3 metastases. The median diameter of lung metastasis was 16.0 mm (6.00–57.0). The median volume by lesion was 0.847 cc (0.08–99.2) and the median volume of total pulmonary disease was 1.99 cc (0.113–99.2). Ninety-seven lesions (56.1%) received a total dose of 30 to 34 Gy in a single fraction (BED10 ≥ 120 Gy) and the remaining lesions received a total dose of 40 to 50 Gy in 4 to 5 fractions. Details regarding the dose-fractionation scheme and BED10 are shown in Supplementary File — Table S1.
The median follow-up was 29 months (range: 2.9–84.2 months). At the time of analysis, 38 patients were dead: 35 (32.1%) died of disease progression and 3 (2.75%) died from other causes. Nineteen (17.4%) patients presented local failure, 57 (52.3%) patients, regional progression and 20 (18.3%) patients, distance progression (Supplementary File — Tab. S2).
One and 2-year LPFS rates were 87.6% and 81.0%, respectively. Two-year OS and PFS rates were 85.8% and 30.8%, respectively (Fig. 1). Median OS was 51 months, median PFS was 11.7 months and median LPFS was 23.8 months.
Only one patient experienced grade 2 acute pulmonary toxicity (pneumonitis). No patient presented grade ≥ 3.
In UVA (Tab. 2), the lesion diameter was the only variable marginally significant (p = 0.058) for LC. The volume of pulmonary metastases was associated with worse OS (≥ 5 cc, p = 0.016) and PFS (≥ 10 cc, p = 0.007). The location of the lesion (central, p <0.001) and the BED10 (< 100, p = 0.044) demonstrated significant effect in OS. Systemic treatment before (≥ 3 lines of chemotherapy, p = 0.017) or after SBRT (p = 0.034) and age ≥ 70 years (p = 0.003) were also significant predictive factors for PFS. The volume of pulmonary metastases (≥ 10 cc, p = 0.007) and the age ≥ 70 years (p = 0.002) were also significant predictive factors for RPFS. The volume of pulmonary metastases (p < 0.001) and the extrapulmonary disease (p < 0.001) were associated with poor DPFS. For the remaining tested variables, no effect on survival was found.
|
Univariate analysis |
||||||||||
|
Endpoint |
OS |
LPFS |
RPFS |
DPFS |
PFS |
|||||
|
Clinical variables |
HR (95% CI) |
p-value |
HR (95% CI) |
p-value |
HR (95% CI) |
p-value |
HR (95% CI) |
p-value |
HR (95% CI) |
p-value |
|
Age (< 70 vs. ≥70 y) |
0.88 (0.46–1.70) |
0.705 |
0.74 (0.32–1.73) |
0.488 |
0.39 (0.21–0.70) |
0.002 |
0.85 (0.39–1.85) |
0.687 |
0.47 (0.29–0.75) |
0.002 |
|
Sex (Female vs. Male) |
1.55 (0.76–3.14) |
0.225 |
0.86 (0.38–1.97) |
0.724 |
0.85 (0.49–1.46) |
0.550 |
1.15 (0.52–2.55) |
0.726 |
1.01 (0.63–1.62) |
0.973 |
|
Primary tumor (rectal vs. colon) |
0.81 (0.42–1.59) |
0.547 |
1.21 (0.54–2.73) |
0.647 |
1.07 (0.63–1.83) |
0.793 |
2.13 (1.00–4.56) |
0.051 |
1.41 (0.90–2.21) |
0.138 |
|
State of oligometastatic disease (metachronous vs. synchronous) |
0.52 (0.18–1.46) |
0.214 |
0.94 (0.32–2.75) |
0.911 |
1.46 (0.76–2.82) |
0.259 |
0.61 (0.18–2.04) |
0.425 |
1.37 (0.77–2.44) |
0.289 |
|
Nr. of metastases (1 vs. >1) |
0.83 (0.43–1.60) |
0.577 |
1.15 (0.51–2.56) |
0.740 |
1.43 (0.86–2.41) |
0.171 |
0.79 (0.36–1.74) |
0.563 |
1.13 (0.72–1.78) |
0.583 |
|
Total volume of disease (cc) |
1.06 (1.04–1.08) |
< 0.001 |
1.03 (1.00–1.07) |
0.067 |
1.03 (1.02–1.05) |
< 0.001 |
1.04 (1.02–1.06) |
< 0.001 |
1.05 (1.03–1.07) |
< 0.001 |
|
< 1 vs. ≥ 1 – < 5 |
1.91 (0.70–5.18) |
0.206 |
0.85 (0.30–2.41) |
0.766 |
1.11 (0.58–2.09) |
0.758 |
1.18 (0.47–2.97) |
0.721 |
1.05 (0.61–1.78) |
0.866 |
|
< 1 vs. ≥5 – < 10 |
4.00 (1.29–12.4) |
0.016 |
2.66 (0.86–8.27) |
0.091 |
1.34 (0.57–3.15) |
0.510 |
1.18 (0.30–4.62) |
0.807 |
1.32 (0.64–2.73) |
0.450 |
|
< 1 vs. ≥ 10 |
6.92 (2.28–21.0) |
< 0.001 |
2.36 (0.59–9.47) |
0.226 |
3.17 (1.37–7.31) |
0.007 |
3.10 (0.98–9.88) |
0.055 |
2.83 (1.33–6.02) |
0.007 |
|
Diameter [mm] |
1.07 (1.04–1.10) |
< 0.001 |
1.05 (1.01–1.10) |
0.023 |
1.03 (1.00–1.06) |
0.050 |
1.04 (1.00–1.08) |
0.038 |
1.03 (1.00–1.06) |
0.021 |
|
< 15 vs. 15 – < 25 |
1.86 (0.79–4.41) |
0.16 |
0.33 (0.11–1.05) |
0.060 |
0.91 (0.50–1.66) |
0.757 |
0.97 (0.39–2.38) |
0.940 |
0.89 (0.53–1.49) |
0.663 |
|
< 15 vs. ≥ 25 |
4.46 (1.90–10.49) |
0.005 |
1.93 (0.80–4.66) |
0.146 |
1.33 (0.69–2.55) |
0.395 |
2.18 (0.88–5.41) |
0.092 |
1.47 (0.84–2.58) |
0.177 |
|
Nº of ChT lines before SBRT |
||||||||||
|
0 vs. 1–2 |
0.70 (0.24–2.05) |
0.517 |
0.80 (0.23–2.79) |
0.725 |
2.16 (0.77–6.08) |
0.143 |
1.40 (0.32–6.11) |
0.653 |
1.89 (0.86–4.17) |
0.115 |
|
0 vs. ≥ 3 |
1.33 (0.42–4.25) |
0.631 |
1.30 (0.34–5.04) |
0.702 |
2.84 (0.95–8.43) |
0.061 |
2.58 (0.56–12.0) |
0.225 |
2.84 (1.21–6.67) |
0.017 |
|
M/T before SBRT (No vs. Yes) |
0.95 (0.47–1.94) |
0.895 |
0.32 (0.10–1.09) |
0.068 |
0.90 (0.50–1.63) |
0.738 |
0.53 (0.20–1.41) |
0.206 |
0.79 (0.48–1.32) |
0.371 |
|
ChT after SBRT (No vs. Yes) |
1.13 (0.58–2.18) |
0.724 |
1.74 (0.78–3.89) |
0.176 |
1.52 (0.90–2.56) |
0.115 |
1.55 (0.72–3.30) |
0.361 |
1.63 (1.04–2.55) |
0.034 |
|
Extrapulmonary disease (No vs. Yes) |
0.96 (0.47–1.98) |
0.914 |
0.58 (0.22–1.55) |
0.277 |
1.37 (0.80–2.34) |
0.254 |
5.04 (2.31–11.0) |
< 0.001 |
1.52 (0.95–2.42) |
0.078 |
|
RAS status (mutated vs. wild-type) |
0.8 (0.36–1.79) |
0.586 |
1.83 (0.67–4.99) |
0.240 |
1.05 (0.56–1.95) |
0.878 |
0.73 (0.31–1.73) |
0.472 |
1.03 (0.61–1.76) |
0.903 |
|
Location of lung metastases (central vs. peripheral) |
2.70 (1.56–4.67) |
< 0.001 |
1.60 (0.64–3.95) |
0.313 |
|
|
|
|
|
|
|
BED10 (< 100 vs. ≥ 100) |
0.55 (0.31–0.98) |
0.044 |
0.55 (0.22–1.35) |
0.194 |
|
|
|
|
|
|
|
Multivariate analysis |
||||||||||
|
Age (≥ 70 y) |
|
|
|
|
0.39 (0.21–0.68) |
0.002 |
|
|
0.48 (0.30–0.79) |
0.003 |
|
Total volume of disease (≥ 10 cc) |
|
|
|
|
2.91 (1.27–6.70) |
0.012 |
|
|
2.48 (1.17–5.28) |
0.018 |
|
Nr. of ChT lines before SBRT (≥ 3) |
|
|
|
|
|
|
|
|
2.44 (1.03–5.79) |
0.042 |
|
ChT after SBRT (Yes) |
|
|
|
|
|
|
|
|
1.59 (1.01–2.49) |
0.045 |
|
Extrapulmonary disease (Yes) |
|
|
|
|
|
|
6.05 (2.68–13.7) |
<0.001 |
|
|
|
Location of lung metastases (Central) |
2.23 (1.28–3.90) |
0.005 |
|
|
|
|
|
|
|
|
In MVA, the lesion location (central) remained significantly associated to worse OS [hazard ratio (HR): 2.23], whereas the volume was marginally significant (HR: 1.05). The volume (HR: 2.48), the systemic treatment before or after SBRT (HR: 2.44 and 1.59, respectively) and the age (≥ 70 years, HR: 0.48) were significant prognostic factors for PFS (Tab. 2). Regarding RPFS, the volume of pulmonary metastases (≥ 10 cc, HR: 2.91) and the age (≥ 70 years, HR: 0.48) were significant factors, with impact in regional progression. The presence of extrapulmonary disease (HR: 6.05) was the only variable associated with poor DPFS, in MVA, whereas the volume of pulmonary metastases was marginally significant (HR: 1.05).
Discussion
Local ablative treatment has been applied in the treatment of oligometastatic disease [6]. In recent years, the radiation oncology community has focused on the study of lung oligometastases treated with SBRT [21–28]. Most of the studies showed acceptable toxicity profiles and good outcomes in terms of LC, OS and PFS.
In our study, local failure occurred in 19 patients (17.4%), corresponding to 29 lesions (16.8%). One- and 2-year LPFS rates were 87.6% and 81.0%, respectively, which are in agreement with the literature. Jung et al. [21] obtained a LC rate of 88.7% and 70.6% for 1- and 3-year of follow-up. The Radiotherapy Department of Humanitas Clinical and Research Center presented 1- and 2-year LC rates of 85% and 75%, respectively [22]. A meta-analysis based on 15 studies estimated a 1-, 2- and 3-year LC rates of 81%, 66% and 60%, respectively [23]. Regional progression was the major pattern of failure (52.3% of patients), with a RPFS rate of 61.1%, at 1 year after SBRT. A distance progression was observed in 18.3% of patients, with a 1-year DPFS rate of 83.2%.
The OS and PFS obtained in our study are comparable with published data. OS at 1 and 2 years was 95.4% and 85.8%. One- and 2-year PFS rates were 50.0% and 30.8%, respectively. Filippi et al. [24] obtained a 1- and 2-year OS rates of 84% and 73%, and a PFS of 49% and 27%, respectively. Jung et al. [21] presented similar outcomes with a 3-year OS and PFS rates of 64.0% and 24.0%, respectively. A recent meta-analysis reported a 3-year OS and PFS of 52% and 13%, respectively [23]. In the study conducted by Agolli and collaborators [8], the outcomes were slightly lower with OS and PFS rates at 2 years of 67.7% and 20.3%, respectively.
The analyses of possible prognostic factors with an impact on the survival and LC was conducted through UVA and MVA. In our study, the lesion diameter was the only variable marginally significant (p = 0.058) for LC. These results may be explained by the limited number of events of local progression that occurred in our study. The variables with significant impact in OS were: lesion dimension (diameter ≥25 mm and total volume of pulmonary metastases ≥ 5 cc), its location (central) and the BED10 (< 100). In MVA, the lesion location remained a significant prognostic factor for OS (HR: 2.23), whereas the volume by lesion was marginally significant (HR: 1.05). Jung et al. [21] observed a significantly better OS and LC for patients with a tumor volume ≤ 1.5 mL, than those with a tumor volume >1.5 mL. In their study, the timing to SBRT (first versus second or third metastasis) was also statistically a significant prognostic factor for LC, whereas a dose of 60 Gy showed a trend towards better LC. Kim et al. [25] also described ITV as a prognostic factor for LC. Tumor dimension was the only predictor of LC in two other studies [26, 27]. In the study conducted by Comito and co-works [22], a correlation was observed between GTV dimensions (> 3 cm) and OS, but not with LC.
As mentioned above, BED10 and lesion location were predictive factors for OS in the UVA, with a worst OS in patients with lesions sited centrally and the ones treated with a BED10 < 100. These two variables were probably related, as the central lesions frequently require the reduction of total dose and the use of more fractionated schemes, with a common decrease of BED10. A large retrospective analysis of centrally located lung tumors, stage I NSCLC, found a statistically significant association with a BED10 ≥100 Gy [28]. Ohri and collaborators [29] collected the results of 30 articles regarding the treatment of liver lesions with SBRT and also observed a significant improvement in the outcomes for liver metastases treated with a BED10 ≥ 100 Gy (3 years LC of 93%) compared to a BED10 < 100 Gy (3 years LC of 65%).
Systemic treatment, namely chemotherapy, is a part of the treatment of metastatic disease, as initial or as consolidation treatment. In our study the systemic treatment before or after SBRT was correlated with a poor PFS. This is perhaps explained by the selection of patients with different tumor characteristics, including those with a more aggressive or higher disease burden; therefore, having a higher risk of disease progression and more frequently requiring systemic treatment. Qiu et al. [27] also identified chemotherapy before or after SBRT as a significant prognostic factor for OS in UVA.
In our study, another variable was associated with a poor PFS, namely the total volume of pulmonary metastases, which was also a significant prognostic factor for RPFS. Agolli et al. [8], observed a worse PFS and metastases-free survival in patients with multiple lung metastases and synchronous oligometastatic disease.
Regarding DPFS, extrapulmonary disease was the most important prognostic factor for distance progression. In the study conducted by Qiu et al. [27] extra-pulmonary disease at the time of initial metastases or at the time of SBRT was an independent predictor of OS, PFS and distant metastases-free survival. Comito et al. [22], on the other hand, did not observe a correlation between the presence of extra-pulmonary disease and survival outcomes.
Age (≥ 70 years) was related to longer PFS and RPFS. This may be related to a slower growth of cancer in the elderly age [30]. Moreover, older patients are more frequently non-candidates for systemic treatment and SBRT is offered earlier to these patients. Younger patients usually present more aggressive and advanced colorectal cancer disease compared to older patients [31]. However, the impact on the OS rate does not seem proportionally worse. O’Connell et al. [32] observed an equivalent 5-year cancer-specific survival between younger and older patients (60–80 years). In another study, UVA showed 5- and 10-year OS rates lower in younger patients, but age was not an independent prognostic factor in the MVA [33].
Several studies reported low pulmonary toxicity by SBRT, considering it a safe treatment. According to some clinical trials, 10% to 15% of patients experience symptomatic radiation-induced toxicities (RILT) [34, 35]. In our study, the treatment was well tolerated, with one grade 2 and no grade 3 acute pulmonary toxicity (pneumonitis) recorded. Other studies also described reduced side effects for lung SBRT. Agolli [8], Jung [21] and Kobayashi [36] did not observe grade 3 toxicity in their studies. Liu et al. [35] observed grade 2 radiation pneumonitis in 9.7% of patients and grade 3 in 5% of them. Liu and co-authors evaluated possible risk factors for symptomatic radiation pneumonitis after SBRT. History of respiratory comorbidity, previous thoracic radiation, right lung location, mean lung doses of total or ipsilateral lung, and total lung volume receiving 20 Gy were related to significant risk of grade 2 radiation pneumonitis. In a polled analysis of 88 studies of lung SBRT, V20 was associated with risk of grade ≥ 2 RITL [37]. Another study showed that the grade ≥ 2 of radiation pneumonitis was best predicted by a composite lung V35 of ≥ 6.5% [38]. The Mayo Clinic study also performed a dosimetric analysis, but they did not find correlations between dosimetric factors (V5, V10, V20, V40 or MLD) and the development of radiation pneumonitis [39].
This is one of the largest cohorts of patients with CRC lung oligometastases treated with SBRT ever published. It is a retrospective study and, therefore, has some inherent limitations, namely different treatments previous to SBRT and different dose-fractionation schemes. We observed a good LC in our study, with a 2 years LPFS rate of 81.0%, which is in agreement with published data. Our data was also roughly comparable to surgery outcomes [40], with a 1-year OS rates of 95.4% and 88–96%, respectively. Furthermore, SBRT is a feasible and safe modality, with no grade ≥ 3 toxicity recorded in our data.
Conflict of interests
Authors declare no conflict of interests.
Funding
This publication was prepared without any external source of funding.
Disclosure
The authors report no conflicts of interest.