1Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul, Korea
2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Copyright © 2023 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
This study was conducted in accordance with the 1964 Declaration of Helsinki. This study was approved by the Institutional Review Board of Asan Medical Center (#2022-1153), and written informed consent was waived due to the retrospective nature of this study.
Author Contributions
Conceived and designed the analysis: Jang JY, Kim SS.
Collected the data: Jang JY, Kim SS.
Contributed data or analysis tools: Jang JY, Kim SS, Song SY, Shin YS, Lee SW, Ji W, Choi CM, Choi EK.
Performed the analysis: Jang JY, Kim SS.
Wrote the paper: Jang JY.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Variable | No. (%) (n=89) |
---|---|
Age (yr), median (range) | 72 (45–90) |
Sex | |
Male | 49 (55.1) |
Female | 40 (44.9) |
ECOG PS | |
0 | 14 (15.7) |
1 | 61 (68.5) |
2 | 13 (14.6) |
3 | 1 (1.1) |
Underlying lung diseasea) | |
Yes | 13 (14.6) |
No | 76 (85.4) |
Smoking status | |
Never-smoker | 53 (59.6) |
(Ex-) Smoker | 36 (40.5) |
Pulmonary function test, median (range) | |
FVC (%) | 83 (50–129) |
FEV1 (L) | 2.04 (0.51–3.70) |
FEV1 (%) | 79 (33–121) |
DLCO (%) | 76 (34–113) |
Past history of lung cancer | |
Yes | 51 (57.3) |
Surgery for previous lung cancer | 47 (52.8) |
SBRT for previous lung cancer | 2 (2.2) |
Both surgery and SBRT for previous lung cancer | 2 (2.2) |
No | 38 (42.7) |
No. of tumors, median (range) | 1 (1–4) |
Single primary lung cancer | 72 (80.9) |
Multiple primary lung cancer | 17 (19.1) |
Treatment for multiple primary lung cancer | |
SBRT only | 13 (76.5) |
SBRT+observation | 2 (11.8) |
SBRT+operation | 2 (11.8) |
DLCO, diffusing capacity of the lung for carbon monoxide; ECOG PS, Eastern Cooperative Oncology Group performance status; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; SBRT, stereotactic body radiotherapy.
a) The underlying lung diseases include chronic obstructive pulmonary disease, asthma, and interstitial lung disease. The sum of percentages may not be 100, rounded to one decimal place.
Variable | No. (%) (n=99a)) |
---|---|
Biopsy for diagnosis | |
Yes | 44 (44.4) |
No | 55 (55.6) |
Reason for unproven pathology | |
Lesion close to blood vessels | 19 (34.5) |
Deeply located lesions that are difficult to access | 10 (18.2) |
Lesions that are too small to obtain a sufficient sample | 9 (16.4) |
Clinically diagnosable lesions through follow-up images | 17 (30.9) |
Ground-glass opacity nodules | |
Pure ground-glass opacity nodules | 43 (43.4) |
Subsolid nodules | 56 (56.6) |
Location of tumorb) | |
Central tumor | 5 (5.1) |
Peripheral tumor | 94 (94.9) |
Tumor size | |
Maximum tumor diameter (mm), median (range) | 15.7 (5.7–45.0) |
Maximum consolidation diameter (mm), median (range) | 4.5 (0.0–16.0) |
Consolidation-to-tumor ratio, median (range) | 0.3 (0.0–0.5) |
T category (AJCC eighth edition) | |
cTis | 43 (43.4) |
cT1mi | 8 (8.1) |
cT1a | 33 (33.3) |
cT1b | 14 (14.1) |
cT1c | 1 (1.0) |
SBRT dose, median (range) | |
Total dose (Gy) | 56.0 (48.0–60.0) |
Fraction size (Gy) | 14 (10–15) |
BED (Gy10)c) | 134.4 (105.6–150.0) |
PTV size (cm3) | 10.9 (4.1–56.7) |
PTV margin from ITV (mm) | 5.0 (3.0–8.0) |
AJCC, American Joint Committee on Cancer; BED, biologically effective dose; ITV, internal target volume; PTV, planning target volume; SBRT, stereotactic body radiotherapy.
a) Seventy-two patients with a single lesion were treated for each lesion corresponding to 72 cases. Of the 17 patients with multiple lesions, 10 patients treated with SBRT for two ground glass nodules simultaneously, three patients with SBRT for all the multiple lesions (but with only one lesion included in the analysis due to inclusion criteria regarding the consolidation to tumor ratio), and four patients with SBRT to only one lesions, corresponding to total 27 cases totally - all together making 99 cases,
b) As defined by RTOG 0236, lesions within 2 cm of the proximal bronchial tree were classified as central tumors and lesions outside of them were classified as peripheral tumors,
c) Biologically effective doses are calculated using an α/β ratio of 10 Gy. The sum of percentages may not be 100, rounded to one decimal place.
Patient characteristics
Variable | No. (%) (n=89) |
---|---|
Age (yr), median (range) | 72 (45–90) |
Sex | |
Male | 49 (55.1) |
Female | 40 (44.9) |
ECOG PS | |
0 | 14 (15.7) |
1 | 61 (68.5) |
2 | 13 (14.6) |
3 | 1 (1.1) |
Underlying lung disease | |
Yes | 13 (14.6) |
No | 76 (85.4) |
Smoking status | |
Never-smoker | 53 (59.6) |
(Ex-) Smoker | 36 (40.5) |
Pulmonary function test, median (range) | |
FVC (%) | 83 (50–129) |
FEV1 (L) | 2.04 (0.51–3.70) |
FEV1 (%) | 79 (33–121) |
DLCO (%) | 76 (34–113) |
Past history of lung cancer | |
Yes | 51 (57.3) |
Surgery for previous lung cancer | 47 (52.8) |
SBRT for previous lung cancer | 2 (2.2) |
Both surgery and SBRT for previous lung cancer | 2 (2.2) |
No | 38 (42.7) |
No. of tumors, median (range) | 1 (1–4) |
Single primary lung cancer | 72 (80.9) |
Multiple primary lung cancer | 17 (19.1) |
Treatment for multiple primary lung cancer | |
SBRT only | 13 (76.5) |
SBRT+observation | 2 (11.8) |
SBRT+operation | 2 (11.8) |
DLCO, diffusing capacity of the lung for carbon monoxide; ECOG PS, Eastern Cooperative Oncology Group performance status; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; SBRT, stereotactic body radiotherapy.
a)The underlying lung diseases include chronic obstructive pulmonary disease, asthma, and interstitial lung disease. The sum of percentages may not be 100, rounded to one decimal place.
Characteristics of lesions after SBRT
Variable | No. (%) (n=99 |
---|---|
Biopsy for diagnosis | |
Yes | 44 (44.4) |
No | 55 (55.6) |
Reason for unproven pathology | |
Lesion close to blood vessels | 19 (34.5) |
Deeply located lesions that are difficult to access | 10 (18.2) |
Lesions that are too small to obtain a sufficient sample | 9 (16.4) |
Clinically diagnosable lesions through follow-up images | 17 (30.9) |
Ground-glass opacity nodules | |
Pure ground-glass opacity nodules | 43 (43.4) |
Subsolid nodules | 56 (56.6) |
Location of tumor | |
Central tumor | 5 (5.1) |
Peripheral tumor | 94 (94.9) |
Tumor size | |
Maximum tumor diameter (mm), median (range) | 15.7 (5.7–45.0) |
Maximum consolidation diameter (mm), median (range) | 4.5 (0.0–16.0) |
Consolidation-to-tumor ratio, median (range) | 0.3 (0.0–0.5) |
T category (AJCC eighth edition) | |
cTis | 43 (43.4) |
cT1mi | 8 (8.1) |
cT1a | 33 (33.3) |
cT1b | 14 (14.1) |
cT1c | 1 (1.0) |
SBRT dose, median (range) | |
Total dose (Gy) | 56.0 (48.0–60.0) |
Fraction size (Gy) | 14 (10–15) |
BED (Gy10) |
134.4 (105.6–150.0) |
PTV size (cm3) | 10.9 (4.1–56.7) |
PTV margin from ITV (mm) | 5.0 (3.0–8.0) |
AJCC, American Joint Committee on Cancer; BED, biologically effective dose; ITV, internal target volume; PTV, planning target volume; SBRT, stereotactic body radiotherapy.
a)Seventy-two patients with a single lesion were treated for each lesion corresponding to 72 cases. Of the 17 patients with multiple lesions, 10 patients treated with SBRT for two ground glass nodules simultaneously, three patients with SBRT for all the multiple lesions (but with only one lesion included in the analysis due to inclusion criteria regarding the consolidation to tumor ratio), and four patients with SBRT to only one lesions, corresponding to total 27 cases totally - all together making 99 cases,
b)As defined by RTOG 0236, lesions within 2 cm of the proximal bronchial tree were classified as central tumors and lesions outside of them were classified as peripheral tumors,
c)Biologically effective doses are calculated using an α/β ratio of 10 Gy. The sum of percentages may not be 100, rounded to one decimal place.
Patients with regional recurrence or distant metastasis
Patient No. | |||||
---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | |
Sex/Age (yr) | M/59 | M/77 | M/74 | M/75 | F/76 |
ECOG PS | 0 | 1 | 1 | 2 | 1 |
Previous lung cancer stage | pT2aN0M0 | pT3N0M0 | pT2aN0M0 | pT1bN0M0 | pT2aN0M0 |
TNM stage | cTisN0M0 | cT1aN0M0 | cTisN0M0 | cT1aN0M0 | cT1aN0M0 |
No. of nodules | 1 | 1 | 1 | 1 | 1 |
GGN type | Pure GGN | Subsolid nodule | Pure GGN | Subsolid nodule | Subsolid nodule |
Pathologic confirmation | No | No | No | Yes | Yes |
Regional recurrence | Same lobe lung mass and both hilar LN | Same lobe lung mass and ipsilateral hilar LN | Ipsilateral lung mass | - | - |
Distant metastasis | Abdominal LN | - | - | Pleural seeding | Pleural seeding |
Salvage treatment | Systemic therapy | Systemic therapy | Surveillance | Systemic therapy | Systemic therapy |
ECOG PS, Eastern Cooperative Oncology Group performance status; GGN, ground-glass opacity nodule; LN, lymph node; TNM, tumor–node–metastasis.
Factors influencing disease-free survival and overall survival rates after stereotactic body radiotherapy
Variable | Univariate analysis | Comparison group | |||
---|---|---|---|---|---|
| |||||
Disease-free survival | Overall survival | ||||
|
| ||||
HR (95% CI) | p-value | HR (95% CI) | p-value | ||
Male sex | 3.398 (0.379–30.471) | 0.274 | 6.831 (0.837–55.736) | 0.073 | Female |
| |||||
Age | 1.028 (0.926–1.421) | 0.602 | 1.214 (1.086–1.356) | 0.001 | (Continuous) |
| |||||
ECOG PS, 2–3 | 1.842 (0.204–16.634) | 0.587 | 4.079 (0.967–17.204) | 0.056 | 0–1 |
| |||||
Underlying lung disease, yes | 1.392 (0.155–12.466) | 0.768 | 2.032 (0.410–10.078) | 0.385 | No |
| |||||
Smoking, (Ex-)smoker | 2.246 (0.375–13.459) | 0.376 | 2.621 (0.624–11.015) | 0.188 | Never-smoker |
| |||||
FVC (%) | 1.001 (0.947–1.059) | 0.961 | 0.952 (0.907–1.000) | 0.050 | (Continuous) |
| |||||
FEV1 (L) | 1.027 (0.287–3.678) | 0.968 | 0.679 (0.230–2.008) | 0.484 | (Continuous) |
| |||||
FEV1 (%) | 0.992 (0.948–1.037) | 0.716 | 0.745 (0.957–1.032) | 0.745 | (Continuous) |
| |||||
DLCO (%) | 1.016 (0.965–1.070) | 0.544 | 0.933 (0.892–0.976) | 0.003 | (Continuous) |
| |||||
Metachronous lung cancer, yes | 45.429 (0.027–76,854.241) | 0.314 | 0.494 (0.117–2.080) | 0.336 | No |
| |||||
Multiple primary lung cancer, yes | 28.060 (0.002–403,571.066) | 0.495 | 0.561 (0.069–4.563) | 0.589 | No |
| |||||
Biopsy-proven lung cancer | 1.073 (0.179–6.438) | 0.939 | 0.146 (0.660–16.329) | 0.146 | Unproven |
| |||||
Pure ground-glass nodule | 0.732 (0.122–4.383) | 0.732 | 2.682 (0.541–13.310) | 0.227 | Subsolid nodule |
CI, confidence interval; DLCO, diffusing capacity of the lung for carbon monoxide; ECOG PS, Eastern Cooperative Oncology Group performance status; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HR, hazard ratio.
Acute and late toxicities after stereotactic body radiotherapy
Event | No. of patients (%) | |||
---|---|---|---|---|
Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
Acute toxicities | ||||
Fatigue | 8 (9.0) | 0 | 0 | 0 |
Cough | 0 | 1 (1.1) | 0 | 0 |
Sputum | 0 | 1 (1.1) | 0 | 0 |
Nausea | 1 (1.1) | 0 | 0 | 0 |
Late toxicities | ||||
Radiation pneumonitis | 73 (82.0) | 5 (5.6) | 0 | 0 |
Rib fracture | 1 (1.1) | 3 (3.4) | 0 | 0 |
Sputum | 1 (1.1) | 0 | 0 | 0 |
DLCO, diffusing capacity of the lung for carbon monoxide; ECOG PS, Eastern Cooperative Oncology Group performance status; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; SBRT, stereotactic body radiotherapy. The underlying lung diseases include chronic obstructive pulmonary disease, asthma, and interstitial lung disease. The sum of percentages may not be 100, rounded to one decimal place.
AJCC, American Joint Committee on Cancer; BED, biologically effective dose; ITV, internal target volume; PTV, planning target volume; SBRT, stereotactic body radiotherapy. Seventy-two patients with a single lesion were treated for each lesion corresponding to 72 cases. Of the 17 patients with multiple lesions, 10 patients treated with SBRT for two ground glass nodules simultaneously, three patients with SBRT for all the multiple lesions (but with only one lesion included in the analysis due to inclusion criteria regarding the consolidation to tumor ratio), and four patients with SBRT to only one lesions, corresponding to total 27 cases totally - all together making 99 cases, As defined by RTOG 0236, lesions within 2 cm of the proximal bronchial tree were classified as central tumors and lesions outside of them were classified as peripheral tumors, Biologically effective doses are calculated using an α/β ratio of 10 Gy. The sum of percentages may not be 100, rounded to one decimal place.
ECOG PS, Eastern Cooperative Oncology Group performance status; GGN, ground-glass opacity nodule; LN, lymph node; TNM, tumor–node–metastasis.
CI, confidence interval; DLCO, diffusing capacity of the lung for carbon monoxide; ECOG PS, Eastern Cooperative Oncology Group performance status; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HR, hazard ratio.