Progression of Pulmonary Function and Correlation with Survival Following Stereotactic Body Radiotherapy of Central and Ultracentral Lung Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Pulmonary Function Parameters
2.2. Overall Survival
3. Discussion
3.1. Central vs. Peripheral SBRT
3.2. Clinical and Dosimetry Correlation
3.3. Overall Survival
3.4. Limitations and Strenghts
4. Materials and Methods
4.1. Patients
4.2. Radiation Treatment
4.3. Follow-Up
4.4. Statistics
4.5. Ethics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Pulmonary _Function Parameter | Baseline (n = 107) | 6 Months (n = 73) | 12 Months (n = 55) |
---|---|---|---|
FEV1s [l] (Δ baseline) | 1.7 ± 0.8 (0) | 1.5 ± 0.6 (−0.2 ± 0.3) | 1.5 ± 0.6 (−0.2 ± 0.3) |
β estimate [l/6 months] | β = −0.1 [−0.2–−0.1], p = 2 × 10−9 | ||
FEV1s [% predicted] (Δ baseline) | 69.5 ± 26.5 (0) | 61.9 ± 21.1 (−8.5 ± 12.6) | 60.8 ± 22.9 (−7.7 ± 12.4) |
β estimate [%/6 months] | β = −4.4 [−6.0–−2.9], p = 1 × 10−8 | ||
VC [l] (Δ baseline) | 2.8 ± 1.0 (0) | 2.6 ± 1.0 (−0.2 ± 0.5) | 2.5 ± 0.9 (−0.3 ± 0.5) |
β estimate [l/6 months] | β = −0.2 [−0.2–−0.1], p = 6 × 10−8 | ||
VC [% predicted] (Δ baseline) | 85.6 ± 20.4 (0) | 77.6 ± 18.4 (−7.8 ± 14.9) | 76.3 ± 19.9 (−9.4 ± 14.5) |
β estimate [%/6 months] | β = −5.1 [−6.9–−3.3], p = 2 × 10−8 | ||
FEV1s/VC [%] (Δ baseline) | 61.5 ± 16 (0) | 61.3 ± 16.0 (−0.9 ± 6.1) | 60.9 ± 16.6 (0.5 ± 6.8) |
β estimate [l%/6 months] | β = 0.1 [−0.7–0.8], p = 0.89 |
Fixed Effects | VC [% Predicted] | FEV1s [% Predicted] | ||
---|---|---|---|---|
β [95% CI] | p-Value | β [95% CI] | p-Value | |
Age (1 year) | 0 [−0.4–0.4] | 0.98 | 0 [−0.5–0.4] | 0.91 |
Time (6 months) | −14.2 [−26.4–−1.9] | 0.02 | −9.8 [−23.4–−2.4] | 0.02 |
Age Time | 0.1 [0–0.3] | 0.14 | 0.1 [0–0.3] | 0.11 |
CCI (1 point) | −1.5 [−3.6–0.6] | 0.15 | −3.1 [−5.7–−0.6] | 0.02 |
Time (6 months) | −4.9 [−9.6–0.2] | 0.04 | −5.7 [−10.3–−2.4] | 2 × 10−3 |
CCI Time | 0 [−1.1–1.0] | 0.93 | 0.2 [−0.4–1.3] | 0.31 |
Localization (central) | 6.0 [−1.4–13.5] | 0.11 | 7.5 [−1.8–16.8] | 0.12 |
Time (6 months) | −5.3 [−7.6–−3.0] | 6 × 10−6 | −4.5 [−6.4–−2.5] | 1 × 10−5 |
Localization • Time | 0.6 [−3.0–4.2] | 0.75 | −1.1 [−3.0–3.1] | 0.97 |
Following ST (none) | −0.3 [−10.4–9.8] | 0.95 | 6.3 [−6.3–18.9] | 0.33 |
Time (6 months) | −5.0 [−7.1–−2.8] | 5 × 10−6 | −4.0 [−5.8–−2.2] | 2 × 10−5 |
Following ST Time | −0.3[−5.0–4.5] | 0.91 | −1.3 [−5.6–2.5] | 0.45 |
Pneumonitis (none) | 3.8 [−7.0–14.5] | 0.49 | 6.8 [−17.8–15.8] | 0.32 |
Time (6 months) | −5.1 [−7.1–−3.2] | 1 × 10−7 | −4.4 [−6.1–−2.9] | 1 × 10−7 |
Pneumonitis Time | 0.4 [−4.9–5.7] | 0.88 | −0.2[−4.1–5.0] | 0.94 |
Local Progression (none) | 5.1 [−8.3–18.6] | 0.46 | −1.0 [−20.5–15.8] | 0.91 |
Time (6 months) | −5.1 [−7.0–−3.2] | 2 × 10−7 | −4.5 [−6.6–−3.1] | 7 × 10−8 |
Local Progression Time | −0.3 [−5.6–5.0] | 0.88 | 0.4 [−3.3–6.7] | 0.85 |
PBT Max (10 Gy) | 0.4 [−0.4–1.2] | 0.33 | 0.1 [−0.9–1.1] | 0.82 |
Time (6 months) | 2.6 [−2.7–7.9] | 0.34 | 0.5 [−4.2–5.2] | 0.82 |
PBT Max Time | −0.6 [−1.0–−0.2] | 3 × 10−3 | −0.4 [−0.7–0] | 0.03 |
Total Lung Mean (10 Gy) | 14.2 [5.7−22.6] | 1 × 10−3 | 21.0 [10.6–31.4] | 8 × 10−5 |
Time (6 months) | −0.2 [−5.0–4.7] | 0.95 | −1.1 [−5.2–3.0] | 0.61 |
Total Lung Mean Time | −4.8 [−9.2–−0.4] | 0.03 | −3.1 [−6.8–0.6] | 0.10 |
PTV Size (10 cm³) | 0.6 [0.1–1.0] | 0.01 | 0.6 [0.1–1.2] | 0.03 |
Time (6 months) | −3.5 [−6.4–−0.7] | 0.02 | −3.6 [−6.1–−1.1] | 5 × 10−3 |
PTV Time | −0.1 [−0.4–0.1] | 0.16 | −0.1 [−0.3–0.1] | 0.31 |
Time (6 months) | 6.7 [0.1–13.4] | 0.05 | 0.6 [−4.1–5.3] | 0.80 |
CCI (1 point) | −−− | −−− | −2.8 [−5.3–−0.4] | 0.02 |
PBT Max Time (10 Gy • 6 months) | −0.5 [−0.9–−0.2] | 5 × 10−3 | −0.4 [−0.7–0] | 0.03 |
PTV Size (10 cm³) | 0.3 [−0.2–0.8] | 0.18 | 0.2 [−0.4–0.9] | 0.44 |
Total Lung Mean (10 Gy) | 10.3 [0.4–20.1] | 0.04 | 13.6 [2.0–5.2] | 0.02 |
Total Lung Mean Time (10 Gy • 6 months) | −4.6 [−8.9–−0.2] | 0.04 | −−− | −−− |
Univariate | ||
---|---|---|
Pulmonary Function Parameter | HR (95% CI) | p-Value |
FEV1s [l] | 0.93 (0.64–1.37) | 0.73 |
FEV1s [% pred] | 0.99 (0.98–1.0) | 0.03 |
VC [l] | 1.22 (0.92–1.62) | 0.18 |
VC [% pred] | 0.99 (0.98–1.01) | 0.34 |
FEV1s/VC [%] | 0.98 (0.96–1.0) | 0.01 |
Δ FEV1s (0–6 months) [l] | 1.25 (0.39–3.97) | 0.71 |
Δ FEV1s (0–6 months) [% pred] | 1.02 (0.99–1.04) | 0.29 |
Δ FEV1s (0–12 months) [l] | 0.40 (0.13–1.26) | 0.12 |
Δ FEV1s (0–12 months) [% pred] | 0.99 (0.96–1.01) | 0.30 |
Δ FEV1s (6–12 months) [l] | 0.02 (0–0.21) | 1 × 10-3 |
Δ FEV1s (6–12 months) [% pred] | 0.91 (0.86–0.97) | 4 × 10-3 |
Δ VC (0–6 months) [l] | 0.951 (0.48–1.87) | 0.88 |
Δ VC (0–6 months) [% pred] | 1.0 (0.98–1.02) | 0.81 |
Δ VC (0–12 months) [l] | 0.35 (0.17–0.74) | 6 × 10−3 |
Δ VC (0–12 months) [%pred] | 0.97 (0.95–1.0) | 0.03 |
Δ VC (6–12 months) [l] | 0.30 (0.15–0.63) | 1 × 10−3 |
Δ VC (6–12 months) [%pred] | 0.95 (0.92–0.98) | 1 × 10−3 |
Δ FEV1s/VC (0–6 months) [%] | 1.03 (0.98–1.09) | 0.19 |
Δ FEV1s/VC (0–12 months) [%] | 1.02 (0.97–1.07) | 0.42 |
Δ FEV1s/VC (6–12 months) [%] | 1.0 (0.95–1.06) | 0.93 |
Multivariate | ||
FEV1s/VC [%] | 1.0 (0.95–1.05) | 0.86 |
FEV1s [% pred] | 0.97 (0.94–1.0) | 0.09 |
Δ FEV1s (6–12 months) [% pred] | 0.90 (0.84–0.97) | 6 × 10−3 |
Δ VC (0–12 months) [% pred] | 0.95 (0.91–0.98) | 4 × 10−3 |
Δ VC (6–12 months) [% pred] | 1.0 (0.95–1.05) | 0.94 |
Patient Characteristics | |
---|---|
Age (years) | |
Mean ± SD | 71.6 ± 10.4 |
Sex | |
Male | 52 |
Female | 55 |
CCI | |
Median (IQR) | 4 (3–5) |
Localization | |
Central | 62 |
Ultracentral | 45 |
Tumor Entity | |
NSCLC | 88 |
PET Positive Lung Nodule * | 12 |
Extrapulmonary Primary | 7 |
SBRT Target | |
Primary | 68 |
Local Recurrence | 20 |
Lung Metastasis | 19 |
Systemic Therapy during Follow-Up | |
Chemotherapy | 8 |
Checkpoint Inhibition | 6 |
Chemotherapy + Checkpoint Inhibition | 1 |
Other | 4 |
None | 74 |
Unknown | 14 |
Maximum BED3 in PBT | |
Mean ± SD | 115.7 ± 49.2 |
Mean BED3 in Total Lung | |
Mean ± SD | 10.1 ± 4.4 |
PTV Size (cm³) | |
Mean ± SD | 105.0 ± 84.0 |
PFT Time Intervals (days) | |
Δ Baseline–SBRT Start (Mean ± SD) | −42 ± 30 |
Δ SBRT Start–1st Follow-Up (Mean ± SD) | 182 ± 37 |
Δ SBRT Start–2nd Follow-Up (Mean ± SD) | 359 ± 45 |
Pneumonitis during Follow-Up | |
II° | 10 |
III° | 5 |
Local Progression during Follow-Up | 9 |
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Regnery, S.; Eichkorn, T.; Weykamp, F.; Held, T.; Dinges, L.-A.; Schunn, F.; Winter, H.; Thomas, M.; Debus, J.; El Shafie, R.A.; et al. Progression of Pulmonary Function and Correlation with Survival Following Stereotactic Body Radiotherapy of Central and Ultracentral Lung Tumors. Cancers 2020, 12, 2862. https://doi.org/10.3390/cancers12102862
Regnery S, Eichkorn T, Weykamp F, Held T, Dinges L-A, Schunn F, Winter H, Thomas M, Debus J, El Shafie RA, et al. Progression of Pulmonary Function and Correlation with Survival Following Stereotactic Body Radiotherapy of Central and Ultracentral Lung Tumors. Cancers. 2020; 12(10):2862. https://doi.org/10.3390/cancers12102862
Chicago/Turabian StyleRegnery, Sebastian, Tanja Eichkorn, Fabian Weykamp, Thomas Held, Lisa-Antonia Dinges, Fabian Schunn, Hauke Winter, Michael Thomas, Jürgen Debus, Rami A. El Shafie, and et al. 2020. "Progression of Pulmonary Function and Correlation with Survival Following Stereotactic Body Radiotherapy of Central and Ultracentral Lung Tumors" Cancers 12, no. 10: 2862. https://doi.org/10.3390/cancers12102862