skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Simple Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies

Abstract

Purpose: To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax. Methods and Materials: Published studies on lung toxicity in patients with early-stage non–small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT. Results: Eighty-eight studies (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio = 0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that providedmore » detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT. Conclusions: The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk.« less

Authors:
 [1];  [2];  [3];  [1];  [2];  [4];  [5];  [6];  [4];  [7];  [1];  [8];  [3];  [9];  [10];
  1. Department of Radiation Oncology, GRU Cancer Center/Medical College of Georgia, Georgia Regents University, Augusta, Georgia (United States)
  2. (China)
  3. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States)
  4. Department of Radiation Oncology, University of Colorado, Denver, Colorado (United States)
  5. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)
  6. Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States)
  7. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York (United States)
  8. Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, New Jersey (United States)
  9. Bott Cancer Center, Holy Redeemer Hospital, Meadowbrook, Pennsylvania (United States)
  10. Department of Radiation Oncology, University of Rochester, Rochester, New York (United States)
Publication Date:
OSTI Identifier:
22648754
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 5; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEST; DOSIMETRY; LUNGS; NEOPLASMS; PATIENTS; RADIATION HAZARDS; RADIOTHERAPY; TOXICITY

Citation Formats

Zhao, Jing, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Yorke, Ellen D., Li, Ling, Department of Shanghai Cancer Hospital, Fudan University, Shanghai, Kavanagh, Brian D., Li, X. Allen, Das, Shiva, Miften, Moyed, Rimner, Andreas, Campbell, Jeffrey, Xue, Jinyu, Jackson, Andrew, Grimm, Jimm, Milano, Michael T., and and others. Simple Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.03.024.
Zhao, Jing, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Yorke, Ellen D., Li, Ling, Department of Shanghai Cancer Hospital, Fudan University, Shanghai, Kavanagh, Brian D., Li, X. Allen, Das, Shiva, Miften, Moyed, Rimner, Andreas, Campbell, Jeffrey, Xue, Jinyu, Jackson, Andrew, Grimm, Jimm, Milano, Michael T., & and others. Simple Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies. United States. doi:10.1016/J.IJROBP.2016.03.024.
Zhao, Jing, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Yorke, Ellen D., Li, Ling, Department of Shanghai Cancer Hospital, Fudan University, Shanghai, Kavanagh, Brian D., Li, X. Allen, Das, Shiva, Miften, Moyed, Rimner, Andreas, Campbell, Jeffrey, Xue, Jinyu, Jackson, Andrew, Grimm, Jimm, Milano, Michael T., and and others. 2016. "Simple Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies". United States. doi:10.1016/J.IJROBP.2016.03.024.
@article{osti_22648754,
title = {Simple Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies},
author = {Zhao, Jing and Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan and Yorke, Ellen D. and Li, Ling and Department of Shanghai Cancer Hospital, Fudan University, Shanghai and Kavanagh, Brian D. and Li, X. Allen and Das, Shiva and Miften, Moyed and Rimner, Andreas and Campbell, Jeffrey and Xue, Jinyu and Jackson, Andrew and Grimm, Jimm and Milano, Michael T. and and others},
abstractNote = {Purpose: To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax. Methods and Materials: Published studies on lung toxicity in patients with early-stage non–small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT. Results: Eighty-eight studies (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio = 0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT. Conclusions: The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk.},
doi = {10.1016/J.IJROBP.2016.03.024},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 95,
place = {United States},
year = 2016,
month = 8
}
  • Purpose: To performed a systematic review and pooled analysis to compare clinical outcomes of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for the treatment of medically inoperable stage I non-small cell lung cancer. Methods and Materials: A comprehensive literature search for published trials from 2001 to 2012 was undertaken. Pooled analyses were performed to obtain overall survival (OS) and local tumor control rates (LCRs) and adverse events. Regression analysis was conducted considering each study's proportions of stage IA and age. Results: Thirty-one studies on SBRT (2767 patients) and 13 studies on RFA (328 patients) were eligible. The LCR (95%more » confidence interval) at 1, 2, 3, and 5 years for RFA was 77% (70%-85%), 48% (37%-58%), 55% (47%-62%), and 42% (30%-54%) respectively, which was significantly lower than that for SBRT: 97% (96%-98%), 92% (91%-94%), 88% (86%-90%), and 86% (85%-88%) (P<.001). These differences remained significant after correcting for stage IA and age (P<.001 at 1 year, 2 years, and 3 years; P=.04 at 5 years). The effect of RFA was not different from that of SBRT on OS (P>.05). The most frequent complication of RFA was pneumothorax, occurring in 31% of patients, whereas that for SBRT (grade ≥3) was radiation pneumonitis, occurring in 2% of patients. Conclusions: Compared with RFA, SBRT seems to have a higher LCR but similar OS. More studies with larger sample sizes are warranted to validate such findings.« less
  • Purpose: To compare toxicity after stereotactic body radiation therapy (SBRT) for “central” tumors—within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum—versus noncentral (“peripheral”) lung tumors. Methods and Materials: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non–small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/β=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up usingmore » Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ{sup 2} and 2-tailed t tests, adverse events with χ{sup 2} test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). Results: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups. Conclusion: Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.« less
  • Purpose: To estimate the risk of radiation-induced changes in the lung before single-dose treatment (stereotactic body radiation therapy [SBRT]) of lung cancer, the quantitative dose-response and volume-response relations must be known. Methods and Materials: A total of 64 patients treated for non-small-cell lung cancer with single doses of 20-30 Gy were classified according to the occurrence or nonoccurrence of perifocal changes in the lung detected by CT. Patients without toxic events in the lung were required to have {>=}6 months of follow-up. The mean dose (D{sub mean}) in the ipsilateral lung and the volume receiving >7 or 10 Gy (V{submore » 7} and V{sub 10}, respectively) were used to calculate the dose-response and volume-response curves. The predictive value of additional variables was also investigated. Results: Of the 64 patients, 83% exhibited the selected endpoint. The tolerance values at a 50% probability of toxic events were 1.2 {+-} 0.7 Gy for the D{sub mean} and 5.8 {+-} 3.0% and 3.1 {+-} 2.0% for V{sub 7} and V{sub 10}, respectively. A nonsignificant shift to higher doses was seen for the dose-response curve for the upper compared with the lower part of the lung. Conclusion: The D{sub mean}, V{sub 7}, and V{sub 10} can be used to predict the risk of lung toxicity after SBRT treatment of non-small-cell lung cancer. Because of the lack of patients with low prescribed doses, however, the related uncertainty of this prediction is still relatively large. The D{sub mean}, V{sub 7}, and V{sub 10} are equally well suited. The additional investigated variables did not provide significant advantages. The lower part of the lung appears to be more radiosensitive than the upper.« less
  • Purpose: To identify dose-volume factors associated with radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for lung cancer. Methods and Materials: This study analyzed 74 patients who underwent SBRT for primary lung cancer. The prescribed dose for SBRT was uniformly 48 Gy in four fractions at the isocenter. RP was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3. Symptomatic RP was defined as grade 2 or worse. Optimal cut-offs dividing the patient population into two subgroups based on the incidence of symptomatic RP were sought using the following dose-volume metrics: PTV volume (ml), mean lungmore » dose (Gy), and V5, V10, V15, V20, V25, V30, V35, and V40 (%) of both lungs excluding the PTV. Results: With a median follow-up duration of 31.4 months, symptomatic RP was observed in 15 patients (20.3%), including 1 patient with grade 3. Optimal cut-offs for pulmonary dose-volume metrics were V25 and V20. These two factors were highly correlated with each other, and V25 was more significant. Symptomatic RP was observed in 14.8% of the patients with V25 <4.2%, and the rate was 46.2% in the remainder (p = 0.019). PTV volume was another significant factor. The symptomatic RP rate was significantly lower in the group with PTV <37.7 ml compared with the larger PTV group (11.1% vs. 34.5%, p = 0.020). The patients were divided into three subgroups (patients with PTV <37.7 ml; patients with, PTV {>=}37.7 ml and V25 <4.2%; and patients with PTV {>=}37.7 ml and V25 {>=}4.2%); the incidence of RP grade 2 or worse was 11.1%, 23.5%, and 50.0%, respectively (p = 0.013). Conclusions: Lung V25 and PTV volume were significant factors associated with RP after SBRT.« less
  • Purpose: To evaluate the dose–response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm{sup 3} up to 2.0 cm{sup 3}]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showedmore » a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm{sup 3} (D{sub 0.1cm3}) was used for further analysis. The median value of D{sub 0.1cm3} (α/β = 3 Gy) was EQD{sub 2,LQ} = 147 Gy{sub 3} (range, 20-293 Gy{sub 3}). For patients who developed atelectasis the median value was EQD{sub 2,LQ} = 210 Gy{sub 3}, and for patients who did not develop atelectasis, EQD{sub 2,LQ} = 105 Gy{sub 3}. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose–response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.« less