TY - JOUR
T1 - Predicting 5-Year Progression and Survival Outcomes for Early Stage Non-small Cell Lung Cancer Treated with Stereotactic Ablative Radiation Therapy
T2 - Development and Validation of Robust Prognostic Nomograms
AU - Kang, Jingjing
AU - Ning, Matthew S.
AU - Feng, Han
AU - Li, Hongqi
AU - Bahig, Houda
AU - Brooks, Eric D.
AU - Welsh, James W.
AU - Ye, Rui
AU - Miao, Hongyu
AU - Chang, Joe Y.
N1 - Funding Information:
This work was supported by the National Institutes of Health (grant number CA016672) and the Joan and Herb Kelleher Charitable Foundation. Dr Kang's stipend was partly supported by the China Scholarship Council, P. R. China. Disclosures: The authors report no proprietary or commercial conflicts of interest with respect to any product mentioned or concept discussed in this article. Outside of the present submitted work, Dr James Welsh reports research support from GlaxoSmithKline, Bristol Meyers Squibb, Merck, Nanobiotix, Mavu Pharma, and Checkmate Pharmaceuticals. Dr Welsh serves on the scientific advisory board for RefleXion Medical, MolecularMatch, OncoResponse, CheckMate, Mavu Pharmaceuticals, Alpine Immune Sciences. He is cofounder of Helios Oncology, MolecularMatch, and OncoResponse and serves as an advisor to Astra Zeneca, Merck, MolecularMatch, Incyte, Aileron, and Nanobiotix. Dr Welsh has the following patents: MP470 (amuvatinib), MRX34 regulation of PDL1, XRT technique to overcome immune resistance. MD Anderson Cancer Center has a trademark for RadScopal. Dr Chang reports grants from BMS as well as personal fees from AstraZenaca and Varian, and is a shareholder in Global Oncology One, all outside of the submitted work.
Publisher Copyright:
© 2019
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Purpose: Our purpose was to develop predictive nomograms for overall survival (OS), progression-free survival (PFS), and time-to-progression (TTP) at 5 years in patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: The study cohort included 714 ES-NSCLC patients treated with SABR from 2004-2015 with median follow-up of 59 months, divided into training and testing sets (8:2), with the former used for nomogram development. The least absolute shrinkage and selection operator were initially employed to screen for predictors of OS, PFS, and TTP, and identified predictors were subsequently applied toward Cox proportional hazards regression modeling. Significant predictors (P < .05) on multivariable regression were then used to develop nomograms, which were validated via evaluation of concordance indexes (C-index) and calibration plots. Finally, Kaplan-Meier method and Gray's test were employed to compare and confirm differences in outcomes among various groups and explore prognostic factors associated with local versus distant disease progression. Results: Significant predictors of both OS and PFS at 5 years included age, sex, Charlson comorbidity index, diffusing capacity of carbon monoxide, systemic immune-inflammation index, and tumor size (P ≤ .01 for all). Eastern Cooperative Oncology Group performance status predicted for OS as well (P = .01), and both tumor size (P < .01) and minimum biological equivalent dose to 95% of planning target volume (PTV D95 BED10; P < .01) were predictive of TTP. The C-indexes for the OS, PFS, and TTP nomograms were 0.73, 0.68, and 0.60 in the training data set and 0.72, 0.66, and 0.59 in the testing data set, respectively. Tumor size > 2.45 cm and PTV D95 BED10 < 113 Gy were significantly associated with both local and distant progression. Conclusions: These prognostic nomograms can accurately predict for OS, PFS, and TTP at 5 years after SABR for ES-NSCLC and may thus help identify high-risk patients who could benefit from additional systemic therapy.
AB - Purpose: Our purpose was to develop predictive nomograms for overall survival (OS), progression-free survival (PFS), and time-to-progression (TTP) at 5 years in patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: The study cohort included 714 ES-NSCLC patients treated with SABR from 2004-2015 with median follow-up of 59 months, divided into training and testing sets (8:2), with the former used for nomogram development. The least absolute shrinkage and selection operator were initially employed to screen for predictors of OS, PFS, and TTP, and identified predictors were subsequently applied toward Cox proportional hazards regression modeling. Significant predictors (P < .05) on multivariable regression were then used to develop nomograms, which were validated via evaluation of concordance indexes (C-index) and calibration plots. Finally, Kaplan-Meier method and Gray's test were employed to compare and confirm differences in outcomes among various groups and explore prognostic factors associated with local versus distant disease progression. Results: Significant predictors of both OS and PFS at 5 years included age, sex, Charlson comorbidity index, diffusing capacity of carbon monoxide, systemic immune-inflammation index, and tumor size (P ≤ .01 for all). Eastern Cooperative Oncology Group performance status predicted for OS as well (P = .01), and both tumor size (P < .01) and minimum biological equivalent dose to 95% of planning target volume (PTV D95 BED10; P < .01) were predictive of TTP. The C-indexes for the OS, PFS, and TTP nomograms were 0.73, 0.68, and 0.60 in the training data set and 0.72, 0.66, and 0.59 in the testing data set, respectively. Tumor size > 2.45 cm and PTV D95 BED10 < 113 Gy were significantly associated with both local and distant progression. Conclusions: These prognostic nomograms can accurately predict for OS, PFS, and TTP at 5 years after SABR for ES-NSCLC and may thus help identify high-risk patients who could benefit from additional systemic therapy.
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U2 - 10.1016/j.ijrobp.2019.09.037
DO - 10.1016/j.ijrobp.2019.09.037
M3 - Article
C2 - 31586665
AN - SCOPUS:85075983730
SN - 0360-3016
VL - 106
SP - 90
EP - 99
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -