Skip to main content
Top
Published in: Radiation Oncology 1/2020

Open Access 01-12-2020 | NSCLC | Research

Development and external validation of a nomogram to predict overall survival following stereotactic body radiotherapy for early-stage lung cancer

Authors: Sarah Baker, Katerina Bakunina, Marloes Duijm, Mischa S. Hoogeman, Robin Cornelissen, Imogeen Antonisse, John Praag, Wilma D. Heemsbergen, Joost Jan Nuyttens

Published in: Radiation Oncology | Issue 1/2020

Login to get access

Abstract

Background

Prognostication tools for early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) are currently lacking. The purpose of this study was to develop and externally validate a nomogram to predict overall survival in individual patients with peripheral early-stage disease.

Methods

A total of 587 NSCLC patients treated with biologically effective dose > 100 Gy10 were eligible. A Cox proportional hazards model was used to build a nomogram to predict 6-month, 1-year, 3-year and 5-year overall survival. Internal validation was performed using bootstrap sampling. External validation was performed in a separate cohort of 124 NSCLC patients with central tumors treated with SBRT. Discriminatory ability was measured by the concordance index (C-index) while predictive accuracy was assessed with calibration slope and plots.

Results

The resulting nomogram was based on six prognostic factors: age, sex, Karnofsky Performance Status, operability, Charlson Comorbidity Index, and tumor diameter. The slope of the calibration curve for nomogram-predicted versus Kaplan-Meier-estimated overall survival was 0.77. The C-index of the nomogram (corrected for optimism) was moderate at 0.64. In the external validation cohort, the model yielded a C-index of 0.62.

Conclusions

We established and validated a nomogram which can provide individual survival predictions for patients with early stage lung cancer treated with SBRT. The nomogram may assist patients and clinicians with treatment decision-making.
Appendix
Available only for authorised users
Literature
1.
go back to reference Videtic GMM, Donington J, Giuliani M, Heinzerling J, Karas TZ, Kelsey CR, et al. Stereotactic body radiation therapy for early-stage non-small cell lung cancer: executive summary of an ASTRO evidence-based guideline. Pract Radiat Oncol. 2017;7:295–301.CrossRef Videtic GMM, Donington J, Giuliani M, Heinzerling J, Karas TZ, Kelsey CR, et al. Stereotactic body radiation therapy for early-stage non-small cell lung cancer: executive summary of an ASTRO evidence-based guideline. Pract Radiat Oncol. 2017;7:295–301.CrossRef
2.
go back to reference Zheng X, Schipper M, Kidwell K, Lin J, Reddy R, Ren Y, et al. Survival outcome after stereotactic body radiation therapy and surgery for stage I non-small cell lung cancer: a meta-analysis. Int J Radiat Oncol Biol Phys. 2014;90:603–11.CrossRef Zheng X, Schipper M, Kidwell K, Lin J, Reddy R, Ren Y, et al. Survival outcome after stereotactic body radiation therapy and surgery for stage I non-small cell lung cancer: a meta-analysis. Int J Radiat Oncol Biol Phys. 2014;90:603–11.CrossRef
3.
go back to reference Klement RJ, Belderbos J, Grills I, Werner-Wasik M, Hope A, Giuliani M, et al. Prediction of early death in patients with early-stage NSCLC-can we select patients without a potential benefit of SBRT as a curative treatment approach? J Thorac Oncol. 2016;11:1132–9.CrossRef Klement RJ, Belderbos J, Grills I, Werner-Wasik M, Hope A, Giuliani M, et al. Prediction of early death in patients with early-stage NSCLC-can we select patients without a potential benefit of SBRT as a curative treatment approach? J Thorac Oncol. 2016;11:1132–9.CrossRef
4.
go back to reference Young KA, Efiong E, Dove JT, Blansfield JA, Hunsinger MA, Wild JL, et al. External validation of a survival Nomogram for non-small cell lung Cancer using the National Cancer Database. Ann Surg Oncol. 2017;24:1459–64.CrossRef Young KA, Efiong E, Dove JT, Blansfield JA, Hunsinger MA, Wild JL, et al. External validation of a survival Nomogram for non-small cell lung Cancer using the National Cancer Database. Ann Surg Oncol. 2017;24:1459–64.CrossRef
5.
go back to reference Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925–31.CrossRef Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925–31.CrossRef
6.
go back to reference Cassidy RJ, Patel PR, Zhang X, Press RH, Switchenko JM, Pillai RN, et al. Stereotactic body radiotherapy for early-stage non-small-cell lung Cancer in patients 80 years and older: a multi-center analysis. Clin Lung Cancer. 2017;18:551–8.CrossRef Cassidy RJ, Patel PR, Zhang X, Press RH, Switchenko JM, Pillai RN, et al. Stereotactic body radiotherapy for early-stage non-small-cell lung Cancer in patients 80 years and older: a multi-center analysis. Clin Lung Cancer. 2017;18:551–8.CrossRef
7.
go back to reference Baumann P, Nyman J, Hoyer M, Gagliardi G, Lax I, Wennberg B, et al. Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study. Radiother Oncol. 2008;88:359–67.CrossRef Baumann P, Nyman J, Hoyer M, Gagliardi G, Lax I, Wennberg B, et al. Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study. Radiother Oncol. 2008;88:359–67.CrossRef
8.
go back to reference Takeda A, Enomoto T, Sanuki N, Handa H, Aoki Y, Oku Y, et al. Reassessment of declines in pulmonary function ≥1 year after stereotactic body radiotherapy. Chest. 2013;143:130–7.CrossRef Takeda A, Enomoto T, Sanuki N, Handa H, Aoki Y, Oku Y, et al. Reassessment of declines in pulmonary function ≥1 year after stereotactic body radiotherapy. Chest. 2013;143:130–7.CrossRef
9.
go back to reference Koshy M, Malik R, Spiotto M, Mahmood U, Weichselbaum R, Sher D. Disparities in treatment of patients with inoperable stage I non-small cell lung cancer: a population-based analysis. J Thorac Oncol. 2015;10:264–71.CrossRef Koshy M, Malik R, Spiotto M, Mahmood U, Weichselbaum R, Sher D. Disparities in treatment of patients with inoperable stage I non-small cell lung cancer: a population-based analysis. J Thorac Oncol. 2015;10:264–71.CrossRef
10.
go back to reference Liang W, Zhang L, Jiang G, Wang Q, Liu L, Liu D, et al. Development and validation of a nomogram for predicting survival in patients with resected non-small-cell lung cancer. J Clin Oncol. 2015;33:861–9.CrossRef Liang W, Zhang L, Jiang G, Wang Q, Liu L, Liu D, et al. Development and validation of a nomogram for predicting survival in patients with resected non-small-cell lung cancer. J Clin Oncol. 2015;33:861–9.CrossRef
11.
go back to reference Xiao HF, Zhang BH, Liao XZ, Yan SP, Zhu SL, Zhou F, et al. Development and validation of two prognostic nomograms for predicting survival in patients with non-small cell and small cell lung cancer. Oncotarget. 2017;8:64303–16.PubMedPubMedCentral Xiao HF, Zhang BH, Liao XZ, Yan SP, Zhu SL, Zhou F, et al. Development and validation of two prognostic nomograms for predicting survival in patients with non-small cell and small cell lung cancer. Oncotarget. 2017;8:64303–16.PubMedPubMedCentral
12.
go back to reference van der Voort van Zyp NC, Prévost JB, Hoogeman MS, Praag J, van der Holt B, Levendag PC, et al. Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: clinical outcome. Radiother Oncol. 2009;91:296–300.CrossRef van der Voort van Zyp NC, Prévost JB, Hoogeman MS, Praag J, van der Holt B, Levendag PC, et al. Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: clinical outcome. Radiother Oncol. 2009;91:296–300.CrossRef
13.
go back to reference Nuyttens JJ, van de Pol M. The cyber knife radiosurgery system for lung cancer. Expert Rev Med Devices. 2012;9:465–75.CrossRef Nuyttens JJ, van de Pol M. The cyber knife radiosurgery system for lung cancer. Expert Rev Med Devices. 2012;9:465–75.CrossRef
14.
go back to reference Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176:532–55.CrossRef Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176:532–55.CrossRef
15.
go back to reference Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195:557–82.CrossRef Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195:557–82.CrossRef
16.
go back to reference Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv1–iv21.CrossRef Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv1–iv21.CrossRef
17.
go back to reference Harrell FE Jr. Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis. 2nd ed. Switzerland: Springer; 2015.CrossRef Harrell FE Jr. Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis. 2nd ed. Switzerland: Springer; 2015.CrossRef
18.
go back to reference Kopek N, Paludan M, Petersen J, Hansen AT, Grau C, Høyer M. Co-morbidity index predicts for mortality after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer. Radiother Oncol. 2009;93:402–7.CrossRef Kopek N, Paludan M, Petersen J, Hansen AT, Grau C, Høyer M. Co-morbidity index predicts for mortality after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer. Radiother Oncol. 2009;93:402–7.CrossRef
19.
go back to reference Louie AV, Haasbeek CJ, Mokhles S, Rodrigues GB, Stephans KL, Lagerwaard FJ, et al. Predicting overall survival after stereotactic ablative radiation therapy in early-stage lung Cancer: development and external validation of the Amsterdam prognostic model. Int J Radiat Oncol Biol Phys. 2015;93:82–90.CrossRef Louie AV, Haasbeek CJ, Mokhles S, Rodrigues GB, Stephans KL, Lagerwaard FJ, et al. Predicting overall survival after stereotactic ablative radiation therapy in early-stage lung Cancer: development and external validation of the Amsterdam prognostic model. Int J Radiat Oncol Biol Phys. 2015;93:82–90.CrossRef
20.
go back to reference Rosen JE, Keshava HB, Yao X, Kim AW, Detterbeck FC, Boffa DJ. The natural history of operable non-small cell lung Cancer in the National Cancer Database. Ann Thorac Surg. 2016;101:1850–5.CrossRef Rosen JE, Keshava HB, Yao X, Kim AW, Detterbeck FC, Boffa DJ. The natural history of operable non-small cell lung Cancer in the National Cancer Database. Ann Thorac Surg. 2016;101:1850–5.CrossRef
21.
go back to reference Ou SH, Zell JA, Ziogas A, Anton-Culver H. Prognostic factors for survival of stage I nonsmall cell lung cancer patients: a population-based analysis of 19,702 stage I patients in the California Cancer registry from 1989 to 2003. Cancer. 2007;110:1532–41.CrossRef Ou SH, Zell JA, Ziogas A, Anton-Culver H. Prognostic factors for survival of stage I nonsmall cell lung cancer patients: a population-based analysis of 19,702 stage I patients in the California Cancer registry from 1989 to 2003. Cancer. 2007;110:1532–41.CrossRef
22.
go back to reference Matsuo Y, Shibuya K, Nagata Y, Takayama K, Norihisa Y, Mizowaki T, et al. Prognostic factors in stereotactic body radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;79:1104–11.CrossRef Matsuo Y, Shibuya K, Nagata Y, Takayama K, Norihisa Y, Mizowaki T, et al. Prognostic factors in stereotactic body radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;79:1104–11.CrossRef
23.
go back to reference McGovern SL, Liao Z, Bucci MK, et al. Is sex associated with the outcome of patients treated with radiation for nonsmall cell lung cancer? Cancer. 2009;115:3233–42.CrossRef McGovern SL, Liao Z, Bucci MK, et al. Is sex associated with the outcome of patients treated with radiation for nonsmall cell lung cancer? Cancer. 2009;115:3233–42.CrossRef
24.
go back to reference Firat S, Bousamra M, Gore E, Byhardt RW. Comorbidity, and KPS are independent prognostic factors in stage I non-small cell lung cancer. Int J Radiat Biol Phys. 2002;52:1047–57.CrossRef Firat S, Bousamra M, Gore E, Byhardt RW. Comorbidity, and KPS are independent prognostic factors in stage I non-small cell lung cancer. Int J Radiat Biol Phys. 2002;52:1047–57.CrossRef
25.
go back to reference Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, et al. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol. 2007;2:S94–S100.CrossRef Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, et al. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol. 2007;2:S94–S100.CrossRef
26.
go back to reference Allibhai Z, Taremi M, Bezjak A, Brade A, Hope AJ, Sun A, et al. The impact of tumor size on outcomes after stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2013;87:1064–70.CrossRef Allibhai Z, Taremi M, Bezjak A, Brade A, Hope AJ, Sun A, et al. The impact of tumor size on outcomes after stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2013;87:1064–70.CrossRef
27.
go back to reference Dunlap NE, Larner JM, Read PW, Kozower BD, Lau CL, Sheng K, et al. Size matters: a comparison of T1 and T2 peripheral non-small-cell lung cancers treated with stereotactic body radiation therapy (SBRT). J Thorac Cardiovasc Surg. 2010;140:583–9.CrossRef Dunlap NE, Larner JM, Read PW, Kozower BD, Lau CL, Sheng K, et al. Size matters: a comparison of T1 and T2 peripheral non-small-cell lung cancers treated with stereotactic body radiation therapy (SBRT). J Thorac Cardiovasc Surg. 2010;140:583–9.CrossRef
28.
go back to reference Wao H, Mhaskar R, Kumar A, Miladinovic B, Djulbegovic B. Survival of patients with non-small cell lung cancer without treatment: a systematic review and meta-analysis. Syst Rev. 2013;2:10.CrossRef Wao H, Mhaskar R, Kumar A, Miladinovic B, Djulbegovic B. Survival of patients with non-small cell lung cancer without treatment: a systematic review and meta-analysis. Syst Rev. 2013;2:10.CrossRef
29.
go back to reference Baker S, Sharma A, Peric R, Heemsbergen WD, Nuyttens JJ. Prediction of early mortality following stereotactic body radiotherapy for peripheral early-stage lung cancer. Acta Oncol. 2019;58:237–42.CrossRef Baker S, Sharma A, Peric R, Heemsbergen WD, Nuyttens JJ. Prediction of early mortality following stereotactic body radiotherapy for peripheral early-stage lung cancer. Acta Oncol. 2019;58:237–42.CrossRef
30.
go back to reference Baine MJ, Verma V, Schonewolf CA, Lin C, Simone CB 2nd. Histology significantly affects recurrence and survival following SBRT for early stage non-small cell lung cancer. Lung Cancer. 2018;118:20–6.CrossRef Baine MJ, Verma V, Schonewolf CA, Lin C, Simone CB 2nd. Histology significantly affects recurrence and survival following SBRT for early stage non-small cell lung cancer. Lung Cancer. 2018;118:20–6.CrossRef
31.
go back to reference Verstegen NE, Lagerwaard FJ, Haasbeek CJ, Slotman BJ, Senan S. Outcomes of stereotactic ablative radiotherapy following a clinical diagnosis of stage I NSCLC: comparison with a contemporaneous cohort with pathologically proven disease. Radiother Oncol. 2011;101:250–4.CrossRef Verstegen NE, Lagerwaard FJ, Haasbeek CJ, Slotman BJ, Senan S. Outcomes of stereotactic ablative radiotherapy following a clinical diagnosis of stage I NSCLC: comparison with a contemporaneous cohort with pathologically proven disease. Radiother Oncol. 2011;101:250–4.CrossRef
32.
go back to reference Burotto M, Thomas A, Subramaniam D, Giaccone G, Rajan A. Biomarkers in early-stage non-small-cell lung cancer: current concepts and future directions. J Thorac Oncol. 2014;9:1609–17.CrossRef Burotto M, Thomas A, Subramaniam D, Giaccone G, Rajan A. Biomarkers in early-stage non-small-cell lung cancer: current concepts and future directions. J Thorac Oncol. 2014;9:1609–17.CrossRef
Metadata
Title
Development and external validation of a nomogram to predict overall survival following stereotactic body radiotherapy for early-stage lung cancer
Authors
Sarah Baker
Katerina Bakunina
Marloes Duijm
Mischa S. Hoogeman
Robin Cornelissen
Imogeen Antonisse
John Praag
Wilma D. Heemsbergen
Joost Jan Nuyttens
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2020
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-020-01537-z

Other articles of this Issue 1/2020

Radiation Oncology 1/2020 Go to the issue