Stereotactic body radiotherapy (SBRT) vs. surgery in elderly early stage non-small cell lung cancer (NSCLC) patients Open Access

Abstract

Background: Lung cancer remains the leading cause of cancer death worldwide, also in the United State, of which more than 85 percent are classified as non-small cell lung cancer (NSCLC). For operable early stage NSCLC, the surgical treatment is still considered as the gold standard treatment. However, for 70+ years old elderly patients with increasing risk of comorbidities, SBRT has been proved to be an excellent alternative to surgery for inoperable patients and show less treatment morbidity and treatment related mortality than surgery.

Purpose: To determine if SBRT offers equivalent overall survival compared to surgery in elderly early stage non-small cell lung cancer patients.

Methodology: Comparing hazard ratio between SBRT and surgery using cox proportional hazard regression model along with propensity score matching method. If proportional hazard assumption is violated, Cox non-proportional hazard regression model will be used.

Results: The hazard ratio between SBRT and surgery is 2.04 (1.92-2.16) after controlling covariates. It indicates that the hazard for a 70+ early stage NSCLC patient who got SBRT is around 2 times high as the hazard for one who got surgery. However, when comparing SBRT with Pneumonectomy, the hazard ratio is non-proportional. At 6th month after treatment, the hazard ratio between SBRT and pneumonectomy is 0.76 (0.50, 0.81), which indicates that SBRT offers better overall survival than pneumonectomy at 6th month after treatment. After one year (12 months), the hazard ratio between SBRT and Pneumonectomy is greater than 1, which indicates that SBRT offers worse overall survival compared with pneumonectomy (HR=2.00 (1.09, 2.71) at 36th month and HR=4.35 (2.74, 11.52) at 60th month).

Conclusion: SBRT offers worse overall survival comparing with surgery in elderly early stage NSCLC patients, especially compared with lobectomy and resection. But SBRT offers better overall survival comparing with pneumonectomy at less than 12 months after treatment and worse overall survival at more than 12 months after treatment.

Table of Contents

CHAPTER 1 INTRODUCTION......................................................................................................1

1. Introduction to non-small cell lung cancer...............................................................................1

2. Surgical treatment for NSCLC patients.....................................................................................1

3. Introduction to SBRT..............................................................................................................2

4. Surgery types and their operation criteria................................................................................3

CHAPTER 2 STUDY PURPOSE.....................................................................................................5

1. Study Purpose........................................................................................................................5

CHAPTER 3 METHODOLOGY......................................................................................................5

1. Introduction to National Cancer Database................................................................................5

2. Non-small cell lung cancer data set..........................................................................................6

3. Include/Exclude Criteria..........................................................................................................7

4. Statistical Analysis..................................................................................................................8

CHAPTER 4 STUDY RESULTS.....................................................................................................13

1. Description of data set...........................................................................................................13

2. Associate with treatment group for each covariate...................................................................14

3. Univariate association with overall survival.............................................................................14

4. Multiunivariate association with overall survival by treatment group........................................15

5. Propensity score matching.....................................................................................................16

6. Multivariate association with overall survival by treatment interaction with covariates..............18

7. Comparing overall survival between SBRT and three types of surgery........................................18

8. Test the proportional hazard assumption in Cox model............................................................20

9. Comparing outcomes between SBRT and pneumonectomy using Cox non-proportional hazard regression model...21

CHAPTER 5 DISCUSSION..........................................................................................................22

1. Outcome of SBRT versus surgery............................................................................................22

2. Strengths and limitations......................................................................................................24

CHAPTER 6 CONCLUSION AND RECOMMENDATIONS...............................................................26

1. Study conclusion..................................................................................................................26

2. Recommendations................................................................................................................27

CHAPTER 7 REFERENCES........................................................................................................28

CHAPTER 8 TABLES AND FIGURES...........................................................................................31

Table 1: Variables Selected from NACLC data set........................................................................31

Table 2: Diagram for Study Population Selection........................................................................32

Table 3: Descriptive statistics for each selected variable..............................................................34

Table 4: Univariate association of each covariate with two treatment group..................................42

Table 5: Overall Survival of SBRT vs. Surgery..............................................................................48

Table 6: Univariate association with overall survival (Months).....................................................49

Table 7: Multivariate association with overall survival by treatment group...................................55

Table 8: Balance check after 1:1 matching of SBRT and Surgery....................................................61

Table 9: Association with overall survival in matched samples.....................................................67

Table 10: Overall survival for treatment group in matched sample...............................................67

Table 11: Multivariate Association with Overall Survival by Treatment interaction with Age..........68

Table 12: Multivariate Association with Overall Survival by Treatment interaction with Charlson-Deyo Score...69

Table 13: Multivariate Association with Overall Survival by Treatment interaction with Tumor Stage...71

Table 14: Overall survival for treatment type SBRT vs pneumonectomy........................................72

Table 15: Overall survival for treatment type SBRT vs wedge and segmental resection...................72

Table 16: Overall survival for treatment type SBRT vs lobectomy.................................................73

Table 17: Overall Survival by Treatment SBRT vs. Pneumonectomy in matched samples...............73

Table 18: Linear hypotheses testing results................................................................................73

Table 19: Analysis of Maximum Likelihood Estimates.................................................................74

Table 20: Hazard ratio between SBRT and pneumonectomy against time.....................................79

Figure 1: Survival Curves by Treatment SBRT vs. Surgery............................................................79

Figure 2: Kaplan-Meier curves in mached samples.....................................................................80

Figure 3: Survival curves by SBRT versus Pneumonectomy..........................................................80

Figure 4: Survival curves by SBRT versus wedge and segmental resection.....................................81

Figure 5: Survival curves by SBRT versus lobectomy...................................................................82

Figure 6: Survival Curves by Treatment SBRT vs. Pneumonectomy..............................................82

Figure 7: Plot of Schoenfeld residual for treatment type against overall survival...........................83

Figure 8: Hazard ratio changes over time between SBRT vs Pneumonectomy................................83

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Surgery Health Sciences, Public Health Health Sciences, Epidemiology
Keyword	NSCLC SBRT survival analysis lung cancer Cox model
Committee Chair / Thesis Advisor	Liu, Yuan, Emory University
Committee Members	Tolbert, Paige, Emory University Ryan, P Barry, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs Hospital or other health care provider

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