Date of Award

January 2017

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

James B. Yu

Abstract

Purpose

To examine outcomes after postoperative radiation (PORT) and the impact of chemoradiation facility case volume in various populations of patients with non-small cell lung cancer (NSCLC).

Methods

We used patients within the National Cancer Data Base. In our analysis of outcomes after PORT, we examined two populations: 1) incompletely-resected patients with pathologic stage N0-N2, overall American Joint Committee on Cancer stage II-III NSCLC who had undergone a lobectomy or pneumonectomy with positive surgical margins coded as receiving external beam PORT at 50-74 Gy or observation were included and 2) completely-resected patients with stage II-III N0-N1 margin-negative NSCLC who received a total radiotherapy dose within the range of 45.0-74.0 Gy given within the initial treatment course. To examine the impact of chemoradiation (CRT) facility case volume, we identified clinical stage III NSCLC patients diagnosed in 2004-2006 who were treated with definitive concurrent CRT to 59.4-74.0 Gy. High-volume facilities (HVF) were defined as those in the 90th percentile of annual CRT volume (≥12 cases/year). For all populations, multivariable logistic regression was used to determine factors associated with PORT receipt and independent predictors of receiving CRT at HVF. Cox proportional hazards regression was performed for multivariable analyses of overall survival for all populations.

Results

Among 3,395 included incompletely-resected patients, 1,207 (35.6%) received PORT. On multivariable analysis adjusting for demographic and clinicopathologic covariates, PORT (HR=0.80; 95%CI: 0.70-092) was associated with improved survival among margin-positive patients. Subset analysis by nodal stage showed PORT improved survival across all nodal stages.

We then identified 2,167 (6.7%) and 30,269 (93.3%) patients with completely-resected stage II or III N0-N1 NSCLC who were treated with and without PORT, respectively. Overall, completely-resected patients who received PORT had worse survival (HR=1.30; 95% CI 1.20-1.40) compared to those not receiving PORT. This association was unchanged when limited to patients receiving modern treatment with 3-CRT or IMRT (HR=1.35; 95% CI: 1.10-1.65].

Among 10,072 included chemoradiation patients, 1,207 (12.0%) were treated at HVF. When controlling for demographic and clinical covariates including academic affiliation, treatment at HVF was independently associated with a significantly decreased risk of death (HR=0.93; 95% CI: 0.87-0.99; p=0.03). Propensity score matching showed that these findings were robust (HR=0.91; 95% CI: 0.84-0.99; p=0.04).

Conclusions

Our findings suggest that PORT is associated with improved overall survival in incompletely-resected Stage II-III N0-N2 NSCLC patients. However, we found no evidence of benefit from PORT for completely-resected N0-N1 NSCLC, regardless of dose or technique. We also found that treatment at high-volume facilities is associated with improved overall survival among stage III NSCLC patients receiving definitive concurrent CRT. Thus, delivery of PORT in incompletely-resected early stage NSCLC and centralization of care to HVF for stage III NSCLC patients receiving definitive concurrent CRT may be beneficial strategies to optimize patient outcomes.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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