Date of Award

January 2015

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Daniel J. Boffa

Second Advisor

John Geibel

Subject Area(s)

Medicine, Surgery

Abstract

BACKGROUND

The National Cancer Database (NCDB) is the largest clinical database resource available. Using this remarkable tool, we completed two studies with the goal of answering two questions about non-small cell lung cancer (NSCLC) in the United States: 1) How is clinical stage IIIA-cN2 NSCLC managed? and 2) What is the survival and optimal treatment approach following incomplete resection of NSCLC?

Clinical stage IIIA (cStage IIIA) NSCLC that results from mediastinal lymph node disease (stage IIIA-cN2) represents a difficult lung cancer scenario. In addition to the disappointing prognosis, the accuracy of mediastinal staging is uncertain, the optimal treatment approach is unclear, and the outcomes are variable.

Incomplete resection of NSCLC resulting in microscopic residual disease is known to portend a dramatic decline in survival. In the past, adjuvant radiation and chemotherapy have been offered to treat residual disease at the surgical margins, yet the efficacy of this treatment is unknown.

METHODS

In order to assess the current state of clinical stage IIIA-cN2 NSCLC in the United States, the NCDB was queried for patients diagnosed between 1999 and 2011 with NSCLC, clinically staged to have mediastinal lymph node metastases without systemic metastases (T1-3, N2, M0, cStage IIIA).

In order to determine the survival among incompletely resected NSCLC patients and identify the optimal response to positive NSCLC surgical margins, the NCDB was queried for surgically managed pathologic stage I-III NSCLC between 2003 and 2006 (N=54,512). The prevalence, predictors, impact, and optimal treatment approaches to positive surgical margins were investigated.

RESULTS

Management of Clinical Stage IIIA Primary Lung Cancers

83,913 cStage IIIA NSCLC patients with mediastinal lymph node metastases were identified. Clinical staging of the mediastinum was not consistently performed. In surgical patients, clinical N2 status was pathologically confirmed in only 56% of treatment naïve patients while lymph nodes were only biopsied in 23% of patients who were treated without surgery. The most utilized treatment approach was nonsurgical, involving chemotherapy, radiation, or both (69% of patients) followed by surgery (14%). The 5-year survival varied by treatment and was highest for patients treated with surgery in combination with chemotherapy, radiation, or both (38%), followed by surgery alone (30%), nonsurgical treatment (11%), and worst for untreated patients (5%).

Impact of Adjuvant treatment for Microscopic Residual disease

3,102 NSCLC patients (5.7% of resections) with positive surgical margin were identified, including 1,688 with microscopically positive (R1) margins (3.1%). When compared with complete resections (R0), patients with R1 resections had a worse 5-year survival; stage pI (62% vs 37%;p<0.0001), stage pII (41% vs. 29%;p<0.0001) and stage pIII (33% vs 19%;p<0.0001). At all stages, postoperative administration of both chemotherapy and radiation were associated with superior survival compared to surgery alone; stage pI (44% vs 35%;p=0.05), stage pII (33% vs 21%;p=0.0013), and stage pIII NSCLC (30% vs 12%;p<0.0001). Administration of chemotherapy or radiation alone was less consistently associated with improved outcome in R1 patients. Of note, radiation alone did not improve survival for stage pI patients with R1 resections (26% vs. 35%;p=0.0399).

CONCLUSIONS

Management of Clinical Stage IIIA Primary Lung Cancers

The accuracy of the clinical staging of the mediastinum among cStage IIIA-cN2 patients in the United States is concerning. Surgery as a treatment approach is less common but is associated with an encouraging 5-year survival. Further study is needed to clarify the accuracy of mediastinal staging in the United States for cStage IIIA-cN2 NSCLC.

Impact of Adjuvant treatment for Microscopic Residual disease

In all pathologic stages, the administration of both chemotherapy and radiation is associated with improved survival in patients with microscopically positive surgical margins. Further study is needed to clarify the optimal stage-specific adjuvant approach to incompletely resected NSCLC.

Comments

This is an Open Access Thesis.

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