Follicular Lymphoma in the Medicare Population: Determinants and Outcomes of Management Approaches 公开

Abstract

Recent advances that have changed the management paradigm for follicular lymphoma (FL) include positron emission tomography (PET)-staging and the monoclonal antibody, rituximab (R). However, there is lack of consensus on the optimal management of FL. The three chapters of this dissertation use the linked Surveillance, Epidemiology, and End Results-Medicare data to examine the determinants and outcomes of management approaches in FL.

In Chapter 2, we study the factors associated with the use of PET-staging in FL and examine the extent to which the variations in PET use are influenced by physician preferences, availability, access, and reimbursement policies. Our findings of widespread use of PET-staging in FL, along with the socio-demographic, local and regional variations in its use underscore the importance of non-clinical factors in the utilization of new technology.

In Chapter 3, we examine the effect of clinical and non-clinical factors on management patterns in FL, given the clarity of guidelines (or lack thereof) and the status of emerging evidence. We find that involved field radiation therapy for stage I/grade 1-2 disease was not the standard approach despite the National Comprehensive Cancer Network (NCCN) recommending this use, but treatment with R + chemotherapy (R-chemo) or single-agent R was common, even though observation is a reasonable approach in these patients. Most grade 3 patients received upfront R-chemo even in the absence of clear recommendations in the NCCN guidelines. Our findings emphasize that emerging evidence and financial incentives of providers may play a more important role in determining treatment patterns in FL than guideline recommendations.

In Chapter 4, we examine the relationship between R-chemo use and PET-staging, and the implications of the PET-R-chemo interface on survival. We find a possible bi-directional association between PET-staging and R-chemo use. Patients who received PET-staging or R-chemo (or both) had longer survival than those who received neither, with the PET + R-chemo group having the most superior outcomes. Our findings motivate future research into the role of PET-staging in informing surveillance or treatment decisions and the influence of PET-staging on survival outcomes in FL.

Table of Contents

Table of Contents

Chapter 1: Introduction………………………………………………………………..……….…….1

1.1 Clinical Overview………………………………………………………………............……..1

1.2 Innovation in Imaging……………………………………………………..........…..……..2

1.3 Innovation in Treatment……………………………......…………………………….…....3

1.4 The Three Chapter………………………………………........………….……………….....4

1.5 Conclusions and Implications………………………......……………………...…………9

References…………………………………………………………...........…..………………......11

Chapter 2: Patterns of Use of Positron Emission Tomography for Initial

Staging in Elderly Follicular Lymphoma Patients…………………………..….…....14

2.1 Introduction…………………………………………………………....…….…...........……14

2.2 Materials and Methods……………………………………………..……..….….....…….15

2.2.1 Data Sources and Study Population……………………...……..…….……......15

2.2.2 Study Variables…………………………………………….....….............……………16

2.2.3 Statistical Analyses………………………………………………...............………..19

2.3 Results……………………………………………………………………..............…………..19

2.4 Discussion……………………………………………………………..............………………21

References………………………………………………………………..............………………..32

Chapter 3: Variations in the Management of Follicular Lymphoma: the

Role of ClinicalPractice Guidelines in Shaping Management Decisions.......35

3.1 Introduction………………………………………………………...………....................…35

3.2 Materials and Methods……………………………………………….………...……….......38

3.2.1 Data Sources and Study Population……………………………..………...........38

3.2.2 Study Variables…………………………………………………….…..................……39

3.2.3 Statistical Analyses…………………………………………………................….…..42

3.3 Results…………………………………………………………………………................……..43

3.4 Discussion…………………………………………………………………..................………45

References………………………………………………………………………...........….......…..61

Chapter 4: Survival Outcomes in Follicular Lymphoma and the Role of

Positron Emission Tomography (PET)-Staging………………….......................64

4.1 Introduction………………………………………………………………..…............…..……64

4.2 Materials and Methods……………………………………………………............……….67

4.2.1 Data Sources and Study Population……………………………..…….............68

4.2.2 Study Variables…………………………………………………....…...............………69

4.2.3 Statistical Analyses……………………………………………........…........………..72

4.3 Results…………………………………………………………….........……...……......……..78

4.4 Discussion……………………………………………………………...………...............……81

References…………………………………………………………………...………................…106

List of Tables

Table 2.1 Baseline characteristics of the cohort stratified by the receipt of PET-staging……..............................................................................................…26

Table 2.2 Results from multivariable logistic regression with receipt of PET-staging as the dependent variable…………………………………………………………………….……….….28

Table 3.1 Baseline characteristics of the sample stratified by analytic group…………..........................................................................................................50

Table 3.2 Results from multinomial logistic regression comparing management choice in stage I/grade 1 or 2 patients………………………………..………………………………….52

Table 3.3 Results from multinomial logistic regression comparing management choice in grade 3 FL…………………………………………………………..………………………….….....…55

Table 4.1 Baseline characteristics of the cohort stratified by receipt of PET-staging…….…................................................................................................…86

Table 4.2 Results from the 2nd-stage multinomial logistic regression predicting receipt of R-chemo……………………………………………………………………………………...……......88

Table 4.3 Associations between patient and disease characteristics and risk of death from the base CPH models (propensity scores or 2SRI not applied)………………89

Table 4.4 Associations between patient and disease characteristics and risk of death, weighted by inverse probabilities of management approaches….................91

Table 4.5 Associations between patient characteristics and risk of death from the secondstage of 2SRI-based CPH models…..………...........................................93

Table 4.6 Adjusted Cox proportional hazards models comparing survival of management approaches by analytic method…………….……………………….......………….………95

Appendix Table 3.4 ICD-9-CM and CPT/HCPCS codes used to identify management

strategy and PET-staging……..…………………………………………………………………..57

Appendix Table 4.7 ICD-9-CM and CPT/HCPCS codes used to identify management strategy and PET-staging…………………………………………………………....…………………..….96

Appendix Table 4.8 Results from the first stage multinomial regression in the 2SRI survival model (no PET + others is the reference category)…………………………....97

List of Figures

FIGURE 2.1 Selection criteria for the study cohort……………………………...............................................................................................................................30

FIGURE 2.2 Proportions of patients receiving one or more PET-staging scans by years of diagnosis…………………………………………………………………….....……………….....…….31

FIGURE 3.1 Current National Comprehensive Cancer Network Clinical Practice Guidelines for management of follicular lymphoma…………………………………………………….58

FIGURE 3.2 Selection criteria for the study cohort…………...………………….............................................................................................................................59

FIGURE 3.3 Time trends in management choice in stage I/ grade 1-2 FL and grade 3 FL patients……………………………......…………………………………………………………….......…60

FIGURE 4.1 Conceptual model………………………..............................................................................................................................................................101

FIGURE 4.2 Selection criteria for the study cohort……….................................................................................................................................................102

FIGURE 4.3 Unadjusted Kaplan-Meier survival curves by packages of management

approaches……………………………………...…………………………….................................................................................................................................……………….…103

FIGURE 4.4 Direct-adjusted survival functions from propensity score-weighted multivariable Cox proportional hazards models………………..………………………………………104

FIGURE 4.5 Direct-adjusted survivor functions from the 2SRI multivariable Cox proportional hazards models……………………………………………………………………………….....105

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School	Laney Graduate School
Department	Health Services and Research Health Policy
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Health Sciences, Public Health
关键词	Follicular Lymphoma Patterns of Care SEER-Medicare Positron Emission Tomography
Committee Chair / Thesis Advisor	Lipscomb, Joseph, Emory University
Committee Members	Howard, David H, Emory University Ward, Kevin C., Emory University Flowers, Christopher R, Emory University

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