Please discuss the following concepts
ought up
1) the statement "... a possible statistical cure, in that patients may be able to live long enough .with disease to die of other causes" - This concept is sometimes described as a competing risk - meaning that in a Survival analysis model we are interested in looking for a particular event (i.e. death by
east cancer) but a different event (i.e. death by heart disease) may occur first. Discuss what implications this type of situation may have on being able to perform a survival analysis and being able to interpret the results
2) The authors discuss the concept of turning a fatal disease into a chronic disease - from a patient's perspective discuss the Pros and Cons of having this occur for a disease such as MBC.
Metastatic
east cancer survival improvement restricted by regional disparity: Surveillance, Epidemiology, and End Results and institutional analysis: 1990 to 2011
390 Cancer January 15, 2020
Original Article
Metastatic Breast Cancer Survival Improvement Restricted
y Regional Disparity: Surveillance, Epidemiology, and End
Results and Institutional Analysis: 1990 to 2011
Judith A. Malmgren, PhD 1,2; Gregory S. Calip, PharmD, MPH, PhD 3; Mary K. Atwood, CTR4; Musa Mayer, MS, MFA5;
and Henry G. Kaplan, MD4
BACKGROUND: The extent of
east cancer outcome disparity can be measured by comparing Surveillance, Epidemiology, and End
Results (SEER)
east cancer-specific survival (BCSS) by region and with institutional cohort (IC) rates. METHODS: Patients who were
diagnosed with a first primary, de novo, stage IV
east cancer at ages 25 to 84Â years from 1990 to 2011 were studied. The change in
5-year BCSS over time from 1990 to 2011 was compared using the SEER 9 registries (SEER 9) without the Seattle-Puget Sound (S-PS)
egion (n = 12,121), the S-PS region alone (n = 1931), and the S-PS region IC (n = 261). The IC BCSS endpoint was
east cancer death con-
firmed from chart and/or death certificate and cause-specific survival for SEER registries. BCSS was estimated using the Kaplan-Meier
method. Hazard ratios (HzR) were calculated using Cox proportional-hazards models. RESULTS: For SEER 9 without the S-PS region,
5-year BCSS improved 7% (from 19% to 26%) over time, it improved 14% for the S-PS region (21% to 35%), and it improved 27% for the
S-PS IC (29% to 56%). In the IC Cox proportional-hazards model, recent diagnosis year, chemotherapy, surgery, and age <70Â years were
associated with better survival. For SEER 9, additional significant factors were white race and positive hormone receptor status and
S-PS region was associated with better survival (HzR, 0.87; 95% CI, XXXXXXXXXXIn an adjusted model, hazard of BC death decreased in
the most recent time period XXXXXXXXXXby 28% in SEER 9 without S-PS, 43% in the S-PS region and 45% in the IC (HzR, 0.72 [95%
CI, XXXXXXXXXX], 0.57 [95% CI, XXXXXXXXXX], and 0.55 [95% CI, XXXXXXXXXX], respectively). CONCLUSIONS: Over 2 decades, the survival of
patients with metastatic
east cancer improved nationally, but with regional survival disparity and differential improvement. To achieve
equitable outcomes, access and treatment approaches will need to be identified and adopted. Cancer 2020;126:390-399. © 2019 The
Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms
of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the
original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
KEYWORDS: differential survival, disease-specific survival (DSS), metastatic
east cancer, regional disparity.
INTRODUCTION
Variation in
east cancer recu
ence and survival may be influenced by age, race, access to care, insurance coverage,
socioeconomic status, geographic area of residence (u
an
ural or metropolitan/nonmetropolitan), and timely diagnosis
and treatment.1-4 From national statistics, factors contributing to state variations in cancer incidence rates include risk
factor prevalence, access to and utilization of early detection services, and completeness of reporting.5 Despite survival
improvements across poverty levels for all stages of disease, relative survival remains lower among women residing in poor
areas compared with affluent women.6 Some evidence links guideline compliance to improved and optimal outcomes, but
a lack of ability to compare guideline adherence in national databases inhibits the ability to evaluate widespread adherence
or efficacy.7,8
We previously observed significant improvement in 5-year disease-specific survival of patients with de novo stage IV
metastatic
east cancer (MBC) over time from 1990 to 2010 without a concu
ent improvement in the survival of pa-
tients with recu
ent MBC from our study of an institutional cohort of
east cancer registry patients.9 The 5-year
east
cancer-specific survival (BCSS) rates in our institutional cohort of patients with stage IV
east cancer were significantly
higher than the rates previously reported for stage IV
east cancer from Surveillance, Epidemiology, and End Results
(SEER) registry data.10
Regional disparity in
east cancer outcomes can be measured by comparing BCSS rates from SEER across geo-
graphic regions and with the rates from a SEER-embedded institutional cohort. We compared SEER aggregate data to
Co
esponding author: Judith A. Malmgren, PhD, 12025 Ninth Avenue NW, Seattle, WA 98177; XXXXXXXXXX
1 HealthStat Consulting, Inc., Seattle, Washington; 2 Department of Epidemiology, University of Washington, Seattle, Washington; 3 Center for Pharmacoepidemiology and
Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois; 4 Swedish Cancer Institute, Seattle, Washington; 5 Metastatic Breast Cancer Alliance, New
York, New York
We acknowledge and sincerely thank Dr. Marc Hurlbert for his invaluable assistance.
DOI: XXXXXXXXXX/cncr.32531, Received: May 10, 2019; Revised: August 25, 2019; Accepted: August 30, 2019, Published online October 22, 2019 in Wiley Online Li
ary
(wileyonlineli
ary.com)
mailto:
https:
orcid.org/ XXXXXXXXXX
https:
orcid.org/ XXXXXXXXXX
http:
creativecommons.org/licenses
y-nc-nd/4.0
mailto: XXXXXXXXXX
Metastatic Breast Cancer Survival Disparity/Malmgren et al
391Cancer January 15, 2020
the regional subset from the Seattle-Puget Sound (S-PS)
area registry and to an institutional cohort (IC) located
in the S-PS registry area whose cases are included in the
S-PS Cancer Surveillance System (SEER 9 without S-PS,
n = 12,121; S-PS, n = 1931; and Seattle IC, n = 261).
Our objectives were to compare survival rates to evaluate
egional disparity in de novo MBC survival, to compare
survival rate improvement over time by region and insti-
tution, and to assess the impact of temporal advances in
systemic therapies on trends in de novo stage IV MBC
survival rates. In particular, our focus was on regional
survival differences and the potential for survival rate
improvement over time as patients with metastatic disease
have a poor prognosis and are often treated with palliative
ather than with stabilizing or curative intent.
MATERIALS AND METHODS
The analysis included patients aged 25 to 84 years with
first primary
east cancer who were diagnosed with
de novo stage IV
east cancer from 1990 to 2011 in
the SEER 9 registries and an institutional cohort (IC)
located in the SEER 9 S-PS region (vital status through
2016). We calculated 5 -year
east cancer-specific sur-
vival (BCSS) for 3 time periods XXXXXXXXXX, XXXXXXXXXX,
and XXXXXXXXXX), during which adjuvant chemotherapy
treatments changed significantly and was available for
the IC patients (Table 1).11 For the IC, the BCSS end-
point was
east cancer death confirmed from chart and
or death certificate. For SEER, SEER*Stat-documented
cause-specific survival was used.12 The SEER S-PS region
was used separately for comparison with SEER 9 without
S-PS and the IC. Five-year BCSS and 95% CIs and Cox
proportional hazard models were calculated using SPSS
25.0 (IBM Corporation) for the institutional cohort and
STATA (StataCorp LLC) for SEER 9.13,14 BCSS was
estimated as the net measure representing survival from
death caused by the primary diagnosed
east cancer in
the absence of other causes of death. Patients who died
of causes other than those specified were considered to be
censored.15
Cox proportional hazards modelling was used to es-
timate adjusted hazard ratios (HzR) with co
esponding
95% CIs, with death from disease as the endpoint. The
IC was used to build an a priori model informed by a
chi-square analysis and tested by stepwise entry into the
model with a subsequent forced-entry model to include
all variables of interest in the SEER 9 population. The
proportional hazards assumption was evaluated graph-
ically using the log(-log[survival]) versus log of survival
time. We found no evidence suggesting violation of the
proportionality assumption. All P values were 2-sided
using a .05 level of significance.
Data from the SEER 9 population-based cancer
egistries (Connecticut, Detroit, Atlanta, San Francisco-
Oakland, Hawaii, Iowa, New Mexico, Seattle-Puget Sound,
and Utah) were included in our analysis.16 The SEER pro-
gram is funded by the National Institutes of Health and the
National Cancer Institute and represents cancer incidence
data for approximately 28% of the US population.
The institutional cohort (IC)
east cancer registry
database, which was created in 1990, contains detailed
information on diagnosis, pathology, staging, surgery,
chemotherapy, radiation therapy, tumor markers, and
vital status at follow-up, including cause-specific death.
Incident
east cancer cases are entered at the time of diag-
nosis in a Health Insurance Portability and Accountability
Act of 1996 (HIPAA)-compliant and Institutional Review
Board (IRB)-approved research registry. This project was
HIPAA compliant and IRB approved. Patient vital and
disease status, including date, site and type of recu
ence,
and date and cause of death, is collected prospectively
through annual updates by a certified cancer registrar.
Follow-up is obtained from: 1) electronic chart review;
2) an IRB-approved, physician-directed follow-up letter;
3) an institutional cancer registry; and 4) the SEER S-PS
egistry.17
TABLE 1. Change in Systemic Therapy From 1990 to 2011: Stage IV Breast Cancer, IC Patients only, n = 261
Systemic Therapy
No. of Patients (%)
P XXXXXXXXXX XXXXXXXXXX
Initial chemotherapy, n = XXXXXXXXXX XXXXXXXXXX
Taxane therapy, n = XXXXXXXXXX64 (76) <.001
Anthracycline therapy, n = XXXXXXXXXX XXXXXXXXXX
Trastuzumab therapy: HER-2–positive patients, n = XXXXXXXXXX100) <.001
Neoadjuvant therapy, n = XXXXXXXXXX XXXXXXXXXX
Hormone therapy: HR-positive patients, n = XXXXXXXXXX XXXXXXXXXX
A
eviation: HR, hormone receptor.
Original Article
392 Cancer January 15, 2020
RESULTS
The SEER 9 without S-PS population and the SEER S-PS
egion population were both