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Hospital visits among women with skeletal-related events secondary to breast cancer and bone metastases: A nationwide population-based cohort study in Denmark

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Skeletal-related events (SREs) among women with breast cancer may be associated with considerable use of health-care resources. We characterized inpatient and outpatient hospital visits in a national population-based cohort of Danish women with SREs secondary to breast cancer and bone metastases. We identified first-time breast cancer patients with bone metastases from 2003 through 2009 who had a subsequent SRE (defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone). Hospital visits included the number of inpatient hospitalizations, length of stay, number of hospital outpatient clinic visits, and emergency room visits. The number of hospital visits was assessed for a pre-SRE period (90 days prior to the diagnostic period), a diagnostic period (14 days prior to the SRE), and a post-SRE period (90 days after the SRE). Patients who experienced more than one SRE during the 90-day post-SRE period were defined as having multiple SREs and were followed until 90 days after the last SRE. We identified 569 women with SREs secondary to breast cancer with bone metastases. The majority of women had multiple SREs (73.1%). A total of 20.9% and 33.4% of women with single and multiple SREs died in the post-SRE period, respectively. SREs were associated with a large number of hospital visits in the diagnostic period, irrespective of the number and type of SREs. Women with multiple SREs generally had a higher number of visits compared to those with a single SRE in the post-SRE period, eg, median length of hospitalization was 5 days (interquartile range 0-15) for women with a single SRE and 13 days (interquartile range 4-30) for women with multiple SREs. SREs secondary to breast cancer and bone metastases were associated with substantial use of hospital resources.
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Clinical Epidemiology 2013:5 97–103
Clinical Epidemiology
Hospital visits among women with skeletal-related
events secondary to breast cancer and bone
metastases: a nationwide population-based cohort
study in Denmark
Marie Louise Svendsen1
Henrik Gammelager1
Claus Sværke1
Mellissa Yong2
Victoria M Chia2
Christian F Christiansen1
Jon P Fryzek1
1Department of Clinical Epidemiology,
Aarhus University Hospital, Aarhus,
Denmark; 2Center for Observational
Research, Amgen, Thousand Oaks,
CA, USA
Correspondence: Henrik Gammelager
Department of Clinical Epidemiology,
Aarhus University Hospital, 43–45 Olof
Palmes Allé, Aarhus N 8200, Denmark
Tel +45 8716 8063
Fax +45 8716 7215
Email hg@dce.au.dk
Objective: Skeletal-related events (SREs) among women with breast cancer may be associ-
ated with considerable use of health-care resources. We characterized inpatient and outpatient
hospital visits in a national population-based cohort of Danish women with SREs secondary to
breast cancer and bone metastases.
Methods: We identified first-time breast cancer patients with bone metastases from 2003
through 2009 who had a subsequent SRE (defined as pathologic fracture, spinal cord compres-
sion, radiation therapy, or surgery to bone). Hospital visits included the number of inpatient
hospitalizations, length of stay, number of hospital outpatient clinic visits, and emergency
room visits. The number of hospital visits was assessed for a pre-SRE period (90 days prior to
the diagnostic period), a diagnostic period (14 days prior to the SRE), and a post-SRE period
(90 days after the SRE). Patients who experienced more than one SRE during the 90-day
post-SRE period were defined as having multiple SREs and were followed until 90 days after
the last SRE.
Results: We identified 569 women with SREs secondary to breast cancer with bone metastases.
The majority of women had multiple SREs (73.1%). A total of 20.9% and 33.4% of women
with single and multiple SREs died in the post-SRE period, respectively. SREs were associated
with a large number of hospital visits in the diagnostic period, irrespective of the number and
type of SREs. Women with multiple SREs generally had a higher number of visits compared
to those with a single SRE in the post-SRE period, eg, median length of hospitalization was
5 days (interquartile range 0–15) for women with a single SRE and 13 days (interquartile range
4–30) for women with multiple SREs.
Conclusion: SREs secondary to breast cancer and bone metastases were associated with
substantial use of hospital resources.
Keywords: breast neoplasms, bone metastases, skeletal-related events, hospital services,
utilization
Introduction
Breast cancer accounts for an annual estimated 1.4 million new cases worldwide,
representing a leading cause of death in high-income countries and the main cause
of cancer deaths among females.1,2 Breast cancer is the most common cancer among
women in Denmark, accounting for 26% of all new cancers among women in 2010.3
Breast cancer treatment is associated with the highest costs of all cancer sites, and the
cost is expected to increase due to the aging population and advances in diagnostic
and treatment modalities.4
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Approximately 5%–6% of women have metastasized at
breast cancer diagnosis, with bone metastases representing
the most common site of metastatic lesions.5–8 The clinical
course of metastatic bone disease is relatively long and
characterized by sequential skeletal complications, includ-
ing bone pain, fractures, hypercalcemia, and spinal cord
compression.9 Metastatic bone disease represents a highly
resource-intensive and costly stage of disease, primarily
attributable to hospitalizations and hospital outpatient clini-
cal visits.9–13 Among patients presenting with bone metas-
tases at the time of primary diagnosis, up to 43% develop
skeletal-related events (SREs), defined as radiation to the
bone, pathological fracture, bone surgery, or spinal cord
compression,5 probably adding substantially to the resource
utilization and costs of metastatic bone disease.14 However,
published data about the use of hospital resources in breast
cancer patients with SREs are scarce.15,16 Having up-to-date
information on the allocation of hospital resources would be
important in health-care planning. Therefore, we analyzed
the use of hospital visits in a cohort of Danish women with
SREs secondary to breast cancer and bone metastases.
Methods
Setting and study period
This nationwide population-based cohort study was con-
ducted in Denmark from 2003 through 2009, based on
prospectively collected data from Danish medical registries.
The entire Danish population receives tax-supported health
care from the Danish National Health Service, with free
access to hospital care.17 All Danish citizens are assigned
a unique ten-digit civil registration number, administered
by the Central Office of Civil Registration, which allows
unambiguous linkage among the registries.18
Data sources
The Danish Cancer Registry (DCR) includes data on the
incidence of cancer in the Danish population since 1943. In
1987, it became mandatory for all physicians to report inci-
dent cancers. The quality of newly reported data is checked
against any previous records in the DCR and linked to the
pathology registry and the Danish registry of causes of
death.19 Recorded data include personal and tumor charac-
teristics such as date of birth and diagnosis codes, and tumor
staging. Since 2004, cancers have been classified according
to the International Classification of Diseases, 10th revision
(ICD-10). Coding of cancers diagnosed between 1978 and
2004 has been converted by the DCR from the ICD-7 to the
ICD-10 system. Additional tumor staging at diagnosis was
until 2004 recorded as local, regional, or distant (summary
staging), and according to the tumor, nodes, metastasis
(TNM) classification thereafter.19 Conversion of TNM clas-
sifications to summary staging is presented in Table S1.20
The Danish National Patient Registry holds information
on all Danish somatic hospitalizations since 1977, and on
outpatient activities, emergency room contacts, and activities
in psychiatric wards since 1995.21 The registry serves as a
basis for reimbursement in the Danish health-care system and
holds information on hospital activity, including diagnosis
codes according to the ICD-10 (since 1994), surgical proce-
dures, major treatments performed, hospital and department
identification codes, and date and time of activity.21 The
Danish Civil Registration System has kept up-to-date records
on date of birth, sex, address, date of emigration, and changes
in vital status for all Danish citizens since 1968.18
Study population
We identified all women diagnosed with incident breast
cancer in the Danish Cancer Registry and subsequent bone
metastases in the Danish National Patient Registry between
January 1, 2003 and December 31, 2009. These women were
followed through December 31, 2010 for development of
SREs, defined as first date of spinal cord compression, patho-
logical fracture, surgery to bone, or conventional external
radiation therapy using the Danish National Patient Registry.
The procedure code of conventional external radiation was
not implemented before 2002. To make SRE identification
consistent throughout the study period, we restricted the study
period to 2003, allowing 1 year pre-SRE history (relevant
codes are listed in Table S2).
Hospital contacts
We assessed the number of inpatient hospitalizations, inpa-
tient bed days, hospital outpatient clinic visits, and emergency
room visits. This hospital use was assessed for different
observation periods, including a pre-SRE period (90 days
prior to a diagnostic period), a diagnostic period (14 days
prior to the SRE), and a post-SRE period (90 days after the
SRE). Patients who experienced more than one SRE during
the post-SRE period were defined as having multiple SREs
and followed until 90 days after the last SRE.
Statistical analysis
The number of inpatient hospitalizations, inpatient bed days,
hospital outpatient clinic visits, and emergency room visits
was analyzed using frequency distributions, median, and inter-
quartile range (IQR). Furthermore, the rate (and 95% confidence
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Svendsen et al
Clinical Epidemiology 2013:5
interval [CI]) of hospital contacts was assessed per 100 person-
days according to the number of SREs (1 SRE, .1 SREs), the
observation period (pre-SRE, diagnostic period, post-SRE),
and type of SRE. We compared differences in rates of hospital
contacts between the observation periods using rate ratios with
the pre-SRE period as reference.
Results
We identified 569 women with SREs secondary to breast
cancer and bone metastases among 30,700 women diagnosed
with breast cancer from 2003 through 2009. Radiation therapy
accounted for the vast majority of SREs. The median age at
breast cancer diagnosis was 61.7 years (IQR 52.9–70.7), and
the median length from first SRE to end of follow-up was
3.0 months (IQR 2.8–3.2) (Table 1). A total of 20.9% (32/153)
and 33.4% (139/416) of women with single and multiple
SREs died in the post-SRE period, respectively.
SREs were associated with a high rate of hospital visits
in the diagnostic period, irrespective of the number and type
of SREs (Table 2 and Figure 1). For example, the rate of
bed days per 100 person-days was up to four times higher
in the diagnostic period compared with the pre-SRE period
(rate ratio for women with one SRE: 3.7, 95% CI 3.4–4.1)
(Table 2). Conversely, the absolute number of hospital visits
was lower in the diagnostic period compared with the pre- and
post-SRE period, due to the shorter time window (14 days).
Furthermore, women with multiple SREs generally had a
higher rate of hospital visits compared to those with a single
SRE, particularly in the post-SRE period (Table 2); the rate
of inpatient bed days was 14.2 days per 100 person-days
among women with a single SRE and 23.1 days per 100
person-days among women with multiple SREs. In addition,
Figure 1 shows that patients with one SRE and diagnosed
with pathologic fracture had a higher rate of inpatient bed
days in the diagnostic period. In the post-SRE period, patients
with spinal cord compression had a higher rate of inpatient
bed days and outpatient clinic visits, whereas patients under-
going radiation therapy generally had fewer hospital contacts
in this post SRE-period.
Discussion
In this population-based cohort of 569 Danish women with
breast cancer, bone metastases, and subsequent SREs, we
observed substantial use of hospital resources in relation to
SREs. Notably, SREs were associated with more hospital
visits in the diagnostic period, irrespective of the number
and type of SRE. Furthermore, women with multiple SREs
generally had more hospital visits compared to those with
a single SRE.
Previous studies support our findings that SREs follow-
ing metastatic bone disease are associated with consider-
able use of resources, particularly in relation to inpatient
hospitalizations.14–16 A Spanish study showed that patients
with cancer who developed metastatic bone disease and
subsequent SREs had longer inpatient lengths of stay and
incurred higher inpatient costs compared to those with can-
cer only.15 Furthermore, breast cancer patients who develop
metastatic bone disease subsequent to their index hospital
admission for cancer require more clinical attention from
health-service providers than those who have cancer only,
with this burden increasing further in those who subsequently
develop an SRE.15
A Portuguese retrospective study on 121 women with
breast cancer, bone metastases, and at least one SRE in the
preceding 12 months (defined as spinal cord compression,
pathologic fracture, hypercalcemia of malignancy, and radia-
tion therapy) showed that patients diagnosed with spinal cord
compressions had the highest total costs in the 12-month
observation period, whereas patients undergoing radiation
therapy had the lowest costs.16 Similarly, the highest mean
inpatient costs were observed among patients with spinal
cord compression; however, patients with pathologic fracture
had the lowest costs in a study from the US on 1542 patients
with breast cancer, bone metastasis, and at least one subse-
Table 1 Descriptive characteristics of 569 breast cancer patients
with bone metastases and subsequent SREs
Characteristics
Age at primary cancer diagnosis, yearsa61.7 (52.9–70.7)
Tumor stage at primary cancer diagnosis, n (%)
Local 78 (13.7)
Regional 253 (44.5)
Distant metastases 191 (33.6)
Unknown 47 (8.3)
SRE, n (%)
One SRE 153 (100)
RT 117 (76.5)
PF 19 (12.4)
SSC 14 (9.2)
SB 3 (2.0)
Multiple SREs 416 (100)
Multiple treatments with RT alone 268 (64.4)
RT combined with PF, SSC, and/or SB 119 (28.6)
PF, SCC, and/or SB 29 (7.0)
Months from primary cancer diagnosis to
bone metastasesa
12.3 (0.8–29.0)
Months from bone metastases to rst SREa0.8 (0.1–6.0)
Months from rst SRE to end of follow-upa3.0 (2.8–3.2)
Note: aMedian (interquartile range).
Abbreviations: PF, pathological fracture; RT, radiation therapy; SB, surgery to
bone; SCC, spinal cord compression; SREs, skeletal-related events.
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Hospital visits among women with SREs secondary to breast cancer
Clinical Epidemiology 2013:5
Table 2 Hospital visits and follow-up time among 569 breast cancer patients with bone metastases and subsequent SREs
Hospital services 1 SRE (n = 153) .1 SRE (n = 416)
Pre-SRE Diagnostic
period
Post-SRE Pre-SRE Diagnostic
period
Post-SRE
Inpatient visits
Patients, n (%) 79 (51.6) 85 (55.6) 105 (68.6) 226 (54.3) 233 (56.0) 335 (80.5)
Visits 128 96 184 433 271 734
Median (range) 1 (0–1) 1 (0–2) 1 (0–11) 1 (0–12) 1 (0–3) 1 (1–13)
Per 100 person-days
(95% CI)
0.9 (0.8–1.1) 4.2 (3.4–5.1) 1.5 (1.3–1.8) 1.2 (1.1–1.3) 4.3 (3.9–4.9) 1.9 (1.8–2.1)
Rate ratioa1 (ref) 4.5 (3.4–5.9) 1.7 (1.3–2.1) 1 (ref) 3.8 (3.2–4.4) 1.7 (1.5–1.9)
Bed days
Patients, n (%) 79 (51.6) 85 (55.6) 105 (68.6) 226 (54.3) 233 (56.0) 335 (80.5)
Days 1201 742 1690 2415 1706 8757
Median (range) 1 (0–72) 2 (0–15) 5 (0–90) 2 (0–90) 1 (0–15) 13 (0–158)
Per 100 person-days
(95% CI)
8.7 (8.2–9.2) 32.3 (30.1–34.7) 14.2 (13.5–14.9) 6.5 (6.2–6.7) 27.3 (26.1–28.7) 23.1 (22.6–23.6)
Rate ratioa1 (ref) 3.7 (3.4–4.1) 1.6 (1.5–1.8) 1 (ref) 4.2 (4.0–4.5) 3.6 (3.4–3.7)
Emergency room visits
Patients, n (%) 14 (9.2) 16 (10.5) 12 (7.8) 38 (9.1) 39 (9.4) 90 (21.6)
Visits 18 16 14 45 43 110
Median (range) 0 (0–2) 0 (0–1) 0 (0–3) 0 (0–2) 0 (0–2) 0 (0–3)
Per 100 person-days
(95% CI)
0.1 (0.1–0.2) 0.7 (0.4–1.1) 0.1 (0.1–0.2) 0.1 (0.1–0.2) 0.7 (0.5–0.9) 0.3 (0.2–0.3)
Rate ratioa1 (ref) 5.3 (2.5–11.1) 0.9 (0.4–1.9) 1 (ref) 5.7 (3.7–8.9) 2.4 (1.7–3.5)
Outpatient visits
Patients, n (%) 139 (90.8) 109 (71.2) 145 (94.8) 359 (86.3) 325 (78.1) 395 (95.0)
Visits 675 196 760 1847 683 4154
Median (range) 3 (0–30) 1 (0–11) 4 (0–26) 4 (1–34) 1 (1–12) 8 (0–71)
Per 100 person-days
(95% CI)
4.9 (4.5–5.3) 8.5 (7.4–9.8) 6.4 (5.9–6.9) 4.9 (4.7–5.2) 10.9 (10.2–11.8) 10.9 (10.6–11.3)
Rate ratioa1 (ref) 1.7 (1.5–2.0) 1.3 (1.2–1.4) 1 (ref) 2.2 (2.0–2.4) 2.2 (2.1–2.3)
Follow-up time, days 13,770 2295 11,899 37,440 6240 37,948
Note: aThe number of visits or days per person-day with the prediagnostic period as reference and 95% CIs.
Abbreviations: CI, condence interval; SREs, skeletal-related events.
quent hospitalization for an SRE (defined as bone surgery,
pathologic fracture, and spinal cord compression).22 These
observations support our finding that patients with spinal
cord compression require substantial hospital resources in
the post-SRE period. However, our study also suggests that
patients diagnosed with pathologic fracture require substan-
tial hospital resources in the diagnostic period.
To the best of our knowledge, this study is the first to
compare the allocation of hospital use during adjacent time
periods prior to and after the first SRE. However, our finding
of a high number of hospital contacts in the diagnostic period
(ie, 14 days prior to the SRE occurrence) is partly supported
by previous studies. A study among Medicare beneficiaries
suggests that the imaging costs in breast cancer patients
have increased at a markedly higher rate than the increase in
overall costs during 1999–2006.23 These observations may
denote a growing use of diagnostic modalities in cancer
care. Furthermore, diagnostic evaluation is complex and
may be conducted in a sequential process involving several
investigations and referrals to hospital before a definitive
diagnosis is made.24
A main strength of our study includes the nationwide
population-based design, with up-to-date data on the num-
ber of hospital contacts in relation to inpatient bed days,
emergency room visits, and hospital outpatient clinic visits
reflecting major cost items in breast cancer care. The data
were registered blind to the study hypothesis, minimizing the
risk of differential misclassification and bias. Furthermore,
patients who died during follow-up had a shortened observa-
tion time (which may be reflected in a moderated number of
hospital contacts), but virtually complete information on vital
status allowed for taking the observation time into account.
Limitations of the study include the inability to distin-
guish between the use of hospital resources for SRE and
non-SRE-related purposes. Furthermore, we did not have
information on other resource items that may impact costs,
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Svendsen et al
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including medications used during hospitalization, which
may also represent a considerable cost category in SRE.16 As
a consequence, we likely underestimated the use of hospital
resources in our study population. The generalizability of our
findings may also be limited by the reliance on the diagnosis
codes in the Danish National Patient Registry to identify
bone metastases and SREs. A previous study showed that
bone metastases secondary to breast cancer in the Danish
National Patient Registry have a sensitivity of 0.32 (95%
CI 0.13–0.57) and specificity of 0.99 (95% CI 0.93–1.00),
and SREs secondary to breast cancer have a sensitivity of
0.75 (95% CI 0.43–0.95) and a specificity of 0.97 (95% CI
0.90–0.99).25 In addition we used Danish procedure codes
and ICD-10 codes to define SREs, and our results may not be
directly applicable to other health-care systems using other
coding systems and practice. Furthermore, it is necessary to
evaluate whether any distinguishing factors in patient and
health-service characteristics could somehow modify the
observed findings before generalizing the results to other
populations and settings, due to differences in the treatment
of breast cancer across countries.26
Conclusion
In conclusion, SREs secondary to breast cancer and bone
metastases were associated with substantial use of hospital
resources.
Disclosure
Funding was provided by a research grant to Aarhus
University by Amgen Inc. VMC is employed by and a share-
holder of Amgen Inc. MY and JPF are former employees
of Amgen Inc. None of the other authors report receiving
fees, honoraria, grants, or consultancies from Amgen.
MLS, HG, CS, and CFC are on the staff of the Department
of Clinical Epidemiology, Aarhus University Hospital,
Aarhus, Denmark. The department receives funding from
various companies (including Amgen Inc) as research grants
to and administered by Aarhus University.
References
1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer
statistics. CA Cancer J Clin. 2011;61(2):69–90.
2. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and
regional burden of disease and risk factors, 2001: systematic analysis
of population health data. Lancet. 2006;367(9524):1747–1757.
3. Danish National Board of Health. Cancer registry 2010. Copenhagen,
Denmark: Danish National Board of Health; 2011. Available from:
http://www.ssi.dk/Sundhedsdataogit/Registre/Cancerregisteret.aspx.
Accessed February 18, 2013.
4. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of
the cost of cancer care in the United States: 2010–2020. J Natl Cancer
Inst. 2011;103(2):117–128.
5. Jensen AØ, Jacobsen JB, Nørgaard M, Yong M, Fryzek JP, Sørensen HT.
Incidence of bone metastases and skeletal-related events in breast cancer
patients: a population-based cohort study in Denmark. BMC Cancer.
2011;11:29.
6. Louwman WJ, Voogd AC, van Dijck JA, et al. On the rising trends of
incidence and prognosis for breast cancer patients diagnosed 1975–
2004: a long-term population-based study in southeastern Netherlands.
Cancer Causes Control. 2008;19(1):97–106.
7. Coleman RE, Rubens RD. The clinical course of bone metastases from
breast cancer. Br J Cancer. 1987;55(1):61–66.
8. van den Hurk CJ, Eckel R, van de Poll-Franse LV, et al. Unfavourable
pattern of metastases in M0 breast cancer patients during 1978–2008:
a population-based analysis of the Munich Cancer Registry. Breast
Cancer Res Treat. 2011;128(3):795–805.
9. Coleman RE. Metastatic bone disease: clinical features, pathophysiology
and treatment strategies. Cancer Treat Rev. 2001;27(3):165–176.
10. Lidgren M, Wilking N, Jönsson B, Rehnberg C. Resource use and costs
associated with different states of breast cancer. Int J Technol Assess
Health Care. 2007;23(2):223–231.
11. Schulman KL, Kohles J. Economic burden of metastatic bone disease
in the US. Cancer. 2007;109(11):2334–2342.
12. Warren JL, Yabroff KR, Meekins A, Topor M, Lamont EB, Brown ML.
Evaluation of trends in the cost of initial cancer treatment. J Natl Cancer
Inst. 2008;100(12):888–897.
13. Foster TS, Miller JD, Boye ME, Blieden MB, Gidwani R, Russell MW.
The economic burden of metastatic breast cancer: a systematic
review of literature from developed countries. Cancer Treat Rev.
2011;37(6):405–415.
4540353025
RT PF SCC
Bed-days/100 person-days
RT PF SCC
Outpatient visits/100 person-days
2015105
Post-SRE
Diagnostic
period
Pre-SRE
20151050
Post-SRE
Diagnostic
period
Pre-SRE
RT PF SCC
Emergency room visits/100 person-days
4.5 5.04.03.53.02.0 2.51.51.00.50.0
Post-SRE
Diagnostic
period
Pre-SRE
Figure 1 Hospital visits for women with only one SRE by SRE type.
Abbreviations: RT, radiation therapy; PF, pathological fracture; SCC, spinal cord compression; SRE, skeletal-related event.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
101
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Clinical Epidemiology 2013:5
14. Delea T, McKiernan J, Brandman J, et al. Retrospective study of the
effect of skeletal complications on total medical care costs in patients
with bone metastases of breast cancer seen in typical clinical practice.
J Support Oncol. 2006;4(7):341–347.
15. Pockett RD, Castellano D, McEwan P, Oglesby A, Barber BL, Chung K.
The hospital burden of disease associated with bone metastases and
skeletal-related events in patients with breast cancer, lung cancer, or
prostate cancer in Spain. Eur J Cancer Care (Engl). 2010;19(6):
755–760.
16. Félix J, Andreozzi V, Soares M, et al. Hospital resource utilization
and treatment cost of skeletal-related events in patients with metastatic
breast or prostate cancer: estimation for the Portuguese National Health
System. Value Health. 2011;14(4):499–505.
17. Frank L. Epidemiology. When an entire country is a cohort. Science.
2000;287(5462):2398–2399.
18. Pedersen CB. The Danish Civil Registration System. Scand J Public
Health. 2011;39(Suppl 7):22–25.
19. Gjerstorff ML. The Danish Cancer Registry. Scand J Public Health.
2011;39(Suppl 7):42–45.
20. Ording AG, Nielsson MS, Frøslev T, Friis S, Garne JP, Søgaard M.
Completeness of breast cancer staging in the Danish Cancer Registry,
2004–2009. Clin Epidemiol. 2012;4 Suppl 2:11–16.
21. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient
Register. Scand J Public Health. 2011;39(Suppl 7):30–33.
22. Barlev A, Song X, Ivanov B, Setty V, Chung K. Payer costs for inpa-
tient treatment of pathologic fracture, surgery to bone, and spinal cord
compression among patients with multiple myeloma or bone metas-
tasis secondary to prostate or breast cancer. J Manag Care Pharm.
2010;16(9):693–702.
23. Dinan MA, Curtis LH, Hammill BG, et al. Changes in the use and
costs of diagnostic imaging among Medicare beneficiaries with cancer,
1999–2006. JAMA. 2010;303(16):1625–1631.
24. Hansen RP, Vedsted P, Sokolowski I, Søndergaard J, Olesen F. Time
intervals from first symptom to treatment of cancer: a cohort study
of 2,212 newly diagnosed cancer patients. BMC Health Serv Res.
2011;11:284.
25. Jensen AØ, Nørgaard M, Yong M, Fryzek JP, Sørensen HT. Validity
of the recorded International Classification of Diseases, 10th edition
diagnoses codes of bone metastases and skeletal-related events in breast
and prostate cancer patients in the Danish National Registry of Patients.
Clin Epidemiol. 2009;1:101–108.
26. Kiderlen M, Bastiaannet E, Walsh PM, et al. Surgical treatment of
early stage breast cancer in elderly: an international comparison. Breast
Cancer Res Treat. 2012;132(2):675–682.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
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Clinical Epidemiology 2013:5
Appendix
Table S1 Conversion of TNM classication system to summary
staging
Summary staging TNM
Local T1–4, N0, M0
T1–2, N0, Mx
T1, Nx, M0 or Mx
Regional T1–4 or Tx, N1–3, M0
Distant Any T, Any N, M1
Unknown T2–4 or Tx, Nx, M0 or Mx
T3–4 or Tx, N0, Mx
T1–4 or Tx, N1–3, Mx
T0, N1–3, M0–1 or Mx
T0, N0 or Nx, M1
Note: x, variable not specied in the Danish Cancer Registry.
Abbreviation: TNM, tumor, nodes, metastasis.
Table S2 Codes to identify skeletal related events in the DNPR
among patients with breast cancer and bone metastases
Pathologic fracture (ICD-10 codes)
M80.0: postmenopausal osteoporosis with pathological fracture
M84.4: fracture of bone in neoplastic disease
M90.7: fracture of bone in neoplastic disease
S12.0–12.9: fracture of neck
S22.0: fracture of thoracic vertebra
S22.1: multiple fractures of thoracic spine
S32.0–S32.8: fracture of lumbar spine and pelvis
S52.5–S52.6: fracture of lower end of radius and/or ulna
S72.0–72.9: fracture of femur
Spinal cord compression (ICD-10 codes)
M43.9: deforming dorsopathy, unspecied
M48.5: collapsed vertebra, not elsewhere classied
M49.5: collapsed vertebra I disease classied elsewhere; metastatic
fracture of vertebrae
G95.2: cord compression, unspecied
G95.8: other specied diseases of spinal cord
Surgery to bone (NOMESCO classication of surgical
procedure code)
KNxJxx: surgical fracture treatment
Radiation therapy (Danish treatment code)
BWGC1: conventional external radiation therapy
Abbreviations: DNPR, Danish National Patient Registry; ICD-10, 10th revision of
the International Classication of Diseases; NOMESCO, Nordic Medicostatistical
Committee.
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Hospital visits among women with SREs secondary to breast cancer
... Our models predicted a higher risk of SREs with a greater number of clinic visits including 1 inpatient hospital visit. This prediction is supported by previous reports on the risk of developing SREs in relation to inpatient hospitalizations associated with metastatic bone disease [39][40][41]. We found a frequency of 4-6+ visits per month, regardless of visit type from 6 months before diagnosis of bone metastasis up to denosumab discontinuation, were associated with an increased SRE risk 3-12 months following discontinuation. ...
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Background Clinical practice guidelines recommend the use of bone–targeting agents for preventing skeletal-related events (SREs) among patients with bone metastases from solid tumors. The anti-RANKL monoclonal antibody denosumab is approved for the prevention of SREs in patients with bone metastases from solid tumors. However, real-world data are lacking on the impact of individual risk factors for SREs, specifically in the context of denosumab discontinuation. Purpose We aim to identify risk factors associated with SRE incidence following denosumab discontinuation using a machine learning approach to help profile patients at a higher risk of developing SREs following discontinuation of denosumab treatment. Methods Using the Optum PanTher Electronic Health Record repository, patients diagnosed with incident bone metastases from primary solid tumors between January 1, 2007, and September 1, 2019, were evaluated for inclusion in the study. Eligible patients received ≥ 2 consecutive 120 mg denosumab doses on a 4-week (± 14 days) schedule with a minimum follow-up of ≥ 1 year after the last denosumab dose, or an SRE occurring between days 84 and 365 after denosumab discontinuation. Extreme gradient boosting was used to develop an SRE risk prediction model evaluated on a test dataset. Multiple variables associated with patient demographics, comorbidities, laboratory values, treatments, and denosumab exposures were examined as potential factors for SRE risk using Shapley Additive Explanations (SHAP). Univariate analyses on risk factors with the highest importance from pooled and tumor-specific models were also conducted. Results A total of 1,414 adult cancer patients (breast: 40%, prostate: 30%, lung: 13%, other: 17%) were eligible, of whom 1,133 (80%) were assigned to model training and 281 (20%) to model evaluation. The median age at inclusion was 67 (range, 19–89) years with a median duration of denosumab treatment of 253 (range, 88–2,726) days; 490 (35%) patients experienced ≥ 1 SRE 83 days after denosumab discontinuation. Meaningful model performance was evaluated by an area under the receiver operating curve score of 77% and an F1 score of 62%; model precision was 60%, with 63% sensitivity and 78% specificity. SHAP identified several significant factors for the tumor-agnostic and tumor-specific models that predicted an increased SRE risk following denosumab discontinuation, including prior SREs, shorter denosumab treatment duration, ≥ 4 clinic visits per month with at least one hospitalization (all-cause) event from the baseline period up to discontinuation of denosumab, younger age at bone metastasis, shorter time to denosumab initiation from bone metastasis, and prostate cancer. Conclusion This analysis showed a higher cumulative number of SREs, timing of SRE relative to denosumab initiation, a higher number of hospital visits, and a shorter denosumab treatment duration as the primary risk factors for heightened SRE risk after discontinuation of denosumab, in both the tumor-agnostic and tumor-specific models. Our machine learning approach to SRE risk factor identification reinforces treatment guidance on the persistent use of denosumab and has the potential to help clinicians better assess a patient’s need to continue denosumab treatment and improve patient outcomes.
... Up to 70% of patients with advanced breast cancer [1,2] and up to 90% of patients with advanced prostate cancer [3] are affected. Bone complications are known as skeletal-related events (SRE) and commonly defined as radiation therapy or surgery to bone, pathologic fractures, spinal cord compression, or tumor-induced hypercalcemia [4]. They may cause pain, impair physical activity and negatively impact patients' quality of life (QoL) [5]. ...
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Background In breast cancer and prostate cancer patients, bone metastases (BM) present the main cause of morbidity and often cause debilitating pain, impaired functioning and subsequent deterioration of quality of life (QoL). The management of BM is still challenging. Maintenance or improvement in QoL is the main goal of treatment. Antiresorptive treatment, such as denosumab and bisphosphonates, can help to reduce the frequency of skeletal complications, to control bone pain and potentially to improve QoL. The optimal time point for initiation of antiresorptive therapy is still discussed controversially. In patients with BM, bone pain can be used as a surrogate measure of QoL. However, limited data exist on health-related QoL in patients with BM under antiresorptive treatment. The PROBone registry study evaluated complaints and limitations caused by BM of breast and prostate cancer patients using patient-reported outcomes (PROs) in real-world in Germany. Methods Between 2014 and 2019, 500 patients with histological confirmation of advanced breast or prostate cancer, diagnosed with BM at start of their first antiresorptive therapy were prospectively enrolled in 65 outpatient-centers specialized in medical oncology across Germany. Changes of QoL were assessed monthly from baseline until a maximum of 12 months using the validated pain score Functional Assessment of Cancer Therapy Quality of Life Measurement in patients with bone pain (FACT-BP) supplemented by questions on general pain and on the impact of time spent for treatment of illness on patients’ daily activities. Statistical analysis was performed descriptively by relative and absolute frequencies. Results In total, 486 patients were eligible for final analysis, of these 310 were diagnosed with breast cancer and 176 with prostate cancer. Median age was 67 years for breast cancer and 76 years for prostate cancer patients. 79.7% of breast cancer and 59.7% of prostate patients started antiresorptive treatment within 3 months after diagnosis of BM. More than 75% of patients suffered from bone pain at study inclusion. In total 52% of breast cancer patients and 47.9% of prostate cancer patients reported to take pain medication during the observation period. In breast and prostate cancer patients an initial pain reduction after start of BTA was observed: General pain and bone pain levels as well as the median FACT-BP score showed a constant improvement over the first months and maintained stable at a constant level afterwards. Subgroup analysis showed that patients without pain at baseline reported distinctly better FACT-BP scores throughout the whole observation period than patients with pain at baseline. Looking at time-stress (M)-scores, younger breast cancer patients (<65 years) showed highest burden especially during the first months of treatment. Conclusions Our results indicate overall good adherence to current guideline recommendation, with most breast and prostate cancer patients starting antiresorptive therapy within the first 3 months after diagnosis of BM. This point gains even more importance as our data support current recommendations by ESMO guidelines as well as by German evidence-based S3-guidelines for diagnosis and treatment of breast and prostate cancer to initiate bone-targeted agents (BTA) as soon as BM are diagnosed, to keep pain levels at the lowest level possible, to minimize the debilitating effects of metastatic bone pain and maintain a good QoL. Bone pain management by an early use of BTA following BM diagnosis might improve patient care
... Anti-estrogen hormone therapies and bisphosphonates each have a proven benefit in reducing the development and progression of osteolytic ER+ BMETs; however, BMETs still occur in ~80% of women with ER+ metastatic breast cancer and remain incurable [4,[66][67][68][69][70][71] . The recent addition of agents acting downstream of ERα to decrease proliferation (CDK4/6 inhibitors), while not curative, has yielded significant benefits [72] , likely due in part to the high prevalence of ligand-independent, activating ERα mutations in ER+ metastatic breast cancer [12] . ...
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Full-text available
Aim: Estrogen receptor α-positive (ER+) subtypes of breast cancer have the greatest predilection for forming osteolytic bone metastases (BMETs). Because tumor-derived factors mediate osteolysis, a possible role for tumoral ERα signaling in driving ER+ BMET osteolysis was queried using an estrogen (E2)-dependent ER+ breast cancer BMET model. Methods: Female athymic Foxn1nu mice were inoculated with human ER+ MCF-7 breast cancer cells via the left cardiac ventricle post-E2 pellet placement, and age- and dose-dependent E2 effects on osteolytic ER+ BMET progression, as well as direct bone effects of E2, were determined. Results: Osteolytic BMETs, which did not form in the absence of E2 supplementation, occurred with the same frequency in young (5-week-old) vs. skeletally mature (16-week-old) E2 (0.72 mg)-treated mice, but were larger in young mice where anabolic bone effects of E2 were greater. However, in mice of a single age and across a range of E2 doses, anabolic E2 bone effects were constant, while osteolytic ER+ BMET lesion incidence and size increased in an E2-dose-dependent fashion. Osteoclasts in ER+ tumor-bearing (but not tumor-naive) mice increased in an E2-dose dependent fashion at the bone-tumor interface, while histologic tumor size and proliferation did not vary with E2 dose. E2-inducible tumoral secretion of the osteolytic factor parathyroid hormone-related protein (PTHrP) was dose-dependent and mediated by ERα, with significantly greater levels of secretion from ER+ BMET-derived tumor cells. Conclusion: These results suggest that tumoral ERα signaling may contribute to ER+ BMET-associated osteolysis, potentially explaining the greater predilection for ER+ tumors to form clinically-evident osteolytic BMETs.
... [3][4][5][6][7][8] Early diagnosis and treatment of skeletal metastases are crucial because the impact on patient morbidity, including bone pain, fractures, hypercalcemia, and spinal cord compression, is significant and associated with considerable use of healthcare resources. 3,[9][10][11][12][13] Only 20% of breast cancer patients remain alive 5 years after the discovery of bone metastasis. 13 A prompt multimodal management approach depends on early diagnosis, which is most often based on a combination of imaging, clinical information, blood samples, and, to a lesser extent, bone biopsies. ...
Article
Full-text available
Background The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies. Purpose To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy. Material and Method A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated. Results 210 of 215 biopsies (98%; 95% CI 0.94–0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001–0.03), and three were equivocal (lack of imaging description). Conclusion Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.
... Previous studies using commercial claims databases show that healthcare resource utilization and economic burden are increased in adults with bone metastases [7][8][9] or MM [10,11] who experience SREs. A study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database also showed increased healthcare resource utilization and Medicare costs associated with incident SREs in men with prostate cancer metastatic to bone [12] One study of 569 Danish women with SREs secondary to breast cancer and bone metastases showed that patients with multiple SREs experienced more visits and longer hospitalization stays during the 90 days after an SRE than patients with a single SRE [13] Previous studies have shown that hospitalization cost is the primary contributor to SRE cost [7][8][9][10][11]. Resource use and associated costs are likely to be substantial after SRE hospitalizations, depending on hospital discharge status. ...
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Background Previous studies have quantified direct inpatient costs of skeletal-related events (SREs); however, costs associated with subsequent post-SRE care have not been examined. Methods We identified two study cohorts using 2011–2015 Medicare 20% sample data: patients diagnosed with 1) bone metastases from solid tumors or 2) multiple myeloma (MM), both with SRE-related hospitalization discharge dates January 1, 2011-September 30, 2015. We assessed discharge status and costs from discharge to the earliest of death, end of Medicare enrollment, or December 31, 2015. Discharge status was defined as: skilled nursing facility (SNF), rehabilitation facility, hospice, home health agency (HHA), long-term care (LTC) nursing home, LTC hospital, or rehospitalization within or after 30 days. Percentage, stay duration, and Medicare costs were calculated for each setting. All analyses were descriptive. Results We identified 7988 bone metastases patients and 4277 MM patients discharged from index SRE-related hospitalizations; corresponding mean ages were 76.9 and 76.6 years. The largest proportion of bone metastases patients were discharged to SNF (32.9%), then HHA (13.7%), hospice (13.5%), and LTC (11.3%); the pattern was similar for MM patients (SNF, 35.9%; HHA, 18.2%; hospice, 7.2%; LTC, 1.5%). Almost 10% of patients in both cohorts were re-hospitalized within 30 days. Mean Medicare cost per patient per facility stay was < $10,000 for hospice, and from $15,517 for LTC nursing home to $49,729 for LTC hospital for MM patients. Conclusion Most elderly cancer patients (>75%) require healthcare facility support after SRE-related hospitalization, with substantial associated costs. Post-discharge management is clinically and economically important.
... In addition, breast cancer patients with BM are extremely susceptible to bone-related complications, also known as skeletal-related events (SREs), that require medical and surgical interventions. Common forms of SREs include pain, pathological fractures, spinal cord compression and hypercalcemia (6,7). Currently, bisphosphonates and the recently developed monoclonal antibody (mAb) denosumab are the most commonly used therapeutic agents for managing BM derived from breast cancer. ...
Article
Background: The bone-derived insulin-like growth factor I (IGF-1) and its receptor IGF-1R play a crucial role in promoting the survival and proliferation of cancer cells, and have thus been considered as prime targets for the development of novel antitumor therapeutics. Methods: By using the MDA-MB-231BO cell line, which is the osteotropic metastatic variant of the human breast adenocarcinoma cell line MDA-MB-231, and an in vivo model of breast cancer metastasis to bone, the current study evaluated the effect of AZD3463, an IGF-1R inhibitor, used alone or in combination with zoledronic acid (ZA), on the regulation of IGF-1R associated signal pathway and treatment of bone metastases (BM). Cell proliferation and invasion were measured by methyl thiazolyl tetrazolium (MTT) and Transwell assay respectively. Apoptotic cell number was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Results: AZD3463 was shown to alleviate IGF-1R phosphorylation promoted by IGF-1 treatment in MDA-MB-231BO cells in a dose-dependent manner. In both the cells and the mouse model, 5 nM of AZD3463 stimulated cell apoptosis and suppressed proliferation on a level similar to that of 100 µM of ZA. Remarkably, the combined use of AZD3463 and ZA exhibited a synergistic effect and greater antitumor activity compared to when they were employed individually. Mechanistic investigations indicated that the apoptosis-inducing activity of AZD3463 could be associated to its role in the activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Conclusions: These findings suggested that AZD3463 could serve as a promising therapeutic molecule for treating BM in breast cancer patients, particularly when applied in conjunction with ZA or other antitumor agents.
... As discussed by Ruchlemer et al the standard R-CHOP steroid dose exceeds ≥7.5 mg/day for more than 3 months which is the threshold of prednisone dose recommended by the American College of Rheumatology for prophylactic bisphosphonate use. 20,21 The therapeutic efficacy of bisphosphonates via inhibition of osteoclastic bone resorption and their therapeutic efficacy in many malignancy related bone conditions is well established. 22,23 The efficacy of prophylactic bisphosphonate use in NHL patients has been demonstrated in 2 studies, but standard recommendations and guidelines remain absent. ...
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Chemotherapy associated osteoporosis is a severe problem in patients with malignant diseases as it increases the risk for fractures and deteriorates quality of life. There are very limited data in the literature for the effect of chemotherapy on bone metabolism of adult patients with Non-Hodgkin Lymphoma (NHL). We prospectively evaluated bone remodeling pre- and post-chemotherapy in 61 patients with newly diagnosed NHL. First-line chemotherapy resulted in high bone turnover, which led to increased bone loss and reduced bone mineral density (BMD) of lumbar spine (L1-L4) and femur neck (FN). The reduction of L1-L4 and FN BMD post-chemo was more profound in males and in older patients (>55 years). Patients who received 8 cycles of chemotherapy had a greater reduction of L1-L4 and FN BMD as compared to 6 cycles. The administration of chemotherapy also resulted in a dramatic increase of bone resorption markers (CTX and TRACP-5b), bone formation markers, (bALP and Osteocalcin) and of osteoblast regulator Dickkopf-1. During study period, one patient had a pathological fracture in his right FN.
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