Utility of the Multinational Association for Supportive Care in Cancer

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ORIGINAL RESEARCH & CONTRIBUTIONS
Utility of the Multinational Association for Supportive Care in Cancer
(MASCC) Risk Index Score as a Criterion for Nonadmission in Febrile
Neutropenic Patients with Solid Tumors
Roger A Bitar, MD, MPH
Perm J 2015 Summer;19(3):37-47
http://dx.doi.org/10.7812/TPP/14-188
ABSTRACT
Objectives: This retrospective study was initiated in febrile neutropenic inpatients
with solid tumors in 4 community hospitals, to discover how the Multinational
Association for Supportive Care in Cancer (MASCC) risk index score (RIS) of 21 or
greater correlated with complications occurring in 198 episodes: whether it could
help determine which patients not to admit, the savings of not admitting patients
without complications, and whether an algorithm could facilitate management of
those not admitted.
Methods: Febrile neutropenic episodes in patients with solid tumors were identified electronically between October 1, 2008, and November 15, 2010. Electronic
charts were reviewed manually for inclusion criteria and data extraction. Episodes
were stratified by an MASCC RIS below 21 or 21 or greater. Complications were
correlated with the index.
Results: Inclusion criteria were met in 198 episodes. Sensitivity, specificity, and
positive and negative predictive values of the MASCC RIS vs complications were
94%, 29.6%, 57.7%, and 82.9%, respectively. In episodes with an RIS 21 or greater,
42.3% had complications, misclassifying to low risk 69 episodes with complications.
“Unable to eat” correlated with complications in 84% of episodes. In 3 patients
stratified to no complication, a complication developed 24 hours after admission.
Conclusions: An MASCC RIS of 21 or greater could not be used as a criterion for
“no complication/do not admit.” Inability to eat should be an admission criterion.
Savings of approximately $1 million per 100 uncomplicated admissions could be
realized if appropriate criteria for nonadmission could be devised. An algorithm to
facilitate outpatient management is suggested.
INTRODUCTION
Treatment of malignancies is routine
in community hospitals. Chemotherapy, one of the common forms of treatment, frequently results in neutropenic
fever. Guidelines for the management
of febrile neutropenia include antimicrobial therapy and, for patients with
solid tumors, antecedent granulocyte
colony-stimulating factor.1,2 Before these
guidelines, virtually all febrile neutropenic patients were hospitalized. However,
the depth and duration of neutropenia
in patients receiving chemotherapy for
hematologic and lymphoproliferative
neoplasms is more profound than that
occurring following chemotherapy for
patients with solid tumors; thus, complications following chemotherapy for
solid tumors are less frequent. Some
investigators postulated that patients
not experiencing complications would
not need hospitalization, and thus, they
have striven to identify these noncomplicated cases prospectively and manage
them on an outpatient basis, resulting
in substantial savings.
To this end, a stratification tool, the
Multinational Association for Supportive Care in Cancer (MASCC) risk index
score (RIS) was developed to predict the
risk of serious complications. These risk
criteria are listed in the Sidebar: Klastersky Criteria.3
There are 2 important features to
note. First, only 2 of the 10 Klastersky
criteria are objective, which introduces
a problem in the methods. There is no
objective definition of these criteria:
confusion or altered mental state, such
as the Glasgow Coma Scale; congestive
heart failure requiring treatment, such
as pulmonary edema with a Pao2 below
60 mmHg; bleeding severe enough to
require transfusion, such as a hemoglobin level below 7 g/dL; arrhythmia
or electrocardiographic changes requiring treatment, such as systolic blood
pressure (BP) below 90 mmHg; or
renal failure requiring treatment, such
as a creatinine level above 4 mg/dL.
Furthermore, the last criterion is completely subjective: “other complications
judged serious and clinically significant
by the investigator.” Second, an exclusion to this criterion was included as a
footnote: “Viral or fungal, microbiologically documented primary infection
during the febrile episode, without any
described complication and resolving
under therapy, was considered a part
of the infectious process and was not
considered a serious complication.”3p3040
Table 1 lists the components of the
MASCC RIS.3 (Note that only 4 of
the 7 criteria are objective. Burden of
illness, chronic obstructive pulmonary
disease (COPD), and “no dehydration”
are not objective criteria.) An MASCC
RIS of 21 or above equals a low risk of
complications; an MASCC RIS below
21 equals a high risk of complications.
Using an MASCC RIS of 21 or greater
as low risk, only 6% of a validation group
(n = 551) experienced serious complications compared with 39% who had a
score below 21. Validation of this index
Roger A Bitar, MD, MPH, is a Consultant with Mission Infectious Disease and Infusion Consultants, Inc, in Poway, CA,
and a former Infectious Disease Specialist at the San Diego Medical Center. E-mail: [email protected]
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
37
ORIGINAL RESEARCH & CONTRIBUTIONS
Utility of the MultinationalAssociation for Supportive Care in Cancer (MASCC)
RiskofIndex
as a Criterion
for Nonadmission
in FebrileCare
Neutropenic
Patients
with Solid
Utility
the Score
Multinational
Association
for Supportive
in Cancer
(MASCC)
RiskTumors
Index
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
METHODS
Patient Selection
Table 1. Components of the Multinational Association for Supportive Care
in Cancer Indexa
Clinical characteristic
Burden of illness (1 of the 3 options only):
No or mild symptoms
Moderate symptoms
Scoreb
5
3
Severe symptoms
0
No hypotension (systolic BP > 90 mmHg)
No chronic obstructive pulmonary disease
Solid tumor or no prior fungal infection in patient with hematologic neoplasm
5
4
4
No dehydration (hydration with IV fluids not required)
Outpatient at onset of fever
Age < 60 years
3
3
2
Burden of illness, no chronic obstructive pulmonary disease, and no dehydration are not objective criteria.
Maximum score: 26 (5 + 5 + 4 + 4 + 3 + 3 + 2). Low risk for complication = score ≥ 21; high risk for
complication = score < 21.
BP = blood pressure; IV = intravenous.
a
b
has been declared in publications from
academic (university) medical centers.
However, the definitions in all these
studies (eg, burden of illness, COPD,
or dehydration) were not consistently
provided, and the mix of patients with
solid vs hematologic and lymphoproliferative neoplasms was not the same, raising the question of whether the results
are comparable.4-8
The current retrospective study of
inpatients from 4 community hospitals
Klastersky criteria1
Systolic blood pressure (BP) < 90 mmHg or need
for [vaso]pressor support to maintain BP
Arterial oxygen pressure (Pao2) ≤ 60 mmHg
while breathing room air or need for mechanical
ventilation
Intensive care unit admission
Disseminated intravascular coagulation
Confusion or altered mental state
Congestive cardiac failure seen on chest x-ray and
requiring treatment
Bleeding severe enough to require transfusion
Arrhythmia or ECG [electrocardiographic]
changes requiring treatment
Renal failure requiring investigation and/or treatment with IV [intravenous] fluids, dialysis, or any
other intervention
Other complications judged serious and clinically
significant by the investigator
1. Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational
Association for Supportive Care in Cancer risk index: a multinational
scoring system for identifying low-risk febrile neutropenic cancer
patients. J Clin Oncol 2000 Aug;18(16):3038-51.
38
was devised to answer the following
questions.
1.How many times were the named
items in the Klastersky criteria used as
reasons for admission to the hospital
by the general internists admitting patients? (As noted earlier, when a febrile
neutropenic patient with an infection
makes initial contact with a health care
practitioner for that febrile episode,
the Klastersky criteria do not consider
that infection a complication, and, in
addition, there are unnamed complications in the Klastersky criteria.)
2.Are there additional complications,
not listed by name in the Klastersky
criteria, that a physician might consider important in the nonadmission
decision?
3.Would the course of patients stratified to the low-risk category (MASCC
RIS ≥ 21) be without serious complications and, thus, be able to be
managed as outpatients (ie, stratified
to “Do not admit”)?
4.If inpatients with an MASCC RIS of
21 or higher did experience complications, what were they and on what
day of hospitalization did they occur?
5.If the patients with an MASCC RIS
of 21 or above were not admitted and
experienced complications, what management algorithm could be proposed
to identify these complications early?
6.What savings would be realized if all
the patients without serious complications were not admitted to the
hospital?
Management of febrile neutropenic
patients, at the time of this study and at
the medical centers listed, was admission
to the hospital, evaluation in the usual
manner with appropriate laboratory
tests and imaging studies, administration of granulocyte colony-stimulating
factor (89%), and antimicrobial agents.
All but 10 patients received acceptable
antimicrobial regimens. Charts were retrospectively reviewed for the following
inclusion criteria: adult inpatients with
solid tumors who became neutropenic
(absolute neutrophil count < 500/μL,
except for 2 that were 600/uL) after chemotherapy, who were given an admission
or discharge diagnosis of neutropenic
fever, who had documented fever by
self-report or on admission, and who
received antimicrobial therapy for neutropenic fever. Patients younger than 18
years and those whose admissions lasted
less than 24 hours were excluded. All
inpatient electronic medical records of
patients admitted to 4 Kaiser Permanente (KP) hospitals in California were
searched for drug-induced neutropenia
(International Classification of Diseases,
Ninth Revision, code 288.0) and feverpresenting conditions classified elsewhere (code 780.61). The hospitals were
San Diego Medical Center (admissions
from October 1, 2008, to November 15,
2010); Irvine Medical Center and Anaheim Medical Center (Orange County;
admissions from October 1, 2008, to
April 30, 2010); and Woodland Hills
Medical Center (admissions from October 1, 2008, to April 30, 2010). The
charts of these patient episodes were
sequentially and manually screened for
inclusion criteria and reviewed in detail.
If inclusion criteria were met, data were
extracted.
Data included: age, sex, admission
date, discharge date, death date, the
type of solid tumor, whether it was
metastatic beyond local nodes, admitting physician’s reason for admission, length of stay (LOS), reason for
extended hospital stay, intensive care
unit care, comfort care, other diagnoses in the problem list which might be
considered immunocompromising,
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
ORIGINAL RESEARCH & CONTRIBUTIONS
Utilityofofthethe
Multinational
Association
forSupportive
CareinCancer
(MASCC)
IndexScore
aCriterionforNonadmissioninFebrileNeutropenicPatientswithSolidTumors
Utility
Multinational
Association
for Supportive
Care in
CancerRisk
(MASCC)
RiskasIndex
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
smoking status, diagnosis of COPD,
occurrence of fever associated with
neutropenia, days to temperature
≤ 37.5 and ≤ 38 C, an ANC < 500 cells/uL,
return of ANC to greater than
500 cells/uL, duration of neutropenia,
death, reception of filgrastim before
and subsequently after admission,
gastrointestinal symptoms (nausea,
vomiting, diarrhea, abdominal pain,
“unable to eat,”), serum biochemical
tests (creatinine > 2 mg/dL, potassium
< 3 mEq/L, sodium of < 130 mEq/L,
phosphorus of < 2.7 mg/dL), density/
intensity of chemotherapy, types of
infections, positive bacterial cultures,
microorganisms isolated, antimicrobial
agents prescribed when outpatient and
inpatient, results of pertinent imaging
studies, MASCC RIS components,
and medical complications listed in the
Klastersky criteria.
All febrile neutropenic patient episodes meeting inclusion criteria were
divided into 2 groups on the basis of
complications: Group 1, no complication (equivalent to “do not admit”),
or Group 2, complication (equivalent to “admit”). Group 1 (n = 100)
had only fever and neutropenia, had
none of the medical complications
(Table 2) on admission or within 24
hours of admission, and were able to
eat. Group 2 (n = 98) had 1 or more
of the complications listed in Table 2
at admission or within 24 hours of
admission. There were 3 patients in
Group 1 in whom complications
developed 24 hours after admission,
which if they had been present on
presentation would have classified
each patient into Group 2 initially.
Each patient episode was assigned to
an MASCC RIS of 21 or greater or
below 21, and these scores were correlated with the no complication and
complication groups (Figure 1). The
KP Southern California institutional
review board approved the study.
Medical Centers
In 2012, beds and discharges per
month were as follows: San Diego,
392 beds and 32,491 discharges;
Orange County, 350 beds (2 hospitals),
28,564 discharges; and Woodland
Hills, 262 beds and 13,741 discharges.
All 4 hospitals fall into the tertiary care
category, providing a full range of basic
and sophisticated diagnostic and treatment services, including many specialized services.
Statistical Analysis
A sample size of 200 episodes was
chosen as the basis for another study,
not yet published, from which this
analysis was done. Two episodes did
not meet criteria, leaving 198 episodes.
Standard methods of calculating sensitivity, specificity, positive predictive
value, and negative predictive value
were used. The Wilcoxon rank sum
test was used to compare for those who
were unable to eat and for those who
were able to eat.
RESULTS
Patient characteristics are shown in
Table 3.
Klastersky Criteria versus Complications
Table 2 lists the components of the
Klastersky criteria; complications,
which includes the reasons for admission and subsequent complications;
the MASCC RIS; and LOS. There
are 69 patients in Table 2 who had an
MASCC RIS of 21 or above and had
reasons for admission and/or complications. Only 20 patients of the 69 had
complications named in the Klastersky
criteria as a reason for admission. If the
Klastersky criteria were to be applied,
the other 49 reasons for admission
would have to be assumed to fall into
the last Klastersky category, “other
complications judged serious or clinically significant by the investigator.”
Thirty-eight patients were unable to
eat, 22 had identified infections, 21
could be considered to have mucositis,
and 5 were found to have typhlitis.
Risk Index Score versus Complications
The sensitivity of the MASCC RIS
was 94% (94 of 100 episodes) with
a 95% confidence interval (CI) of
87.4% to 97.8%, and specificity was
29.6% (29/98; 95% CI = 20.8% to
39.7%). The positive predictive valve
was 57.67% (94/163; 95% CI = 49.7%
to 65.4%), and the negative predictive
valve was 82.9% (29/35; 95% CI =
66.34% to 93.4%).
Figure 1. Assignment of episodes of febrile neutropenia to Multinational Association for Supportive Care in Cancer (MASCC) risk index score (RIS)
and complications.a
a
Three complications occurred after admission to the hospital in patients stratified to “no complication” and would have occurred on an outpatient basis if the patients
had not been admitted.
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
39
ORIGINAL RESEARCH & CONTRIBUTIONS
Utility of the MultinationalAssociation for Supportive Care in Cancer (MASCC)
RiskofIndex
as a Criterion
for Nonadmission
in FebrileCare
Neutropenic
Patients
with Solid
Utility
the Score
Multinational
Association
for Supportive
in Cancer
(MASCC)
RiskTumors
Index
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
Table 2. Klastersky criteria and complications in 69 patients with an MASCC RIS > 21
Patient
episode
number
Klastersky criteria
(named)
Klastersky criteria
(Presumed to be in ”Other complications
judged serious and clinically significant
by the investigator”)
Reason for
admission
Complication after
admission
MASCC
RIS
Length
of stay,
days
1
None
None
Cellulitis
None
21
3
2
SBP < 90 mmHg/need for
vasopressors
Nausea, vomiting
SBP < 98 mmHg in a 90 year old
None
21
5
3
None
Unable to eat
Unable to eat, mucositis
None
21
5
4
None
Unable to eat, K 2.9 mEq/L
Unable to eat, K 2.9 mEq/L
Day 3: K 3 mEq/L
21
5
5
None
Unable to eat, nausea, diarrhea,
abdominal pain
Unable to eat, nausea, diarrhea,
abdominal pain
None
21
5
6
None
Unable to eat, nausea, vomiting,
abdominal pain
Unable to eat, nausea, vomiting,
abdominal pain
None
21
5
7
SBP < 90 mmHg/need for
vasopressors
Diarrhea
Diarrhea/SBP < 90 mmHg
None
21
6
8
Arrhythmia, ECG changes
Unable to eat, nausea, vomiting
Unable to eat, nausea, vomiting, atrial flutter
None
21
6
9
None
Unable to eat, difficulty swallowing
Unable to eat, difficulty swallowing
None
21
6
10
None
Nausea, vomiting
Nausea, vomiting, bacteremia
None
21
7
11
None
Nausea, abdominal pain, K < 3 mEq/L
Nausea, abdominal pain, Typhlitis, K < 3 mEq/L
None
21
7
12
None
Unable to eat, diarrhea
Unable to eat, diarrhea
Stomatitis
21
7
13
None
Nausea, vomiting,
Nausea, Vomiting, positive blood culture
None
21
7
14
SBP < 90 mmHg/need for
vasopressors, arrhythmia, ECG
changes
Nausea, vomiting
Nausea, vomiting,
Low SBP within first 24 hours,
SVT 3 days
21
8
15
SBP < 90 mmHg/need for
vasopressors, bleeding
requiring transfusion
Penile bleeding
Penile bleeding
Day 3: Na 124 mEq/L, Day 4:
SBP < 90 mmHg, Day 7: fluid
overload
21
9
16
Confusion, altered mental state
Unable to eat
Unable to eat, confusion, brain metastases
None
21
9
17
None
Unable to eat, nausea, diarrhea
Unable to eat, nausea, diarrhea, C diff
Day 2: K 2.6 mEq/L, Day 5: atrial
fibrillation
21
11
18
None
Unable to eat, nausea, abdominal pain
Unable to eat, nausea, abdominal pain,
mucositis
Day 5: K 2.3 mEq/L, required
TPN, fever
21
13
19
None
Unable to eat, nausea, vomiting, diarrhea,
lower GI bleeding, K 2.8 mEq/L, Mg 0.8 mEq/L
Unable to eat, nausea, vomiting, diarrhea,
lower GI bleeding, K 2.8 mEq/L, Mg 0.8 mEq/L
None
21
15
20
SBP < 90 mmHg/need for
vasopressors, ICU admission
Unable to eat, diarrhea, K 2.2 mEq/L
Unable to eat, diarrhea, mucositis,
K 2.2 mEq/L
Day 4: hypotension, ICU,
pneumonia, C diff, MI
21
18
21
None
Unable to eat, nausea, vomiting, diarrhea
Unable to eat, nausea, vomiting, diarrhea,
C diff
None
21
19
22
Renal failure
Nausea, vomiting, abdominal pain
Nausea, vomiting, abdominal pain, ARF,
bilateral hydronephrosis
Day 10: K 2.9 mEq/L, Day 14:
colostomy
21
20
23
Confusion, altered mental state
Unable to eat
Unable to eat, cellulitis, mucositis
Day 4: confusion, carcinomatous
meningitis
21
29
24
None
Unable to eat, abdominal pain, inpatient
chemotherapy required,
Unable to eat, abdominal pain, SBO
Inpatient chemotherapy required,
neutropenia, fever, bacteremia
21
31
25
None
Nausea, diarrhea, abdominal pain
Nausea, diarrhea, abdominal pain, typhlitis
None
22
4
26
None
None
Pleural effusion
None
22
6
27
None
K 2.2 mEq/L, Hb 6.6 g/dL
Bacteremia, K 2.2 mEq/L, decubitus
débridement
Day 2: Hb 6.6 g/dL
22
6
28
None
Nausea, K 2.6 mEq/L
Nausea, K 2.6 mEq/L
None
22
6
29
SBP < 90 mmHg/need for
vasopressors, confusion,
altered mental state, or seizure
Nausea, vomiting, diarrhea, abdominal
pain, K 2 mEq/L,
Nausea, vomiting, diarrhea, abdominal
pain, altered mental state
Day 2: K 2 mEq/L, Day 3 SBP <
90 mmHg
22
8
30
SBP < 90 mmHg/need
for vasopressors, Pao2
< 60 mmHg/need for ventilation
Impending hip fracture
Impending hip fracture
Day 3: hypotension, Day 5:
hypoxia, ARDS
22
8
31
None
Unable to eat, difficulty swallowing, Day 4:
K 5.6 mEq/L, Day 9: K 6.1 mEq/L
Unable to eat, difficulty swallowing,
mucositis
Day 4: K 5.6 mEq/L, Day 9: K
6.1 mEq/L
22
10
32
Pao2 < 60 mmHg/need for
ventilation,
Nausea, diarrhea
Nausea, diarrhea, dehydration, Cr 2.7 mg/dL
Day 3: hypoxia: Day 4: Cr 5.3 mg/dL,
Day 6: colitis, hemodialysis
22
11
33
None
Na 126 mEq/L
Pneumonia, Na 126 mEq/L
None
23
3
34
None
Nausea, diarrhea, abdominal pain, Na 118
Nausea, diarrhea, abdominal pain,
hypotension, Na 118 mEq/L
None
23
3
(Continued on next page.)
40
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
ORIGINAL RESEARCH & CONTRIBUTIONS
Utilityofofthethe
Multinational
Association
forSupportive
CareinCancer
(MASCC)
IndexScore
aCriterionforNonadmissioninFebrileNeutropenicPatientswithSolidTumors
Utility
Multinational
Association
for Supportive
Care in
CancerRisk
(MASCC)
RiskasIndex
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
(Continued from previous page.)
Patient
episode
number
Klastersky criteria
(named)
Klastersky criteria
(Presumed to be in ”Other complications
judged serious and clinically significant
by the investigator”)
Reason for
admission
Complication after
admission
MASCC
RIS
Length
of stay,
days
35
None
Unable to eat, nausea, vomiting, diarrhea,
difficulty swallowing, Hb 6.6 g/dL
Unable to eat, nausea, vomiting, diarrhea,
difficulty swallowing
Day 2: Hb 6.6 g/dL
23
6
36
None
None
Pneumonia
None
23
7
37
None
Unable to eat, nausea, vomiting, diarrhea
Unable to eat, nausea, vomiting, diarrhea,
abdominal pain, mucositis, colitis
None
23
8
38
None
Unable to eat, nausea, vomiting,
abdominal pain, intestinal perforation
Unable to eat, nausea, vomiting,
abdominal pain, intestinal perforation
None
23
8
39
None
Unable to eat, nausea, vomiting,
abdominal pain, SBO
Unable to eat, nausea, vomiting,
abdominal pain SBO
None
23
10
40
None
Unable to eat
Unable to eat, mucositis
None
24
3
41
None
Cellulitis
None
24
5
42
None
Unable to eat, nausea
Unable to eat, nausea, difficulty swallowing,
mucositis
None
24
5
43
None
Unable to eat
Unable to eat, mucositis
None
24
5
44
None
Nausea, vomiting, diarrhea, abdominal
pain
Nausea, vomiting, diarrhea, abdominal
pain, typhlitis
None
24
6
45
None
None
Abscess
None
24
6
46
SBP < 90 mmHg/need for
vasopressors
None
Perirectal abscess
Day 1: hypotension
24
6
47
None
Unable to eat, nausea, vomiting
Unable to eat, nausea, vomiting, mucositis
None
24
6
48
SBP < 90 mmHg/need for
vasopressors
Unable to eat
Unable to eat
Day 3: hypotension
24
7
49
Pao2 < 60 mmHg/need for
ventilation, arrhythmia, ECG
changes
None
Syncope, K 2.1 mEq/L
Day 2: SVT, hypoxia
24
8
50
None
Nausea, vomiting, abdominal pain
Nausea, vomiting, abdominal pain, colitis
None
24
8
51
None
Unable to eat, diarrhea, K 2.5 mEq/L
Unable to eat, diarrhea, difficulty
swallowing, mucositis, K 2.5 mEq/L
None
24
8
52
None
Unable to eat, nausea, vomiting, diarrhea,
K 2.7 mEq/L
Unable to eat, nausea, vomiting, diarrhea,
difficulty swallowing, K 2.7 mEq/L
None
24
8
53
None
None
Bacteremia
ARF
24
12
54
None
None, chest pain
Chest pain
None
24
13
55
None
Unable to eat, nausea, vomiting,
intractable hiccups
Unable to eat, nausea, vomiting,
esophagitis
Day 1: intractable hiccups
24
20
56
None
Unable to eat, nausea, vomiting
Unable to eat, nausea, vomiting
None
26
3
57
None
None
Cellulitis
None
26
4
58
None
Nausea, vomiting, diarrhea, abdominal
pain
Nausea, vomiting, diarrhea, abdominal
pain, typhlitis
None
26
4
59
None
Nausea, vomiting, abdominal pain
Nausea, vomiting, abdominal pain, typhlitis
None
26
5
60
None
Unable to eat, abdominal pain
Unable to eat, abdominal pain, typhlitis
None
26
5
61
None
Unable to eat, nausea, vomiting
Unable to eat, nausea, vomiting
Day 1: perianal herpes simplex
virus
26
5
62
None
Nausea, diarrhea, K 2.6 mEq/L
Nausea, diarrhea, K 2.6 mEq/L
Enterovaginal fistula
26
6
63
None
Unable to eat, vomiting, abdominal pain
Unable to eat, vomiting, abdominal pain,
mucositis
None
26
7
64
None
Unable to eat, nausea, vomiting, diarrhea,
abdominal pain, hypokalemia
Unable to eat, nausea, vomiting, diarrhea,
abdominal pain, enteritis
Low K
26
7
65
None
Unable to eat, nausea, vomiting, rectal pain
Unable to eat, nausea, vomiting, rectal pain
None
26
9
66
None
Hb < 6 g/dL, unable to eat, abdominal pain,
K 2.9 mEq/L
Unable to eat, abdominal pain, Hb 5.4 g/dL,
K 2.9 mEq/L
None
26
9
67
None
Unable to eat, nausea, difficulty swallowing
Unable to eat, nausea, mucositis,
difficulty swallowing
None
26
10
68
None
Unable to eat, nausea
Unable to eat, nausea, mucositis
Day 2: fever, Day 6: ARF
26
11
69
None
Unable to eat, nausea, vomiting, diarrhea,
abdominal pain
Unable to eat, nausea, vomiting, diarrhea,
abdominal pain, esophagitis, colitis
Day 6: ARF
26
13
ARDS = acute respiratory distress syndrome; ARF = acute renal failure; C diff = Clostridium difficile; Cr = creatinine; ECG = electrocardiogram; GI = gastrointestinal tract; Hb = hemoglobin; ICU = intensive
care unit admission; K = potassium; MASCC = Multinational Association for Supportive Care in Cancer; Mg = magnesium; MI = myocardial infarction; Na = sodium; Pao2 = partial pressure of oxygen;
RIS = risk index score; SBO = small-bowel obstruction; SBP = systolic blood pressure; SVT = supraventricular tachycardia; TPN = total parenteral nutrition.
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
41
ORIGINAL RESEARCH & CONTRIBUTIONS
Utility of the MultinationalAssociation for Supportive Care in Cancer (MASCC)
RiskofIndex
as a Criterion
for Nonadmission
in FebrileCare
Neutropenic
Patients
with Solid
Utility
the Score
Multinational
Association
for Supportive
in Cancer
(MASCC)
RiskTumors
Index
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
Table 3. Characteristics of 198 patient episodes of solid tumors,a
Characteristic
Age, years
Median
Range
Sex
Male
Female
Neoplasms
Breast
Gastrointestinal
Lung
Sarcoma
Head and neck
Ovary
Prostate
Bladder
Testis
PNET
Unknown
Melanoma
Uterus
Total neoplasms
Comorbidities
Diabetes mellitus
CKD stage ≥ 3
Cirrhosis
Rheumatoid arthritis
Systemic lupus
CREST
Polymyalgia rheumatica
Transplant
Anti-TNF
Hepatitis B
Hepatitis C
HIV infection
Hypogammaglobulinemia
Hemochromatosis
Ulcerative colitis
Other
Unable to eat
GCSF, inpatient after admission
GCSF, outpatient before admission
Chemotherapy density and intensity
meeting GCSF criteria
Documented infection
Antimicrobials before admission
Adequate antimicrobial regimen on
admission
No. of
patients
(%)
MASCC RIS
score < 21
(n = 35), no. (%)
MASCC RIS
score ≥ 21
(n = 163), no. (%)
61
18-86
67.5
35-81
59
18-86
57 (29)
141 (71)
17
18
40
123
93 (47.0)
39 (19.7)
18 (9.1)
12 (6.1)
9 (4.5)
8 (4.0)
7 (3.5)
4 (2.0)
2 (1.0)
2 (1.0)
2 (1.0)
1 (0.5)
1 (0.5)
198 (100)
7 (20.0)
6 (17.1)
7 (20.0)
5 (14.3)
2 (5.7)
3 (8.6)
2 (5.7)
2 (5.7)
0 (0)
1 (2.9)
0 (0)
0 (0)
0 (0)
35 (100)
86 (52.8)
33 (20.3)
11 (6.8)
7 (4.3)
7 (4.3)
5 (3.1)
5 (3.1)
2 (1.2)
2 (1.2)
1 (0.6)
2 (1.2)
1 (0.6)
1 (0.6)
163 (100)
16 (8.1)
18 (9.1)
2 (1.0)
2 (1.0)
0 (0)
0 (0)
2 (1.0)
1 (0.5)
1 (0.5)
4 (11.4)
6 (17.1)
1 (2.9)
1 (2.9)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
15 (9.2)
12 (7.4)
1 (0.6)
1 (0.6)
0 (0)
1 (0.6)
2 (1.2)
1 (0.6)
1 (0.6)
1 (0.5)
5 (2.5)
1 (0.5)
2 (1.0)
2 (1.0)
1 (0.5)
0 (0)
0 (0)
0 (0)
0 (0)
1 (2.9)
0 (0)
1 (0.6)
5 (3.1)
1 (0.6)
2 (1.2)
1 (0.6)
1 (0.6)
54 (27.3)
177 (89.4)
33 (16.7)
51 (25.8)
16 (45.7)
31 (88.6)
6 (17.1)
5 (14.3)
38 (23.3)
146 (89.6)
27 (16.6)
46 (28.2)
38 (19.2)
18 (9.1)
187 (94.4)
12 (34.3)
4 (11.4)
34 (97.1)
26 (16)
14 (8.6)
153 (93.9)
Some percentages may not total to 100 because of rounding.
CKD = chronic kidney disease; CREST = calcinosis, Raynaud syndrome, esophageal dysmotility, sclerodactyly,
and telangiectasia; GCSF = granulocyte colony-stimulating factor; HIV = human immunodeficiency virus; MASCC
= Multinational Association for Supportive Care in Cancer; PNET = primitive neuroectodermal tumor; RIS = risk
index score; TNF = tumor necrosis factor.
a
42
There were 163 inpatient episodes
with an MASCC RIS of 21 or higher.
Sixty-nine of these had complications
and/or reasons for admission on presentation. Thirty-eight of the 69 were unable to eat; 32 of the 38 had reasons for
admission and/or complications. The
other 31 of the 69 patients, those who
were able to eat, required admission for
various other reasons. See Table 2 for the
reasons for admission and subsequent
complications of the 32 episodes.
There were 35 episodes with an
MASCC RIS below 21 (high risk for
complication). Six of these patient episodes were misclassified by the MASCC
RIS because no complication occurred
that required hospitalization. The mean
LOS for these 6 patients was 4.7 days
(5, 3, 5, 5, 4, and 6 days, the last with a
urinary tract infection that could have
been treated orally with ciprofloxacin)
compared with a mean LOS of 4.6 days
for Group 1 and 7.6 days for Group 2.
Inability to Eat
Inability to eat was considered a serious complication and reason for admission; thus, it placed a patient episode
in Group 2: complication. There were
54 episodes of 198 in which patients
were unable to eat, 38 of whom had an
MASCC RIS of 21 or above and 16
of whom had a score below 21. These
38 patient episodes were a subset of
the 69 discordant patient episodes with
an MASCC RIS of 21 or greater and a
complication (Table 2). Inability to eat
was associated with other serious complications in 32 of 38 episodes (84%). The
38 patients who were unable to eat had
a mean LOS of 9.66 days compared with
the mean LOS of the 31 patients who
could eat, 7.0 days (p = 0.08 by Wilcoxon
rank sum test). The mean MASCC RIS
of those unable to eat and those able to
eat was 23.1 and 22.8, respectively.
Correlation of Index
with Other Outcomes
There was no useful correlation between the MASCC RIS and either the
days to a body temperature at or below
37.5°C or the LOS (data not shown).
Table 4 shows a correlation with deaths
and the potential cost savings of preventing hospital admission (Table 5).
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
ORIGINAL RESEARCH & CONTRIBUTIONS
Utilityofofthethe
Multinational
Association
forSupportive
CareinCancer
(MASCC)
IndexScore
aCriterionforNonadmissioninFebrileNeutropenicPatientswithSolidTumors
Utility
Multinational
Association
for Supportive
Care in
CancerRisk
(MASCC)
RiskasIndex
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
DISCUSSION
If patients with identified infections;
intractable vomiting and diarrhea, either of the latter caused by mucositis
or another complication; and inability
to eat are included in the patients to
whom the MASCC RIS is applied, the
sensitivity of an MASCC RIS of 21 or
greater to identify patients as a criterion
for nonadmission was high (94%), but
the positive predictive value was only
57.7% and the specificity only 29.6%.
The range of the specificity of the
MASCC RIS in some published studies (Table 6) varied from 40% to 95%
(mean = 67.5%) in prospective studies and from 52% to 63.7% (mean =
60.9%) in retrospective studies. The
variance of the specificity in these studies and the present study has not been
explained, and a detailed analysis is beyond the scope of this article; however,
a more detailed analysis is available in
the guideline from the American Society
of Clinical Oncology (ASCO).9 In most
of these publications, it is not clear if
patients, presenting with identifiable
infections; intractable vomiting and
diarrhea, either of the latter caused by
mucositis or another complication; and
the inability to eat and swallow medications were excluded before the calculation of the MASCC RIS because these
clinical features were considered aspects
of the febrile neutropenic syndrome and
not complications. Thus, study design
is a possible factor accounting for the
variance. Another factor might be that
the median age of the patients in the
studies listed in the references was about
51 years compared with 61 years in the
present study. In the MASCC RIS, 2
points are awarded for age younger than
60 years, indicating that those patients
aged 60 years or older are at increased
risk of complications. As noted earlier,
in 69 of 163 inpatient episodes with an
MASCC RIS of 21 or more, admission
was necessary because of complications
present on admission or which occurred
during hospitalization (Table 2). The
patients with these 69 misclassified inpatient episodes would not have been
admitted if an MASCC RIS of 21 or
greater was used as the criterion for
nonadmission. If these patients were
not admitted, the complications that
occurred during hospitalization would
have occurred outside the hospital, resulting in either reevaluation in a health
care setting or death.
There were also 3 inpatient episodes
with an MASCC RIS of 21 or above
(Group 1), in which a complication
occurred 24 hours after admission, a
complication that would have been
Table 4. Patient deaths
MASCC
RIS
13
19
19
19
Circumstances and causes
leading to death
Bacteremia, Staphylococcus aureus
Readmitted with intestinal perforation,
died same day
Unable to eat, became obtunded
on TPN
Pneumonia
Death
related
to initial
infection
Yes
No
Comfort
care
Yes
No
No
Yes
Yes
Yes
Clostridium difficile, low BP, ICU,
HAP, AMI
SBO, died 31 days after admission
Encephalopathy
No
Yes
No
No
Yes
Yes
No
No
Yes
22
Multiple intraabdominal, extraintestinal
air-fluid levels
ARDS, progressive hypoxemia,
hypotension
Diarrhea, colitis, ARF, hypotension
Yes
Planned for
next day
Yes
23
Sepsis, then acute hypotension
Yes
Yes
23
Admitted with SBO and discharged;
readmitted following week with
intestinal perforation, intraabdominal
abscess (declined abcess drainage)
Fluid overload, failed to respond to
diuresis
Readmitted obtunded, ARF,
hypotensive
New SVT, hypoxemia
No
No
No
Yes
No
No
21
21
21
22
22
24
24
24
Neoplasm
Sarcoma
Advanced lung
cancer
Advanced ovarian
cancer
Lung cancer
Advanced
esophageal cancer
Colon cancer
Advanced breast
cancer
Advanced
endometrial cancer
Advanced prostate
cancer
Advanced lung
cancer
Advanced breast
cancer
Ovarian cancer
Death after
discharge,
within 28 days
of admissiona
No
No
Duration of
neutropenia/
length of stay,
days
7/7
3/8
Days to temperature
≤ 38°C/days to
temperature ≤ 37.5°C
6/6
8/8
No
2 / 18
1/2
No
1/4
1/1
No
9 / 18
3/3
No
No
6 / 31
1 / 29
1/1
7/9
Yes
5/6
2/4
No
2/8
8/8
No
4/8
4/4
No
2/3
1/3
Yes
3/4
3/3
No
6/9
6/9
No
Metastatic; primary
cancer not known
Breast cancer
Yes
3 / 14
3/8
Yes
Gastric cancer
No
8/8
4/7
“No” = died in hospital.
AMI = acute myocardial infarction; ARDS = acute respiratory distress syndrome; ARF = acute renal failure; BP = blood pressure; HAP = hospital-acquired pneumonia; ICU = intensive care
unit admission; MASCC = Multinational Association for Supportive Care in Cancer; RIS = risk index score; SBO = small-bowel obstruction; SVT = supraventricular tachycardia; TPN = total
parenteral nutrition.
a
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
43
ORIGINAL RESEARCH & CONTRIBUTIONS
Utility of the MultinationalAssociation for Supportive Care in Cancer (MASCC)
RiskofIndex
as a Criterion
for Nonadmission
in FebrileCare
Neutropenic
Patients
with Solid
Utility
the Score
Multinational
Association
for Supportive
in Cancer
(MASCC)
RiskTumors
Index
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
Table 5. Savings of preventing hospital admission
Savings
Approximate cost of 1 day of hospitalization (2012 US dollars)
Number of patient episodes
Number of patient episode days x number of patient episodes
Estimated cost of hospitalization (2012 US dollars)
best managed in the hospital. If the
patients had not been admitted, or had
been admitted and discharged after
24 hours of observation, they would
have experienced these complications
as outpatients. Those complications
were hypokalemia (serum potassium
concentration of 2.9 mEq/L) on Day
2, hypophosphatemia (phosphorus level
of 2.2 mg/dL) on Day 3, and recurrent
fever on Day 4. An additional 52-yearold woman, not identified as feeling or
appearing sick or being dehydrated, had
a temperature of 38.7°C, a BP of 81/54
mmHg, and a pulse of 130/min (3 criteria for systemic inflammatory response
syndrome10) in urgent care. She was
referred to the Emergency Department,
where she was hydrated and placed on
an intravenous antimicrobial regimen.
She was intermittently hypotensive
until the BP finally stabilized 25 hours
and 37 minutes later. Her MASCC RIS
was 21 at the time of admission, but the
RIS would have been different
depending on when, in the
If the MASCC
course of this patient episode,
index were
it was calculated.
to be used to
Because many complicadetermine
tions, such as hypokalemia,
hypophosphatemia, and recur“do not admit,”
rent fever, cannot be predicted
it would have
with an MASCC RIS of 21
to be employed
or higher, use of a protocol,
after determining
algorithm, or guideline seems
whether a person
appropriate to help clinicians
was or was not
decide on the proper manable to eat or
agement. One is the ASCO
swallow …
guideline from 2012, 9 and
another is the National Comprehensive Cancer Network (NCCN)
guideline. 11 The recommended initial observation period in the ASCO
guideline is 4 hours, and in the NCCN
guideline it is 2 to 12 hours. The hypotensive patient described could have
been considered stable at 2 to 4 hours
and possibly discharged to home.
44
No complication
$2124
100
455
$966,420
However, the physician, simply using
clinical judgment, decided this patient
needed admission. This decision was
consistent with the ASCO guideline,
which clearly states that a patient with
criteria for systemic inflammatory response syndrome should be admitted.
Therefore, following the ASCO guideline
would have ensured admission for this
last patient, but using an MASCC RIS
of 21 or higher would not. The limitataion of the MASCC RIS is evident by
consulting Table 4 of the ASCO guideline (available at: http://jco.ascopubs.
org/content/31/6/794/T4.expansion.
html).9 The table lists 41 exclusions
(42 if the footnote regarding systemic
inflammatory response syndrome is
included) to using an MASCC RIS of
21 or greater as a criterion for treating a febrile neutropenic patient as
an outpatient.9 Furthermore, neither
the NCCN guideline for the management of nonadmitted patients nor the
ASCO guideline specify frequency of
laboratory testing for these potential
outpatients. Rubenstein et al12 suggested
obtaining a complete blood cell count
every other day and biochemical panels
on Day 7 or the last day of observation.
If the biochemical panels for the patients
with hypokalemia and hypophosphatemia had been drawn on Day 7, a delay
in detection would have occurred. The
protocol for patients discharged from the
hospital on a regimen of oral antimicrobial therapy in the article by Klastersky
et al13 included temperature recorded every 6 hours, laboratory tests every other
day for 5 days, and phone contact with
the patient every other day. The ASCO
guideline recommends daily telephone
contact and “frequent evaluation for at
least 3 days in clinic or at home.”
Data in the present study support
the ASCO guideline for management
of these patients. Although the ASCO
guideline recognizes the lack of data
supporting multiple aspects of outpatient management, modifications to
the guideline, following discharge to
an outpatient setting, could include
recording the patient’s vital signs approximately every 6 to 8 hours, establishing phone contact with the patient
or caregiver within 8 to 12 hours following discharge, and serum biochemical
tests (electrolytes, creatinine, calcium,
phosphorus, and magnesium) daily or
every other day for 3 times, or until
results are normal.
Importance of Inability to Eat
This study chose inability to eat, as
an admission criterion, vs inability to
swallow oral medications because “unable to eat” was recorded in the progress
notes. In my view, neither is adequate
or objective because outpatients need
both adequate nutrition and appropriate medications. Some patients who
are unable to eat can swallow oral
medications, and some patients who
are unable (or unwilling) to swallow
oral medications are able and willing
to swallow nutritional liquid drinks.
Inability to swallow oral medications
is considered by the ASCO guideline
to be an exclusion for outpatient management. It is not named as one of the
complications in the Klastersky criteria. In the study by Klastersky et al,13
which identified patients who were
stable and ready for discharge from the
hospital after 24 hours of observation,
the equivalent of “unable to eat”—
“able to swallow”—was employed after
stratification by the MASCC index and
was not incorporated into the MASCC
index. Those unable to swallow were
excluded from early discharge despite
an MASCC RIS of 21 or higher. If the
MASCC RIS were to be used to determine “do not admit,” it would have to
be employed after determining whether
a person was or was not able to eat or
swallow, or the criterion “unable to eat/
unable to swallow oral medications”
would have to be incorporated into the
MASCC RIS.
As noted earlier, inability to eat was
associated with other serious complications, and all physicians admitting
patients in this study considered it a criterion for admission. However, because
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
ORIGINAL RESEARCH & CONTRIBUTIONS
Utilityofofthethe
Multinational
Association
forSupportive
CareinCancer
(MASCC)
IndexScore
aCriterionforNonadmissioninFebrileNeutropenicPatientswithSolidTumors
Utility
Multinational
Association
for Supportive
Care in
CancerRisk
(MASCC)
RiskasIndex
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
there are 42 exclusions in the ASCO
guideline9 for managing a patient as an
outpatient, as mentioned earlier, there
is questionable utility to modifying the
MASCC RIS to include “unable to eat/
unable to swallow oral medications.”
That inability to eat is important has
been highlighted in a study by Escalante
et al,14 who noted that 80% of patients
with Grade 3 or higher mucositis required admission. The NCCN guideline
also includes Grades 3 to 4 mucositis as
a criterion for high risk. Until patients
who are unable to eat or to swallow oral
medications, yet who have no other
complications, can be managed as outpatients, they will require admission.
are objective; 2) the majority, 49 of the
69, of the complications experienced
by the patients in this study with an
MASCC RIS of 21 or higher were not
among the named complications; and 3)
inability to eat and inability to swallow
are not named.
The MASCC RIS of 21 or above is
inadequate for the nonadmission decision for these reasons: 1) only 4 of the
7 components of the MASCC RIS are
objective; 2) it misclassified to low risk
42.3% of patient episodes with complications; 3) it has to be checked against
42 other exclusions based on the ASCO
guideline9; and 4) “unable to eat/unable
to swallow” are not incorporated.
Limitations of Klastersky
Criteria and Index
Alternative to Index
The Klastersky criteria are inadequate
as nonadmission criteria for these reasons: 1) only 2 of the 10 complications
The alternative to the MASCC RIS
is clinical judgment or a more reliable
index. Although the MASCC RIS has
been incorporated into both Infectious
Diseases Society of America1 and ASCO
guidelines,9 I believe a fair question is:
Is this index really superior to clinical
judgment? Furthermore, I believe it
would be beneficial to conduct a study
in which a physician assigns an MASCC
RIS at the point of entry to health care
and again at the point when an admitting physician, blinded to the MASCC
RIS, evaluates the patient regarding admission. The admitting physician would
decide, on the basis of clinical acumen
and the ASCO guideline, whether the
patient should be admitted. The patient
would be observed in the hospital for
24 hours. Complications would be correlated with the MASCC RIS and the
clinical decision.
Savings
The cost of intensive outpatient
management would probably be less
than the cost of inpatient management
Table 6. Sensitivity and specificity of the MASCC RIS in various studies
Source,
year
Uys,8
2004
Type of study
Prospective
Total
Baskaran,5
2008
Retrospective
Total
Innes,6
2008
Prospective
Total
André,18
2010
Prospective
Solid tumor,
lymphoma, %
70
34.5
100
No serious
medical
complication
57
3
60
68
5
73
87
8
95
Not SS/SSh
70
38
108
308
15
323
1349
410
1759
137
Serious
medical
complication
1
19
20
14
29
43
3
2
5
SS/SSh
22
67
89
35
38
73
139
244
383
23
< 21
32
169
Don’t admit
35
58
Admit
67
227
> 21
< 21
94
6
100
69
29
98
163
35
198
MASCC
RIS
> 21
< 21
> 21
< 21
> 21
< 21
56
> 21
< 20
Total
Ahn,19
2011
Retrospective
Total
Paesmans,20
2011
Retrospective
Total
Hui,4
2011
Prospective
Total
Bitar,
2013a
Retrospective
71.5
57
79.7
> 21
< 21
> 21
< 21
> 21
100
Total
Total
58
22
80
82
34
116
90
10
100
92
105
197
343
53
396
1488
654
2142
160
Sensitivity,
%
95
Specificity,
%
95
Deaths,
%
0
36.4
67
7
29
93
91.6
40
70
75
NA
NA
52
1.5
18.9
63.7
1
14.2
95
77
81
1.9
60
9
29.6
4.9
11.4
94
Results of the current study.
MASCC = Multinational Association for Supportive Care in Cancer; NA = not available; RIS = risk index score; SS/SSh = severe sepsis or septic shock.
a
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
45
ORIGINAL RESEARCH & CONTRIBUTIONS
Utility of the MultinationalAssociation for Supportive Care in Cancer (MASCC)
RiskofIndex
as a Criterion
for Nonadmission
in FebrileCare
Neutropenic
Patients
with Solid
Utility
the Score
Multinational
Association
for Supportive
in Cancer
(MASCC)
RiskTumors
Index
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
(approximately $10,000 per uncomplicated admission12). In 1993, Rubenstein
and colleagues12 estimated the medication cost of outpatient management as
$2302 for oral therapy and $7336 for
intravenous therapy, but the total cost
of managing the patients was not provided. Elting et al15 calculated the costs
of outpatient vs inpatient management
in 2008 and found the total cost of inpatient management to be about twice
that of outpatients.
Study Limitations
There are some limitations to this
study. First, as noted earlier, the MASCC
RIS lists only 4 actual objective criteria.
The burden of illness category is purely
subjective, dependent on the recorder
(Table 1). The burden of illness was assigned following a detailed review of the
chart by the physician author and not by
the admitting physician. The physician
reviewing the charts for this study did
review the publication by Pompei and
associates,16 which originally proposed
the burden of illness designation. Although a retrospective chart review has
some element of subjectivity, it is no less
objective than the criteria used to evaluate charts in the original publication by
Klastersky et al.3
Second, this study accepted designations such as COPD, dehydration,
and other terms such as vomiting,
diarrhea, unable to eat, and so on,
without requiring an objective definition. (The ASCO guideline, Table 2,
[available at: http://jco.ascopubs.org/
content/31/6/794/T2.expansion.html]
attempts to address this problem, but
does not resolve it.9)
Third, this was a retrospective review
of the charts by a single physician. However, his experience included more than
37 years as a physician and 23 years as
an infectious disease physician.
Fourth, the definition of febrile neutropenia was based on the admitting
physician’s acceptance of the self-report
of fever or the documentation of fever
in the clinic or Emergency Department
and not a documented temperature of
above 38.3°C on one occasion or above
38°C on 2 or more occasions during a
12-hour period.17
Fifth, this was a study of only febrile
neutropenic patients with solid tumors,
so the sensitivity and specificity of the
MASCC RIS in this study should be
compared only with similar studies of
febrile neutropenic patients with solid
tumors. (Table 6 shows data extracted
from 7 studies with the percentage of
patients with solid tumors or lymphoma
and the sensitivity and specificity of the
MASCC RIS for each.4-6,8,18-20)
CONCLUSIONS
Figure 2. Proposed outpatient management algorithm.b
Modified from the American Society of Clinical Oncology (ASCO) guideline, to include the following:
Patient agrees to outpatient treatment while neutropenic, including potential frequent visits to clinic/hospital.
Residence ≤ 1 hour or ≤ 30 miles (48 km) from clinic or hospital, even in inclement weather.
Patient’s primary care physician and infectious disease physician, or oncologist agrees to outpatient management.
Attendant or attendants who agree to outpatient treatment and are competent at observation and communication,
and at home 24 hours a day until neutropenia and other clinical problems resolve.
Telephone and transportation available 24 hours a day.
Either an oncology or infectious disease nurse practitioner or physician’s assistant or a clinically trained home infusion
pharmacist or clinically trained oncology nurse or infectious disease nurse able to communicate with patient daily.
b
High risk indicates usual clinical criteria for admission (criteria on which a general internist bases a decision to
admit or to not admit) using the 2013 clinical practice guideline from the ASCO, which includes all patients unable
to eat. Low risk indicates absence of usual admission criteria/ASCO guideline.
Ca = calcium; CBC = complete blood count; Cr = creatinine; h = hours; Mg = magnesium; VS = vital signs.
a
46
This study answered the 6 questions
presented in the Introduction. First, of 69
misclassified patients with complications
and an MASCC RIS of 21 or greater,
only 20 had serious complications named
in the Klastersky criteria, meaning that
the other 49 patients had complications
not named and which had to be assumed
to be included in the last component,
“other complications judged serious and
clinically significant by the investigator.”
Second, there were additional complications, not named in the Klastersky
criteria, which were important in the
nonadmission decision, such as inability
to eat (Table 2).
Third, the MASCC RIS of 21 or
greater could not be used to make the
nonadmission decision for a febrile
neutropenic patient with a solid tumor
because, in this study, a score of 21 or
higher misclassified 42.3% of patients
with complications to low risk.
Fourth, 3 patients with an MASCC
RIS of 21 or greater experienced complications 24 hours after admission; the
The Permanente Journal/ Summer 2015/ Volume 19 No. 3
ORIGINAL RESEARCH & CONTRIBUTIONS
Utilityofofthethe
Multinational
Association
forSupportive
CareinCancer
(MASCC)
IndexScore
aCriterionforNonadmissioninFebrileNeutropenicPatientswithSolidTumors
Utility
Multinational
Association
for Supportive
Care in
CancerRisk
(MASCC)
RiskasIndex
Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors
complication and the day of occurrence
were noted. Because 2 of the 3 complications that occurred were biochemical
and the additional one was recurrent
fever, the index is unlikely to be able to
predict their occurrence.
Fifth, therefore, an algorithm or
protocol for the management of outpatients is advisable. An algorithm has
been constructed from the implications
of the data in this study and the ASCO
guideline (Figure 2).
Sixth, substantial savings could be
realized if uncomplicated patients could
be managed as outpatients (approximately $1 million per 100 uncomplicated admissions in 2012 dollars).
The possibility of creating an MASCClike RIS from truly objective data, which
could be used to predict complications
and the safety of not admitting a febrile
neutropenic patient, requires further
investigation. v
3.
4.
5.
6.
7.
Disclosure Statement
The author(s) have no conflicts of interest to
disclose.
Acknowledgment
The author thanks Elizabeth Le for data
extraction and formulation, without which this
study would not have been possible.
Kathleen Louden, ELS, of Louden Health
Communications provided editorial assistance.
8.
9.
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State of Mind
A cancer is not only a physical disease, it is a state of mind.
— Michael Baden, MD, b 1934, physician and forensic pathologist
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