original articles
Annals of Oncology
Annals of Oncology 26: 393–399, 2015
doi:10.1093/annonc/mdu537
Published online 18 November 2014
Outcome determinants for transformed indolent
lymphomas treated with or without autologous
stem-cell transplantation
C. Madsen1, M. B. Pedersen1, M. Ø. Vase1, K. Bendix2, M. B. Møller3, P. Johansen4, B. A. Jensen5,
P. Jensen6, L. Munksgaard5, P. D. Brown7, E. K. Segel1 & F. A. d’Amore1*
Departments of 1Hematology; 2Pathology, Aarhus University Hospital, Aarhus; 3Department of Pathology, Odense University Hospital, Odense; 4Department of Pathology,
Aalborg University Hospital, Aalborg; 5Department of Haematology, Odense University Hospital, Odense; 6Department of Haematology, Aalborg University Hospital,
Aalborg; 7Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Received 3 July 2014; revised 21 October 2014; accepted 10 November 2014
Background: Transformation of indolent lymphomas (IL) to an aggressive histology (TIL) often results in a rapid clinical
course, treatment refractoriness and shortened survival. Although rituximab-containing regimens (R-chemo) have
become standard of care in CD20-positive TIL, the role of autologous stem-cell transplantation (ASCT) is still debated.
The purpose of this study was to determine whether the outcome of TIL patients improved if they, at transformation, also
received ASCT. Furthermore, we investigated the outcome of cases with histologically low- and high-grade components
diagnosed either simultaneously or after a period of overt indolent disease. We also analyzed, whether prior rituximab
treatment during the indolent course of the disease affected outcome after transformation.
Patients and methods: Eighty-five patients (≤68 years) with histologically confirmed TIL were included. Five-year
overall (OS) and progression-free survival (PFS) were calculated. Selected parameters were tested in a multivariate analysis. All analyses were conducted on three cohorts: (i) whole cohort (all TIL), (ii) patients with co-existing evidence of both
indolent and aggressive histology at diagnosis (Composite/discordant TIL) and (iii) patients transformed after prolonged
prior indolent disease (sequential TIL).
Results: Fifty-four patients (64%) received ASCT consolidation and 31 (36%) did not. Within the ‘all TIL’ cohort, the 5year OS and PFS for R-chemo + ASCT versus R-chemo alone, were 67% versus 48% (P = 0.11) and 60% versus 30%
(P = 0.02), respectively. Furthermore, in ‘Composite/discordant TIL’ R-chemo + ASCT showed no impact on OS (76%
versus 67%; P = 0.66) or PFS (71% versus 62%; P = 0.54). Conversely, R-chemo + ASCT improved the outcome of ‘sequential TIL’ (OS 62% versus 36%; P = 0.07; PFS 53% versus 6%; P = 0.002), regardless of prior rituximab therapy. The
beneficial effect of ASCT was significantly higher in patients who had not received rituximab at IL stage.
Conclusions: ASCT improved the outcome in sequential, but not composite/discordant TIL. The beneficial impact
of ASCT was greater in patients, who were rituximab-naïve at transformation.
Key words: transformed indolent lymphoma, autologous stem-cell transplantation, rituximab era
introduction
In the natural history of indolent lymphoma (IL), transformation to a high-grade histology (transformed indolent lymphomas, TIL) is a known event often resulting in an aggressive
clinical course, treatment refractoriness and shortened survival.
Transformation can occur months to years after the initial IL
diagnosis (sequential TIL, S-TIL) at an estimated 3% per year
[1–4]. In some cases, an indolent and aggressive component
*Correspondence to: Prof Francesco d’Amore, Department of Haematology, Aarhus
University Hospital, Tage Hansens Gade 2, Aarhus 8000, Denmark. Tel: +45-7846-7856;
E-mail: [email protected]
co-exist at diagnosis, a condition often referred to as ‘composite’
or ‘discordant’ lymphoma (CD-TIL), depending on whether the
different histologies are detected within a single or distinct
lesions. Although it can be argued that CD-TIL merely reflects
an S-TIL with undetected prior indolent course, some reports
have suggested a more favorable outcome in CD-TIL, similar to
that of ‘de novo’ diffuse large B-cell lymphoma (DLBCL) [5–7].
Currently, the majority of TIL patients are treated with rituximab-containing chemoimmunotherapy regimens. The role of
high-dose-chemotherapy with autologous stem-cell transplantation (ASCT) in eligible TIL patients is still debated [6, 8–18],
and for CD-TIL in particular, the available data are very limited
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: [email protected].
original articles
[6, 12, 14]. Furthermore, outcome results from ASCT carried
out in TIL patients after the introduction of rituximab are still
scarce [6, 9–11, 18]. Therefore, the aim of the present study was
to evaluate the role of ASCT in S- as well as CD-TIL and investigate related outcome determinants within the rituximab era.
methods
patients
Patients aged 18–68 years with histologically verified TIL diagnosed between
1999 and 2012 at three Danish tertiary lymphoma referral centers (Aarhus,
Odense and Aalborg) were identified using the National Danish Pathology
Registry [19]. Pathology reports from all patients diagnosed with DLBCL
within the study period were reviewed. TIL was defined by a biopsy proven IL
in addition to a DLBCL lesion that was either coexisting at primary diagnosis
or histologically ascertained over time through a subsequent biopsy (supplementary Figure S1, available at Annals of Oncology online). A total of 85
patients with either follicular lymphoma (FL; n = 72, histological grade 1–3A:
Table 1) or IL not otherwise specified (NOS) (n = 13) were included.
Pretherapeutic clinico-pathological features as well as treatment- and outcome
data at baseline and follow-up were collected through the Danish lymphoma
registry (LYFO), a population-based database of all new cases of lymphoma
diagnosed in Denmark since 1983 (www.lymphoma.dk). The LYFO database
has previously been described in detail [20, 21]. If needed for data completeness, additional clinical information was obtained from the patient records at
each participating center. Only patients with a complete set of evaluable clinical data were included.
treatment background
All included patients received rituximab at TIL stage. An important feature of
the present study was the subdivision of the patient cohort into two major
subsets according to treatment strategy: (i) those in which the upfront
approach included a subsequently implemented ASCT consolidation and
(ii) those in which ASCT was neither part of the primary treatment strategy
nor carried out at a later stage (supplementary Figure S1, available at Annals of
Oncology online). The criteria for selecting the centers contributing to this
study, were based on the systematic use by each center of either the former
(Aarhus, where all patients reported in the present study received upfront
ASCT) or the latter (Odense and Aalborg, where none of the patients reported
in the present study received upfront ASCT) of the above-mentioned treatment strategies, thus reducing the risk of selection bias. All patients, regardless
of therapeutic approach, were transplant eligible and patients that, according
to clinical records, were not offered ASCT due to poor performance score secondary to e.g. co-morbidity, were not included in the comparative analysis of
ASCT versus no ASCT. Stem-cell mobilization and conditioning regimens as
well as supportive care were applied according to local guidelines. The detailed
treatment background of the study cohort is summarized in supplementary
Table S2, available at Annals of Oncology online.
response criteria
All pretherapeutic staging procedures were carried out according to local
guidelines and included diagnostic imaging with CT or PET-CT scans,
bone-marrow biopsy (only repeated if pretherapeutically involved) and ad
hoc investigations in case of specific organ involvements. For treatment response assessment, the 1999 International Working Group criteria were
used [22].
statistical methods
Patient characteristics were compared using Fisher’s exact or Student’s t-test.
The time-related end points chosen in the present study were overall (OS)
 | Madsen et al.
Annals of Oncology
and progression-free survival (PFS). OS was defined from the date of TIL
diagnosis to the date of death of any cause or censoring. PFS was calculated
from the date of TIL diagnosis to the date of progression/relapse or censoring. Survival proportions were estimated by Kaplan–Meier time-to-event
analyses and compared using the log-rank test (Figure 1). Selected factors of
potential clinical relevance were tested in a multivariate analysis using a Cox
proportional hazards model. End point analyses were carried out on (i) all
TIL patients, (ii) CD-TIL and (iii) S-TIL (supplementary Figure S1, available
at Annals of Oncology online).
results
study cohorts
An overview of all cohorts analyzed in the present study is outlined in supplementary Figure S1, available at Annals of
Oncology online. The whole study population consisted of 85
patients with histologically verified TIL. CD-TIL was detected in
34 patients and S-TIL in 51. Among the latter, 12 had been previously treated with rituximab during the indolent stage of their
disease, while 39 had not.
patient characteristics
Pretherapeutic clinico-pathological features are outlined in
Table 1. The two treatment cohorts (non-ASCT versus ASCT)
were comparable in all features, the only difference being a
slightly higher amount of FL grade 1–2 in the non-ASCT subset
and a corresponding moderate preponderance of FL/IL NOS
histology in the ASCT group (P = 0.001) (Table 1). For patients
with S-TIL, the median time to transformation was similar
between those who later underwent ASCT (6.9 years; range:
0.7–24 years) and those who did not (3.9 years; range: 0.5–18
years) (P = 0.10). In the S-TIL subset, 7 of the 33 (21%) patients
who later received ASCT and 5 of the 18 (28%) (P = 0.49) who
did not, were treated with rituximab at some point during the
indolent stage of their disease (supplementary Figure S1and
Table S2, available at Annals of Oncology online). Rituximab
therapy at IL stage did not affect the median time to transformation (5.1 versus 5.9 years; P = 0.32). Further details on treatment background are outlined in supplementary Table S2,
available at Annals of Oncology online.
survival analysis
The median follow-up from the time of TIL diagnosis was 3.4
years (0.1–10.3 years) for the entire cohort, 3.2 years (0.7–10.3
years) for transplanted patients and 3.4 years (0.1–9.8 years) for
not transplanted ones. The 5-year OS for all ASCT- versus nonASCT-treated patients was 67% and 48%, respectively (P = 0.11).
The corresponding values for CD-TIL and S-TIL were 76%
versus 67% (P = 0.66) and 62% versus 36% (P = 0.07) (Table 2,
Figure 2). ASCT-treated patients had significantly higher PFS
values in the overall (60% versus 30%; P = 0.02) and the S-TIL
cohort (53% versus 6%; P = 0.002). In S-TIL, ASCT was associated with superior outcome irrespective of prior rituximab treatment (supplementary Figure S3, available at Annals of Oncology
online). However, the favorable impact of ASCT was greatest in
patients who were rituximab-naïve at transformation (supplementary Figure S3, available at Annals of Oncology online). The
outcome of CD-TIL patients did not differ depending on whether
Volume 26 | No. 2 | February 2015
original articles
Annals of Oncology
Table 1. Clinico-pathological features of TIL subcohorts
Characteristic
All TIL (N = 85)
R-Chemo
ASCT
(n = 31)
(n = 54)
n (%)
n (%)
Center
Aarhus
0 (0)
Aalborg
12 (39)
Odense
19 (61)
Sex
Male
18 (58)
Female
13 (42)
Age at TIL, years
Median
59
Range
35–64
Ann Arbor stage
1–2
4 (13)
3–4
27 (87)
Time to TIL, years
Median
–
Range
–
FLIPIb
Low
12 (39)
Intermediate
8 (26)
High
11 (35)
Nodal involvement >4
14 (45)
Bulky disease
4 (13)
B-symptoms
14 (45)
WHO Performance score
0–1
27 (87)
≥2
4 (13)
Bone marrow
14 (45)
involvement
Anemiac
3 (10)
LDH elevation
9 (29)
Indolent histology
FL NOS
13 (42)
FL grade 1–2
15 (48)
FL grade 3A
3 (10)
Low-grade B-cell
0 (0)
NOS
P
54(100)
0 (0)
0 (0)
–
34 (63)
20 (37)
NS
56
37–67
7 (13)
47 (87)
–
–
NSa
NS
Composite/discordant TIL (N = 34)
R-Chemo
ASCT
(n = 13)
(n = 21)
n (%)
n (%)
P
0 (0)
7 (54)
6 (46)
10 (77)
3 (23)
57
35–63
–
0 (0)
5 (28)
13 (72)
33(100)
0 (0)
0 (0)
–
14 (67)
7 (33)
NS
8 (44)
10 (56)
20 (61)
13 (39)
NS
1 (5)
20 (95)
–
–
NSa
NS
–
–
–
20 (37)
19 (35)
15 (28)
26 (48)
15 (28)
17 (31)
NS
3 (23)
4 (31)
6 (46)
6 (46)
4 (31)
8 (62)
3 (14)
7 (33)
11 (52)
14 (57)
14 (67)
10 (48)
NS
49 (91)
5 (9)
26 (48)
NS
19 (90)
2 (10)
15 (71)
NS
NS
10 (77)
3 (23)
6 (46)
7 (13)
21 (39)
NS
NS
3 (23)
5 (38)
28 (52)
12 (22)
1 (2)
13 (24)
0.001
7 (54)
5 (38)
1 (8)
0 (0)
NS
NS
NS
P
21(100)
0 (0)
0 (0)
56
37–67
2 (15)
11 (85)
Sequential TIL (N = 51)
R-Chemo
ASCT
(n = 18)
(n = 33)
n (%)
n (%)
–
59
38–64
2 (11)
16 (89)
3.4
0.2–18
56
38–67
6 (18)
27 (82)
6.5
0.7–24
NSa
NS
NSa
9 (50)
4 (22)
5 (28)
8 (44)
0 (0)
6 (33)
17 (52)
12 (36)
4 (12)
12 (36)
1 (3)
7 (21)
NS
30 (91)
3 (9)
11 (33)
NS
NS
17 (94)
1 (6)
8 (44)
NS
5 (24)
14 (67)
NS
NS
0 (0)
4 (22)
2 (6)
7 (21)
NS
NS
7 (33)
4 (19)
0 (0)
10 (48)
0.01
6 (33)
10 (56)
2 (11)
0 (0)
21 (64)
8 (24)
1 (3)
3 (9)
0.04
NS
NS
NS
NS
NS
NS
a
t-Test.
One missing.
c
Serum hemoglobin <12 g/l.
ASCT, autologous stem-cell transplantation; TIL, transformed indolent lymphoma; R-Chemo, Rituximab-containing chemotherapy; FLIPI, follicular
lymphoma prognostic index; LDH, lactate dehydrogenase; CR, complete remission; Cru, unconfirmed remission; PR, partial remission; PD, progressive
disease; BEAM, carmustine (BICNU®), etoposide, cytarabin (arabinoside), melphalan; TBI/Cy, total body irradiation/cyclophosphamide; IL, indolent
lymphoma.
b
they received upfront transplantation or not (71% versus 62%;
P = 0.54) (Table 2, Figure 2). In general, CD-TIL had significantly
higher survival than S-TIL (5-year OS: 75% versus 50%; P = 0.01;
5-year PFS: 75% versus 38%; P = 0.002) (supplementary Table S4,
available at Annals of Oncology online). When comparing the
outcome of all TIL patients based on the number of prior chemotherapy regimens, a higher number of prior regimens correlated
Volume 26 | No. 2 | February 2015
with an inferior outcome (P = 0.05) (supplementary Table S4,
available at Annals of Oncology online).
multivariate analysis
ASCT had independent favorable impact on PFS in both the
overall (P = 0.03) and S-TIL cohorts (P = 0.004), but not in CDTIL (P = 0.56) (supplementary Table S5, available at Annals of
doi:10.1093/annonc/mdu537 | 
original articles
Annals of Oncology
B 1.00
All TIL
Overall survival
0.80
Progression-free survival
A 1.00
ASCT
0.60
0.40
R-Chemo
0.20
P = 0.11
0.00
0
1
2
3
4
5
6
Time (years)
7
8
9
0.40
R-Chemo
0.20
P = 0.02
0.00
0
1
2
3
4
5
6
Time (years)
7
8
9
10
D 1.00
0.80
ASCT
0.60
R-Chemo
Progression-free survival
CD-TIL
Overall survival
ASCT
0.60
10
C 1.00
0.40
0.20
P = 0.66
0.00
0
1
2
3
4
5
6
Time (years)
7
8
9
ASCT
0.80
0.60
R-Chemo
0.40
0.20
P = 0.54
0.00
10
0
1
2
3
4
5
6
Time (years)
7
8
9
10
F 1.00
Progression-free survival
E 1.00
0.80
S-TIL
Overall survival
0.80
ASCT
0.60
0.40
R-Chemo
0.20
P = 0.07
0.00
0
1
2
3
4
5
6
Time (years)
7
8
9
10
0.80
0.60
ASCT
0.40
0.20
R-Chemo
P = 0.02
0.00
0
1
2
3
4
5
6
Time (years)
7
8
9
10
Figure 1. Overall survival and progression-free survival by treatment modality. Time calculated from time of transformation. (A) Overall survival and (B) progression-free survival in all TIL patients (R-Chemo, n = 31; R-Chemo + ASCT, n = 64); (C) overall survival and (D) progression-free survival in Composite/discordant TIL patients (R-Chemo, n = 13; R-Chemo + ASCT, n = 25); (E) overall survival and (F) progression-free survival in sequential TIL patients (R-Chemo,
n = 18; R-Chemo + ASCT, n = 39). ASCT, autologous stem-cell transplantation; R-Chemo, Rituximab-containing chemotherapy; TIL, transformed indolent
lymphoma.
Oncology online). A high FLIPI score had independent adverse
impact on OS and PFS in S- but not CD-TIL patients (P = 0.01
and P = 0.12) (supplementary Table S5, available at Annals of
Oncology online).
discussion
The aim of the present study was to evaluate the impact of
ASCT in TIL. Furthermore, we investigated the outcome of
cases with histologically low- and high-grade components diagnosed either simultaneously, CD-TIL, or after a period of overt
indolent disease, S-TIL. It has been debated whether the
 | Madsen et al.
distinction between CD-TIL and S-TIL is biologically meaningful or merely an arbitrary distinction of the same biological
process (transformation) identified at different time points in
the evolution of the original indolent disease [23–25]. However,
the biological background of the two conditions may be, this
distinction reflects the two clinical scenarios in which treatment-related decisions are made in the face of histological transformation, thus justifying such an approach.
In the present material, CD-TIL had a better outcome than STIL regardless of treatment strategy at transformation. With
regard to ASCT in particular, we found that it had a beneficial
influence on outcome limited to S-TIL.
Volume 26 | No. 2 | February 2015
original articles
Annals of Oncology
Table 2. Outcome according to TIL subset
5-year
OS
5-year
PFS
All TIL
R-Chemo, N = 31
(36%)
ASCT, N = 54
(64%)
P
Composite/discordant TIL
R-Chemo, N = 13 ASCT, N = 21
(38%)
(62%)
48 (29–65)
30 (15–47)
P
Sequential TIL
R-Chemo, N = 18
(35%)
ASCT, N = 33
(65%)
P
67 (52–78)
0.11
67 (34–86)
76 (52–89)
0.66
36 (15–58)
62 (43–77)
0.07
60 (45–72)
0.02
62 (31–82)
71 (46–86)
0.54
6 (4–25)
53 (35–69)
0.002
OS, overall survival; PFS, progression-free survival; ASCT, autologous stem-cell transplantation; TIL, transformed indolent lymphoma.
B 1.00
1.00
Progression-free survival
A
R-Chemo
Overall survival
0.80
No rituximab at IL-stage
0.60
0.40
0.20
Rituximab at IL-stage
P < 0.001
0.00
0
2
3
7
8
9
0.60
0.40
No rituximab at IL-stage
0.20
0.00
10
Rituximab at IL-stage
0
1
2
3
4
5
6
Time (years)
P = 0.04
7
8
7
8
9
10
D 1.00
1.00
0.80
ASCT
Overall survival
4
5
6
Time (years)
Progression-free survival
C
1
0.80
No rituximab at IL-stage
0.60
0.40
0.20
Rituximab at IL-stage
P = 0.06
0.00
0
1
2
3
4
5
6
Time (years)
7
8
9
10
0.80
No rituximab at IL-stage
0.60
0.40
0.20
Rituximab at IL-stage
P = 0.11
0.00
0
1
2
3
4
5
6
Time (years)
9
10
Figure 2. Overall survival and progression-free survival for sequential TIL according to treatment with rituximab at some point during IL stage and to treatment at TIL stage. Time calculated from time of transformation. (A) Overall survival and (B) progression-free survival in patients treated with R-Chemo at TIL
stage (No rituximab, n = 13; rituximab n = 5). (C) Overall survival and (D) progression-free survival in patients treated with R-Chemo + ASCT at TIL stage (No
rituximab, n = 32; rituximab n = 7). TIL, transformed indolent lymphoma; ASCT, autologous stem-cell transplantation; IL, indolent lymphoma; R-Chemo,
Rituximab-containing chemotherapy.
Only few reports have investigated the role of ASCT in TIL in
the rituximab era [6, 8, 9, 11, 18] and almost all focus on S-TIL
only as CD-TIL traditionally have been excluded from these analyses and are instead included on DLBCL studies. A recent retrospective study of the Canadian Blood and Marrow Transplant
Group [9] included 154 S-TIL patients of which 97 were consolidated with ASCT and 57 treated with R-Chemo alone. No
Volume 26 | No. 2 | February 2015
outcome difference was found at univariate level (5-year OS 65%
versus 61%, P = 0.24; 5-year PFS 55% versus 40%, P = 0.12), but in
a multivariate analysis, ASCT emerged as an independent favorable
parameter for outcome (hazard ratio = 0.13; P < 0.001). Additional
studies from single institutions [8, 11, 18] or the NCCN outcome
database [10] showed 5-year OS and PFS for ASCT-treated S-TIL
in the range of 60%–70% and 40%–45%, respectively.
doi:10.1093/annonc/mdu537 | 
original articles
Reddy et al. investigated the outcome of 44 ASCT-treated TIL
patients, of which 32 had signs of transformation either at initial
diagnosis (comparable with CD-TIL patients in our report) or
within 1 year from it, while 12 transformed >1 year from initial
diagnosis. The long-term outcome was significantly better in
‘early’ than in ‘late’ transformed patients (5-year OS: 80% versus
32%; P = 0.018; 5-year event-free survival: 59% versus 16%;
P = 0.027) [6]. These findings are in line with our observation of
a better outcome for CD-TIL when compared with S-TIL.
Previous studies have also suggested that CD-TIL have outcomes comparable with those of ‘de novo’ DLBCL [5–7, 12, 14,
26, 27]. This may be partly due to underlying biological differences between CD-TIL and S-TIL. Another reason can be that
CD-TIL patients are chemotherapy-naïve and therefore more
likely to exhibit genuine sensitivity to first-line chemoimmunotherapy when compared with a heavily pre-treated, more refractoriness-prone S-TIL setting. In our study, CD-TIL outcome
was not influenced by the addition of ASCT (Figure 2C and D)
suggesting that ASCT may be more useful to overcome chemoresistant or residual/relapsed disease (as in the S-TIL setting),
than to consolidate an already pristine response in the upfront
setting.
We also analyzed, whether prior rituximab treatment during
the indolent course of the disease affected outcome after transformation. Interestingly, the use of rituximab at IL-stage resulted
in an overall outcome after transformation inferior to that of
corresponding patients, who had not received the antibody.
This difference was not abrogated, even if patients subsequently
received ASCT as consolidation strategy. A similar observation
was reported by Ban-Hoefen et al. and Blaker et al. [11, 18], who
found 5-year OS of 80% and 75%, respectively, for patients who
were rituximab-naïve at time of TIL diagnosis and 45% and
30%, respectively, for patients exposed to rituximab before
transformation (P = 0.03 and P = 0.04). Similar results have
been reported in relapsed/refractory de novo DLBCL [28] and
could indicate selection of rituximab-resistant subclones, even
though the underlying biological mechanisms are still unclear
[29–35]. This could suggest a need to consider alternative
approaches, e.g. novel anti-CD20-agents or clinical trials for
patients with prior rituximab exposure.
In spite of the caveat inherent to the retrospective nature of
the present analysis and the relatively limited size of the analyzed cohort, this study is among the very few trying to compare
the two main clinical settings in which histological transformation occurs in IL with regard to treatment features both prior
and after transformation. In this study, the choice of performing
ASCT was relatively unbiased, due to predetermined treatment
strategies adopted at the different selected centers. Patients that,
according to clinical records, were not offered ASCT due to
poor performance score secondary to e.g. co-morbidity, were
not included in the comparative analysis of ASCT versus no
ASCT. Moreover, important confounding characteristics such as
age, sex, performance status and disease stage were comparable
at univariate level and did not influence outcome when entered
into a multivariate analysis. Based on this and other similar
reports, prospective clinical trials, specifically designed for TIL
patients, should be encouraged in order to investigate the
optimal treatment strategy for this still largely unmet clinical
need.
 | Madsen et al.
Annals of Oncology
funding
This work was supported by Region Midtjyllands Forskningsfond,
Aarhus University Research Foundation and the Karen Elise
Jensen Foundation (grant number 4/09-10).
disclosure
The authors have declared no conflicts of interest.
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Annals of Oncology 26: 399–406, 2015
doi:10.1093/annonc/mdu534
Published online 27 November 2014
Incidence and determinants of 1-month mortality after
cancer-directed surgery
B. A. Mahal1,†, G. Inverso2, †, A. A. Aizer3, D. R. Ziehr1, A. S. Hyatt3, T. K. Choueiri4, K. E. Hoffman5,
J. C. Hu6, C. J. Beard3, A. V. D’Amico3, N. E. Martin3, P. F. Orio, III3, Q.-D. Trinh7 & P. L. Nguyen3*
1
Department of Medical Oncology, Harvard Medical School; 2Harvard School of Dental Medicine; Departments of 3Radiation Oncology; 4Medical Oncology, Dana-Farber
Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston; 5Department of Radiation Oncology, The University of Texas MD Anderson Cancer
Center, Houston; 6Department of Urology, UCLA Medical Center, Los Angeles; 7Division of Urology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
Received 29 September 2014; revised 4 November 2014; accepted 5 November 2014
Background: Death within 1 month of surgery is considered treatment related and serves as an important health care
quality metric. We sought to identify the incidence of and factors associated with 1-month mortality after cancer-directed
surgery.
Patients and methods: We used the Surveillance, Epidemiology and End Results Program to study a cohort of
1 110 236 patients diagnosed from 2004 to 2011 with cancers that are among the 10 most common or most fatal who
received cancer-directed surgery. Multivariable logistic regression analyses were used to identify factors associated with
1-month mortality after cancer-directed surgery.
Results: A total of 53 498 patients (4.8%) died within 1 month of cancer-directed surgery. Patients who were married,
insured, or who had a top 50th percentile income or educational status had lower odds of 1-month mortality from cancer*Correspondence to: Dr Paul L. Nguyen, Dana Farber Cancer Institute/Brigham and
Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Tel: +1-617-732-7936; Fax: +1-617-975-0912; E-mail: [email protected]
†
Both authors contributed equally.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: [email protected].