Download Does delay of adjuvant chemotherapy impact survival in patients

Original Article
Does Delay of Adjuvant Chemotherapy
Impact Survival in Patients With Resected
Stage II and III Colon Adenocarcinoma?
Ulas Darda Bayraktar, MD1; Emerson Chen, BA2; Soley Bayraktar, MD1; Laurence R. Sands, MD3;
Floriano Marchetti, MD3; Alberto Jose Montero, MD1; and Caio Max S. Rocha-Lima, MD1
BACKGROUND: It is unclear whether delays in commencing adjuvant chemotherapy after surgical resection of colon
adenocarcinoma adversely impact survival. METHODS: Patients with stage II-III colon adenocarcinoma who received
adjuvant chemotherapy at 2 centers were identified through the institutional tumor registry. Time to adjuvant chemotherapy, overall survival (OS), and relapse-free survival (RFS) were calculated from the day of surgery. Patients were
dichotomized into early (time to adjuvant chemotherapy 60 days) and late treatment (time to adjuvant chemotherapy >60 days) groups. OS and RFS were compared using log-rank test and multivariate analysis by the Cox proportional hazards model. RESULTS: Of 186 patients included in the study, 49 (26%) had received adjuvant chemotherapy
>60 days after surgical resection. Thirty percent of the delays were system related (eg, late referrals, insurance
authorizations). Time to adjuvant chemotherapy >60 days was associated with significantly worse OS in both univariate analysis and a Cox proportional hazards model (hazard ratio, 2.17; 95% confidence interval, 1.08-4.36). Although
difference in RFS between the 2 groups favored time to adjuvant chemotherapy <60, this did not reach statistical
significance. CONCLUSIONS: Adjuvant chemotherapy delay >60 days after surgical resection of colon cancer is assoC 2010 American Cancer Society.
ciated with worse OS. Cancer 2011;117:2364–70. V
KEYWORDS: colon cancer, adjuvant chemotherapy, cancer therapy delay, disparity, 5-fluorouracil, oxaliplatin.
Adjuvant chemotherapy after surgical resection in stage III colon adenocarcinoma decreases recurrences and
improves survival.1 5-Fluorouracil with leucovorin,2,3 5-fluorouracil/leucovorin with oxaliplatin,4,5 and capecitabine
monotherapy6 are current standard adjuvant chemotherapy regimens in colon cancer. The role of adjuvant chemotherapy
in patients with resected stage II colon cancer remains controversial. However, in the subset of stage II colon cancer
patients with high-risk features such as T4 tumors, poor differentiation, perforation, and inadequate number of evaluated
lymph nodes, there might be a role for adjuvant chemotherapy.7
Adjuvant chemotherapy is thought to increase cancer cure rates by eradicating micrometastases after surgical resection.
Surgery can stimulate angiogenesis and suppress the immune system, leading to tumor growth.8-10 Consequently, it is intuitive that there exists a time-dependent point after surgery where adjuvant chemotherapy would fail to eradicate the micrometastases. In a mathematical model, Harless and Qiu11 proposed that the tumor burden at the time of adjuvant chemotherapy
initiation was a function of 4 factors: metastatic load remaining after surgery, intrinsic doubling time of the tumor, relative
effectiveness of the immune system in eradicating residual malignant cancer cells, and the time period elapsing before the
start of effective chemotherapy. Currently, the latter is the only clinically controllable variable in this equation.
Clinical trials for adjuvant chemotherapy in colon cancer generally have required a time interval between surgery
and adjuvant chemotherapy initiation of no more than 6 to 8 weeks.1,2,12-14 However, it is unclear from the published literature to what extent the time to initiating adjuvant chemotherapy for colon cancer correlates with patients’ survival. Various analyses of prospective clinical trials and a few retrospective studies have reported conflicting results.13,15-25 It can be
postulated from the published studies that delay of adjuvant chemotherapy for >56 to 60 days could have a detrimental
effect on survival. However, a major limitation of these studies is that confounding factors such as urgency of the surgical
Corresponding author: Ulas D. Bayraktar, MD, Sylvester Comprehensive Cancer Center, 1475 NW 12th Ave St 3300, Miami, FL 33136; Fax: (305) 585-0037;
[email protected]
1
Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida; 2University of Miami Miller School of Medicine,
Miami, Florida; 3Division of Surgical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida
DOI: 10.1002/cncr.25720, Received: June 10, 2010; Revised: August 20, 2010; Accepted: September 24, 2010, Published online December 17, 2010 in Wiley
Online Library (wileyonlinelibrary.com)
2364
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June 1, 2011
Colon Cancer Adjuvant Chemotherapy Delay/Bayraktar et al
resection, reason for the adjuvant chemotherapy delay,
delays during adjuvant chemotherapy, and early adjuvant
chemotherapy discontinuation were not incorporated
into the analyses. Here, we compared the survival between
colon cancer patients who received adjuvant chemotherapy within and after 60 days of surgical resection while
controlling for confounding factors.
MATERIALS AND METHODS
After approval by our institutional review board, we identified patients diagnosed with stage II-III colon adenocarcinoma who received adjuvant chemotherapy after
complete surgical resection between January 2000 and
December 2008 at Jackson Memorial Hospital (the tertiary-care county hospital in Miami, Fla) and The University of Miami Sylvester Comprehensive Cancer Center (a
private academic cancer center), through the institutional
tumor registry. Patients with rectal carcinoma, those who
received adjuvant chemotherapy >120 days after surgery,
and those with <90 days of follow-up were excluded from
the study. By using a standardized data collection form,
the following data were gathered from the medical records
and institutional tumor registry: age, sex, race/ethnicity,
marital status, serum creatinine and albumin levels within
2 weeks of surgery, cancer diagnosis (colonoscopy/computerized tomography that first identified the tumor)
date, surgical resection date, urgency of the surgical resection, pathology from surgical resection, staging information, follow-up data, and adjuvant chemotherapy data
including the type, number of cycles, and dates of first
and last doses. Survival data and date of death were
obtained from the institutional tumor registry, chart
reviews, and social security death index searches. Time to
adjuvant chemotherapy and overall survival (OS) were
calculated from the surgery date. Relapse-free survival
(RFS) was calculated from the surgery date until the date
of disease relapse, death, or last follow-up. Reasons for
adjuvant chemotherapy delay were classified as 1 of the
following: secondary to surgical complications, systemrelated reasons (late referral from outside hospital, late
appointments within the hospital, extended time required
for insurance authorization), patient-related reasons
(missed appointments and extensive time a patient
required to decide on adjuvant chemotherapy), or medical
reasons (extra time needed for additional tests and tumor
board discussions; and extensive discussions between physician and patients). Early discontinuation was defined as
cessation of adjuvant chemotherapy before at least 80% of
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June 1, 2011
planned adjuvant chemotherapy cycles were delivered
unless adjuvant chemotherapy was discontinued because
of disease relapse. Delay during adjuvant chemotherapy
was defined as adjuvant chemotherapy duration (time
between the first and last adjuvant chemotherapy cycle)
>25% of the treatment optimal duration. Optimal duration was calculated as: (number of chemotherapy cycles
the patient received 1) required interval between
each chemotherapy cycle. However, this is not a validated
approach and was designed to address the heterogeneity
of the number of delivered treatments and the duration of
therapy in the adjuvant setting. Urgent surgery was
defined as a resection in a patient who presented to an
emergency room with bowel obstruction or severe anemia
that necessitated an immediate operation.
Patients were dichotomized into early (time to adjuvant chemotherapy 60 days) and late (time to adjuvant
chemotherapy >60 days) treatment groups. The 2 groups’
demographic and clinical characteristics were compared
with 2-sided Student t test and chi-square test. While
comparing chemotherapy regimens that include oxaliplatin to those that do not, the patients who received chemotherapy regimens that incorporate irinotecan were
excluded from the univariate analysis. Kaplan-Meier survival curves were constructed and compared between subgroups using the log-rank test. To assess the impact of
adjuvant chemotherapy delay on survival independent of
other confounding variables, a multivariate Cox proportional hazards model was constructed incorporating the
significant prognostic factors found in the univariate logrank test. Variables for which data were missing for
>10% of the patients were excluded from the model. Second, subgroup analyses were performed using univariate
Cox proportional hazards models in the subgroups with
prognostic significance identified in the log-rank test.
Finally, OS of patients in whom adjuvant chemotherapy
was delayed for specific reasons was compared with OS of
the patients in the late treatment group using univariate
Cox proportional hazards models. Log transformation
was used to calculate 95% confidence intervals of survival
estimates. A P value <.05 was considered statistically significant. PASW Statistics 17.0 (SPSS Inc., Chicago, Ill)
was used for all statistical analyses.
RESULTS
One hundred eighty-six patients were included in the
study. Thirty-eight and 148 patients had stage II and
III colon cancer, respectively. Time to adjuvant
2365
Original Article
Table 1. Selected Demographic and Clinical Characteristics of
Patients in the Early and Late Treatment Groups
Characteristics
Early
Treatment,
n5137,
No. (%)
Late
Treatment,
n549,
No. (%)
P
Agea
Sex ¼ male
55.7 1.1
52 (38)
56.9 1.8
20 (41)
.559
.724
20 (15)
80 (58)
37 (27)
13 (26)
24 (49)
12 (25)
27 (20)
73 (53)
36 (26)
1 (1)
0.83 0.02
3.92 0.09
68 (50)
36/124 (29)
25/76 (33)
7 (14)
28 (57)
14 (29)
Marital status
Single
Married
Divorced or widow
.169
Race
White non-Hispanic
White Hispanic
Black
Asian
Creatininea
Albumina
Diagnosed before 2004
Urgent surgery
TTS > 30 days
.775
0
0.82 0.03
3.87 0.13
18 (37)
20/43 (47)
5/18 (28)
T stage
1-2
3
4
Tumor dimensiona
Differentiation ¼ poor
Margins involved
AC at JMH
Oxaliplatin included in AC
AC early discontinuation
Delay during AC
.036
.675
.242
20 (15)
110 (82)
5 (4)
5 (10)
40 (82)
4 (8)
N stage
0
1
2
.940
.772
.463
25 (18)
64 (47)
48 (35)
4.79 0.23
27/129 (21)
11/116 (10)
72 (53)
64/109 (59)
11/102 (11)
36/105 (34)
13 (26)
21 (43)
15 (31)
4.76 0.37
6/46 (13)
6/42 (14)
32 (65)
30/42 (71)
11 /40 (27)
15/40 (37)
.877
.240
.592
.123
.149
.013
.849
TTS indicates time to surgery (from diagnosis date); AC, adjuvant chemotherapy; JMH, Jackson Memorial Hospital.
a
Mean standard error.
chemotherapy ranged between 22 and 118 days (median,
48). Forty-nine (26%) patients received adjuvant chemotherapy >60 days after surgery. Adjuvant chemotherapy
was delayed because of system-related factors in 15
(31%), patient-related factors in 10 (20%), medical reasons in 9 (18%), surgical complications in 8 (16%), and
unknown reasons in 7 (14%) patients.
Demographic and clinical characteristics of the
patients in the 2 groups are demonstrated in Table 1.
More patients in the late treatment group underwent
urgent surgery and discontinued adjuvant chemotherapy
early. Of note, in only 3 (5%) of 56 patients who had
undergone urgent surgeries, adjuvant chemotherapy was
delayed because of surgical complications (wound dehis-
2366
cence and infection). All 159 patients for whom we had
the details of adjuvant chemotherapy had received fluoropyrimidine-based chemotherapy. The most frequently
used adjuvant chemotherapy regimens were FOL-FOX (n
¼ 64), Mayo Clinic schedule (n ¼ 30), and Roswell-Park
schedule (n ¼ 17).
In the early treatment group, 27 (20%) patients
were followed until death, and 110 patients were alive after a median follow-up of 42.9 months (range, 7.2-112.2
months). In the late treatment group, 14 (29%) patients
were followed until death, and 35 patients were alive after
a median follow-up of 26.6 months (range, 10.7-80.3
months). Twenty-three (85%) and 9 (64%) deaths in the
early and late treatment groups were cancer-related,
whereas cause of death could not be identified in 1 and 3
patients in the early and late treatment groups, respectively. The 5-year disease-specific survival in early and late
treatment groups was 80.3% and 70.4%.
Table 2 demonstrates the 5-year OS and RFS rates
in various patient subgroups. Whereas OS was found to
be significantly worse in the late treatment group compared with the early treatment group in the univariate
analysis (Fig. 1A), the difference in RFS between the 2
groups did not reach statistical significance (Fig. 1B).
Other identified prognostic factors for OS in univariate
analyses included diagnosis year, urgency of the surgery, T
and N stages of the cancer, treating hospital, and whether
adjuvant chemotherapy included oxaliplatin (irinotecancontaining regimens were excluded from this comparison). Data for urgency of the surgery and adjuvant chemotherapy type were missing for >10% of patients. The
Cox proportional hazards model incorporating age, diagnosis year, T and N stages of the tumor, treating hospital,
and adjuvant chemotherapy delay demonstrated time to
adjuvant chemotherapy >60 days as a poor prognostic
factor for OS (Table 3, right-most column).
Subgroup analyses demonstrated that delay of adjuvant chemotherapy >60 days after surgery was associated
with numerically worse OS in almost all patient subgroups (Table 3). Perhaps due in part to overall relatively
small sample size, the only subgroups where time to adjuvant chemotherapy >60 days was associated with significantly worse OS were the patients treated at Sylvester
Comprehensive Cancer Center and those who were diagnosed with colon cancer before 2004.
In a small patient cohort, OS was significantly worse
in patients whose adjuvant chemotherapy was delayed
beyond 60 days because of patient-related factors and
unknown reasons than in patients who received
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Colon Cancer Adjuvant Chemotherapy Delay/Bayraktar et al
Table 2. Five-Year OS and RFS Rates in Patient Subgroups
Characteristic
Value
5-Year RFS,
% (95% CI)
Pa
Age
60
>60
Male
Female
Single
Married
DW
W, non-Hisp
W, Hisp
B
Before 2004
Beyond 2004
Nonurgent
Urgent
30 days
>30 days
0
1
2
1-2
3
4
SCCC
JMH
60
>60
FP alone
FP þ OX
No
Yes
No
Yes
64.7
65.9
55.6
70.2
78.2
65.1
59.0
56.3
66.4
70.7
54.3
76.4
73.7
51.3
73.8
76.0
71.7
74.5
49.4
80.6
66.2
29.6
74.9
57.5
67.6
57.6
61.3
73.1
74.7
64.5
68.9
75.1
.673
Sex
Marital status
Race/ethnicity
Diagnosis year
Surgical resection
TTS
N stage
T stage
Hospital
TTC
AC type
AC early discontinuation
Delay during AC
(54.7-76.5)
(54.5-79.7)
(42.0-73.8)
(61.3-80.4)
(63.9-95.8)
(55.0-77.1)
(45.1-77.2)
(40.2-78.9)
(56.1-78.5)
(58.2-85.8)
(44.1-66.8)
(65.4-89.3)
(64.8-83.9)
(36.5-72.2)
(63.1-86.4)
(58.7-98.4)
(57.0-90.1)
(64.1-86.6)
(36.7-66.5)
(64.6-100.0)
(57.8-75.9)
(10.0-87.6)
(64.7-86.7)
(47.0-70.3)
(59.2-77.2)
(41.5-80.0)
(49.4-76.0)
(60.9-87.7)
(65.9-84.7)
(39.7-100.0)
(58.7-81.0)
(61.6-91.6)
HR for
RFSb
.111
.434
.266
.003
Reference
0.53 (0.30-0.96)
.005
.421
.001
<.001
.035
.372
.087
.691
.317
Reference
0.92 (0.40-2.10)
2.53 (1.16-5.52)
Reference
1.70 (0.67-4.34)
6.30 (1.83-21.72)
Reference
1.51 (0.86-2.64)
Reference
1.21 (0.66-2.20)
5-Year OS,
% (95% CI)
Pa
HR for OSb
78.6
66.7
70.9
75.3
88.6
71.0
69.4
67.5
73.7
77.8
65.1
84.8
82.4
61.4
79.4
81.8
82.0
82.3
56.2
83.9
74.4
37.0
81.0
67.5
78.6
56.7
66.7
85.8
83.1
68.9
77.9
76.8
.068
Reference
1.41 (0.74-2.70)
(69.8-88.4)
(54.6-81.4)
(59.0-85.2)
(66.2-85.7)
(76.8-100.0)
(60.6-83.2)
(55.8-86.3)
(51.5-88.4)
(63.9-85.1)
(64.1-94.4)
(55.0-77.1)
(76.1-94.4)
(74.3-91.3)
(47.5-79.3)
(69.0-91.4)
(63.8-100.0)
(68.5-98.2)
(72.3-93.7)
(43.0-73.5)
(65.8-100.0)
(66.5-83.3)
(13.8-99.8)
(70.4-93.2)
(57.6-79.2)
(71.0-87.1)
(40.0-80.3)
(54.8-81.2)
(77.2-95.4)
(74.9-92.2)
(46.0-100.0)
(68.5-88.6)
(61.8-95.5)
.351
.265
.637
.018
Reference
0.47 (0.23-0.99)
.021
.288
<.001
.004
.016
.036
Reference
1.10 (0.38-3.13)
3.98 (1.47-10.77)
Reference
2.17 (0.65-7.23)
8.20 (1.71-39.21)
Reference
2.09 (1.06-4.15)
Reference
2.07 (1.02-4.19)
.046
.288
.433
OS indicates overall survival; RFS, relapse-free survival; CI, confidence interval; HR, hazard ratio; DW, divorced or widowed; W, white; Hisp, Hispanic; B,
black; TTS, time to surgery; SCCC, Sylvester Comprehensive Cancer Center; JMH, Jackson Memorial Hospital; AC, adjuvant chemotherapy; FP, fluoropyrimidine; OX, oxaliplatin.
a
Derived from univariate comparisons of the survival curves with log-rank test.
b
Derived from the multivariate Cox proportional hazards model.
chemotherapy within 60 days of surgery (Table 4). No
significant difference was found between OS of patients
in the early treatment group and OS of those in whom
adjuvant chemotherapy was delayed because of surgical
complications or medical reasons; however, this is likely
because of small numbers of patients in these subgroups.
DISCUSSION
To the best of our knowledge, this is the first study that in
addressing whether delays in the initiation of adjuvant
chemotherapy adversely impact survival in colon cancer
patients, also dissects the contribution of other confounding factors, such as urgency of surgical resection, reason
for adjuvant chemotherapy delay, delays during adjuvant
chemotherapy, and early adjuvant chemotherapy disconCancer
June 1, 2011
tinuation. On univariate analysis and a Cox proportional
hazards model, we found that patients who had received
adjuvant chemotherapy within 60 days of surgical resection for colon cancer had a better OS than those who
began adjuvant chemotherapy >60 days after the resection. Although RFS in the early treatment group was
numerically better than RFS in the late treatment group,
the difference was not statistically significant.
Most of the adjuvant chemotherapy delays in our
cohort were system- and patient-related, indicating a mix
of intra-/interhospital referral system deficiencies and
patient behavior as the primary culprits for the adjuvant
chemotherapy delay. Similarly, administrative problems
were found to be the most common cause of delay in the
treatment of breast cancer in a retrospective study published in 1980.26
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Original Article
Table 3. HRs for Adjuvant Chemotherapy Delay on Overall
Survival in Selected Patient Subgroups
Characteristic
Subgroup
No.
HR (95% CI)a
Diagnosis year
2000-2003
2004-2009
SCCC
JMH
0
1
2
0-2
3
4
Elective
Urgent
FP alone
FP þ OX
Adequate
Inadequate
Not delayed
Delayed
86
100
82
104
38
85
63
13
150
9
112
56
57
94
120
22
95
51
2.49
1.67
3.70
1.30
4.86
1.93
1.84
2.89
1.93
0.64
1.52
1.26
2.24
2.12
2.11
0.60
1.33
1.97
Hospital
N stage
T stage
Surgery
AC type
Number of AC cycles
Delay during AC
(1.15-5.38)
(0.48-5.74)
(1.19-11.48)
(0.56-2.99)
(0.88-26.72)
(0.56-6.64)
(0.71-4.78)
(0.26-32.30)
(0.93-4.04)
(0.10-3.92)
(0.55-4.24)
(0.43-3.70)
(0.89-5.64)
(0.59-7.68)
(0.72-6.15)
(0.08-4.60)
(0.47-3.75)
(0.44-8.81)
HR indicates hazard ratio; CI, confidence interval; SCCC, Sylvester Comprehensive Cancer Center; JMH, Jackson Memorial Hospital; AC, adjuvant
chemotherapy; FP, fluoropyrimidine; OX, oxaliplatin.
a
Derived from the univariate analyses comparing early and late initiation of
adjuvant chemotherapy in the subgroups specified in the first column.
Table 4. HRs for Overall Survival in the Late Treatment Group
Stratified According to the Reason for Delay of Adjuvant
Chemotherapy
Reason for Delay
No. (%)
HR (95% CI)a
Early treatment
137
Reference
Late treatment
49 (100)
System-related reasons
Patient-related reasons
Medical reasons
Surgical complications
Unknown
15
10
9
8
7
(31)
(20)
(18)
(16)
(14)
1.07 (0.25-4.54)
4.99 (2.03-12.26)
No deaths recorded
1.93 (0.58-6.37)
5.45 (1.60-18.60)
a
Derived from the univariate comparison of the overall survival between the
individual subsets of the late treatment group and the early treatment
group.
Figure 1. Comparison of overall (A) and relapse-free survival
(B) between patients in early and late treatment groups is
shown (P values are derived from log-rank test).
Patients who required urgent surgical resection
tended to have delayed adjuvant chemotherapy. This can
be partly explained by the higher surgical complication
rates after urgent surgeries compared with elective ones.27
However, only 3 patients who had urgent surgeries in our
study cohort started adjuvant chemotherapy late because
of surgical complications. Equally, lack of insurance coverage and patient behavior in face of sickness may lead to
delays in seeking medical care, consequently leading to
both urgent operations and late referrals to the oncolo-
2368
gists. Accordingly, Langenbach et al reported that patients
with additional insurance had a mean delay of 18 days
between the time of initial diagnosis of colorectal cancer
and referral to the surgeon, whereas those without additional private insurance had a mean delay of 57 days in
Germany.28 Although not statistically significant, we
found that married patients were more likely to start adjuvant chemotherapy within 60 days of surgery compared
with single patients, coinciding with Hershman et al’s
findings.25 We did not find any association between adjuvant chemotherapy delay and race/ethnicity, time to surgery, or significant delays in administering adjuvant
chemotherapy once initiated.
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June 1, 2011
Colon Cancer Adjuvant Chemotherapy Delay/Bayraktar et al
On univariate analysis, we found a significant association between adjuvant chemotherapy delay and OS but
not RFS. Similarly, Chau et al20and Czaykowski et al22
also demonstrated worse OS in patients who received adjuvant chemotherapy >8 weeks after surgery but no difference in RFS. This may be because of relatively small
numbers of patients in both studies and the confounding
variables that may have obscured the difference in RFS
between the 2 groups. Another reason for the difference
between the impact of delay on OS and RFS may be more
cancer-unrelated deaths in patients whose adjuvant chemotherapy is delayed. However, because <15% of deaths
were because of cancer-unrelated reasons in both groups
(time to adjuvant chemotherapy <60 and time to adjuvant chemotherapy >60), it is unlikely that observed differences are unrelated to treatment or to colon cancer.
It is still unclear if the process of delaying administration of adjuvant chemotherapy itself adversely impacts
survival. It is possible that other factors, such as surgical
complications, patient noncompliance with planned
chemotherapy schedule, and system-related factors that
lead to delays in adjuvant chemotherapy, may also
increase mortality independent of time to adjuvant chemotherapy. However, subgroup and multivariate analyses
support the hypothesis that delay in adjuvant chemotherapy worsens survival independent of confounding
variables.
This study has certain limitations. It is a retrospective study with no control over confounding variables.
However, a controlled prospective study on the subject is
not feasible for ethical reasons. In addition, a retrospective
study is better suited to identify the factors leading to
deviation from the optimal care. Second, our study cohort
was not large enough for the detailed analysis of delay’s
impact on survival, and not all data on chemotherapy
were available to us. Consequently, our proportional hazards model was reduced and deprived of important confounding variables such as urgency of surgical resection,
which was found to be a prognostic factor on OS and was
significantly different between early and late treatment
groups. Third, lack of data on patient comorbidities and
performance status may have decreased the accuracy of
our survival analyses.
In summary, delay of adjuvant chemotherapy for
>60 days after surgical resection was found to be associated with poor OS in colon cancer patients. More extensive retrospective studies are needed to confirm the impact
of adjuvant chemotherapy delay on colon cancer survival
independent of confounding factors. Finally, it is possible
Cancer
June 1, 2011
that disparities in clinical outcomes in colon cancer could
be reduced by precisely identifying all major factors that
lead to significant delays (>60 days) in initiating adjuvant
chemotherapy and devising strategies that are effective in
decreasing time to chemotherapy.
CONFLICT OF INTEREST DISCLOSURES
We would like to thank Miami Tumor Registry for providing
the list of patients.
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