Gynecologic Oncology 125 (2012) 362366

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Gynecologic Oncology
journal homepage: www.elsevier.com/locate/ygyno

Changes in serum CA-125 can predict optimal cytoreduction to no gross

residual disease in patients with advanced stage ovarian cancer treated with
neoadjuvant chemotherapy
Noah Rodriguez a, 1, J. Alejandro Rauh-Hain a, b, Melina Shoni a, Ross S. Berkowitz a, Michael G. Muto a,
Colleen Feltmate a, John O. Schorge c, Marcela G. del Carmen c, Ursula A. Matulonis d, Neil S. Horowitz a,
a

Brigham and Women's Hospital, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Harvard Medical School, Boston, MA, USA
Massachusetts General Hospital, Department of Obstetrics and Gynecology, Boston, MA, USA
c
Massachusetts General Hospital, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Harvard Medical School, Boston, MA, USA
d
Dana Farber Cancer Institute, Boston, MA, USA
b

a r t i c l e

i n f o

Article history:
Received 8 December 2011
Accepted 3 February 2012
Available online 12 February 2012
Keywords:
CA 125
Neoadjuvant chemotherapy
Advanced ovarian cancer
Interval debulking
Optimal cytoreduction

a b s t r a c t
Objective. To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis
of epithelial ovarian carcinoma (EOC).
Methods. Using the Cancer Registry databases from our institutions, a retrospective review of patients
with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006
and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy,
and surgicalpathologic information were obtained. Continuous variables were evaluated by Student's t
test or WilcoxonMannWhitney test.
Results. One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of
neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients
(47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval
debulking was 1749 U/mL and 161 U/mL, respectively. Comparing patients with NRD v. optimal macroscopic
disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL,
p = 0.1). There was a signicant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL
(p = 0.001). In the NRD group, 38 patients (80%) had preoperative CA-125 100 U/mL compared to 33
patients (63.4%) in the OMD group (p = 0.04).
Conclusions. Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series,
after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of
100 U/mL were highly likely to be cytoreduced to no residual disease.
2012 Published by Elsevier Inc.

Introduction
Epithelial ovarian carcinoma (EOC) is the leading cause of death
due to a gynecologic malignancy in the United States. In 2010, there
were approximately 21,880 new ovarian cancer cases and 13,850
deaths with over 70% of women with newly diagnosed EOC presenting with advanced stage disease [1]. Primary debulking surgery (PDS)
followed by platinum based chemotherapy has been considered the
standard of care for advanced ovarian cancer [210]. However, the

Corresponding author at: Brigham and Women's Hospital, Francis Street, Boston,
MA 02115, USA. Fax: + 1 617 738 5124.
E-mail address: nhorowitz@partners.org (N.S. Horowitz).
1
Present address: Loma Linda University Medical Center, Division of Gynecologic
Oncology, Department of Obstetrics and Gynecology, Loma Linda School of Medicine,
Loma Linda, CA, USA.
0090-8258/$ see front matter 2012 Published by Elsevier Inc.
doi:10.1016/j.ygyno.2012.02.006

results of a recent randomized controlled trial which compared PDS

to neoadjuvant chemotherapy followed by interval debulking surgery
(NACT-IDS) in patients with advanced EOC demonstrated similar progression free survival and overall survival among the two groups [11].
Among both groups, complete resection of all macroscopic disease
was the strongest independent variable in predicting overall survival.
Therefore, it is important to identify a reliable clinical strategy that
can predict the likelihood of achieving resection to no residual
disease.
Previous studies have attempted to use preoperative computed
tomography (CT) [12,13] and preoperative CA-125 levels [14,15] to
predict optimal PDS in patients with advanced stage ovarian cancer.
However, the radiologic studies were limited by their low sensitivity,
low positive predictive value, and lack of reproducibility. Preoperative CA-125 levels to predict optimal PDS yielded mixed results. The
goals of the current study were to evaluate the changes in serum

N. Rodriguez et al. / Gynecologic Oncology 125 (2012) 362366

CA-125 and patient characteristics to predict the likelihood of achieving optimal interval cytoreduction in patients undergoing taxane
and platinum-based neoadjuvant chemotherapy followed by interval
debulking surgery for a new diagnosis of advanced stage ovarian cancer and to determine an ideal number of neoadjuvant chemotherapy
cycles before attempting interval debulking surgery. A secondary aim
of our study was to identify factors associated with platinum resistance in patients receiving neoadjuvant chemotherapy.
Patients and methods
Institutional Review Board approval of the study was obtained
from both participating institutions. All patients with advanced
stage EOC who were treated with NACT-IDS between January 1,
2006 and December 31, 2009 were identied from the cancer registry
databases at the Brigham and Women's Hospital (BWH) and the Massachusetts General Hospital (MGH). Some patients were diagnosed
with International Federation of Gynecology and Obstetrics (FIGO)
stage IIIC or IV EOC by formal staging criteria, some were noted to
have advanced disease radiographically and determined to be unresectable by the primary surgeon, and others had a performance status
that precluded PDS. Demographic data, chemotherapy regimen and
number of cycles, surgical-pathologic information, CA-125 levels at
diagnosis, before each treatment cycle, and prior to interval debulking
surgery were retrospectively obtained from patient medical records,
as was timing of recurrence and/or disease status at last follow-up.
The decision to perform PDS vs. NACT-IDS was based on the attending
physician's judgment. In addition, chemotherapy regimen and the
number of cycles that the patient received were determined by the
patient's treating oncologist. Debulking surgery was performed by
board eligible/board certied gynecologic oncologists. All patients
underwent an exploratory laparotomy with the intention of achieving
optimal cytoreduction. An operation that left the patient with a maximal diameter of 1 cm residual disease was considered optimal. All
operative and pathologic reports were reviewed by two individuals.
Following initial eligibility screening, the following inclusion
criteria were applied to determine the nal study population: (1) an
elevated serum CA-125 at time of diagnosis (>35 U/mL); (2) at
least two serum CA-125 level determinations (at the time of diagnosis
and prior to IDS); and (3) clinical and/or radiographic determination
of disease status at the time of last follow-up or recurrence. Denitive
diagnosis of recurrence was taken as a rising CA-125, the histologic

363

presence of cancer at the time of secondary cytoreductive surgery

and/or the appearance of new lesions by CT scan or by positron emission tomography (PET) scan imaging. Patients were excluded from
the study for the following reasons: surgery performed at another institution, incomplete surgicalpathologic data, and non-platinum and
taxane based neoadjuvant chemotherapy.
Platinum-sensitive disease was dened as patients who relapsed
more than 6 months after completing platinum therapy. Platinumresistant was dened as patients that have relapsed within 6 months of
prior platinum therapy. Finally, platinum-refractory disease was dened
as disease that progressed or was stable during initial platinum therapy.
For statistical analyses, standard univariate logistic regression
models were used to compare absolute and percent changes (predictor variables) in serum CA-125 levels among patients with no visible
residual disease (NRD) and optimal cytoreduction but macroscopic
disease 1 cm (OMD)(outcome variables). Absolute changes were
calculated by subtracting the CA-125 at diagnosis from the CA-125
level within 30 days of surgery. Relative changes were calculated as
a percentage of the CA-125 level within 30 days of surgery and the
CA-125 at diagnosis.
Continuous variables were evaluated by Student's t test or WilcoxonMannWhitney test, as appropriate. Categorical variables
were evaluated by chi square test or Fisher's exact test as appropriate
for category size. Standard univariate analyses were performed, as
were multivariable analysis with logistic regression to control for potential confounding variables. For continuous variables, the cutoff
level chosen was their median value, unless otherwise specied. All
statistical tests were 2-sided and differences were considered statistically signicant at P b 0.05. Data analysis was performed with SPSS
statistical software (version 18.0, SPSS, Inc, Chicago, IL).
Results
A total of 113 patients who received NACT during the study period
were identied. Ten patients were excluded for the following reasons: nine patients did not have CA-125 level determinations at the
time of diagnosis or within 30 days of interval debulking surgery.
One patient received only platinum based chemotherapy and was excluded. The nal analysis included 103 patients with advanced stage
ovarian cancer who received platinum and taxane-based NACT and
all of whom underwent cytoreductive surgery. The median age of
the study population was 66 years (range, 4485 yo). Forty-one

Table 1
Patient characteristics.
NRD (N = 47)
Age (years)
Stage
IIIC
IV
Time to surgery (days)
Chemotherapy
Platinum
Taxol
Cycles of neoadjuvant chemotherapy
3
>3
CA-125 U/mL presentation
CA-125 U/mL preoperatively
CA-125 100 U/mL preoperatively
Change CA-125 presentation to preop (%)
Change CA-125 > 80% presentation to preop (%)
Hysterectomy
Bilateral salpingo-ophorectomy
Omentectomy
Bowel surgery
Splenectomy
Diaphragmatic surgery
Liver surgery

66
18
29
102
47
47
25
22
1566
92
38
86
36
47
47
47
12
7
3
0

OMD (N = 52)
( 9)
28.30%
61.70%
( 48)
100%
100%
53.10%
46.90%
( 1810)
( 139)
80.00%
( 18)
76.50%
100%
100%
100%
25.50%
14.20%
6.30%

p-Value

66

( 10)

0.5

21
31
102

40.40%
59.60%
( 45)

0.2

100%
100%

0.9

48%
52%
( 2900)
( 492)
63.40%
( 16)
73%
100%
100%
100%
36.50%
9.60%
21.10%
5.70%

0.8

52
52
25
27
2077
233
33
86
38
52
52
52
19
5
11
3

0.3

0.1
0.001
0.04
0.07
0.06
0.9
0.9
0.9
0.3
0.6
0.1
0.3

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N. Rodriguez et al. / Gynecologic Oncology 125 (2012) 362366

patients (40.5%) had stage IIIC disease, and 60 (59.5%) were stage IV.
Eighty-three patients (82.5%) had papillary serous histology. Optimal
interval cytoreduction was achieved in 99 patients (96.1%), and 47
patients (47.5%) had complete resection to no residual disease
(NRD). Four patients (3.9%) were suboptimally cytoreduced. The median CA-125 level at diagnosis and before interval debulking was
1749 U/mL (range, 38 to 10,150 U/mL) and 161 U/mL (range, 5 to
2945 U/mL), respectively. Four patients with advanced EOC had a
CA-125 b100 U/mL at the time of diagnosis, prior to initiating NACT.
All patients received platinum and taxane based chemotherapy. Median number of neoadjuvant cycles was 3 (range 18).
Given that 96% of the patients in our study population had optimal
interval cytoreduction, we compared patients with NRD vs. patients
with OMD. Table 1 summarizes the demographic and clinical characteristics in these two groups. There was no statistical difference in the mean
CA-125 level at diagnosis in patients with NRD compared to patients
with OMD (1566 U/mL vs. 2077 U/mL, p = 0.1). However, the mean
CA-125 level prior to interval debulking surgery was lower for patients
with NRD compared to patients with OMD (92 vs. 233 U/mL,
p = 0.001). Fig. 1 compares the CA-125 levels at presentation and preoperatively in patients who underwent IDS to NRD and OMD. Among
the NRD group, 38 patients (80%) had preoperative CA-125 levels
100 U/mL compared to 33 patients (63.4%) in the OMD group
(p= 0.04). Patients with a preoperative CA-125 100 U/mL had a
higher likelihood of optimal cytoreduction to NRD compared to patients
who had a preoperative CA-125 >100 U/mL (OR 2.6, 95% CI 1.056 .5).
The four patients who had CA-125 levels 100 U/mL at diagnosis
were cytoreduced to NRD. Neither the age, the number of patients that
received three or more cycles of neoadjuvant chemotherapy, CA-125
at presentation, nor the change (absolute value nor percentage) in CA125 obtained at presentation and preoperatively were signicantly different between NRD patients and OMD patients.

Table 2
Variables associated with platinum sensitive disease.

Age (years)
b60
60
Stage
IIIC
IV
Cytoreduction
No residual disease
Optimal but macroscopic
Suboptimal
Cycles of neoadjuvant chemotherapy
3
>3
CA-125 b 35 U/mL prior to surgery
Yes
No
CA-125 drop > 80% initial diagnosis to preop
Yes
No

Platinum
sensitive
(N = 65)

Platinum
resistance
(N = 36)

30
35

46.2%
53.8%

16
20

44.4%
55.6%

0.8

26
39

40%
60%

15
21

41.7%
58.3

0.8

33
30
2

50.8%
46.2%
3.1%

14
22
0

38.9%
61.1%
0%

0.2

26
39

40%
60%

25
11

69.4%
30.6%

0.005

26
39

40%
60%

12
24

33.3%
66.7%

0.5

52
13

80%
20%

22
14

61.1%
38.9%

0.04

Forty-seven patients exhibited a 50% decrease in CA-125 after one

cycle of chemotherapy. However, the number of patients with an early
decrease of at least 50% after 1 cycle of chemotherapy was not signicantly different between patients who had NRD and OMD (57% vs.
50%; p = 0.09). Of note, two patients with suboptimal cytoreduction
had a CA-125 drop approximately 40% after 1 cycle of chemotherapy.
At 6 months from the completion of chemotherapy, 36 patients
(36.5%) exhibited platinum resistance. Table 2 shows prognostic variables associated with platinum sensitive disease. Only a change >80%

Fig. 1. CA-125 at presentation and preoperatively in patients cytoreduced to NRD and OMD.

N. Rodriguez et al. / Gynecologic Oncology 125 (2012) 362366

in CA-125 obtained at presentation and preoperatively, and receiving

four or more cycles of neoadjuvant chemotherapy were signicantly
associated with an increased rate of platinum sensitive disease. When
multivariate logistic regression was performed with the two variables
that were statistically signicant in univariate analysis, only receiving
four or more cycles of neoadjuvant chemotherapy was associated
with platinum sensitive disease (OR 2.9; 95% CI 1.27.2).
Discussion
In the current study, we analyzed the changes in serum CA-125 to
predict the likelihood of achieving optimal interval cytoreduction in
patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy. In our study population, 96% of patients with
advanced ovarian cancer who underwent NACT-IDS were optimally
cytoreduced. Several studies have demonstrated that patients with
advanced ovarian cancer who have been optimally cytoreduced during
primary debulking surgery have improved survival rates compared to
patients who had suboptimal debulking surgery [3,7,9,16,17]. Achieving
optimal cytoreduction in advanced stage ovarian cancer is more common following neoadjuvant chemotherapy as compared to PDS [11].
In their randomized trial, Vergote et al. reported an optimal debulking
rate of 41.6% in patients who underwent PDS compared to 80.6% in patients who had NACT-IDS. In our retrospective study, 96% of patients
with advanced ovarian cancer who were treated with NACT-IDS were
optimally cytoreduced with only 4 patients undergoing suboptimal
cytoreduction at the time of IDS. Although it would be useful to have a
method to identify these women preoperatively, the number (n= 4)
in our group was too small to produce meaningful conclusions and
therefore were excluded from further analysis. Still, our results indicate
that optimal cytoreduction is highly achievable in the setting of neoadjuvant chemotherapy.
Although historically the goal for optimal cytoreduction has been
residual disease no greater than 1 cm in diameter, data from GOG
182 indicate a survival advantage among patients debulked to microscopic disease (i.e. NRD) compared to patients who were optimally
debulked to 1 cm of macroscopic disease (i.e. OMD) [18]. This
data provides signicant evidence that the goal of PDS should be resection of all visible disease. In patients with advanced ovarian cancer
treated with NACT-IDS, Vergote et al. showed that the mean overall
survival for patients who were left with NRD compared to patients
with OMD was 38 and 27 months (P b 0.001), respectively [11].
Vergote's data adds critical clinical evidence to support cytoreduction
to NRD following NACT. Moreover, in patients who have received
neoadjuvant chemotherapy, there is evidence that the remaining disease may contain cancer stem cells and may harbor a chemo-resistant
population [19,20]. Therefore, in the setting of neoadjuvant chemotherapy where optimal cytoreduction is highly feasible, the goal
should in fact be resection of all visible disease.
Of the 99 patients who were optimally cytoreduced in the current
study, 47 patients (47.5%) underwent resection to no residual disease
(NRD). The mean CA-125 level prior to interval debulking surgery
was lower in NRD patients compared to OMD patients (92 v. 233 U/
mL, p = 0.001). In fact, among the 47 patients with NRD, 38 (80%)
had a preoperative CA-125 level of 100 U/mL. Our data suggests
that preoperative serum CA-125 100 U/mL may be useful in predicting optimal cytoreduction to no gross residual disease in patients
treated with NACT. Conversely, neither CA-125 level at presentation,
nor a precipitous drop of 50% in CA-125 level after 1 cycle of chemotherapy, nor change (percentage or absolute value) in CA-125
obtained at presentation and preoperatively were signicantly different between patients with NRD and OMD.
We acknowledge that there is variability among CA-125 assays
between laboratories and that standardization of a CA-125 assay
may not be possible, thus a strict cutoff of 100 U/mL may not be applicable to all institutions. Nevertheless, we believe that a CA-125 target

365

of approximately b100 U/mL in patients treated with NACT is a good

indication of achieving cytoreduction to NRD when attempting IDS.
Because 9 patients in our cohort were cytoreduced to NRD and had
a preoperative CA-125 level of >100 U/mL and, given the high likelihood of optimal cytoreduction to OMD with IDS, our institutions currently offer IDS to patients with a preoperative CA-125 >100 U/mL.
However, a preoperative CA-125 of b100 U/mL has helped us identify
patients in whom we can expect IDS to NRD.
Since its discovery in 1983 [21], CA-125's clinical application has
been widely explored. Previous studies have reported on the utility of
preoperative serum CA-125 levels to help predict optimal debulking
in PDS. One report by Chi et al. found that patients with a CA-125 greater than 500 U/mL have a 20% chance of being optimally debulked in PDS
[14]. A later report by the same author concluded that preoperative CA125 >500 U/mL was associated with more upper abdominal procedures in PDS but did not predict a patient's cytoreducibility [15].
Although CA-125 did not prove to be a reliable predictor of optimal
debulking in PDS, other studies have demonstrated the clinical utility
of serum CA-125 in other aspects pertaining to ovarian cancer. Zivanovic et al. showed a perioperative increase in CA-125 following optimal
debulking surgery to be associated with an increased risk of relapse
[22]. Other studies have demonstrated that reduction in serum CA125 after adjuvant chemotherapy is an independent prognostic factor
of recurrence and an independent predictor of survival [2327]. To
our knowledge, the clinical utility of CA-125 in the neoadjuvant setting
has not been explored. Our study is the rst to investigate the changes
in serum CA-125 in response to chemotherapy in the neoadjuvant
setting and to describe the preoperative ability of CA-125 to predict
the cytoreductive outcomes of IDS. In our study population, 38 of 47
patients (80%) who were cytoreduced to no residual disease had a
preoperative CA-125 level 100 U/mL following initiation of NACT.
There are several important limitations to this study among which
are its retrospective nature, lack of central pathology review, and the
variability of CA-125 assays among laboratories as well as the complex biokinetics of serum CA-125 levels. Still, our study is the rst to
report on the clinical utility of CA-125 in the neoadjuvant setting.
The results of our study need to be conrmed in larger, prospective
studies. Given the favorable cytoreductive outcomes that are possible
with neoadjuvant chemotherapy, clinicians need a clinically reliable
and reproducible strategy that will allow them to identify at what
point a patient can undergo interval debulking surgery and expect
optimal debulking to no gross residual disease.
Conict of interest statement
All authors have no conict of interests to disclose.

References
[1] Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin 2010;60:277300
2010.
[2] Bertelsen K. Tumor reduction surgery and long-term survival in advanced ovarian
cancer: a DACOVA study. Gynecol Oncol 1990;38:2039.
[3] Grifths CT. Surgical resection of tumor bulk in the primary treatment of ovarian
carcinoma. Natl Cancer Inst Monogr 1975;42:1014.
[4] Grifths CT, Fuller AF. Intensive surgical and chemotherapeutic management of
advanced ovarian cancer. Surg Clin North Am 1978;58:13142.
[5] Hacker NF, Berek JS, Lagasse LD, Nieberg RK, Elashoff RM. Primary cytoreductive
surgery for epithelial ovarian cancer. Obstet Gynecol 1983;61:41320.
[6] Delgado G, Oram DH, Petrilli ES. Stage III epithelial ovarian cancer: the role of
maximal surgical reduction. Gynecol Oncol 1984;18:2938.
[7] Hoskins WJ. Epithelial ovarian carcinoma: principles of primary surgery. Gynecol
Oncol 1994;55:S916.
[8] McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients
with stage III and stage IV ovarian cancer. N Engl J Med 1996;334:16.
[9] Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of
maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum
era: a meta-analysis. J Clin Oncol 2002;20:124859.
[10] Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, et al. Phase
III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in
patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology
Group study. J Clin Oncol 2003;21:3194200.

366

N. Rodriguez et al. / Gynecologic Oncology 125 (2012) 362366

[11] Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant
chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med
2010;363:94353.
[12] Bristow RE, Duska LR, Lambrou NC, Fishman EK, O'Neill MJ, Trimble EL, et al. A model
for predicting surgical outcome in patients with advanced ovarian carcinoma using
computed tomography. Cancer 2000;89:153240.
[13] Axtell AE, Lee MH, Bristow RE, Dowdy SC, Cliby WA, Raman S, et al. Multi-institutional
reciprocal validation study of computed tomography predictors of suboptimal
primary cytoreduction in patients with advanced ovarian cancer. J Clin Oncol
2007;25:3849.
[14] Chi DS, Venkatraman ES, Masson V, Hoskins WJ. The ability of preoperative serum
CA-125 to predict optimal primary tumor cytoreduction in stage III epithelial
ovarian carcinoma. Gynecol Oncol 2000;77:22731.
[15] Chi DS, Zivanovic O, Palayekar MJ, Eisenhauer EL, Abu-Rustum NR, Sonoda Y, et al.
A contemporary analysis of the ability of preoperative serum CA-125 to predict
primary cytoreductive outcome in patients with advanced ovarian, tubal and
peritoneal carcinoma. Gynecol Oncol 2009;112:610.
[16] Le T, Krepart GV, Lotocki RJ, Heywood MS. Does debulking surgery improve survival
in biologically aggressive ovarian carcinoma? Gynecol Oncol 1997;67:20814.
[17] Chi DS, Liao JB, Leon LF, Venkatraman ES, Hensley ML, Bhaskaran D, et al. Identication of prognostic factors in advanced epithelial ovarian carcinoma. Gynecol
Oncol 2001;82:5327.
[18] Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, et al.
Evaluation of new platinum-based treatment regimens in advanced-stage ovarian
cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. J Clin Oncol
2009;27:141925.
[19] Tiersten AD, Moon J, Smith HO, Wilczynski SP, Robinson III WR, Markman M, et al.
Chemotherapy resistance as a predictor of progression-free survival in ovarian

[20]

[21]

[22]

[23]

[24]

[25]

[26]
[27]

cancer patients treated with neoadjuvant chemotherapy and surgical cytoreduction followed by intraperitoneal chemotherapy: a Southwest Oncology Group
Study. Oncology 2009;77:3959.
Lim MC, Song YJ, Seo SS, Yoo CW, Kang S, Park SY. Residual cancer stem cells after
interval cytoreductive surgery following neoadjuvant chemotherapy could result
in poor treatment outcomes for ovarian cancer. Onkologie 2010;33:32430.
Bast Jr RC, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian
cancer. N Engl J Med 1983;309:8837.
Zivanovic O, Sima CS, Iasonos A, Bell-McGuinn KM, Sabbatini PJ, Leitao MM, et al.
Exploratory analysis of serum CA-125 response to surgery and the risk of relapse
in patients with FIGO stage IIIC ovarian cancer. Gynecol Oncol 2009;115:20914.
van der Burg ME, Lammes FB, van Putten WL, Stoter G. Ovarian cancer: the
prognostic value of the serum half-life of CA125 during induction chemotherapy.
Gynecol Oncol 1988;30:30712.
Gadducci A, Zola P, Landoni F, Maggino T, Sartori E, Bergamino T, et al. Serum halflife of CA 125 during early chemotherapy as an independent prognostic variable
for patients with advanced epithelial ovarian cancer: results of a multicentric
Italian study. Gynecol Oncol 1995;58:427.
Riedinger JM, Wafart J, Ricolleau G, Eche N, Larbre H, Basuyau JP, et al. CA 125
half-life and CA 125 nadir during induction chemotherapy are independent
predictors of epithelial ovarian cancer outcome: results of a French multicentric
study. Ann Oncol 2006;17:12348.
Crawford SM, Peace J. Does the nadir CA125 concentration predict a long-term
outcome after chemotherapy for carcinoma of the ovary? Ann Oncol 2005;16:4750.
Markman M, Federico M, Liu PY, Hannigan E, Alberts D. Signicance of early
changes in the serum CA-125 antigen level on overall survival in advanced
ovarian cancer. Gynecol Oncol 2006;103:1958.