Download The role of laparoscopy in the evaluation and treatment of epithelial

Practice Guidelines
The role of laparoscopy in
the evaluation and treatment
of epithelial ovarian cancer
J. Hauspy, B. Pouseele, J. Van Wiemeersch, A. Rutten, L. Verkinderen, P.A. Van Dam
Laparotomy has been the standard approach for diagnosis and treatment of ovarian cancer.
The goal of this article was to collect and summarise the evidence concerning the use of
laparoscopy in ovarian cancer. We performed a Medline search of studies and reviews
about the laparoscopic approach for evaluation of surgery of ovarian cancer.
Laparoscopy appears to be a safe, accurate and patient-friendly alternative for laparotomy
in primary surgery for early-stage ovarian cancer and in accurate staging and evaluation of
operability in advanced ovarian cancer. Very little evidence is available on the role of laparoscopy in advanced ovarian cancer.
Belg J Med Oncol 2012;6:157-163)
Introduction
Approximately 25-30% of patients with ovarian
cancer present with early stage disease, limited to the
gynaecological organs and not spread to adjacent
structures in the pelvis or the upper abdomen.1,2
The majority of ovarian cancer patients are diagnosed in an advanced stage for which the standard
approach is surgical exploration of the abdomen with
the aim of achieving maximal cytoreduction at the
end of the surgery. Since 2010 it has been shown
that neo-adjuvant chemotherapy followed by interval
debulking has an equal disease-free survival (DFS)
and overall survival (OS) outcome for inoperable
advanced disease, but reduces the complications
and extent of the surgery.3 In the patients’ interest it
is important to evaluate the possibility of maximal
cytoreduction prior to surgery. Imaging techniques
including MRI, CT and Ultrasound, have proven to
be poor indicators of optimal debulkability. Only
the last decades, the laparoscopic approach has
been introduced in the diagnosis and treatment of
ovarian tumours suspected of malignancy. The first
authors to report on the use of laparoscopy in ovarian
cancer were Bagley et al. in 1973.4
The International Federation of Gynecology and
Obstetrics (FIGO) indicates three mayor independent factors for prognosis of ovarian cancer: stage at
diagnosis, histological grade and residual tumour
after surgery.5
Laparoscopy has become the standard procedure
for benign ovarian surgery, and several studies have
demonstrated that laparoscopic treatment of patients
Authors: J. Hauspy, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, GZA Hospitals, Wilrijk, Belgium;
J. Van Wiemeersch, Department of Obstetrics and Gynaecology, GZA Hospitals, Wilrijk, Belgium; A. Rutten, Department of Medical
Oncology, GZA Hospitals, Wilrijk, Belgium; L. Verkinderen, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology,
GZA Hospitals, Wilrijk, Belgium; P.A. Van Dam, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, GZA
Hospitals, Wilrijk, Belgium.
Please send all correspondence to: J. Hauspy, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, GZA
hospitals campus Sint Augustinus, Oosterveldlaan 24, 2610 Wilrijk, Belgium.
Conflict of interest: the authors have nothing to disclose and indicate no conflicts of interest.
Keywords: ovarian cancer, laparoscopy, minimally invasive surgery.
Belgian Journal of Medical Oncology
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ovarian mass
ultrasound
benign aspect
laparoscopic
evaluation
benign aspect
laparoscopic
adnexectomy or
ovarian cystectomy
suspicious for malignancy
laparoscopy
(frozen section)
suspicious for
malignancy
apparent early stage
ovarian cancer
advanced
ovarian cancer
laparoscopic staging
operation*
debulking surgery vs
neoadjuvant
chemotherapy**
Figure 1. Decision diagram for laparoscopy in ovarian cancer:
* includes hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, omentectomy
and multiple peritoneal biopsies
** laparoscopy to evaluate the feasibility of primary debulking surgery versus neoadjuvant chemotherapy with interval
debulking.
with other gynaecological malignancies is equivalent to traditional surgery, with clear benefits such
as better visualisation, lower morbidity, less pain, a
shorter hospital stay, a lower risk of postoperative
infection and better cosmetic results.6-8
In general, laparoscopy appears to induce less morbidity, shortens hospital stay due to a faster recovery
and produces a better cosmetic result compared to
laparotomy. Immediate costs related to the surgery
appear to be higher for laparoscopic interventions
when compared to open surgery, due to disposable
instrument costs in the operating room. However,
taking other factors into account, such as hospital
stay, postoperative medication and investigations,
rehabilitation and lost productivity, laparoscopy
proves to be very cost-efficient.
Pre-operative assessment of the
ovarian mass
The most widely used ultrasound methods to
classify an ovarian mass are the risk of malignancy
index (RMI) and the risk of ovarian malignancy
algorithm (ROMA).9,10
The RMI is based on three criteria: serum CA125
level (U/ml), the ultrasound scan result (expressed
as a score of 0, 1 or 3) and the menopausal status
(1 if premenopausal and 3 if postmenopausal). The
RMI is simply calculated using the product of these
parameters (Figure 1). Using a RMI cut-off level of
200, the sensitivity in the original study of Jacobs
was 85% and the specificity was 97%. Patients with
a RMI score over 200 had, on average, 42 times the
background risk of cancer and those with a lower
value 0.15 times the background risk.9
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Practice Guidelines
In 2009, Moore et al presented a new algorithm, the
ROMA, which is based on both CA125 and human
epididymis secretory protein 4 (HE4).11 By this
method, patients are classified into high and low
risk groups. In the original article, 93.8% of ovarian
cancers were correctly classified as high-risk. One
year later, they presented a study comparing ROMA
to RMI. Their conclusion was that the ROMA method
achieves a significantly higher sensitivity for identifying women with ovarian cancer than RMI.12
A very recent study performed by Van Gorp and his
colleagues compared the ROMA system to the RMI
method and with subjective assessment by ultrasound.10 They concluded that, although new tumour
marker models are promising, they do not contribute
significantly to the diagnosis of ovarian cancer.
Ultrasound, especially subjective assessment by
ultrasound, remains superior in discriminating
malignant from benign ovarian masses.
Early-stage ovarian cancer
Early-stage ovarian cancer accounts for 25-30% of
all ovarian cancer cases, and has a good prognosis
with five-year survival rates that vary between 75%
and 85%.1,2 Diagnosis of ovarian cancer at an early
stage is difficult. In most cases, early-stage disease
is incidentally found by laparoscopic salpingooophorectomy for a presumed benign ovarian cyst.8
Accurate staging is crucial for optimal and correct
adjuvant treatment of ovarian cancer. Disease upstaging does not only have implications in providing
correct prognostic information, it also affects indications for adjuvant therapy and may ultimately result
Table 1. Jacobs Risk of Malignancy Index.9
RMI = CA 125 (U/ml) x menopausal state x ultrasound
score
menopausal status:
- premenopausal = 1
- postmenopausal = 3
ultrasound score criteria:
- multilocular
- solid parts
- ascites
- bilateral
- intra-abdominal metastases
no criteria = score 0
one criterium = score 1
two or more criteria = score 3
in an improved DFS and OS. A European Organization for Research and Treatment of Cancer (EORTC)
study in 2003 showed that patients with occult
residual disease benefit from adjuvant chemotherapy,
increasing the DFS and OS.2 If staging is suboptimal,
this could lead to residual tumour and undertreatment with a worse outcome.
Proper staging of an incidentally found -presumed
early stage- ovarian cancer should be performed in all
patients. Further staging should include peritoneal
washings, hysterectomy and contralateral oophorectomy as well as omentectomy, pelvic and para-aortic
lymph node dissection and multiple peritoneal biopsies as well as thorough inspection of the entire
abdominal cavity. In most patients this procedure
can be performed laparoscopically.13,14 In 2006,
Lécuru and his colleagues performed a retrospective review of patients with stage I ovarian cancer.1
They compared staging and survival in patients
with laparoscopy versus laparotomy as the first surgical access. The study did not find any harmful
influence of laparoscopy as first initial access on the
outcome in this group of patients. Careful inspection of the entire abdomen, including large and
small intestines should be performed. For a thorough
inspection of the liver surface and diaphragm, the
use of a 30-degree laparoscope is often required.
A recent study compared surgical outcomes, complications and costs between laparotomy and laparoscopy in early-stage ovarian cancer.8 The laparoscopy
group had less perioperative complications, less intraoperative blood loss, less transfusion requirement,
shorter hospital stay, less postoperative pain and a
shorter time to adjuvant chemotherapy compared to
the laparotomy group. Operative time was comparable, but costs for laparoscopy were significantly
higher than those for laparotomic staging surgery.
One of the concerns in laparoscopic treatment of
early-stage ovarian cancer is the risk of intraoperative rupture of the adnexal mass with tumour spilling. Therefore careful extraction of any ovarian
mass using a laparoscopic bag is always indicated.
Advanced Stage Ovarian Cancer
The majority of women diagnosed with ovarian
cancer present with advanced intra-abdominal
disease, and subsequently a low cure rate. Since
Griffiths published his article in 1975, we know
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that the amount of residual tumour after primary
cytoreductive surgery is one of the most important
factors for DFS and OS of these patients.15 Optimal
debulking is now considered to leave no residual
laesions larger than 1cm in diameter after primary
surgery, but even better outcomes have been reported
if no visible disease is present at the end of surgical
cytoreduction.16 Success rates of achieving optimal
cytoreductive surgery vary between reporting institutions, but generally do not exceed 50%, even in
the hands of experienced oncological surgeons.17
Primary cytoreductive surgery by laparotomy is
considered the standard of care for advanced ovarian
carcinoma.3 Diagnostic laparoscopy in advanced
disease has a lot of theoretical advantages: magnification of the pelvic and abdominal anatomy,
enhanced visualisation of metastases of the upper
abdomen, surface of the liver and diaphragm.17
Besides, imaging techniques such as CT-scan,
ultrasound, MRI and PET-scan have failed to accurately assess the potential for optimal cytoreduction
in advanced ovarian cancer.18,19 Of all these techniques, PET/CT has proven to be the most accurate.18 Knowing that the amount of residual tumour
has a strong prognostic impact, patients with initial
unresectable disease have been successfully treated
with neoadjuvant chemotherapy followed by interval
debulking.3,20 This leads to fewer peri- and postoperative complications and better optimal debulking rates. Diagnostic laparoscopy is a useful tool in
the evaluation of patients suspected for unresectable disease.17,21 By avoiding a laparotomy, recovery
is faster and chemotherapy can be started quicker.
Vergote et al reported the results of an EORTC study
comparing primary debulking and neoadjuvant
chemotherapy.3 Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior
to primary debulking surgery followed by chemotherapy as a treatment option for patients with
bulky stage IIIC or IV ovarian carcinoma.
Abdominal wall metastases
When using laparoscopy in oncological surgery, one
must ascertain safety issues of iatrogenic disease
spread. Spread of cancer cells is facilitated by the
use of CO2, creating a pressure gradient with a
chimney effect , floating tumour cells through the
port wounds.6 Likewise, removal of tumour-loaded
specimens can provoke implantation of cells at the
wounds. The chimney effect and tumour removal
can cause port sites to be contaminated with tumour cells. Heitz et al reported a retrospective study
of 537 patients with a first diagnosis of ovarian
cancer.22 They investigated the incidence, risk
factors and complications of abdominal wall metastases after laparoscopy conducted before cytoreductive surgery. The incidence of abdominal wall
metastasis was considerably high: 47% of investigated patients had histological proven port metastasis. However, there was no impact on survival.
This incidence was much higher than the earlier reported incidence of 0 to 21%, probably due to
selection of patients with more advanced disease
and to the rather long period between laparoscopy
and cytoreductive therapy.23,24 Also, the diagnosis
was based on histopathology of all trocar sites, and
not only on clinical metastasis. In this way, subclinical metastases were also diagnosed.
Van Dam et al investigated the difference in closing
of the laparoscopy ports.25 A recurrence developed
at the trocar site in 58% of patients undergoing a
laparoscopy in which only the skin was closed at
the end of the procedure and in only 2% of patients
undergoing a laparoscopy with closure of all layers.
Second-look laparoscopy
Although the indications remain controversial,
second-look laparotomies have been performed
since decades to evaluate the effect of chemotherapy
in advanced ovarian cancers. Despite initial good
response to chemotherapy, the majority of patients
with advanced ovarian cancer will eventually die of
their disease. Approximately 50% of patients with
negative second-look laparotomy will eventually
develop recurrent disease, so it must be assumed
that all these patients have microscopic disease.
Nevertheless, the subgroup of patients with a negative second-look operation has a better prognosis
with continued chemotherapy.26
The accuracy and safety of second-look laparoscopy
was investigated in several studies, and seemed
similar to laparotomy.26-28 Sometimes the procedure
can be difficult because of severe postoperative adhesions, which makes visualisation of the whole
peritoneal cavity impossible and gives a higher risk
of perioperative complications.
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Practice Guidelines
Littell et al studied the negative predictive value of
second-look laparoscopy compared to laparotomy
for assessment of pathological complete response in
patients who achieved a clinical complete remission.28
Their conclusion was that a negative second-look
laparoscopy with negative peritoneal pathology and
cytology is 91.5% predictive of negative laparotomy
and is associated with a low complication rate even
in the setting of prior extensive surgery. In their
study, laparotomy thus had a slightly higher sensitivity and negative predictive value, but this does
not warrant the increased morbidity.
Borderline ovarian cancer
Borderline tumours of the ovary account for 15% of
all epithelial ovarian tumours. Because of their slow
growth and limited potential to metastasise, they
are generally detected at an early stage and have
a good prognosis with an overall recurrence rate
of 10-20%. However, recurrence rates of FIGO
stages II and III borderline ovarian tumours can be
as high as 30% with a median time to recurrence
of 5-7 years.29
Maneo and his colleagues analysed 62 patients
with a borderline ovarian tumour, 30 were operated
on laparoscopically, 32 by laparotomy.30 They concluded that the diameter of the cyst is a significant
factor to predict failure of laparoscopy, with a bigger
risk of rupture or persistence of the tumour in
masses larger than 5cm. The use of lymph node dissections in borderline ovarian tumours is limited.
It is however important to perform a thorough
inspection of the entire abdomen as well as an
omentectomy and multiple peritoneal biopsies.
A small number of patients with serous borderline
ovarian tumours, present with tumoural implants
which can be found throughout the abdomen
and in the omentum. Rarely, these implants consist
of invasive tumour cells, in which case adjuvant
systemic treatment is recommended. However,
given the rarity of these occurrences, no randomised
controlled trials are available to support this treatment approach.
Robotic surgery
The experience with robotic surgery in ovarian cancer is very limited, and the use of robotics in ovari-
an tumours should be considered as experimental.
Recently, Magrina et al published a series of 25 patients who underwent robot-assisted surgical treatment.31 The results were compared to laparoscopic
and laparotomic approach. They concluded that
laparoscopy and robotic surgery are preferable to
laparotomy for early-stage ovarian cancer. They
could not prove any significant benefit of robotics
compared to laparoscopy. One can assume that the
advantages found by laparoscopy will be similar
when using robot-assisted surgery. The first reports
comparing all three techniques are being presented
currently, although prospective trials are lacking.
Conclusion
Although tumour marker models are promising,
until now they do not contribute significantly to the
preoperative assessment of ovarian cancer. Ultrasound evaluation remains the most reliable investigation, together with PET/CT scan.
The use of laparoscopy as first surgical access in
ovarian cancer increases the diagnostic power,
allowing a more accurate staging. For selected patients
with early-stage ovarian cancer, laparoscopic staging
surgery is therefore a good alternative to laparotomy.
It results in less postoperative pain, shorter hospital
stay, faster recovery and better cosmetic results.
Laparoscopic treatment should be performed by
experienced laparoscopic surgeons, to minimalise
intraoperative spilling and avoid understaging. In
case of intraoperative rupture of the tumour, a careful
pelvic washing should be performed. Manipulation
of the tumour should be kept to a minimum, and
any biopsy specimen should be extracted with a laparoscopic bag to avoid abdominal wall metastases.
In advanced disease, laparoscopy can safely be used
to evaluate the feasibility of complete debulking and
accurately assess patients with no or very difficult
primary resectable disease who might benefit from
neoadjuvant chemotherapy.
The risk of abdominal wall metastases appears to be
higher after laparoscopy in advanced ovarian cancer
and in the presence of ascites, but the risk can be
reduced by closure of all layers. Abdominal wall
metastases appear to have no influence on longterm outcome.
If there is indication for second-look to evaluate
complete remission, laparoscopy is preferred to
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Key messages for clinical practice
•
Laparoscopic surgical staging for ovarian cancer is safe.
•
It is at least as adequate as surgical staging by laparotomy.
•
Also, early-stage ovarian cancer can safely be treated by laparoscopy alone in
most cases.
•
Currently, debulking surgery by laparoscopy for advanced ovarian cancer is not
recommended.
laparotomy because of the lower morbidity. The use
of robotic surgery in ovarian cancer is promising, but
should be used with caution in the absence of data
showing non-inferiority to laparoscopy.
9. Jacobs I, Oram D, Fairbanks J, et al. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. British journal of obstetrics and
gynaecology 1990;97:922-9.
10.Van Gorp T, Veldman J, Van Calster B, et al. Subjective assessment by
ultrasound is superior to the risk of malignancy index (RMI) or the risk of
References
ovarian malignancy algorithm (ROMA) in discriminating benign from malignant
1. Lécuru F, Desfeux P, Camatte S, et al. Impact of initial surgical access on
adnexal masses. European journal of cancer 2012.
staging and survival in patients with stage I ovarian cancer. International
11.Moore RG, McMeekin DS, Brown AK, et al. A novel multiple marker
journal of gynecological cancer : official journal of the International Gyneco-
bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in
logical Cancer Society 2006;16:87-94.
patients with a pelvic mass. Gynecologic oncology 2009;112:40-6.
2. Trimbos JB, Vergote I, Bolis G, et al. Impact of adjuvant chemotherapy
12.Moore RG, Jabre-Raughley M, Brown AK, et al. Comparison of a novel
and surgical staging in early-stage ovarian carcinoma: European Organisation
multiple marker assay vs the Risk of Malignancy Index for the prediction of
for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian
epithelial ovarian cancer in patients with a pelvic mass. American journal of
Neoplasm trial. Journal of the National Cancer Institute 2003;95:113-25.
obstetrics and gynecology 2010;203:228 e1-6.
3. Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or
13.Mangioni C, Bolis G, Molteni P, et al. Indications, advantages, and limits
primary surgery in stage IIIC or IV ovarian cancer. The New England journal
of laparoscopy in ovarian cancer. Gynecologic oncology 1979;7:47-55.
of medicine 2010;363:943-53.
14.Lehner R, Wenzl R, Heinzl H, et al. Influence of delayed staging laparot-
4. Bagley CM, Young RC, Schein PS, et al. Ovarian carcinoma metastatic
omy after laparoscopic removal of ovarian masses later found malignant.
to the diaphragm--frequently undiagnosed at laparotomy. A preliminary
Obstetrics and gynecology 1998;92:967-71.
report. American journal of obstetrics and gynecology 1973;116:397-400.
15.Griffiths CT. Surgical resection of tumour bulk in the primary treatment
5. Benedet JL, Bender H, Jones H III, et al S. FIGO staging classifications
of ovarian carcinoma. National Cancer Institute monograph 1975;42:101-4.
and clinical practice guidelines in the management of gynecologic cancers.
16.Aletti G, Dowdy S, Gostout B, et al. Aggressive surgical effort and
FIGO Committee on Gynecologic Oncology. International journal of gynae-
improved survival in advanced-stage ovarian cancer. Obstetrics and gyne-
cology and obstetrics: the official organ of the International Federation of
cology 2006;107:77-85.
Gynaecology and Obstetrics 2000;70:209-62.
17.Angioli R, Palaia I, Zullo MA, et al. Diagnostic open laparoscopy in the
6. Tozzi R, Kohler C, Ferrara A, et al. Laparoscopic treatment of early
management of advanced ovarian cancer. Gynecologic oncology
ovarian cancer: surgical and survival outcomes. Gynecologic oncology
2006;100:455-61.
2004;93:199-203.
18.Nam EJ, Yun MJ, Oh YT, et al. Diagnosis and staging of primary ovarian
7. Mourits J, Bijen C, Arts H, et al. Safety of laparoscopy versus laparotomy
cancer: correlation between PET/CT, Doppler US, and CT or MRI. Gyneco-
in early-stage endometrial cancer: a randomised trial. Lancet Oncol
logic oncology 2010;116:389-94.
2010;11:763-71.
19. Togashi K. Ovarian cancer: the clinical role of US, CT, and MRI. European
8. Lee M, Kim SW, Paek J, et al. Comparisons of surgical outcomes, com-
radiology 2003;13 Suppl 4:L87-104.
plications, and costs between laparotomy and laparoscopy in early-stage
20.Fanfani F, Ferrandina G, Corrado G, et al. Impact of interval debulking
ovarian cancer. International journal of gynecological cancer : official journal
surgery on clinical outcome in primary unresectable FIGO stage IIIc ovarian
of the International Gynecological Cancer Society 2011;21:251-6.
cancer patients. Oncology 2003;65:316-22.
Belgian Journal of Medical Oncology
volume 6, issue 5, 2012
162
5
Practice Guidelines
21.Fagotti A, Fanfani F, Ludovisi M, et al. Role of laparoscopy to assess
reduced? American journal of obstetrics and gynecology 1999;181:536-41.
the chance of optimal cytoreductive surgery in advanced ovarian cancer:
26.Husain A, Chi DS, Prasad M, et al. The role of laparoscopy in second-
a pilot study. Gynecologic oncology 2005;96:729-35.
look evaluations for ovarian cancer. Gynecologic oncology 2001;80:44-7.
22.Heitz F, Ognjenovic D, Harter P, et al. Abdominal wall metastases in
27. Clough K, Ladonne J, Nos C, Renolleau C, Validire P, Durand J. Second
patients with ovarian cancer after laparoscopic surgery: incidence, risk factors,
look for ovarian cancer: laparoscopy or laparotomy? A prospective compar-
and complications. International journal of gynecological cancer: official
ative study. Gynecologic oncology 1999;72:411-7.
journal of the International Gynecological Cancer Society 2010;20:41-6.
28.Littell RD, Hallonquist H, Matulonis U, et al Negative laparoscopy is
23.Kruitwagen RF, Swinkels BM, Keyser KG, et al. Incidence and effect on
highly predictive of negative second-look laparotomy following chemother-
survival of abdominal wall metastases at trocar or puncture sites following
apy for ovarian, tubal, and primary peritoneal carcinoma. Gynecologic
laparoscopy or paracentesis in women with ovarian cancer. Gynecologic
oncology 2006;103:570-4.
oncology 1996;60:233-7.
29.Gershenson DMW, Gore M, Thomas G. Gynecologic Cancer.: Elsevier
24.Vergote I, Marquette S, Amant F, et al. Port-site metastases after open
Ltd; 2004.
laparoscopy: a study in 173 patients with advanced ovarian carcinoma.
30.Maneo A, Vignali M, Chiari S, et al. Are borderline tumours of the ovary
International journal of gynecological cancer: official journal of the Interna-
safely treated by laparoscopy? Gynecologic oncology 2004;94:387-92.
tional Gynecological Cancer Society 2005;15:776-9.
31.Magrina JF, Zanagnolo V, Noble BN, et al. Robotic approach for ovarian
25.Van Dam PA, DeCloedt J, Tjalma WA, et al. Trocar implantation metasta-
cancer: perioperative and survival results and comparison with laparoscopy
sis after laparoscopy in patients with advanced ovarian cancer: can the risk be
and laparotomy. Gynecologic oncology 2011;121:100-5.
Belgian Journal of Medical Oncology
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volume 6, issue 5, 2012