METHODS
A total of 93 patients with a primary ovarian cancer diagnosis (Group 1 n=41) or suspicion of recurrent
ovarian cancer (Group 2 n=52) were included in this study from January 2007 to January 2013.
RESULTS
The ages of the patients were between 15 and 82 years. In cases with PET positive lesions (n=84); Ovarian
lesion (n=34), infradiaphragmatic lymph node metastasis (n=46), supradiaphragmatic lymph node
metastasis (n=14), peritoneal implant (n=67), and distant metastasis (n=14) were detected. Histopathological
examination of 4 PET positive ovarian lesions was not compatible with cancer. In 14 cases with
low CA-125 value, 18F FDG PET/CT was able to detect primary/recurrent lesions accurately. In the
evaluation of primary/recurrent ovarian cancer, 18F FDG PET/CT had 93% sensitivity, 42.8% specificity,
89.2% accuracy, whereas CA-125 had 79.1% sensitivity, 42.8% specificity, and 76.3% accuracy.
CONCLUSION
In conclusion; even in low CA-125 values, 18F FDG PET/CT is a prominent method that can detect
especially extra-abdominal distant metastatic foci in the initial staging of primary ovarian cancer and
diagnosis and follow-up of recurrent ovarian cancer.
Keywords: 18F labeled fluoro-2-deoxy-D-glucose; cancer antigen-125; ovarian cancer; positron emission tomography/ computed tomography; SUV<sub>max</sub>
The most important prognostic factor is the disease stage at the time of diagnosis. Although the grade and histology of the tumor are not important in general, small cell and clear cell subtypes affect the prognosis negatively.
Due to their rapid growth and early asymptomatic
nature; at the time of diagnosis, 15% of the cases were
at the local stages, 18% were at the regional stages, and
61% were at the advanced stages.[
When all stages are evaluated, the 5-year survival
rate is 44.2%; 93% for Stage I, 70% for Stage II, 37% for
Stage III, and 25% for Stage IV.[
Although 80% of patients respond to surgery and
adjuvant chemotherapy, recurrence is detected in 80%
of patients at an advanced stage. Small residual tumor
volume (1-2 cm3) after primary cytoreductive surgery
is an important prognostic parameter in ovarian cancer
surgery.[
18F labeled fluoro-2-deoxy-D-glucose positron
emission computed tomography (CT)/CT (18F-FDGPositron
Emission Tomography [PET]/CT), is a functional
imaging method that provides information
about both anatomy and metabolism and is used to
determine restaging and treatment response in ovarian
cancer. Our study aims are to investigate the importance
of 18F-FDG PET/CT in the initial staging and in
detecting the recurrence of ovarian cancer and compare
it with Cancer antigen-125 (CA-125) levels.
Patients who had 18F-FDG PET/CT scan at short intervals for control purpose and had no clinical, laboratory, and radiological suspicion of the disease or received chemotherapy 3 weeks before the PET scan and radiotherapy within 3 months before PET scan have not been included in this study.
The patients" age, primary ovarian cancer subtype, grade, stage, CA-125 value in the last month, and maximum standard uptake values (SUVmax) of lesions accepted as PET-positive, were noted.
18F-FDG PET/CT Imaging
PET/CT imaging of all cases was performed with a
high-resolution PET scanner integrated with 6-slice CT
(Siemens Biograph LSO HI-REZ PET/CT Illinois, USA).
444-629 MBq (12-17 mCi) F-18 FDG was injected intravenously,
with a minimum of 4 h of fasting and blood glucose
level below 160 mg/dl. After FDG injection, the patients
were rested in a quiet room for 1-1.5 h to complete
the biodistribution of the radiopharmaceutical. After the
bladder emptied, the patients were placed in the supine
position on the PET/CT scanner. After the topogram,
non-contrast low-dose CT and PET images (3 min/bed)
from the vertex to the mid of the thigh were obtained.
PET images were reconstructed with iterative configuration
and CT images were used for attenuation correction.
Interpretation of 18F-FDG PET/CT Data
PET, CT, and PET/CT fusion images were analyzed
simultaneously. In visual evaluation, the main criterion
for accepting it as a lesion was the detection of increased
focal FDG uptake compared to background activity.
Lesion equivalent of each focal FDG uptake was
investigated on corresponding CT images. Focal FDG
involvements corresponding to salivary gland, muscle,
adipose tissue, and reactive lymph node on CT scans
were considered as physiological involvements. Any
focal FDG uptake detected in ascites, abnormal soft tissue
mass, or pathological lymph node was considered
as a lesion. Mild FDG involvement with signs of infection/
inflammation on CT images was not considered
as recurrence/metastasis. Semi-quantitative SUVmax
was calculated from the Region of Interest drawn over
the focus considered as a lesion in both PET and CT.
Statistical Analysis
Number Cruncher Statistical System 2007 and Power
Analysis and Sample Size 2008 Statistical Software
(Utah, USA) program was used for statistical analysis.
Student's t-test and Mann Whitney U test were used
according to the distribution pattern of the data. While
Fisher's exact test and Yates Continuity Correction
test were used to compare qualitative data, ROC curve
analysis was used to determine the cutoff value. Statistical
significance was accepted as p<0.05.
The verification of the lesions considered as suspicious in PET/CT was performed histopathologically in 28 patients in Group 1 and 17 patients in Group 2 (48.4% of all cases). In the remaining, verification was performed with clinical follow-up, CA-125 levels, conventional imaging methods, and control PET/CT images.
According to the clinical follow-up, CA-125 values,
control imaging, and histopathologic examination;
primary/recurrent ovarian cancer was detected in 86
patients (92.5%), benign lesions were detected in 4 patients
(4.3%). Three patients (3.2%) had no malignant
lesions (Table
When four false-positive cases in Group 1 were
evaluated histopathologically, tuberculosis in two patients,
amyloidosis in one patient, and serous cystadenoma
in one patient were found (Fig.
*Maximum intensitiy projection (MIP). Positron emission tomography/Computed tomography (PET/CT); CA: Cancer antigen.
According to PET images, total of six false-negative cases were detected. PET could not detect lesions in 2% metasof postmenopausal patients and 4% of premenopausal patients as false-negative. Two of these six patients had a history of neoadjuvant chemotherapy. In four of them, it has been noted that the lesions did not cause a mass effect in the ovary and there was quite a low FDG uptake in normal-sized ovaries.
The accuracy rate reached 92% in Group 1. When all cases were evaluated, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy rates of FDG-PET/CT were 93%, 42.8%, 95.2%, 33.3%, and 89.2%, respectively.
Lesion localizations on FDG-PET/CT images of 84 patients were as follows: primary ovarian cancer in 37 patients, infradiaphragmatic lymph node metastasis in 46 patients, supradiaphragmatic lymph node metastasis in 14 patients, peritoneal implant in 67 patients, and distant organ metastasis in 14 patients. Implants were located mostly in ovarian neighborhoods, large intestine serosa, and liver-spleen capsular surfaces. PET was able to detect the lesion in 82.5% of patients with primary malignancy. The presence of nodal disease in primary and recurrent lesions was 65% and 70%, respectively. Serous and endometrioid histology were found to be independent predictors of nodal metastases, but other advanced ovarian cancer patients who did not belong to these pathologies also had nodal metastases.
In Group 1, the mean ovarian lesion SUVmax is 15.4
(serous papillary CA SUVmax: 15.5, endometrioid CA
SUVmax: 12, clear cell CA SUVmax: 4.5, mucinous ovary
CA SUVmax: 5.8, Germ cell CA SUVmax: 2.4). The mean
SUVmax was 13.8 for peritoneal implants, 13.9 for lymph
node metastases, and 2.3 for peritoneal acid. As the
SUVmax value of the primary lesion increased, the SUVmax
value of the implant also increased (r=0.64, Fig.
CA-125 value was below normal in 21 cases (<35 U/ ml) and above normal in 72 cases (mean: 1460 U/ml, max: 18000 U/ml). Of the 21 patients with low CA-125 levels, 18 of them had proven malignancy. Four of 72 cases with elevated CA-125 value were negative for malignancy with radiologic imaging and clinical followup. The sensitivity, specificity, PPV, NPV, and accuracy rates of CA-125 were 79.1%, 42.8%, 94.4%, 14.3%, and 76.3%, respectively. PET/CT could not detect lesions in 6% of patients with elevated CA-125.
Although ovarian cancer predominantly metastases
to the peritoneal cavity and pelvic lymph nodes, recent
evidence suggests the possibility of hematogenous metastasis
of ovarian cancer. Implants are mostly localized
in the pelvis, right hemidiaphragm, liver capsular surface,
right paracolic area, intestines, and omentum.[
FDG-PET/CT is superior to other imaging methods
in detecting distant organ or lymph node metastasis in
primary ovarian cancer. It has shown that patients with supradiaphragmatic lymph node metastases develop
more frequent ascites. That confirms the information
that tumor cells cross the diaphragm mainly by cardiophrenic
lymph nodes and parasternal lymphatics.[8] In
our series, the supradiaphragmatic lymph node metastasis
rate was found to be 11.5% in the group whose
recurrence was investigated.
Due to the high incidence of recurrence in ovarian
cancers, clinical follow-up is very important; there-fore, CA-125 is a very useful parameter. Von Georgi
et al.,[
PET/CT can detect early recurrences even with low
CA-125 value (<35 U/ml). Palomar et al.,[
CT is the first imaging method used in the follow-up
of patients and evaluation of relapse. In the literature, the
sensitivity of CT in detecting relapses has been reported
as 40-93%.[
Diagnosis of peritoneal implants by radiological
methods has been a problem due to their small size and
location. In the study of De Rosa et al.,[
In the study by Chung et al.,[
It has been shown that FDG PET/CT can give
false-negative results in the early period of the disease
and in the detection of recurrences in mucinous subtypes
of ovarian cancer.[
Our study is valuable in terms of including a large
number of patients and only cases with suspected disease.
PET: Positron emission tomography.
PET: Positron emission tomography; CT: Computed tomography; CA: Cancer antigen.
*PET Maximum Intensitiy Projection; PET: Positron emission tomography.
Although peritoneal implants and metastatic paraaortic lymph nodes were detected in most cases in our study, mediastinal, supraclavicular, and cervical metastatic lymph nodes and distant organ metastases were also detected in some cases and very important information was given to the clinicians about the current status of the disease.
FDG-PET/CT, which can detect extra-abdominal distant metastatic lesions, in particular, was found to be more sensitive and important in the follow-up and treatment of the disease than CA-125.
Acknowledgments: All authors have read and agreed with the content of the manuscript. Each author has participated sufficiently in the work to take public responsibility for appropriate portions of the content.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: The study was approved by The İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine Ethics Committee (No: 83045809/604/02-8850, Date: 04/04/2014).
Financial Support: This study has received no financial support.
Authorship contributions: Concept - R.A., E.A., ; Design - E.A.; Supervision - S.S., K.S.; Funding - R.A., E.A.; Materials - R.A., O.E.Ş.; Data collection and/or processing - E.A., B.A., Z.R.K.D.; Data analysis and/or interpretation - E.A.; Literature search - E.A., R.A.; Writing - E.A., R.A.; Critical review - K.S., A.S.A., S.S.
