Review
FOCUS ON: Nuclear Medicine and Molecular Imaging
July 24, 2013

The Role of PET/CT in the Management of Cervical Cancer

Abstract

OBJECTIVE. Cervical cancer is the second most common malignancy in women worldwide and the third most common cause of cancer mortality in the United States. The aim of this article is to describe cervical cancer and outline the value of 18F-FDG PET/CT in the management of cervical malignancy.
CONCLUSION. The value of PET/CT has been found in staging and treatment strategy for cervical cancer. FDG PET/CT facilitates decision-making and radiation treatment planning and provides important information about treatment response, disease recurrence, and long-term survival.
Cervical cancer is the second most common malignancy in women worldwide [1] and the third most common cause of cancer mortality in the United States [2]. The incidence of cervical cancer varies widely among countries, world age-standardized rates ranging between less than 1 case and more than 50 cases per 100,000 [3]. Although the widespread introduction of the Papanicolaou test for cervical cancer screening and human papillomavirus vaccination have been credited with dramatically reducing the incidence and mortality of cervical cancer in developed countries, cervical carcinoma remains a major threat to women's health globally [4], resulting in approximately 150,000 deaths per annum worldwide [5, 6]. In approximately one third of cervical cancer patients, disease recurs, usually within the first 2 years after completion of primary treatment [7]. Before treatment, accurate staging and assessment of prognostic factors are essential for directing the multidisciplinary approach to therapy.
Initial staging of cervical cancer has been achieved with integrated data from physical examination, CT, and MRI [3, 8]. These modalities have the high resolution needed for excellent anatomic depiction. PET/CT also has become an established imaging method for the evaluation of cervical cancer [7]. The functional information about regional glucose metabolism obtained with 18F-FDG PET provides for superior sensitivity and specificity in most cancer imaging applications in comparison with CT and other anatomic imaging methods [7].
The objectives of this review are to provide an overview of cervical cancer and to outline the value of multimodality imaging with a focus on FDG PET/CT in the management of cervical malignancy. Successful treatment that leads to a better outcome of cervical cancer necessitates accurate diagnostic evaluation.

Cervical Cancer Overview

Classification

Squamous cell carcinoma accounts for most cases of cervical cancer, representing 80–85% of all cases; 15–20% of cases are adenocarcinoma and adenosquamous carcinoma [9]. The incidences of adenocarcinoma and adenosquamous carcinoma have been increasing in many areas [10], and these tumors carry a worse prognosis than squamous cell carcinoma [11].

Presentation and Risk Factors

One half of all cervical cancer diagnoses are made in the care of women 35–55 years old [12]. The major risk factor for the development of cervical malignancy is infection with human papillomavirus (serotypes 16 and 18). Other factors associated with development of cervical cancer include early onset of sexual activity (< 16 years), a high number of sexual partners (> 4), history of genital warts, and cigarette smoking. Women receiving immunosuppressive agents and those who are HIV positive are also at increased risk [12].
Cervical cancer is often asymptomatic in the early stages [13, 14]. Postcoital bleeding in a young patient is a specific symptom of possible cervical cancer, and intermenstrual bleeding and postmenopausal bleeding are common and nonspecific symptoms that may indicate the presence of malignancy [15]. In North America, owing to the use of active public health screening programs, approximately 60% of cases of cervical cancer are recognized at stage I, and 25%, 10%, and 5% are detected in stages II, III, and IV, respectively [16]. Cervical cancer usually spreads directly to contiguous structures, including the vagina, parametrium, urinary bladder, ureters, rectum, and paracervical tissue. Patients with more advanced disease may have hematogenous dissemination by direct blood vessel invasion [17].

Staging Systems

The most widely used staging systems include the International Federation of Gynecology and Obstetrics (FIGO) and the American Joint Committee on Cancer TNM classification systems [8, 18] (Table 1). However, substantial inaccuracies occur in these staging systems because they do not include important prognostic factors such as tumor size and volume, histologic grade, lymphovascular involvement, and local or retroperitoneal lymph node status (especially paraaortic nodal metastasis) [18]. These limitations of the FIGO clinical staging system for cervical cancer emphasize the need for more accurate noninvasive methods of assessing disease extent for a more reliable determination of optimal treatment strategies [8, 18].
TABLE 1: TNM and International Federation of Gynecology and Obstetrics (FIGO) Classifications of Cervical Cancer
FIGOCharacteristicTNM
 Primary tumor cannot be assessedTX
 No evidence of primary tumorT0
0Carcinoma in situ (preinvasive carcinoma)Tis
ICervical carcinoma confined to uterus (extension to corpus should be disregarded)T1
IAInvasive carcinoma diagnosed only with microscopy. All macroscopically visible lesions—even with superficial invasion— are stage IB or category T1bT1a
IA1Stromal invasion no greater than 3.0 mm in depth and 7.0 mm or less in horizontal spreadT1a1
IA2Stromal invasion more than 3.0 mm and not more than 5.0 mm with horizontal spread 7.0 mm or lessaT1a2
IBClinically visible lesion confined to the cervix or microscopic lesion larger than IA2/T1a2T1b
IB1Clinically visible lesion 4.0 cm or less in greatest dimensionT1b1
IB2Clinically visible lesion more than 4 cm in greatest dimensionT1b2
IITumor invades beyond the uterus but not to pelvic wall or to lower third of the vaginaT2
IIAWithout parametrial invasionT2a
IIBWith parametrial invasionT2b
IIITumor extends to pelvic wall, involves lower third of vagina, causes hydronephrosis or nonfunctioning kidney, or any or a combination of these featuresT3
IIIATumor involves lower third of vagina, no extension to pelvic wallT3a
IIIBTumor extends to pelvic wall, causes hydronephrosis or nonfunctioning kidney, or bothT3b
IVATumor invades mucosa of bladder or rectum, extends beyond true pelvis, or bothbT4
IVBDistant metastasisM1
a
Depth of invasion should not be more than 5 mm obtained from the base of the epithelium, either surface or glandular, from which it originates. The depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial epithelial papilla to the deepest point of invasion. Vascular space involvement, venous or lymphatic, does not affect classification.
b
Presence of bullous edema is not sufficient to classify a tumor as T4.

Multimodality Imaging in the Staging of Cervical Cancer

The use of cross-sectional imaging (CT and MRI) has greatly improved the clinical staging of cervical cancer [19]. Several studies have shown 85–90% accuracy of MRI in the detection of malignant tumors larger than 1 cm [20]. MRI can be used for triage of patients to surgery versus chemoradiotherapy. The sensitivity of MRI for detecting parametrial involvement of cervical cancer varies between 75% and 100%. The specificity ranges from 46% to 86%, and the negative predictive value is high at 94–100%. The positive predictive value is notably lower, ranging from 28% to 77%. The overall accuracy of MRI in staging cervical cancer is approximately 90%. Although lymph node status is not included in the FIGO system, studies have shown it is an important prognostic factor and important for determining therapy. The reported accuracy of MRI is 86% in the detection of lymph node metastasis of cervical cancer [2125].
CT provides useful information about the size of the cervix, obstruction of the ureter, and distant metastasis, but it plays a minor role in detection of local tumor extent because of its limited soft-tissue resolution [26]. The sensitivity of CT in the assessment of parametrial invasion is 55% and the specificity approximately 74%, but the positive predictive value is low at 32%, and the negative predictive value is 67% [27]. CT has an accuracy of 65% for staging cervical cancer and an accuracy of 86% for detecting lymph node involvement in cervical cancer [21, 27].
Neither CT nor MRI depicts microinvasion in lymph nodes smaller than 1 cm in short axis dimension. These modalities also have limited utility for differentiation of metastatic lymph nodes from hyperplasia [28]. Thus on the basis of on size criteria alone, both modalities are limited in the preoperative evaluation of metastatic nodal spread.
Pelvic ultrasound imaging is a reasonable choice for delineating the uterine and cervical contours and for evaluating central disease. Transrectal ultrasound is helpful in determining the size, shape, thickness, and diameter of cervical tumors. In a study by Fischerova et al. [29], ultrasound had an accuracy of 94% in the detection of cervical cancer. Innocenti et al. [30] reported sensitivity, specificity, and accuracy in the ultrasound evaluation of parametrial involvement of 78%, 89%, and 87% respectively. Overall the accuracy of transrectal ultrasound in staging cervical cancer is approximately 83% [30]. Few studies have been conducted to assess the feasibility of transvaginal ultrasound in evaluating cervical lesions [17, 18]. The results of those studies showed that strain ratio (a value used to quantify the hardness of cervical tissue) was useful in differentiating cervical carcinoma from benign cervical lesions [31, 32]. Ultrasound can also provide information about tumor vascularity [26, 30].

Role of FDG PET/CT

PET performed with the structural glucose analogue 2-fluoro-2-deoxy-D-glucose labeled with the positron emitter fluorine-18 (18F-FDG) is a noninvasive molecular functional imaging modality. FDG PET/CT is a valuable imaging modality in the management of many human solid tumors [3341]. FDG PET/CT has become an essential modality for staging and restaging and for assessment of response to therapy in the care of patients with cervical cancer [8, 42]. Integrated PET/CT precisely combines metabolic PET images with anatomic CT images and has proved more accurate than high-resolution CT alone, particularly in showing the presence of regional lymph node involvement and extrapelvic disease extension [18] (Table 2).
TABLE 2: Value of PET/CT in Evaluation of Cervical Cancer
PurposeValue
StagingFDG PET/CT is effective in lymph node staging particularly of locally advanced cervical carcinoma (stage = IB2).
Therapy planningPET staging affects management by extending the radiation field and administered dose to the involved nodes.
Therapy response assessmentPET/CT has a high accuracy in the assessment of locally recurrent and distant metastatic disease.
 Posttherapy standardized uptake value (SUV) and qualitative assessment (positive versus negative) help in identifying recurrence and residual disease after therapy and help in assessment of disease status.
PrognosisThe maximum SUV of the primary cervical tumor is predictive of disease outcome.
 Metabolic tumor volume and total lesion glycolysis, which are volume-based metabolic parameters, and lymph node status on PET images are significant independent prognostic factors.
 Posttherapy FDG uptake, as detected with whole-body PET, is predictive of survival.
 Studies of 60Cu–diacetyl-bis(N4-methylthiosemicarbazone) (60Cu-ATSM), which has a high affinity for hypoxic tissue, show that the pretreatment oxygenation status of tumors can be predictive of overall survival, disease-free survival, local tumor control, or any or a combination of these features.

FDG PET/CT Protocols

Two general approaches have been adopted for PET/CT of cervical cancer [43]. In the first approach low-radiation (low-dose) CT is used for attenuation correction and coregistration. The other approach entails use of standard-radiation-dose diagnostic contrast-enhanced CT for attenuation correction, coregistration, and diagnosis.
At our institution, FDG PET/CT images are obtained in 3D with a 16-MDCT system (Discovery VCT RX, GE Healthcare) or in 2D with a 4-MDCT PET/CT scanner (Discovery LS, GE Healthcare). Patients must fast for a minimum of 6 hours, and serum glucose concentration should be less than 200 mg/dL before administration of an IV injection of a weight-based amount of FDG (0.22 mCi/kg [8.14 MBq/kg]). Oral contrast material is administered for the CT portion of the study. After a targeted 60-minute radiotracer uptake phase, combined PET/CT scan is obtained. An initial whole-body CT acquisition is performed without IV contrast administration under shallow-breathing conditions for attenuation correction of positron emission data and lesion size measurements. CT parameters are specific for the particular scanner, but CT attenuation correction for 16-MDCT typically includes a 50-cm axial dynamic FOV, weight-based amperage (automated 20–200 mA), 120–140 kVp, 3.75-mm reconstructed slice thickness, pitch of 0.984, 0.5-second gantry rotation speed, and 512 matrix. Whole-body PET data acquisition is begun from proximal thigh level to the skull base after the patient voids. At some institutions the urinary bladder may be catheterized to decrease intense physiologic pelvic bladder FDG activity.
Diagnostic standard-dose contrast-enhanced CT of the chest, abdomen, and pelvis is performed after PET. Iodinated contrast material is administered IV. Iohexol (Omnipaque, GE Healthcare) at a dose of 120 mL containing 350 mg/mL of iodine is administered by power injection at a rate of 2 mL/s injection through a 22-gauge catheter with a prescan delay of 50–60 seconds. Iodixanol (Visipaque, GE Healthcare) with 320 mg/mL of iodine is used for patients with a creatinine concentration greater than 1.1 mg/dL, chronic kidney disease, chronic lung disease, or diabetes and for elderly patients. The CT parameters include 120 kVp, 30–400 mA, noise index of 14, 2.5-mm reconstructed slice thickness, 44.4-cm dynamic FOV, 512 matrix size, 0.5-second rotation time, and breath-hold acquisition. For image fusion, 3.75-mm slices are reconstructed.
The ordered-subsets expectation maximization algorithm is used to reconstruct all PET images. The 2D implementation on the Discovery LS scanner has two iterations, 28 subsets, a 5.5-mm postreconstruction gaussian filter, and 3.9-mm pixels. The fully 3D implementation on the Discovery VCT RX system has two iterations, 21 subsets, a 3.0-mm postreconstruction gaussian filter, and 4.7-mm pixels. All PET data are reconstructed with and without CT based attenuation correction. The CT and PET images are transferred to a workstation (Advanced Workstation, GE Healthcare) for optimal analysis and fusion of the images.

FDG PET/CT Analysis

Visual qualitative and quantitative analysis of the tumor can be performed with PET/CT. The maximum standardized uptake value (SUVmax) in the target tumor reflects the level of tumor glucose metabolism [44]. SUV is a semiquantitative measure of radiotracer uptake that reflects the tissue activity concentration as a function of the injected dose at a certain time and patient weight. Quantitative FDG can be used for initial staging and for follow-up response assessment. Assessments can be made with the absolute SUVmax—a threshold technique performed with, for example, liver or blood pool as background activity—or percentage decline in the SUVmax at follow-up studies to determine response assessment. Some groups use an arbitrary SUVmax cutoff of 2–2.5 to attempt to differentiate malignancy from physiologic or inflammatory uptake. These cutoffs, however, may miss less FDG avid tumors, and overlap can exist [44]. An absolute SUVmax threshold for cervical cancer has not been validated, likely owing to the aforementioned factors and the different grades and stage of tumors at presentation.
Other quantitative metabolic metrics include total lesion glycolysis (TLG) and metabolic tumor volume (MTV). MTV is defined as the volume of tumor with FDG uptake, and TLG is defined as MTV × SUVmean. Advances in software enable contouring of hypermetabolic foci with volumetric PET parameters such as MTV and TLG in threshold-based automated volumes of interest at a standard PET/CT workstation. For MTV a volume of interest is placed over the lesion with an automated segmentation software system to detect the threshold level that separates the target volume from the background tissue by weighting of the SUVmax and the SUVmax within the target volume with a specified weighting factor. There are, however, several methods of calculating MTV, which may explain the apparent lack of significant association with primary cervical cancer in several trials. Some groups have used a percentage, such as 40–60% of SUVmax, as a threshold [45].
The methods for determining gross tumor volume are inherently different for MRI and PET/CT. Ma et al. [46] compared MRI gross tumor volume contoured manually on axial T2-weighted images with MTV contoured with a 40% SUV automatic threshold. The MRI and FDG PET tumor volumes were similar, but the location of the tumor (volume) varied, especially for small tumor volumes. Compared with FDG PET/CT, MRI was better at depicting larger tumors. FDG PET/CT depicted tumor volumes differently than did T2-weighted MRI, especially tumors smaller than 14 cm3, with respect to location.

Initial Staging

FDG PET/CT can be used for the initial evaluation of cervical carcinoma, which is typically highly FDG avid.

Primary Tumor

Although CT shows the normal cervix with variable enhancement patterns depending on the phase of imaging, accumulation of FDG in the normal cervix is not significantly greater than that of surrounding background tissue [26, 47]. After IV administration of contrast material, the primary cervical tumor appears isoattenuating or hypoattenuating relative to normal cervical stroma [8]. The low-attenuation areas seen at CT usually represent necrosis, ulceration, or decreased vascularity [28, 48, 49]. The presence of FDG activity has been found in almost all primary cervical cancers 7 mm and larger (Figs. 1 and 2), and it is usually not appreciated in the necrotic component of the tumor or within the uterine cavity distended by the accumulation of blood, serous fluid, or pus secondary to obstruction of the endocervical canal by the tumor.
Fig. 1A —Role of PET/CT in initial staging of cervical cancer. 57-year-old woman with clinical stage IB cervical cancer found to have infiltration of anterior rectum and posterior bladder wall.
A, Contrast-enhanced CT image from PET/CT shows loss of fat plane (arrow, C) between cervix and rectum and infiltration of rectal wall. Disease was upstaged to stage IVA, which altered management. Sagittal fused PET/CT (A), axial fused PET/CT (B), and contrast-enhanced CT (C) images show hypermetabolic cervical mass (green arrow, A) (maximum standardized uptake value, 10) and infiltration of rectum (yellow arrow, B) and bladder (red arrow).
Fig. 1B —Role of PET/CT in initial staging of cervical cancer. 57-year-old woman with clinical stage IB cervical cancer found to have infiltration of anterior rectum and posterior bladder wall.
B, Contrast-enhanced CT image from PET/CT shows loss of fat plane (arrow, C) between cervix and rectum and infiltration of rectal wall. Disease was upstaged to stage IVA, which altered management. Sagittal fused PET/CT (A), axial fused PET/CT (B), and contrast-enhanced CT (C) images show hypermetabolic cervical mass (green arrow, A) (maximum standardized uptake value, 10) and infiltration of rectum (yellow arrow, B) and bladder (red arrow).
Fig. 1C —Role of PET/CT in initial staging of cervical cancer. 57-year-old woman with clinical stage IB cervical cancer found to have infiltration of anterior rectum and posterior bladder wall.
C, Contrast-enhanced CT image from PET/CT shows loss of fat plane (arrow, C) between cervix and rectum and infiltration of rectal wall. Disease was upstaged to stage IVA, which altered management. Sagittal fused PET/CT (A), axial fused PET/CT (B), and contrast-enhanced CT (C) images show hypermetabolic cervical mass (green arrow, A) (maximum standardized uptake value, 10) and infiltration of rectum (yellow arrow, B) and bladder (red arrow).
Fig. 2A —PET/CT and MRI in initial staging of cervical mass with local metastasis. 55-year-old woman with stage IB cervical cancer.
A, Contrast-enhanced sagittal PET/CT (A), contrast-enhanced sagittal CT (B), coronal T2-weighted MR (C), and sagittal T2-weighted MR (D) images show cervical mass (arrow) abutting anterior rectal wall without local invasion or local or distant metastasis.
Fig. 2B —PET/CT and MRI in initial staging of cervical mass with local metastasis. 55-year-old woman with stage IB cervical cancer.
B, Contrast-enhanced sagittal PET/CT (A), contrast-enhanced sagittal CT (B), coronal T2-weighted MR (C), and sagittal T2-weighted MR (D) images show cervical mass (arrow) abutting anterior rectal wall without local invasion or local or distant metastasis.
Fig. 2C —PET/CT and MRI in initial staging of cervical mass with local metastasis. 55-year-old woman with stage IB cervical cancer.
C, Contrast-enhanced sagittal PET/CT (A), contrast-enhanced sagittal CT (B), coronal T2-weighted MR (C), and sagittal T2-weighted MR (D) images show cervical mass (arrow) abutting anterior rectal wall without local invasion or local or distant metastasis.
Fig. 2D —PET/CT and MRI in initial staging of cervical mass with local metastasis. 55-year-old woman with stage IB cervical cancer.
D, Contrast-enhanced sagittal PET/CT (A), contrast-enhanced sagittal CT (B), coronal T2-weighted MR (C), and sagittal T2-weighted MR (D) images show cervical mass (arrow) abutting anterior rectal wall without local invasion or local or distant metastasis.
Kidd et al. [50] found that in cervical tumors, FDG uptake varied by histologic features and differentiation [44, 48]. Squamous cell and poorly differentiated tumors had a significantly higher SUVmax than nonsquamous cell cancers [8]. The degree of FDG uptake correlates with tumor proliferation rates, reflecting tumor aggressiveness. Kidd et al. found a tumor mean SUVmax of 11.62 (range, 2.50–50.39) in 240 patients with all stages of cervical cancer. Higher SUV was associated with poorly differentiated tumor types, although this finding did not reach significance. Squamous cell tumors (SUVmax, 11.91) had statistically significantly higher SUV than did adenocarcinoma (SUVmax, 8.85) and adenosquamous (SUVmax, 8.05) subtypes. Higher SUVmax was associated with increased risk of lymph node metastases. Only SUVmax was found to be a significant predictive biomarker of risk of lymph node involvement compared with stage, histologic features, and tumor differentiation. The primary tumor SUVmax was also predictive of persistent disease after treatment, pelvic recurrence, and overall survival. In particular, the primary tumor SUVmax at diagnosis was a more significant predictor of outcome of cervical cancer than FIGO stage, tumor volume, histologic features, or lymph node involvement. As in other tumors, higher SUV was associated with a shorter disease-free survival.
Lee et al. [45] also reported a median SUVmax of 12.3 in 44 untreated patients with histopathologically confirmed FIGO stage IB–IIA invasive cervical carcinoma. The mean SUVmax was 9.5 ± 6.2 (SD) for stage IB1, 17.0 ± 9.5 for IB2, and 15.1 ± 6.4 for IIA disease with significant differences observed between the groups. The median or mean SUVmax was significantly higher in patients with deep stromal invasion and pathologically confirmed large tumors compared with the control patients. However, no significant differences were noted in SUVmax among the patients at high risk with respect to lymph node status and microscopic parametrial invasion.
PET/CT is less useful in the care of patients with disease in stage IB or lower because disease, particularly lymph node micrometastasis, can be missed [51]. The presence of urinary bladder activity can impair assessment of the pelvis; hence, patients should always void before PET/CT. Visual assessment of the whole-body scan is routinely performed after imaging and before the patient is discharged to ensure there are no artifacts or bladder activity that may impair assessment of pelvic adenopathy or the cervix. Repeat imaging of a particular bed position can be performed once the bladder is emptied. These steps obviate urinary bladder catheterization and diuretic administration before imaging.

Local Extension of Disease

PET/CT delineates the margins of an invasive tumor in cases of superior tumor extension into the uterine cavity and inferior extension into the vaginal cuff [49]. However, because of limited spatial resolution of subcentimeter lesions and partial volume effect, small lesions and micrometastatic deposits can be missed with PET, resulting in false-negative findings [52]. Pandharipande et al. [53] reported that PET/CT plays an indispensable complementary role to MRI in the evaluation of local extent of disease. They developed a decision analysis model to compare important clinical outcomes consequent to pretreatment MRI and PET/CT of patients with FIGO stage IB clinically operable cervical cancer. Three outcomes were compared: 5-year overall survival rate, percentage of patients receiving correct primary therapy, and percentage of patients spared trimodality therapy (surgery followed by chemoradiation). The 5-year overall survival rates were comparable among strategies. Triage to the correct primary therapy was highest with PET/CT (89.27%) and lowest with MRI (68.21%). Avoidance of trimodality therapy was highest with combined MRI and PET/CT (95.01%) and lowest with the no-imaging strategy (82.32%). The authors concluded that pretreatment imaging of patients with FIGO stage IB cervical cancer can optimize triage to appropriate therapy. Even though use of imaging does not appear to improve survival, PET/CT maximizes patient triage to correct therapy, and the combination of MRI and PET/CT spares most patients unnecessary trimodality therapy.
Sala et al. [54] stated that MRI is the best single imaging investigation for accurately determining tumor location, tumor size, depth of stromal invasion, and extension into the lower uterine segment. They reported that MRI is accurate for evaluation of tumor size, usually within 0.5 cm of the surgical size, in 70–90% of cases. They also stated that MRI is useful in the evaluation of lymph node metastases. They reported sensitivity of MRI in the evaluation of bladder and rectal invasion of 71–100% and specificity of 88–91%. An important pitfall of MRI staging is overestimation of parametrial invasion in large tumors compared with small ones (accuracy, 70% vs 96%) on T2-weighted images owing to stromal edema caused by tumor compression or inflammation [54]. The absence of bladder or rectal invasion can be diagnosed with MRI with enough confidence (negative predictive value, 100%) to safely prevent invasive cystoscopic or endoscopic staging in patients with cervical cancer [54].
Mitchell et al. [55] compared MRI, CT, and clinical examination in the detection of early cervical cancer and for measuring tumor size. They enrolled 208 patients with biopsy-proven invasive cervical cancer for MRI and CT before attempted curative radical hysterectomy and found that neither MRI nor CT was accurate for evaluating cervical stroma. For uterine body involvement, the area under the receiver operating characteristic curve was greater for MRI than for CT for both prospective (0.80 vs 0.66; p = 0.01) and retrospective (0.68 vs 0.57; p = 0.02) readings. Retrospective readers could measure diameter with CT in 35–73% of patients and with MRI in 79–94% of patients. Prospective readings had the highest Spearman correlation coefficient with pathologic measurement for MRI (r = 0.54), followed by CT (r = 0.45) and clinical examination (r = 0.37) (p < 0.0001 for all). Spearman correlation of multiobserver diameter measurements for MRI (r = 0.58; p < 0.0001) was double that for CT (r = 0.27; p = 0.03). Mitchell et al. concluded that in patients with cervical cancer, MRI is superior to CT and clinical examination for evaluating uterine body involvement and measuring tumor size, but no method was accurate for evaluating cervical stroma.

Lymph Node Involvement

Lymph node status in cervical cancer is one of the most important and valuable predictive and prognostic factors. Many authors have assessed the sensitivity and specificity of FDG PET/CT in the evaluation of early and advanced cervical cancer. In patients with disease in more advanced stages (≥ IB2), in which extrapelvic spread is frequent, including paraaortic lymph node involvement, FDG PET/CT is potentially effective for lymph node staging, particularly of locally advanced cervical carcinoma when CT findings are normal. Several patients have had substantial changes in treatment planning [56]. Grigsby et al. [57] retrospectively compared the results of CT lymph node staging and whole-body FDG PET in the care of 101 consecutively registered patients with carcinoma of the cervix. PET showed abnormal FDG uptake in pelvic lymph nodes in 67 (67%) of the patients, in paraaortic lymph nodes in 21 (21%), and in supraclavicular lymph nodes in eight (8%).
Lee et al. [58] assessed the diagnostic accuracy of FDG PET in the detection of metastatic supraclavicular lymph nodes and found a high incidence of metastasis in PET-detected supraclavicular lymph nodes in cancer patients. One hundred supraclavicular nodes detected with FDG PET alone were biopsied, and 86 were found to be malignant. With application of the cutoff value obtained by receiver operating characteristic analysis (SUVmax, 3.0), the diagnostic accuracy of FDG PET was 75.0% with sensitivity of 74.4% and specificity of 78.6%. For supraclavicular lymph nodes with an SUVmax of more than 3.0, FDG PET had a positive predictive value of 95.5%. For supraclavicular lymph nodes with an SUVmax of 3.0 or less, sonographic findings excluded all false-negative FDG PET cases and had a high negative predictive value of 100%. When sonography was selectively applied to cases with an SUVmax of 3.0 or less, the overall diagnostic accuracy increased to 92%.
Grigsby [7] found that lymph node status determined with FDG PET was the most significant independent pretreatment predictor of progression-free and overall survival of patients with cervical cancer. Use of PET improved initial staging (Fig. 3) in cases of advanced disease by showing unexpected sites of metastasis beyond the pelvis and retroperitoneum, such as supraclavicular nodal metastasis (8%), which changed disease management. Yildirim et al. [59] suggested that PET/CT is an effective imaging technique in the treatment of patients with stage IB2-II cervical carcinoma and that it might replace lymphadenectomy.
Fig. 3A —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
A, Initial staging. Axial (A and B), sagittal (C), and coronal (D) fused PET/CT images show large hypermetabolic (maximum standardized uptake value, 17.2) cervical mass (arrow, A) involving lower uterine body, upper vagina, parametrium, and bladder. Pelvic and paraaortic lymphadenopathy (arrow, C and D) also is evident.
Fig. 3B —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
B, Initial staging. Axial (A and B), sagittal (C), and coronal (D) fused PET/CT images show large hypermetabolic (maximum standardized uptake value, 17.2) cervical mass (arrow, A) involving lower uterine body, upper vagina, parametrium, and bladder. Pelvic and paraaortic lymphadenopathy (arrow, C and D) also is evident.
Fig. 3C —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
C, Initial staging. Axial (A and B), sagittal (C), and coronal (D) fused PET/CT images show large hypermetabolic (maximum standardized uptake value, 17.2) cervical mass (arrow, A) involving lower uterine body, upper vagina, parametrium, and bladder. Pelvic and paraaortic lymphadenopathy (arrow, C and D) also is evident.
Fig. 3D —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
D, Initial staging. Axial (A and B), sagittal (C), and coronal (D) fused PET/CT images show large hypermetabolic (maximum standardized uptake value, 17.2) cervical mass (arrow, A) involving lower uterine body, upper vagina, parametrium, and bladder. Pelvic and paraaortic lymphadenopathy (arrow, C and D) also is evident.
Fig. 3E —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
E, Follow-up FDG PET/CT. Axial (E and F), sagittal (G), and coronal (H) fused PET/CT images show distant metastasis within lungs (arrow, F), liver (arrow, E), and mediastinal (arrow, G) and paraaortic (arrows, H) nodes.
Fig. 3F —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
F, Follow-up FDG PET/CT. Axial (E and F), sagittal (G), and coronal (H) fused PET/CT images show distant metastasis within lungs (arrow, F), liver (arrow, E), and mediastinal (arrow, G) and paraaortic (arrows, H) nodes.
Fig. 3G —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
G, Follow-up FDG PET/CT. Axial (E and F), sagittal (G), and coronal (H) fused PET/CT images show distant metastasis within lungs (arrow, F), liver (arrow, E), and mediastinal (arrow, G) and paraaortic (arrows, H) nodes.
Fig. 3H —Progression of disease with new lung, liver, mediastinal, and paraaortic metastasis. 60-year-old woman with inoperable stage IVB cervical carcinoma with pelvic and paraaortic lymph node metastasis and distant metastases. Chemotherapy was started but with abbreviated course owing to thrombocytopenia, and interstitial brachytherapy was performed. Follow-up PET/CT was performed 4 months after initial staging as part of subsequent treatment strategy.
H, Follow-up FDG PET/CT. Axial (E and F), sagittal (G), and coronal (H) fused PET/CT images show distant metastasis within lungs (arrow, F), liver (arrow, E), and mediastinal (arrow, G) and paraaortic (arrows, H) nodes.
Loft et al. [60] conducted a prospective study that included 120 patients with newly diagnosed cervical cancer in FIGO stage IB or greater imaged with whole-body PET/CT within 2 weeks of initial staging. They performed diagnostic IV contrast-enhanced CT, which was used for PET attenuation correction. Patients were divided into two groups: patients whose condition allowed radical hysterectomy including lymph node dissection and patients referred for combined chemoradiation therapy. FIGO staging and whole-body PET/CT were performed, and the results were compared with the histopathologic or follow-up findings or both. Twentyseven patients underwent radical surgery; four of these had PET/CT scans showing pathologic foci in the pelvis. Three (11%) of the PET/CT findings were true-positive, and one was false-positive. Twenty-two patients had true-negative PET/CT findings for pelvic lymph nodes. One patient had a false-negative node. In these patients, PET/CT had sensitivity of 75% and a specificity of 96% for nodal status in the pelvis. In the patients who did not undergo surgery (92 patients), the sensitivity and specificity were 75% and 87%. PET/CT had sensitivity of 100% and a specificity of 99% for paraaortic nodal disease in all patients and sensitivity and specificity of 100% and 94% for distant metastases in all cases. Loft et al. concluded that whole-body FDG PET/CT for newly diagnosed cervical cancer in FIGO stage IB or greater had higher sensitivity and specificity for staging than did diagnostic CT with IV contrast administration. Thus FDG PET/CT is a valuable supplement to the FIGO staging system and useful for treatment planning. Because histologic confirmation is necessary before change of treatment, Loft et al. also concluded that PET/CT scan can be used to guide biopsy.
Wright et al. [61] determined the sensitivity and specificity of PET in detecting lymph node metastasis in women with early-stage cervical carcinoma (stage IA2–IIA). Those authors performed a retrospective review of patients with stage IA–IIA cervical carcinoma who underwent PET before surgery from 1999 to 2004 and correlated the status of regional lymph nodes with lymph node pathologic results. They concluded that PET had sensitivity of 53% and specificity of 90% in the detection of lymph node metastasis in patients with early-stage cervical carcinoma. FDG PET played a more valuable role in more advanced disease (stage IIB–IVB), in which lymph node involvement is more prevalent.
Havrilesky et al. [62] in a meta-analysis found that the pooled sensitivity of PET for the detection of aortic node metastasis is 84% and the pooled specificity 95%. These values for detection of pelvic node metastasis are 79% and 99%. Singh et al. [63] found that the 3-year cause-specific survival rate was highly dependent on the extent of lymph node metastasis visualized with FDG PET/CT in 47 patients with FIGO clinical stage IIIB cervical carcinoma. Rose et al. [64] conducted a prospective study to evaluate the role of FDG PET in detecting paraaortic nodal metastasis in 32 patients with locally advanced cervical carcinoma and without evidence of extrapelvic disease before planned surgical staging lymphadenectomy. PET had sensitivity of 75%, specificity of 92%, positive predictive value of 75%, and negative predictive value of 92% in the detection of paraaortic nodes. Paraaortic nodal FDG uptake conferred a relative risk of 9.0 (95% CI, 2.3–36.0) for paraaortic nodal metastasis. Rose et al. concluded that FDG PET is accurate in the prediction of both the presence and the absence of pelvic and paraaortic nodal metastatic disease.
An early study, by Sugawara et al. [65], showed that FDG PET has sensitivity of 86% in the detection of lymph node metastasis in advanced cervical cancer. Those authors found that FDG PET had promise for detecting untreated and recurrent cervical cancer and lymph node metastasis but that the excreted renal FDG was problematic in some patients. Other authors [66, 67], however, have found that the accuracy of PET/CT in prediction of pelvic nodal status is low in patients with early-stage cervical cancer and thus PET/CT cannot replace lymphadenectomy. Approximately 15–30% of patients with locoregionally advanced cervical cancer will have paraaortic lymph node metastatic involvement [68].

Distant Metastasis

Use of PET/CT improves initial staging by providing information on extrapelvic and paraaortic sites, such as supraclavicular lymph nodes, mediastinal lymph nodes, lung, bone, peritoneum, omentum, adrenal gland, and liver [56]. Wong et al. [69] assessed the accuracy of FDG PET for evaluating local and distant disease in patients with cervical cancer. With FDG PET, the primary disease was identified in all patients at initial staging. At follow-up, patients with locoregional disease were differentiated from those with distant metastases with 100% accuracy. FDG PET had sensitivity of 82%, specificity of 97%, and accuracy of 92% for evaluating local recurrence during cervical cancer restaging. PET had sensitivity of 100%, specificity of 90%, and accuracy of 94% for evaluating distant disease in these patients. The study showed that FDG PET is an accurate modality for both initial staging and restaging of cervical cancer.

Value of FDG PET/CT in Radiotherapy Planning

External Beam Radiotherapy

Combined with cisplatin-based chemotherapy, external beam radiation therapy continues to be the standard therapy for patients with locally advanced cervical cancer [56]. Several studies have shown a survival benefit in patients with paraaortic nodal involvement treated by extended field irradiation and simultaneous radiosensitizing chemotherapy [7072]. Evaluation of pelvic nodes with PET/CT does not significantly change the management of locoregional disease; however, pathologic paraaortic nodal FDG uptake may affect therapeutic strategy [56]. Extrapelvic nodal involvement may modify the treatment approach, particularly in patients who appear to have localized disease limited to the cervix at initial clinical staging.
Belhocine et al. [73] found that the results of PET staging altered management in 18% of the study population, either by extension of the radiation field to include the paraaortic area (Fig. 4) or by a change in the total administered dose to the involved nodes in the pelvic area [74]. Narayan et al. [75] conducted a study to determine whether use of FDG PET/CT or MRI could obviate surgical staging in radiotherapy planning for patients with locally advanced cervical carcinoma. Those authors concluded that the 91% positive predictive value of PET in depicting pelvic and paraaortic nodes appeared sufficient to obviate lymph node sampling and to extend the radiation field without surgery. However, sampling is still required to exclude small-volume disease, and MRI is insufficiently accurate for nodal staging to affect management.
Fig. 4A —Radiation therapy planning. 65-year-old woman with locally advanced stage IIIB cervical cancer with endometrial involvement and pelvic and paraaortic lymphadenopathy.
A, Axial (A), coronal (B), and sagittal (C) fused PET/CT images show gross tumor volume (GTV) with red border delineating hypermetabolic (maximum standardized uptake value, 10) cervical mass with vaginal and possible bladder wall involvement and clinical tumor volume (CTV) with green border including bilateral iliac chain and aortocaval nodes. GTV was considered extension of tumor, taking into account macroscopic disease at clinical examination and visible tumor on PET/CT images. Accurate target CTV is vital for definitive treatment of cervical cancer with intensity-modulated radiotherapy. Patient was treated with 45-Gy dose of radiation therapy to pelvic, inguinal, and paraaortic lymph nodes with concurrent chemotherapy and 14.4-Gy boost radiation to involved nodal region.
Fig. 4B —Radiation therapy planning. 65-year-old woman with locally advanced stage IIIB cervical cancer with endometrial involvement and pelvic and paraaortic lymphadenopathy.
B, Axial (A), coronal (B), and sagittal (C) fused PET/CT images show gross tumor volume (GTV) with red border delineating hypermetabolic (maximum standardized uptake value, 10) cervical mass with vaginal and possible bladder wall involvement and clinical tumor volume (CTV) with green border including bilateral iliac chain and aortocaval nodes. GTV was considered extension of tumor, taking into account macroscopic disease at clinical examination and visible tumor on PET/CT images. Accurate target CTV is vital for definitive treatment of cervical cancer with intensity-modulated radiotherapy. Patient was treated with 45-Gy dose of radiation therapy to pelvic, inguinal, and paraaortic lymph nodes with concurrent chemotherapy and 14.4-Gy boost radiation to involved nodal region.
Fig. 4C —Radiation therapy planning. 65-year-old woman with locally advanced stage IIIB cervical cancer with endometrial involvement and pelvic and paraaortic lymphadenopathy.
C, Axial (A), coronal (B), and sagittal (C) fused PET/CT images show gross tumor volume (GTV) with red border delineating hypermetabolic (maximum standardized uptake value, 10) cervical mass with vaginal and possible bladder wall involvement and clinical tumor volume (CTV) with green border including bilateral iliac chain and aortocaval nodes. GTV was considered extension of tumor, taking into account macroscopic disease at clinical examination and visible tumor on PET/CT images. Accurate target CTV is vital for definitive treatment of cervical cancer with intensity-modulated radiotherapy. Patient was treated with 45-Gy dose of radiation therapy to pelvic, inguinal, and paraaortic lymph nodes with concurrent chemotherapy and 14.4-Gy boost radiation to involved nodal region.
Chao et al. [76] reported the results of a prospective trial that included 47 cervical cancer patients with paraaortic, inguinal, or supraclavicular nodal involvement as found at CT or MRI. Additional FDG PET or PET/CT had a positive clinical effect on the care of 21 patients (44.7%), including depiction of additional curable sites, downstaging of disease, enabling metabolic biopsy of involved sites, and changing the treatment strategy to palliation.

Brachytherapy

The goal of brachytherapy is to encompass the maximum amount of target tumor volume within the prescribed dose without exceeding dose constraints to the critical organs [56]. Lin et al. [77] found value of FDG PET for brachytherapy in a study in which they compared intracavitary brachytherapy by both conventional and custom loading and intended to cover a PET-defined tumor volume in patients with cervical cancer. The authors concluded that FDG PET–based treatment planning allowed improved dose coverage of the tumor without significantly increasing the dose to the bladder and rectum. In previous work [44] Lin et al. had verified a mean 50% tumor volume reduction within 20 days from the beginning of radiation therapy. Malyapa et al. [78] compared conventional 2D orthogonal radiography-based brachytherapy treatment planning for cervical cancer with a 3D treatment planning technique based on FDG PET. The study showed not only that 3D treatment planning was feasible and accurate in relation to conventional 2D treatment planning but also that the 3D technique has potential for improving isodose tumor coverage for patients with cervical cancer while critical structures are spared.

Therapy Response

Depending on the stage, cervical carcinoma is treated with surgery, radiation therapy, and chemotherapy. Several studies have shown the value of FDG PET/CT in assessment of treatment response (Figs. 3, 5, and 6). Grigsby et al. [79] completed a retrospective study with the aims of evaluating response to therapy with posttherapy molecular imaging with FDG PET and comparing the response with patient outcome. In that retrospective study, 152 medical records of patients with cervical cancer were reviewed. All patients underwent pretreatment and posttreatment whole-body FDG PET. Patients were treated with external irradiation and intracavitary brachytherapy, and most underwent concurrent weekly cisplatin treatments. Posttherapy whole-body FDG PET was performed 1–12 months (mean, 3 months) after completion of treatment. Posttherapy PET did not show any abnormal FDG uptake in 114 patients, and their 5-year cause-specific survival estimate was 80%. There was persistent (in the irradiated region) abnormal FDG uptake in the cervix or lymph nodes in 20 patients. The 5-year cause-specific survival estimate was 32%. New anatomic sites (in unirradiated regions) of abnormal FDG uptake were present in 18 patients, and none was alive at 5 years. The study showed that FDG PET findings in the posttherapy evaluation of patients with cervical carcinoma are predictive of survival outcome. In this line, a prospective study by Schwarz et al. [80] to validate the association between metabolic response at 3-month posttherapy FDG PET and long-term survival outcome showed that the 3-year survival estimates were 78%, 33%, and 0% in patients with complete metabolic response, partial metabolic response, and progressive disease, respectively. That study proved that posttherapy FDG uptake, as detected with whole-body PET, is predictive of survival.
Fig. 5A —Partial metabolic response after external beam radiation therapy with cisplatin chemosensitization. 47-year-old woman with stage IIB squamous cervical cancer with bladder involvement. Patient received total dose of 45–50 cGy.
A, Initial staging. Sagittal (A) and axial (B) fused PET/CT and axial CT (C) images show heterogeneously intense FDG activity (maximum standardized uptake value [SUVmax], 11.2) fusing to large pelvic mass arising from cervix (red arrow). Mass displaces urinary bladder (yellow arrow) in anterior aspect and is contiguous with bladder trigone.
Fig. 5B —Partial metabolic response after external beam radiation therapy with cisplatin chemosensitization. 47-year-old woman with stage IIB squamous cervical cancer with bladder involvement. Patient received total dose of 45–50 cGy.
B, Initial staging. Sagittal (A) and axial (B) fused PET/CT and axial CT (C) images show heterogeneously intense FDG activity (maximum standardized uptake value [SUVmax], 11.2) fusing to large pelvic mass arising from cervix (red arrow). Mass displaces urinary bladder (yellow arrow) in anterior aspect and is contiguous with bladder trigone.
Fig. 5C —Partial metabolic response after external beam radiation therapy with cisplatin chemosensitization. 47-year-old woman with stage IIB squamous cervical cancer with bladder involvement. Patient received total dose of 45–50 cGy.
C, Initial staging. Sagittal (A) and axial (B) fused PET/CT and axial CT (C) images show heterogeneously intense FDG activity (maximum standardized uptake value [SUVmax], 11.2) fusing to large pelvic mass arising from cervix (red arrow). Mass displaces urinary bladder (yellow arrow) in anterior aspect and is contiguous with bladder trigone.
Fig. 5D —Partial metabolic response after external beam radiation therapy with cisplatin chemosensitization. 47-year-old woman with stage IIB squamous cervical cancer with bladder involvement. Patient received total dose of 45–50 cGy.
D, Follow-up FDG PET/CT. Sagittal (D) and axial (E) fused PET/CT and axial CT (F) images show interval partial treatment response. Infiltrative FDG avid cervical mass (arrow) has decreased in size and FDG activity (SUVmax, 8.3). There is no evidence of metastatic disease.
Fig. 5E —Partial metabolic response after external beam radiation therapy with cisplatin chemosensitization. 47-year-old woman with stage IIB squamous cervical cancer with bladder involvement. Patient received total dose of 45–50 cGy.
E, Follow-up FDG PET/CT. Sagittal (D) and axial (E) fused PET/CT and axial CT (F) images show interval partial treatment response. Infiltrative FDG avid cervical mass (arrow) has decreased in size and FDG activity (SUVmax, 8.3). There is no evidence of metastatic disease.
Fig. 5F —Partial metabolic response after external beam radiation therapy with cisplatin chemosensitization. 47-year-old woman with stage IIB squamous cervical cancer with bladder involvement. Patient received total dose of 45–50 cGy.
F, Follow-up FDG PET/CT. Sagittal (D) and axial (E) fused PET/CT and axial CT (F) images show interval partial treatment response. Infiltrative FDG avid cervical mass (arrow) has decreased in size and FDG activity (SUVmax, 8.3). There is no evidence of metastatic disease.
Fig. 6A —Complete metabolic and anatomic response to therapy. 82-year-old woman with invasive poorly differentiated carcinoma with features of squamous cell carcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma features with diffuse and strong cellular protein p16 positivity at cold knife cone biopsy after abnormal findings in Pap smear.
A, Initial staging. Sagittal (A) and axial (B and C) fused PET/CT images show intense FDG activity (maximum standardized uptake value, 6.1) fusing to heterogeneous soft-tissue pelvic mass in cervix and lower uterine segment (red arrow, A and C) posterior to bladder (green arrow, A and C). Endometrial cavity (arrow, B) is fluid filled.
Fig. 6B —Complete metabolic and anatomic response to therapy. 82-year-old woman with invasive poorly differentiated carcinoma with features of squamous cell carcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma features with diffuse and strong cellular protein p16 positivity at cold knife cone biopsy after abnormal findings in Pap smear.
B, Initial staging. Sagittal (A) and axial (B and C) fused PET/CT images show intense FDG activity (maximum standardized uptake value, 6.1) fusing to heterogeneous soft-tissue pelvic mass in cervix and lower uterine segment (red arrow, A and C) posterior to bladder (green arrow, A and C). Endometrial cavity (arrow, B) is fluid filled.
Fig. 6C —Complete metabolic and anatomic response to therapy. 82-year-old woman with invasive poorly differentiated carcinoma with features of squamous cell carcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma features with diffuse and strong cellular protein p16 positivity at cold knife cone biopsy after abnormal findings in Pap smear.
C, Initial staging. Sagittal (A) and axial (B and C) fused PET/CT images show intense FDG activity (maximum standardized uptake value, 6.1) fusing to heterogeneous soft-tissue pelvic mass in cervix and lower uterine segment (red arrow, A and C) posterior to bladder (green arrow, A and C). Endometrial cavity (arrow, B) is fluid filled.
Fig. 6D —Complete metabolic and anatomic response to therapy. 82-year-old woman with invasive poorly differentiated carcinoma with features of squamous cell carcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma features with diffuse and strong cellular protein p16 positivity at cold knife cone biopsy after abnormal findings in Pap smear.
D, Follow-up FDG PET/CT. Sagittal (D) and axial (E and F) fused PET/CT images show interval complete metabolic and anatomic response after three cycles of etoposide and carboplatin interval neoadjuvant chemotherapy and modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy with no focal FDG uptake in abdomen or pelvis to suggest residual or recurrent disease. Mild FDG uptake fuses to laparotomy wound (arrow, D and F).
Fig. 6E —Complete metabolic and anatomic response to therapy. 82-year-old woman with invasive poorly differentiated carcinoma with features of squamous cell carcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma features with diffuse and strong cellular protein p16 positivity at cold knife cone biopsy after abnormal findings in Pap smear.
E, Follow-up FDG PET/CT. Sagittal (D) and axial (E and F) fused PET/CT images show interval complete metabolic and anatomic response after three cycles of etoposide and carboplatin interval neoadjuvant chemotherapy and modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy with no focal FDG uptake in abdomen or pelvis to suggest residual or recurrent disease. Mild FDG uptake fuses to laparotomy wound (arrow, D and F).
Fig. 6F —Complete metabolic and anatomic response to therapy. 82-year-old woman with invasive poorly differentiated carcinoma with features of squamous cell carcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma features with diffuse and strong cellular protein p16 positivity at cold knife cone biopsy after abnormal findings in Pap smear.
F, Follow-up FDG PET/CT. Sagittal (D) and axial (E and F) fused PET/CT images show interval complete metabolic and anatomic response after three cycles of etoposide and carboplatin interval neoadjuvant chemotherapy and modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy with no focal FDG uptake in abdomen or pelvis to suggest residual or recurrent disease. Mild FDG uptake fuses to laparotomy wound (arrow, D and F).

Recurrence

One third of patients have disease recurrence within 2 years. Recurrence is defined as cancer development at least 6 months after the treated disease has regressed [81]. A study by Wong et al. [69] to assess the accuracy of FDG PET for evaluating local and distant disease in 41 patients with cervical cancer, 35 presenting for restaging following therapy, showed the following: For restaging cervical cancer, FDG PET had sensitivity of 82%, specificity of 97%, and accuracy of 92% for evaluation of local recurrence. For evaluating distant disease in these patients, PET had sensitivity of 100%, specificity of 90%, and accuracy of 94%. That study proved that PET/CT has high accuracy for locally recurrent and distant metastatic disease, has prognostic value for disease outcome, and contributes to management change. Crivellaro et al. [82] assessed the role of the metabolic characteristics of cervical tumor uptake as predictors of lymph node metastasis and recurrence in preoperative staging in the care of 89 patients with early-stage cervical cancer. They found the primary tumor MTV and TLG correlated with the presence of nodal metastasis. In their series, the pretreatment FDG PET/CT findings were not predictive of recurrence of early-stage FIGO stage IB1 and IIA cervical cancers smaller than 4 cm. No significant correlations were found between relapse and SUVmax, SUVmean, MTV, or TLG in this group of patients (mean follow-up period, 29.2 ± 15.5 months).

Value of PET/CT in Prognosis

Previous studies have shown that PET/CT plays an important role in predicting prognosis among patients with cervical cancer. Yilmaz et al. [83] conducted a study that included 43 patients with cervical cancer who underwent FDG PET/CT for staging before initiation of treatment. The patients were divided into low and high-SUV groups by use of the median primary tumor SUVmax. The investigators found that the probability of lymph node metastasis in cervical cancer patients increases with increasing primary tumor SUVmax. Kidd and Grigsby [84] found that for cervical cancer, SUVmax at FDG PET is predictive of disease outcome. In that study, which included 72 patients, intratumor heterogeneity of cervical tumors was obtained with the derivative (dV / dr) of the volume-threshold function from 40% to 80%. They concluded that cervical intratumoral FDG metabolic heterogeneity at pretreatment FDG PET may be predictive of risk of lymph node involvement at diagnosis, response to therapy, and risk of pelvic recurrence. Those authors also found that the maximum dimension and SUVmax of the most FDG avid pelvic lymph node is a prognostic biomarker, being predictive of treatment response, pelvic recurrence risk, and disease specific survival in patients with cervical cancer [85]. Yoo et al. [86] also found that TLG and lymph node status at PET may be significant independent prognostic factors, in both univariate and multivariate analyses, for predicting recurrence and event-free survival.
Sharma et al. [87] found FDG uptake on PET scans predictive of postradiation clinical outcome of recurrent cervical carcinoma. Most of the patients had stage III disease at initial presentation and were treated with definitive radiation therapy. The median SUVmax was 5.8 (range, 1.8–50.6), and the median MTV was 43 (range, 5.8–243 cm3). The cumulative progression-free survival rate for all patients was 20% at 30 months. This was relatively worse than that previously reported, possibly owing to advanced disease at the time of recurrence and fewer patients eligible for salvage surgery. The 1-year progression-free survival rate was 28% for patients with an SUVmax greater than 5.8 versus 42% for those with an SUVmax less than 5.8 (p = 0.01). The 1-year progressionfree survival rate was 43% for patients with an MTV value greater than 43 cm3 versus 45% for those with an MTV value less than 43 cm3 (p = 0.8).

Tumor Hypoxia and PET/CT

Tumor hypoxia is an important prognostic factor in cervical cancer. Hypoxic tumors are resistant to radiation and chemotherapy and are aggressive in their development. Tumor hypoxia has been suggested as an adverse prognostic factor unrelated to standard prognostic factors such as tumor stage [88]. In a study of cervical cancer [89], direct assessment of tumor oxygenation with oxygen electrodes showed that patients with hypoxic tumors have worse disease-free survival rates then do those with nonhypoxic tumors. An invasive microelectrode approach is used as the reference standard for direct measurement of hypoxia, but the procedure is invasive and technically difficult to perform, limiting its clinical use. Hence, noninvasive imaging methods such as PET have been studied as alternatives. Single-center studies of PET/CT with the copper-labeled dithiosemicarbazone tracer 60Cu-diacetyl-bis(N4-methylthiosemicarbazone (60Cu-ATSM), which has a high affinity for hypoxic tissue, showed that the pretreatment oxygenation status of tumors can be predictive of overall survival, disease-free survival, and local tumor control [90]. Lewis et al. [91] compared PET image quality and tumor uptake with 60Cu-ATSM and 64Cu-ATSM in women with cancer of the uterine cervix. They found that the image quality with 64Cu-ATSM was better than that with 60Cu-ATSM because of lower noise and concluded that 64Cu-ATSM is a safe radiopharmaceutical that can be used to obtain high-quality images of tumor hypoxia in human cancers. A multicenter study, American College of Radiology Imaging Network 6682, is being conducted to investigate the hypothesis that findings at hypoxia imaging with 64Cu-ATSM PET/CT are predictive of outcome among patients with cervical squamous cell carcinoma.

Conclusion

The role of FDG PET/CT in the evaluation of patients with cervical cancer has expanded rapidly. Value of PET/CT has been found in the detection of locoregional and distant nodal metastases and subsequent change in management. Use of FDG PET/CT facilitates radiation therapy planning. The FDG PET-derived parameters SUVmax, MTV, and TLG are emerging as predictive markers and possible stratification tools.

Footnote

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References

1.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55:74–108
2.
Howlader N, Noone AM, Krapcho M, et al., eds. SEER Cancer Statistics Review, 1975-2008. National Cancer Institute website. seer.cancer.gov/csr/1975_2008. Based on November 2010 SEER data submission. Posted 2011. Accessed March 26, 2013
3.
Arbyn M, Castellsagué X, de Sanjosé S, et al. Worldwide burden of cervical cancer in 2008. Ann Oncol 2011; 22:2675–2686
4.
Stanley M. Human papillomavirus vaccines versus cervical cancer screening. Clin Oncol (R Coll Radiol) 2008; 20:388–394
5.
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58:71–96
6.
Plummer M, Franceschi S. Strategies for HPV prevention. Virus Res 2002; 89:285–293
7.
Grigsby PW. The prognostic value of PET and PET/CT in cervical cancer. Cancer Imaging 2008; 8:146–155
8.
Son H, Kositwattanarerk A, Hayes MP, et al. PET/CT evaluation of cervical cancer: spectrum of disease. RadioGraphics 2010; 30:1251–1268
9.
Chaturvedi AK, Kleinerman RA, Hildesheim A, et al. Second cancers after squamous cell carcinoma and adenocarcinoma of the cervix. J Clin Oncol 2009; 27:967–973
10.
Schorge JO, Knowles LM, Lea JS. Adenocarcinoma of the cervix. Curr Treat Options Oncol 2004; 5:119–127
11.
Imadome K, Iwakawa M, Nakawatari M, et al. Subtypes of cervical adenosquamous carcinomas classified by EpCAM expression related to radiosensitivity. Cancer Biol Ther 2010; 10:1019–1026
12.
Waggoner SE. Cervical cancer. Lancet 2003; 361:2217–2225
13.
Kumar VA, Fausto N, Mitchell RN. Robbins basic pathology. Philadelphia, PA: Saunders Elsevier, 2007:718–721
14.
Canavan TP, Doshi NR. Cervical cancer. Am Fam Physician 2000; 61:1369–1376
15.
James RM, Cruickshank ME, Siddiqui N. Management of cervical cancer: summary of SIGN guidelines. BMJ 2008; 336:41–43
16.
Kanthan R, Senger JL, Diudea D, Kanthan S. A review of duodenal metastases from squamous cell carcinoma of the cervix presenting as an upper gastrointestinal bleed. World J Surg Oncol 2011; 9:113
17.
Kindermann G, Jabusch HP. The spread of squamous cell carcinoma of the uterine cervix into the blood-vessels. Arch Gynakol 1972; 212:1–8
18.
Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009; 105:103–104
19.
Hricak H, Gatsonis C, Chi DS, et al. Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the Intergroup Study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183. J Clin Oncol 2005; 23:9329–9337
20.
Yang WT, Lam WW, Yu MY, Cheung TH, Metreweli C. Comparison of dynamic helical CT and dynamic MR imaging in the evaluation of pelvic lymph nodes in cervical carcinoma. AJR 2000; 175:759–766
21.
Subak LL, Hricak H, Powell CB, Azizi L, Stern JL. Cervical carcinoma: computed tomography and magnetic resonance imaging for preoperative staging. Obstet Gynecol 1995; 86:43–50
22.
Hricak H, Lacey CG, Sandles LG, Chang YC, Winkler ML, Stern JL. Invasive cervical carcinoma: comparison of MR imaging and surgical findings. Radiology 1988; 166:623–631
23.
Sheu MH, Chang CY, Wang JH, Yen MS. Preoperative staging of cervical carcinoma with MR imaging: a reappraisal of diagnostic accuracy and pitfalls. Eur Radiol 2001; 11:1828–1833
24.
Kim SH, Choi BI, Han JK, et al. Preoperative staging of uterine cervical carcinoma: comparison of CT and MRI in 99 patients. J Comput Assist Tomogr 1993; 17:633–640
25.
Chung HH, Kang SB, Cho JY, et al. Can preoperative MRI accurately evaluate nodal and parametrial invasion in early stage cervical cancer?. Jpn J Clin Oncol 2007; 37:370–375
26.
Follen M, Levenback CF, Iyer RB, et al. Imaging in cervical cancer. Cancer 2003; 98:2028–2038
27.
Bipat S, Glas AS, van der Velden J, Zwinderman AH, Bossuyt PM, Stoker J. Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review. Gynecol Oncol 2003; 91:59–66
28.
Hricak H. Role of imaging in the evaluation of pelvic cancer. Important Adv Oncol 1991; 103–133
29.
Fischerova D, Cibula D, Stenhova H, et al. Transrectal ultrasound and magnetic resonance imaging in staging of early cervical cancer. Int J Gynecol Cancer 2008; 18:766–772
30.
Innocenti P, Pulli F, Savino L, et al. Staging of cervical cancer: reliability of transrectal US. Radiology 1992; 185:201–205
31.
Sun LT, Ning CP, Liu YJ, et al. Is transvaginal elastography useful in pre-operative diagnosis of cervical cancer? Eur J Radiol 2012; 81:e888–e892
32.
Thomas A, Kummel S, Gemeinhardt O, Fischer T. Real-time sonoelastography of the cervix: tissue elasticity of the normal and abnormal cervix. Acad Radiol 2007; 14:193–200
33.
Davison JM, Ozonoff A, Imsande HM, Grillone GA, Subramaniam RM. Squamous cell carcinoma of the palatine tonsils: FDG standardized uptake value ratio as a biomarker to differentiate tonsillar carcinoma from physiologic uptake. Radiology 2010; 255:578–585
34.
Karantanis D, O'Neill BP, Subramaniam RM, et al. Contribution of F-18 FDG PET-CT in the detection of systemic spread of primary central nervous system lymphoma. Clin Nucl Med 2007; 32:271–274
35.
Dibble EH, Alvarez AC, Truong MT, Mercier G, Cook EF, Subramaniam RM. 18F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nucl Med 2012; 53:709–715
36.
Jackson T, Chung MK, Mercier G, Ozonoff A, Subramaniam RM. FDG PET/CT interobserver agreement in head and neck cancer: FDG and CT measurements of the primary tumor site. Nucl Med Commun 2012; 33:305–312
37.
Romesser PB, Qureshi MM, Shah BA, et al. Superior prognostic utility of gross and metabolic tumor volume compared to standardized uptake value using PET/CT in head and neck squamous cell carcinoma patients treated with intensity-modulated radiotherapy. Ann Nucl Med 2012; 26:527–534
38.
Subramaniam RM, Wilcox B, Aubry MC, Jett J, Peller PJ. 18F-fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging of malignant pleural mesothelioma. J Med Imaging Radiat Oncol 2009; 53:160–169
39.
Sacks A, Peller PJ, Surasi DS, Chatburn L, Mercier G, Subramaniam RM. Value of PET/CT in the management of primary hepatobiliary tumors. Part 2. AJR 2011; 197:[web]W260–W265
40.
Sacks A, Peller PJ, Surasi DS, Chatburn L, Mercier G, Subramaniam RM. Value of PET/CT in the management of liver metastases. Part 1. AJR 2011; 197:[web]W256–W259
41.
Davison JM, Subramaniam RM, Surasi DS, Cooley T, Mercier G, Peller PJ. FDG PET/CT in patients with HIV. AJR 2011; 197:284–294
42.
Park W, Park YJ, Huh SJ, et al. The usefulness of MRI and PET imaging for the detection of parametrial involvement and lymph node metastasis in patients with cervical cancer. Jpn J Clin Oncol 2005; 35:260–264
43.
Antoch G, Freudenberg LS, Beyer T, Bockisch A, Debatin JF. To enhance or not to enhance? 18F-FDG and CT contrast agents in dual-modality 18F-FDG PET/CT. J Nucl Med 2004; 45(suppl 1):56S–65S
44.
Lin LL, Yang Z, Mutic S, Miller TR, Grigsby PW. FDG-PET imaging for the assessment of physiologic volume response during radiotherapy in cervix cancer. Int J Radiat Oncol Biol Phys 2006; 65:177–181
45.
Lee YY, Choi CH, Kim CJ, et al. The prognostic significance of the SUVmax (maximum standardized uptake value for F-18 fluorodeoxyglucose) of the cervical tumor in PET imaging for early cervical cancer: preliminary results. Gynecol Oncol 2009; 115:65–68
46.
Ma DJ, Zhu JM, Grigsby PW. Tumor volume discrepancies between FDG-PET and MRI for cervical cancer. Radiother Oncol 2011; 98:139–142
47.
Kaur H, Loyer EM, Minami M, Charnsangavej C. Patterns of uterine enhancement with helical CT. Eur J Radiol 1998; 28:250–255
48.
Vick CW, Walsh JW, Wheelock JB, Brewer WH. CT of the normal and abnormal parametria in cervical cancer. AJR 1984; 143:597–603
49.
Grigsby PW. The contribution of new imaging techniques in staging cervical cancer. Gynecol Oncol 2007; 107:S10–S12
50.
Kidd EA, Spencer CR, Huettner PC, et al. Cervical cancer histology and tumor differentiation affect 18F-fluorodeoxyglucose uptake. Cancer 2009; 115:3548–3554
51.
Chou HH et al. Low value of [18F]-fluoro-2-deoxy-D-glucose PET in primary staging of earlystage cervical cancer before radical hysterectomy. J Clin Oncol 2006; 24:123–128
52.
Gouy S, Morice P, Narducci F, et al. Nodal-staging surgery for locally advanced cervical cancer in the era of PET. Lancet Oncol 2012; 13:e212–e220
53.
Pandharipande PV, Choy G, del Carmen MG, Gazelle GS, Russell AH, Lee SI. MRI and PET/CT for triaging stage IB clinically operable cervical cancer to appropriate therapy: decision analysis to assess patient outcomes. AJR 2009; 192:802–814
54.
Sala E, Wakely S, Senior E, Lomas D. MRI of malignant neoplasms of the uterine corpus and cervix. AJR 2007; 188:1577–1587
55.
Mitchell DG, Snyder B, Coakley F, et al. Early invasive cervical cancer: tumor delineation by magnetic resonance imaging, computed tomography, and clinical examination, verified by pathologic results, in the ACRIN 6651/GOG 183 intergroup study. J Clin Onco 2006; 24:5687–5694
56.
Magné N, Chargari C, Vicenzi L, et al. New trends in the evaluation and treatment of cervix cancer: the role of FDG-PET. Cancer rreat Rev 2008; 34:671–681
57.
Grigsby PW, Siegel BA, Dehdashti F. Lymph node staging by PET in patients with carcinoma of the cervix. J Clin Oncol 2001; 19:3745–3749
58.
Lee JH, Kim J, Moon HJ, et al. Supraclavicular lymph nodes detected by 18F-FDG PET/CT in cancer patients: assessment with 18F-FDG PET/CT and sonography. AJR 2012; 198:187–193
59.
Yildirim Y, Sehirali S, Avci ME, et al. Integrated PET/CT for the evaluation of para-aortic nodal metastasis in locally advanced cervical cancer patients with negative conventional CT findings. Gynecol Oncol 2008; 108:154–159
60.
Loft A, Berthelsen AK, Roed H, et al. The diagnostic value of PET/CT scanning in patients with cervical cancer: a prospective study. Gynecol Oncol 2007; 106:29–34
61.
Wright JD, Dehdashti F, Herzog TJ, et al. Preoperative lymph node staging of early-stage cervical carcinoma by [18F]-fluoro-2-deoxy-D-glucosepositron emission tomography. Cancer 2005; 104:2484–2491
62.
Havrilesky LJ, Kulasingam SL, Matchar DB, Myers ER. FDG-PET for management of cervical and ovarian cancer. Gynecol Oncol 2005; 97:183–191
63.
Singh AK, Grigsby PW, Dehdashti F, Herzog TJ, Siegel BA. FDG-PET lymph node staging and survival of patients with FIGO stage IIIb cervical carcinoma. Int J Radiat Oncol Biol Phys 2003; 56:489–493
64.
Rose PG, Adler LP, Rodriguez M, Faulhaber PF, Abdul-Karim FW, Miraldi F. Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study. J Clin Oncol 1999; 17:41–45
65.
Sugawara Y, Eisbruch A, Kosuda S, Recker BE, Kison PV, Wahl RL. Evaluation of FDG PET in patients with cervical cancer. J Nucl Med 1999; 40:1125–1131
66.
Loubeyre P, Navarria I, Undurraga M, et al. Is imaging relevant for treatment choice in early stage cervical uterine cancer? Surg Oncol 2012; 21:e1–e6
67.
Bentivegna E, Uzan C, Gouy S, et al. Correlation between [18F]fluorodeoxyglucose positron-emission tomography scan and histology of pelvic nodes in early-stage cervical cancer. Anticancer Res 2010; 30:1029–1032
68.
Lagasse LD, Creasman WT, Shingleton HM, Ford JH, Blessing JA. Results and complications of operative staging in cervical cancer: experience of the Gynecologic Oncology Group. Gynecol Oncol 1980; 9:90–98
69.
Wong TZ, Jones EL, Coleman RE. Positron emission tomography with 2-deoxy-2-[(18)F]fluoro-D-glucose for evaluating local and distant disease in patients with cervical cancer. Mol Imaging Biol 2004; 6:55–62
70.
Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999; 340:1137–1143
71.
Ansink A, de Barros Lopes A, Naik R, Monaghan JM. Recurrent stage IB cervical carcinoma: evaluation of the effectiveness of routine follow up surveillance. Br J Obstet Gynaecol 1996; 103:1156–1158
72.
Stryker JA, Mortel R. Survival following extended field irradiation in carcinoma of cervix metastatic to para-aortic lymph nodes. Gynecol Oncol 2000; 79:399–405
73.
Belhocine T, Thille A, Fridman V, et al. Contribution of whole-body 18FDG PET imaging in the management of cervical cancer. Gynecol Oncol 2002; 87:90–97
74.
Haie-Meder C, Mazeron R, Magne N. Clinical evidence on PET-CT for radiation therapy planning in cervix and endometrial cancers. Radiother Oncol 2010; 96:351–355
75.
Narayan K, Hicks RJ, Jobling T, Bernshaw D, McKenzie AF. A comparison of MRI and PET scanning in surgically staged loco-regionally advanced cervical cancer: potential impact on treatment. Int J Gynecol Cancer 2001; 11:263–271
76.
Chao A, Ho K, Wang CC, et al. Positron emission tomography in evaluating the feasibility of curative intent in cervical cancer patients with limited distant lymph node metastases. Gynecol Oncol 2008; 110:172–178
77.
Lin LL, Mutic S, Low DA, et al. Adaptive brachy-therapy treatment planning for cervical cancer using FDG-PET. Int J Radiat Oncol Biol Phys 2007; 67:91–96
78.
Malyapa RS, Mutic S, Low DA, et al. Physiologic FDG-PET three-dimensional brachytherapy treatment planning for cervical cancer. Int J Radiat Oncol Biol Phys 2002; 54:1140–1146
79.
Grigsby PW, Siegel BA, Dehdashti F, Rader J, Zoberi I. Posttherapy [18F] fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: response and outcome. J Clin Oncol 2004; 22:2167–2171
80.
Schwarz JK, Siegel BA, Dehdashti F, Grigsby PW. Association of posttherapy positron emission tomography with tumor response and survival in cervical carcinoma. JAMA 2007; 298:2289–2295
81.
Heron CW, Husband JE, Williams MP, Dobbs HJ, Cosgrove DO. The value of CT in the diagnosis of recurrent carcinoma of the cervix. Clin Radiol 1988; 39:496–501
82.
Crivellaro C, Signorelli M, Guerra L, et al. 18F-FDG PET/CT can predict nodal metastases but not recurrence in early stage uterine cervical cancer. Gynecol Oncol 2012; 127:131–135
83.
Yilmaz M, Adli M, Celen Z, Zincirkeser S, Dirier A. FDG PET-CT in cervical cancer: relationship between primary tumor FDG uptake and metastatic potential. Nucl Med Commun 2010; 31:526–531
84.
Kidd EA, Grigsby PW. Intratumoral metabolic heterogeneity of cervical cancer. Clin Cancer Res 2008; 14:5236–5241
85.
Kidd EA, Siegel BA, Dehdashti F, et al. Lymph node staging by positron emission tomography in cervical cancer: relationship to prognosis. J Clin Oncol 2010; 28:2108–2113
86.
Yoo J, Choi JY, Moon SH, et al. Prognostic significance of volume-based metabolic parameters in uterine cervical cancer determined using 18F-fluorodeoxyglucose positron emission tomography. Int J Gynecol Cancer 2012; 22:1226–1233
87.
Sharma DN, Rath GK, Kumar R, et al. Positron emission tomography scan for predicting clinical outcome of patients with recurrent cervical carcinoma following radiation therapy. J Cancer Res rher 2012; 8:23–27
88.
Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 2007; 26:225–239
89.
Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 1996; 56:4509–4515
90.
Dehdashti F, Grigsby PW, Lewis JS, Laforest R, Siegel BA, Welch MJ. Assessing tumor hypoxia in cervical cancer by PET with 60Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone). J Nucl Med 2008; 49:201–205
91.
Lewis JS, Laforest R, Dehdashti F, Grigsby PW, Welch MJ, Siegel BA. An imaging comparison of 64Cu-ATSM and 60Cu-ATSM in cancer of the uterine cervix. J Nucl Med 2008; 49:1177–1182

Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: W192 - W205
PubMed: 23883234

History

Submitted: August 27, 2012
Accepted: January 22, 2013

Keywords

  1. cervical cancer
  2. hypoxia
  3. outcome
  4. PET/CT

Authors

Affiliations

Sahar Mirpour
Russell H. Morgan Department of Radiology and Radiologic Science, Johns Hopkins University, JHOC 3235, 601 N Caroline St, Baltimore MD 21287.
Joyce C. Mhlanga
Russell H. Morgan Department of Radiology and Radiologic Science, Johns Hopkins University, JHOC 3235, 601 N Caroline St, Baltimore MD 21287.
Prashanti Logeswaran
Department of Radiology, Boston University School of Medicine, Boston, MA.
Gregory Russo
Department of Radiation Oncology, Boston University School of Medicine, Boston, MA.
Gustavo Mercier
Department of Radiology, Boston University School of Medicine, Boston, MA.
Rathan M. Subramaniam
Russell H. Morgan Department of Radiology and Radiologic Science, Johns Hopkins University, JHOC 3235, 601 N Caroline St, Baltimore MD 21287.
Department of Radiology, Boston University School of Medicine, Boston, MA.

Notes

Address correspondence to R. M. Subramaniam ([email protected]).

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