FDG-PET Evaluation of Carcinoma of the Cervix

doi:10.1016/S1095-0397(99)00008-4

Clinical Positron Imaging

Volume 2, Issue 2, March–April 1999, Pages 105-109

https://doi.org/10.1016/S1095-0397(99)00008-4 Get rights and content

Abstract

We performed fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) in 23 women with carcinoma of the uterine cervix to determine sites of metastatic disease. PET results were compared with those of computed tomography (CT) or lymphangiography. Increased FDG uptake was seen in the primary tumor in 10 of 11 patients with newly diagnosed disease. Additional sites of FDG uptake were identified in pelvic lymph nodes in 8, in extrapelvic lymph nodes in 5, and at distant metastatic sites in 3. In 12 patients with suspected recurrent disease, FDG uptake was present in 11; the presence of tumor was confirmed by CT in 10 and by biopsy in 9. For both patient groups, FDG-PET demonstrated more sites of tumor metastasis than did conventional imaging studies. Our results suggest that FDG-PET is a sensitive method for detecting regional and distant metastasis in patients with cervical carcinoma and has the potential to replace conventional imaging studies and allow more rational treatment planning.

Introduction

Carcinoma of the uterine cervix is the most common gynecologic neoplasm in the world. Its incidence is decreasing in developed countries but is increasing in underdeveloped countries. Women with early clinical stage disease may be treated with surgery or with radiotherapy. Those with advanced stage disease and those with known lymph node metastasis are treated with radiotherapy.

The diagnosis of cervical cancer is established by obtaining biopsies of the cervix. Clinical staging of carcinoma of the cervix is defined by the International Federation of Obstetrics and Gynecology (FIGO) Staging System¹ and includes a pelvic examination, a general history and physical examination, and selected imaging studies (chest radiography, excretory urography, and radiographic skeletal survey). These studies are not capable of evaluating lymph node status. Carcinoma of the cervix spreads by local extension within the pelvis and by lymphatic spread to the pelvic, para-aortic, and supraclavicular lymph nodes. Metastasis to lung, bone, brain, and liver may then occur. Lymph node status does not alter clinical staging but the presence of positive lymph nodes significantly alters therapy (i.e., radiotherapy versus surgery). The presence of distant metastasis may alter the intent of therapy (i.e., palliative versus curative).

Conventional imaging methods [lymphangiography, computed tomography (CT), and magnetic resonance imaging (MRI)] are utilized to determine lymph node status and sites of distant metastasis. There are major limitations to these studies, especially in the evaluation of lymph node metastasis.

Positron emission tomography with the glucose analogue 2-[¹⁸F] fluoro-2-deoxy-d-glucose (FDG) yields physiologic information that provides a means for diagnosing sites of metastatic cancer based on altered tissue metabolism. This imaging modality takes advantage of the principle that biochemical changes often precede or are more specific than the structural changes that are visualized by conventional imaging studies.

On the basis of the results of FDG-PET in pretreatment staging of a wide variety of malignant neoplasms, we have used this technique clinically in patients with newly diagnosed cervical cancer and in patients with suspected recurrent disease as an aid in planning additional diagnostic studies and treatment.² We have retrospectively assessed the performance of FDG-PET in this clinical setting and have compared the results of PET with those of CT and lymphangiography and with the pathologic findings (when available) in these patients.

Section snippets

Methods

We studied 23 patients with carcinoma of the uterine cervix by FDG-PET between January 1998 and May 1998; 11 of these were imaged as part of their pretreatment evaluation and 12 were imaged for evaluation of clinically suspected recurrent disease. The clinical stages of the 11 patients with newly diagnosed disease were as follows: Ia2 in one; Ib1 in one; Ib2 in four; IIb in one; IIIb in three; IVb in one. Histologic confirmation of the primary tumor was obtained in all patients with primary

Newly Diagnosed Cancer

Table 1 shows the clinical data, CT findings, LAG findings, and PET findings for 11 patients listed by increasing clinical stage, with newly diagnosed carcinoma of the uterine cervix.

Discussion

Carcinoma of the cervix metastasizes from the cervix in a predictable pattern. Tumor usually spreads from the primary cervical lesion to the pelvic lymph nodes, to the para-aortic lymph nodes, to the supraclavicular lymph nodes, and then to non-nodal metastatic sites such as lung, bone, and liver. Staging for carcinoma of the cervix is a clinically based system. The presence of lymph node metastasis does not alter the clinical stage but it is a significant finding that does alter the method of

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Cited by (63)

Accurate segmenting of cervical tumors in PET imaging based on similarity between adjacent slices
2018, Computers in Biology and Medicine
Because in PET imaging cervical tumors are close to the bladder with high capacity for the secreted ¹⁸FDG tracer, conventional intensity-based segmentation methods often misclassify the bladder as a tumor. Based on the observation that tumor position and area do not change dramatically from slice to slice, we propose a two-stage scheme that facilitates segmentation. In the first stage, we used a graph-cut based algorithm to obtain initial contouring of the tumor based on local similarity information between voxels; this was achieved through manual contouring of the cervical tumor on one slice. In the second stage, initial tumor contours were fine-tuned to more accurate segmentation by incorporating similarity information on tumor shape and position among adjacent slices, according to an intensity-spatial-distance map. Experimental results illustrate that the proposed two-stage algorithm provides a more effective approach to segmenting cervical tumors in 3D¹⁸FDG PET images than the benchmarks used for comparison.
FDG-PET-based prognostic nomograms for locally advanced cervical cancer
2012, Gynecologic Oncology
Citation Excerpt :
For this study, we aimed to create a PET-based prognostic model for cervical cancer. Recently, positron emission tomography (PET) with the glucose analogue F-18 fluorodeoxyglucose (FDG) has been shown to be a useful diagnostic tool in the evaluation of patients with cervical cancer, aiding in identifying the extent of the primary cervical tumor, lymph node involvement, and distant disease [6–9]. Additionally, FDG-PET has helped further define new prognostic factors for cervical cancer.
We previously found several individual FDG/PET-based prognostic factors for cervical cancer, specifically cervical tumor SUV_max, tumor volume, and highest level of lymph node (LN) involvement. For this study, we evaluate the combined use of these three prognostic factors assessed on pretreatment FDG-PET for predicting recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS).
The study included 234 cervical cancer patients, FIGO stage Ib1–IVa, treated with definitive radiation or chemoradiation therapy. All patients underwent FDG-PET or FDG-PET/CT at diagnosis, from which cervical tumor volume, SUV_max, and LN status were recorded. Using these PET-based factors, prognostic nomograms were created for RFS, DSS, and OS, and their prediction accuracies were measured using the concordance index (c-statistic).
Fifty-three percent of patients had FDG-avid LN on PET; the highest level of nodal involvement was pelvic in 84, para-aortic in 41, and supraclavicular in 10. The average cervix tumor SUV_max was 12.4 (range, 2.1–50.4) and PET tumor volume average was 66.4 cm³ (range, 3.0–535.7 cm³). The median follow-up was 40.7 months for patients alive at last follow-up. PET LN status had the greatest influence on outcome. The c-statistics for the 3 nomograms were 0.741 for RFS, 0.739 for DSS, and 0.658 for OS. The PET-based nomograms performed better than FIGO stage with c-statistics of 0.605, 0.600 and 0.559 for RFS, DSS and OS, respectively.
Pretreatment FDG-PET LN status, cervical tumor SUV_max, and tumor volume combined in a nomogram create good models for predicting cervical cancer RFS, DSS, and OS.
The role of FDG-PET/CT in cervical cancer: Diagnosis, staging, radiation treatment planning and follow-up
2010, PET Clinics
Citation Excerpt :
A prognostic value of SUVmax measurements has also been reported for other malignancies, such as lung and head and neck cancers.56–61 FDG-PET has a superior ability to detect regional and distant metastatic disease in patients with cervical cancer as compared with CT and MR imaging (Fig. 1).10,40,47,62–64 In a retrospective analysis of 59 subjects with Stage IA-IIA disease, Wright and colleagues65 reported that FDG-PET before definitive surgery had a sensitivity and specificity of 53% and 90% respectively for detection of metastases.
Clinical Outcomes of Definitive Intensity-Modulated Radiation Therapy With Fluorodeoxyglucose-Positron Emission Tomography Simulation in Patients With Locally Advanced Cervical Cancer
2010, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
Some have suggested cervical cancer is particularly difficult to treat with IMRT because IMRT requires specific target volume definition and cervical tumors are difficult to distinguish from surrounding tissue using computed tomography (CT) (15). Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has good sensitivity for detecting sites of disease in cervical cancer and, at our institution, we have significant experience in using FDG-PET to aid radiation treatment planning in patients with cervical cancer (16, 17). In addition, we have found, in a prospectively validated study, that treatment response in cervical cancer, as evaluated on the 3-month post-therapy FDG-PET, predicts overall survival (18).
This study aimed to evaluate the toxicity and clinical outcomes for cervical cancer patients treated definitively with intensity-modulated radiation therapy (IMRT) compared with non-IMRT treatment.
This prospective cohort study included 452 patients with newly diagnosed cervical cancer treated with curative intent (135 IMRT and 317 non-IMRT). Treatment involved external irradiation and brachytherapy, and 85% of patients received concurrent chemotherapy. All IMRT patients underwent an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) simulation. A 3-month post-therapy PET was obtained to evaluate treatment response. Toxicity was scored by the Common Terminology Criteria for Adverse Events Version 3.0.
The IMRT and non-IMRT groups had similar stage distribution and histology. For all patients, the post-therapy FDG-PET response correlated with overall recurrence risk (p < 0.0001) and cause-specific survival (p < 0.0001). Post-treatment FDG-PET findings were not significantly different between the IMRT and non-IMRT patients (p = 0.9774). The mean follow-up for all patients alive at the time of last follow-up was 52 months (72 months non-IMRT, 22 months IMRT). At last follow-up, 178 patients (39 IMRT, 139 non-IMRT) had developed a recurrence. The difference in recurrence-free survival between the two groups did not reach statistical significance (p = 0.0738), although the IMRT group showed better overall and cause-specific survivals (p < 0.0001). Of the patients, 62 patients (8 IMRT and 54 non-IMRT) developed Grade 3 or greater bowel or bladder complications, and by cumulative hazard function analysis the risk was significantly less for patients treated with IMRT (p = 0.0351).
Cervical cancer patients treated with FDG-PET/CT-guided IMRT have improved survival and less treatment-related toxicity compared with patients treated with non-IMRT radiotherapy.
Additional value of MR/PET fusion compared with PET/CT in the detection of lymph node metastases in cervical cancer patients
2009, European Journal of Cancer
We evaluated the additional diagnostic value of magnetic resonance/positron emission tomography (MR/PET) fusion in the detection of metastatic lymph nodes in cervical cancer patients.
Seventy nine patients with FIGO stage IB-IVA cervical cancer who had undergone both magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) before lymphadenectomy were included in this study. Image analysis was first performed with PET/CT images only. A second analysis was then performed with MR/PET fused images that focused on the additional information obtained from the MR images. Lymphadenectomy involved removing all visible lymph nodes in the surgical field. To enable nodal group-specific comparisons, para-aortic and pelvic lymph nodes were divided into seven nodal groups: para-aortic, both common iliac, both external iliac and both internal iliac/obturator areas. Histopathological evaluation of lymph nodes has been the diagnostic standard. The value of the additional information from the MR images was evaluated by means of receiver operating characteristic (ROC) analysis.
Fused MR/PET rendered readers to detect six more metastatic lymph node groups. The sensitivity and specificity of PET/CT and fused MR/PET were 44.1%, 93.9% and 54.2%, 92.7% respectively. The ROC analysis demonstrated a higher diagnostic performance of fused MR/PET compared to PET/CT alone for detecting lymph node metastases (p = 0.0259).
The findings of this study demonstrate the additional diagnostic value of fused MR/PET images compared with PET/CT in the detection of metastatic lymph nodes in patients with uterine cervical cancer.
The role of PET/CT in the management of patients with cervical cancer: Practice patterns of the members of the Society of Gynecologic Oncologists
2009, Gynecologic Oncology
Citation Excerpt :
PET uses the glucose analogue [18F]-fluoro-2-deoxy-d-glucose (FDG) and relies on increased metabolism of cancer cells and thus increased glucose uptake. Substantial evidence has now emerged documenting the important value of PET/CT in the management of cervical cancer patients, not only at the time of initial diagnosis, but also at post-treatment follow-up visits and for routine surveillance [4,6–12]. The use of PET/CT has been shown to detect recurrences in otherwise asymptomatic women, improve survival after recurrence, and provide important prognostic information for women post-therapy that may alter treatment plans [11,12,16,17].
Recent data has highlighted the role of PET/CT in the pretreatment evaluation and follow-up of patients with cervical cancer. The objective of our study was to assess the acceptance of PET/CT into the management of patients with cervical cancer. We also explored potential barriers to the use of these imaging modalities in patients with cervical cancer.
A 14-item electronic questionnaire was initially sent to all working addresses of members of the SGO (n = 1048). An opt-out option was offered. For members who did not respond within 3 weeks, a second electronic invitation was sent. A third request was finally sent to further improve response rates. Data were collected and analyzed using a commercially available on-line survey database.
A total of 305 responses were collected for an overall 30% response rate. PET/CT appears to be widely available (99%) and accessible (75%) in most practices. Although 83% of members order routine CT imaging for all newly diagnosed cervical cancer cases, only 28% routinely order a PET/CT. Conversely, 64% would order a PET/CT for newly diagnosed patients with advanced disease or those at high risk for distant metastatic disease. Most members (82%) do not routinely use PET/CT to assess response to treatment. Twenty percent of members believe that no useful prognostic information can be obtained from routine use of molecular imaging in patients with cervical cancer. The most common barriers for use of PET/CT cited by members were perceived lack of third-party payer coverage and lack of scientific evidence.
Despite clear scientific data supporting the use of PET/CT in patients with cervical cancer and apparent widespread availability, this imaging modality remains highly underutilized in clinical practice. Clarifying insurance coverage early in the evaluation process and replicating studies that have shown effectiveness of PET/CT in multiple roles may improve adoption of this potentially useful imaging modality.

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Original articleFDG-PET Evaluation of Carcinoma of the Cervix

Abstract

Introduction

Section snippets

Methods

Newly Diagnosed Cancer

Discussion

Gynecol. Oncol.

Lancet

Ann. Thorac. Surg.

Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose

Eur. J. Nucl. Med.

Utility of FDG-PET for investigating unexplained plasma CEA elevation in patients with colorectal cancer

Ann. Surg.

Local threshold for segmented attenuation correction of PET imaging of the thorax

IEEE Trans Nucl Sci

Original article
FDG-PET Evaluation of Carcinoma of the Cervix