|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 1999 American Society for Clinical Oncology Positron Emission Tomography for Evaluating Para-aortic Nodal Metastasis in Locally Advanced Cervical Cancer Before Surgical Staging: A Surgicopathologic StudyFrom the Division of Gynecologic Oncology, Department of Reproductive Biology, Ireland Cancer Center; Departments of Radiology and Department of Pathology, University Hospitals of Cleveland; and Case Western Reserve University, Cleveland, OH. Address reprint requests to Peter G. Rose, MD, Department of Obstetrics and Gynecology, University Hospitals of Cleveland, 11100 Euclid Ave, Cleveland, OH 44106.
PURPOSE: Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS: After 20 mCi of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS: Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION: Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.
CANCER OF THE CERVIX remains the second most frequent cancer in women worldwide.1 In patients with locally advanced disease (stages IIB to IVA), 24% have para-aortic nodal disease.2 In a collective series of Gynecologic Oncology Group protocols, para-aortic nodal status was the most significant indication of recurrence.3 Identification of para-aortic nodal status allows modification of radiation therapy fields to include this nodal disease, which, because of intestinal morbidity, is not routinely included in the treatment field by many radiation oncologists. Extended-field radiation therapy that includes the para-aortic nodes is associated with a 31% to 50% survival, depending on the location and extent of para-aortic nodal metastasis and the likelihood of controlling the pelvic disease.4-6 A number of noninvasive modalities have been used to evaluate the status of para-aortic nodal metastasis. Lymphangiography has been used extensively in this disease; however, it has a relatively high false-positive rate, which limits its specificity.7-9 The introduction of computed tomographic (CT) scanning in the mid-1970s provided an alternative method of para-aortic nodal disease evaluation, which could be confirmed by fine-needle biopsy.10 Feigen et al11 reported an improved specificity and accuracy with only a minimal decrease in sensitivity favoring CT scanning over lymphangiography for the evaluation of pelvic nodal metastasis in early-stage cervical carcinoma (stages IB and IIA). A recent Gynecologic Oncology Group study involving 264 patients found the sensitivity of the CT scan for identifying para-aortic nodal metastasis to be only 34%.2 Identification of sensitive and specific imaging modalities would be a useful adjunct in this disease, because it could affect selection of radiation treatment fields. Positron emission tomographic (PET) imaging, once considered a research tool, has been gaining acceptance in a wide area of clinical settings. The role of PET imaging is defined, in part, by the radiopharmaceuticals used. One of these, 2-[18F]fluoro-2-deoxy-D-glucose (FDG), is useful in oncology, because of the high glycolytic rate of many tumors, as first described by Warburg.12 Its value has been demonstrated in a wide variety of solid cancers, including colorectal, lung, breast, and head and neck cancer, among others.13-17 We have previously reported the use of PET scanning to determine locoregional metastasis in cancer of the breast.18 The role of PET scanning in determining metastatic disease in cervical cancer has not previously been evaluated. Para-aortic lymphadenectomy, which, at our center, is offered to patients with locally advanced cervical cancer and no evidence of extrapelvic metastasis, provides an excellent opportunity to compare PET imaging and surgicopathologic findings in a CT scan-negative population. In the current study, we evaluated the utility of PET scanning in evaluating para-aortic nodal disease status before surgical staging lymphadenectomy.
From May 13, 1994, to April 6, 1998, patients with primary, previously untreated, histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, stages IIB to IVA, and no evidence of extrapelvic disease by CT scanning of the abdomen and pelvis and chest x-ray, were studied. Additionally, patients had to be at least 18 years of age and medically stable to undergo a surgical para-aortic staging lymphadenectomy. Patients who were pregnant or lactating were excluded; in addition, patients whose body weight exceeded 350 pounds were excluded because of weight limitations of the scanner table. All patients signed an informed consent form approved by the investigational review board at University Hospitals of Cleveland. Positron emission tomographic scanning was performed with a Siemens ECAT EXACT whole-body PET system. It is a three-ring system with a 16.2 field of view. Its axial resolution is 5.4 mm full-width half-maximal height at 0 cm and 6.3 mm full-width half-maximal height at 10 cm. After patients underwent 4-hour fast and a baseline scan, 20 mCi of FDG, previously checked for radiochemical purity (> 90%), sterility, and pyrogenicity, was administered intravenously. After a 60-minute delay, scanning of the entire abdomen and pelvis, including the domes of the diaphragms, was performed. To avoid artifacts due to urinary tract activity, a triple-lumen Foley catheter was placed in the bladder for continuous irrigation and drainage before imaging of the pelvis, as previously described.19 Additionally, patients received intravenous hydration and furosemide. Images were reconstructed both with and without attenuation correction in three orthogonal planes. Para-aortic lymphadenectomy with removal of lymph nodes from the mid common iliac artery to at least the inferior mesenteric artery bilaterally was performed by either a paramedian or midline approach, as previously described.20,21 Pelvic nodal dissection was routinely performed if nodes seemed suspicious, to increase pelvic control22 or at the discretion of the surgeon. Patients were classified by the presence or absence of para-aortic nodal metastasis. Patients who also underwent pelvic lymphadenectomy were evaluated for the presence of iliac metastasis by PET scanning, CT findings, and pathology. Statistical analysis was performed using Epi-Info 6 software (Centers for Disease Control and Prevention, Atlanta, GA, 1995). Two-tailed P values are reported.
Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Twenty-four tumors were squamous, and eight were nonsquamous (adenocarcinoma [n = 5] or adenosquamous [n = 3]). Overall, FDG uptake was present in 91% of cervical tumors. Fluorodeoxyglucose uptake was seen in both stage IVA patients, 92% of IIIB patients, and 83% of stage IIB patients. Uptake of FDG was seen in 87.5% of squamous tumors and all eight nonsquamous tumors.
Retroperitoneal lymphadenectomy was performed a median of 3 days (range, 0 to 10 days) after the PET scan. The PET and histopathologic findings are listed in Tables 1
Among 17 patients who underwent pelvic node resection, all 11 patients with metastasis were predicted by PET scanning (P < .0001). Five of the patients with pelvic node metastasis had abnormalities on the CT scan. However, in only two of the five was adenopathy definitively diagnosed, and in three it was suggested but could not be differentiated from adnexal enlargement or primary cervical tumor extension. In the pelvis, there were no false-positives or false-negatives, resulting in 100% sensitivity, specificity, and negative and positive predictive values. No adverse effects from the PET scan were noted.
Positron emission tomography is a functional test of the glycolytic activity of the tumor and the relative deficiency of glucose-6-phosphatase in tumor cells.12 It has been widely studied in solid tumors but has not previously been studied in cervical cancer. Our objective was to determine the sensitivity, specificity, and positive and negative predictive values of PET imaging for para-aortic nodal metastasis in a population of locally advanced cervical cancer patients with no evidence of extrapelvic metastasis. Secondary objectives were to determine the frequency of FDG uptake in cervical cancer and the sensitivity, specificity, and predictive values of PET scanning for pelvic nodal metastasis and to compare these findings with CT scanning results. Cervical cancers of both squamous and nonsquamous histologies were avid for FDG, and PET-FDG scanning predicted both the presence and absence of pelvic and para-aortic nodal metastatic disease. Previous studies have demonstrated uptake in both squamous and nonsquamous histologies at other sites, including the head, neck, and lung.16,17 One of the limitations of PET scanning of the pelvis with FDG is excreted FDG activity in the urine.23 However, the use of continuous bladder irrigation and vigorous hydration overcomes this problem.19 In our study, uptake of FDG in the para-aortic region was associated with a relative risk of 9.0 for para-aortic nodal metastasis. In the pelvic nodes, PET-FDG scanning had a sensitivity, specificity, and predictive value of 100%. The lack of FDG uptake was highly specific for the absence of nodal metastasis. Such a finding suggests that surgical staging in patients with FDG-avid primary tumors and absence of nodal uptake could be avoided. A similar study in 52 breast cancer patients reported only one false-negative scan.18 The sensitivity of PET-FDG scanning for metastasis was greater than that of CT scanning in both the para-aortic and pelvic nodes. The study design was to evaluate para-aortic nodal surgical findings in patients without CT scan evidence of para-aortic metastatic disease. The positive predictive value for para-aortic metastasis, 75%, is remarkably high considering that lesions identifiable by abnormalities on the CT scan were excluded. In the pelvic nodes, PET-FDG scanning was twice as sensitive as CT scanning for abnormalities. Only two of the 10 patients with pelvic nodes were definitely diagnosed on CT scans. The use of PET-FDG scanning complemented CT scanning by correctly identifying the remaining three nondiagnostic CT scan findings. The complementary use of PET-FDG scanning and imaging modalities in breast cancer has previously been reported.14,24 The sensitivity of PET-FDG scanning for nodal metastasis in the pelvic nodes was greater than in the para-aortic nodes. This is finding was expected, because of the known pattern of metastasis in advanced cervical cancer. First, there is an approximately two-fold higher frequency of pelvic node metastasis than para-aortic node metastasis.25 Second, metastases in the pelvic nodes are larger in size than in the para-aortic region. In conclusion, PET-FDG scanning of cervical cancers was well tolerated and demonstrated a high avidity for FDG. In FDG-avid cervical cancers, PET-FDG scanning can accurately predict both the presence and absence of pelvic and para-aortic nodal metastatic disease. Further study of PET-FDG scanning of advanced cervical cancers is warranted.
1. Parkin DM, Laara E, Muir CS: Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer 41:184-197, 1988[Medline] 2. Heller PB, Malfetano JH, Bundy BN, et al: Clinical-pathologic study of stage IIB, III, and IVA carcinoma of the cervix: Extended diagnostic evaluation for paraaortic node metastasis—A Gynecologic Oncology Group study. Gynecol Oncol 38:425-430, 1990[Medline] 3. Stehman FB, Bundy BN, DiSaia PJ, et al: Carcinoma of the cervix treated with radiation therapy: I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 67:2776-2785, 1991[Medline] 4. Podczaski E, Stryker JA, Kaminski P, et al: Extended-field radiation therapy for carcinoma of the cervix. Cancer 66:251-258, 1990[Medline] 5. Vigliotti AP, Wen BC, Hussey DH, et al: Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes. Int J Radiat Oncol Biol Phys 23:501-509, 1992[Medline] 6. Rubin SC, Brookland R, Mikuta JJ, et al: Para-aortic nodal metastases in early cervical carcinoma: Long-term survival following extended-field radiotherapy. Gynecol Oncol 18:213-217, 1984[Medline] 7. Piver MS, Barlow JJ: Para-aortic lymphadenectomy, aortic node biopsy, and aortic lymphangiography in staging patients with advanced cervical cancer. Cancer 32:367-370, 1973[Medline] 8. Brown C, Buchsbaum HJ, Tewfik HH, et al: Accuracy of lymphangiography in the diagnosis of paraaortic lymph node metastases from carcinoma of the cervix. Obstet Gynecol 54:571-575, 1979[Medline] 9. Pendlebury SC, Cahill S, Crandon AJ, et al: Role of bipedal lymphangiogram in radiation treatment planning for cervix cancer. Int J Radiat Oncol Biol Phys 27:959-962, 1993[Medline] 10. Bandy LC, Clarke-Pearson DL Silverman PM, et al: Computed tomography in evaluation of extrapelvic lymphadenopathy in carcinoma of the cervix. Obstet Gynecol 65:73-76, 1985[Medline] 11. Feigen M, Crocker EF, Read J, et al: The value of lymphoscintigraphy, lymphangiography and computer tomography scanning in the preoperative assessment of lymph nodes involved by pelvic malignant conditions. Surg Gynecol Obstet 165:107-110, 1987[Medline]
12.
Warburg O: On the origin of cancer cells. Science 123:309-314, 1956
13.
Strauss LG, Conti PS: The applications of PET in clinical oncology. J Nucl Med 32:623-648, 1991 14. Crowe JP, Adler LP, Shenk RR, et al: Positron emission tomography and breast masses: Comparison with clinical, mammographic, and pathologic findings. Ann Surg Oncol 1:132-140, 1994[Medline]
15.
Avril N, Dose J, Janicke F, et al: Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose. J Clin Oncol 14:1848-1857, 1996 16. Bailet JW, Abemayor E, Jabour BA, et al: Positron emission tomography: A new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy. Laryngoscope 102:281-288, 1992[Medline]
17.
Knight SB, Delbeke D, Stewart JR, et al: Evaluation of pulmonary lesions with FDG-PET: Comparison of findings in patients with and without a history of prior malignancy. Chest 109:982-988, 1996
18.
Adler LP, Faulhaber PF, Schnur KC, et al: Axillary lymph node metastases: Screening with [F-18]2-deoxy-2-fluoro-D-glucose (FDG) PET. Radiology 203:323-327, 1997 19. Leisure GP, Vesselle HJ, Faulhaber PF, et al: Technical improvements in fluorine-18-FDG PET imaging of the abdomen and pelvis. J Nucl Med Technol 25:115-119, 1997[Abstract] 20. Berman ML, Lagasse LD, Watring WG, et al: The operative evaluation of patients with cervical carcinoma by an extraperitoneal approach. Obstet Gynecol 50:658-664, 1977[Medline] 21. Gallup DG, Jordan GH, Talledo OE: Extraperitoneal lymph node dissections with use of a midline incision in patients with female genital cancer. Am J Obstet Gynecol 155:559-564, 1986[Medline] 22. Cosin JA, Fowler JM, Chen MD, et al: Pretreatment surgical staging of patients with cervical carcinoma: The case for lymph node debulking. Cancer 82:2241-2248, 1998[Medline] 23. Kosuda S, Kison PV, Greenough R, et al: Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer. Eur J Nucl Med 24:615-620, 1997[Medline]
24.
Inokuma T, Tamaki N, Torizuka T, et al. Evaluation of pancreatic tumors with positron emission tomography and F-18 fluorodeoxyglucose: Comparison with CT and US. Radiology 195:345-352, 1995 25. Shingleton HM, Orr JW. Cancer of the Cervix. Philadelphia, PA, Lippincott, 1995, pp 111-112 Submitted June 17, 1998; accepted September 18, 1998.
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
