Role of PET/CT in Ovarian Cancer

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1 Residents Section Structured Review rticle Prakash et al. PET/T in Ovarian ancer Residents Section Structured Review rticle Downloaded from by on 04/26/18 from IP address opyright RRS. For personal use only; all rights reserved Priyanka Prakash 1 armel G. ronin Michael. lake Prakash P, ronin G, lake M Keywords: ovarian cancer, PET/T DOI: /JR Received October 18, 2009; accepted after revision November 18, ll authors: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., oston, M ddress correspondence to M.. lake (mblake2@partners.org). WE This is a Web exclusive article. JR 2010; 194:W464 W X/10/1946 W464 merican Roentgen Ray Society Role of PET/T in Ovarian ancer OJETIVE. The purpose of this article is to review the role of FDG PET/T in ovarian cancer, which is the leading cause of death among gynecologic cancers. onclusion. FDG PET/T can significantly modify the assessment of the extent of primary and recurrent ovarian cancer and, hence, often alters patient management substantially. FDG PET/T has thus become a critical tool for the preoperative evaluation of women with primary ovarian cancer and for postoperative follow-up assessment for evidence of recurrence in these patients. mong gynecologic cancers, ovarian cancer is the leading cause of death. ccording to the estimates by the merican ancer Society, ovarian cancer accounted for 3% of new cases of female malignancies and 5% of cancer-related deaths in 2009 in the United States [1]. Imaging, especially ultrasound and T, has become a critical part of the evaluation of patients with ovarian cancer. s for many other malignancies, the role of FDG PET and PET/T is being extensively studied for the evaluation of ovarian malignancy. In this article, we review the role of FDG PET/T in ovarian cancer. Imaging Technique t our institution, PET/T examinations are performed on an integrated PET/ T scanner that includes an MDT and a PET system with 3D lutetium oxyorthosilicate crystals. Patients are instructed to fast for a minimum of 4 hours before scanning, and blood glucose should be < 200 mg/dl before the injection of FDG. fter attaining the desired blood sugar levels, FDG is administered within the dose range of mi ( Mq), according to patient weight. pproximately an hour after administration of the tracer, attenuation correction T is initially performed from the skull base to mid-thigh. This T is used for mainly anatomic localization of FDG and attenuation correction purposes. Immediately after the T, PET images are acquired in 2D mode over the same anatomic region start- ing from midthigh. The attenuation correction T images are then fused with PET, and fused PET/T is used for visual interpretation and tumor volume measurements. In addition, a diagnostic neck, chest, and abdominal T examination with IV administration of 120 ml of iodinated contrast medium (iopamidol 370 mg [Iopamiro, racco Diagnostics]) is also performed. The attenuation correction T parameters for a 16-MDT are as follows: 0.5 seconds per gantry rotation time, detector configuration of mm, 10-mm slice thickness, 40 m, and 120 kvp. The corresponding imaging parameters for diagnostic T examination on the 16-MDT are 120 kvp, 200 reference ms (an imaging quality parameter for applying automatic exposure control technique [RE Dose 4D, Siemens Healthcare]), detector configuration of mm, gantry rotation time of 0.5 second, 2.5-mm slice thickness at 2.5- mm slice interval, and a pitch of 1.2. For 64- MDT, the attenuation correction T parameters are 120 kvp, m, 1.5 pitch, 0.5 second per gantry rotation time, detector configuration of mm, and 10-mm slice thickness. The diagnostic 64-MDT is performed at 120 kvp, 200 ms, 0.75 pitch, 0.5 second per gantry rotation time, detector configuration of mm, and 2.5-mm slice thickness. Imaging Features Physiologic versus pathologic uptake In premenopausal women, the amount of FDG uptake in the ovaries varies with the W464 JR:194, June 2010

2 PET/T in Ovarian ancer Downloaded from by on 04/26/18 from IP address opyright RRS. For personal use only; all rights reserved phase of menstrual cycle, with physiologic uptake particularly present in the early luteal phase (Fig. 1). This can be avoided by performing the scan just subsequent to menstruation. Moreover, the typical appearance of physiologic uptake in the ovary is spherical or discoid with smooth margins and is located above the urinary bladder or around the uterus, which can be used to distinguish it from pathologic changes. In addition, the characteristic T appearance of a small rimenhancing cyst, the absence of any lymph nodes, and concordance with the appropriate stage of menstrual cycle are also helpful E D Fig year-old-woman with ovarian cancer. and, Transverse PET/T () and PET () images show presence of physiologic PET activity in right ovary. and D, Similar findings can be seen in coronal PET/ T () and PET (D) images. E, orresponding axial T image shows corpus luteum cyst (arrow) in corresponding ovary. in recognizing the benign nature of the uptake [2]. In postmenopausal ovaries, however, any ovarian uptake is pathologic, whether benign or malignant. enign versus malignant lesions few studies have evaluated the role of PET for early diagnosis of ovarian cancer but have reported a low sensitivity (58%) and specificity (76%) [3]. However, with the advent of PET/T, the anatomic and metabolic data can be acquired in the same setting and provide precise localization of suspicious areas of increased FDG uptake and help with the assessment of incidental ovarian findings. Ovarian lesions will show variable increase in FDG uptake on PET/T. In a study by astellucci et al. [4], a focally increased standardized uptake value (SUV) of 3 or higher in the ovary was considered positive for ovarian malignancy, whereas an SUV of 2.7 or lower was considered benign. Moreover, differentiation between benign and malignant uptake on PET can be aided by the contemporaneously acquired T scan on the basis of the characteristic pattern and location of FDG uptake and the lack of discrete lymph nodes in patients with benign lesions. That study reported a sensitivity of 87% and specificity of 100% for differentiating benign from malignant ovarian cancer using these criteria [4]. lso, three of four falsenegative PET/T scans in this study had primary tumors measuring 5 mm. In another study, PET/T was found to have a sensitivity of 80% and specificity of 97% for the diagnosis of malignancy in the contralateral ovary in patients with primary ovarian cancer [5]. Thus, although PET/T has a high specificity for lesions greater than 5 mm in size, its sensitivity is much lower than that of sonography. Hence, PET/T has not replaced sonography for the screening of ovarian cancer. However, because of its high specificity, FDG PET/T may be used to confirm the diagnosis and assess for metastases before the patient undergoes surgical evaluation. Staging of Ovarian ancer Ovarian cancer is staged surgically according to the International Federation of Gynecol- JR:194, June 2010 W465

3 Prakash et al. Downloaded from by on 04/26/18 from IP address opyright RRS. For personal use only; all rights reserved TLE 1: International Federation of Obstetric Gynecology (FIGO) and TNM Staging Systems for Ovarian ancer Tumor Type, TNM ategory FIGO Stage Description Primary tumor (T) TX T0 Primary tumor cannot be assessed No evidence of primary tumor T1 I Tumor limited to ovaries (one or both) T1a I Tumor limited to one ovary; capsule intact, no tumor on ovarian surface; no malignant cells in ascites or peritoneal washing T1b I Tumor limited to both ovaries T1c I Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings T2 II Tumor involves one or both ovaries with pelvic extension or implants T2a II Extension or implants on uterus or tube(s); no malignant cells in ascites or peritoneal washings T2b II Extension to or implants on other pelvic tissues; no malignant cells in ascites or peritoneal washings T2c II Pelvic extension or implants (T2a or T2b) with malignant cells in ascites or peritoneal washings T3 III Tumor involves one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvis T3a III Microscopic peritoneal metastasis beyond pelvis (no macroscopic tumor) T3b III Macroscopic peritoneal metastasis beyond pelvis 2 cm in greatest dimension T3c III Peritoneal metastasis beyond pelvis > 2 cm in greatest dimension or regional lymph node metastasis Regional lymph nodes (N) NX N0 Regional lymph nodes cannot be assessed No regional lymph node metastasis N1 III Regional lymph node metastasis Distant metastasis (M) MX M0 Distant metastasis cannot be assessed No distant metastasis M1 IV Distant metastasis (excludes peritoneal metastasis) TLE 2: Summary of TNM and International Federation of Obstetrics Gynecology Staging of Ovarian ancer Stage Grouping Primary Tumor Stage (T) Regional Lymph Node Stage (N) Distant Metastasis Stage (M) I T1 N0 M0 I T1a N0 M0 I T1b N0 M0 I T1c N0 M0 II T2 N0 M0 II T2a N0 M0 II T2b N0 M0 II T2c N0 M0 III T3 N0 M0 III T3a N0 M0 III T3b N0 M0 III T3c N0 M0 ny T N1 M0 IV ny T ny N M1 ogy and Obstetrics TNM staging [6] (Tables 1 and 2). T has been the imaging technique of choice in the primary staging of women with ovarian cancer preoperatively. Recent studies have shown that FDG PET, when used in conjugation with T, is useful in evaluating distant metastases as well as equivocal lesions [4, 5]. PET/T had high sensitivity in identifying peritoneal deposits larger than 1 cm and lymph nodes larger than 7 mm. It has been shown to increase the pretreatment staging accuracy to 69 75% compared with 53 55% with T alone (Figs. 2 and 3) [4]. lthough both of these studies show definite evidence of improved accuracy in staging with the use of PET/T, they also suggest that PET/T is particularly useful in distinguishing patients with stages III IV cancer from those with stages I III cancer. For this classification, the specificity, sensitivity, and accuracy of FDG PET/T was 91%, 100%, and 98%, respectively, in comparison with 64%, 97%, and 88% for T [5]. Thus, PET/T can help W466 JR:194, June 2010

4 PET/T in Ovarian ancer Downloaded from by on 04/26/18 from IP address opyright RRS. For personal use only; all rights reserved in identifying the clinically important group of patients for whom optimal debulking is not possible and who thus need to undergo preoperative chemotherapy. Posttreatment follow-up The survival of patients after treatment has increased significantly as a result of advances in the surgical and chemotherapy drugs. However, this lengthened survival has simultaneously increased the incidence of recurrence, and it has been reported that 75% of patients with ovarian cancer have a likelihood of disease relapse [7]. Early diagnosis of recurrence and exact anatomic localization of metastatic disease are crucial for Fig year-old woman with primary ovarian cancer. and, Transverse PET/T images show abnormal FDG uptake in pelvis corresponding to areas of malignancy., orresponding T image depicts soft-tissue masses (arrow) in areas of FDG uptake and ascites (asterisk) also present. Fig year-old woman (same patient as in Fig. 2) with primary ovarian malignancy. and, Transverse PET/T images show marked FDG uptake in peritoneal soft tissue, indicating presence of peritoneal carcinomatosis along with malignant ascites., orresponding axial T image shows presence of both ascites and peritoneal carcinomatosis (arrow). determination of the best treatment strategy. Even though the -125 tumor marker has high sensitivity for early diagnosis of recurrence in epithelial ovarian cancer; it does not give any information about the extent or location of recurrence. Moreover, it has a poor negative predictive value [8]. T has been the standard imaging technique for evaluation of suspected recurrence of ovarian cancer. ccuracy of T however, has varied from 38% to 88% in the published literature [9]. Recently, PET/T has been extensively studied and has been shown to add confidence and accuracy to the diagnosis (Figs. 4, 5, and 6). The patient-based sensitivity, specificity, and accuracy of PET/T have ranged from 53% to 97%, 80% to 97%, and 68% to 92%, respectively [9 11]. Sironi et al. [9] have reported the lowest sensitivity of 53%. However, all the lesions missed on PET/T in that study were < 5 mm in size, which is below the resolution of PET/T and indeed essentially any other currently available imaging technique. In addition, PET/T has a high positive predictive value of 89% 98% for recurrence of ovarian cancer. Iagaru et al. [12] classified the lesions of recurrent ovarian malignancy into pelvic and extrapelvic lesions and found that PET/T is much more sensitive for extrapelvic lesions than for pelvic lesions. This is true, in part, because the physiologic uptake in the bladder obscures the pathologic uptake in the JR:194, June 2010 W467

5 Prakash et al. Downloaded from by on 04/26/18 from IP address opyright RRS. For personal use only; all rights reserved Fig year-old woman with primary ovarian cancer. and, oronal PET/T images depict mm FDG-avid soft-tissue mass in liver, which is consistent with metastasis., orresponding coronal T image shows presence of metastatic lesion in liver (arrow). D E Fig year-old woman with primary ovarian cancer., Transverse PET/T image in soft-tissue window shows presence of intensely avid soft-tissue nodule in right hemipelvis adjacent to right ureter, representing recurrent ovarian cancer., Same image on bone windows shows presence of intense uptake in right paraspinal region secondary to inflammatory changes following laminectomy., Image shows false-positive uptake, which might be misinterpreted as metastasis and thus could be pitfall of PET alone without T for clarification. D, orresponding axial T image in softtissue window shows presence of nodule in retroperitoneum (arrow). E, xial T image on bone window shows presence of postsurgical changes in vertebra (asterisk) associated with false-positive FDG uptake. pelvis. lso, the postsurgical inflammatory changes in the pelvis can lead to false-positive areas of uptake on PET/T. PET/T not only helps in diagnosing recurrence but also affects subsequent management. With its ability to precisely localize the lesion as well as the extent of recurrence and distant metastases, PET/T plays an important role in restaging for recurrent ovarian cancer. Fagotti et al. [13] studied the ability of PET/T to predict the possibility of optimal cytoreduction in recurrent ovarian cancer and reported an accuracy of 79%, sensitivity of 93%, specificity of 56%, positive predictive value of 77%, and negative predictive value of 83% and, hence, good efficacy of PET/T in planning surgical treatment of patients with recurrent W468 JR:194, June 2010

6 PET/T in Ovarian ancer Downloaded from by on 04/26/18 from IP address opyright RRS. For personal use only; all rights reserved ovarian cancer. PET/T was found to be comparable to staging laparoscopy for this purpose. gain, the false-negative results on PET/T in that study were small peritoneal implants < 7 mm in size. Mangili et al. [14] not only reported a much higher sensitivity of PET/T (91%) in comparison with contrast-enhanced T (62%) alone for diagnosis of recurrent ovarian cancer, they also showed that the result on PET/T changes the treatment technique for 44% of the patients. In another similar study, findings on PET/T were found to significantly change the management of recurrent ovarian cancer in 57% of the patients [15]. Fig year-old woman with history of ovarian cancer undergoing imaging for follow-up. and, Transverse PET/T images show presence of multiple soft-tissue nodules in mid pelvis with increased FDG uptake consistent with recurrence of patient s known ovarian cancer., orresponding axial T image shows presence of nodules in pelvis corresponding to areas of FDG uptake (arrow). Fig year-old-woman (same patient as in Fig. 6) with history of ovarian cancer undergoing imaging for follow-up. and, Transverse PET/T images show presence of increased FDG uptake along anterior abdominal wall corresponding to ill-defined soft-tissue density at site of previous surgery (note presence of surgical clips). ecause previous surgery in this patient was 2 years earlier, new uptake was consistent with recurrence of patient s known ovarian cancer., orresponding axial T image shows presence of soft tissue adjacent to surgical clips (arrow). dvantages of the imaging technique FDG PET/T has high positive predictive value and accuracy for diagnosing primary as well as recurrent ovarian cancer. Moreover, it helps significantly in planning the treatment of patients in both categories. Pitfalls or limitations of the imaging technique FDG PET/T is limited in its ability to identify lesions < 1 cm, in particular, those smaller than 5 mm, leading to a false-negative rate of 5% 10%. Moreover, in the abdomen and pelvis, a large number of misregistrations can occur as a result of the physiologic uptake in bowel and bladder and as a result of bowel peristalsis; knowledge of these issues and careful review are required for accurate interpretation. Similarly, in recurrent ovarian cancer, PET/T is somewhat limited in its ability to distinguish postoperative inflammatory changes from tumor recurrence or persistence (Fig. 5b), but correlation with the T findings and the patient s history and examination helps to determine the significance and thus guide management. onclusion FDG PET/T can significantly modify the assessment of the extent of primary and recurrent ovarian cancer and, hence, often alters patient management substantially. FDG PET/T has thus become a critical tool for the preoperative evaluation of women with primary ovarian cancer and for postoperative follow-up assessment for evidence of recurrence in these patients (Fig. 7). References 1. Jemal, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. ancer statistics, ancer J lin 2009; 59: Liu Y. enign ovarian and endometrial uptake on FDG PET-T: patterns and pitfalls. nn Nucl JR:194, June 2010 W469

7 Prakash et al. Med 2009; 23: : Sebastian S, Lee SI, Horowitz NS, et al. PET-T 3. Fenchel S, Grab D, Nuessle K. symptomatic ad- 7. Greenlee RT, Hill Harmon M, Murray T, Thun vs T alone in ovarian cancer recurrence. bdom Downloaded from by on 04/26/18 from IP address opyright RRS. For personal use only; all rights reserved nexal masses: correlation of FDG PET and histopathologic findings. Radiology 2002; 223: astellucci P, Perrone M, Picchio M. Diagnostic accuracy of 18 F-FDG PET/T in characterizing ovarian lesions and staging ovarian cancer: correlation with transvaginal ultrasonography, computed tomography, and histology. Nucl Med ommun 2007; 28: Kitajima K, Murakami K, Yamasaki E. Diagnostic accuracy of integrated FDG-PET/contrast-enhanced T in staging ovarian cancer: comparison with enhanced T. Eur J Nucl Med Mol Imaging 2008; 35: Mironov S, kin O, Pandit-Taskar N, Hann LE. Ovarian cancer. Radiol lin North m 2007; M. ancer statistics, ancer J lin 2001; 51: Rustin GJ, Nelstrop E, Tuxen MK, Lambert HE. Defining progression of ovarian carcinoma during follow-up according to 125: a North Thames Ovary Group study. nn Oncol 1996; 7: Sironi S, Messa, Mangili G, et al. Integrated FDG PET/T in patients with persistent ovarian cancer: correlation with histological findings. Radiology 2004; 233: hung HH, Kang WJ, Kim JW, et al. Role of [ 18 F] FDG PET/T in the assessment of suspected recurrent ovarian cancer: correlation with clinical or histological findings. Eur J Nucl Med Mol Imaging 2007; 34: Imaging 2008; 33: Iagaru H, Mittra ES, McDougall IR, et al. 18 F-FDG PET/T evaluation of patients with ovarian carcinoma. Nucl Med ommun 2008; 29: Fagotti, Fanfani F, Rositto, et al. treatment selection protocol for recurrent ovarian cancer patients: the role of FDG-PET/T and staging laparoscopy. Oncology 2008; 75: Mangili G, Picchio M, Sironi S. Integrated PET/ T as a first-line re-staging modality in patients with suspected recurrence of ovarian cancer. Eur J Nucl Med Mol Imaging 2007; 34: Simcock, Neesham D, Quinn M. The impact of PET/T in the management of recurrent ovarian cancer. Gynecol Oncol 2006; 103: W470 JR:194, June 2010