FDG-PET/CT in Gynaecologic Cancers

Friday, August 31, 2012 Session 6, 9:00-9:30 FDG-PET/CT in Gynaecologic Cancers (Uterine) cervical cancer Endometrial cancer & Uterine sarcomas Ovarian cancer Little mermaid (Edvard Eriksen 1913) honoring Hans Christian Andersen.

Diagnosis and monitoring Guidelines (ESMO*) Clinical examination Routine biochemistry CA-125 (ovarian cancer) Ultrasound (US) Abdominal-pelvic MR or CT Surgical staging: standard approach to ovarian malignancies. FDG PET/CT has great potential in each step of gynaecologic malignancies assessment; staging, treatment monitoring and recurrence *European Society for Medical Oncology

Cervical cancer staging Positron emission tomography (PET) has been reported to have sensitivity and specificity of 100% and 99%, respectively. PET is still under evaluation

Cervical cancer primary lesion Diagnosis Local staging Literature is poor Predictive marker 287 patient staged from FIGO IA to IVB underwent pre-treatment 18F-FDG PET: SUVmax was a predictive biomarker of lymph node status at diagnosis persistent disease after treatment risk of pelvic recurrence distant metastasis overall survival SUVmax was better than patient- and tumourrelated factors Kidd EA et al. The standarsized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival. Cancer 2007

Cervical cancer nodal staging Retrospective, n=206 Locoregionally advanced cc % alive and relapse free Naravan et al International Journal of Gynaecological Cancer 2009 Conclusion: Nodal status on PET was the major predictor of outcome and was superior to FIGO staging Aim: Lymph node involvement provide incremental prognostic value compared with FIGO stage Staging Examination (anesthesia) MRI FDG-PET Prognostic factors clinical (age, FIGO, clinical diameter, histology) MRI (invasion, tumor volume) PET (lymph node metastasis) Outcome measures OOS, relapse free survival, time to failure, local failure, nodal failure, and distant failure.

Cervical cancer - pelvic & paraaortic LN status Important prognostic factor (survival rates) Alters individual treatment planning SUVmax is a predictive biomarker of lymph node status distant metastasis overall survival Paraaortic LN Pelvic LN 31 y female

Cervical cancer nodal staging Sironi S et al. 2006 N =47 patients (1081 nodes), Histopathologic cancer positive: 15 patients (18 nodes) Short axis diameter > 0.5 cm all 13 metastatic nodes Five missed nodes </= 0.5 cm (micrometastasis)

Cervical cancer nodal staging Histopathologic analysis: 15/47 cancer positive nodes FDG PET/CT FDG-positive = cancer positive TP = 11/15 FDG-negative = cancer negative TN = 31/32

Cervical cancer staging Please note, the pelvic and paraaortic lymph node status is not included in FIGO clinical staging.

Cervical cancer M-staging Hematogenous mets: Lung: 5-35% Bowel/liver: 30% Bone: 16% RESULTS: N = 200 PET was more sensitive than CT and was more specific than MR imaging

Cervical cancer M-staging Recurrent CCU (55 y female) Indication: Biopsy from bladder wall Has shown recurrence of CCU Treatment planning LN in mediastinum, paraaortal and in the pelvis Lesions in relation to liver Surface carcinosis

Cervical cancer treatment monitoring Summary For locally advanced cervical cancer, the current literature supports the use of 18F- FDG PET for assessing treatment response 3 mo after the completion of concurrent chemoradiation. 18F-FDG PET can provide reliable longterm prognostic information for these patients and, in the future, may be used to guide additional therapy. Investigational areas: monitoring response during radiotherapy and chemotherapy in the metastatic and neoadjuvant settings. Schwart JK et al. The role of 18F-FDG PET in Assessing Therapy Response in Cancer of the Cervix and Ovaries JNM 2009

Cervical cancer relapse Sironi et al 2007 25 92,9 100 Kitajima K et al 2008 25 92,0 92,6 Mittra E et al 2009 30 93,0 93,0 Yen TC et al 200455 65 Chung 2007 52 90,3 81,0 23,1 Conclusion: FDG PET/CT provides good anatomic and functional localization of suspicious lesions in CC patients.

Cervical cancer relapse The better diagnostic interpretation has an impact not only on clinical management and treatment planning of patients, but also on disease-free survival. Kaplan-Meir survival graph of 2-year disease-free survival rate of patients with negative PET/CT and positive PET/CT in 52 patients with suspected cervical cancer recurrence (Chung HH et al. Gynaec Oncol 2007)

Cervical cancer conclusions Not for T-stage Good for N- and M- stage Very good for relapse Potential role in treatment monitoring Potential role in radiptherapy planning 15

Ovarian cancer FIGO stage 75% dissiminated at diagnosis; 15% in stage IV 5-year survival: 75% (all stage I), 20-40% (stage III) < 10% stage IV 16

Ovarian cancer primary lesion Diagnostic work up Transvaginal ultrasound examinations CA-125 level in blood Menopausal status RMI Exploratory laparotomy is performed when the pelvic tumor is suspected to be malignant. It is still necessary to perform 8 9 benign ovarian cyst operations for the detection of one cancer patient 17 Co morbidity in the elderly

Ovarian cancer primary lesion 97 patients, RMI>150 (US, CA125, meopausal status) 57/57 TP (sensitivity = 100%) 37/40 TN (specificity 92.5%) 3 FP (fibroma ovarii, leiomyoma uteri, endometriosis) Conclusion: FDG-PET/CT is the image modality of choice when US shows a pelvic tumour, and additional information prior to surgery is needed. 18

Ovarian cancer staging Surgery could be postponed/cancelled in asymptomatic patients with a pelvic tumor suspected to be benign after PET/CT Especially in patients in poor performance status where the estimated risk of complications to surgery is high The patients need follow-up to make sure that a future malignant transformation in a benign tumor is detected. 19

Ovarian cancer treatment planning The clinical impact of imaging is limited to the ability to discover and localize peritoneal implants giving indications to the surgeons to perform a complete debulking and to identify other sites of metatstatic disease preventing surgery Advanced stage ovarian cancer Debulking surgery Systemic therapy The complete resection is related to the best survival rates. Post-operative residual tumor is one of the most important negative prognostic factors 20

Ovarian cancer staging 2010 Results: 89 MDCT 91 SDCT 48 FDG-PET/CT True positives MDCT: 81% SDCT: 72.5% FDG-PET/CT :77%. False negatives MDCT 19% SDCT 27.5% FDG-PET/CT 23% 21

Ovarian cancer staging PET/CT stage III FIGO III PET/CT stage IV 22

Ovarian cancer 23

Ovarian cancer 24

Ovarian cancer 25

Ovarian cancer treatment monitoring Clinical protocol Complete metabolic response after 3 series of neoadjuvant chemotherapy 26

Ovarian cancer treatment monitoring Clinical protocol Complete metabolic response of the ovarian cancer Questions High uptake in colon? Focal high uptake in the sigmoid 27

Ovarian cancer treatment monitoring Clinical protocol 28

Ovarian cancer - relapse The incidens of relapse 75% Highest the first 2 years after primary treatment 50% of the patients will die of their disease. Strict follow-up by gynaecologic examination and CA-125 serum level monitoring is the common practice to detect early relapse. 29

Ovarian cancer - relapse Results 34 studies (meta-analysis) CA 125 had the highest pooled specificity, 0.93 (95% CI: 0.89 0.95) PET CT had highest pooled sensitivity, 0.91 (95% CI: 0.88 0.94) Conclusion PET CT might be a useful supplement to current surveillance techniques, particularly for those patients with an increasing CA 125 level and negative CT or MR imaging. 30

Ovarian cancer relapse Normal conventional Work up Chung HH et al Role of 18FFDG PET/CT in the assessment of suspected recurrent ovarian cancer Eur J Nucl Mol Imaging 2007

Ovarian cancer conclusion FDG PET/CT can postpone/cancel surgery in asymptomatic patients with a pelvic tumor if it is FDG-negative provides an accurate depiction of the sites of abnormal disease helps to perform optimal primary cytoreductive surgery useful in follow-up (in patients an increasing CA 125 level) 32

Endometrial cancer Common cancer Generally good prognosis Advanced stage and relapse: poor outcome < 20% have positive lymph nodes at diagnosis The overall sensitivity of FDG-PET to detect lymph node metastasis is poor-moderate The specificity is high (100%)

Endometrial cancer - case Endometroiid cancer stage IIIb. Recurrence in vagina

Uterine sarcomas Rare cancer Poor prognosis Early metastatization Risk of distant spread Usually very FDG-avid Excellent in relapse Sensitivity: 92.9% Specificity:100% PPV: 100% NPV: 84% *Park JY et al. Role of OET or PET/CT in the post-therapy surveillance of uterine sarcoma. Gynecol Oncol 2008

Uterine sarcoma - case 23th January 20th March 9th July 59 y female Uterine leiomyosarcoma Trabectadin treatment