PET/CT for the evaluation of gynecological
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1 PET/CT for the evaluation of gynecological cancer Gynecological cancer Barcelona, September 16 th 2018 Dr. Pilar Paredes, MD, PhD Nuclear Medicine Department Hospital Clínic Barcelona (Spain)
2 PET/CT in gynecological cancer Radiotracers and metabolic activity Indications Vulvar cancer Cervical cancer Endometrial cancer Ovarian cancer What s new?
3 Positron emission tracers PET/CT for the evaluation of gynecological cancer PET TRACER LIGAND MoA 18 F-FDG FLUORODEOXYGLUCOSE GLUCOSE METABOLISM 18 F FLUORIDE ION BONE METABOLISM 18 F-MISO FLUOROMISONIDAZOL HYPOXIA 18 F-FES ESTRADIOL ESTROGEN RECEPTORS
4 Metabolic activity and quantification Whole body scan (WB) Visual analysis Quantification SUV (Standardized Uptake Value) FDG dose Weight/height Maximum/minimum/mean MTV: metabolic tumoral volume TLG: total lesion glycolysis
5 PET/CT PET/CT for the evaluation of gynecological cancer
6 Vulvar cancer PET/CT
7 PET/CT in vulvar cancer PET/CT for the evaluation of gynecological cancer The most common histology is SQUAMOUS carcinoma MELANOMA has also a hypermetabolic behaviour POTENTIAL INDICATIONS Staging Recurrence: recurrence suspiction staging of recurrent disease Response assessment CONFIRM LOCAL RECURRENCE DETECTION OF DISTANT METASTASIS IN LOCAL RECURRENT DISEASE PET/CT in vulvar cancer
8 Se 50% Sp 100% PPV 100% NPV 57,1% PET/CT cannot replace surgical staging (lymphadenectomy +/- SLNB) It is useful for treatment planning prior surgical staging Accuracy 70% PET/CT in vulvar cancer Karmran MV. Eur J Gynaecol Oncol 2014;35:230-5
9 PET/CT Cervical cancer
10 PET/CT in cervical cancer PET/CT for the evaluation of gynecological cancer STAGING FOLLOW-UP RECURRENCE PET/CT in cervical cancer
11 PET/CT in cervical cancer PET/CT for the evaluation of gynecological cancer STAGING I PET/CT - is recommended in IB2 and when suspicious lymph nodes on CT - can be considered in IB1 - for treatment planning before chemoradiotherapy with curative intent - considered after histerectomy when CC is diagnosed as an incidental finding PET/CT in cervical cancer NCCN Guidelines Cibula D. ESGO-ESTRO-ESP Guidelines. Int J Gynecol Oncol 2018;28:641-55
12 PET/CT in cervical cancer PET/CT for the evaluation of gynecological cancer STAGING II-IV PET/CT - considered after histerectomy when CC is diagnosed as an incidental finding - to detect distant metastasis NCCN Guidelines Cibula D. ESGO-ESTRO-ESP Guidelines. Int J Gynecol Oncol 2018;28:641-55
13 Se 58% Sp 93% PPV 78% NPV 84% PET/CT in cervical cancer 80 Decreases multimodal treatment from 30% to 12.5% of patients. PET/CT in cervical cancer Goyal BK. Int J Gynecol Cancer 2010; 20:1041
14 SUVmax 13.4 PET/CT in cervical cancer Lee YY. Gynecol Oncol 2009;115:65
15 PET/CT in cervical cancer PET/CT for the evaluation of gynecological cancer STAGING FOLLOW-UP RECURRENCE PET/CT in cervical cancer
16 PET/CT in cervical cancer PET/CT for the evaluation of gynecological cancer FOLLOW-UP After chemoradiotherapy to assess complete treatment persistence of disease early relapse When: 3-6 months after completion of treatment DO NOT perform before 8 weeks PET/CT in cervical cancer NCCN Guidelines Cibula D. ESGO-ESTRO-ESP Guidelines. Int J Gynecol Oncol 2018;28:641-55
17 PET/CT in cervical cancer Liu FY. Eur J Nucl Med Mol Imaging 2018;45:
18 Higher cost 16,579 vs 15,450 USD Lower recurrence rate (32% vs 26%) The incremental cost-effectiveness ratio of PET was $20,761 per recurrence prevented. When the probability of recurrence after hysterectomy dropped to 25% or less, PET/CT proves to be cost-effective. PET/CT in cervical cancer Phippen NT. Int J Gynecol Cancer 2016;26:944-50
19 PET/CT in cervical cancer PET/CT for the evaluation of gynecological cancer STAGING FOLLOW-UP RECURRENCE PET/CT in cervical cancer
20 PET/CT in cervical cancer DETECTION OF RECURRENCE PET/CT in cervical cancer NCCN Guidelines Cibula D. ESGO-ESTRO-ESP Guidelines. Int J Gynecol Oncol 2018;28:641-55
21 PET/CT in cervical cancer DETECTION OF RECURRENCE higher Sensitivity and Specificity increases the identification of the number of lesions clinical impact 33-48% When CT/MRI are positive and salvage treatment is considered (surgery or radiation) when CT/MRI are equivocal PET/CT in cervical cancer Bjurberg M. Int J Gynecol Cancer 2013;23: Pallardy A Eur J Nucl Med Mol Imaging 2010; 37:1270-8
22 PET/CT in cervical cancer PET/CT for the evaluation of gynecological cancer INITIAL WORK-UP (STAGE I) INITIAL WORK-UP (STAGE II-IV) FOLLOW-UP RECURRENCE IB2 for planning before CTRT incidental finding on histerectomy to detect distant metastasis incidental finding on histerectomy 3-6 mo after chemoradiotherapy When abdominal nodes or distant mets are suspectec When CT/MRi are equivocal When CT/MRI are positive and salvage treatment is considered PET/CT in cervical cancer
23 PET/CT Endometrial cancer
24 PET/CT in endometrial cancer PET/CT for the evaluation of gynecological cancer STAGING RESPONSE ASSESSMENT FOLLOW-UP RECURRENCE PET/CT in endometrial cancer
25 PET/CT in endometrial cancer PET/CT for the evaluation of gynecological cancer STAGING RESPONSE ASSESSMENT FOLLOW-UP RECURRENCE Surgery of the primary tumour is always considered Surgical staging is mandatory MRI and US are recommended for local staging No additional exams for distant staging EXCEPT for: patients unfit for surgery (comorbidities )* difficult to complete surgical staging* extrauterine disease suspected on MRI or clinical exam OPTIONAL: for radiotherapy planning PET/CT in endometrial cancer *not in low risk group (only high or intermediate risk) **cepet/ct is preferred
26 CERVICAL INVOLVEMENT PET/CT MRi 2DUS Sensitivity Specificity PPV NPV Accuracy MYOMETRIAL INVOLMENT PET/CT MRi 2DUS Sensitivity Specificity PPV NPV Accuracy LYMPH NODE INVOLVEMENT PET/CT MRi Sensitivity Specificity PPV NPV Accuracy PET/CT in endometrial cancer 318 Antonsen SL.. Gynecol Oncol 2013;128:300-8
27 PET/CT in endometrial cancer Antonsen SL.. Gynecol Oncol 2013;128:300-8
28 Preoperative PET/CT in endometrial cancer Se 72% Sp 94% AUC 94% LNM: forest plot of sensitivity pooling (A); forest plot of specificity pooling (B); SROC curve (C). Vikram Rao Bollineni et al. J Nucl Med 2016;57: PET/CT in endometrial cancer (c) Copyright 2014 SNMMI; all rights reserved VR Bollineni et al. J Nucl Med 2016;57:
29 PET/CT in endometrial cancer PET/CT for the evaluation of gynecological cancer STAGING High sensitivity RESPONSE ASSESSMENT Controversial (low cost-effectiveness) FOLLOW-UP RECURRENCE PET/CT in endometrial cancer
30 PET/CT in endometrial cancer PET/CT for the evaluation of gynecological cancer STAGING RESPONSE ASSESSMENT local (vaginal) recurrence: clinical exam + biopsy + MRI once confirmed: PET/CT is recommended to study the extension of recurrence FOLLOW-UP clinical or biochemical suspicion of recurrence PET/CT is the first study (PET with cect is preferred) RECURRENCE PET/CT in endometrial cancer
31 PET/CT in recurrent endometrial cancer 11 original works Se 95.8% Sp 92.5% LR LR Clinical impact: 22-35% 541 PET/CT in endometrial cancer Kadkhodayan S. Gynecol Oncol 2013; 128: 397
32 PET/CT in recurrent endometrial cancer Se 95% Sp 91% AUC 97% ECR: forest plot of sensitivity pooling (A); forest plot of specificity pooling (B); SROC curve (C). Vikram Rao Bollineni et al. J Nucl Med 2016;57: PET/CT in endometrial cancer (c) Copyright 2014 SNMMI; all rights reserved VR Bollineni et al. J Nucl Med 2016;57:
33 PET/CT in endometrial cancer PET/CT for the evaluation of gynecological cancer
34 PET/CT in endometrial cancer PET/CT for the evaluation of gynecological cancer
35 PET/CT in endometrial cancer PET/CT for the evaluation of gynecological cancer STAGING Surgical staging recommended inoperable patients distant metastasis suspected DETECTION OF RECURRENCE High sensitivity accuracy Clinical impact on management 22-35% PET/CT in endometrial cancer
36 Ovarian cancer PET/CT
37 Ovarian cancer Diagnosis ovarian masses Staging of EOC Response assessment Surveillance Detection of recurrence PET/CT in ovarian cancer
38 Characterisation of adnexal masses FDG uptake & histology High uptake: High grade serous Carcinosarcoma Endometrioid Clear cell carcinoma Low uptake: Borderline Mucinous Low grade serous PET/CT in ovarian cancer n benign 31 borderline 66 malignant SUV max Mucinous 3.3 Non mucinous 8.4 Tsuboyama T. Investigative Radiology 2014;49:524-31
39 Characterisation of adnexal masses FDG uptake & histology High uptake: High grade serous Carcinosarcoma Endometrioid Clear cell carcinoma Low uptake: Borderline Mucinous Low grade serous carcinoma PET/CT in ovarian cancer n benign 31 borderline 66 malignant SUV max Mucinous 3.3 Non mucinous Clear cell carcinoma Other non mucinous 9.4 Tsuboyama T. Investigative Radiology 2014;49:524-31
40 3D ultrasonography MRI (better than CT) MRI and/or CT better than PET PET/CT in ovarian cancer Dodge JE. Gynecol Oncol 2012; 126:
41 CHARACTERISATION OF ADNEXAL MASS STAGING RESPONSE ASSESSMENT FOLLOW-UP DETECTION OF RECURRENCE LOW SENSITIVITY Malignant histologies Clear cell carcinoma Mucinous carcinoma Borderline tumours Peritoneal carcinomatosis in upper abdomen Extra-abdominal disease WHEN advanced disease is suspected Mid-treatment (NAC monitoring) After primary treatment Surgery (PCR) ChT (NAC) Not indicated Higher sensitivity when recurrence is suspected) Highest sensitivity Tumoral markers rising Abnormal image on surveillance studies PET/CT in ovarian cancer
42 Author Year n Stage Comparing PET vs CT Hynninen J II-IV PET vs CT Better in mesenteric nodes, upper abdomen (liver) Worse in small nodes on bowel surface Michielsen K RMdwi vs CT & PET/CT PET/CT for the evaluation of gynecological cancer Staging of EOC MRi and PET better in thoracic lesions MRi better in mesenteric and serous bowel lesions Signorelli M PET (Nodal) Se /Sp/Acc/PPV/NPV 83.3%, 98.2%, 95.6%, 90.9% and 96.5% Hynninen J IIc-IV PET vs CT Better in detection of extra-abdominal disease (67% vs 10%) Fruscio R III-IV PET 25/95 (26%). No clinical impact on OS Funicelli L CT vs PET CT better in peritoneal carcinomatosis PET for response assessment / detection of recurrence Nam E PET, CT, MRi, US Concordance PET- surgery 78% PET better in extra-abdominal detection (15.8%) De Iaco P PET/CT Better in lesions more than 5 mm (overall Se/Sp) 78% and 68% Worse in lesions less than 5 mm (carcinomatosis) Risum S PET Upstaging. Impact on OS (residual disease) Chung HH PET Predictor of recurrence Cardiophrenic Internal mammary chain Mediastinal Axillary Supraclavicular PROS: -Extraabdominal lesions Kitajima K I-IV PET vs cepet Better PET/ceCT than PET/low-dose CT and than PET + CT Lopez-Lopez PET vs CT Better in detection of metastasis Worse in peritoneal carcinomatosis Alessi A PET Upstaging Upstaging CONS: - Detection of small volume carcinomatosis PET/CT in ovarian cancer
43 PET/CT in ovarian cancer Stage IV
44 A B C D PET/CT in ovarian cancer Stage IV
45 Suspicious mass Symptoms PET/CT in ovarian cancer
46 CHARACTERISATION OF ADNEXAL MASS STAGING RESPONSE ASSESSMENT FOLLOW-UP DETECTION OF RECURRENCE LOW SENSITIVITY Malignant histologies Clear cell carcinoma Mucinous carcinoma Borderline tumours Peritoneal carcinomatosis in upper abdomen Extra-abdominal disease WHEN advanced disease is suspected (IIIc-IV) Mid-treatment (NAC monitoring) After primary treatment Surgery (PCR) ChT (NAC) Not indicated Higher sensitivity when recurrence is suspected) Highest sensitivity Tumoral markers rising Abnormal image on surveillance studies PET/CT in ovarian cancer
47 Staging post-primary treatment/response assessment After primary surgery: - Assess residual disease - Nodal activity + - Increase risk of progression disease - Decrease OS - Prognostic value - Correlates with PFS - Better risk stratification than FIGO PET/CT in ovarian cancer
48 Response assessment PET/CT for the evaluation of gynecological cancer AFTER PRIMARY SURGERY AFTER CHEMOTHERAPY DURING CHEMOTHERAPY DURING CHEMOTHERAPY PET/CT in ovarian cancer
49 Response assessment PET/CT for the evaluation of gynecological cancer Baseline PET Midtreatment Avril (33 p) Vallius (26 p) Martoni (42 p) Nishiyama (8 p) Final PET 1 cycle 3 cycles 6 cycles PET 1 c Avril (33 p) Interval surgery PET/CT in ovarian cancer Avril N. J Clin Oncol 2005; 23: Martoni AA. Q J Nucl Med Mol Imaging 2011; 55:81-90 Vallius T. Gynecol Oncol 2016; 140:29-35
50 33 PET/CT in ovarian cancer Avril N. J Clin Oncol 2005; 23:
51 Response assessment 37 year old woman High Grade Serous Carcinoma Stage IIIc: - intrabdominal lesions - high volume of disease Primary treatment: NAC PET/CT in ovarian cancer
52 Baseline PET/CT for the evaluation of gynecological cancer 3 cycles PET/CT in ovarian cancer Metabolic Response > 50%
53 Baseline PET/CT for the evaluation of gynecological cancer 3 cycles PET/CT in ovarian cancer Metabolic Response > 50%
54 Baseline PET/CT for the evaluation of gynecological cancer 3 cycles PET/CT in ovarian cancer
55 Baseline PET/CT for the evaluation of gynecological cancer 3 cycles PET/CT in ovarian cancer Metabolic Response > 50%
56 CHARACTERISATION OF ADNEXAL MASS STAGING RESPONSE ASSESSMENT FOLLOW-UP DETECTION OF RECURRENCE LOW SENSITIVITY Malignant histologies Clear cell carcinoma Mucinous carcinoma Borderline tumours Peritoneal carcinomatosis in upper abdomen Extra-abdominal disease WHEN advanced disease is suspected Mid-treatment (NAC monitoring) After primary treatment Surgery Chemotherapy Not indicated Higher sensitivity when recurrence is suspected) Highest sensitivity Tumoral markers rising Abnormal image on surveillance studies PET/CT in ovarian cancer
57 Surveillance PET/CT for the evaluation of gynecological cancer PET/CT in ovarian cancer Chen YM. Nucl Med Commun 2014; 35:
58 Follow-up CA125, Imaging - Suspicion recurrence Staging of recurrence Response assessment PET/CT in ovarian cancer Chen YM. Nucl Med Commun 2014; 35:
59 PET/CT in ovarian cancer PET/CT for the evaluation of gynecological cancer
60 CHARACTERISATION OF ADNEXAL MASS STAGING RESPONSE ASSESSMENT FOLLOW-UP DETECTION OF RECURRENCE LOW SENSITIVITY Malignant histologies Clear cell carcinoma Mucinous carcinoma Borderline tumours Peritoneal carcinomatosis in upper abdomen Extra-abdominal disease WHEN advanced disease is suspected Mid-treatment (NAC monitoring) After primary treatment Surgery Chemotherapy Not indicated Higher sensitivity when recurrence is suspected Highest sensitivity Tumoral markers rising Abnormal image on surveillance studies PET/CT in ovarian cancer
61 Detection of recurrence PET/CT for the evaluation of gynecological cancer PET/CT in ovarian cancer Suppiah S. W J Nucl Med 2017;16:176-85
62 Detection of recurrence Clinical impact: 52% 1 High correlation with surgical findings 2 Detection even with negative tumoral markers PET/CT for the evaluation of gynecological cancer Better Sensitivity, Specificity and PPV than other techniques (also) Useful in low grade tumours Recommended by NCCN ESMO Needed for treatment decision: surgery vs. chemotherapy ESMO PET/CT in ovarian cancer 1 Bilici A.. Arch Gynecol Obstet 2010; 282: Antunovic L et al. Clin Nucl Med 2012;37:e184-8
63 PET/CT for follow-up. No relapse is suspected Recurrence suspicion (6 mo later)
64
65 PET/CT in ovarian cancer PET/CT for the evaluation of gynecological cancer CHARACTERISATION OF ADNEXAL MASS STAGING RESPONSE ASSESSMENT FOLLOW-UP DETECTION OF RECURRENCE Malignant histologies Clear cell carcinoma Mucinous carcinoma Borderline tumours Peritoneal carcinomatosis in upper abdomen Extra-abdominal disease WHEN advanced disease is suspected Mid-treatment (NAC monitoring) After primary treatment Surgery Chemotheraphy Not indicated Higher sensitivity when recurrence is suspected Highest sensitivity Tumoral markers rising Abnormal image on surveillance studies PET/CT in ovarian cancer
66 PET/CT in ovarian cancer PET/CT for the evaluation of gynecological cancer CHARACTERISATION OF ADNEXAL MASS STAGING RESPONSE ASSESSMENT FOLLOW-UP DETECTION OF RECURRENCE LOW SENSITIVITY Malignant histologies Clear cell carcinoma Mucinous carcinoma Borderline tumours Peritoneal carcinomatosis in upper abdomen Extra-abdominal disease WHEN advanced disease is suspected Mid-treatment (NAC monitoring) After primary treatment Surgery Chemotherapy Not indicated Higher sensitivity when recurrence is suspected Highest sensitivity Tumoral markers rising Abnormal image on surveillance studies PET/CT in ovarian cancer
67 WHAT S NEW IN GYNECOLOGICAL PET/CT? PET/CT for the evaluation of gynecological cancer
68 What s new? 18 F-Fluorestradiol 68 Ga-DOTATATE 68 Ga-DOTANOC Equipment Image interpretation
69 Volumetric parameters PET/CT for the evaluation of gynecological cancer Volumetric PET parameters Metabolic Tumor Volume (MTV) Total Lesion Glycolysis (TLG) The highest activity of the highest lesion (SUVmax) Volume of disease Metabolic activity of disease PET/CT in ovarian cancer from Vallius T. Eur J Nucl Med Mol Imaging 2018; 45:
70 SUVmax MTV TLG PET/CT in ovarian cancer
71 Volumetric parameters in staging PET/CT for the evaluation of gynecological cancer PET/CT in ovarian cancer MTV p 0.01 TLG p Chung HH. Ann Surg Oncol 2012; 19:
72 Volumetric parameters in re-staging PET/CT for the evaluation of gynecological cancer SUVmax MTV TLG PET/CT in ovarian cancer Gallicchio R. Eur J Radiol 2017; 93:107-13
73 Volumetric parameters in response assessment PET/CT for the evaluation of gynecological cancer PET/CT in ovarian cancer Vallius T. Eur J Nucl Med Mol Imaging 2018; 45:
74 Volumetric parameters in recurrence PET/CT for the evaluation of gynecological cancer PET/CT in ovarian cancer Mayoral M. Rev Esp Med Nucl Imagen Mol 2016; 35:88-95
75 Volumetric parameters in recurrence PET/CT for the evaluation of gynecological cancer PET/CT in ovarian cancer Mayoral M. Rev Esp Med Nucl Imagen Mol 2016; 35:88-95
76 MTV in CC PET/CT for the evaluation of gynecological cancer PET/CT in cervical cancer Chong GO. PLoS One 2015;10: e
77 PET/CT in cervical cancer Lima GM. Eur J Nucl Med Mol Imaging 2018; in press
78 Volumetric parameters from PET/CT in EOC and CC In Ovarian Cancer: Correlate with PFS in staging Correlate with PFS in restaging after debulking surgery Correlacionan con la PFS after primary surgery (Liao S. Clin Nucl Med 2013; 38:715-20) Correlacionan con la PFS after secondary citorreduction (Vargas HA. Eur Radiol 2013; 25: ) Correlate with PFS after first recurrence (Mayoral M Rev Esp Med Nucl Imagen Mol 2016; 35:88-95) Identify patients with poor response to NAC In Cervical Cancer: Correlate with higher OS in pretreatment PET/CT (Lima GM. Eur J Nucl Med Mol Imaging 2018; in press) Correlate with DFS in patients treated with chemoradiotherapy (Chong GO. PLoS One 2015;10: e )
79 Vulvar cancer detection of distant metastasis detection of recurrence Ovarian cancer staging when advanced disease suspected resp. assessment during/after NAC detection of recurrence PET/CT Cervical cancer stage in LACC >IB2 F-Up: after ChRT Recurrence: when extra-uterine disease suspected Endometrial Cancer staging when surgical staging not possible detection of recurrence
80 Thank you for your attention
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