10 jaar Respons monitoring / meting met MRI (PET) in het NKI -AVL: Wat valt er te leren?

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1 10 jaar Respons monitoring / meting met MRI (PET) in het NKI -AVL: Wat valt er te leren? Claudette Loo, radioloog NKI-AVL 10 e NKI-AVL mammacarcinoom symposium Een dynamisch decenium Woensdag 2 november 2011 The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital

2 Neoadjuvante Chemotherapie (NAC) Micrometastasen Reductie tumorvolume Monitoren tumorrespons

3 Learned lessons 1 baseline MRI Triple Negative HER2 + ER + / ILC

4 Learned lessons 2 Voorspellende waarde MRI tijdens NAC MRI is effectief in het monitoren van tumorrespons bij Triple Negative en HER2+ tumoren, maar niet bij ER+ tumoren Langste diameter tijdens late contrastfase

5 MST 37% ILC 50% incompl Learned lessons 3 AVL MRI na NAC planning chirurgie MRI is meest accuraat in vaststellen tumorresidu bij TN en HER2+ tumoren. selectie MST: - tumor omvang baseline - tumorreductie - subtype

6 MRI studie (1) NKI-AVL tijdens NAC Doel: identificeren MRI kenmerken tijdens NAC die voorspellende waarde hebben voor uiteindelijke respons. N= 54 (training set) MRI voor (scan 1) en tijdens (scan 2) NAC MST / Mastectomie Pathologie: p CR of non-pcr Multivariate analyse ; functionele & morfologische kenmerken Loo et al AJR 2008;191:

7 MRI studie (1) NKI-AVL tijdens NAC Resultaat: verandering van langste diameter van late aankleuring op MRI scan 2 ten opzichte van MRI scan 1 meest voorspellend voor resttumor. Late contrastfase Loo et al AJR 2008;191:

8 MRI studie (2) NKI-AVL tijdens NAC Purpose MRI Response Monitoring of Breast Cancer during Neoadjuvant Chemotherapy: Relevance of Breast Cancer Subtype Loo et al JCO 2011; 29(6): To evaluate the relevance of breast cancer subtype on MRI markers of therapy response during chemotherapy

9 Response monitoring during NAC MRI Patients and Methods Neoadjuvant chemotherapy AVL MRI baseline, MRI during NAC Breast cancer subgroup receptor based: Triple-Negative HER2+ ER+/HER2- Excluded HER2+ without trastuzumab Loo et al. JCO 2011; 29(6):660-6

10 Response monitoring during NAC MRI Patients and Methods Response of the primary breast tumor Pathology surgical specimen Complete remission Residual tumor Loo et al. JCO 2011; 29(6):660-6

11 MRI markers Tumor morphology Largest diameter (initial / late) Relative enhancement (initial / late) Pattern of reduction Breast cancer subtype Chemotherapy regimen Age Response monitoring during NAC MRI Patients and Methods Statistical analysis (Multivariate) Loo et al. JCO 2011; 29(6):660-6

12 N. (%) Mean age 46 years Range years T stage prior to NAC T1 6 (3) T2 97 (52) T3 62 (33) T4 23 (12) pn stage prior to NAC pn0 (SNB -) pn1 (SNB+ / FNAC +) 28 (15) 125 (66) pn3 (infra/supraclavicular) 11 (6) pnx (cn0) 24 (13) Histology Ductal Carcinoma 139 (74) Lobular Carcinoma 21 (11) Adenocarcinoma NOS 28 (15) Subtype based on receptor status Response monitoring during NAC MRI Results Patients and tumor characterstics N=188 ER-positive (ER-positive,HER2-negative) 103(55) Loo et al. JCO 2011; 29(6):660-6 Triple negative 47 (25) (ER,PR,HER2 negative) HER2-positive 38 (20)

13 Response monitoring during NAC MRI Results Subtype, pathological response, chemotherapy regimen, histology and ER receptor Triple-negative Her2- positive ER- positive Total N=47 N=38 N=103 Pathological response Residual disease 31 (66) 23 (60) 96 (93) Complete remission 16 (34) 15 (40) 7 (7) Chemotherapy Regimen AC AC + CD CD or AD 4 11 Trastuzumab based 38 Histology ER Ductal carcinoma Lobular carcinoma Adenocarc NOS negative positive Loo et al. JCO 2011; 29(6):660-6

14 Response monitoring during NAC MRI Results MRI Total N=188 Triple-Negative Her2+ ER+/HER- N = 47 N=38 N=103 Pathology residual tumor 31 (66) 23 (61) 96 (93) Lesion morphology at baseline MRI 1 mass unifocal 27 (57) 7 (18) 34 (33) mass multifocal 15 (32) 20 (53) 31 (30) diffuse 5 (11) 11 (29) 38 (37) Pattern of reduction from MRI 1 to MRI 2 shrinking mass 26 (55) 11 (29) 43 (42) diffuse decrease 3 (6) 6 (16) 36 (35) small foci 6 (13) 4 (11) 7 (7) no enhancment 5 (11) 12 (32) 5 (5) no change 7 (15) 5 (13) 12 (12) Loo et al. JCO 2011; 29(6):660-6

15 Response monitoring during NAC MRI Results Multivariate logistic regression Significant associations breast cancer subtype and MRI markers Area under ROC curve 0.84 (p<0.001) Subset analysis only significant for triplenegatives (p<0.001) and HER2+ (p=0.05) No associations for ER+/HER2- (p=0.07) Loo et al. JCO 2011; 29(6):660-6

16 120 A Triple Negative 120 B HER2-positive Baseline tumor diameter late enhancement Baseline tumor diameter late enhancement ,2-1,0-0,8-0,6-0,4-0,2 0,0 0,2 0,4 Change largest tumor diameter late enhancement 0-1,2-1 -0,8-0,6-0,4-0,2 0 0,2 0,4 Change largest tumor diameter late enhancement Loo et al. JCO 2011; 29(6):660-6 Baseline tumor diameter late enhancement la te enhancement M RI ba seline C ER-positive/HER2-negative ,2-1 -0,8-0,6-0,4-0,2 0 0,2 0,4 Change largest tumor diameter late enhancement Subset analysis Residual tumor Complete remission

17 Response monitoring during NAC MRI Conclusions MRI during NAC to monitor response is effective in triple-negative and HER2- positive disease, but is inaccurate in ER+/HER2- breast cancer Loo et al. JCO 2011; 29(6):660-6

18 Response monitoring during NAC PET & MRI How medical imaging can influence the efficacy of a new treatment strategy Can PET complement MRI during response evaluation? What is the role of breast-cancer subtypes? Is it feasible to establish a response prediction model? Kenneth Pengel, Bas Koolen et al., SABCC 2011

19 Response monitoring during NAC PET & MRI Material and Methods PET and MRI prone position Baseline & during chemotherapy Hanging breast Time interval as small as possible Integrated PET /MRI machines are not widely available! Kenneth Pengel, Bas Koolen et al., SABCC 2011

20 Response monitoring during NAC PET & MRI Material and Methods ± 250 patients needed Currently 176 patients enrolled study Preliminary analysis of 77 cases PET and MRI baseline & during NAC Subtypes: ER+/HER2 -, HER2+ and Triple Negative Statistics, including multivariate (MV)-and receiver operating curve (ROC) analysis Pathology response: non responders vs p (near) CR Kenneth Pengel, Bas Koolen et al., SABCC 2011

21 Response monitoring during NAC PET & MRI Results N=77 Age: means 45.9 ± 10.2 years Response: 36 tumors (47%) Non response : 41 tumors (53%) MV analysis: - change LD late MRI diameter, - change PET SUV max - breast cancer subtypes Best accuracy for TN tumors MRI and PET complementary in other subgroups Kenneth Pengel, Bas Koolen et al., SABCC 2011

22 Response monitoring during NAC PET & MRI Material and Methods 41/36 Kenneth Pengel, Bas Koolen et al., SABCC 2011

23 Response monitoring during NAC PET & MRI Material and Methods 5 / 16 Kenneth Pengel, Bas Koolen et al., SABCC 2011

24 Response monitoring during NAC PET & MRI Results 29 / 5 Kenneth Pengel, Bas Koolen et al., SABCC 2011

25 Response monitoring during NAC PET & MRI Results 7 / 15 Kenneth Pengel, Bas Koolen et al., SABCC 2011

26 Response monitoring during NAC PET & MRI Results ROC curves AUC= 0.81 for PET, AUC= 0.82 for MRI AUC= 0.89 for combined MRI, PET and breast cancer subtype model P= % sensitivity at 95% specificity Conclusions MRI and PET show complementary potential to evaluate response during NAC Breast cancer subtypes important Kenneth Pengel, Bas Koolen et al., SABCC 2011

27 MRI &PET MRI perfusion Glucose uptake PET/MR fusion Courtesy Dmitriev / Gilhuijs

28 Response monitoring after NAC Planning Surgery The Relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy Straver et al. Ann Surg Oncol. 2010;17: N=254 surgery prior to NAC vs surgery performed after NAC overall increase BCS 37% (IDC 41% vs ILC 20%) 50% ILC incomplete resection increase BCS subtype: TN : 45% ER+ : 39% HER2+ : 24%

29 Response monitoring after NAC MRI Planning Surgery MRI Model to guide the surgical treatment in breast cancer patients after neoadjuvant chemotherapy Straver et al. Ann of Surgery 2010;251; Aim: Assess accuracy of MRI in detecting residual disease Assess MRI based interpretation model to select patients for BCS after NAC

30 Response monitoring after NAC MRI Correlatie MRI & Pathologie MRI > 20 mm PA PA > 20 mm MRI Courtesy Marie Jeanne Vrancken Peeters Straver et al. Ann of Surgery 2010;251;

31 Response monitoring after NAC MRI Accuracy MRI Straver et al. Ann of Surgery 2010;251;

32 Response monitoring after NAC MRI Accuracy MRI Results PPV 90% (130/144) NPV 44% (28/64) MRI features most predictive of feasibility BCS: - Largest diameter at baseline MRI - Reduction in diameter - Breast cancer subtype Straver et al. Ann of Surgery 2010;251;

33 Response monitoring after NAC MRI MRI model planning surgery 103 ER pos = 49 % 58 Her pos = 28 % 47 TN = 23 % Straver et al. Ann of Surgery 2010;251; Courtesy Marie Jeanne Vrancken Peeters

34 Response monitoring after NAC MRI Multivariate MRI model to guide surgical planning Straver et al. Ann of Surgery 2010;251;

35 Learned lessons 1 baseline MRI Triple Negative HER2 + ER + / ILC

36 Learned lessons 2 Voorspellende waarde MRI tijdens NAC MRI is effectief in het monitoren van tumorrespons bij Triple Negative en HER2+ tumoren, maar niet bij ER+ tumoren Langste diameter tijdens late contrastfase

37 MST 37% ILC 50% incompl Learned lessons 3 AVL MRI na NAC planning chirurgie MRI is meest accuraat in vaststellen tumorresidu bij TN en HER2+ tumoren. selectie MST: - tumor omvang baseline - tumorreductie - subtype

38 Acknowledgements Radiologie Kenneth Pengel Saar Muller Kenneth Gilhuijs (UMCU) Anita Paape Ivan Dmitriev (UMCU) Pathologie Jelle Wesseling Marc vd Vijver (AMC) Esther Lips Jorma de Ronde Chirurgie Marie Jeanne Vrancken Peeters Marieke Straver Nucleaire Geneeskunde Bas Koolen Wouter Vogel Oncologie Sjoerd Rodenhuis Marjo Holtkamp Margaret Schot

39 Bedankt voor uw aandacht The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital

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