Functional MRI (DCE-MRI) in the follow-up of prostate cancer after beam radiotherapy (EBRT)

Transcription

1 Functional MRI (DCE-MRI) in the follow-up of prostate cancer after beam radiotherapy (EBRT) Poster No.: C-0748 Congress: ECR 2015 Type: Scientific Exhibit Authors: J. E. Méndez Escalante, D. Hernandez, G. Sancho, C. A. Nuñez Peralta, J. C. Pernas, M. M. Menso, L. F. Granados Palacio, C. Pérez Martínez; Barcelona/ES Keywords: Pelvis, Oncology, Genital / Reproductive system male, MR, MRFunctional imaging, Diagnostic procedure, Neoplasia DOI: /ecr2015/C-0748 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 39

2 Aims and objectives Review the utility of DCE-MRI in the follow up of prostate cancer after EBRT+/- androgen deprivation. Study whether morphological and functional MRI is associated with final response. Investigate whether DCE- MRI provides additional information to the PSA values in therapy response assessment and interpretation of temporary benign rise in PSA (bouncing PSA). Determine if DCE-MRI improve the detection of remaining tumor or early recurrence. Methods and materials Prospective pilot study N: 18 Patients underwent MRI and prostate-specific antigen levels before EBRT and 6,12 and 24 months after EBRT. Written informed consent was obtained from all patients. MRI technique: 3T MR scanner (Achieva Philips Medical Systems). Page 2 of 39

3 MRI data processing: Workstation viewforum (RS.1VL2 Philips) to generate signal intensity versus time curves from selected regions of interest. All data processing has been performed by a specifically trained radiologist. Purpose: To evaluate the 3D dynamic contrast-enhanced MRI (DCE-MRI) in the follow-up of prostate cancer after EBRT and its relation with PSA. Introductio: - Prostate cancer is the most common among the male population of Western countries excluding skin cancer; constitutes the second and third leading cause of cancer death in the United States and Europe respectively (1,2). - The treatment of prostate cancer at early stages is based on radiotherapy, which can be external (EBRT) or internal (brachytherapy), surgery and hormone therapy, and is often a combination of different techniques (3). Active surveillance is also included in the guidelines in selected patients. - Most localized prostate cancers can be treated with EBRT with a rate of success of 50-70% (no relapse in a period of 5 year). Therefore monitoring and diagnosis of possible relapses is necessary. Follow-up in patients treated with EBRT is based on: -Digital rectal exam (DRE): low sensitivity and specificity. - Prostate-specific antigen (PSA):Biochemical relapse PSA nadir+2ng/ml Page 3 of 39

4 (Phoenix consensus). - Transrectal ultrasonographically (US) guided biopsy, having a rate of false negatives around 20% after radiation treatment. PSA evolution after EBRT could be difficult to interpretate: - Time to reach nadir after EBRT treatment can be long and variable. - Bouncing PSA after RT treatment is common without relapse. - Testosterone recovery after androgen deprivation is associated with PSA increase. MRI in the follow-up: - Magnetic resonance (MRI) shows excellent soft tissue contrast which makes it very useful in the study of prostate cancer patients before and after treatment. - However MRI may be hampered by changes produced by radiation therapy to the prostate leading to poor differentiation of normal tissues from those affected by neoplasia, as the normal high signal intensity of the peripheral zone on T2-weighted images is often lost after radiotherapy treatment (figure 1-2). Page 4 of 39

5 Fig. 1: Prostate MRI before RT treatment. Normal high signal intensity of the peripheral zone on T2-weighted. References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Page 5 of 39

6 Fig. 2: Peripheral and transitional zone low density due to radiotherapy changes. References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES DCE-MRI: - Tumors have increased vascularization compared with normal tissues, through angiogenesis. This explains why tumoral tissue generally have a quick enhancement followed by earlier washout, compared with normal tissues. - DCE-MRI is a gadolinium administration based technique. Gadolinium is an intravenous contrast agent, that leads to a quick brightening of signal Page 6 of 39

7 in T1-weighted sequences, in vessels and the extracellular tissues. - Contrast agents are captured and washed quickly by prostate tumors. This behavior is not shown by normal tissues, and helps to the assessment of possible relapses. - The intensity of the enhancement in DCE-MRI is expressed graphically, and is related with the time. A slope is obtained, showing a different shape related with the characteristics of different tissues. - MRI in prostate cancer shows intense enhancement with fast rise of the slope, followed by quick washout (figure 3) or plateau enhancement (figure 4). The contrast enhancement in non-neoplastic tissues show a slow and steady increase in the slope (figure 5) (4). Page 7 of 39

8 Fig. 3: Quick and strong enhancement observed in tumor tissues (L13) References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Page 8 of 39

9 Fig. 4: Plateau enhancement References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Page 9 of 39

10 Fig. 5: Slow enhancement References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Images for this section: Page 10 of 39

11 Fig. 1: Prostate MRI before RT treatment. Normal high signal intensity of the peripheral zone on T2-weighted. Page 11 of 39

12 Fig. 2: Peripheral and transitional zone low density due to radiotherapy changes. Page 12 of 39

13 Fig. 3: Quick and strong enhancement observed in tumor tissues (L13) Page 13 of 39

14 Fig. 4: Plateau enhancement Page 14 of 39

15 Fig. 5: Slow enhancement Page 15 of 39

16 Results N:18 Biopsy - Positive : right 22,2%, left 22,2%, both 22,2% - Percentage infiltration: range 5,6-11,1% - Perineural infiltration: + 38,9%, - 61,1% - Vascular invasion: absent 100% - PIN: + 38,9%, - 61,1% - Gleason Score: 5 ( 5,6%), 6 (5,6%), 7 (66,7%), 8 (11,1%) Radiotherapy treatment - All patients treated with 3D-CRT. ICRU dose prescription. - Fractionation Gy. - Median prostate dose: Gy (74-4 Gy Gy). - Treatment volums: PTV1: pelvic lymph nodes+prostate and seminal vesicles: 10 patients PTV1.1: prostate and seminal vesicles. PTV1.2: prostate - Androgen deprivation: 13 patients ( 72,2%) Page 16 of 39

17 Toxicity GENITOURINARY TOXICITY (RTOG SCORE) Time postrt(m) NE INTESTINAL TOXICITY (RTOG SCORE) Time postrt(m) NE PSA - Median Nadir PSA: 0,03ng/ml 38,9% (7) range (0,03-1,35) - Bounce PSA : in 4 patients (22,2%) - At last follow-up: 16 patients alive and disease free 1 patient with biochemical failure 1 patient lost Page 17 of 39

18 TNM c Frequency Percent Valid Cumulative Percent Percent Valid T1c T2a T2b T2c T3a T3b Total Frequency Percent Valid Cumulative Percent Percent TNM MRI Valid T2a T2b T2c T2c T3a Total PSA/TIME Page 18 of 39

19 Fig. 6 References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES MRI/Time MAX_B MAX-6m MAX-12m MAX-24m Mean std. Deviation Median Minimum Maximum MRI/TIME Page 19 of 39

20 Fig. 7 References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES PSA/HT Page 20 of 39

21 Fig. 8 References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES MRI/HT Page 21 of 39

22 Fig. 9 References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Results Bounce PSA /Time Page 22 of 39

23 Fig. 10: Slightly serum PSA increase secondary to bouncing PSA in 4 patients. References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES MRI/Time Page 23 of 39

24 Fig. 11: Patients with bounce PSA didn't showed increases in MRI intensity. References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Page 24 of 39

25 Fig. 12: 75 years old man with PSA of 14.6 ng/ml and positive biopsy 90% in left peripheral zone with perineural invasion and Gleason score 3+4. Low signal intensity in left peripheral zone in T2- weighted sequences (FSE) with extracapsular extension (T3a). DCE-MRI shows faster and stronger enhancement in left peripheral zone. EBRT(45 Gy pelvic lymph nodes and 75 Gy to prostate) and androgen deprivation treatment was indicated. References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Page 25 of 39

26 Fig. 13: MR and PSA values 12 and 24 months after radiotherapy treatment. Progressive descending of initial slope and changes in the curve shape with correlated descending PSA. References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Page 26 of 39

27 Fig. 14 References: Hospital de la Santa Creu i Sant Pau, HOSPITAL DE LA SANTA CREU Y SANT PAU - Barcelona/ES Images for this section: Page 27 of 39

28 Fig. 6 Page 28 of 39

29 Fig. 7 Page 29 of 39

30 Fig. 8 Page 30 of 39

31 Fig. 9 Page 31 of 39

32 Fig. 10: Slightly serum PSA increase secondary to bouncing PSA in 4 patients. Page 32 of 39

33 Fig. 11: Patients with bounce PSA didn't showed increases in MRI intensity. Page 33 of 39

34 Fig. 12: 75 years old man with PSA of 14.6 ng/ml and positive biopsy 90% in left peripheral zone with perineural invasion and Gleason score 3+4. Low signal intensity in left peripheral zone in T2- weighted sequences (FSE) with extracapsular extension (T3a). DCE-MRI shows faster and stronger enhancement in left peripheral zone. EBRT(45 Gy pelvic lymph nodes and 75 Gy to prostate) and androgen deprivation treatment was indicated. Page 34 of 39

35 Fig. 13: MR and PSA values 12 and 24 months after radiotherapy treatment. Progressive descending of initial slope and changes in the curve shape with correlated descending PSA. Page 35 of 39

36 Fig. 14 Page 36 of 39

37 Conclusion - DCE-MR have shown the ability to identify tumor recurrence post radiotherapy: local recurrences can be benefit from further salvage treatments. - DCE-MR can contribute to overcome the limitations of PSA and DRE to depict local relapse and optimize salvage treatment. Personal information References Jemal A, Siegel R, Xu J, Ward E. Cancer statisitics CA Cancer J Clin 2012;62: Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in Eur J Cancer 2010,46: Donati OF, Jung SII et al. Multiparametric Prostate MR Imaging with T2weighted, Diffusion-weighted, and Dynamic Contrast-enhanced Sequences: Are All Pulse Sequences Necessary to Detect Locally Recurrent Prostate Cancer after Radiation Therapy?. Radiology. vol. 268: , / radiol Boonsirikamchai P, Choi S et al. MR Imaging of Prostate Cancer in Radiation Oncology: What Radiologists Need to Know. RadioGraphics 2013; 33: Boonsirikamchai P, Kau H et al. Use of Maximum Slope Images Generated From Dynamic Contrast-Enhanced MRI to Detect Locally Recurrent Prostate Carcinoma After Prostatectomy: A Practical Approach. AJR 2012; 198:W228-W236. Futterer JJ, Stijn WT, Heijmink J. et al. Prostate Cancer Localization with Dynamic Contrastenhanced MR Imaging and Proton MR Spectroscopic Imaging. Radiology, Nov 2006, Vol. 241: , / radiol Franiel T, Lüdemann L. et al. MRI before and after external beam intensitymodulated radiotherapy of patients with prostate cancer: The feasibility of Page 37 of 39

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