MCC 2011 - Slide 2


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  • Purpose: To prospectively determine diagnostic performance of predictive criteria for nodal staging with ultrasmall superparamagnetic iron oxide (USPIO)–enhanced magnetic resonance (MR) imaging in primary rectal cancer patients, with histopathologic findings as reference standard. Materials and Methods: Institutional review board approval and informed consent were obtained. Twenty-eight rectal cancer patients (18 men, 10 women; mean age, 68 years) underwent USPIOenhanced MR. Two observers with different experience evaluated each node on three-dimensional T2*-weighted images for border irregularity, short- and long-axis diameter, and estimated percentage (30%, 30%–50%, or 50%) of white region within the node. Ratio of measured surface area of white region within the node to measured surface area of total node (ratioA) was calculated. Signal intensity (SI) of gluteus muscle (SIGM), total node (SITN), and white (SIWR) and dark (SIDR) regions within the node were used to calculate SITN/SIGM and SIWR/SIDR ratios. Lesion-by-lesion, receiver operating characteristic curve, and interobserver agreement analyses were performed. The most accurate and practical criterion was evaluated by observer 3. Results: In 28 patients, 236 lymph nodes were examined. Area under the receiver operating characteristic curve (AUC) of estimated percentage of white region and ratioA were 0.96 and 0.99 (observer 1) and 0.95 and 0.97 (observer 2), respectively. AUC of estimated percentage criterion for observer 3 was 0.96. AUC of border, short- and long-axis diameter, and SITN/SIGM and SIWR/SIDR ratios were 0.65, 0.75, 0.79, 0.85, and 0.75 (observer 1) and 0.58, 0.75, 0.79, 0.89, and 0.79 (observer 2), respectively. Interobserver agreement ( value) for estimated white region between observers 1 and 2, 1 and 3, and 2 and 3 were 0.77, 0.79, and 0.84, respectively. For observers 1 and 2, value for border was 0.28. For observers 1 and 2, intraclass correlation coefficient for short- and long-axis diameters, ratioA, and SITN/SIGM and SIWR/SIDR ratios were 0.91, 0.96, 0.91, 0.72, and 0.92, respectively. Conclusion: Estimated percentage of white region and measured ratioA are the most accurate criteria for predicting malignant nodes with USPIO-enhanced MR imaging; the first criterion is the most practical.
  • Purpose: To retrospectively assess sensitivity and specificity of magnetic resonance (MR) imaging after chemotherapy and radiation therapy for predicting tumor invasion of the mesorectal fascia (MRF) in locally advanced primary rectal cancer, by using results of histologic examination and surgery as the reference standard, and to determine morphologic MR imaging criteria for MRF invasion. Materials and Methods: The Ethical Committee of University Hospital Maastricht approved this study and waived informed consent. Two observers independently scored postchemoradiation MR images in 64 patients with rectal cancer (38 male [mean age, 60 years] and 26 female [mean age, 64 years] patients) for MRF tumor invasion with a confidence level scoring system defined by subjective criteria. In a subsequent consensus reading session, morphologic MR criteria for invasion were defined by comparing morphologic changes with histologic findings. These criteria were evaluated and compared with the subjective criteria by comparing areas under the receiver operating characteristic curves (AUCs). Results: AUCs of postchemoradiation MR imaging for predicting MRF tumor invasion were 0.81 and 0.82 for observers 1 and 2, respectively. The following four types of morphologic tissue patterns at MR imaging were associated with whether or not MRF invasion was present at histologic examination: (a) development of fat pad larger than 2 mm (seen in no quadrants with and in four quadrants without invasion), (b) development or persistence of spiculations (seen in no quadrants with and in 22 quadrants without invasion), (c) development of diffuse hypointense “ fibrotic” tissue (seen in 21 quadrants with and in 32 quadrants without invasion), and (d) persistence of diffuse isoor hyperintense tissue (seen in 19 quadrants with and in two quadrants without invasion). AUC of postchemoradiation MR imaging for predicting MRF invasion on the basis of morphologic criteria was 0.80. There was no significant difference between the performance of subjective and morphologic criteria ( P .73–.76). Conclusion: Postchemoradiation MR imaging findings have moderate accuracy for predicting tumor invasion of the MRF related to the limitation in differentiating between diffuse “fibrotic” tissue with and that without small tumor foci. Specific other types of morphologic patterns atMRimaging can highly predict a tumor-free or invaded MRF.
  • Location of metastases Liver 43 Lung 15 (Retro)peritoneal lymph nodes 4 Bone 2
  • MCC 2011 - Slide 2

    1. 1. Department of Surgery, University Medical Center Groningen Staging of rectal cancer as an example in oncology Theo Wiggers Cascais, Portugal Sunday February 13 th ,2011
    2. 2. Staging of rectal cancer Aim and limitations of the workshop <ul><li>Aim: </li></ul><ul><ul><li>Imaging necessary for decision making in the treatment of rectal cancer </li></ul></ul><ul><ul><li>Role of rectal examination </li></ul></ul><ul><li>In this workshop we do not encounter the effect of : </li></ul><ul><ul><li>Co morbidity </li></ul></ul><ul><ul><li>Blood testing </li></ul></ul><ul><ul><li>Endoscopy </li></ul></ul><ul><ul><li>Pathology </li></ul></ul><ul><ul><li>Genetics </li></ul></ul>
    3. 3. <ul><li>Why staging in Rectal Cancer </li></ul><ul><li>Treatment modalities in Rectal Cancer </li></ul><ul><li>Discriminating moments </li></ul><ul><li>Imaging modalities </li></ul><ul><li>New developments </li></ul><ul><li>Conclusions </li></ul>Elements in the workshop
    4. 4. <ul><li>Staging </li></ul><ul><ul><li>TNM,UICC,Dukes </li></ul></ul><ul><li>Reason for staging of rectal cancer </li></ul><ul><ul><li>Rationale for individual treatment based on guide lines </li></ul></ul><ul><ul><li>Prognostic value for groups or individuals </li></ul></ul><ul><ul><li>Comparison of series </li></ul></ul>
    5. 5. <ul><li>Tx : Primary tumor cannot be assessed </li></ul><ul><li>T0 : No evidence of primary tumor </li></ul><ul><li>Tis : Carcinoma in situ: intraepithelial or invasion of the lamina propria </li></ul><ul><li>T1 : Tumor invades submucosa </li></ul><ul><li>T2 : Tumor invades muscularis propria </li></ul><ul><li>T4 : Tumor invades through the muscularis propria into the subserosa or perirectal tissues </li></ul><ul><li>V and L substaging identification of vascular or lymphatic invasion </li></ul><ul><li>Nx : Regional nodes cannot be assessed </li></ul><ul><li>N0 : No regional lymph node metastasis </li></ul><ul><li>N1 : Metastases in 1 to 3 regional lymph nodes </li></ul><ul><li>N2 : Metastases in 4 or more regional lymph nodes </li></ul><ul><li>A tumor nodule in the fat without evidence of residual lymph node =N+ or if it has an irregular contour in the T category and code as V1 or V2 </li></ul><ul><li>Mx : Distant metastases cannot be assessed </li></ul><ul><li>M0 : No distant metastases </li></ul><ul><li>M1 : Distant metastases </li></ul>TNM=pTNM Stage 0: Tis, N0, M0 Stage I: T1-T2, N0, M0 Stage IIA: T3, N0, M0 Stage IIB: T4, N0, M0 Stage IIIA: T1-T2, N1, M0 Stage IIIB: T3-T4, N1, M0 Stage IIIC: Any T, N2, M0 Stage IV: Any T, Any N, M1 TNM definitions AJCC 6 th manual 2002 Dukes
    6. 6. S ystematic review(1): Preoperative staging of rectal cancer <ul><li>Eighty-three studies 78 papers </li></ul><ul><li>Including 4897 patients </li></ul><ul><li>CT, ES, MRI, MRI with endorectal coil </li></ul><ul><li>Bowel wall penetration = T </li></ul><ul><li>Involvement of lymph nodes = N </li></ul><ul><li>Accuracy, sensitivity, specificity positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood </li></ul>Kwok et al Int J Colorectal Dis 2000
    7. 7. S ystematic review(2): Preoperative staging of rectal cancer <ul><li>Relevant articles between 1985 and 2002 </li></ul><ul><li>Ninety fulfilled all inclusion criteria </li></ul>Bipat et al Radiology 2004
    8. 8. <ul><li>Outdated imaging techniques </li></ul><ul><ul><li>MRI with body coil versus phased array </li></ul></ul><ul><ul><li>Conventional CT versus multislice CT </li></ul></ul><ul><ul><li>High versus low frequency ultrasound </li></ul></ul><ul><li>No standardized surgery </li></ul><ul><li>No standardized pathology </li></ul><ul><li>The relevant questions are often not answered </li></ul>Keep in mind Literature and staging of rectal cancer
    9. 9. Treatment modalities <ul><li>No treatment </li></ul><ul><li>Symptom relief </li></ul><ul><li>Transanal Endoscopic Microsurgery </li></ul><ul><li>Total Mesorectal Excision (TME) without XRT </li></ul><ul><li>TME after 5x5 Gray </li></ul><ul><li>TME after 50 Gray and waiting 6-8 weeks </li></ul><ul><li>TME after 50 Gray and 6-8 weeks “en bloc” resection </li></ul>
    10. 10. <ul><li>Symptom relief/ palliative treatment </li></ul><ul><li>Transanal Endoscopic </li></ul><ul><li>Microsurgery (TEM) </li></ul><ul><li>TME (Total Mesorectal Excision) without radiotherapy </li></ul><ul><li>TME after radiotherapy 5x5 Gray </li></ul><ul><li>TME after chemoradiation 50 Gray </li></ul><ul><li>TME “en bloc” </li></ul><ul><li>resection </li></ul><ul><li>after chemoradiation </li></ul><ul><li>50 Gray </li></ul>Treatment modalities
    11. 11. Discriminating elements <ul><li>Layers of the bowel wall </li></ul><ul><li>Closeness to the endopelvic fascia </li></ul><ul><li>Lymph node metastases </li></ul><ul><li>Adjacent organ invasion </li></ul><ul><li>Distant metastases </li></ul>
    12. 12. Discriminating elements Pathological Lymph Nodes <ul><li>Within the mesorectal fat </li></ul><ul><li>In relation to the endopelvic fascia </li></ul><ul><li>Outside the endopelvic fascia </li></ul>
    13. 13. Lymph nodes within the mesorectum <ul><li>In case of TEM procedure </li></ul><ul><ul><li>T1 lymph node metastases: 5-10% </li></ul></ul><ul><ul><li>T2 lymph node metastases: 10-15% </li></ul></ul><ul><li>In case of considering preoperative radiation (based on the data of the Dutch TME study) </li></ul>Stage I Stage II Stage III Stage VI
    14. 14. Lymph nodes in relation to the endopelvic fascia <ul><li>Distance from pathological lymph node to the endopelvic fascia </li></ul><ul><ul><li>is relevant : Adam IJ Quirke P, Lancet. 1994 ;344:707-11 </li></ul></ul><ul><ul><li>is not relevant : Nagtegaal ID, Am J Surg Pathol. 2002;26:350-7 </li></ul></ul><ul><ul><ul><li>“ there is a relation between metastatic lymph nodes and local recurrence but not with the distance to the fascia” </li></ul></ul></ul>
    15. 15. Lymph nodes outside the primary resection field <ul><li>16 cadavers </li></ul><ul><li>28.6 nodes per pelvis </li></ul><ul><li>lymph node size 2-13mm </li></ul><ul><li>three groups: </li></ul><ul><li>presacral 4.4 (2-10) </li></ul><ul><li>hypogastric 5.2(1-11) </li></ul><ul><li>obturator 7 (2-18) </li></ul>Canessa, Dis Col Rect 2004;47:297-303 Data from Japan: metastases in 8-23 %
    16. 16. Pathological lymph nodes outside the endopelvic fascia
    17. 17. Modern staging for large tumors =from the outside cTNM T1 T2 T3 T3 T4 Primary resectable Locally Advanced T3 T3 T4
    18. 18. Three possibilities “ resectable”, “ operable”, “fixed” , “ tethered”, “I can get it out” <ul><li>Real life </li></ul><ul><li>The expert </li></ul><ul><li>Ideal world </li></ul>
    19. 19. The ideal world
    20. 20. The expert <ul><li>150 patients 1994-1999 </li></ul><ul><li>Clinical assessment on tumor size, fixation, </li></ul><ul><li>distance to the anal verge </li></ul><ul><li>Judged on risk of mesorectal fascia involvement </li></ul><ul><li>35 preoperative radiation local recurrence rate 17.1 % </li></ul><ul><li>115 primary resection local recurrence rate 2.6% </li></ul>Simunovic et al; Br J Surg 2003
    21. 21. Real life <ul><li>98 patients </li></ul><ul><li>Digital rectal examination, </li></ul><ul><li>endoluminal ultrasound </li></ul><ul><li>or magnetic resonance imaging </li></ul><ul><li>Agreement between staging </li></ul><ul><li>and histological assessment </li></ul><ul><li>94% for MRI, 65% DRE, 69% EUS </li></ul><ul><li>DUTCH TME 17 % R1,R2 resections </li></ul>Brown; Br J Cancer 2004
    22. 22. Imaging modalities <ul><li>Conventional: Barium enema, Chest X-Ray </li></ul><ul><li>Endoluminal Ultrasound </li></ul><ul><li>Phased array MRI </li></ul><ul><li>Multislice spiral CT scan </li></ul><ul><li>Positron Emission Tomography /CT </li></ul>
    23. 23. Possibilities
    24. 24. Layers of the bowel wall EUS Accuracy: EUS: 87% CT: 73% MRI: 82% Kwok et al Int J Colorectal Dis 2000
    25. 25. Bowel wall layers CT Not well visible CT: 73% EUS: 87% MRI: 82% Kwok et al Int J Colorectal Dis 2000
    26. 26. Bowel wall layers MRI
    27. 27. Bowel wall layers MRI <ul><li>EUS: 87% </li></ul><ul><li>CT: 73% </li></ul><ul><li>MRI: 82% </li></ul>Kwok et al Int J Colorectal Dis 2000
    28. 28. Bowel wall layers PET-FDG Not visible
    29. 29. Endopelvic fascia EUS Not visible
    30. 30. Endopelvic fascia CT <ul><li>250 patients multislice spiral CT sensitivity 74% specificity 94% </li></ul><ul><li> = 0.90 </li></ul><ul><li>False positive: anterior at the level of the vesicles </li></ul><ul><li>Distant metastases are visualized </li></ul><ul><li>Available, accessible and reproducible </li></ul>Wolberink Dis Colon Rectum 2009 EUS: 87% CT: 73% MRI: 82%
    31. 31. Endopelvic fascia MRI
    32. 32. MRI & CRM: a meta-analysis <ul><li>Blomqvist et al. Br J Rad 1999 </li></ul><ul><li>Beets-Tan et al. The Lancet 2001 </li></ul><ul><li>Botterill et al. Col Dis 2001 </li></ul><ul><li>Bissett et al. Dis Col Rect 2001 </li></ul><ul><li>Brown et al. BJS 2003 </li></ul><ul><li>Mathur et al. Col Dis 2003 </li></ul><ul><li>Branagan Dis Col Rect 2004 </li></ul>Lahaye, Beets, vd Velde, Beets-Tan. Semin US, CT & MRI 2005
    33. 33. Endopelvic fascia PET/CT Not visible
    34. 34. Lymph node metastases EUS <ul><li>EUS: 74% </li></ul><ul><li>CT: 66% </li></ul><ul><li>MRI: 74% </li></ul>Kwok et al Int J Colorectal Dis 2000
    35. 35. Lymph node metastases CT <ul><li>EUS: 74% </li></ul><ul><li>CT: 66% </li></ul><ul><li>MRI: 74% </li></ul>Kwok et al Int J Colorectal Dis 2000
    36. 36. Lymph node metastases MRI <ul><li>EUS: 74% </li></ul><ul><li>CT: 66% </li></ul><ul><li>MRI: 74% </li></ul>Kwok et al Int J Colorectal Dis 2000
    37. 37. Lymph node metastases PET-FDG Sometimes visible
    38. 38. In growth other organs EUS Prostate, vagina, Pelvic floor
    39. 39. In growth other organs CT
    40. 40. In growth other organs MRI
    41. 41. In growth other organs PET-FDG Not visible
    42. 42. Distant metastases EUS
    43. 43. Distant metastases CT <ul><li>Evaluation of 212 scans, 42 liver metastases(19,2%) </li></ul><ul><li>Sensitivity 64% </li></ul><ul><li>Specificity 94% </li></ul>Chest CT 200 patients 7% pulmonary metastases 25% intermediate lesions Grossmann 2009
    44. 44. Distant metastases MRI
    45. 45. Distant metastases PET-FDG
    46. 46. CRC: CT versus FDG PET Wiering Ann Surg Oncol 2007; 14:818–826
    47. 47. Summary
    48. 48. EUS <ul><li>Positive </li></ul><ul><li>Bowel wall layers </li></ul><ul><li>Negative </li></ul><ul><li>Endopelvic fascia not visible </li></ul><ul><li>Distant metastases difficult reproducible </li></ul>New possibilities New contrast agents Three dimensional EUS
    49. 49. CT <ul><li>Positive </li></ul><ul><li>With one technique local tumor growth and distant metastases visible in a few seconds “one stop shop” </li></ul><ul><li>Negative </li></ul><ul><li>Limited contrast resolution </li></ul><ul><li>Intermediate lesions chest CT </li></ul>New possibilities Multidetector, Reconstructions in all directions
    50. 50. MRI <ul><li>Positive </li></ul><ul><li>Extension local tumor growth </li></ul><ul><li>Negative </li></ul><ul><li>Investigator dependent </li></ul><ul><li>Not available in many situations </li></ul>New possibilities “ Whole body MRI” New contrast agents Assessment of the MRF after neoadjuvant treatment
    51. 51. USPIO
    52. 52. USPIO MRI MRI
    53. 53. USPIO <ul><li>28 rectal cancer patients </li></ul><ul><li>USPIO enhanced MR and histopathology </li></ul><ul><li>236 lymph nodes examined </li></ul>Lahaye et al. Radiology 2008; 246: 804-811
    54. 54. Liver metastases Bipat et al. Radiology 2005; 237:123–131
    55. 55. MRF assessment after chemoradiation <ul><li>64 locally advanced primary rectal cancer (54 more extensive surgery than TME or APR) </li></ul><ul><li>MRF assessment after chemoradiation </li></ul><ul><li>Morphologic MR criteria for invasion defined </li></ul><ul><li>Histopathology reference standard </li></ul>Vliegen et al. Radiology 2008; 246:454–462
    56. 56. Response on MRI Department of Surgery, University Medical Center Groningen preradiation postradiation 0/26 (0%) MRF+
    57. 57. Response on MRI Department of Surgery, University Medical Center Groningen postradiation preradiation 21/53 (40%) MRF+
    58. 58. Post CRT involvement of CRM <ul><li>PPV 45%, NPV 98% </li></ul><ul><li>n= 97 </li></ul><ul><li>PPV 57%, NPV 100% </li></ul><ul><li>AUC 0.81 </li></ul><ul><li>n= 64 </li></ul>Department of Surgery, University Medical Center Groningen MERCURY study group, BMJ 2006 Vliegen, et al, Radiology 2008
    59. 59. PET/CT <ul><li>Positive </li></ul><ul><li>Detection of metastases at unusable sites for example retroperitoneum </li></ul><ul><li>Negative </li></ul><ul><li>False positive due to inflammation primary tumor </li></ul>New possibilities Better fusion options Response after chemoradiation
    60. 61. FDG PET: POLEM study <ul><li>RCT in colorectal liver metastases </li></ul><ul><li>Patients candidates for surgery based on CT chest, liver, abdomen </li></ul><ul><li>CT versus CT and additional FDG PET (in CT negatives) </li></ul><ul><li>In FDG-PET-arm 4 patients (8%) no laparotomy based on FDG PET </li></ul><ul><li>In 14 patients (29%) in CT-arm and 5 patients (11%) in PET-arm laparotomy no resection (extensive liver metastases or extra hepatic disease) (p = 0.02). </li></ul>Oyen et al. Unpublished data
    61. 62. CRC FDG PET chemotherapy response de Geus-Oei. Ann Oncol 2008; 19: 348–352, 2008
    62. 63. Response on PET <ul><li>Overestimation of response </li></ul><ul><li>No correlation with free CRM </li></ul>Department of Surgery, University Medical Center Groningen before after Vliegen et al. submitted
    63. 64. From clinical to imaging=fusing of disciplines
    64. 65. “ Take home message” <ul><li>CT as a first screening tool: “one stop principle” for metastases and proximal tumors </li></ul><ul><li>EUS in case of considering TEM </li></ul><ul><li>MRI in distal/advanced tumors to define resection margins close to or outside the circumferential resection margin </li></ul><ul><li>Lymph node staging improves </li></ul><ul><li>PET/CT useful extra hepatic metastases </li></ul><ul><li>Assessment after neoadjuvant treatment difficult </li></ul><ul><li>Change in treatment or improvement of modality will alter this schedule </li></ul>