Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Full recist violet

8,104 views

Published on

my department presentation

Published in: Health & Medicine, Business
  • Be the first to comment

Full recist violet

  1. 1. Response evaluation in solid tumors <br />PRESENTER: DR.B.SATHISH<br />(JR,1ST Yr RT)<br />MODERATOR:DR.ASHUTOSH MUKHERJEE,<br />Asst Prof RT<br />
  2. 2. Why Measure Response?<br />The word “response” is used in a number of contexts:<br />To describe outcomes in daily practice (“my patient is responding to treatment”) and make decisions about continuing therapy<br />As a surrogate for benefit (e.g. in randomized trial)<br />As the primary endpoint in phase II “screening” trials<br />
  3. 3. Why Measure Response?<br />The word “response” is used in a number of contexts:<br />To describe outcomes in daily practice (“my patient is responding to treatment”)<br />As a surrogate for benefit (e.g. in randomized trial)<br /><ul><li>As the primary endpoint in phase II “screening” trials where a decision is being taken about future of drug or regimen.RECIST criteria developed for this</li></li></ul><li>phase I<br />
  4. 4. PHASE II<br />
  5. 5.
  6. 6.
  7. 7. PHASE III<br />
  8. 8.
  9. 9. PHASE IV<br /><ul><li>“Post-Marketing” Studies
  10. 10. Expanded Treatment Groups
  11. 11. Under studied groups (racial/gender)
  12. 12. Long term benefit
  13. 13. Long term risk
  14. 14. Low frequency toxicity</li></li></ul><li>history<br />Early attempts 1960s<br />Pre imaging era –blood was used to assess tumor response <br />WHO first published tumor response criteria for solid tumors in 1981<br />RECIST was presented in 1999 to ASCO and published in 2000<br />RECIST VERSION 1.1 published in October 2008<br />
  15. 15. Response Criteria in Clinical Trials<br />Mid-late 1990s: International working group began to meet to address some shortcomings of WHO. For example:<br />Complexity (bidimensional measurements)<br />New technologies (CT)<br />Silent on many areas so open to varying interpretation <br />i.e. the “standard” was no longer the standard<br />
  16. 16. Response Evaluation Criteria in Solid Tumors: “RECIST” Working Group<br />1995: International representation from different research organizations<br />Revisit definitions, assumptions, implications<br />Harmonize to the best standards<br />Simplify where possible<br />Update with new concepts<br />An ongoing process………<br />
  17. 17. RECIST version 1.1<br />Response Evaluation Criteria in Solid Tumors<br /><ul><li>Standardized repeatable method for measuring response to therapy for solid tumors
  18. 18. NOT EQUIVALENT TO A CLINICAL READ!!!</li></ul>RECIST is a combination of both qualitative and quantitative assessment<br />Based on concept of target lesions and non-target lesions<br /><ul><li>Target lesions are quantitatively assessed
  19. 19. Non-target lesions are qualitatively assessed</li></li></ul><li>Key RECIST Elements<br />One-dimensional measurement of longest diameters<br />Measurable lesion > 10 mm (5 mm Spiral CT)<br />Identify up to 5 measurable lesions; maximum 2 per organ. Follow sum of longest diameters (SLD)<br />The “SLD” is a quantitative assessment<br />Major application intended for trials where response is primary endpoint<br />Separate criteria used for malignant lymphoma so RECIST not used<br />Can be used in brain tumors but separate criteria are also published<br />
  20. 20. Target Lesions<br /><ul><li>Target lesions are chosen based on 3 factors:</li></ul>Must be EASILY (and reproducibly) measurable<br />Must be representative of the disease (clearly metastasis)<br />Must be representative of distribution (choose measurable lesions from all involved organs)<br />Target lesions must be measurable<br />Definition of Measurable Lesions<br />Size Matters <br />Conventional CT or MRI (non-spiral):<br />If slice collimation <10mm, minimum lesion size is 20 mm<br />If slice collimation >10mm, minimum lesion size is 2 x collimationex. Slice collimation = 15mm, minimum lesion size = 30mm<br />Spiral CT<br />If slice collimation <5mm, minimum lesion size is 10 mm<br />If slice collimation >5mm, minimum lesion size is 2 x collimationex. Slice collimation = 7mm, minimum lesion size = 14mm<br />16<br />
  21. 21. Measure the longest in plane diameter<br />
  22. 22. Measurable lesion<br />The round shape and sharp boundaries of this lung lesion (arrow) makeit ideally suited for linear measurement.<br />
  23. 23. Target Lesions<br />Target lesions must be reproduciblymeasurable<br />Definition of reproducibly measurable lesions<br />Consistency across time points <br />Pick lesions with well defined edges or margins<br />Always measure longest diameter<br />Measure lesions on same phase or same sequence (MRI)<br />Only measure lesions that are definitely metastases(If unsure don’t measure)<br />Pick lesions that are stable in position, try to avoid mobile lesions (Avoid mesenteric masses that change in position)<br />
  24. 24.
  25. 25. Target Lesions<br />Target lesions should represent distribution of disease<br />Representative of disease throughout body <br />Pick lesions from different areas of the body<br />Do not choose > 2 lesions in any one organ or anatomic location<br />Organs are well defined <br />For lymphoma choose nodes from different nodal stations<br />
  26. 26. Non – Target Lesions<br />All aspects of disease not chosen as Target Lesions<br />All non-measurable lesions(LD < 10 mm and LN 10-14mm in short axis)<br />Measurable lesions that were not chosen as target lesions<br />Lesions that may be (but not definitely) metastases<br />Non- measurable lesions<br />Not suitable for accurate repeated measurements<br /><ul><li>Ascites
  27. 27. Pericardial effusion• Leptomeningeal disease
  28. 28. Pleural effusions • Inflammatory breast disease
  29. 29. Cystic lesions •Lymphangitis cutis/pulmonis
  30. 30. Bone lesions • Brain lesions
  31. 31. Irradiated lesions • Ground glass lung lesions</li></li></ul><li>Non measurable lesion<br />
  32. 32. Special considerations<br />Lytic bone lesions with soft tissue component which meets the definition of measurability by CT /MRI can be considered measurable<br />Blastic bone lesions are not measurable<br />Simple cysts are not considered malignant so not taken as targets<br />Cystic metastases meeting the criteria can be considered but if non cystic lesions are present they are preferred as targets<br />
  33. 33. Clinical evaluation<br />Considered measurable only if superficial(e.g. skin nodules and lymph nodes)<br />10mm minimum size by caliper measurement{if immeasurable by calipers it is termed as non-measurable}<br />Documentation with color photo and ruler is needed<br />Imaging is always better than clinical assessment<br />
  34. 34. CXR<br />Measurable lesion<br />20 mm minimum size <br />Clearly defined <br />Surrounded by aerated lung<br />Full inspiration, PA view with constant tube- chest distance at every follow up<br />
  35. 35. Best modality<br />
  36. 36. Ct scan<br />If 5mm slice thickness then the lesion should be minimum 10mm<br />Minimum size of lesion>=double slice thickness<br />LD is selected in axial plane only<br />Para spinal tumors are better measured in coronal/sagittal plane<br />Lesions bordering chest wall and mediastinal lesions(don’t use CXR as slight motion can affect interpretation)<br />Oral and iv contrast to accentuate bowel/vessels against soft tissue mass is routinely done<br />Most abdominal images are taken in the portal venous phase<br />
  37. 37. MRI <br />Complex issue<br />MRI Scanners vary in images produced based on<br />Magnet strength<br />Coil design <br />Patient cooperation<br />Motion artifacts<br />Use same scanner and same anatomical plane<br />As far as possible use a CT scan<br />IOC for follow up of breast lesions in NACT (not CT or mammogram)<br />
  38. 38. USG<br />Not used in clinical trials because interpretation is subjective<br />Alternative to clinical measurements for<br />Superficial palpable lymph nodes<br />Subcutaneous lesions<br />Thyroid nodules<br />To confirm disappearance of superficial lesions assessed clinically<br />If there is a paraaortic node and distended bowel USG wont detect it and so downstage the disease<br />Reproducibility of entire examination at later date not accurate<br />
  39. 39. Endoscopy and laparoscopy<br />Not yet been fully or widely validated<br />Requires expertise and restricted availability<br />Can be used to confirm CR by taking biopsy<br />
  40. 40. Tumor markers<br />Cant be used alone to assess response<br />Specific guidelines for PSA and CA125 have been published<br />Gynecological cancer intergroup has developed CA125 progression criteria which are to be integrated with objective tumor assessment for use in first line trials in ovarian cancer<br />
  41. 41. hpe<br />To differentiate partial vs. complete response in rare cases(e.g. residual tumors can be benign in germ cell tumors)<br />Worsening effusion in stable disease or responded disease needs cytology to differentiate progression vs. drug induced e.g. taxanecompunds<br />
  42. 42. Measuring Lesions<br />Baseline Scan – Initial Review<br />Determine if a single measurable lesion is present<br />Once single lesion is found, confirm the neoplastic nature by biopsy<br />Baseline assessment never >4weeks before the beginning of treatment<br />Baseline scan – Full Review<br />Determine target lesions and non-target lesions<br />Target lesions<br />Record site and longest diameter<br />Measure longest diameter (LD) on slice where the lesion is largest<br />Use magnification and appropriate window/level<br />Non-target lesions<br />Record site and description<br />Will be assessed qualitatively in the future<br />
  43. 43. Malignant lymph nodes<br />To be considered pathological a lymph node must be >=15mm in short axis by CT scan with slice thickness not more than 5 mm<br />Only short axis is measured at baseline and follow up(e.g. for an abdominal node 20*30 mm size 20mm is taken as short axis)<br />Multiple lesions in single organ can be recorded as single item e.g. multiple pelvic nodes/multiple liver mets<br />
  44. 44. LYMPH NODE ASSESSMENT<br />THE SOLID LINE IS THE SHORT AXIS<br />
  45. 45. Short axis is 45.316<br />
  46. 46. Example: 10 Lesions<br />
  47. 47. Tumor Response - Target Lesions<br />Complete response (CR): Disappearance of all target lesions and any pathological LN(target or non target must have <10 mm short axis)<br />Partial response (PR): >= 30% decrease in the SLD taking as reference the baseline SLD<br />Progression (PD): >= 20% increase in the SLD taking as reference the smallest SLD since beginning of treatment and also a minimum absolute increase of 5mm<br />Stable decrease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest SLD since beginning of treatment <br />Unknown (UN): If one or more unknown is present and the SLD is not indicative of PD (explanatory comments required)<br />
  48. 48. 6 cm<br />CR<br />PR <br />3cm<br />5cm<br />SD<br />PD<br />9cm<br />7cm<br />
  49. 49. Tumor Response – Non-Target Lesions<br />Complete Response (CR):Disappearance of all lesions and normalization of all tumor marker levels and lymph nodes <10 mm in short axis<br />Non CR/Non-PD :persistence of one or more lesions and/or maintenance of tumor markers above normal limits<br />Progression (PD):appearance of new lesions and/or unequivocal progression of existing lesions<br />Unknown (UN): If “not assessed” or “not imaged” <br />
  50. 50. Tumor Response – New Lesions<br />Unequivocal New Lesions = Progression (PD)<br /><ul><li>Any new malignant lesion in the same or different site
  51. 51. Any re-appearing lesion</li></ul>PET scan( FDG uptake period of 60 min prior to imaging)<br />-ve baseline but +ve follow up –PD<br />No baseline scan and +ve follow up<br />If it is at a new site then –consider PD<br />If not at the same site additional follow up with CT to confirm PD<br />If follow up CT is negative then it is not PD<br /><ul><li>Best overall response is the best response from the start of treatment until disease progression/recurrence</li></li></ul><li>Follow-up: Target Lesions<br />On follow-up scans, once a lesion is identified as Target:<br />Must continue to measure even if LD falls below size criteria<br />Same method(e.g.CT) of assessment as baseline should be used<br />Measure LD regardless of location (slice) or orientation on prior scan<br />Choose slice where lesion is largest, even if different than baseline<br />Measure LD regardless of poor image quality or poorly defined lesion boundaries (i.e., if target lesion is imaged, LD must be measured)<br />If a target lesion is visible but too small to measure, list as “5mm”<br />If radiologist feels lesion has disappeared record as 0 mm<br />If lesion is not imaged, enter “Unknown” (outside FOV) If “unknown” is entered, comments are required<br />
  52. 52. baseline<br />Follow up<br />
  53. 53. Splitting and merging<br />
  54. 54. merging<br />
  55. 55. Follow-up Scans<br />New lesions seen on follow-up:<br />Any lesion that appears after baseline (including new lesions in irradiated areas)<br />Any lesions that re-appear will be considered new lesions<br />If a lesion reappears after CR then it is PD<br />If lesion reappears in PR/SD measure its LD and add to SLD to assess response<br />No miminum diameter is needed for a new lesion and if equivocal repeat CT in the next visit and get a radiologist opinion<br />
  56. 56. Missing assessments and in evaluable designation<br />No imaging done at protocol specified time point-non evaluable(NE)<br />Not all lesions measured at follow up-NE(conditions apply)<br />Lost to follow-up : in evaluable<br />
  57. 57. Special scenarios<br />If global deterioration of health requiring Rx discontinuation then it is classified as symptomatic deterioration<br />It is not an objective response but a reason to discontinue therapy<br />If u cant differentiate normal tissue from residual disease/scarring-- biopsy/PET scan is done before calling it as complete response<br />If equivocal findings at follow up wait till next follow up to confirm PD,SD or PR<br />If solid lesion becomes necrotic still measure LD and make a note of the necrosis<br />
  58. 58. Importance of iv contrast<br />
  59. 59. Continue measuring even if cavity develops<br />
  60. 60. Frequency of reevaluation<br />Protocol specific<br />Which organ?<br />How often?<br />Goal of trial - response or TTP/PFS?<br />Routine calendar scheduled re-evaluation <br />In phase 2 studies follow up every 6-8 weeks is an acceptable norm<br />
  61. 61. Confirmation of response<br />Particularly useful in non randomized trials where response in the primary end point<br />To ensure that response is not a measurement error<br />If criteria for CR or PR are met reassess in no less than 4 weeks to confirm response<br />If SD then criteria must be met at least once after study entry at a minimum interval defined by study protocol<br />
  62. 62. Duration of overall response<br />From the time the criteria for CR/PR is met first till the day 1 of objectively documented PD or recurrence<br />Duration of SD- time from start of Rx/date of randomization till the criteria for PD are met<br />The response is reviewed by a panel of experts independent of the study<br />
  63. 63. Pfs and ttp<br />Baseline estimation of expected PFS/TTP without treatment<br />Methodology to be applied should be thoroughly described in the protocol<br />
  64. 64. Reporting results<br />CR<br />PR<br />SD<br />PD<br />Inevaluable for response<br />Early death from malignancy<br />Early death from toxicity<br />Early death due to some other cause<br />Unknown(not assessable,insufficent data)<br />(1- 4 are called eligible patients to calculate response rate)<br />
  65. 65. Tumor Response – Summarized<br />
  66. 66. Issues Arising since RECIST Implementation<br />Minimum number of lesions: Can fewer than 5 lesions be assessed? <br />Use of RECIST in randomized trials<br />Use of newer imaging technologies such as PET and MRI. <br />Use of RECIST in trials of non-cytotoxic drugs. <br />
  67. 67. Example: 10 Lesions<br />
  68. 68. Example: 6 largest selected<br />
  69. 69. Example: 3 largest selected<br />
  70. 70. RECIST in Randomized Trials<br />This presents two issues:<br />Can rigorous response assessment requirements be relaxed?<br />How to assess progression in patients who do not have measurable lesions?<br />
  71. 71. Measuring Objective Response in Phase III Trials<br />If objective response is the end point then use RECIST 1.1<br />If objective response is not the primary endpoint, then method of reporting results should be pre-specified in the protocol<br />
  72. 72. Progression in Phase III Trials<br />Important issue, since as noted PFS and TTP becoming common primary endpoints.<br />No problem if entry is restricted to patients with measurable lesions!<br />What about patients with non-measurable disease only?<br />
  73. 73. Progression in Non-Measurable Disease<br />Fundamental problem: how to measure an increase in that which is not measurable?<br />Options:<br />Count “new disease” only<br />Look for “unequivocal progression” of non-measurable lesions: subject to external review<br />Something else? <br />Go back to using overall survival?<br />
  74. 74. What about Functional Changes?<br />RECIST: <br />Based on anatomical tumoursize<br />Does not take into account metabolic function<br />Does not take into account blood flow parameters<br />
  75. 75. Are RECIST Applicable in Trials of Non-Cytotoxics?<br />One does not need new “response criteria” for assessing non-cytotoxics<br />One may need to change the “usual” hypotheses that drive phase II design….so instead of a response rate of interest of 20% (typical for many cytotoxic phase II trials), we could:<br />Look for PR + CR rate of 10%<br />Look for SD rate >50%<br />Look for CR + PR + SD rate >60%<br />(or whatever seems meaningful)<br />
  76. 76. What HAS changed in RECIST 1.1<br />
  77. 77.
  78. 78. Limitations of RECIST guidelines<br />Tumor morphology<br />Confluent, Irregular borders<br />Unusual configuration; Circumferential (e.g. mesothelioma)<br />Lesion length > 1.5-2 times lesion width<br />Discordant results due to RECIST technique<br />Uni-dimensional measurement<br />Shape changes may confound results<br />Non-spherical, asymmetric tumor growth<br />Tumor size: Sub-centimeter tumors<br />Choosing representative tumor burden<br />Problematic when tumor burden is substantial<br /> Unpredictable Tumor Behavior<br />Differential tumor shrinkage/growth<br />
  79. 79. Future?<br />RECIST-Unidimensional<br />WHO-Bidimensional<br />Volumetric<br />
  80. 80. Thank you<br />

×