Imaging in diagnosis and treatment of carcinoma cervix

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  • Lymphatic metastases were found in 34% of women; 13% had common iliac nodal metastases, and 9% had paraortic nodal metastases. Early invasive cervical cancer: MRI and CT predictors of lymphatic metastases in the ACRIN 6651/GOG 183 intergroup studyGynecologic OncologyVolume 112, Issue 1, January 2009, Pages 95-103
  • Cross-sectional imaging provide the tumor size and the lymph node status which are important prognostic factors
  • Figure 6a.  Stage IIb cervical carcinoma. Sagittal (a) and axial (b)T2-weighted MR images show that the cervix is almost entirely replaced by a slightly hyperintense mass. The tumor protrudes into the parametrium bilaterally (arrowheads in b); however, it does not reach the pelvic wall. Hydrometra, which is caused by the obstructed internal cervical os, is also noted (arrow in a)
  • Figure 7b.  Stage IIIa cervical carcinoma. (a)Sagittal T2-weighted MR image shows a slightly hyperintense, exophytic, solid mass that extends along the anterior vaginal wall and reaches the lower one-third of the vagina (arrow). (b) Axial T2-weighted MR image shows that the low signal intensity of the anterior vaginal wall is partly disrupted (arrowheads) and the fatty tissue between the mass and the posterior bladder wall has disappeared. However, the mass does not infiltrate the vesical mucosa.
  • Figure 8b.  Stage IIIb cervical carcinoma. (a)Sagittal T2-weighted MR image shows a slightly hyperintense, large, solid mass that extends from the uterine cervix to the lower part of the uterine body. It also extends to the lower one-third of the anterior vaginal wall (arrow). (b) Axial T2-weighted MR image shows that the tumor also reaches the left posterior wall of the bladder, although the thinned vesical muscular layer remains (arrowheads)
  • Figure 9.  Stage IVa cervical carcinoma. Sagittal T2-weighted MR image shows a hypointense mass that occupies the uterine cervix and invades the vaginal wall anteriorly. At the level of the vaginal extension, the tumor reaches the mucosa of the posterior vesical wall (arrows).
  • Figure 10a.  Stage IVb cervical carcinoma. (a)Sagittal T2-weighted MR image shows a large mass in the uterine cervix. (b, c) CT scans show metastases of paraaortic lymph nodes (arrows in b) and hematogenous hepatic metastases (c). These findings are classified as stage IVb disease
  • Imaging in diagnosis and treatment of carcinoma cervix

    1. 1. Role of Imaging in Diagnosis and Treatment of Carcinoma CervixPresenter : Jagadesan PandjatcharamModerators : Assoc.Prof. D.N. Sharma : Assoc.Prof. Sanjay Thulkar Dr.BRA IRCH, AIIMS, New Delhi, 2009
    2. 2. Introduction• Cancer cervix is the second most common cancer in the world among females [Globocan 2002]• Commonest Cancer in females in most part of India• It ranks second in Delhi [NCRP]• Highest incidence in Chennai• 30-50 years * Global Cancer Statistics,CA Cancer J Clin 2005;55;74-108 ** National Cancer Registry Programme,India 2005
    3. 3. Delhi ChennaiBhopal Bangalore
    4. 4. Risk Factors• Human Papillomaviruses-Types16,18,31,33• Young age at first intercourse (<16 years)• Multiple sexual partners• High parity• Low socioeconomic status• Poor Sexual Hygiene » Eur J Gynaecol Oncol. 1990;11(1):51-6
    5. 5. Prognostic factors Tumor size Lymph node metastases Stromal invasion Lympho-Vascular space invasion Hemoglobin status
    6. 6. Stages FIGO Staging [1994] Confined to cervix – microscopic (1A) or clinical (1B)I I A1 Less than 3 mm depth of invasion, <7 mm horizontal spread I A2 3-5 mm depth of invasion I B1 >5 mm depth of invasion, macroscopically visible I B2 > 4 cm of primary tumor size Invasion of upper vagina (2A) or parametrium (2B)II* Invasion of lower vagina (3A), pelvic wall/ hydronephrosis (3B)III Invasion of UB/ rectum (4A) or distant metastases (4B)IV *modified in FIGO 2010
    7. 7. Errors in FIGO StagingFIGO staging Errors in comparison to surgical stagingI 20-30%II 23%III 65-90%IV -Obs&Gyn,1995;86((1):43-5 -Vidaurreta J et al Gynecol Oncol 1999;75:366–71
    8. 8. FIGO Imaging tests• IVP• Barium enema• Chest x-ray• Cross sectional imaging is not mentioned, but it is increasingly used in the form of – USG / CT / MRI
    9. 9. Ultrasonography
    10. 10. Ultrasound• Transabdominal , Transvaginal• Advantages – Detect abdominal visceral metastases, hydronephrosis, bladder invasion [TVS]* – Cost-effective , Portable, Non-Ionising• Disadvantages – poor sensitivity and specificity for detection of primary *Heinrich W, Anticancer Res. 2007 Nov-Dec;27(6C):4289-94
    11. 11. COMPARISON OF DIAGNOSTIC ABILITY OF DIFFERENT IMAGING TESTS Diagnostic or prognostic Lymph Ultra Lymphatic factor angiography sonography CT MRI PET mappingDepth and width of invasion YesTumor size Yes Yes Yes YesExtension into parametria Yes YesExtension into vagina Yes Yes YesInvasion of bladder orrectum Yes YesMetastases to distant organs Yes Yes YesLymph node metastases Yes Yes Yes Yes Yes YesIntratumoral oxygenation (contrast) Yes YesTumor vascularity (contrast) Yes Follen M, Cancer 2003;98(9Suppl):2028–38.
    12. 12. Computed Tomography
    13. 13. Computed Tomography• Advantages – Detection of parametrial extension, local organ invasion, metastases, renal abnormality – Replace IVP• Disadvantages – Primary tumor may not be seen
    14. 14. CT findings• Poorly depicted – Not seen – Bulky cervix – Necrotic mass
    15. 15. Computed Tomography• Parametrial invasion – Streakiness – Extension of mass – Encasement of ureter – Thickening of uterosacral ligament
    16. 16. Computed Tomography• Pelvic wall invasion* – Tumor within 3 mm from muscles – Invasion of muscles, bone – Vascular encasement• Invasion of UB/ rectum – Loss of fat planes – Wall thickening, irregularity*H.K. Pannu, RadioGraphics, 2001;21:1155-1168
    17. 17. Computed Tomography• Lymphadenopathy – Pelvic – Para aortic• Peritoneal deposits• Ascites• Liver/ lung metastases
    18. 18. Magnetic Resonance Imaging
    19. 19. Magnetic Resonance Imaging• Advantages – Superior imaging resolution – Multi-planar imaging – Better soft tissue contrast
    20. 20. Magnetic Resonance Imaging• Parametrial invasion – Focal bulge – Extension of tumor SI – Encasement of ureter/ vessels• Intact cervical stroma excludes parametrial invasion (NPV>95%)
    21. 21. Magnetic Resonance Imaging• Pelvic wall involvement – Tumor proximity (3mm or less) – Hyperintensity of muscles
    22. 22. Magnetic Resonance ImagingT1W: isointense T2W: hyperintense CE-T1W: hyperintense
    23. 23. IBOkamoto Y et al. Radiographics 2003;23:425-445
    24. 24. II AOkamoto Y et al. Radiographics 2003;23:425-445
    25. 25. II BOkamoto Y et al. Radiographics 2003;23:425-445
    26. 26. III AOkamoto Y et al. Radiographics 2003;23:425-445
    27. 27. III B
    28. 28. IV AOkamoto Y et al. Radiographics 2003;23:425-445
    29. 29. IV BOkamoto Y et al. Radiographics 2003;23:425-445
    30. 30. Para-Aortic Nodes Okamoto Y et al. Radiographics 2003;23:425-445
    31. 31. Okamoto Y et al. Radiographics 2003;23:425-445
    32. 32. Sensitivity Specificity Accuracy *CT vs MRI$ CT MRI CT MRI CT MRIParametrial 55% 74% - - 76% 94%invasion [44-66 %] [68-79 %]Lymph nodes 43% 60% - - 86% 86% [37-57 %] [52-68 %]Bladder invasion - - 73% 91% - - [52-87 %] [83-95 %]Bladder and rectal 71% 75% - - - -invasionStromal invasion - - - - 78% 88%Staging - - - - 65% 90% $ Bipat S,et al, Gynecol Oncol. 2003 Oct;91(1):59-66 *Obs&Gyn,1995;86(1):43-5
    33. 33. Positron Emission Tomography• Scanning of the radioisotope activity in the body from the head to mid-thighs• Functional scan as it reflects the amount of function related to the substance to which the isotope is tagged• Commonly used 2-F18-Fluoro,2-Deoxy Glucose
    34. 34. Positron Emission Tomography• Advantages – Pelvic and Para-aortic nodes – Distant visceral metastases – SUV*• Disadvantages – Poor local tumor description – Poor visibility of local extension – Longer scanning time Kidd EA, Cancer. 2007 Oct 15;110(8):1738-44
    35. 35. PET in cervix
    36. 36. PET images of invasive cervical cancer
    37. 37. MRI vs PET-CT – lymph nodes Sensitivity Specificity AccuracyMRI 30.3 92.6 72.7PET-CT 57.6 92.6 85.1 P = 0.026 P=1.000 P=0.180 22 pts with stage IB - IVA Choi HJ, Cancer. 2006 Feb 15;106(4):914-22
    38. 38. Positron Emission Tomography No. of PPV NPV Sensitivity Specificity Positives /Total No.Pelvic lymph 3/27 75% 96% 75% 96%nodesPara aortic 15/119 94% 100% 100% 99%lymphnodesDistant 10/19 63% 100% 100% 94%metastases Annika Loft et al, Gyn Onc July 2007;106(1):29-34
    39. 39. PET Fusion Sensitivity SpecificityPET-CT 44.1% 93.9%PET-MR 54.2% 92.7% 79 pts had lymphadenectomy Kim SK et al, Eur J Cancer. 2009 Aug;45(12):2103-9.
    40. 40. Prognostic use of PET• 20 patients of II and III were studied for pre treatment SUVmax of the primary tumor• Responses were related to the uptake• There is a trend of poor response to standard therapy with increasing SUV. MD Thesis of Jagadesan P, Jun 2009 under Dr D.N.Sharma
    41. 41. SUV comparisons between different responsesFIGO stage No. of patients Complete Partial Responders(4) responders(16)IIa 0 Mean 7.90 9.96IIb 8 Minimum 2.90 5.40IIIa 0 Maximum 12.60 22.40 Standard ±3.02 ±8.30IIIb 12 deviation
    42. 42. Stages Revised FIGO Staging - w.e.f Jan 2009 Confined to cervix – microscopic (1A) or clinical (1B)I I A1 Less than 3 mm depth of invasion, <7 mm horizontal spread I A2 3-5 mm depth of invasion I B1 >5 mm depth of invasion, macroscopically visible I B2 > 4 cm of primary tumor size Invasion of upper vagina (2A) or parametrium (2B)II II A1 Mass ≤ 4.0cm involving upper 2/3 vagina II A2 Mass ≥ 4.0cm involving upper 2/3 vagina Invasion of lower vagina (3A), pelvic wall/ hydronephrosis (3B)III Invasion of UB/ rectum (4A) or distant metastases (4B)IV
    43. 43. FIGO 2009 recommended investigations• Mandatory • Optional – Biopsy – IVP – Chest X-ray – EUA – Cystoscopy – Sigmoidoscopy – CT – MRI – PET-CT
    44. 44. Can MRI/CT replace endoscopic evaluation?• CT and MRI have good sensitivity and specificity in detecting local invasion into bladder• NPV of 100% with MR as well as CT imaging
    45. 45. AIIMS - IRCH Attribute All patients Patients with on CT scan Patients with bladder invasion bladder invasion on Cystoscopystudy No. of patients Median age (yrs) 305 50 43 [14.1%] 45 17 [5.6%] 48 Age range (yrs) 25-85 30-77 30-75 IB 36 2 0Distribution of bladder IIA 9 0 0 IIB 65 3 1invasion in cervical cancer IIIA 10 2 1patients IIIB 139 26 11Effectiveness of CT scan in IVA 17 6 4 IVBdetecting bladder invasion 9 1 1 Unknown 20 3 0 Histopathology- 283 39 15 Squamous Adeno 14 4 2 Others 8 0 0 Grade- Well differentiated 71 5 1 Mod. differentiated 130 8 4 Poorly differentiated 84 25 11 Unknown 20 5 1
    46. 46. Bladder Bladder invasion confirmed on invasion cystoscopyobserved on CT scan Positive NegativePositive: 43 TP: 17 FP: 26 PPV: 40%Negative: 262 FN: 0 TN: 288 NPV: 100% Sensitivity Specificity 100% 92%
    47. 47. Study Sensitivity Specificity PPV NPVBipat et al, 2003 64 73 - -Sundborg et al, 1998 - - 60 100Liang et al, 2000 100 98 80 100Chung et al., 2001 - - - 100Hricack et al., 2005 42 82 39 84IRCH study, 2009 100 92 40 100
    48. 48. Treatment Outline• Surgery • Radiation – Radical – Radical – Salvage • Single modality • Combined• Chemotherapy – Hemostatic – Neoadjuvant – Palliative – Concurrent – Palliative
    49. 49. Five year survivals
    50. 50. Early stage– Ia1, Ia2 • Wertheim’s hysterectomy– Ib1, Ib2 Type III hysterectomy– IIa • TAH+BSO • Pelvic lymphadenectomy • ± Para-aortic LN sampling
    51. 51. Advanced stages• IB2 • Concurrent Radiation• Bulky IIA [>4cm] with chemotherapy• II B to IV A – EBRT plus CISPLATIN – Intra-cavitary brachytherapy Palliation with chemotherapy and/or radiation in late metastatic disease
    52. 52. Imaging in RTP [Radiation treatment planning]• EBRT • Brachytherapy – Fluoroscopy – ICRT – CT • CT • MRI – MRI • PET – PET – Interstitial – Combined • Ultrasound[TRUS] • CT
    53. 53. Imaging in RTP [Radiation treatment planning]• Simulators • Remote sensing – X-ray[fluoroscopy] – Image verification [during – CT Rad treatment] • EPID [Electronic Portal Imaging• Image acquisition Device] – CT, MRI, PET-CT, PET-MR, • Cone-beam CT USG – LASER and InfraRed positioning systems
    54. 54. Fluoroscopy Demarcate thetarget areas inrelation to bonyanatomyBorders of the fieldvaries according tothe involved levelsof lymph nodestations
    55. 55. Treatment fields
    56. 56. CT
    57. 57. CT Informationregarding electrondensity – dosimetricutility 3D-CRT, IMRT,IGRT are possible
    58. 58. MRI• Better target delineation• Need to fuse with CT to obtain Dosimetric Info.• USPIO [Ultrasmall Super- Paramagnetic Iron Oxide ] used to identify involved nodes* *Dinniwell et al, IJROBP, 2009 Jul 1;74(3):844-51
    59. 59. PET Better sensitivity indetection of pelvicand para-aortic nodes Being tried intreatment planning* *Mutic S et aI, Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):28-35
    60. 60. Brachytherapy- ICRT• CT• MRI – GEC-ESTRO guidelines for image based brachytherapy – Helps in accurate description of OARs [organ at risk]• PET* *Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):91-6
    61. 61. 2D brachytherapy planning
    62. 62. MR based brachytherapy
    63. 63. Interstitial Brachytherapy• Image Guided – Appropriate insertion of implants – TRUS {Trans-Rectal Ultrasound], MRI*• Image Based – CT [good dosimetry/ implant geometry] – MRI [better resolution but needs MR compatible applicators] – Difficult in intraoperative settings *Haie-Meder, Radiother Oncol. 2009 Jul 6
    64. 64. TRUS
    65. 65. MUPIT after perineal fixation
    66. 66. Dose distribution
    67. 67. Image guided brachytherapy - EBM• 35 patients underwent catheter insertion• CT imaging confirmed accurate placement within the uterine canal in all cases[100%] {perforation rate of 10% with unaided insertions}• Visualizing patient anatomy during insertion altered the selection of tandem length and angle in 49% of cases, resulting in improved applicator matching to anatomy.• Average insertion time significantly decreased from 34 to 26 minutes (p=0.01)• Requests for assistance from gynecologic surgical oncology declined from 38% to 5.7% of procedures Davidson MT et al, Brachytherapy. 2008 Jul-Sep;7(3):248-53
    68. 68. Conclusions• Though cervical cancer is a clinically staged disease, imaging plays an important role in deciding its management• Imaging is helpful in describing local disease extent and nodal involvement which are important prognostic factors• CT scan is a good imaging modality for pre-treatment evaluation as it is relatively easily available with good sensitivity and specificity• MRI is the best option, presently available in evaluating cervical cancer• PET scan is useful in detecting nodal spread
    69. 69. Conclusions• Image-Guided methods – It is needed for disease assessment, provisional treatment planning ("pre-planning"), applicator placement and reconstruction• Image BASED processes – contouring, definitive treatment planning and quality control of dose delivery• Image-Guided and Image-Based radiation treatments are aimed at better target localization and effective sparing of organs at risk [OAR].
    70. 70. Sample slides
    71. 71. Role of imaging• Image-Guidance – It is needed for disease assessment, provisional treatment planning ("pre-planning"), applicator placement and reconstruction• Image BASED processes – contouring, definitive treatment planning and quality control of dose delivery• MRI in staging primary - IB and above• PET-CT in staging the Nodes• CT is a cheap alternative to MRI and PET-CT
    72. 72. CE-T1W:isointense T2W: hyperintense T1W: hyperintense K.Togashi et al Ca cervix- Staging with MR imaging Radiology 1989;171:245-251
    73. 73. GEC-ESTRO guidelines for reporting IGBT• DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100.• The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes.• V100 is recommended for quality assessment only within a given treatment schedule.• For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3.
    74. 74. Brachytherapy
    75. 75. Recurrent disease• Most common within two years• Sites – Vaginal vault – Lymph nodes – Liver/ lung metastases• Imaging – MRI is preferred – High sensitivity, poor specificity • Early RT changes/ infection can not be differentiated from tumor
    76. 76. @ Department of Radiotherapy, AIIMS TRUS Probe
    77. 77. Selectron OT, Dr.BRA IRCH, Department of Radiation Oncology (Radiotherapy), AIIMS
    78. 78. Dose reduction to normal structures Rectal dose (of Pt A) Bladder dose (of Pt A)ICRT 60-70% 70-80%Interstitial 20-25% 20-25% Practised in Department of Radiation Oncology, AIIMS

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