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Role of Imagingin
Diagnosis and Treatmentof
Carcinoma Cervix
Presenter : Jagadesan Pandjatcharam
Moderators : Assoc.Prof. D.N. Sharma: Assoc.Prof. Sanjay Thulkar
Dr.BRA IRCH, AIIMS, New Delhi, 2009
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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
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Delhi
Bangalore
Chennai
Bhopal
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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
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Prognostic factors
Tumor size Lymph node metastases Stromal invasion Lympho-Vascular space invasionHemoglobin status
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Stages FIGO Staging [1994]
I Confined to cervix – microscopic (1A) or clinical (1B)
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
II* Invasion of upper vagina (2A) or parametrium (2B)
III Invasion of lower vagina (3A), pelvic wall/ hydronephrosis (3B)
IV Invasion of UB/ rectum (4A) or distant metastases (4B)
*modified in FIGO 2010
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Errors in FIGO Staging
FIGO staging Errors in comparison to surgical staging
I20-30%
II 23%
III 65-90%
IV
-Obs&Gyn,1995;86((1):43-5-Vidaurreta J et al Gynecol Oncol 1999;75:366–71
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• IVP• Barium enema• Chest x-ray• Cross sectional imaging is not mentioned, but
it is increasingly used in the form of – USG / CT / MRI
FIGO Imaging tests
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Ultrasonography
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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
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Diagnostic or prognostic factor
Lymph angiography
Ultra sonography CT MRI PET
Lymphatic mapping
Depth and width of invasion Yes Tumor size Yes Yes Yes Yes Extension into parametria Yes Yes Extension into vagina Yes Yes Yes Invasion of bladder or rectum Yes Yes
Metastases to distant organs Yes Yes Yes Lymph node metastases Yes Yes Yes Yes Yes
Intratumoral oxygenation Yes
(contrast) Yes
Tumor vascularity Yes
(contrast) Yes
COMPARISON OF DIAGNOSTIC ABILITY OF DIFFERENT IMAGING TESTS
Follen M, Cancer 2003;98(9Suppl):2028–38.
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Computed Tomography
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Computed Tomography
• Advantages– Detection of parametrial extension, local organ
invasion, metastases, renal abnormality– Replace IVP
• Disadvantages– Primary tumor may not be seen
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• Poorly depicted– Not seen– Bulky cervix– Necrotic mass
CT findings
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• Parametrial invasion– Streakiness– Extension of mass– Encasement of ureter– Thickening of uterosacral
ligament
Computed Tomography
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• 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
Computed Tomography
*H.K. Pannu, RadioGraphics, 2001;21:1155-1168
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• Lymphadenopathy– Pelvic– Para aortic
• Peritoneal deposits• Ascites• Liver/ lung metastases
Computed Tomography
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Magnetic Resonance Imaging
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Magnetic Resonance Imaging
• Advantages– Superior imaging resolution– Multi-planar imaging– Better soft tissue contrast
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• Parametrial invasion– Focal bulge– Extension of tumor SI– Encasement of ureter/ vessels
• Intact cervical stroma excludes parametrial invasion (NPV>95%)
Magnetic Resonance Imaging
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• Pelvic wall involvement– Tumor proximity (3mm
or less)– Hyperintensity of
muscles
Magnetic Resonance Imaging
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Magnetic Resonance Imaging
T1W: isointense
T2W: hyperintense
CE-T1W: hyperintense
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Okamoto Y et al. Radiographics 2003;23:425-445
IB
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Okamoto Y et al. Radiographics 2003;23:425-445
II A
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II B
Okamoto Y et al. Radiographics 2003;23:425-445
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III A
Okamoto Y et al. Radiographics 2003;23:425-445
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III B
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IV A
Okamoto Y et al. Radiographics 2003;23:425-445
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IV B
Okamoto Y et al. Radiographics 2003;23:425-445
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Para-Aortic Nodes
Okamoto Y et al. Radiographics 2003;23:425-445
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Okamoto Y et al. Radiographics 2003;23:425-445
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CT vs MRI$ Sensitivity Specificity Accuracy *
CT MRI CT MRI CT MRIParametrial invasion
55%[44-66 %]
74%[68-79 %]
- - 76% 94%
Lymph nodes 43%[37-57 %]
60%[52-68 %]
- - 86% 86%
Bladder invasion - - 73%[52-87 %]
91%[83-95 %]
- -
Bladder and rectal invasion
71% 75% - - - -
Stromal 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
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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
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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
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PET in cervix
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PET images of invasive cervical cancer
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MRI vs PET-CT – lymph nodes
Sensitivity Specificity Accuracy
MRI 30.3 92.6 72.7
PET-CT 57.6 92.6 85.1
P = 0.026 P=1.000 P=0.180
Choi HJ, Cancer. 2006 Feb 15;106(4):914-22
22 pts with stage IB - IVA
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Positron Emission TomographyNo. of Positives/Total No.
PPV NPV Sensitivity Specificity
Pelvic lymph nodes
3/27 75% 96% 75% 96%
Para aortic lymph nodes
15/119 94% 100% 100% 99%
Distant metastases
10/19 63% 100% 100% 94%
Annika Loft et al, Gyn Onc July 2007;106(1):29-34
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PET Fusion
Sensitivity Specificity
PET-CT 44.1% 93.9%
PET-MR 54.2% 92.7%
Kim SK et al, Eur J Cancer. 2009 Aug;45(12):2103-9.
79 pts had lymphadenectomy
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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
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SUV comparisons between different responses
Complete
responders(16)
Partial Responders(4)
Mean 7.90 9.96
Minimum 2.90 5.40
Maximum 12.60 22.40
Standard
deviation
±3.02 ±8.30
FIGO stage No. of patients
IIa 0
IIb 8
IIIa 0
IIIb 12
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Stages Revised FIGO Staging - w.e.f Jan 2009
I Confined to cervix – microscopic (1A) or clinical (1B)
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
II Invasion of upper vagina (2A) or parametrium (2B)
II A1 Mass ≤ 4.0cm involving upper 2/3 vagina
II A2 Mass ≥ 4.0cm involving upper 2/3 vagina
III Invasion of lower vagina (3A), pelvic wall/ hydronephrosis (3B)
IV Invasion of UB/ rectum (4A) or distant metastases (4B)
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FIGO 2009 recommended investigations
• Mandatory– Biopsy– Chest X-ray
• Optional– IVP– EUA– Cystoscopy– Sigmoidoscopy– CT– MRI– PET-CT
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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
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AIIMS - IRCH study
Attribute All patients Patients with bladder invasion
on CT scan
Patients with bladder invasion on Cystoscopy
No. of patients 305 43 [14.1%] 17 [5.6%]Median age (yrs) 50 45 48Age range (yrs) 25-85 30-77 30-75
IB 36 2 0IIA 9 0 0IIB 65 3 1
IIIA 10 2 1IIIB 139 26 11IVA 17 6 4IVB 9 1 1
Unknown 20 3 0Histopathology-
Squamous283 39 15
Adeno 14 4 2Others 8 0 0
Grade- Well differentiated 71 5 1Mod. differentiated 130 8 4
Poorly differentiated 84 25 11Unknown 20 5 1
Distribution of bladder invasion in cervical cancer patientsEffectiveness of CT scan in detecting bladder invasion
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Bladder invasion
observed on CT scan
Bladder invasion confirmed on cystoscopy
Positive Negative
Positive: 43 TP: 17 FP: 26 PPV: 40%
Negative: 262 FN: 0 TN: 288 NPV: 100%
Sensitivity100%
Specificity92%
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Study Sensitivity Specificity PPV NPV
Bipat et al, 2003 64 73 - -
Sundborg et al, 1998 - - 60 100
Liang et al, 2000 100 98 80 100
Chung et al., 2001 - - - 100
Hricack et al., 2005 42 82 39 84
IRCH study, 2009 100 92 40 100
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Treatment Outline • Surgery
– Radical– Salvage
• Chemotherapy– Neoadjuvant– Concurrent– Palliative
• Radiation– Radical
• Single modality• Combined
– Hemostatic– Palliative
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Five year survivals
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Early stage– Ia1, Ia2
– Ib1, Ib2
– IIa
• Wertheim’s hysterectomy Type III hysterectomy
• TAH+BSO• Pelvic lymphadenectomy• ± Para-aortic LN sampling
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Advanced stages• IB2
• Bulky IIA [>4cm]• II B to IV A
• Concurrent Radiation with chemotherapy– EBRT plus CISPLATIN– Intra-cavitary
brachytherapy
Palliation with chemotherapy and/or radiation in late metastatic disease
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Imaging in RTP[Radiation treatment planning]
• EBRT– Fluoroscopy– CT– MRI– PET– Combined
• Brachytherapy– ICRT
• CT• MRI• PET
– Interstitial• Ultrasound[TRUS]• CT
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Imaging in RTP[Radiation treatment planning]
• Simulators– X-ray[fluoroscopy]– CT
• Image acquisition– CT, MRI, PET-CT, PET-MR,
USG
• Remote sensing– Image verification [during
Rad treatment]• EPID [Electronic Portal Imaging
Device]
• Cone-beam CT
– LASER and InfraRed positioning systems
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Fluoroscopy Demarcate the target areas in relation to bony anatomyBorders of the field varies according to the involved levels of lymph node stations
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Treatment fields
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CT
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CT Information regarding electron density – dosimetric utility 3D-CRT, IMRT, IGRT are possible
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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
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PET
Better sensitivity in detection of pelvic and para-aortic nodes Being tried in treatment planning*
*Mutic S et aI, Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):28-35
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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
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2D brachytherapy planning
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MR based brachytherapy
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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
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TRUS
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MUPIT after perineal fixation
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Dose distribution
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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
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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
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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].
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Thank You
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Sample slides
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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
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T1W: isointense
T2W: hyperintense
CE-T1W: hyperintense
K.Togashi et alCa cervix- Staging with MR
imagingRadiology 1989;171:245-251
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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.
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Brachytherapy
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• 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
Recurrent disease
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TRUS Probe
@ Department of Radiotherapy, AIIMS
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Selectron OT, Dr.BRA IRCH, Department of Radiation Oncology (Radiotherapy), AIIMS
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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