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

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

Delhi

Bangalore

Chennai

Bhopal

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

Prognostic factors

Tumor size Lymph node metastases Stromal invasion Lympho-Vascular space invasionHemoglobin status

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

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

• 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

Ultrasonography

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

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.

Computed Tomography

Computed Tomography

• Advantages– Detection of parametrial extension, local organ

invasion, metastases, renal abnormality– Replace IVP

• Disadvantages– Primary tumor may not be seen

• Poorly depicted– Not seen– Bulky cervix– Necrotic mass

CT findings

• Parametrial invasion– Streakiness– Extension of mass– Encasement of ureter– Thickening of uterosacral

ligament

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

Computed Tomography

*H.K. Pannu, RadioGraphics, 2001;21:1155-1168

• Lymphadenopathy– Pelvic– Para aortic

• Peritoneal deposits• Ascites• Liver/ lung metastases

Computed Tomography

Magnetic Resonance Imaging

Magnetic Resonance Imaging

• Advantages– Superior imaging resolution– Multi-planar imaging– Better soft tissue contrast

• Parametrial invasion– Focal bulge– Extension of tumor SI– Encasement of ureter/ vessels

• Intact cervical stroma excludes parametrial invasion (NPV>95%)

Magnetic Resonance Imaging

• Pelvic wall involvement– Tumor proximity (3mm

or less)– Hyperintensity of

muscles

Magnetic Resonance Imaging

Magnetic Resonance Imaging

T1W: isointense

T2W: hyperintense

CE-T1W: hyperintense

Okamoto Y et al. Radiographics 2003;23:425-445

IB

Okamoto Y et al. Radiographics 2003;23:425-445

II A

II B

Okamoto Y et al. Radiographics 2003;23:425-445

III A

Okamoto Y et al. Radiographics 2003;23:425-445

III B

IV A

Okamoto Y et al. Radiographics 2003;23:425-445

IV B

Okamoto Y et al. Radiographics 2003;23:425-445

Para-Aortic Nodes

Okamoto Y et al. Radiographics 2003;23:425-445

Okamoto Y et al. Radiographics 2003;23:425-445

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

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

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

PET in cervix

PET images of invasive cervical cancer

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

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

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

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

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

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)

FIGO 2009 recommended investigations

• Mandatory– Biopsy– Chest X-ray

• Optional– IVP– EUA– Cystoscopy– Sigmoidoscopy– CT– MRI– PET-CT

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

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

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%

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

Treatment Outline • Surgery

– Radical– Salvage

• Chemotherapy– Neoadjuvant– Concurrent– Palliative

• Radiation– Radical

• Single modality• Combined

– Hemostatic– Palliative

Five year survivals

Early stage– Ia1, Ia2

– Ib1, Ib2

– IIa

• Wertheim’s hysterectomy Type III hysterectomy

• TAH+BSO• Pelvic lymphadenectomy• ± Para-aortic LN sampling

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

Imaging in RTP[Radiation treatment planning]

• EBRT– Fluoroscopy– CT– MRI– PET– Combined

• Brachytherapy– ICRT

• CT• MRI• PET

– Interstitial• Ultrasound[TRUS]• CT

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

Fluoroscopy Demarcate the target areas in relation to bony anatomyBorders of the field varies according to the involved levels of lymph node stations

Treatment fields

CT

CT Information regarding electron density – dosimetric utility 3D-CRT, IMRT, IGRT are possible

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

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

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

2D brachytherapy planning

MR based brachytherapy

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

TRUS

MUPIT after perineal fixation

Dose distribution

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

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

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].

Thank You

Sample slides

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

T1W: isointense

T2W: hyperintense

CE-T1W: hyperintense

K.Togashi et alCa cervix- Staging with MR

imagingRadiology 1989;171:245-251

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.

Brachytherapy

• 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

TRUS Probe

@ Department of Radiotherapy, AIIMS

Selectron OT, Dr.BRA IRCH, Department of Radiation Oncology (Radiotherapy), AIIMS

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