Transcript
Page 1: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Advances in Cervical Cancer Advances in Cervical Cancer Akila Viswanathan, MD MPHAssociate Professor of Radiation Oncology

ManagementManagementAssociate Professor of Radiation Oncology

BWH/Dana-Farber Cancer InstituteHarvard Medical School

April 14, 2012

Page 2: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

DisclosuresDisclosures

• No financial disclosuresNo financial disclosures

• Board member of American Brachytherapy SocietySociety

Page 3: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Learning Objectives:Learning Objectives:

1. Early stage cervical cai di i-Post operative radiation

2. Locally advanced cervical cancer- External beam w conc chemo

3. Brachytherapyy py

Viswanathan ASTRO 2012

Page 4: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis
Page 5: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Presentation• Vaginal bleedingVaginal bleeding

• Discharge

B k i• Back pain

• Superficial ulceration

• Exophytic tumor

• May spread to the vaginal fornices,May spread to the vaginal fornices, parametria, bladder or rectum

Viswanathan ASTRO 2012

Page 6: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Diagnostic work-up

Visible lesion:

• EUA• EUA

• Chest X-ray, CBC, Labs, Urinalysis

• Stage > 3: Cystoscopy, Rectosigmoidoscopy

• Optional: MRI, PET, CT, US, IVP

• Lymphangiogram not in U.S.

Viswanathan ASTRO 2012

Page 7: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Manual Examination

Viswanathan ASTRO 2012

Page 8: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

FIGO Staging System

• Studies permitted by FIGO for staging:– EUA, colposcopy, endocervical curettage, hysteroscopy,

cystoscopy, proctoscopy, IVP, CXR, skeletal x-raycystoscopy, proctoscopy, IVP, CXR, skeletal x ray

• Studies not permitted but often obtained in the U.S.: CT, MRI pelvis, PET

• If there is disagreement about parametrial invasion, the earlier stage should be chosen.N LN i l d d i FIGO t i• No LN included in FIGO staging

Viswanathan ASTRO 2012

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2009 Staging revision2009 Staging revision

• Stage IIA1: upper 2/3 vag involvement with size < 4cm

• Stage IIA2: upper 2/3 vag involvement with size > 4cm

Page 10: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Prognostic FactorsPrognostic Factors

• FIGO Stage• Tumor Size• Lymph node status• HistologyHistology• Smoking• Hemoglobin ? (> 10) • Post hysterectomy• Post-hysterectomy

- Lymphovascular invasion- Percent stromal invasion

Parametrial extension- Parametrial extension• Others: SCC-Ag, Age• Predictive factors: duration

of treatment use of chemoof treatment, use of chemo-RT, brachytherapy

Page 11: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

PET at diagnosis: Detection of Nodal Metastases

Page 12: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Rule of 15Rule of 15

Stage 5 yr survival %+ pelvic LNStage 5 yr survival %+ pelvic LN

I 85 15

II 70 30II 70 30

III 55 45

Prophylaxis of para-aortic LN? Not standardized

If + pelvic LN large tumor size LVI prophylactic PAN RTIf + pelvic LN, large tumor size, LVI - prophylactic PAN RT

Resect or boost LNs >3cm

Page 13: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

PET + LN predict survivalPET + LN predict survival

• 513 patients513 patients

• Stage independent

• Positive pelvic LNPositive pelvic LN

better than PAN

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Post-treatment PET predicts survivalPost treatment PET predicts survival

Schartz et al. JAMA 21;298(19):2289-95

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Locally advanced casesMR: Sag and Axial T2-weighted

ImagesImages

Page 16: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Predictive value of MRIWang et al. Cancer 2010; 116(21):5093-101

• MRI at diagnosis, 2-3 k i EBRT fweeks into EBRT; after

45Gy, 1-2 mo post Tx

R i ti• Regression ratio predictive of recurrencerecurrence

• Initial MR Volume 40 cc and ratio:cc and ratio:

• post-EB vol/initial vol <20%– significantly lower LC

and DSS

Page 17: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Management of Stage IA

• Cryotherapy

• Laser Conization or AblationAblation

• Cold Knife Conization

• Loop Electrosurgical p gExcision Procedure (LEEP)

• If LVI+: Radical h t thysterectomy

• Trachelectomy

• Simple Cone + LND

Viswanathan ASTRO 2012

• Simple Cone + LND

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Management of IB1: RadicalManagement of IB1: Radical Hysterectomy

Viswanathan ASTRO 2012

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Radiation or h sterectomRadiation or hysterectomy Landoni et al. Lancet 350: 535, 1997

• Randomized trial of 469 patients

• IB or IIA cervical cancer• IB or IIA cervical cancer

• Median f/u: 87 months

• 54% of IB1 & 84% of IB2 surgical pts had adjuvant radiation for high risk features

Viswanathan ASTRO 2012

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Radiation or Hysterectomy

5 year OS DFS Rec tox

RT 83% 74% 25% 12%RT 83% 74% 25% 12%

Surgery 83% 74% 26% 28%

(p=0.0004)

SBO risk increased with LND

Viswanathan ASTRO 2012

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Post-operative RT : GOG 92I t di t i k f tIntermediate risk factors

Sedlis et al. 1999;73:177-83.

LVI Stromal invasion Tumor size

+ D 1/3 A+ Deep 1/3 Any

+ Middle 1/3 > 2cm

+ Superficial 1/3 > 5cm

-- Deep or middle 1/3 > 4cmDeep or middle 1/3 4cm

N d 2 f 3 f tNeed 2 of 3 features

Page 22: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

GOG 92 update IJROBP 65(1):169-176, 2006

• Median f/u 10 years• 46% reduction in risk of

recurrence (HR 0 54)recurrence (HR 0.54) – 30% improvement in

overall survival (p=0.07)Increases Grade 3/4– Increases Grade 3/4 toxicity by 4.5%

– 42% reduction in risk of progression/deathprogression/death

– Reduction in adenoca 8.8% vs. 44%

Viswanathan ASTRO 2012

Accruing GOG 263: concurrent weekly Cisplatin vs. no chemo

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Post-op Chemo-RT: SWOG 8797Post op Chemo RT: SWOG 8797High-risk patients

• + LN• + Margins• + Parametria• 4 yr PFS

– 63% vs. 80% (p=0.003)

• 4yr OS 71% 81% ( 0 007)– 71% vs. 81% (p=0.007)

Peters et al. JCO 18:1606-13, 2000

A i RTOG 0724 dj C b /T l

Viswanathan ASTRO 2012

Accruing RTOG 0724: adj Carbo/Taxol

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Locally Advanced Cervical Locally Advanced Cervical Cancer Cancer

Viswanathan ASTRO 2012

Page 25: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Chemo-sensitizationChemo sensitization

MM G1

RT sensitiveTaxol

Cell cycleTaxol

SG2 Cis-platinumHydrea

RT resistant

Page 26: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

CisplatinumCisplatinumcis-Diammine dichloroplatinum[II]

• Cytotoxic and supra-additive with RT

• Inhibits repair of sublethal and potentially lethal b s epa o sub e a a d po e a y e aRT injury

• Toxicities: renal, hematologic, GI, g ,– Check Creatinine – stent if obstructed

– CBC – transfuse if Hct <30

– Caution low performance status, medical comorbidities, nutritional status (cardiac, pulmonary)

Page 27: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Randomized trials of cisplatin-containing CT-RT leading p g gto NIH clinical alert in April, 1999

ailu

ree

risk

of fa

Rel

ativ

e

Page 28: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

CT-RT of Cervical CancerCT-RT of Cervical CancerCT RT of Cervical CancerSettings in which chemoradiation has

demonstrated advantage over RT alone

CT RT of Cervical CancerSettings in which chemoradiation has

demonstrated advantage over RT alone

• Locally-regionally advanced (PAN -)• Locally-regionally advanced (PAN -)Locally regionally advanced (PAN )– IB2-IVA disease

• Pre operative (bulky IB)

Locally regionally advanced (PAN )– IB2-IVA disease

• Pre operative (bulky IB)• Pre-operative (bulky IB)

• Post-operative, high risk

• Pre-operative (bulky IB)

• Post-operative, high risk– Positive nodes, margins, parametria – Positive nodes, margins, parametria

Page 29: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

RT versus RT and chemotherapyRT versus RT and chemotherapyRTOG 90-01: Morris et al.

NEJM 340:1137, 1999

• IB1, IB2, IIA (N+ or >5cm); IIB-IVA; PAN neg (lymphangiogram or surgery)

• 403 patients• Arm 1: Extended field RT (pelvic & PAN)

RT dose: 45Gy pelvis and PAN + 40 Gy point A• Arm 2: RT+CDDP 75 mg/m2 + 5FU 4g

d1 5 q3w x 3 cyclesd1-5 q3w x 3 cycles

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RTOG 90 01: 8 yr updateRTOG 90-01: 8 yr updateJ Clin Oncol 22(5):872-880, 2004

8yOS DFS LRF DM PAN

RT+CDDP+5FU 67% 61% 18% 20% 9%RT+CDDP+5FU 67% 61% 18% 20% 9%

EF RT 41% 36% 35% 35% 4%

p= <0.0001 p=0.15

• Only trial with RT alone arm

• Largest RR reduction (0.48)

• G3+ toxicity: 13% vs. 12% (p=0.65)

• St IB-IIA (272 pts): 78% vs. 55% (p<0.001)

St III IVA (117 t ) 59% 47% ( 0 066)• St III-IVA (117 pts): 59% vs. 47% (p=0.066)

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Weekly CDDP Chemoradiotherapy for CervicalWeekly CDDP Chemoradiotherapy for Cervical Cancer

GOG 120 526 (1999 2007) HU+RT +++

Trial Year Control Result

GOG 120 526 (1999, 2007) HU+RT +++

GOG 123 374 (1999, 2003) RT only +++

NCIC 259 (2002) RT only -

Page 32: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

NCIC trial: why negative?y g

• Smallest # patients, lowest % stage III-IVp g

insufficient power to detect difference

• Shortest treatment duration

– Improved outcome in both arms

• Anemia higher in chemotherapy armAnemia higher in chemotherapy arm

• Para-aortic LN staged CT only

• Only squamous cell caOnly squamous cell ca

• Variable brachytherapy (HDR, MDR, LDR)

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d f / h d hStudies of CDDP/5FU Chemoradiotherapy

Trial Year Control Result

RTOG 90-01 (1999) RT (EF) +++

SWOG 87 97 (2000) RT (postop) +++SWOG 87-97 (2000) RT (postop) +++

GOG 85 (1999) HU + RT +

Plat/5FU never compared directly with weekly CDDPPlat/5FU never compared directly with weekly CDDP

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Weekly CDDP Chemoradiotherapy as the standardWeekly CDDP Chemoradiotherapy as the standard arm

GOG 165 316 (2005) PVI 5FU ++

Trial # Year Control Result

(terminated early 35% failure rate)

Conclude: 5FU alone inferior to weekly CDDP

J Clin Oncol 2005;23(33):8289-95

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Meta-AnalysisGreen JA et al, Lancet 358: 781, 2001

• Review of 19 randomizedReview of 19 randomized Trials of CT+RT for cervical cancer (1981-2000) – 4580 pts randomized,4580 pts randomized,

3656 evaluable• 16% absolute improvement

in PFS (47% to 63%)( )– Benefit both local control

and distant failures• 12% absolute improvement12% absolute improvement

in survival (40% to 52%)– Greater benefit for St IB-

IIB• Increased acute toxicity with

CT+RT, but not late toxicity

Page 36: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

LDR Treatment SchemaLDR Treatment SchemaT/O #1T/O #1 T/O #2T/O #2CDDP

1 2 3 4 5 6 7 8 wks1 2 3 4 5 6 7 8 wks

T/O #1T/O #1 T/O #2T/O #2CDDP

1 2 3 4 5 6 7 8 wks

E t l b

1 2 3 4 5 6 7 8 wks

E t l b

40-45 Gy Boosts

External beam External beam

HDR Treatment SchemaHDR Treatment Schema#1#1 #2#2CDDP

HDR Treatment SchemaHDR Treatment Schema#3#3 #4#4 #5#5

40-45 Gy Boosts1 2 3 4 5 6 7 8 wks1 2 3 4 5 6 7 8 wks

Viswanathan ASTRO 9/25/08

y oosts

External beam External beam

Page 37: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Management of IB2-IVA

• Concurrent chemotherapy (Cisplatinum 40 mg/m2 weekly) and radiation therapy

• RT – pelvic and brachytherapy• Pelvic – APPA or 4F, 180cGy/fraction, 45Gy,Pelvic APPA or 4F, 180cGy/fraction, 45Gy,

15-18 MV. • Boost parametria, sidewallBoost parametria, sidewall• Brachytherapy TD 80-90 Gy

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Outback ChemotherapyDueñas-González A et al. JCO 2011;29:1678-1685

Outback Chemotherapy

• Concurrent Cis + RTConcurrent Cis + RT versus

• Concurrent Gem/Cis

Kaplan-Meier estimates of (A)

/plus outback Gem/Cis

progression-free survival (PFS) and (B) overall survival

for patients who were prandomly assigned to arm A or arm B. PFS at 3 years is shown by the dotted black y

lines and was 74.4% for arm A and 65.0% for arm B (P = .029)

Page 39: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

TECHNIQUES

Page 40: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Bowel sparing simulation

Supine ProneSupineIntact cervix Post-op pelvis

Radioth Oncol 2005;74:267-74

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Cervical Cancer Simulation

Superior L4-5

APPA Most inclusive

Viswanathan ASTRO 9/25/08

Page 42: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Lateral DRR

Could miss external iliac, pre-sacral, peri-rectal andrectal and internal iliac LN posteriorly

Viswanathan ASTRO 9/25/08

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IMRThttp://www.rtog.org/gynatlas/mai

n.htmln.html

Viswanathan ASTRO 2012

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MOVEMENTMOVEMENT

Page 45: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Heisenberg’s Uncertainty PrincipleHeisenberg s Uncertainty Principle

• The more precisely the p yposition is determined,

the less precisely the momentum is known inmomentum is known in

this instant, and vice versa.

--Heisenberg, Uncertainty paper,

19271927

Page 46: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Heisenberg ≅ 4D RT• Locate the target• Locate the target

• But as soon as you locate it, it moves

• Vaginal, parametrial mobility

• How much over-contouring is necessary to g ycompensate ‘uncertainity’

• A sim CT is a STATIC imageA sim CT is a STATIC image

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Variation in Vaginal PositionBladder Full vs. Empty

Page 48: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Parametria & changeParametria & change depending on volume of bladderof bladder

PTV: 1-4 cm

Courtesy of Karen Lim, Princess Margaret

Page 49: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

RTOG IMRT AtlasRTOG IMRT Atlas

• Obturator nodal contours /inferior extensionObturator nodal contours /inferior extension

• Vaginal ITV

i l i• Parametrial tissues

• Uterosacral ligaments/parametria

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/PET/CT Fusion Nodal Contour

N d l b 4 6 GNodal boost 54-65 Gy

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Location of Dose Limiting Structures

P tiPara-aortics

Small Bowel

Bone Marrow

Viswanathan ASTRO 2012

IMRT looks like an attractive option…

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Disadvantages of IMRT

C iContouringNeed accurate contouring to avoid misses

ImmobilizationPatient setup must be accurate and reproducible

Knowledge of Internal Motion

Margins could vary greatly depending on organ motion

Viswanathan ASTRO 2012

Page 53: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Disadvantage…..

• Underdosing a critical region….– Uterosacral ligamentsUterosacral ligaments

– Parametrial tissues

– Uterine cavity– Uterine cavity

• ConsequenceR l– Relapse

– DEATH

Viswanathan ASTRO 2012

Page 54: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Can IMRT replace Can IMRT replace brachytherapy?brachytherapy?

After 45 Gy EBRT• Complex internal

organ motion• Complex internal

organ motion

After 45 Gy EBRT

– Brachy fixed to target• Tumor response

– Brachy fixed to target• Tumor response• The proximity of

critical structures l littl f

• The proximity of critical structures l littl fleaves little room for error in EBRT planningleaves little room for error in EBRT planning

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Brachy better than IMRTBrachy better than IMRTyy

BrachytherapyBrachytherapy IMRTIMRTMoves with patientMoves with patient Does not move with patient

Difficult to adjust with responseDoes not move with patientDifficult to adjust with response

y pyy py

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Does brachytherapy increase local control and increase survival?

Viswanathan ASTRO 2012

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Brachytherapy is Necessaryy py y• Brachytherapy: internally delivered radiation using

radioactive sourcesS l t t l b• Supplements external beam

• Tumor control probability correlated with RT dose and cervix ca volume Fletcher, J Radiol Electrol 56:383-400, 1975

External beam only

External Beam + brachytherapyonly brachytherapy

4 y Pelvic Control

45%

19%

67%

46%Control

4 y SurvivalLanciano JROBP 20:95, 1991

19% 46%

Local Control Montana Cancer 57:148, 1986

40% 52%

Page 58: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Individual Patient Assessment• Where is the diseaseWhere is the disease• What is the patient’s anatomy

– MRI– Clinical exam

• Preparation for the OR– Ante vs. retroversion– Os visible or palpable– Inferior extent of disease– Inferior extent of disease– Proximity of posterior uterus to both rectum and

small bowel

Viswanathan ASTRO 2012

– Bladder

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Applicators for BrachytherapyApplicators for Brachytherapy

A B C

INTERSTITIAL Tandem and Tandem and Ring Ovoids

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Interstitial BrachytherapyInterstitial Brachytherapy

Fistula

Interstitial BrachytherapyInterstitial Brachytherapy

Postop recurrenceExtensive distal vaginal involvementCervical stump CaCervical stump Ca

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IMAGING

Plain x rayComputed

Tomography Magnetic

Resonance ImagingPlain x ray g p y(CT)

Resonance Imaging (MRI)

-International standard-BWH until 2002

2002-2011 2002-2006 0.5T2011- 3.0T

-prescribe to points2011 3.0T

Page 62: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Ultrasound for Dilation

• Suspected uterine preforation

• Retroverted uterus

• Absence of endocervical canal

• Extreme anteversion of uterus

Viswanathan ASTRO 2012

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What might appear acceptable on Xray, may not be acceptable in 3D

Posterior placementPosterior placement

Proper placement

Viswanathan ASTRO 9/25/08

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RTOG O116/0128: Brachy QualityRTOG O116/0128: Brachy QualityRTOG O116/0128: Brachy QualityRTOG O116/0128: Brachy Quality

ff idid•• Asymmetry of Asymmetry of ovoidsovoids

•• Displaced Displaced ovoidsovoids

•• Inappropriate packingInappropriate packing

Viswanathan et al. IJROBP 2012; Viswanathan et al. IJROBP 2012; 22(1):12322(1):123--3131

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Unacceptable TandemUnacceptable Tandempp

Midline on lateral filmMidline on lateral film Bisecting ovoidsBisecting ovoids

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Local RecurrenceLocal Recurrence

Parameter*HR†

(95% C.I.) p-valueSymmetry of Ovoids to Tandem

2.61(1.05, 6.45) 0.039

Displacement of Ovoids in Relation to Cervical Os

2.54(1 11 5 80) 0 027Relation to Cervical Os (1.11, 5.80) 0.027

Position of Tandem in Mid-Pelvis on Lateral Film

1.01(0.43, 2.37) 0.98

T d Bi ti O id 0 68Tandem Bisecting Ovoids on Lateral Film

0.68(0.27, 1.67) 0.39

Appropriateness of Packing

1.66(0 73 3 77) 0 23Packing (0.73, 3.77) 0.23

*Model included pelvic/iliac, para-aortic node positive, FIGO stage

†This represents the HR of unacceptable/not evaluated scores compared to acceptable scores

Viswanathan et al. Int J Gyn Ca 2012; 22(1):123-31

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DiseaseDisease--Free SurvivalFree Survival

Parameter*HR†

(95% C.I.) p-valueSymmetry of Ovoids to Tandem

1.43(0.73, 2.80) 0.29

Displacement of Ovoids in Relation to Cervical Os

2.12(1 16 3 89) 0 02Relation to Cervical Os (1.16, 3.89) 0.02

Position of Tandem in Mid-Pelvis on Lateral Film

1.15(0.63, 2.09) 0.65

T d Bi ti O id 0 79Tandem Bisecting Ovoids on Lateral Film

0.79(0.42, 1.48) 0.47

Appropriateness of Packing

1.95(1 08 3 55) 0 028Packing (1.08, 3.55) 0.028

*Model included pelvic/iliac, para-aortic node positive, and FIGO stage

†This represents the HR of unacceptable/not evaluated scores compared to acceptable scores† p p p p

Viswanathan et al. Int J Gyn Ca 2012; 22(1):123-31

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Standard prescription: Point A

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CT-detected perforation

Slide courtesy of Dr Beriwal

Page 70: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

ABS SurveyyMethod used for dose specification to

the cervixthe cervix

10%

12%Point Amg/hours

2%

3%mg/hoursCTVGTV/CTV

73%

GTV/CTVOther

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Point A vs. 3D

Narrow cervix Wide cervix

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Therapeutic Ratio: Balance between tumor cure andbetween tumor cure and

complicationsyy

babi

lity

babi

lity

Prob

Prob Tumor

controlComplications

Poor anatomy

DoseDose

p

Viswanathan ASTRO 2012

DoseDoseSlide courtesy of Dr Eifel

Page 73: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

GEC ESTRO recommended dose recording

Organs at risk: 0 1D0.1cc,

D2cc

Target: D90 V100D90, V100

@ 2cm difference ICRU Bladder and D2cc value

Page 74: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

f fPlan required for each HDR fractionRadioth Oncol 81:269, 2006

NORMAL TISSUE VARIATION

Page 75: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

CT versus MR contouringgViswanathan et al. Int J Radiat Oncol Biol 2007;68(2):491-498.

Bladder

• Width of contoured tumor larger on MRI

MR

Bladder

• OAR differences depend on filling status

HR-CTVCT • Nodal dose may be

estimated

Rectum• Point A constant

Page 76: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

MR guided interstitial brachytherapybrachytherapyViswanathan et al. IJROBP 66(1):91-99, 2006

• Interstitial reconstruction CT vs. MR– Patients must be imaged with legs down

• Protection of bladder or rectum– No inadvertent insertion of interstitial catheter into bladder or

d CT f MRrectum noted on CT after MR

Page 77: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

MR-Interstitial OutcomesMR Interstitial Outcomes

• 25 patients• 15 recurrent ca• Interstitial

brachytherapy• 0.5 T MR• No LR• 2 yr PFS 65%, • 2 yr OS 60%

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Recommendations based on MR-imaging

• GTV – T2 bright areas g

• HR-CTV – cervix + visible/palpable IR CTVvisible/palpable disease at brachy

• IR CTV 1 cm margin

IR CTV

• IR-CTV – 1 cm margin around HR-CTV + initial sites of

GTVHR CTV

initial sites of involvement

Viswanathan ASTRO 2012

GYN GEC ESTRO Recommendations (I) Radioth.Oncol. 2005, 74:235-245

Page 79: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

MR T/R Brachytherapy OutcomesRad Onc 2011:100:116-123Rad Onc 2011:100:116-123

• 156 patients• HistoricalHistorical

comparison• Med FU 42 mo• CR 97%• Significant ↑Significant ↑

– 3y OS 53 to 68%

– CSS 62 to 74%

– Tumors > 5cm• OS 28 to 65% Pötter et al. Rad Oncol 2007

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Tumor control related to doseDimopoulos JC et al. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):56-63

• D90 for HRCTV > 87 Gy y– LR 4% (3 of 68)

D90 f HRCTV < 87 G• D90 for HRCTV < 87 Gy – LR 20% (15 of 73)

• The effect was most pronounced in patients that had tumors >5cm w athat had tumors >5cm w a poor response

Page 81: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

The OR and MR rooms of AMIGOAMIGO

Advanced Multimodality Image Guided Operating (AMIGO) SuiteP41 RR019703 – National Center for Image Guided Therapy (NCIGT) 2005-2015

Ferenc Jolesz, MD Clare Tempany, MD

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3T MR Treatment Planning3T MR Treatment Planning

Page 83: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Standard vs Optimized PlanStandard vs Optimized Plan

Page 84: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis
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Biologically Equivalent DoseE i l t D i 2 G F ti

Biologically Equivalent DoseE i l t D i 2 G F tiEquivalent Dose in 2 Gy Fractions

(EQD2)Equivalent Dose in 2 Gy Fractions

(EQD2)( )( )BED= nd(1+d/α/β )/(1+2/ α/β )

EQD2 BED/1 2

BED= nd(1+d/α/β )/(1+2/ α/β )

EQD2 BED/1 2EQD2= BED/1.2n = # fractions

d d /f

EQD2= BED/1.2n = # fractions

d d /fd = dose/fraction

α/β for tumor ~ 10

α/β for normal tissue ~ 3

d = dose/fraction

α/β for tumor ~ 10

α/β for normal tissue ~ 3α/β for normal tissue 3

Example:

α/β for normal tissue 3

Example:

Viswanathan ASTRO 9/25/08(5 fractions) x (5.5 Gy) x (1+5.5 Gy/10) / 1.2 = 35.5 Gy10(5 fractions) x (5.5 Gy) x (1+5.5 Gy/10) / 1.2 = 35.5 Gy10

Page 87: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

HDR Doses (after 45 Gy EB)HDR Doses (after 45 Gy EB)HDR Doses (after 45 Gy EB)HDR Doses (after 45 Gy EB)

6 Gy x 56 Gy x 57 Gy x 48 Gy x 3

Consider lower doses with concurrent chemo

8 Gy x 3

5.0 Gy x 5 - small volume disease 5.5 Gy x 5 - large volume disease

Viswanathan ASTRO 2012

5.5 Gy x 5 large volume disease

Page 88: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Standard Fractionation and EQD2 lvalues

Fractional # EQD2 EB+EQD2Dose

9 Gy 2 28.5 73

8 Gy 3 36 80

7 Gy 4 39.7 847 Gy 4 39.7 84

6 Gy 5 40 84

5 5 Gy 5 35 5 805.5 Gy 5 35.5 80

6 Gy 4 32 76

Page 89: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

DVH analysis and late side effects Georg et al. Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):356-62

• Rectum: D2cc rectum >75 Gy predicted >Rectum: D2cc rectum 75 Gy predicted G2 side effects

• Sigmoid: No dose limit identified given low number of sigmoid specific sidelow number of sigmoid specific side effects

• Bladder: D2cc >95 Gy appeared to increase side effects though furtherincrease side effects though further analysis needed

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Strategize your approachStrategize your approach

• Experience matters– Training programsTraining programs

• Follow guidelines

• Standardize approach• Standardize approach

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Follow-UpFollow Up

• Pelvic examination and Biopsy if evidence of newPelvic examination and pap smears at regular intervals

Biopsy if evidence of new lesions or abnormal pap smearI i t di d d– Every 3 months for the

first 2 years

E 4 th th 3 d

Imaging studies as neededVaginal Dilator

– Every 4 months the 3rd year

– Every 6 months years e y 6 o t s yea s4th and 5th

– Yearly thereafter

Page 92: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Summary: Cervical Cancer

• Screening effective• Treatment effectiveTreatment effective

– Pre-invasive– Invasive– RT very effective

• Individualize careIndividualize care– Emphasizes role as a comprehensive

oncologist

Viswanathan ASTRO 2012

Page 93: Associate Professor of Radiation Oncology ... - ASTRO · Associate Professor of Radiation Oncology Management Associate Professor of Radiation Oncology ... :5093-101 • MRI at diagnosis

Thank you


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