Radiotherapy planning in carcinoma cervix

Dr. Rekha Arya

SR .RADIOTHERAPY DEPT

MAMC

3D-CRT/IMRT OF CA CERVIX

CONFORMAL THERAPY

It is described as radiotherapy

treatment that creates a high dose

to the desired target volume

while minimizing the dose to

critical normal tissues.

Figure: differences between

(a. conventional radiotherapy,

(b. conformal radiotherapy (CFRT) without intensity-modulation and

(c. CFRT with intensity modulation (IMRT).

RATIONALE OF USING IMRT IN CA Cx• Conventional RT → toxicities due to the inclusion of

considerable volumes of various normal tissues

• Small bowel → diarrhea, SBO, enteritis, malabsorption

• Rectum → diarrhea, proctitis, rectal bleeding

• Bladder → urgency, dysuria, haematuria,

• Bone Marrow → ↓WBC, ↓platelets, anemia

• Reduction in the volume of normal tissues irradiated with

IMRT may thus ↓risk of acute and chronic RT sequelae

• Allow for simultaneous boost of involved lymph nodes

WORKFLOW OF CONFORMAL RT

POSITIONING• Important component of conformal RT.• Patients may be positioned in Supine position Prone position with belly board

• supine position is preferred because Most comfortable Reproducible position Stabilizes pelvis Can be combined with immobilization device.

• For this purpose positioning devices may be used

• Positioning devices are ancillary devices used to help maintain the patient in anon-standard treatment position.

• knee rest can be used Relaxes lower back making pt. more comfortable Minimize rotation of pelvis Knee rest with indexing limits superior-inferior and lateral motion

Prone position on a belly board

Belly Board is used to allow the intestinal tract to drop out of treatment field.

Made of foam material has a low absorption of the beam.

In hysterectomy pts: • small bowel may drop into the pelvic area so prone position

may be beneficial

For patients with an intact cervix, the small bowel often lies superior to the uterus and above the pelvic brim, creating less need to shift the bowel out of the pelvis.

TIMO

Face rest

Breast boardKnee wedge

Belly boardPITUITARY BOARD

IMMOBILIZATION

• Patient is immobilized using individualized casts ormoulds.

• An immobilization device is any device that helps toestablish and maintain the patient in a fixed, well-defined position over a course of radiotherapytreatment everyday.

Immobilization

Thermoplastics form the basis for immobilization in head and neck

In the pelvis these are difficult to be used as:

Lack of bony points for fixation

Continuing abdominal movements with respiration

Presence of fat pads and folds

simple supine positioning with skin markings:

Cheap

Reproducible

Ease of use and comfortable for patient.

IMAGE ACQUISITION

It provides foundationfor treatment planning

Usually more than oneimaging modalities arerequired for betterdelineation of targetvolume

Images are acquired for :Treatment planning

Image guidance and/or treatmentverification

Follow-up studies (during & aftertreatment)

Need of contrast during simulation

• Usually not needed in CT simulation

• because structures can be contoured

even without contrast on CT.

• May be helpful in conventional simulation

to enhance the soft-tissue detail

• contrast may be placed at following sites

iv contrast to localize the pelvic vessels

oral contrast to delineates small bowel.

Foley’s catheter with bladder contrast

barium in the rectum,

vaginal tube in the vagina,

IMAGE ACQUISITION

• CT is done with pt in the treatment position with immobilization

device if used.

• Radio opaque fiducial are placed .

• These fiducial assist in any coordinate transformation needed as

a result of 3D planning and eventual plan implementation.

• A topogram is generated to insure that patient alignment is

correct & then using localizer, area to be scanned is selected.

• The FOV??? is selected to permit visualization of the external

contour, which is required for accurate dose calculations.

• Using site dependent protocols, images are acquired.

• The planning CT data set is transferred to a 3D-TPS or

workstation via a computer network.

IMAGING MODALITIES

• No single imaging modality produces all theinformation, needed for the accurate identificationand delineation of the target volume and criticalorgans.

• Various imaging modalities used are :

– CT

– MRI

– PET-CT

High Tech Diagnostic Machines

CT Simulator

PET Scan

MRI

CT SIMULATOR

• Images are acquired on adedicated CT machine calledCT simulator with followingfeatures– A large bore (75-85cm) to

accommodate various treatmentpositions along with treatmentaccessories.

– A flat couch insert to simulatetreatment machine couch.

– A laser system consisting of

• Inner laser

• External moving laserto position patients forimaging & for marking

TREATMENT PLANNING SYSTEM

• TPS provides tools for

– Image registration

– Image segmentation or contouring

– Virtual Simulation

– Dose calculations

– Plan Evaluation

– Data Storage and transmission to console

– Treatment verification

VOLUMES• The International Commission on Radiation Units and

Measurements (ICRU),( inception in 1925,)has its principal

objective the development of internationally acceptable

recommendations .

• There are different type of ICRU reports for different type of

procedure like:

• ICRU 38 (1985) - "Dose and Volume Specification for Reporting

Intracavitary Therapy in Gynecology“

• ICRU 50 (1993) - "Prescribing, Recording, and Reporting Photon

Beam Therapy“

• ICRU 58 (1997) - interstitial brachytherapy

• ICRU 62 (1999) - "Prescribing, Recording and Reporting Photon

Beam Therapy (Supplement to ICRU Report 50)"

ICRU 50 & 62

• When delivering Radiotherapy treatment, parameters such asvolume & dose have to be specified for:– Prescription

– Recording

– Reporting

• Such specifications serve a number of purposes– To enable the Radiation Oncologist to maintain a consistent treatment

policy and improve it in the light of experience.

– To compare the results of treatment and benefit from otherdepartmental treatments.

– It is particularly important in multi-center studies in order to keeptreatment parameters well defined, constant & reproducible.

• It is expected that rapid development of new techniques wouldincrease the complexity of radiotherapy and emphasize theneed for general strict guidelines.

Gross Tumor Volume (GTV): Gross palpable or visible/demonstrable extent and location of malignant growth. This may consist of primary tumor, metastatic lymphadenopathy.

Clinical Target Volume (CTV): Anatomical concept. GTV + sub clinical microscopic disease.

The PTV (planning target volume) - Geometrical concept defined to select appropriate beam sizes and beam arrangements.

• It considers the net effect of the geometrical variations to ensure that the prescribed dose is actually absorbed in the CTV.

• These variations may be intra-fractional or inter-fractional due to number of factors like

1. Movement of tissues/patient.

2. Variations in size & shape of tissues.

3. Variations in beam characteristics.

4. The uncertainties may be random or systematic.

Treated Volume: Volume enclosed by an isodose surface (e.g. 95% isodose),

selected and specified by radiation oncologist as being appropriate to achieve

the purpose of treatment.

Ideally, Treated Volume would be identical to PTV, but may also be

considerably larger than PTV.

Irradiated Volume: Tissue volume which receives a dose that is considered

significant in relation to normal tissue tolerance. Dose should be expressed

either in absolute values or relative to the specified dose to the PTV.

Organs at Risk Organs at Risk: Normal tissues whose radiation sensitivity may significantly

influence treatment planning and/or prescribed dose.

• Any possible movement of the organ at risk as well as uncertainties in thesetup during the whole treatment course must be considered.

• Organs at risk may be divided into three different classes:

– Class I (Radiation lesions are fatal & result in severe morbidity.)

– Class II (Result in moderate to mild morbidity.)

– Class III (Radiation lesions are mild, transient and reversible or result inno significant morbidity.)

9/25/2010

Organs at Risk

OARs

• Lungs

• Spinal Cord

ICRU 62 (1999) - "Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50)“

• No change to definition of GTV and CTV, since they are oncologic concepts independent of any technical development

• Global concept and definition of PTV is not changed, but definition is supplemented

• Internal Margin (IM): Variations in size, shape, and position of the CTV relative to anatomic reference points; e.g., filling of bladder, movements of respiration. The internal variations are physiological ones, and result in change in site, size, and shape of the CTV

• Internal Target Volume (ITV): Volume encompassing the CTV and IM. (ITV = CTV + IM)

Set up Margin (SM):

• It accounts for the uncertainties in patient positioning and aligning oftherapeutic beams.

• The uncertainities may vary with selection of beam geometries, and maydepend on variations in patient positioning, mechanical uncertainities ofthe equipment (e.g. sagging of gantry, collimators, or couch), dosimetricuncertainities, transfer setup errors from CT simulator to treatment unit,and human factors.

Planning organ at risk volume (PRV):

• An integrated margin must be added to the OR to compensate forvariations including the movement of organ as well as setup uncertainties.

• In particular the internal margin & the setup margin for the OR must beidentified. This leads to the concept of PRV.

9/25/2010

IM = Internal MarginSM = Setup Margin

IM

CTV

SM

PRV

OR

ICRU 62 – Volume definitions

ITV

PTV

9/25/2010

ICRU 62 report

Target volumes

•GTV = Gross Tumour Volume= Macroscopic tumour

•CTV = Clinical Target Volume= Microscopic tumour

•PTV = Planning target Volume

PTV

Advice: Always use the

ICRU reports to specify and

record dose and volumeBaumert et al. IJROBP 2006 Sep 1;66(1):187-94

Target Volume delineation

For definitive treatment of carcinoma cervix with conformal

radiation techniques, accurate target delineation is vitally

important,

Various guidelines for CTV delineation are published in the

literature yet a consensus definition of clinical target volume

(CTV) remains variable

Clinical judgement remains the most important aspect of

determining the target volumes

ContouringSeveral contouring guidelines available for CTV

Taylor et al pelvic nodal delineation (CT based)

Toita et al for CTV delineation in intact cervix EBRT (CT based)

Lim et al for CTV delineation in intact cervix IMRT (MRI based)

Small et al for CTV delineation in post operative IMRT (CT based)

PGI literature review & guidelines for delineation of CTV for intact carcinoma cervix (CT based)

Guidelines for organ at risk

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas (CT based)

Components of CTV

The group consensus was that entire uterus should be included in the CTV because:• Uterus & cervix are

embryologically one unit with interconnected lymphatics and no clear separating fascial plane.

• Determination of myometrial invasion can be difficult.

• uterine recurrences have been reported (2%), but exact location of these recurrences (fundal vs. corpus) have not been stated.

uterus

parametrium

rectum

Sigmoid colon

superior boundaries of parametriaare at the top of the fallopian tube,and contours should stop onceloops of bowel are seen next to theuterus as this is clearly above thebroad ligament.

For the very anteverted uterus,particularly where the fundus liesbelow the cervix, the parametrialvolume should stop once thecervix is seen

Inferiorly, the parametrial tissuefinish at the muscles of the pelvicfloor.

Parametrial Contouring Guidelines

Anteriorly boundary lies at the posterior wall ofthe bladder. Bladder or In patients with a verysmall bladder (which lies deep in the pelvis),posterior border of the external iliac vessel.

Posteriorly: bounded by the mesorectal fasciaand uterosacral ligaments parametrial volumeswould extend up to the rectal contour inadvances stages.

Laterally, the parametrial volume shouldextend to the pelvic sidewall (excludingbone and muscle).

some overlap of this volume with nodalCTV, particularly along the obturator strip

Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition.

Clinical Oncology. 2007 Sep ;19(7):542-550.

lateral external iliac nodes (blue), inguino-femoral nodes (green) parametria and upper vagina (red).pre-sacral (PS), internal iliac (II), obturator (Obt), lateral (EIl), medial(EIm) and anterior (EIa) external iliac, parametrial and paravaginal (Pm),

1. CTV definition for the post-operative therapy of endometrial and cervical cancer should include the common, external, and internal iliac lymph node regions.

2. The upper 3.0 cm of vagina and paravaginal soft tissue lateral to the vagina should also be included.

3. For patients with cervical cancer, or endometrial cancer with cervical stromal invasion, it is also recommended that the CTV include the presacral lymph node-region

Post-operative CTV delineation (Small et al)

Common Iliac

Pre-Sacral

External & Internal iliac

External & Internal iliac

Presacral

External & Internal Iliacs

ParavaginalExternal & Internal iliacs

Presacral

Vagina & Paravaginal Tissues

Vagina

The aim of the article was to review the guidelines for CTV delineation published in the literature and to present the guidelines practiced at their institute

6 articles : 2 articles from Taylor et al and Toita et al and 1 from Small et al.,Lim et al., were reviewed

The CTV in cervical cancer consists of the CTV nodal and CTV primary. CTV nodal consists of common iliac, external iliac, internal iliac, pre-sacral

and obturator group of lymph nodes, and CTV primary consists of the gross tumor

volume, uterine cervix, uterine corpus, parametrium, upper third of vagina and uterosacral ligaments.

Pelvic LN CTV is contoured in accordance with the latest Taylor’s guidelines with some modifications

This was the first report to provide the complete set of guidelines for delineating both the CTV primary and CTV nodal in combination

Normal Tissue Delineation (RTOG)

• Bowel: The small and large bowel can be contoured together as a Bowel-Bag.

• Inferiorly, the bowel bag should begin with the first small or large bowel loop or above the ano-rectum, whichever is most inferior.

• The contours should end 1 cm. above the PTV .

• Ano-Rectum: Ano-Rectum should be contoured from the level of the anus to the sigmoid flexure. It should extend from the anal verge (marked by a radiopaque marker at simulation) to superiorly where it loses its round shape in the axial plane and connects anteriorly with the sigmoid.

• Bladder: Contoured inferiorly from its base, and superiorly to the dome.

• Femoral Heads:The ball of the femur, trochanters, and proximal shaft to the level of the bottom of ischial tuberosities

Gay HA, Barthold HJ, O′Meara E, Bosch WR, El Naqa I, Al-Lozi R, et al. Pelvic normal tissue

contouring guidelines for radiation therapy: A Radiation Therapy Oncology Group consensus panel

atlas. Int J Radiat Oncol Biol Phys 2012;83:e353-62.

• To evaluate the toxicity and clinical outcome in patients with LACC treated with WP-CRT versus WP-IMRT

• METHODS AND MATERIALS:• Between January 2010 and January 2012, • 44 patients with (FIGO 2009) stage IIB-IIIB SCC cervix randomized to receive

50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m2 followed by high-dose-rate HDR) IICRT, 7 Gy to point A in 3 once-weekly sessions

• In patients deemed unsuitable for ICRT, interstitial brachytherapy (IBT) 10 Gy in 2 once-weekly sessions based on our previous experience

• Acute toxicity : graded according to the CTCAE version 3.0• Late toxicity: graded according to RTOG• Primary end point :acute gastrointestinal toxicity• secondary endpoints: disease-free survival

The median time to completion of treatment in the WP-CRT arm was 9.1 weeks(range, 8.3-12.9 weeks), and in the WP-IMRT arm it was 9.1 weeks (range, 8.3-11.7 weeks).

The median number of chemotherapy cycles in both arms was 5 (range, 3-6).

The median follow-up timein the WP-CRT arm was 21.7 months (range, 10.7-37.4 months),in the WP-IMRT arm was 21.6 months (range, 7.7-34.4 months).

RESULTS

Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute

gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3

gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving

WP-CRT

RESULTS:

At 27 months,

disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651)overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645).

CONCLUSION:

WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome.

LIMITATION: small sample sizes and short follow-up times.no use of image guidance

Caveats of IMRT Significantly increased expenditure:

Machine with treatment capability

Imaging equipment: Planning and Verification

Software and Computer hardware

Extensive physics manpower and time required.

Immobilization: Patient setup must be accurate and reproducible

Contouring: Need accurate contouring to avoid misses.

Knowledge of Internal Motion: Margins could vary greatly depending on organ motion

Concerns with integral dose and secondary malignancy

RADIATION SIDE EFFECTS

Acute Side Effects:

Acute gastrointestinal side effects: include diarrhea, abdominal cramping, rectal discomfort, and occasionally, rectal bleeding, which may be caused by transient enteroproctitis.

Genitourinary symptoms:secondary to cystourethritis, are dysuria, frequency, and nocturia,microscopic or even gross hematuria.

Skin reactions: erythema and dry or moist desquamation may develop in the perineum or intergluteal fold.

acute radiation vaginitis, superficial ulceration of the vagina, and vagianlstenosis can also occur

• Late Side Effects:

Late radiation effects are closely related to total doses given to the pelvic organs.

• Retrovaginal or vesicovaginal fistula and proctitis or cystitis can occur but in small percentages.

• Injury to the gastrointestinal tract usually appears within 2 years of radiation therapy

• Complications of the urinary tract more frequently are seen 3- 4 years after treatment.

• Vaginal stenosis is associated with dyspareunia

• Anal incontinence is observed occasionally

Dose limitation• HDR: limit bladder and rectal points to <70% of point A dose with

HDR.

• LDR: limit rectal point <70 Gy and bladder point <75 Gy.

• Limit upper vaginal mucosa <120 Gy, midvaginal mucosa <80–90 Gy, and lower vaginal mucosa <60–70 Gy.

• Vaginal doses >50–60 Gy cause significant fibrosis and stenosis.

• Ovarian failure with 5–10 Gy and sterilization with 2–3 Gy.

• Limit uterus <100 Gy, ureters <75 Gy, and femoral heads <50 Gy.

To be continued…….brachytherapythanks

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