Slide 1

3D CRT and IMRT in Cervical CancersDepartment of RadiotherapyPGIMERChandigarh

Conformal Radiotherapy

Conformal radiotherapy (CFRT) is a technique that aims to exploit the potential biological improvements consequent on better spatial localization of the high-dose irradiation volume

- S. Webb

in Intensity Modulated Radiotherapy

IOP

Problems in conformation

Nature of the photon beam is the biggest impediment

Has an entrance dose.

Has an exit dose.

Follows the inverse square law.

Types of CFRT

Two broad subtypes :

Techniques aiming to employ geometric eldshaping alone

Techniques to modulate the intensity of uence across the geometrically-shaped eld (IMRT)

Modulation : Intensity or Fluence ?

Intensity Modulation is a misnomer The actual term is Fluence

Fluence referes to the number of particles incident on an unit area (m-2)

How to modulate intensity

Cast metal compensator

Jaw defined static fields

Multiple-static MLC-shaped elds

Dynamic MLC techniques (DMLC) including modulated arc therapy (IMAT)

Binary MLCs - NOMOS MIMiC and in tomotherapy

Robot delivered IMRT

Scanning attenuating bar

Swept pencils of radiation (Race Track Microtron - Scanditronix)

Comparision

MLC based IMRT

Step & Shoot IMRT

IntesntiyDistanceSince beam is interrupted between movements leakage radiation is less.

Easier to deliver and plan.

More time consuming

Effecient delivery requires fast beam cycling dark current in tube can cause unwanted radiation during movement.

Dynamic IMRT

Faster than Static IMRT

Smooth intensity modulation acheived

Beam remains on throughout leakage radiation increased

More susceptible to tumor motion related errors.

Additional QA required for MLC motion accuracy.

IntesntiyDistance

Potential of Conformal RT

For Whole Pelvic Treatments:

Reduction in acute small bowel morbidity.

Reduction in acute hematological toxicity with bone marrow sparing.

Prevention of late term anorectal/ GI and GU dysfunction.

Escalation of dose to the pelvic lymphnodes.

Better matching of dose profiles in simultaneous treatments.

For simultaneous extended field irradiation ( CCT).

Better target coverage with modern day improvements in conjunction with image based brachytherapy

As an alternative to brachytherapy:

In distorted anatomy to circumvent limitations of brachytherapy.

To give higher dose to pelvic nodes present at time of brachyRx.

In postoperative patients with residual central disease instead of intersitial brachytherapy.

Caveats: Conformal Therapy

Significantly increased expenditure:

Machine with treatment capability

Imaging equipment: Planning and Verification

Software and Computer hardware

Extensive physics manpower and time required.

Conformal nature highly susceptible to motion and setup related errors Achilles heel of CFRT

Target delineation remains problematic.

Radiobiological disadvantage:

Decreased dose-rate to the tumor

Increased integral dose (Cyberknife > Tomotherapy > IMRT)

Conformal Radiation Planning

Initial Steps

Clinical Examination to note down tumor extent:

Vaginal mucosal extension is best appreciated on clinical examination

Preplanning steps:

Oral Contrast

Rectal Contrast

Cervical markers

Patient Preperation

Positioning and Immobilization

Two of the most important aspects of conformal radiation therapy.

Basis for the precision in conformal RT

Needs to be:

Comfortable

Reproducible

Minimal beam attenuating

Affordable

Several types of immobilization options available for cervical cancers

Types of Immobilization

Immoblization devicesFrame basedFramelessInvasiveNoninvasive

Usually based on a combination of heat deformable casts of the part to be immobilized attached to a baseplate that can be reproducibly attached with the treatment couch.

The elegant term is Indexing

Thermoplastics

Immobilization options

Thermoplastics form the basis for immobilzation in head and neck

In the pelvis these are difficult to be used as:

Lack of bony points for fixation for rigid devices.

Continuing abdominal movements with respiration

Presence of fat pads and folds

Therefore other techniques needed for immobilization.

In PGI we use simple supine positioning with skin markings:

Cheap

Reproducible

Ease of use and comfortable for patient.

Patient Positioning

Our Method

Immobilization: Other methods

Elekta Body FrameBody Fix system A third system (BodyFIX, Medical Intelligence) has been evaluated by Fuss et al. (2004). It consists of a base plate with variable sizes of a vacuum cushions and a clear plastic foil covering the patients body. The cushion is modeled using an additional vacuum between the patients front and a plastic foil. An arch-like attachment can be afxed to the base plate providing CT-, MR-, and PET-visible ducials.

Accuracy of systems

With the precision of the body fix frame the target volume will be underdosed (< 90% of prescribed dose) 14% of the time!!!

CT simulator

70 85 cm bore

Scanning Field of View (SFOV) 48 cm 60 cm Allows wider separation to be imaged.

Multi slice capacity:

Speed up acquistion times

Reduce motion and breathing artifacts

Allow thinner slices to be taken better DRR and CT resolution

Allows gating capabilities

Flat couch top simulate treatment table

MRI

Superior soft tissue resolution

Ability to assess neural and marrow infiltration

Ability to obtain images in any plane - coronal/saggital/axial

Imaging of metabolic activity through MR Spectroscopy

Imaging of tumor vasculature and blood supply using a new technique dynamic contrast enhanced MRI

No radiation exposure to patient or personnel

Importance of MRI

Dimopoulos JC, Schard G, Berger D, Lang S, Goldner G, Helbich T, et al. Systematic evaluation of MRI findings in different stages of treatment of cervical cancer: Potential of MRI on delineation of target, pathoanatomic structures, and organs at risk. International Journal of Radiation Oncology*Biology*Physics. 2006 Apr 1;64(5):1380-1388.

PET: Principle

Unlike other imaging can biologically characterize a leison

Relies on detection of photons liberated by annhilation reaction of positron with electron

Photons are liberated at 180 angle and simultaneously detection of this pair and subsequent mapping of the event of origin allows spatial localization

The detectors are arranged in an circular array around the patient

PET- CT scanners integrate both imaging modalities

PET-CT scanner

Flat couch top insertCT ScannerPET scanner

60 cmAllows hardware based registration as the patient is scanned in the treatment position

CT images can be used to provide attenuation correction factors for the PET scan image reducing scanning time by upto 40%

Markers for PET Scans

Metabolic marker

2- 18Fluoro 2- Deoxy Glucose

Proliferation markers

Radiolabelled thymidine: 18F Fluorothymidine

Radiolabelled amino acids:11C Methyl methionine, 11C Tyrosine

Hypoxia markers

60Cu-diacetyl-bis(N-4-methylthiosemicarbazone) (60Cu-ATSM)

Apoptosis markers

99mTechnicium Annexin V

PET FiducialsRadiolabelled Thymidine based markers are based on the principle that they can be used to detect proliferation of cells as onlu actively divinding cells take up thymidine.The use of these markers can thus allow the oncologist to obtain a rough idea of the proliferation markers.

The use of cell proliferation markers namely amino acids provides us with the advantage that the inflammatory cells take up less of the substance and so it is possible to image the tumor bearing tissues seperately.

Hypoxia markers are substances that contain a nitroimidazole entity which is reduced and subsequently the entire molecule is taken up by the concerned cell. It acts as a hypoxia marker in such circumstances.

Among all the hypoxic cell markers the Cu-ASTM is the best as:

The images are produced within 10 min of contrast injection.

Images have high contrast with moderate doses.

The substance is taken up by cells with active mitochondria and thus it is possible to distinguish alive cells from necrotic ones.

Apoptosis markers are based on certain molecules that avidly bind to domains of membrane lipids that are exposed on apoptotic cells, Annexin V is an example of such a molecule and it binds to the membrane bound phosphatidyl serine which is exposed on the outer leaflet of cell membrane on cell death.

Image Registration

Technique by which the coordinates of identical points in two imaging data sets are determined and a set of transformations determined to map the coordinates of one image to another

Uses of Image registration:

Study Organ Motion (4 D CT)

Assess Tumor extent (PET / MRI fusion)

Assess Changes in organ and tumor volumes over time (Adaptive RT)

Types of Transformations:

Rigid Translations and Rotations

Deformable For motion studies

Concept

Image Registration

The algorithm first measures the degree of mismatch between identical points in two images (metric).

The algorithm then determines a set of transformations that minimize this metric.

Optimization of this transformations with multiple iterations take place

After the transformation the images are fused - a display which contains relevant information from both images.

Image Registration

The registration metrics used are of two broad types:

Geometry based metrics: This metric type finds the difference between two images based on several points or surface of a structure(s) in question

Intensity based metrics: This type of metric attempts to evaluate the difference in the two images by using numerical grey scale differences.

The geometry based metrics are limited by the ability to precisely determine the location of identical points or delineate the surface of the organ in question in two image sets. This is allright in certain structures like the brain. However the different levels of imaging contrast provided by different studies makes the use of this process difficult in practice in other areas

The intensity based metrics on the other hand determine the differnce in the intensity distribution of voxels and calculate the degree of transformations required.

Various types of intensity based metrices exist:

Sum of squared differences

Cross correlation metric

Mutual information metric

The mutual information technique is most commonly used to estimate the differnce in the intensity of voxel values. The technique's strength lies in the fact that it can overcome differences due to areas of different contrasts in the two images and in addition it can overcome the problem due to missing data.

Target Volume delineation

The most important and most error prone step in radiotherapy.

Also called Image Segmentation

The target volume is of following types:

GTV (Gross Tumor Volume)

CTV (Clinical Target Volume)

ITV (Internal Target Volume)

PTV (Planning Target Volume)

Other volumes:

Targeted Volume

Irradiated Volume

Biological Volume

Target Volumes

GTV: Macroscopic extent of the tumor as defined by radiological and clinical investigations.

CTV: The GTV together with the surrounding microscopic extension of the tumor constitutes the CTV. The CTV also includes the tumor bed of a R0 resection (no residual).

ITV (ICRU 62): The ITV encompasses the GTV/CTV with an additional margin to account for physiological movement of the tumor or organs. It is defined with respect to a internal reference most commonly rigid bony skeleton.

PTV: A margin given to above to account for uncertainities in patient setup and beam adjustment.

Definitions: ICRU 50/62

GTVCTVITVPTV

TV

IV

Treated Volume: Volume of the tumor and surrounding normal tissue that is included in the isodose surface representing the irradiation dose proposed for the treatment (V95).

Irradiated Volume: Volume included in an isodose surface with a possible biological impact on the normal tissue encompassed in this volume. Choice of isodose depends on the biological end point in mind.

Organ at Risk (ICRU 62)

Normal critical structures whose radiation sensitivity may significantly influence treatment planning and/or prescribed dose.

A planning organ at risk volume (PORV) is added to the contoured organs at risk to account for the same uncertainities in patient setup and treatment as well as organ motion that are used in the delineation of the PTV.

Each organ is made up of a functional subunit (FSU)

Organs can be classified into 4 broad types based on the arrangement of the FSUs:

Serial: Where the FSUs are arranged in serial and damage to one can result in the total impairment of function of the organ. Example: Spinal cord

Parallel: Here the FSU are arranged in parallel so that damage to a certain proportion of the FSUs are required befor e functional deterioration becomes apparent. Example Parotid Gland, Lung and Kidney

Serial in parallel: These organs have serially arranged FSU so that damage to a single FSU can impair the function significantly but damage to a certain proportion is still required before the damage becomes apparent. Example: Heart.

Combination of serial and parallel organs: Here the damage to the serial component can result in the stoppage of function of the organ concerned. Example is the nephron

The concept of the organization of the FSUs has lead to a new classification of organs for purposes of calculation of the equivalent dose. Organs are now classified into 3 categories:

Critical Element(CE): Example Spinal Cord

Critical Volume (CV): Example Lung

Graded Response (GR): Example oral mucosa

CTV Delineation

The CTV to be delineated for cervical cancers consists of three components (if patient is treated with RT CT alone)

Low Risk CTV: Consists volume at risk of potential microscopic disease spread at the time of diagnosis. Typically treated to a dose of 45 -50 Gy.

Intermediate Risk CTV: Major risk of local recurrence in areas that correspond to initial macroscopic extent of disease. The intent is to deliver a total radiation dose appropriate to cure signicant microscopic disease in cervix cancer, which corresponds to a dose of at least 60 Gy.

High Risk CTV: Major risk of local recurrence because of residual macroscopic disease. The intent is to deliver a total dose as high as possible (85 - 90 Gy) and appropriate to eradicate all residual macroscopic tumour.

CTV Parametrium

Ventral: Bladder

Dorsal: Perirectal fascia

Medial: Tumor/cervical rim,

Lateral: Pelvic wall (PW)

At the PW, the space that contains vessels and lymph nodes is particularly important.

Nodal Anatomy

Superficial common iliac 24%Deep Common iliac 20%Internal Iliac 12%External Ilac 24%Superficial Obturator 92%Deep Obturator 8%Presacral - 8%

Delineation of Nodal Volume

Common Iliac Nodes:7 mm margin around vessels. Extend posterior and lateral borders to psoas and vertebral bodyTaylor 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.

Delineation of Nodal Volume

External iliac Nodes:7 mm margin around vessels. Extend anterior border by a further 10 mm anterolaterally along the iliopsoas muscle to include the lateral external iliac nodesInternal iliac Nodes:7 mm margin around vessels. Extend lateral borders to pelvic side wallTaylor 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.

Delineation of Nodal Volume

Presacral Nodes:Subaortic: 10 mm strip over anterior sacrum; Mesorectal: cover entire mesorectal spaceTaylor 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.

Delineation of Nodal Volume

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.

Delineation of Nodal Volume

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.Obturator Nodes:Join external and internal iliac regions with a 17 mm wide strip along the pelvic side wall

Delineation of Nodal Volume

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.

Extent of Nodes Covered

Taylor et al have advocated the use of a 7 mm margin around the blood vessels unlike Chao's recommendations as it was seen that educing margins to 7 mm from 10 mm could result in 20 -30% reduction in the volume of normal tissues included in the PTV.

PTV Delineation

The exact PTV depends on:

Setup inaccuracies

Organ motion

The extent of setup inaccuracies will differ from institution to instituiton

In PGI we use the following margins:

1 cm cranio-caudal direction

0.7 cm lateral

0.7 cm antero posterior

Interfraction Motion: ITV

Uterus:

SI: 7 mm

AP : 4 mm

Cervix:

SI: 4 mm

Rectum:

Diameter: 3 46 mm

Volumes: 20 40%

In many studies decrease in volume found during treatment

Bladder:

Max transverse diameter mean 15 mm variation

SI displacement 15 mm

Volume variation 20% - 50%

Langen, K. M., & Jones, D. T. (2001). Organ motion and its management. International journal of radiation oncology, biology, physics, 50(1), 265-78.

Planning workflow

Define a dose objectiveTotal DoseTotal Time of delivery of doseTotal number of fractions

Choose Number of BeamsChoose beam angles and couch angles

Organ at risk dose levels

Choose Planning Technique

Forward PlanningInverse Planning

Forward Planning

A technique where the planner will try a variety of combinations of beam angles, couch angles, beam weights and beam modifying devices (e.g. wedges) to find a optimum dose distribution.

Iterations are done manually till the optimum solution is reached.

Choice for some situations:

Small number of fields: 4 or less.

Convex dose distribution required.

Conventional dose distribution desired.

Conformity of high dose region is a less important concern.

Planning Beam orientation

Beams Eye View DisplayRoom's Eye ViewDigital Composite RadiographBEV Display: The observers viewing point is at the source of radiation looking out along the axis of the radiation beam.

Allows planner to visualize target volumes and critcal organ volumes facilitating planning of the aperture.

REV Display: The planner can simulate any arbitrary viewing location within the treatment room.

Allows planner to appreciate the composite beam arrangement and geometry

Digitally Composite Radiograph is a type of DRR that allows different ranges of CT numbers that relate to a certain tissue type to be selectively suppressed or enhanced in the image.

Analogous to a transmission radiograph through a virtual patient where certain tissue types have been removed, leaving only the organs of interest to be displayed.

Allow better visualization of the organ of interest

Beam Arrangement

Inverse Planning

1. Dose distribution specified

Forward Planning

2. Intensity map created3. Beam Fluence modulated to recreate intensity map

Inverse Planning

Spatial dose distribution in the 3 dimensional volume is first defined.

Defination of dose coverage for the PTV(s)

Defination of sparing for the organ at risk

Establishment of a hierarchy of targets and organs at risk

Beam intensity distribution required to achieve this dose distribution goal would be calculated.

Photon Fluence required to deliver this intensity distribution is then generated.

Optimization

Refers to the technique of finding the best physical and technically possible treatment plan to fulfill the specified physical and clinical criteria.

A mathematical technique that aims to maximize (or minimize) a score under certain constraints.

It is one of the most commonly used techniques for inverse planning.

Variables that may be optimized:

Intensity maps

Number of beams

Number of intensity levels

Beam angles

Beam energy

Optimization Criteria

Refers to the constraints that need to be fulfilled during the planning process

Types:

Physical Optimization Criteria: Based on physical dose coverage

Biological Optimization Criteria: Based on TCP and NTCP calculation

A total objective function (score) is then derived from these criteria.

Priorities are defined to tell the algorithm the relative importance of the different planning objectives (penalties)

The algorithm attempts to maximize the score based on the criteria and penalties.

Normal Organ Constraints

As per data given by Perez et al:

Gr III rectosigmoid complications:

1-4% with dose < 80 Gy

9% with dose 80 Gy

Moderate Urinary sequale:

2% < 70 Gy

5% 75 Gy

Grade III small bowel sequale:

1% 50 Gy

2% to 4% > 60 Gy

RectumBladderPerez CA, Grigsby PW, Lockett MA, Chao KSC, Williamson J. Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation. International Journal of Radiation Oncology*Biology*Physics. 1999 Jul 1;44(4):855-866.

Normal Organ Constraints

Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies . International Journal of Radiation Oncology*Biology*Physics. 2002 Apr 1;52(5):1330-1337.

Small Intestine: DVH correlates

Acute GI toxicity correlates with small bowel dose

% volume of small intestine receiving doses in the range of 75 -100% of prescribed dose significant predictor.

In a study of 50 patients Volume of small bowel receiving 100% of prescribed dose retained significance in multivariate analysis.

1. Roeske JC, Lujan AE, Krishnamachari U, Mundt AJ. Dose-volume histogram analysis of acute gastrointestinal toxicity for gynecologic patients receiving intensity-modulated whole pelvic radiotherapy. International Journal of Radiation Oncology*Biology*Physics. 2001 Nov 1;51(3, Supplement 1):221-222.

2. Roeske JC, Bonta D, Mell LK, Lujan AE, Mundt AJ. A dosimetric analysis of acute gastrointestinal toxicity in women receiving intensity-modulated whole-pelvic radiation therapy. Radiotherapy and Oncology. 2003 Nov ;69(2):201-207.

Colorectum: DVH Correlates

Anal Canal Dysfunction:

Correlated with radiation doses in the range from 50 to 60 Gy.

Rectal Dysfunction:

Risk of late rectal bleeding significantly high when the rectum is enclosed by the 50 -60 Gy isodose curve for more than 1 cm length

Fokdal L, Honor H, Hyer M, Maase H. Dose-volume Histograms Associated to Long-term Colorectal Functions in Patients Receiving Pelvic Radiotherapy. Radiother Oncol. 2005 ;74(2):203-10.

Bone Marrow: DVH correlates

Significant correlation of volume of bone marrow receiving doses of >10 Gy

1. Mell LK, Kochanski JD, Roeske JC, Haslam JJ, Mehta N, Yamada SD, et al. Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy. International Journal of Radiation Oncology*Biology*Physics. 2006 Dec 1;66(5):1356-1365.

Optimization

Plan Evaluation: Cumulative DVH

Cumulative DVHs give a quick overview of the 3D Dose distribution.

Analysis of a absolute volume vs absolute dose histogram is more intuitive.

Always look for the absolute volume incorporated in the dose limit.

Also look for the tail of the curve and look what is the dose there.

Plan Evaluation: Differntial DVH

Differential DVH allow a visual representation of the dose homogenity in the target volume.

Ideally the DVH should have a sharp peak in the differential DVH

The peak of the curve gives a good representation of the modal dose being received by the volume in question.

Plan Evaluation: Color Wash

The color wash and it's counterpart the isodose views allow quick visual verification of the dose distribution.

Coverage of the PTV should be assessed with the color wash or isodose curve display on each slice

Oragan doses should also be evaluated for the clinically relevant dose limit set.

Verification

Both absolute and relative dosimetric verification is essential for each IMRT plan.

Absolute dose variations should be 3%.

Should be measured in a region of low dose gradient.

Relative dose variation 5% is acceptable.

Clinical Results

Dosimetric Comparisions

Selvaraj et al compared IMRT and conventional 3D CRT plans for cervical cancer patients using 7 field IMRT.

1. Selvaraj RN, Gerszten K, King GC, Sonnik D, Heron DE. Conventional 3-D versus intensity modulated radiotherapy for the adjuvant treatment of gynecologic malignancies: a comparative study of dose-volume histograms and the potential impact on toxicities. International Journal of Radiation Oncology*Biology*Physics. 2001 Nov 1;51(3, Supplement 1):218-219.

WPIMRT: Clinical Results

Chen M, Tseng C, Tseng C, Kuo Y, Yu C, Chen W. Clinical outcome in posthysterectomy cervical cancer patients treated with concurrent Cisplatin and intensity-modulated pelvic radiotherapy: comparison with conventional radiotherapy. International journal of radiation oncology, biology, physics. 2007 Apr 1;67(5):1438-44

Mundt AJ, Roeske JC, Lujan AE, Yamada SD, Waggoner SE, Fleming G, et al. Initial Clinical Experience with Intensity-Modulated Whole-Pelvis Radiation Therapy in Women with Gynecologic Malignancies, . Gynecologic Oncology. 2001 Sep ;82(3):456-463.

Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies . International Journal of Radiation Oncology*Biology*Physics. 2002 Apr 1;52(5):1330-1337.

Kochanski J, Mehta N, Mell L, Roeske J, Sutton H, Mundt A. Outcome of Cervical Cancer Patients Treated with Intensity Modulated Radiation Therapy. International Journal of Radiation Oncology*Biology*Physics. 2005 Oct 1;63(Supplement 1):S214.

.

WPIMRT: Chronic Toxicity

Mundt et al reported a detailed comparision of IMRT vs 3DCRT

WPIMRT reduced chronic GI toxicity to 11% from 50% in conventional 3D CRT.

Significant difference on multivariate analysis

Majority of patients of WPIMRT who had GI toxicity had grade I toxicity only.

Mundt AJ, Mell LK, Roeske JC. Preliminary analysis of chronic gastrointestinal toxicity in gynecology patients treated with intensity-modulated whole pelvic radiation therapy. International Journal of Radiation Oncology*Biology*Physics. 2003 Aug 1;56(5):1354-1360.

IMRT: Extended Pelvic Radiation

RTOG 92-10:

31% acute Grade 3 - 4 nonhematologic toxicity

76% acute Grade 3 - 4 chemotherapy related toxicity

31% of patients did not complete radiotherapy

Salama et al (University of Illinois):

13 patients with various pelvic malignancies (11 mo followup)

Only 2 / 13 patients had Grade III acute toxicity

Late Gr III toxicity:

Small bowel obstruction:1

Lymphedema: 1

Salama JK, Mundt AJ, Roeske J, Mehta N. Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies. International Journal of Radiation Oncology*Biology*Physics. 2006 Jul 15;65(4):1170-1176.

IMRT: Extended Pelvic RT

Beriwal et al (University of Pittsburg):

36 patients with Stage IB2IVA cervical cancer

Para-aortic nodes to the superior border of L1 treated

Weekly Cisplatin CCT

Gr III late toxicity: 10%

2yr LRC: 80%

2yr DFS: 51%

Beriwal S, Gan GN, Heron DE, Selvaraj RN, Kim H, Lalonde R, et al. Early Clinical Outcome With Concurrent Chemotherapy and Extended-Field, Intensity-Modulated Radiotherapy for Cervical Cancer. International Journal of Radiation Oncology*Biology*Physics. 2007 May 1;68(1):166-171.

Bone Marrow Sparing

Dosimetric comparision of bone marrow sparing IMRT (Lujan et al):

Found that between a dose level of 18 20 Gy a significant reduction in volume of bone marrow irradiated was obtained with IMRT.

Brixey and Colleagues specifically compared hematological toxicity of WP-IMRT vs WPRT in the setting of concurrent CCT

Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ. Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies. International Journal of Radiation Oncology*Biology*Physics. 2002 Dec 1;54(5):1388-1396.

Conclusions

Both 3D CRT and IMRT are still investigational tools.

However unless dose escalation is done no significant improvement in the control rates should be expected.

Chronic and acute toxicity amelioration are the more relevant endpoints.

Also may allow tighter integration of brachy therapy/ chemotherpay / biological therapy

Biologically optimized radiotherapy is an exciting new development

Real impact can only be realised with meticulous care in planning and execution.

Thank You

Dr Santam Chakraborty Department of Radiotherapy, PGIMER Chandigarh

SystemTechniqeXYZStereotactic Body FrameNon invasive, vacccum based5-7 mm1 cmHeidelberg frameNon invasive, vaccum based5 mm10 mmBody Fix FrameNon invasive, Vacccum based with plastic foil0.4 3.9 mm0.1 1.6 mm0.3 3.6 mm

???Page ??? (???)11/05/2007, 23:46:34Page / ??????Page Page AuthorYear NCCT DoseResultMundt (P,NR)200336Y (53%)45 Gy (1.8 Gy/#)80% stage I-II; PTV S3 to L4/5 interspace; Chronic GI toxicity 15% (n= 3; 1 Gr II, 2 Gr I); 50% incidence in Conventional Mundt (P,NR)200240Y45 Gy (1.8 Gy/#)60% Acute Gr II toxicity (90% Gr II in Conv.); Less GU toxicity (10% vs 20%); Patients not requiring antidiarrheal halved!Chen (P,NR)200733Y50.4 Gy / 28# All Stage I -II; All Post Hysterectomy; 1 yr LRC 93%; Acute GI toxicity 36% (Gr I-II); Acute Gu toxicity 30% (Gr I-II). Chronic GI toxicity 6% (34% in 3D CRT).Kochanski200562Y (64%)45 Gy (1.8 Gy /#)29% Post op; 20 Stage IIB-IIIB; 3 yr DFS 72.7%; 3 yr pelvic control 87.5%; 5% Gr II or higher late toxicity

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