3D CRT and IMRT in Cervical Cancers Department of Radiotherapy PGIMER Chandigarh

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

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.

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 fieldshaping alone Techniques to modulate the intensity of fluence across the geometrically-shaped field (IMRT)‏

Two broad subtypes :

Techniques aiming to employ geometric fieldshaping alone

Techniques to modulate the intensity of fluence across the geometrically-shaped field (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 ) ‏

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 fields 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) ‏

Cast metal compensator

Jaw defined static fields

Multiple-static MLC-shaped fields

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 Since beam is interrupted between movements leakage radiation is less. Easier to deliver and plan. More time consuming Intesntiy Distance

Since beam is interrupted between movements leakage radiation is less.

Easier to deliver and plan.

More time consuming

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. Intesntiy Distance

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.

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.

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) ‏

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

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

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 devices Frame based Frameless Invasive Noninvasive 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 ”

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.

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 Frame Body Fix system

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

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

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

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 insert CT Scanner PET scanner 60 cm Allows 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%

Allows 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- 18 Fluoro 2- Deoxy Glucose Proliferation markers Radiolabelled thymidine: 18 F Fluorothymidine Radiolabelled amino acids: 11 C Methyl methionine, 11 C Tyrosine Hypoxia markers 60 Cu-diacetyl-bis(N-4-methylthiosemicarbazone) ( 60 Cu-ATSM)‏ Apoptosis markers 99 m Technicium Annexin V PET Fiducials

Metabolic marker

2- 18 Fluoro 2- Deoxy Glucose

Proliferation markers

Radiolabelled thymidine: 18 F Fluorothymidine

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

Hypoxia markers

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

Apoptosis markers

99 m Technicium Annexin V

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

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.

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

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

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.

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 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 (V 95 ). 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. GTV CTV ITV PTV 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 (V 95 ).

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 )‏

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 )‏

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 significant 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.

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 significant 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.

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 body 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 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 nodes Internal iliac Nodes : 7 mm margin around vessels. Extend lateral borders to pelvic side wall 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 Presacral Nodes : Subaortic: 10 mm strip over anterior sacrum; Mesorectal: cover entire mesorectal space 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.

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

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

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%

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%

Planning workflow Define a dose objective Total Dose Total Time of delivery of dose Total number of fractions Choose Number of Beams Choose beam angles and couch angles Organ at risk dose levels Choose Planning Technique Forward Planning Inverse 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.

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 Display Room's Eye View Digital Composite Radiograph

Beam Arrangement

“Inverse” Planning 1. Dose distribution specified Forward Planning 2. Intensity map created 3. Beam Fluence modulated to recreate intensity map Inverse Planning

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

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.

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 Rectum Bladder

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

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.

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.

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

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

Bone Marrow: DVH correlates Significant correlation of volume of bone marrow receiving doses of >10 Gy

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

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.

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.

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.

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.

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.

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

WPIMRT: Clinical Results

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 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.

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

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

IMRT: Extended Pelvic RT Beriwal et al (University of Pittsburg): 36 patients with Stage IB2–IVA 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 et al (University of Pittsburg):

36 patients with Stage IB2–IVA 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%

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

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

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.

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