DR. SUGASHWARAN. J,MODERATOR:PROF.DR.G. V. GIRI,DEPT. OF RADIATION ONCOLOGY,KMIO, BANGALORE.

CLINICAL APPLICATIONS OF LDR-HDR BRACHYTHERAPY

BRACHYTHERAPY

Type of radiation treatment Consists of placing sealed

radioactive sources very close to or in contact with the target tissue.

CLINICAL ADVANTAGES

High biological efficacy Rapid dose fall-off High tolerance Tolerable acute intense reaction Decreased risk of tumor population High control rate Minimal radiation morbidity Day care procedure

LIMITATIONS & DISADVANTAGES Difficult for inaccessible regions Limited for small tumors (T1_T2) Invasive procedures, require GA Higher dose inhomogeneity Greater conformation –small errors in

placement of sources lead to extreme changes from the intended dose distribution

Radioactive hazards (not now) Costly

SELECTION CRITERIA Easily accessible lesions Early stage diseases (Ideal implant ≤ 5

cm) Well localized tumor to organ of origin No nodal or distant metastases (radical

intent) No local infections or inflammation Favorable histology- mod. diff. i.e. SCC Well controlled DM / HTN Proliferative/exophtic lesions preferred

(better outcome)

INDICATIONS

SOLE MODALITY Skin

malignancies- BCC, SCC

Head & neck cancers

Ca cx Ca prostate

BOOST( AFTER EXT.RT±CCT) Head & neck

cancers Ca Breast Esophagus Anal canal

INDICATIONS...

PERIOPERTIVE STS Ca Breast

POSTOP Ca Endometrium Ca cx Ca Breast

PALLIATIVE Bronchogenic Ca Biliary duct

malignancy Ca Esophagus Recurrent tumors

BENIGN Keloids /

Pterygium OTHERS

Endovascular/Rad. stent

CLASSIFICATION

SURGICAL APPROACH / POSITIONING SOURCE IN TUMOR

INTERSTITIAL INTRACAVITARY INTRALUMINAL ENDOVASCULAR

SOURCE IN CONTACT BUT SUPERFICIAL SURFACE

BRACHYTHERAPY/ MOULD

DURATION OF IRRADIATION TEMPORARY-

Cs137,Ir192

PERMANENT-I125,Au198

Pd 103 .Cs 131

DOSE RATE(ICRU 38)

LOW DOSE RATE (LDR) 0.4-2 Gy/hr (clinical practice range 0.4 to

1 Gy per hour) MEDIUM DOSE RATE (MDR)

2-12 Gy/hr HIGH DOSE RATE (HDR)

> 12 Gy/hr ULTRA LOW DOSE RATE

0.01-0.3 Gy/hr

ADVANTAGES

LDR HDR

Predictable clinical effects

Superior radiobiological role

Less morbidity, control is best

Well practised since long Minimum intersession

variability in dose distribution

SHORT TREATMENT TIME Geometry well maintained Better patient compliance /

comfort Day care procedure

DOSE OPTIMIZATION NO RADIATION HAZARDS SMALL APPLICATOR

Less tissue trauma Better packing

AFTER LOADING TECHNIQUE

MANUAL Avoids radiation

protection issue of preloading

Better applicator placement

Verification prior to source placement

More radiation hazard

Advantages of preloading

REMOTE CONTROLLED No radiation hazard Accurate placement Geometry maintained Better dose

distribution Highly precise Short Treatment

time Day care procedure Mainly used for HDR

RADIOBIOLOGY

Biological effects depend on Prescribed dose Treated volume Dose rate Fractionation Treatment duration

RADIOBIOLOGY – 4 Rs

Repair Reassortment / redistribution Repopulation Reoxygenation

INTERSTITIAL BRACHYTHERAPY Sealed Radioactive sources directly

implanted into the tumor in a geometric fashion

ADVANTAGES Higher local dose in shorter time Rapid dose fall Better tumor control Lesser radiation morbidities Superior cosmetics Functional preservation of organs

INTERSTITIAL BRACHYTHERAPY… DISADVANTAGES

Invasive procedure Costly

INTENTION OF TREATMENT RADICAL INTENTION

As radical brachytherapy alone (smaller lesions)

Local boost in combination with EBRT (larger lesion)

SELECTION CRITERIA

Easily accessible lesions, at least from one side

Early stage disease T 1-T2 and sometimes early T3 Ideally total size of implant ≤ 5 cm

Well controlled DM /HTN No local infection

CLINICAL APPLICATIONS

Head & neck tumors Early stage oropharyngeal cancers

Ca breast- Boost /PBI Ca prostate Soft tissue sarcoma Gynecologic malignancies Ca anal canal and rectum Ca lung and pancreas

TYPES OF INTERSTITIAL IMPLANTSACCORDING TO SIZE/LOCATION/PROXIMITY OF TUMOR TO NORMAL STRUCTURES TEMPORARY

Radioactive sources removed after desirable dose has been delivered

Rigid stainless steel needles/flexible Teflon / nylon guides/plastic tubes

Preloaded/After loaded

PERMANENT Preloaded – rigid

needle eg. Ra226 ,Cs137 After loaded –

Manual/ Remote Advantages

Flexibility of implant design

Reduction of radiation exposure levels resulting in more accurate placement of needles and guides

PERMANENT IMPLANTS

ADVANTAGES DISADVANTAGES

Less accessible sites ultra low dose

rate/Max biological effectiveness

Better tissue heal Better effect in slow

and radio resistant tumors

Improved mobility

Environmental issue Dosimetric

uncertainties/ Later part of Treatment becomes less effective

Source displacement Large tumor /Difficult

procedure and geometry

Radio biologically less effective for rapidly proliferating tumors

CLINICAL APPLICATIONSOral Cavity: LIP:

Indications: T1-2N0 Lesions (monotherapy- 0.5to5 cm or boost therapy->5 cm)

T.V.: All visible & palpable tumour with 5-10 mm margin

Dose: 50-70Gy in 5-7 days LDR Technique:

Rigid after loading needles maintained in place by Template

Classical plastic tubes Spacers to decrease dose to gingiva, teeth &

other lip

CLINICAL APPLICATIONS…Buccal Mucosa:

Indications: Brachytherapy alone indicated for small

(<4cm), well-defined lesions in anterior 2/3rd

As boost after EBRT for larger lesions T.V.: GTV +0.5 to 1 cm margins Dose: Alone 65-70 Gy

Boost 25-30 Gy Technique: Guide Gutter Technique: Lesion <

2cm Plastic tube technique: For other lesions

CLINICAL APPLICATIONS…Oral Tongue:

Indications: T1 N0, T2 N0 < 3cm lesion

T.V.: GTV + 5 mm margin Dose: Alone:60-65 Gy LDR

Boost 20-25 Gy after EBRT dose of 45-50 Gy

Techniques: Guide-gutter technique

AP X-ray

CLINICAL APPLICATIONS…Floor of Mouth:

Indications: T1-2N0 lesions, ≥ 5 mm away from mandible

Dose: monotherapy-65Gy;boost-20 to 30 Gy Complication: bone necrosis is most

common, up to 30%Oropharynx: Indications: Ca BOT, soft palate, tonsillar

fossa & vallecula usually as boost after EBRT Lesions < 5 cm (after EBRT)

T.V.: GTV + 10 mm margin Dose: Tonsillar fossa-25-30 Gy; BOT 30-35

Gy Technique: Classical Plastic Loop technique

CLINICAL APPLICATIONS… Nasopharynx: Ind- T1 AND T2 lesions

Dose: LDR -as a sole treatment 60Gy; as a boost 12 to 20 Gy.

HDR- 18 Gy in 6 fr

Opthalmic brachytherapy(I-125,Ru-106,Sr90)

Ind- malignant tumors of the conjuctiva, pterygium,wet macular degeneration,neovascularization

Sr 90 dose rate-100Gy/hr,, I-125 dose rate 0.5 to 1 Gy/hr

Pterygium – Sr 90 dose varying from 20 to 60 Gy in 1 to 6 fr.

CLINICAL APPLICATIONS…Breast

Indications: Boost after BCS & EBRT Postoperative interstitial irradiation alone of the primary tumor site after BCS in selected low risk T1 and small T2N0 (PBI)

Chest wall recurrences

As sole modality As Boost to EBRT

Patient choice: cannot come for 5-6 wks treatment :

Distance Lack of time

Close, positive or unknown margins

Elderly, frail, poor health patient

EIC

Large breasts, unacceptable toxicity with EBRT

Younger patients

Deep tumour in large breast

Irregularly thick target vol.

CLINICAL APPLICATIONS… T.V.: Primary Tumor site + 2-3 cm

margin Dose: As Boost: 10-20 Gy LDR

AS PBI: 45-50 Gy in 4-5 days LDR (30-70 cGy/hour)

34 Gy/10fr, 2fr per day HDR

Technique: Localization of PTV: Surgical clips (at least

6) USG, CT or MRI localization, Intra op USG

During primary surgery Guide needle technique or Plastic tube technique using Template

Double plane implant Skin to source distance: Minimum 5 mm

MAMMOSITE

Used for Accelerated Partial Breast Irradiation(APBI)

Fluid filled balloon placed during surgeryPrescriptionReference Point at 1 cm340cGy per fraction2 fractions per day6 hour separation10 fractions total Weekend break is allowed

Ideal patients for APBI(ASTRO)

Tumor Size < 2 cm Absence of nodal involvement(N0) Absence of Metastatic Status(M0) Age > 60 yr Negative margins Invasive ductal histology in the

absence of DCIS Estrogen receptor positive

HDR Brachytherapy with Savi The Savi applicator is a new single

insertion multicatheter device used for partial breast radiation.

It has a single central catheter and multiple peripheral catheters.

This allows the radiation dose to be tailored to the shape of the lumpectomy cavity.

Contura- multi lumen baloon Consists of a central lumen and 4 outer

lumen offering a total of 40 dwell positions Encased in a polyurethane balloon which

maintains symmetry and reduces potential for balloon ruputre.

NEW ELLIPTICAL BALOON(2004) Provides excellent conformance

Ellipsoidal implant parellel to the chest wall provides appropriate symmentry

AXXENT:NEWER DEVICE Uses a miniaturized x-ray source to deliver low energy

x-rays within a needle or catheter. Use of this device for APBI No need for heavy room shielding Stay in room with patient during treatment No radioactive materials license needed No handling, storing, security concerns One source per patient Must calibrate source before each treatment

CLINICAL APPLICATIONS…Prostate: Indications

Brachytherapy as monotherapy: Stage T1-2a /Gleason score 2-6 / PSA ≤ 10 ng/ml

As boost after EBRT Stage T2b, T2c /Gleason score 7-10 /PSA > 10 ng/ml

Patient factors : Life expectancy > 5 yrs IPSS<15 Prostate volume<60cm22

No defect if previous TURP Minimal pubic arch interfence

T.V.: Whole prostate within capsule + 2-3 mm margin

Methods: Permanent Implant (I125 or Pd103) or

Temporary Implant (Ir192)

CLINICAL APPLICATIONS… Technique for Permanent

implant Retropubic approach with I125 seeds-

Disappointing results Modern technique: Transperineal Approach

TRUS guided Two step approach

Volume study of prostate pubic arch interfence assessment

Computer planning Coverage check -USG & Flouroscopy Bladder irrigation /Cystoscopy can be performed Post-implant image based dosimetry

CLINICAL APPLICATIONS Dose:

I125: 145 Gy as sole RT;100-110 Gy as boost to 40-50 Gy EBRT

Pd103: 125 Gy as sole RT;90-100 Gy as boost to 40-50 Gy EBRT

Cs 131 :115 GY as sole rt;85-95 Gy as boost to 40-50 Gy EBRT

Temporary Implants with Ir192 (LDR or HDR): Procedure same as above; lesser no. of

plastic catheters required (8-15) Dose:

LDR 30-35 Gy seeds left for 3 days(Boost to 45 Gy EBRT)

HDR 20-25 Gy, 4-6 Gy/#(Boost to 45 Gy EBRT)

CLINICAL APPLICATIONSSoft tissue Sarcomas (using Ir192 or I125) Indications:

As sole postop RT: completely resected intermediate or high grade

tumours of extremity or superficial trunk with -ve margins

As boost to postop EBRT: Intermediate or high grade sarcoma with +/-

margins Postop pts with small lesions & +ve/uncertain

margins Deep lesions Low grade sarcomas

T.V.: GTV + 2-5 cm margin GTV based on preop MRI & clinical findings

Dose: LDR (Ir seeds or wires) as sole treatment 45-50 Gy in 4-6 days

As boost to 45-50 Gy EBRT: 15-25 Gy in 2-3 daysHDR: as sole treatment 40 t0 50 Gy in 12 to 15 fr/

as boost to 45-50 Gy EBRT:18-25 Gy in 4-8 fr

CLINICAL APPLICATIONS… Technique:

Usually performed at time of surgery Basic or sealed end temporary implant

technique To delay the start of brachytherapy for

about 4 to 7 days after surgery limit the allowable skin dose the 40 Gy

isodoseline to <25cm2 and the 25 Gy isodose line <100 cm2

CLINICAL APPLICATIONS…Brain: Permanent or temporary (using I125 or

Ir192 seeds/wires ) Indications:

As boost to EBRT or recurrence Anaplastic astrocytoma or GBM, unifocal,

well cicumscribed, peripheral lesions & < 5 cm in diameter

T.V.: Contrast enhancing area on MRI +/- 5mm margin

Dose: LDR 50-60 Gy, 0.4-0.5 Gy/hr

Gliasite

Used to treat brain tumors

Balloon filled with I-125 containing solution Example: used to treat glioblastoma

multiformae to 50 Gy followed by EBRT boost

CLINICAL APPLICATIONS…Ca Anorectum

Indications: As boost to EBRT/ChemoRT

If T.V. does not exceeds 1/2 circumference, 5 mm thick, 5 cm long i.e. T1-2 & small T3 lesions

T1N0 adenocarcinoma of rectum 3-10 cm above anus

T.V.: Visible palpable tumor+5 mm Dose: LDR 15-20 Gy at 0.3-0.6 Gy/hr Technique: Guide needle technique

with plastic perineal template

CLINICAL APPLICATIONS…Gynecological Tumors (Ir192 LDR or HDR) Indications:

Ca Cervix Ca Endometrium

Postop local recurrence Ca Vagina & Vulva

Radical BT in early lesions (T1-2N0)Boost after EBRT in large lesions (T2-3N1)

Technique: Guide-gutter technique Blind plastic tube implant (transperineal technique) Plastic or guide needles

CLINICAL APPLICATION – CA CX ABS Recommendations

Bulky primary disease Prior hysterectomy-inability to place tandem

Post hysterectomy vault rec/cervical stump presentation

Extesive parametrial involvement Distorted anatomy Narrow vagina & fornices Extensive / Distal vaginal wall involvement

Re-irradiation after recurrences

CLINICAL APPLICATIONS… PERINEAL IMPLANTS

Martinez Universal Perineal

Interstitial Template (MUPIT)

Syed-Neblett template

CLINICAL APPLICATIONS…

Ca Lung: Permanent perioperative BT, I125 seeds Persistent or recurrent ds after EBRT or residual

ds after surgery

Ca Pancreas: Permanent perioperative BT, I125 seeds Locally advanced unresectable ds

Ca Penis: scc predominant histology,

Indications – T1,T2 and T3(<4cm)that do not involve the shaft of penis.

Based on paris system using templates(12 &18mm)

Dose ;60 Gy at a dose rate of 0.5 to0.65Gy/hr Ca urethra: as sole treatment is 60 to 70 Gy in 3 to 5 days;

as a boost 20 to 25 Gy.

INTRACAVITARY APPLICATION Radioactive sources are placed in a

existing cavity usually inside a predefined applicator with special geometry

Uses: Cervix Endometrium Vagina Maxilla Nasopharynx

DOSE SCHEDULE LDR (<200cgy/hr)

35-40 Gy at point A MDR (200-1200cgy/hr)

35 Gy LDR EQUIVALENT at point A HDR(>1200cgy/hr)

9 Gy in 2 fr 6.8Gy in 3 fr at point A

EXTERNAL RT WITH BRACHYTHERAPY Brachytherapy can follow external

irradiation SIMULTANEOUS

Stage I - II with very minimal parametriun involvement

HDR -5 sessions (9gy /fr, 1week apart) 40 Gy by EBRT simultaneously

SANDWICH Stage I-II 40 Gy LDR eq.—› EBRT 40 Gy

In both above cases a MIDLINE SHIELD is used

POST OP/ VAULT BRACHYTHERAPY Vault RT

No residual disease 8500 cGy at 5mm from the surface

of the vault 2 sessions 1 week apart

Residual disease CTV of 2 cm given to gross tumor

and the prescription of 8500cgy encompassing the whole CTV is made

2 sessions 1 week apart Mostly after EBRT

POST OP BRACHYTHERAPY CONTRAINDICATIONS

Vaginal wall involvement ( middle- lower 1\3)

Heavy parametrium infiltration VVF or VRF Inadequate space Medical contraindications Metastatic disease

Supplementary radiation 2000 cGy \10fr

SURFACE MOULDS Radiation is delivered by

arranging RA sources over the surface of tumor

Types Planar

Circular Square Rectangular

Line source Cylinder

INDICATIONS Superficial /Accessible tumors keloid : Sr90 , 20 gy in 4 fr after

surgery. Skin ca – HAM applicator, Freiburg flab

are surface template applicators, dose – 35 to 50 Gy in 5 to 10 fr.

Post mastectomy recurrence – LDR- 65 Gy in 2 to 3 fr,monthly intervals.

Oral tumor hard palate ,alveolus,oral cavity,lip as a sole modality 60 GY,as boost to 45 to

50 GY- 15 TO 30 Gy. Penile carcinoma

INTRALUMINAL BRACHYTHERAPY Radioactive source is passed through a

tube and passed into a hollow lumen Sites

Esophagus : TV-tumor+distal and proximal margin of 2 to 3 cm

Dose: palliative-16 GY IN 2 FR or 18 GY IN 3 FR.

as boost EBRT 50 Gy-HDR 10 Gy in 2 fr at 1 cm from surface.

ILBT.. Bronchus : Bronchogenic carcinoma

Definitive : T1-T2tumors

HDR- sole treatment-5Gy in 5 fr or 7.5 Gy in 2 fr prescribed to 1cm.

as boost to EBRT treatment(45 TO 60 Gy)- three 5 Gy fr or two 7.5 GY fr

Palliative : Dyspnea,hemoptysis,post obstructive

pneumonitis Poor lung function Previous EBRT Dose : 7.5Gy/fr in3 weekly fr, 10Gy/fr in 2 fr,

6Gy/fr in 4 fr prescribed at 1 cm. Boost treatment- 30 Gy in 10 to 12 fr

Biliary tract Ind – unresectable tumors Technique – endoscopic retrograde

technique BT delivered throug a transhepatic

cholangiogram TV- tumor +1 to 2 cm proximal and

distal margin Monotherapy- palliative dose 30 gy in 6

fr As boost(45 Gy EBRT) – 15 TO 20 Gy in

3 to 4 fr.

Intra vascular brachytherapy Coronary artery disease

caused by occlusion of cardiac vessels

IVB used to prevent restenosis after angioplasty Radiation delivered either with temporary implant or

radioactive stent

Intra operative Radiation brachytherapy

Attractive for deep tumors because the skin dose was limiting prior to the invention of megavoltage accelerators.

Applications include: retroperitoneal

sarcoma, pancreatic cancer, rectal cancer, pediatric tumors,malignant thoracic tumors.

dose of 10 to 20 Gy in single fr over 10 to 30 minutes.

Image guided brachytherapy

Image-guided brachytherapy may provide better dose distribution to the target tumor and reduced dose volumes to surrounding healthy tissues when compared with image-guided IMRT and IMPT.

The use of imaging techniques, such as ultrasound,CT and MRI for treatment planning, has led to improved visualization of the tumor and surrounding organs.

IGBT… Applicators used for IGBRT should be

such that the applicator does not produce an artifact on the cross sectional imaging technique being used. For this purpose special CT/MRI Compatible applicators should be used. The applicators are usually made up of a titanium alloy Now a days carbon fibre based brachytherapy applicators are also available.

MR is an ideal image guidance modality for image guided brachytherapy. Outstanding visualization of pelvic anatomy.

Adaptive Brachytherapy Adaptive Brachytherapy can be

defined as temporally changing the treatment plan delivered to a patient based on observed anatomic changes caused by tumor shrinkage, weight loss, or internal motion.

Plans are altered throughout the treatment course for every course of treatment depending on tumor volume.

Patient setup and organ motion obtained from imaging during treatment to alter the treatment plan.

ROBOTIC BRACHYTHERAPY

Improve accuracy of needle placement and seed delivery

Improve consistency of seed implant Improve avoidance of critical

structures Reduce radiation exposure MAINLY USED FOR CA PROSTATE Seed placement error is at sub

millimeter level.

Intensity modulated brachytherapy This modulation is specific for the patient and allows for

high intensity radiation treatment of tumor tissue with limited destructive effects on surrounding normal tissue.

Intensity modulated sources based on Monte Carlo simulations

a “modified TG43” (mTG43) dose calculation algorithm developed specifically for IMBT dosimetry. the anisotropic function of a IMBT source, is a function of both the position of measurement and the intensity distribution of the source

an inverse IMBT treatment planning method based on Dose Volume Histogram (DVH) or Dose Surface Histogram (DSH) constraints and simulated annealing optimization algorithm.