This document discusses high-dose-rate brachytherapy (HDR BT) and its clinical applications, with a focus on its use for prostate cancer. It defines HDR BT and compares it to low-dose-rate BT. It outlines many clinical sites where HDR BT is used and describes the procedure for prostate HDR BT in detail, including imaging, catheter placement, treatment planning, and common schedules. Complications are discussed. HDR BT is described as being commonly used as a boost with external beam radiotherapy or as monotherapy for prostate cancer.

1. Radiotherapy: Special Techniques
Mª Teresa Muñoz Migueláñez
Clinical Aspects and Applications of
High-Dose-Rate Brachytherapy

2. INDEX
 Introduction: Definition, History and Types.
 HDR vs LDR.
 Clinical applications.
 Prostate Cancer:
 Introduction.
 Implant Procedure.
 Uses: Boost, Monotherapy or salvage treatment.
 Conclusions.
 Bibliography.

3. INTRODUCTION
Definition, History and Types

4. Definition
 Brachytherapy (BT), from the Greek language, means “ therapy at a short
distance”.
 It involves the precise placement of radiation sources near the site of the
cancer cells. Because the absorbed dose falls off rapidly with increasing
distance from the sources, high doses may be delivered safely to a
localized target region over a short time. (1)
 Compared to external beam radiotherapy (EBRT), brachytherapy has the
advantage of delivering a high dose to the tumor while sparing the
surrounding normal tissues. (1)

5. History
 It was increasingly used in the treatment of
malignant tumors shortly after the discovery
of radium – 226 (226Ra) by Marie Curie in
1898. (2)
 Sustained a rapid growth with the
development of afterloading devices
(treatment with radioactive sources controlled from a distance)
and the introduction of artificial
radionuclides. (2)

6. Types (3)
Source placement
 Interstitial
 Intracavitary (e Intraluminal)
 Superficial (surface applicators)
Duration of dose delivery
 Temporary
 Permanent
Dose rate
 Low-dose rate (LDR): rate of up to 2 Gy/h. (Iodine 125 (125I) or Palladium 103 (103Pd))
 Medium-dose rate (MDR): rate between 2 Gy/h to 12 Gy/h
 High-dose rate (HDR): rate > 12 Gy/h. Iridium-192 (192Ir):
 Is the most commonly used isotope for HDR.
 Has an average energy of 380 KeV, a half-life of 73,8 days and a half value layer of 2,5 mm of lead.

7. HDR VS LDR
While LDR BT has been examinated and assesed the most and become a
standard treatment option, HDR brachytherapy has recently gained
momentum as an alternative.

8. Advantages Disadvantages
Radiation protection.
• HDR eliminates radiation exposure hazard for care givers and visitors.
• HDR eliminates source preparation and transportation.
• Since there is only one source, there is minimal risk of losing a radioactive source.
Radiobiological.
• The short treatment times do not allow for the repair of
sublethal damage in normal tissue or the redistribution of
cells within the cell cycle or reoxygenation of the tumor
cells; hence, multiple treatments are required.
Allows shorter treatments times.
• There is less patient disconfort since prolonged rest is eliminated.
• It is posible to treat patients who may not tolerate long periods of isolation and those who are at high
risk for pulmonary embolism due to prolonged bed rest.
• There is less risk of applicator movement during therapy.
• There are reduced hospitalization costs since outpatient therapy is posible.
• HDR may allow greater displacement of nearby normal tissues (by packing or retraction) which could
potentially reduce morbidity.
• It is posible to treat a larger number of patients in instutions that have a high volumen of BT patients
but insufficient inpatient facilities.
• Allow intraoperative treatments, wich are completed while patient is still in the operating room.
Limited experience.
• Few centers in the United States have long-term (>20 years)
experience.
• Until recently, standarized treatment guidelines were not
available; however, the American Brachytherapy Society
(ABS) has recently provide guidelines for HDR at various
sites (http://www.americanbrachytherapy.org/guidelines/)
HDR sources are of smaller diameter than the cesium sources that are used for
intracavitary LDR.
• This reduces the need of dilatation of the cervix and therefore reduces the need for heavy sedation or
general anesthesia.
• High-risk patients who are unable to tolerate general anesthesia can be more safely treated.
• HDR allows for intesrtitial, intraluminal, and percutaneus insertions.
The economic disadvantage
• The use of HDR BT as compared to manual afterloading
techniques requiers a large initial capital expenditure since
the remote afterloaders cost about $ 300000.
• There are aditional cost for a shielded toom and personnel
cost are higher as the procedures are more labor intensive
HDR makes treatment dose distribution optimization possible.
• Variations of the dwell times of a single stepping source allow an almost infinite variation of the
effective source strengths, and the source position allows for greater control of the dose distribution
and potenctially less morbidity
Greater potential risks
• Since a high activity source is used, there is greater
potential harm if the machine malfunctions or if ther is a
calcualtion error. The short treatment times, compared to
LDR, allow muchs less time to dectect and correct errors(1) Halperin, Edward C; Brady, Luther W; Perez, Carlos A; Wazer, David E (2013) Perez & Brady's Principles and Practice of Radiation Oncology (6th ed)

9. CLINICAL APPLICATIONS
HDR BT has been used in almost every site in the body, generally as a
component of multimodality treatment (4)

10. 1. Cervical cancer
2. Endometrial cancer
3. Prostate
4. Breast
5. Skin
6. Bronchus/Trachea
7. Bile duct
8. Esophagus
9. Head and neck
10. Soft tissue sarcoma
11. Pediatric tumors
12. Intraoperative brachytherapy
13. Anorectal
14. Other indications:
Penis
Bladder
Urethra
Ocular
Blood vessels (coronary and peripheral arteries)…

11. 1. Cervical cancer
2. Endometrial cancer
3. Prostate
4. Breast
5. Skin
6. Bronchus/Trachea
7. Bile duct
8. Esophagus
9. Head and neck
10. Soft tissue sarcoma
11. Pediatric tumors
12. Intraoperative brachytherapy
13. Anorectal
14. Other indications:
Penis
Bladder
Urethra
Ocular
Blood vessels (coronary and peripheral arteries)…

12. PROSTATE CANCER

13. Introduction
 Multiple treatment options are available for clinically localized prostate cancer:
 Radical prostatectomy, EBRT, BT, EBRT + BT….
 BT can deliver a highly localized radiation dose to the tumor.
 While LDR BT has been examined and assessed the most, and become a standard
treatment option (permanent implantation 125I or 103Pd (1)), HDR BT has recently gained
momentum as an alternative (5-6):
 Most commonly as a dose escalating boost delivered in combination with EBRT.
 There is also increasing experience in HDR BT used alone to deliver a radical dose radiation and as a
salvage treatment to local recurrence.
 Recomendations on temporary transperineal prostate BT, were first published on
behalf of GEC/ESTRO-EAU Prostate Brachytherapy Group (PROBATE) in 2005 (7)

14. Advantages Disadvantages
It is possible to individualise the source positions over the full
lenght of the prostate based on a defined planning target volume
and organs at risk. Dose distribution optimisation by inverse
planning enables highly conformal dose delivery.
Use of a fractionated schedule results in more work
load per patient and logistic issues related to quality
assurance across several radiation exposures
The use of image guide catheter or needle placement enables
accurate implantation which can be extended to include
extracapsular disease and seminal vesicles.
The treatments must be executed carefully because
the short treatment times do not allow any time for
correction errors, and mistakes can result in harm to
patients
The fixation of the prostate by the implant and rapid radiation
delivery minimises the problems of target and OAR movement.
During multifractionated HDR treatment, catheter
migration could cause degradation of dosimetry.
The use of high dose per fraction has a biological dose advantage
for tumors with a low alpha beta ratio of which prostate is a
common example.
Temporary BT using a stepping source does not need any source
preparation time and there is good radiation protection for
personnel.
The use of a single source for all patients using a multipurpose
facility makes HDRBT highly cost effective.
(6)(5-6)

15. IMPLANT PROCEDURE (6-9)

16. Equipment
 Operating room or brachytherapy suite suitable for sterile procedures and access to anaesthetic support.
 HDR afterloader.
 TRUS unit with template, the ultrasound should be capable of both transaxial an sagital image acquisition.
 TRUS fixation and stepping unit.
 Intestitial implant catheters of a suitable design compatible with the TRUS based template; They should
also be CT or MR compatible if this imaging method is to be used. Rigid steel or flexible catheters can be
used for the implant procedure. The advantage of flexible catheters is that the may be seen to bend
around the pubic arch and then regain their plane in the more anterior aspects of the prostate gland.
 Appropiate software to enable importation of post implant TRUS or CT or MR imaging with image fusion.
 A planning system which can achieve accurate implant reconstruction and 3D dosimetry.
 A brachytherapy suite with adequate shielding to perform the HDR treatment, according to national
radiation protection rules.
 Access to appropriate imaging post implant with either TRUS, CT or MR.

18. General Considerations
 Brachytherapy is done under spinal anesthesia.
 The patient is placed in the lithotomy position and a
urinary catheter is placed into the urinary bladder.
 The skin is prepared and full sterile theater
precautions should be used.
 TRUS is now the standard means of guiding
applicators. Setting up of the TRUS prior to
implantation is very important.
 The position of the patient and the template position
are critical before implantation is commenced:
 The urethra should be identified and positioned along the central
row of the template (usually row D)
 The inferior row of applicator positions must reflect the lowest part
of the gland to be implanted and if seminal vesicles are to be
included in the PTV it is essential these are also considered in the set
up.

19. Catheter insertion
 The applicators are inserted transperineally under
direct US control.
 When homogenous cover of the gland is required then
catheters should be placed with no greater tan 1 cm
intervals between applicators.
 Peripheral coverage is most important so it is vital to
have a ring of catheters around the edge of the
peripheral zones, with a distance of about 3 mm from
the prostate CTV border. It is advantageous start to
implant with the anterior catheters.

20. Imaging for dosimetry
TRUS
 Obtained whilst the patient remains in the
lithotomy position under anaesthetic or
sedation. The whole prostate should be covered
and in addition at least 5 mm cranially and
caudally outside the gland.
CT or MRI
 Obtained following recovery from anaesthetic
and transfer to the imaging deparment:
 CT acquisition should be at no more tan 3 mm intervals
 T2 will provided optimal anatomical definition but T1 will
provide more accurate catheter reconstruction.
 Image fusion may be used to maximise information. Fiducial
markers are placed in the prostate to compare catheter
localited prior to each treatment.

21. Volumes for treament plannig
 CTV is defined by:
 The prostate capsule.
 Plus any macroscopic extracapsular
disease or seminal vesicle involvement
identified on diagnostic images expanded
by 3 mm. (Usually constrained posteriorly to the
anterior rectal wall and superiorly to the bladder base.)
 Organs at risk (OAR):
 Rectum.
 Urethra: Should extend from bladder
base to 5 – 50 mm bellow the prostatic
apex.
OAR dose constraints
Urethra: Dmax ≤ 120%
Rectum: V70 < 1cc

22. Planning aim and dose prescription
 Once satisfactory dose distribution has
been obtained, this will be transfered into
the HDR control program as a series of
dwell times for each catheter.
 Typical treatment times are very short,
most catheters having total treatment
times for the implant being of the order of
10 – 15 min, depending upon the total
number of catheters.

23. Complications and toxicity
 This technique is well tolerated.
 Perineal presure after catheter removal will minimize the risks of
hematoma formation. Antibiotics, steroid medications and α blockers can
be prescribed.
 Genitourinary:
 Acute urinary irritative symptoms (urgency, frequency…) are common and usually resolve with time.
 Urinary retention occurs in < 5% of cases and can be managed with catheterization.
 Urinary strictures are reported in up to 15% of patients (most commonly in bulbomembranous urethra). TURP
should be avoided after HDR prostate BT, but there is no absolute contraindication to a properly
performed procedure.
 Prolonged urinary incontinencee is extremely rare, < 2%.

24. (9)

25. Complications and toxicity
 Gastrointestinal:
 Rectal irritation causing rectal urgency or frequency is more likely when HDR is use in
conjunction with EBRT.
 Late rectal bleeding may occur and is usually not clinically significant.
 Serius complications, such as a rectal fistula, are extremely rare, and seen in < 1%.
 Sexual dysfunction:
 Erectile dysfunction has been reported in up to 40% of men who were fully potent at
baseline but approximately 80% respond to pharmacologic agents .
 5 – year probability of impotence 49% LDR and 21% HDR (p = 0,006) (2)

26. USES OF HDRBT IN PROSTATE CANCER
Boost with EBRT, Monotherapy or Salvage treatment to local recurrence

27. BOOST with EBRT
 HDRBT as a boost with EBRT is now estabilished as an effective means of
dose escalation in the radical treatment of prostate cancer supported by
level 1 evidence from one randomised trial (10) and a large body of
published series.
 Represents a succesful treatment of choice and results in excellent bNED,
local control and survival rates.

28. Patient Selection Criteria
 Stages T1b to T3b prostate cancers, any Gleason
Score and any PSA level are candidates for HDR
as a boost to EBRT
 Relative Contraindications:
 Large glande size (>60cc)
 Significant urinary obstructive symptons
 Recent TURP within the last 6 months
 Large TURP defects
 Pubic arch interference
 Rectum-prostate distance on TRUS of < 5 mm
 Absolute Contraindications: (9)
 Preexisting rectal fistula.
 Lithotomy position or anesthesia not possible
 No proof of malignancy
GEC-ESTRO/EAU 2005
GEC/ESTRO 2013

29. Treatment Schedules
 It is not possible to make a firm recommendation on plannig aim dose
 EBRT:
 45 Gy in 25 fx, 46 Gy in 23 fx; 35,7 Gy in 13 fx; 37,5 Gy in 15 fx…
 Before currently with or after HDRBT.
 Minimum volumen treated should include the entire prostate and vesicles with
margin +/- pelvic lymph nodes.
 HDR:
 Is given in multiple fractions, generally twice a day with a minimum of 6 h between
fractions, in 1 – 3 implant procedures.
 15 Gy in 3 fx; 11 – 22 Gy in 2 fx; 12 – 15 Gy in 1 fx… A single dose of 15 Gy is gaining
increasing acceptance (11)

30. GEC/ESTRO 2013 (6)

31. A single dose of 15 Gy
1. HDR Brachytherapy 2. EBRT (IMRT)
Pelvic lymph nodes: 45 Gy
Prostate + vesicles: 54 Gy

32. MONOTHERAPY
 First proposed by Yoshioka et al, almost 2 decades ago (12).
 Radiobiological considerations, which asume a low α/β for prostate
cancer, predict a significant advantage for HDRBT alone delivered in a
small number of very large fractions in terms of total biologically effective
dose over EBRT and LDRBT.
 Advantages relating to dosimetry and radioprotection.
 Demands higher degree of technical and planning expertise than boost.

33. Patient Selection Criteria
 Hot debate (5):
 Reported by several institutions, largely for low-risk, but also for low-to-
intermediate-risk patients.
 For high-risk patients should be considered investigational. However,
recently published reports revealed excellent biochemical control rates,
even for intermediate- and high-risk patients (13-15)
 As yet, no guidelines or recommendations have been established .

34. Treatment Schedules
Long term date are not yet available.
34 Gy in 4 fx (1 implant)
36-48 Gy in 4 fx (1 implant)
38 Gy in 4 fx (2 implants)
34,5Gy in 3 fx (3 implants)
31,5 Gy in 3 fx (1 implant)
26 Gy in 2 fx (1 implant)
19 Gy in 1 fx (1 implant)
Gunderson (2)

35. (5)

36. SALVAGE TREATMENT TO LR
 Locally recurrent prostate cancer following RT represent a clinical challenge (16).
 Surgery, cryotherapy and BT are among the most frequently used salvage
treatment options (17)
 Several aspects unique to HDR BT make it ideally suite or use as a salvage
procedure (18):
 Delivers high dose radiation directly to the target tissue.
 Results in very little treatment related uncertainty.
 Is well suited to hypofractionated treatment schedules.
 EBRT is not able to achieve either the high doses to the prostate or the dose sparing effect on normal
tissues that HDR BT is able to achieve (19)

37. Patient Selection Criteria
 Have a biospy-proven recurrence after definitive EBRT, with no evidence of
disease elsewhere.
Treatment schedules
36 Gy in 6 fx (20)
21 Gy in 3 fx (21)
30 Gy in 2 fx after 30 – 40 Gy
EBRT (post prostatectomy) (22)
There is limited experience and this is no
recommended outside a formal prospective
study. OAR constraints are critical in this setting (6)

38. HDRBT 36 Gy in 6 fx (2 implants, 1 week apart)
Mediam followup 18,7m: bNED 89% with 14% G3-4 toxicity. (20)
Mediam followup 60m: bNED 51% with 4% G3-4 toxicity. Suggestig that, with
further time, G3 complicantions trend to improve. (23)

39. CONCLUSIONS

40.  HDRBT is a vehicle for dose escalation that has resulted in high tumor control and
low toxicity rates.
 With proper selection and delivery technique, HDRBT has great promise and
convenience because of avoidance of radiation exposure, short treatment times,
and outpatient therapy.
 The development of well-controlled randomized trials addressing issues of efficacy,
toxicity, quality of life and costs versus benefits will ultimate define the role of HDR
BT in the therapeutic armamentarium.
 With excellent tumor control and a favorable side-effect profile, HDR BT is now an
established and important treatment for prostate cancer.

41. BIBLIOGRAPHY

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44. ”Life is not easy for any of us. But what of that? We
must have perseverance and above all confidence in
ourselves. We must believe that we are gifted for
something and that this thing must be attained.”
Marie Curie