Radiotherapy in Practice - Brachytherapy [2nd ed.] 9780199600908, 0199600902

Table of contents :
1. Introduction
2. Isotopes and delivery systems for brachytherapy
3. Principles of brachytherapy dosimetry
4. Radiation protection issues in brachytherapy
5. The role of brachytherapy in head and neck cancer
6. Brachytherapy for uterine tumours: cervix and endometrium
7. Prostate cancer: permanent low dose rate seed brachytherapy and temporary high dose rate afterloading brachytherapy
8. Endolumenal brachytherapy: bronchus and oesophagus
9. Perineal implants: anal canal, vagina and vulva
10. Breast brachytherapy
11. Rectal brachytherapy
12. Miscellaneous sites
13. Quality assurance

Citation preview

Foreword

Radiotherapy in Practice - Brachytherapy (2 ed.) Edited by Peter Hoskin and Catherine Coyle Publisher: Oxford University Press Print Publication Date: Jan 2011 Print ISBN-13: 9780199600908 Published online: May 2013 DOI: 10.1093/med/ 9780199600908.001.0001

Foreword  

Brachytherapy is one of the earliest forms of radiation delivery and the first interstitial implant was said to have been performed in Dublin in 1912. By the 1950s the Manchester system, with Paterson and Parker’s relatively simple rules and tables, allowed brachytherapy to be disseminated widely and performed safely, throughout the world. In the 1960s radium was gradually replaced by artificial isotopes such as iridium, plus, the development of after loading, which was often used with the then new, Paris System of rules and dosimetry. Until the 1980s trainees in radiation oncology were not only expected to be familiar with the theory, indications and the dosimetry of brachytherapy, but, also to have developed competence in practice, by supervised training in the operating theatre. Over the last few years several factors have arisen which have significantly changed brachytherapy practice. The application of computer dosimetry, remote afterloading with dose optimisation and, 3D image guided source placement have made the process much safer and more effective, but also very much more complicated, requiring considerable multidisciplinary cooperation. Although the indications for brachytherapy have expanded in some areas, such as prostate cancer, other previously common indications, such as head and neck cancer and gynaecological cancer, have reduced substantially, both as a result of falling incidence and, improvements in surgical techniques, which have become the treatment of choice for many patients, previously referred for brachytherapy. This means that, in smaller departments, there are very Page 1 of 2

Foreword

few cases referred for this increasingly complex and demanding technique, so that it is extremely difficult to retain and develop expertise. Many have therefore correctly decided to refer potential cases to larger regional centres where expertise can be maintained and there are sufficient cases for teaching and training. As a result, it is quite possible that some trainees are never exposed to brachytherapy. The risk is not just that they become unable to perform the technique, but also, that they become unaware of the indications and unique advantages of this form of treatment and that many patients who could benefit are denied this option. This book is therefore essential reading for all radiation oncologists and their trainees so that they can become familiar with the theory the indications and the results of brachytherapy, and the new potential that recent advances have made possible. With this knowledge they will be better placed to advise patients on optimum management and if the technique is not available in their own centre be aware of the nearest centre of expertise to which they can be referred. Hopefully, there will also be some who will be sufficiently inspired to specialise in this exciting, effective and satisfying form of treatment themselves. Dan Ash Leeds, 2010 [Dan Ash was the founder of the joint Leeds/Mount Vernon course on which this book is based. Many generations have benefitted from his wisdom and enthusiasm for brachytherapy disseminated through the Leeds course which was first held in 1981 and annually thereafter until its incorporation with a similar course at Mount Vernon into the joint course under the auspices of the Royal College of Radiologists in 2003]

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Contributors

Radiotherapy in Practice - Brachytherapy (2 ed.) Edited by Peter Hoskin and Catherine Coyle Publisher: Oxford University Press Print Publication Date: Jan 2011 Print ISBN-13: 9780199600908 Published online: May 2013 DOI: 10.1093/med/ 9780199600908.001.0001

Contributors  

P Bownes Consultant Physicist, St James Institute of Oncology, Leeds, UK C Coyle Consultant in Clinical Oncology, St James Institute of Oncology, Leeds, UK P J Hoskin Consultant Clinical Oncologist, Mount Vernon Hospital, Northwood, Middlesex, UK and Professor of Oncology, University College London,London, UK C Richardson Principal Physicist, St James Institute of Oncology, Leeds, UK C D Lee Consultant Physicist, Clatterbridge Centre for Oncology, Bebington, Wirral, UK G Lowe Senior Physicist, Mount Vernon Hospital, Northwood, Middlesex, UK A Sun Myint Consultant Clinical Oncologist, Clatterbridge Centre for Oncology, Bebington, Wirral, UK

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Acknowledgements

Radiotherapy in Practice - Brachytherapy (2 ed.) Edited by Peter Hoskin and Catherine Coyle Publisher: Oxford University Press Print Publication Date: Jan 2011 Print ISBN-13: 9780199600908 Published online: May 2013 DOI: 10.1093/med/ 9780199600908.001.0001

Acknowledgements  

We are indebted to the Medical Illustration departments at St James Institute Hospital Leeds and East and North Herts NHS Trust

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Introduction

Radiotherapy in Practice - Brachytherapy (2 ed.) Edited by Peter Hoskin and Catherine Coyle Publisher: Oxford University Press Print Publication Date: Jan 2011 Print ISBN-13: 9780199600908 Published online: May 2013 DOI: 10.1093/med/ 9780199600908.001.0001

Introduction   Chapter: Introduction Author(s): P J Hoskin and C Coyle DOI: 10.1093/med/9780199600908.003.0009 Brachytherapy is the delivery of radiation therapy using sealed sources that are placed as close as possible to the site to be treated. The very term ‘brachytherapy’ means ‘near treatment’. It is therefore applicable for the treatment of tumours where a radiation source can be placed within a body cavity (e.g. the uterus, vagina, oesophagus, or bronchus) or where the tumour is accessible to needle or catheter sources being placed within it (e.g. the breast, head and neck, prostate, and skin). In fact, brachytherapy has potential applications to most tumour sites. It can be used as primary treatment or in combination with external beam radiotherapy. The principal advantages of brachytherapy lie in the physics of the dose distribution around a radiation source, which results in a high concentration of dose imme-diately around the source and a rapid fall-off of dose away from the source with distance according to the inverse square law. Other advantages include accurate localization of the gross tumour volume and immobilization of the area to be treated unlike the situation with external beam treatment when organ movement and set-up errors are introduced. The major disadvantages of brachytherapy lie in Page 1 of 3

Introduction

the need to access the tumour, often with an operative procedure and the requirement for skilled personnel to undertake the treatments. In the early days of radiation therapy, brachytherapy using radium sources was a novel means of delivering a radiation dose to a tumour. The development of high-energy external beam machines and the recognition of the problems associated with radiation protection in the use of radium resulted in a move towards caesium sources and the development of the concepts of afterloading in brachytherapy. Afterloading refers to the use of non-radioactive templates, tubes, or needles to define the implant, which are then later loaded with the active radioisotope. Early systems used manual loading, typically with iridium wire techniques using hairpins or loops. In the modern era, remote afterloading machines have largely replaced the use of manual live sources, with the exception of low dose rate seed brachytherapy. Early afterloading machines used predominantly cobalt or caesium sources; these are gradually being replaced by modern iridium afterloaders delivering either high dose rate or pulsed-dose rate brachytherapy. Sources may be regarded as continuous sources, that is with even distribution of the isotope along their length often encompassed within a sheath, for example, iridium wire, point sources or seeds and discontinuous sources, or source trains, which may be uniform or nonuniform in their dose distribution along their length, such as that found in remote afterloading caesium machines. Dose rate is an important consideration in the radiobiology of brachytherapy. Three dose rate bands are now defined: low dose rate based on radium (1 to 12 Gy per hour). When changing dose rate for a particular technique, it is important to remember that increasing dose rate increases biological effect and, therefore, demands dose reduction. Low- and medium-dose rate systems are increasingly being replaced by high dose rate systems and pulseddose rate systems, which mimic low dose rate delivery by delivering small pulses at high dose rate intermittently, usually hourly. There have been significant developments in external beam radiotherapy techniques over the last decade with the widespread introduction of intensity-modulated radiotherapy, image-guided radiotherapy, and stereotactic techniques. This represents a major challenge to brachytherapy, which used alone still offers the optimal approach to conformal radiation therapy delivery. In combination with external beam radiotherapy, brachytherapy enables dose escalation within an intensitymodulated radiation therapy volume with superior dose volume constraints to surrounding organs at risk compared with external beam techniques. It is therefore essential that expertise in these techniques are maintained and developed.

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Introduction

The following chapters seek to provide the reader with a sound infrastructure in the physics and dosimetry of brachytherapy followed by practical guides on the use of brachytherapy in common disease sites. While low dose rate, medium-dose rate, and high dose rate techniques are covered more emphasis is put on high dose rate afterloading techniques, which are expected to substantially replace the other forms of brachytherapy over the next decade. The advantage of these machines is that despite the requirement for fractionated treatments they allow short radiation exposure times and replace several days of inpatient treatment with outpatient therapy. The small source size, 50% myometrial invasion) and Grade I and II disease. The 5year vaginal relapse rate after brachytherapy was 1.8% compared with 1.6% after external beam, and the rate of pelvic relapse after brachytherapy was 5.1% compared with 2.1% after external beam. There was no difference in survival but quality of life scores were markedly better in the brachytherapy group compared with the external beam Page 6 of 27

Brachytherapy for uterine tumours: cervix and endometrium group. These results suggest that for this group of patients, vaginal vault brachytherapy alone is the preferred treatment. In low-risk patients (stage IAG1/G2) following hysterectomy for uterine cancer, there is no evidence to support the use of postoperative treatment. A large randomized trial from Scandinavia found a relapse rate of 3.1% after hysterectomy alone compared with 1.2% after hysterectomy and postoperative vaginal vault brachytherapy. This difference was not statistically significant and there was no difference in survival and an increased rate of urinary toxicity after postoperative brachytherapy. Where brachytherapy is given alone, the technique is identical to that above. The prescription differs as follows: ◆ LDR/PDR: 40–50 Gy at 5 mm depth at 0.5 Gy per hour dose rate. An appropriate dose rate reduction for higher dose rate sources and PDR pulse rates will be made for example: 36 Gy at 5 mm delivered at 1–1.2 Gy per hour. ◆ HDR: 22 Gy in four fractions at 5 mm depth or 21 Gy in three fractions at 5 mm depth. 6.3.1 Complications from vaginal brachytherapy In general, this procedure is well tolerated; acute reactions are few but may include: ◆ Transient dysuria, often mechanical from catheterization rather than radiation cystitis. ◆ Transient proctitis causing bowel frequency and looser consistency. Late complications are: ◆ Vaginal telangiectasia, which may result in occasional blood loss per vaginam, particularly after intercourse or clinical examination. ◆ Vaginal stenosis is seen in over 50% of women with a mean reduction in vaginal length of over 1 cm in the first 2 years after treatment. Regular use of vaginal dilators can reduce the incidence of stenosis from over 50% to about 10% and should be recommended even in women having regular intercourse. ◆ An increased incidence in sexual dysfunction is seen and rates of dyspareunia over 40% have been reported, particularly where stenosis is allowed to develop. 6.4 Cancer of the cervix: no hysterectomy, radical radiotherapy The use of intracavitary brachytherapy for the treatment of uterine tumours was one of the first routine applications of this form of treatment. Historically, radium was used and later caesium, with a number of different schools evolving using slightly different applicators and dose rates, broadly divided into the LDR school of radium use Page 7 of 27

Brachytherapy for uterine tumours: cervix and endometrium delivering treatment at 0.5–0.8 Gy per hour developed in Manchester and the higher-dose-rate system developed in Stockholm and Paris with dose rates of about 1 Gy per hour. Used within the constraints of their applicator design and treatment times they were all effective forms of treatment. Modern gynaecological brachytherapy has evolved from these systems and today there again is a broad divide between LDR or MDR systems using cobalt or caesium sources, which are now being replaced by equivalent PDR systems, and HDR afterloading brachytherapy systems, in which the common source is iridium. The general principles of applicator design and insertion technique are, however, common. 6.4.1 Applicator design While a number of different applicator designs are available they are all based on the same principle of a central intrauterine tube delivering a dose to the cervix, upper vagina, and parametrial tissues. While a single line source is used by some, most systems include lateral vaginal sources to increase the lateral spread of the dose. Three main types can be considered: 1. Central tube and lateral vaginal sources often termed ovoids because of their shape. Different eponyms are attached to these applicators according to their specific design and origin; for example, the Manchester tube and ovoids, the Fletcher tube and ovoids where the ovoids are angled posteriorly and have shielding and the Joslin Flynn applicator in which a posterior spatula type shield is included. Examples are shown in Fig. 6.4. 2. Central tube and ring applicator in which the vaginal sources are aligned in a ring beneath the cervix. This is typically used for HDR afterloading where the sources are small enough to follow the radius of a cervical ring and the presence of varying dwell positions around the ring, distinct from the fixed positions of the ovoids allow for greater individualization of dose distribution where required. Examples of such applicators are shown in Fig. 6.5. 3. A single line source is advocated by some for its simplicity and ability to conform to an individualized dose shape by adjusting dwell positions in the single line source. The disadvantage of this is that it delivers dose in three dimensions and so a lateral extension by increasing dwell times would also result in an anteroposterior extension, which will increase dose to bladder and rectum. With such a system, a vaginal tube is typically used to act as a spacer separating the vaginal walls. This system may be chosen preferentially in patients with stage IIA or IIIA disease where it is necessary to cover proximally down the vagina rather than extend laterally into the parametria. An example is shown in Fig. 6.6.

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Brachytherapy for uterine tumours: cervix and endometrium

Fig. 6.4 Examples of commercially available applicators for HDR intrauterine treatment using an intrauterine tube and discrete vaginal sources; upper Fletcher Suit applicators, lower Manchester design applicators.

Fig. 6.5 Tube and ring applicator, with posterior spatula to move rectal wall posteriorly (a) and (b) non metallic MR compatible applicator without spatula.

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Brachytherapy for uterine tumours: cervix and endometrium

Fig. 6.6 Single line source applicator (a) and dose distribution (b) for the treatment of cervical cancer.

6.4.2 Patient preparation Most patients will have had preceding external beam radiotherapy and so attention to electrolyte balance with control of gastrointestinal symptoms with appropriate antidiarrhoea medication, diet and fluid replacement is important. Many patients with cancer of the cervix have low-grade anaemia and there is good evidence that this impedes the response to treatment. While the role of transfusion is not clear before brachytherapy their haemoglobin should be assessed and maintained above 11.5 g dl–1. Patients other than those treated with outpatient HDR techniques are at increased risk of thromboembolism while immobile with applicators in situ and should be on prophylactic measures. 6.4.3 Brachytherapy procedure This is demonstrated schematically in Fig. 6.7. 1. In most settings, applicator insertion will be best undertaken under general anaesthetic or spinal anaesthetic. The patient is placed in the lithotomy position and the vulval area cleaned with antiseptic. 2. Examination under anaesthetic should be performed both per vaginum and per rectum to assess the clinical extent of tumour and any extension into the vagina or parametrial tissues. Page 10 of 27

Brachytherapy for uterine tumours: cervix and endometrium 3. The cervix should be identified using a speculum and grasped with Volsellum forceps. It may be difficult in the case of an advanced tumour where there is extensive necrotic tumour tissue replacing the cervix and it may only be possible to retain adjacent vaginal tissue. This may be adequate, however, to provide fixation of the cervix and some counter-traction for dilatation. 4. The cervical canal should be identified using a blunt uterine probe, which is passed into the uterine cavity and the length of the cavity can at this point be measured. Where there is extensive necrotic tumour it may be necessary to gently remove some of this using sponge forceps to identify and access the cervical canal. Reliable identification of the cervical canal and uterine cavity is greatly enhanced by the use of transabdominal ultrasound during this and the subsequent part of the procedure to avoid misplacement of the uterine tube. 5. Having identified the cervical canal this should be dilated with appropriate dilators. The extent of dilatation will depend upon the applicator system to be used; LDR or MDR systems are of larger diameter than HDR systems, the latter often requiring little or no dilatation. 6. Having dilated the cervical canal, if not already inserted, it is best at this point to pass a urinary catheter draining into a urine bag, which will remain for the rest of the treatment. If ultrasound is used this will be required earlier in the procedure and the bladder filled with sterile water to facilitate the ultrasound imaging. 7. Using the dilator, the uterine cavity size can be checked and the intrauterine tube chosen. At this point, it is also necessary to assess the vaginal size for the appropriate vaginal applicator to be chosen. During this time, the cervical dilator should be retained in the canal to prevent it closing down. 8. The dilator should then be replaced by the intrauterine tube followed by the vaginal source. Different applicator systems will have different forms of clamp or fixation of the two or three applicators together so that a rigid geometric relationship is achieved for each insertion. 9. Gauze packing is then inserted into the vagina posteriorly to displace the rectum and prevent movement of the applicators. Alternatively, an applicator system using a posterior spatula (e.g. the Joslin Flynn applicator) can be used. Care should be taken not to pack behind the vaginal source if there is posterior tumour and also to be avoid displacement down the vagina. If plain orthogonal films are to be taken, 5–10 ml of barium should be placed in the rectum; however, this causes considerable artefact on computed tomography (CT) and is better omitted if CT or magnetic resonance imaging (MRI) is to be used. 10. The insertion is then complete. For LDR/MDR and PDR systems, an anchoring corset is often used, as these applicators will have to stay in place for many hours. For HDR systems, less rigid fixation is necessary and a T bandage or elasticated bandage is sufficient. Page 11 of 27

Brachytherapy for uterine tumours: cervix and endometrium 11. Verification imaging is a vital component of the procedure. As a minimum this should be anteroposterior and lateral orthogonal X-ray films with a magnification marker; ideally CT imaging will be undertaken and where MR is available then the soft tissue definition is undoubtedly superior with MRI. It is important to use applicators designed to be compatible with the chosen modality of imaging. 12. Where HDR is used, then imaging is essential before each fraction.

Fig. 6.7 Steps in the procedure for the insertion of intrauterine applicators.

6.4.4 Cervical sleeve technique Because of the need for fractionated treatment with HDR and to avoid repeated procedures under anaesthetic where HDR is to be used a cervical sleeve technique may be employed. This entails, prior to insertion of the intrauterine tube and following dilation of the cervical canal, insertion of a plastic sleeve in the cervical canal and uterine cavity, which will act as a conduit for the cervical tube and allow further insertions as an outpatient procedure. It may be left free in the cervical canal or for added security retained by sutures on to the cervix or where there is extensive tumour the adjacent vaginal walls. An example of such a sleeve is shown in Fig. 6.8.

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Brachytherapy for uterine tumours: cervix and endometrium

Fig. 6.8 Cervical sleeve.

6.4.5 Other special considerations ◆ Haematocolpos may be encountered secondary to cervical canal stenosis and obstruction. This will be drained at the time of dilatation and provided there is no evidence of infection then the insertion can proceed. ◆ Pyocolpos is often unsuspected until pus is released at the time of cervical dilatation. This should be drained during the procedure and broad-spectrum antibiotics commenced, after taking swabs for culture. • If an LDR/PDR insertion is planned this should be abandoned and attempted again following a course of antibiotics; some also recommend that a drain be placed within the uterine cavity to ensure continued drainage of pus. • If an HDR procedure is planned, this can proceed. If a cervical sleeve is to be inserted provided it is of a design having drain holes in the end, then this can also proceed, acting as a drain for any residual pus or fluid. ◆ Fistulae secondary to tumour invasion may be encountered at examination under anaesthetic; they are not in themselves a specific contraindication to intrauterine brachytherapy. If urine leakage is suspected, then instillation of methylene blue into the bladder may aid identification of leakage per vagina. ◆ Perforation may occur even with the most skilled operator. Typically, this is through the posterior wall of the cervical canal into the pouch of Douglas or less often through the fundus. Series using CT scanning Page 13 of 27

Brachytherapy for uterine tumours: cervix and endometrium have suggested that the true rate of perforation, often unsuspected clinically may be as high as 5%. If perforation is suspected, unless the canal can be defined with confidence and the perforation bypassed, the procedure should be abandoned and the patient observed for 24 hours for signs of fever or peritonism. A period of 1 week should be left before attempting the insertion again. 6.4.6 Implant dosimetry Gynaecological brachytherapy was until recently undertaken following the recommendations in the ICRU Report No. 38. This builds on the long tradition of gynaecological brachytherapy, which defines dose at named specific points but also includes the concept of defining a 60-Gy isodose envelope. ICRU 38 is now being superseded by the adoption of threedimensional image-guided brachytherapy. ICRU 38 was based on orthogonal anteroposterior and lateral X-ray films with the applicators in situ. The rectum is defined using barium and the bladder from the balloon of the bladder catheter containing 7 ml of radioopaque liquid. The standard dose points are then defined as follows: ◆ POINT A: 2 cm lateral to the midline and 2 cm above the surface of the ovoid in the lateral vaginal fornix. ◆ POINT B: 3 cm lateral to point A. ◆ ICRU bladder reference point, which is at the inferior part of the bladder catheter balloon. ◆ ICRU rectal reference point, which is on the anterior rectal wall at a point perpendicular from the cervical os or lowest vaginal source. These are shown in Fig. 6.9.

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Brachytherapy for uterine tumours: cervix and endometrium

Fig. 6.9 (a) ICRU 38 dosimetry points based on a lateral x-ray with air or barium to define the rectum and a urethral catheter, the balloon of which contains 7ml of contrast solution.(b) GEC ESTRO Clinical Target Volumes (reproduced from Haie-Meder C. et al (2005) with permission from Elsevier). These reference point doses are, however, not related to the tumour volume and while there is some correlation between the rectal point and the rectal maximum dose no such correlation between bladder point and maximum bladder dose exists and there is also poor correlation with late toxicity. It is therefore now recommended that volumes based on threedimensional imaging be used for dosimetry calculation. CT may be used if MR is not available but MR is superior for the definition of both tumours and organs at risk. The major difference with this approach is that with the imaging a CTV can then be defined together with the bladder, rectal, sigmoid colon, and small bowel contours. 6.4.7 Clinical target volume definition The CTV, which will be used for PTV and the prescription, is defined by the extent of the disease as identified on imaging at the time of brachytherapy. This is best defined by MR at the time of brachytherapy but if this cannot be undertaken then a diagnostic MR in the preceding week of external beam treatment can be used to inform the anatomical location of the disease. The CTV should contain the GTV and any other

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Brachytherapy for uterine tumours: cervix and endometrium region where there is suspicion of residual disease, and always the entire cervix. A more complex description will be found in the published GEC ESTRO guidelines and shown in Fig. 6.9b. This refers to three distinct CTVs as follows: ◆ High-risk CTV (HR_CTV), which conforms to the definition above representing the residual macroscopic disease at the time of brachytherapy and including the GTV and the entire cervix. ◆ Intermediate-risk CTV (IR-CTV), which conforms to the region including the original bulk of the disease and typically includes the HR-CTV with a margin of 5–15 mm constrained to tissue planes such as the bladder and rectal walls. ◆ Low-risk CTV (LR CTV), which includes all the potential areas of microscopic disease at the time of diagnosis. Figure 6.10 shows the HR-CTV defined on MR scans at the time of brachytherapy for both a small, confined cancer and a locally advanced cervical cancer.

Fig. 6.10 Optimised dose distribution for (a) cervical tumour confined to cervix using tube and ring and (b) bulky tumour using tube and ring with additional interstitial applicators to increase dose in parametrium. For a colour version of this figure please .

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Brachytherapy for uterine tumours: cervix and endometrium 6.4.8 Dose prescription Conventionally, the dose prescription has been defined at point A. However, dose definition at a point does not relate to the CTV and is not a full description of the dose distribution; the same point dose can be achieved with varying distributions around that point. The three-dimensional image-based approach defines the dose to the CTV and the most common convention is to prescribe the dose to the HR CTV. The use of dose volume histograms allows a more detailed description of the dose delivered and inclusion of a biological dose conversion will allow a common reporting of doses in terms of 2 Gy equivalent doses. This can be used for both HDR and PDR, which are the two systems likely to predominate in delivery of brachytherapy for cervical cancer, as older LDR/MDR systems become obsolete. The conventional dose prescription was to deliver 75–85 Gy to point A. This dose may be composed of external beam treatment and brachytherapy. Dose rate of the external beam component will be that of a linear accelerator at approximately 1 Gy per hour and typical schedules will deliver 45–50 Gy using chemoradiation with cisplatin. The remainder will then be delivered by brachytherapy. While some schedules have described the use of a mid-line block from a certain external beam dose this is not recommended as accurate measurement of the dose behind the block is complex and matching a brachytherapy distribution to the deficit produced essentially impossible. An HDR afterloading iridium source delivers dose at approximately 1 Gy per minute with some variation from source decay during the typical period of use of about 3 months. When HDR systems are considered, fractionation is required but no correction for dose rate is needed when adding doses to external beam. However, when LDR/PDR systems are used, employing dose rates of between 0.5 and 1 Gy per hour, it is critical to take dose rate into consideration as the biologically equivalent dose for the same delivered dose will increase with dose rate. Randomized trials and meta-analysis comparing LDR with HDR suggests that the ultimate clinical result is very similar provided appropriate dose schedules are used. The following rules of thumb should be used and allow safe brachytherapy delivery: ◆ For a dose rate of 1–1.2 Gy per hour then a 10–15% dose reduction from the dose defined at 0.5 Gy per hour should be used. ◆ For HDR brachytherapy, a biologically equivalent dose calculation should be used, including the external beam component to determine the total dose to the HR-CTV. ◆ A further constraint when using fractionated HDR is that the dose per fraction should be kept below 7 Gy, as an increased risk of late toxicity has been shown with higher doses per fraction. Page 17 of 27

Brachytherapy for uterine tumours: cervix and endometrium Common schedules in use in the United Kingdom therefore would deliver 45–50 Gy external beam and follow this with brachytherapy (shown in Table 6.1). Two different columns of dose equivalent are shown, one using an αβ ratio of 10, which relates to acute reactions and tumour control and the other using an αβ ratio of 3.5 relating to late toxicity.

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Brachytherapy for uterine tumours: cervix and endometrium

Table 6.1 Common dose fractionation schedules for cervical cancer with biological equivalent doses in 2 Gy equivalent doses External beam dose a/b for BED

45 Gy 10

50.4 Gy 10

45 Gy 3.5

50.4 Gy 3.5

14 Gy/2 fractions

64 Gy

69 Gy

59 Gy

64 Gy

21 Gy/3 fractions

74 Gy

79 Gy

66 Gy

72 Gy

28 Gy/4 fractions

84 Gy

89 Gy

74 Gy

79 Gy

HDR dose

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Brachytherapy for uterine tumours: cervix and endometrium A dose–response has been identified for tumour control for cervical cancer and a minimum dose of 80 Gy (2 Gy equivalent: αβ =10) to the HRCTV should be achieved for non-bulky tumours and for bulky tumours a dose of 85–90 Gy (2 Gy equivalent: αβ = 3.5) should be aimed for. Alongside this normal tissue dose constraints must be obeyed. These are defined in terms of the dose to 2 cm3 of each organ derived from the dose volume histogram using an αβ ratio of 3.5 to calculate the 2 Gy equivalent dose. The recommended constraints in 2 Gy equivalent doses are as follows: ◆ Rectum: 70–75 Gy ◆ Bladder: 90–95 Gy ◆ Sigmoid colon:70–75 Gy ◆ Small bowel: 66 Gy. Based on the above, common prescription schedules will be: ◆ 45 Gy in 25 fractions external beam + 28 Gy in four fractions HDR brachytherapy ◆ 45 Gy in 25 fractions external beam + 30 Gy in three fractions at 1 Gy/h PDR brachytherapy ◆ 50 Gy in 25 fractions external beam + 24 Gy in four fractions HDR brachytherapy ◆ 50.4 Gy in 28 fractions external beam + 28 Gy in four fractions HDR brachytherapy. 6.4.9 Treatment delivery 6.4.9.1 Low- to medium (pulsed)-dose rate These treatments will require hospitalization and isolation in a purpose built afterloading brachytherapy room. During treatment, it is important that applicator position is verified and the treatment may be interrupted for this and other nursing tasks. A fiducial mark preferably on the patient in the form of an indelible skin mark adjacent to a similar mark on the applicator should be used to check movement of the applicators 2-hourly through treatment. 6.4.9.2 High dose rate HDR treatment will be delivered in the HDR treatment room with the applicators connected using the appropriate source tubes. Typical treatment time is of the order of 8–10 minutes depending upon the source activity.

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Brachytherapy for uterine tumours: cervix and endometrium 6.4.10 Applicator removal Removal is undertaken in the treatment room whether the LDR or MDR afterloading room, or the HDR treatment room. Following removal of any bandaging support and the gauze vaginal packing the applicators will generally be removed without difficulty without further anaesthesia although anxious patients may benefit from mild sedation or the use of inhaled nitric oxide. The bladder catheter should also be removed at this time. 6.4.11 Clinical results Stage IB: Radical radiotherapy utilizing brachytherapy as described above is highly effective with equivalent cure rates to those achieved with radical surgery and overall 5-year survival figures of 85%. More advanced stage disease will have a worse prognosis with 60–70% of patients with stage II carcinoma of the cervix surviving 5 years or more and only 30–40% of those with stage IIIB achieving this. Early results from using image-guided brachytherapy suggest a substantial improvement in these figures with local control rates of >90% even in advanced disease. It has been shown that patients receiving brachytherapy have a much better prognosis than those who do not and recent series of image-guided brachytherapy have reported no cases of pelvic relapse when a total dose of >87 Gy to the HR-CTV is achieved.

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Brachytherapy for uterine tumours: cervix and endometrium 6.4.12 Treatment complications Complications directly attributable to the brachytherapy relate to the very high dose delivered around the cervix, upper vagina, bladder base, and anterior rectal wall. These may be considered as follows: ◆ Vaginal side-effects are predominantly related to stenosis and shortening of the vagina, which can be prevented to some degree by the use of vaginal dilators. ◆ Rectal complications will also be compounded by the external beam dose delivered and includes rectal frequency and bleeding due to telangiectasia. Severe rectal problems should be seen in no more than 5% of patients but less troublesome grade I and II side-effects are seen in over 30%. ◆ Bladder side-effects will include frequency and haematuria from bladder telangiectasia. Occasionally, urethral structuring may also develop requiring dilatation. These will typically be seen in less than 5% of patients. ◆ Rectal complications develop sooner than bladder complications the mean time to onset for rectal complications being 2–3 years, with bladder problems developing on average a year or two later.

6.5 Intact uterus, carcinoma of the endometrium Endometrial cancer is undoubtedly best managed by primary hysterectomy when localized to the uterus. There will be instances, however, where patients are unfit for hysterectomy particularly as this is a tumour of the obese and related to diabetes and hypertension. In about 20% of patients there will be spread outside the uterus and these patients will also be treated with radical radiotherapy in preference to surgery. The indications for brachytherapy in endometrial carcinoma are therefore as follows: ◆ Localized tumour in the medically unfit. ◆ Inoperable advanced tumour extending beyond the uterus, usually in combination with external beam radiotherapy.

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Brachytherapy for uterine tumours: cervix and endometrium 6.5.1 Applicators In some cases the same applicators as those used for cervical cancer will be employed, either a central intrauterine tube alone or with two vaginal sources. However, it may be difficult when there is a bulky uterus to achieve good coverage from the single line source unless very high surface doses are used. There are therefore other types of applicator, which are designed to achieve better cover of the entire uterine cavity. Examples include the following: ◆ Heyman’s capsules, which were developed in Stockholm for the Stockholm system using caesium pellets. These comprise individual capsules, which are packed into the uterine cavity as shown in Fig. 6.11a. This enables a high activity to be concentrated within the endometrial cavity extending through the myometrium. ◆ Modern afterloading systems have PDR and HDR applicators equivalent to Heyman’s capsules as shown in Fig. 6.11b. ◆ The Rotte Y applicator, which uses two intrauterine line sources forming a ‘Y’ shape within the cavity, the tips ideally extending into the lateral extents of the fundus.

Heymann’s capsules shown (a) diagrammatically, (b) on CT after insertion and (c) with isodoses added.

The type of applicator will to some extent be determined by the individual situation that is being treated, a single line source being adequate for a small uterus and Heyman’s capsules or the Rotte Y applicator being preferred for a bulky uterus.

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Brachytherapy for uterine tumours: cervix and endometrium 6.5.2 Patient preparation This will be the same as for intrauterine insertions for cervical cancer. Specific considerations for those with endometrial cancer are as follows: ◆ Comorbid medical condition are much more common and attention to control of blood pressure and diabetes management is important. ◆ Perhaps as a consequence of the above thrombosis as a postoperative complication is a recognized feature, particularly where LDR or MDR systems are used requiring prolonged immobilization. Patient should therefore receive thrombosis prophylaxis with elasticated stockings and subcutaneous heparin. 6.5.3 Applicator insertion In general, this will follow the same steps as that for cervical cancer with the following modifications: ◆ The uterus is often enlarged but the cervix will be normal and therefore identification and dilation of the cervical canal is usually easier. ◆ Where a single source is to be used then the intrauterine tube is inserted as usual and a vaginal tube applicator placed over it to aid its fixation and separate the vaginal walls. Packing is not required with this type of applicator but suturing of the tube at the introitus to prevent displacement is recommended. Heyman’s capsules are inserted one by one into the cavity until it is packed, the number varies; on average between 9 and 12 capsules are used. It is important that the final capsule is placed in the cervical canal to keep it dilated and enable removal of the capsules at completion of treatment. 6.5.4 Dose prescription The same constraints with regard to dose rate apply to the treatment of uterine endometrial carcinoma. A three-dimensional image-guided approach should be used. The preferred method is to undertake MR scanning with the applicators in situ; however, where this is not possible then CT scanning is adequate. The CTV will include the entire width of the uterine wall and extend from the cervical os to the fundus. If staging investigations and biopsy have identified intermediate or high-risk features (>50% invasion of the wall or G3 histology) or stage II disease then the upper vagina should be included in the CTV. With afterloading, an individualized dose distribution can then be defined as shown in Fig. 6.12.

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Brachytherapy for uterine tumours: cervix and endometrium

Fig. 6.12 CT defined optimised dose distribution for endometrial cancer using single intrauterine tube; prescription isodose is 7Gy. The dose prescription will depend upon the combination with external beam treatment. For stage I disease in medically unfit patients then brachytherapy alone may be considered appropriate in which case the dose prescription should be: ◆ LDR/PDR: 75–80 Gy to point A or the defined tumour volume ◆ HDR: 36–42 Gy in six fractions to point A or the defined tumour volume (PTV). As in all circumstances, the final dose delivered should be within normal tissue constraints; these should be defined on dose volume histograms using the D2cc dose as for cervical cancer. Where external beam radiotherapy is delivered then the prescription will be the same as for cervical cancer; in other words 45–50 Gy delivered by external beam followed by brachytherapy to deliver a total dose of at least 80 Gy to the CTV. 6.5.5 Clinical results Results of treatment of early stage disease are broadly comparable with surgery, although large data sets have not been published. This reflects the fact that this treatment is only chosen for the medically unfit and, in general, the cause-specific survival is much better than overall survival, as most treated patients die as a result of a comorbid condition. Page 25 of 27

Brachytherapy for uterine tumours: cervix and endometrium For more advanced disease (i.e. stage III or IVA), then the outlook is for a 30–40% 5-year survival with stage III disease and 10% or less with stage IV. 6.5.6 Tumour complications These are essentially those described under ‘cancer of the cervix’. As mentioned above, these patients are medically unfit, often obese with comorbid hypertension and diabetes and therefore the risk of medical complications and, in particular, deep venous thrombosis is high.

References and further reading 1 ICRU Report 38 (1985). Dose and volume specification for reporting intracavitary therapy in gynecology. International Commission of Radiation Units and Measurements, Bethesda Maryland, USA. 2 Gerbaulet A, Potter R, Haie-Meder C (2002). Cervix cancer. In: Gerbaulet A, Potter R, Mazeron JJ, Meertens H, van Limbergen E (ed.). The GEC ESTRO handbook of brachytherapy. Brussels: ESTRO; 301–64. 3 Potter R, Gerbaulet A, Haie Meder C (2002). Endometrial cancer. In: Gerbaulet A, Potter R, Mazeron JJ, Meertens H, van Limbergen E (ed.). The GEC ESTRO handbook of brachytherapy. Brussels: ESTRO; 365–402. 4 Joslin CF (2001). High dose rate brachytherapy for treating cervix cancer. In: Joslin CA, Flynn A, Hall EJ (ed.). Principles and practice of brachytherapy: using afterloading systems. London: Arnold; 354–72. 5 Nag S, Erickson B, Thomadsen B, Orton C, Demanes JD, Petereit D for the American Brachytherapy Society (2000). The American Brachytherapy Society recommendations for high dose-rate brachytherapy for carcinoma of the cervix. International Journal of Radiation Oncology, Biology and Physics 48:201–11. 6 Nag S, Chao C, Erickson B, Fowler J, Gupta N, Martinez A, Thomadsen B for the American Brachytherapy Society (2002). The American Brachytherapy Society recommendations for high dose-rate brachytherapy for carcinoma of the cervix. International Journal of Radiation Oncology Biology and Physics 52:33–48. 7 Ladner HA, Pfleidereer A, Ladner S, Karck U (2001). Brachytherapy for treating endometrial cancer. In: Joslin CA, Flynn A, Hall EJ (ed.). Principles and practice of brachytherapy: using afterloading systems. London: Arnold; 333–42. 8 Nag S, Cardenes H, Chang S, Das IJ, Erickson B, Ibbott G et al. (2004). Proposed guidelines for image-based intracavitary brachytherapy for cervical carcinoma: Report from Image-Guided Brachytherapy Working

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Brachytherapy for uterine tumours: cervix and endometrium Group. International Journal of Radiation Oncology Biology Physics 60: 1160–72. 9 Haie-Meder C, Pötter R, Van Limbergen E, Briot E, De Brabandere M, Dimopoulos J, Dumas I, Hellebust TP, Kirisits C, Lang S, Muschitz S, Nevinson J, Nulens A, Petrow P, Wachter-Gerstner N; Gynaecological (GYN) GEC-ESTRO Working Group (2005). Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiotherapy and Oncology 74:235–45. 10 Pötter R, Haie-Meder C, Van Limbergen E, Barillot I, De Brabandere M, Dimopoulos J, Dumas I, Erickson B, Lang S, Nulens A, Petrow P, Rownd J, Kirisits C; GEC ESTRO Working Group (2006). Recommendations from gynaecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D imagebased anatomy, radiation physics, radiobiology. Radiotherapy and Oncology 78:67–77. 11 Pötter R, Dimopoulos J, Georg P, Lang S, Waldhäusl C, WachterGerstner N et al. (2007). Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer. Radiotherapy and Oncology 83:148–55. 12 Pötter R, Fidarova E, Kirisits C, Dimopoulos J (2008). Image-guided adaptive brachytherapy for cervix carcinoma. Clinical Oncology 20:426– 32. 13 Chargari C, Magné N, Dumas I, Messai T, Vicenzi L, Gillion N, Morice P, Haie-Meder C (2009). Physics contributions and clinical outcome with 3D-MRI-based pulsed-dose-rate intracavitary brachytherapy in cervical cancer patients. International Journal of Radiation Oncology Biology Physics 74:133–9. 14 The Royal College of Radiologists (2009).Implementing image-guided brachytherapy for cervix cancer in the UK. London: The Royal College of Radiologists.

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Prostate cancer: permanent low dose rate seed brachytherapy and temporary high dose rate afterloading brachytherapy

Radiotherapy in Practice - Brachytherapy (2 ed.) Edited by Peter Hoskin and Catherine Coyle Publisher: Oxford University Press Print Publication Date: Jan 2011 Print ISBN-13: 9780199600908 Published online: May 2013 DOI: 10.1093/med/ 9780199600908.001.0001

Prostate cancer: permanent low dose rate seed brachytherapy and temporary high dose rate afterloading brachytherapy   Chapter: Prostate cancer: permanent low dose rate seed brachytherapy and temporary high dose rate afterloading brachytherapy Author(s): P J Hoskin DOI: 10.1093/med/9780199600908.003.0069

7.1 Introduction The use of brachytherapy in prostate cancer has increased substantially over the past decades. It is indicated as radical treatment for localized disease. Prostate cancer is classified into low-, intermediateand high-risk disease based on the presenting prostate specific antigen (PSA), Gleason score, and stage, as shown in Table 7.1. Table 7.1 Risk groups for prostate cancer

Low

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PSA (ng ml–1)

Gleason

T Stage