Brachytherapy: Applications and Technique, 1st Edition

8. Prostate Brachytherapy

 

Caroline L. Holloway

I-Chow Joe Hsu

Michele Albert

André-Guy Martin

W. Warren Suh

In the United States, prostate cancer is the most common (excluding nonmelanoma skin tumors) malignancy and the second cause of cancer-specific death in men.1 With the advent of prostate-specific antigen (PSA) screening in the late 1980s, most men being diagnosed with prostate cancer today have early stage disease.1,2 The optimal treatment strategy for these men remains, however, undefined and their treatment options can include radical prostatectomy (RP), brachytherapy, or external beam radiotherapy (EBRT).

For brachytherapy, 5- to 10-year published data support the excellent treatment outcomes that are comparable to those of RP or EBRT (see Table 8.1).3,4,5,6,7,8 Its rising popularity is becoming evident as it is increasingly being selected by patients as their treatment modality.9 Some of its advantages can include a more rapid postoperative recovery time when compared with RP and a shortened overall treatment time when compared with EBRT.

Relatively recent important advances in imaging and procedural technologies have also enabled prostate brachytherapy to evolve further into a minimally invasive, state-of-the-art, computerized planning software–aided treatment approach. Since its inception as a freehanded open laparotomy procedure in the 1960s at Memorial Sloan-Kettering, permanent interstitial prostate brachytherapy has benefited from the development of transrectal ultrasonography guidance approach, template-guided closed transperineal technique, and sophisticated commercialized planning software technology for computed tomography (CT)-based postoperative dosimetry.

As these technologic advances become more refined, prostate brachytherapy procedure continues to adapt and evolve, with the goal of maximizing the therapeutic ratio. Several variations of the basic “Seattle” technique are now utilized by prostate brachytherapists in the field. This chapter reviews the basic modern technique as well as innovations in imaging, seed loading, real-time planning, and high dose rate (HDR) afterloading brachytherapy.

Ultrasound-Guided Permanent Seed Implantation of the Prostate

Very low dose rate (VLDR) transrectal ultrasound (TRUS)-guided transperineal prostate brachytherapy has been used as both monotherapy as well as in conjunction with EBRT for prostate cancer treatment. The treatment-planning principles, implantation techniques, and side effects associated with VLDR prostate brachytherapy are reviewed.

 

Table 8.1 Data Supporting the Treatment Outcomes

Author

N

PSA Control %

Reported f/u (y)

Median f/u (mo)

Grimm

97

87

10

81.4

Merrick

160

97

5

31

Blasko

103

94

5

48.9

Kollmeier

75

88

8

75

D'Amico

196

95

5

47

Zelefsky

145

82

5

24

PSA, prostate-specific antigen; f/u, follow up.

Preplan

Patient selection for VLDR radioactive seed therapy for prostate cancer is based on patient factors and tumor factors (see Table 8.2). If a patient is found to be eligible for prostate brachytherapy, the next step is to determine whether the procedure is technically feasible.

Volume Study

An ultrasound-guided prostate volume study can assess the size of the gland and the relation of the gland to the pubic arch, determine the target volume, and track the course of the urethra through the prostate. For the volume study, the patient is asked to have a full bladder and placed in lithotomy (treatment) position. The rectal ultrasound mount is secured to the examination table or the floor and the rectal ultrasound transducer is secured onto the stepper (see Fig. 8.1). The angle of the mount and transducer are recorded. A cover is secured over the transducer and the apparatus is then lubricated with ultrasound jelly and gently inserted into the rectum. The best visualization of the prostate comes when there is no air interface between the ultrasound transducer and the rectal wall. Once the ultrasound transducer is in position, the bladder, prostate, and seminal vesicles can be identified. The technique developed at the Seattle Prostate Institute10 establishes the base of the prostate first, which can be found at the proximal end of the prostate interfaced with the bladder. This interface can be best confirmed on a sagittal view (see Fig. 8.2). Once the base is identified, the prostate is contoured in 5-mm increments up to the apex. The physician can then define a margin around the prostate for a target. The base and the apex are the most likely locations to be underdosed; therefore, the margin to these areas can be exaggerated. Once the prostate gland has been defined, the number of contours should be compared with the length of the prostate measured on the sagittal views and the volume of the gland recorded. To determine pubic arch interference, a tracing of the pubic arch (see Fig. 8.3) is superimposed over each defined slice of target volume. If there is no pubic arch interference and the prostate volume is within the defined limits, the contours and images can be transferred to a treatment-planning system for prostate brachytherapy. If the prostate gland is large or there is arch interference secondary to gland size, neoadjuvant androgen suppression can be used to shrink the gland. The gland volume may decrease by as much as one third with 4 months of hormonal treatment (HT).11 However, the risk of urinary symptoms that are associated with a large gland do not decrease when the gland size is decreased with androgens.12

Table 8.2 Selection Criteria for Prostate Brachytherapy

Tumor Criteria

Patient Criteria

Monotherapy

Able to undergo general or spinal anesthesia

T1–T2a, Gleason <7, PSA <10 ng/mL

Prostate <60 cc

Boost

IPSS <15

T2b or Gleason >7 or PSA >20 ng/mL

No previous history of TURP

PSA, prostate-specific antigen; IPSS, international prostate symptom score; TURP, transurethral resection of prostate.
ABS Recommendations: Nag S. Brachytherapy for prostate cancer: Summary of American Brachytherapy Society recommendations. Semin Urol Oncol. 2000;18(2):133–136.

Figure 8.1 Sagittal illustration of a prostate volume study demonstrating the relation of the rectum, bladder, and urethra to the prostate. The patient is in lithotomy position with a transrectal ultrasound probe attached to a stepping unit and mount.

 

Figure 8.2 Sagittal transrectal ultrasound image of the prostate and bladder interface (dotted line). Used with permission of the Seattle Prostate Institute.

 

Figure 8.3 Axial ultrasound image of prostate with pubic arch diagram. Used with permission of the Seattle Prostate Institute.

Seed Selection

Isotope

Iodine 125 (125I) and palladium 103 (103Pd) are the most commonly used isotopes in VLDR brachytherapy for prostate cancer. It is felt that 125I is more forgiving in terms of achieving the desired final dosimetry and is therefore used with more frequency at most centers. The dosimetric properties of these two isotopes are compared in Table 8.3. It has been suggested that 103Pd is more effective against dedifferentiated tumors than 125I.13 This assertion, however, has not been upheld in studies evaluating the clinical outcomes for patients with prostate cancer treated with either 103Pd or 125I.14,15,16 The time to reach PSA threshold is different for the two isotopes as would be anticipated; however, the percentage of delivered dose relative to the time to reach the threshold is the same.14 Studies exploring the potential differences in the morbidity outcomes between 125I and 103Pd have shown that patients treated with 103Pd have more intense radiation proctitis in the first month after implantation, but recover from the radiation symptoms faster. The 125I patients had longer-term proctitis complaints.17

Loose Versus Stranded Seeds

Commercially, 125I and 103Pd seeds are available as either loose seeds or stranded seeds (see Fig. 8.4). Dosimetrically, the two are similar. It has been reported that stranded 125I seeds have higher mean D9018 as well as V100 and V15019 in association with higher urethral dosimetry on the day of implant. McLaughlin et al. reported the day 0 and day 14 dosimetry for stranded seeds in 28 patients and noted an z-axis shift of stranded seeds versus the prostate, which impacted final dosimetry and dose to organs at risk (OAR); they recommend that stranded seeds be avoided in the region of the apex for this reason.20 Other groups also recommend that placement of stranded seeds near the urethra be avoided. The incidence of seed migration is decreased with stranded seeds as compared with that with loose seeds (RR of 3.08 vs. 6.97), with the greatest difference being in migration to the lung and perineum.19

Table 8.3 125I and 103Pd Properties

 

125I

103Pd

Half-life (d)

59.4

17

Energy (kV)

28

21

Radiobiologic equivalence

1.4

1.9

Figure 8.4 125Ir loose seeds with spacers and stranded seeds (Rapidstrand). Used with permission of the Seattle Prostate Institute.

Activity

The average activity of 125I seed used in prostate cancer is 0.41 mCi (range 0.16 to 1 mCi) and 1.32 mCi (range 0.50 to 1.90 mCi) for 103Pd.21 Historically, the Seattle group used low activity 125I seeds (0.35 mCi) to improve dose homogeneity within the prostate as well as decrease the dose to the rectum and urethra.22,23 A dose study performed by D'Souza et al. compared dose homogeneity between different seed strengths (0.35, 0.44, and 0.66 mCi). They found the 0.44 mCi activity seed to have the best dose distribution.24 With the use of higher-activity seeds, fewer seeds are required to cover the target volume, especially in peripheral loading techniques, but the placement of each seed becomes more important so as to increase toxicity to normal structures or to underdose the target.25 Figure 8.5 shows a case with a significant local movement from the intended position at implantation. Seed activity effects dose to OAR and target coverage. The overall number of seeds has a direct impact on the number of needles used during the procedure. Eapen et al.26 have reported that needle trauma to the prostate contributes to acute urinary toxicity.

Figure 8.5 Anteroposterior (AP) fluoroscopic image of a loose seed implant from Centre Hospitalier Universitaire de Quebec (HUQ) demonstrating significant shifting of seeds in the prostate especially on the patient's left side (right of the image).

 

Figure 8.6 Typical ultrasound preplan schematic with prostate and organs contoured. Planned isodose distribution is shown. Used with permission of the Seattle Prostate Institute.

Treatment Planning

Prescription Dose

The American Brachytherapy Society (ABS) recommends a prescription dose of 145 Gy and 125 Gy for 125I and 103Pd, respectively, in monotherapy brachytherapy and 110 Gy of 125I and 100 Gy of 103Pd if used as a boost following pelvic EBRT of 40 to 50 Gy.27 Typically, these doses are prescribed to the minimum peripheral dose (MPD) (see Fig. 8.6). The MPD is considered to be the maximum dose that covers 100% of the target volume. This dose is dependent on the position of the seeds within the prostate and the dose may vary by up to 25%. Despite this, usually 90% of the target volume will receive the prescription dose (see Fig. 8.7).28 The mean peripheral dose is the average of the dose at the surface of the target volume and varies less with seed position. Some centers will therefore prescribe to the mean peripheral dose.

Loading Techniques

Many variants of loading techniques exist in treatment planning for transperineal implantation of the prostate. The most basic technique, uniform loading (see Fig. 8.8), uses low energy seeds placed at fixed distances from each other throughout the prostate. This technique, however, gives a high dose to the length of the prostatic urethra. To spare the urethra while maintaining coverage to the target, degrees of peripheral loading were developed including modified uniform loading, nonuniform loading, and peripheral loading. In modified uniform loading, two thirds of the planned seeds occupy the posterior border of the prostate and the base. Nonuniform loading avoids loading seeds in the central aspect of needles inserted close to the prostate and peripheral loading (see Fig. 8.9) uses higher-activity seeds with the posterior implant plane 5-mm anterior to the posterior border of the prostate.29

Figure 8.7 Minimum peripheral dose schematic showing D90. Contributed by Anthony L. Zietman, MD.

Dosimetric Constraints

Target

Postplan

Posttreatment planning is used to confirm the dose delivered to the prostate as well as evaluate the dosimetry to the OAR. Postplan dosimetry can be performed immediately after the procedure, 1 day postoperatively, or up to 1 month from the date of implant. Most wait for 4 weeks to allow for maximal resolution of inflammation and edema associated with the implant. However, it can be done earlier, with the realization that the potentially underdosed implant dosimetry at this point in time is likely to be improved at a later date. Typically, the postplan dosimetry is done using CT scan data. An ultrasound cannot be used because the artifact from the seeds causes image degradation. Magnetic resonance imaging (MRI) can be used to visualize the prostatic tissue better. However, it will have large voids (see Fig. 8.10) demonstrating the seeds, and the dosimetry is technically difficult as it is not known where the seeds are within these voids. CT scans allow visualization of the permanent seeds; however, the target volume is difficult to define. Catheterization at the time of CT allows a better visualization of the urethra.

Figure 8.8 Uniform loading of 40 × 50 × 40 mm I125 implant. Contributed by Mark Phillips, PhD.

Figure 8.9 Peripheral loading of 40 × 50 × 40 mm I125 implant. Contributed by Mark Phillips, PhD.

 

Figure 8.10 Magnetic resonance imaging coronal cut from MRT technique. Real-time verification of the needle position is obtained. I125 seeds can be visualized between the needles.

At the time of follow-up, a chest x-ray (CXR) is routinely acquired to look for migrated seeds, and it is confirmed from the patients whether they noted any seeds being passed in the urine. The CT images are then imported into a treatment-planning system, where the prostate is contoured and the seeds are identified.

Dosimetric data depends on the contours drawn to represent the postimplant prostate and OAR. To evaluate coverage of the target, the dose to 90% of prostate (D90) is calculated (see Fig. 8.11). Implants with a D90 >90% of the prescribed dose or 140 Gy30 have been shown to have better PSA relapse free outcomes.31 Interobserver variation in contouring the prostate based on CT images varies greatly; therefore, it is important to have a standard methodology for contouring the prostate. Image fusion between CT scan and MRI used to evaluate the prostate can also be applied for dosimetry32 and evaluation of prostatic swelling.33 The ABS recommends the reporting of target D90, D80, D100, V80, V90, V100, V150, and V200, as well as rectal and urethral doses.27

Organs at Risk

The rectum, urethra, penile bulb, and neurovascular bundles are the normal structures in close proximity to the prostate and are within the high-dose region of the prostate implant.

Dosimetry to the OAR needs to be reported to better understand dose and volume constraints and their relation to acute and long-term toxicity. Crook et al. highlight the importance of standard dosimetry reporting of the OAR so that data from different centers can be combined to establish dosimetric guidelines for the OAR. They recommend that rectal wall contours be performed on all CT scan slices where seeds can be visualized and the V100 and V150 be reported. The whole urethral volume should be contoured rather than points or a representative volume; the urethral V150, D5, and D30 should be recorded. Contouring of the penile bulb and neurovascular bundles as well as evaluation of dose to these structures requires further study.34

Figure 8.11 Typical computed tomography scan postplan schematic with prostate and organs contoured with actual isodose lines. Used with permission of the Seattle Prostate Institute.

Procedure

Under spinal or general anesthetic, the patient is positioned supine in the same lithotomy position as at the time of the volume study to ensure the same couch angle and ultrasound probe angle. A Foley catheter or a gel/water mixture–filled rubber catheter is then placed. The applicator template is secured to the TRUS apparatus. Figure 8.12 diagrams the classical manually loaded technique. The image plane is confirmed by scaling through the length of the prostate with the ultrasound stepper to ensure that the images correspond with those taken at the time of the volume study. The reference plane 0.0 (base of the prostate) is located.10 The physician is guided by a preprinted legend of the needle location, plane, and number of seeds per needle. Preloaded needles are kept within a shielded vault (see Fig. 8.13) until the physician is ready to insert the individual needle. Each hollow bore needle has a sharp beveled edge and a central stylet (see Fig. 8.14). When the needles are preloaded, the seeds sit within the hollow needle with a plug at the tip preventing them from dislodging. The central stylet sits posterior to the seeds and can be secured in position with a gasket. When removing the needles from the vault, it is important to hold the needle horizontally with the bevel up to avoid dislodging the seeds. Following the preplan legend, the needle is inserted into the correct template location and gentle pressure will advance the needle through the perineal skin and into the prostate. The ultrasound images in both the axial and sagittal views will guide the placement of the needle. Rotation of the needle, if it is in the correct plane of view, will show the beveled edge, sometimes known as the hamburger sign (see Fig. 8.15). To “drop” the seeds within the prostate, the central stylet is held securely in place and the outer needle is slowly pulled back along the stylet. If the stylet is advanced into the needle, it will push the seeds out of the needle and clump them within the prostate. Figure 8.16 is an example of excellent linear alignment and spacing of seeds.

Figure 8.12 Sagittal schematic image depicting the operator's hand, probe, template, needles, and seeds within the prostate.

Figure 8.13 This shielded aluminum needle holder is used in the operating room to hold numbered needles between loading and delivery of seeds. The grid numbering is the same as the perineal template. The unit may be sterilized rapidly.

Some centers recommend stabilizing needles to minimize prostate motion during the implant35,36 but this technique has not widely been adapted. The Seattle group has published on a two-stage needle system to minimize prostate movement, improve needle loading, and decrease surgical time. This technique involves the insertion of sleeves to the base of the prostate, allowing needles with spacers equivalent to the retraction plane at the tip end to be inserted after confirmation of sleeve placement has been made.37

A plain film is routinely taken upon completion of the implant to evaluate symmetry and compare seed placement to the preplan. Seeds that have migrated to the perineum will also be visible. Bladder irrigation and cystoscopy can be performed to evacuate migrated seeds to the bladder as well as eliminate potential blood clots in the bladder.

Following the procedure, the urethral catheter is removed and the patient remains in the recovery area until he is able to urinate. Patients are counseled on seed migration and radiation safety. Recommendations regarding straining while urinating and condom use during intercourse are reviewed. Discharge medications include an α-blocker and a short-course antibiotic.

Toxicity

Toxicity with VLDR prostate brachytherapy is variable with each patient and can be greatly affected by the patient's comorbidities and risk factors. The recently published Radiation Therapy Oncology Group (RTOG) 98-05 found high quality of life for men after prostate brachytherapy with a follow-up of 1 year.

Figure 8.14 Prostate implant needle with central stylet.

 

Figure 8.15 Axial view of ultrasound showing the beveled edge of a prostate needle. Used with permission of the Seattle Prostate Institute.

 

Acute

Urinary

Urinary retention is a multifactorial problem. Before brachytherapy, many patients have urinary dysfunction secondary to benign prostatic hypertrophy (BPH), preexisting prostatism, and small vessel disease. In a review by Stone et al. the rate of acute urinary retention (AUR) following prostate brachytherapy was found to be between 1.5% and 22%.38 The International Prostate Symptom Score (IPSS) pretreatment prostatic volume, urinary flow studies, and the number of needles inserted have all been found to be associated with AUR.26,39,40 Urinary incontinence is more prevalent in men who have had previous TURP. It is also felt that the preimplant IPSS as well as the D10 are related to the degree of incontinence.41

Figure 8.16 Anteroposterior (AP) x-ray of a male pelvis showing a prostate implant with linear deposition of radioactive seeds. Used with permission of the Seattle Prostate Institute.

Rectal

In the acute setting, symptoms can include urgency, diarrhea, proctitis, and/or irritation of hemorrhoids. The onset of the symptoms is related to the isotope used in the treatment.17 A survey of patients conducted by Merrick et al. found <20% of patients to have worse bowel function following the implant but there were no severe changes in late bowel function.42 The rectal V25 has been associated with worse late diarrhea and V10 >40% of prescribed dose has been implicated in long-term toxicity.43

Impotence

The incidence of impotence in long-term follow-up of prostate brachytherapy ranges from 15% to 51%.44 Factors that have been related to impotency include pretreatment potency, microvascular damage, radiation dose to the penile bulb and neurovascular structures, diabetes, and age. Studies by Merrick have studied the dose to the neurovascular structures and penile bulb.45,46 They found no difference in the dose to the neurovascular structures in patients who were impotent compared with those who were potent. The dose to the penile bulb, however, along with pretreatment potency, was related to erectile dysfunction on multivariate analysis.46 Further research with MRI to identify the penile bulb and neurovascular structures as well as comprehensive erectile dysfunction questionnaires will help in identifying patients with erectile dysfunction and show the radiation dose in relation to the periprostatic tissues better.

Radiation Safety

For the families of patients with permanent radioactive seed implants, many questions are raised regarding radiation safety. Studies looking at the measured radiation dose rate at the patient's surface and at 1 m from the patient's surface have determined that these patients do not represent a risk to the general public or to their families.47,48 To follow general ALARA (as low as reasonably achievable) principles, patients should, however, be given written documentation regarding radiation safety and precautions that can be taken when they are in the presence of small children and pregnant women.

Intraoperative Planning

Preoperative planning, as described, involves acquiring images of the prostate in an outpatient setting. The volume study typically occurs between 1 and 2 weeks before the scheduled procedure. Beaulieu et al.49 reported on 35 cases where prostate contours were created in a preplan setting as well as in the operating room (OR). The shape and volume of the prostate were compared for each patient. It was found that in 63% of patients the volume of the prostate drawn had changed between that of the preplan and that taken in the OR. These changes in volume and shape resulted in a mean dose coverage loss of 5.7% and, in extreme cases, the V100 coverage loss was 20.9%. Intraoperative planning would therefore avoid these changes in dosimetric coverage. Further evolution of intraoperative planning involves dynamic or real-time planning where the treatment plan is modified on the basis of the location of the needles and seeds within the prostate gland. There are several commercially available products that allow real-time planning with ultrasound using the location of the needle as well as newer techniques that look to identify the location of individual seeds by combining ultrasound with fluoroscope.50,51 Real-time planning has also been described using an automated seed afterloader and an inverse planning algorithm, as well as for MRI-guided implants.

 

Figure 8.17 A preimplantation ultrasound session determines the volume of the prostate so as to customize the seed order and alert the physician to potential arch interference, and so on. A formal preplan may be created if desired. Positioning reproducibility between preplan imaging and in operating room imaging is difficult to achieve.

Figure 8.18 At the beginning of the implant procedure, optimal ultrasound images are obtained. The patient is under general anesthesia and prepped and draped in the dorsal lithotomy position. A soft catheter is inserted into the rectum to remove any flatus that may interfere with the images.

 

Real-Time Planning, Automated Seed Loading, and Implantation: The Centre Hospitalier Universitaire de Quebec Methodology

Whereas computer-driven high dose rate (HDR) afterloader technology is established as a reliable and safe mechanism for the delivery of brachytherapy, all systems of ultrasound-guided prostate implantation have relied on manual delivery of seeds by the implanting physician. Spurred on by some significant uncertainties in the ability to control the final resting place of prostate seeds, a collaborative clinical research enterprise between a corporation and a university hospital has produced the first automated prostate seed loading system. The Centre Hospitalier Universitaire de Quebec (CHUQ) Department of Radiation Oncology has collaborated with Nucletron Corp (Veenendal, NL) to develop a new system. The system combines inverse planning software that will be described in the HDR prostate section “UCSF Technique and Outcomes”, and an automated seed afterloading mechanism. This mechanism is computer driven by the treatment-planning program and features radioactivity sensors and seed counters so as to assure the number of seeds delivered. The seeds are housed in a shielded cartridge. A second cartridge dispenses inert spacers. The seed afterloader can be mounted on the same stand as the ultrasound probe. The system can also preload seeds away from the patient for manual delivery by the physician if desired. The early impression shows that it has better ability to determine the final location of the seeds. The robotic seed delivery may take away interuser variability. The system allows for very rapid intraoperative iterative real-time planning and delivery using an inverse planning segmented annealing algorithm. Figures 8.17, 8.18, 8.19, 8.20, 8.21, 8.22, 8.23, 8.24, 8.25, 8.26, 8.27 and 8.28 demonstrate the major points of this system and technique.

Real-Time Planning with Magnetic Resonance Imaging–Guided Prostate Brachytherapy—The Brigham and Women's Hospital Methodology

MRI-guided prostate brachytherapy was first described in the late 1990s.52 This approach combines both real-time MRI and real-time dose–volume histogram (DVH) analysis. The use of MRI permits the visualization of the different prostate regions: Peripheral zone (PZ), transition zone (TZ), anterior, and the periurethral zone (see Fig. 8.29).

Several investigators have reported that the presence of cancer in the anterior gland is rare in a subset of patients with highly favorable pretreatment clinical characteristics.53,54 With strict patient selection, this method can permit selective partial prostate gland PZ implantation.

Figure 8.19 The contouring is performed by the physician and the dosimetrist (foreground of picture, sitting at computer). The dosimetrist rapidly generates a plan based on the new images.

 

Figure 8.20 A very conformal plan is generated on the basis of the prostate contour and dose constraints for the organs at risk (urethra and rectum).

Figure 8.21 The seed afterloader can receive loading instructions directly from the treatment-planning computer. In this instance the physician has chosen to load to seeds into the needles for manual loading in the patient. Seeds and spacers are loaded within the needle according to the plan in the operating room. Each needle will be manually unloaded under direct ultrasound observation in the patient.

 

Figure 8.22 The seed afterloader is sequentially attached to numbered needles.

PZ-only loading could result in improved quality of life by decreasing acute urinary morbidity or long-term side effects such as erectile dysfunction and proctitis. Besides, PZ loading allows one to implant prostate glands with a volume of >60 cm3. If there is pubic arch interference, the real-time MRI is used to guide the angle of the needles to avoid the pubic arch and still attain the desired clinical target volume (CTV) coverage.

Patient Selection

The patient selection criteria at Brigham and Women's Hospital (BWH) since the inception of the program in 1997 include serum PSA levels <10 ng per mL; Gleason score of 3 + 4 or less; stage T1c disease according to the 2002 American Joint Committee on Cancer (AJCC) staging system; endorectal coil MRI stage T2 disease; and after June 1999, <50% of core positive biopsies and negative perineural invasion on biopsy. Patients with prior history of a TURP are excluded. No patient receives neoadjuvant or adjuvant androgen suppression therapy. The MRI operating environment precludes 12 lead electrokardiogram (EKG) monitoring, and, therefore, patients are assessed by a cardiologist before the procedure.

Figure 8.23 For preloading the needles, each needle is placed in a steel shield to minimize exposure to the operating room personnel. Each needle is customized to fit the treatment plan. When loaded, it can either be stored in the shielded needle holder (Fig. 8.13) or can be passed directly to the physician for manual insertion.

Figure 8.24 In this case, the needles are placed in the prostate under ultrasound guidance and the seed afterloader is attached directly to each needle sequentially. The needle identity is confirmed and the afterloader delivers the seeds and spacers under direct ultrasound visualization.

 

Figure 8.25 The seed afterloader is connected directly to the implanted needles. Each needle delivery is observed for accuracy by the physician, with ultrasound-updated images. For substantial variance from the projected path, the needle may be withdrawn and repositioned. If the actual seed placement is significantly different, then a new iteration of the plan is quickly performed and the case proceeds.

Figure 8.26 Centre Hospitalier Universitaire de Quebec cases with excellent seed positioning based on automated afterloading of seeds. Compare these with Figure 8.6.

Technique

The procedure is performed in an OR environment with a 56-cm open-bore 0.5-T MRI unit (General Electric Medical Systems, Milwaukee, WI). This interventional magnet is composed of two shorter cylindrical magnets (“donuts”) with imaging coils enclosed. In comparison, a conventional MRI unit has longer coils and a closed bore (see Fig. 8.30).

Under general anesthesia, the patient is placed in lithotomy position. A Foley catheter is inserted and clamped. An MRI-compatible template is secured to the table and placed in close proximity to the patient's perineum. A 3-cm diameter rectal obturator with a central tube, to allow the passage of intrarectal gas, is inserted and secured to the template. Axial, sagittal, and coronal images using 5-mm slices are captured. The PZ as well as the anterior rectal wall and the prostatic urethra are contoured on the axial images. The PZ is selected as the CTV. Real-time dosimetry is performed using a dose algorithm,55 and MRI-compatible catheters are then loaded with 125I seeds as per the dosimetry plan. The guiding MRI radiologist reviews axial, coronal, and sagittal real-time images that may be frequently repeated following insertion of the catheters to compare the position of the catheters with the optimized plan, before the delivery of the seeds (see Figs. 8.31 and 8.32). Catheter repositioning is performed as needed. After the seeds are delivered, new images are made. The DVH are updated and any divergence from the original plan noted. At the end of implant, the real-time DVH is reviewed for cold spots, and if this is the case the plan is adjusted and catheters are added. Patients undergo both CT and endorectal coil MRI 6 weeks' postimplant and dosimetry is performed from the fused images for the final dosimetry report.

Figure 8.27 Centre Hospitalier Universitaire de Quebec cases with excellent seed positioning based on automated afterloading of seeds. Compare these with Figure 8.6.

Figure 8.28 At the beginning and at the end of the case, the seed cartridge is filmed for a seed count. This image shows 14 remaining seeds in the 6 o'clock to 8 o'clock position.

 

Figure 8.29 Magnetic resonance imaging axial cut of the prostate image. The crescent shape of the peripheral zone is well visualized.

Figure 8.30 For pelvic procedures, the MRT technique places the patient between “donut” coil magnets so that the target area is within the range of view. This small area may be imaged quickly and easily. Above the operator's head is a small liquid crystal display screen with the latest catheter location image. A microphone and speaker system allows direct communication between the operator and the guiding radiologist at the control panel. All instruments are specially adapted for the magnetic environment. Lithotomy stirrups adapted for the magnetic environment support the legs.

Outcome

The 5-year estimate of PSA control was reported by D'Amico et al.7 This study compared the PSA outcome after RP with MRI-guided partial prostate brachytherapy. This 5-year estimate of PSA control was 93% compared with 95% for RP and brachytherapy (plog-rank = 0.16).

Urinary Function

AUR was found to be volume dependent and self-limited despite some large prostate volumes (range 16 to 184 cm3) as reported by Landis et al.56 In this study, the first 248 patients treated at BWH with urethral-sparing MRI-guided prostate brachytherapy were evaluated. Of the 248 patients, 18 (7%) developed AUR within 48 hours of removing the Foley catheter. The correlation with the prostate volumes was as follows: patients with prostatic volume <45 cm3, only 2%; volumes between 45 and 60 cm3, 6%; 60 and 90 cm3, 28%; and volume >90 cm3, 40%. By 6 weeks following AUR, no patient required catheterization.

Rectal Toxicity

The 4-year estimate of grade 3 rectal toxicity following MRI-guided prostate brachytherapy with or without neoadjuvant EBRT was 30% versus 8% (plog-rank = 0.0001).57 Control was achieved in all patients who presented with grade 3 rectal bleeding by using cortisone enemas or argon plasma coagulation (APC).58,59 A subset of 91 patients who underwent brachy-monotherapy were evaluated to define a rectal dose constraint that could predict late rectal bleeding.60 It was found that if the rectal volume receiving >100 Gy is kept below 8 cc, none of the patients required APC for rectal bleeding compared with the figure of 20% if >8 cc of rectum receives 100 Gy (plog-rank = 0.004).

Figure 8.31 Magnetic resonance imaging coronal image taken in real time during the procedure. One needle is visualized to the right of the prostate. The location of the needle is checked against the plan and readjusted before seeds are delivered.

Figure 8.32 Magnetic resonance imaging coronal image later in the same case where the previous needle remains and the left needle is placed. Note that the ideal projected path is superimposed in red over the actual placement. Image voids between the catheters represent seeds that were previously delivered.

 

Erectile Dysfunction

Erectile dysfunction following MRI-guided prostate brachytherapy was evaluated by Albert et al.57 Baseline function was recorded. At each follow-up, the patients were asked about their erectile function, specifically if they were able to have vaginal intercourse and if they were taking medications for erectile function. It is of note that no standardized questionnaire was used.61 It was found that, by 4 years, 82% to 93% of the patients experienced some degree of erectile dysfunction as compared with their baseline level. In patients using erectile function aids such as sildenafil citrate (Viagra; Pfizer, Groton, CT), two thirds reported being able to have erectile function comparable or even superior to their baseline.

High Dose Rate Brachytherapy

Dose escalation in prostate cancer has been associated with improved biological outcomes.62,63 Dose escalation, however, is limited by the proximity of the OAR to the prostate. HDR prostate brachytherapy is one of the techniques used to deliver conformal radiation to the prostate while sparing the OAR. It has advantages over other techniques because real-time dosimetry is obtained after catheter placement, varying the dwell positions and times can optimize the dose distribution, and normal structures can be retracted from the field at the time of radiation. Martinez et al.64 reported a prospective dose escalation trial with conformal HDR prostate brachytherapy and EBRT for patients with PSA ≥10 ng per mL, Gleason score ≥7 or clinical stage T2b or higher. A dose of 46 Gy to the pelvis with EBRT was combined with dose escalation HDR brachytherapy (5.5 to 11.5 Gy per fraction). On analysis, patients receiving a biologic effective dose of <93 Gy were compared with those receiving a biologically effective dose of >93 Gy. The 5-year biochemical control rate for the low-dose and high-dose groups were 52% and 87%, respectively (p <0.001). The RTOG grade 3 gastrointestinal and genitourinary complications ranged from 0.5% to 9%.

HDR radiation also takes advantage of the radiobiologic differences between the prostate carcinoma and the surrounding OAR. The α/β ratio for prostate carcinoma has been estimated to be 1.5 Gy. In contrast, most tumors and acute reacting tissues have an α/β ratio of 10 Gy and the dose limiting structures surrounding the prostate have α/β ratios of 3 Gy for late effects. Tissues or tumors with low α/ β ratios are more sensitive to hypofractionated radiation and therefore HDR prostate brachytherapy may have a therapeutic advantage compared with dose escalation techniques that use conventional fractionation or VLDR.65

HDR brachytherapy as monotherapy for low risk prostate cancer has also been described66 and may be associated with decreased urinary and erectile dysfunction compared with VLDR brachytherapy.

HDR prostate brachytherapy has been shown to be feasible; however, multi-institutional studies such as the current RTOG 0321, investigating HDR brachytherapy in combination with EBRT for patients with intermediate and high-risk prostate cancer, are needed to determine the long-term role, morbidity, and efficacy of this technique. The eligibility criteria for this study are reviewed in Table 8.4.

There are many centers performing HDR prostate implantations as either boost or sole therapy for intermediate or early stage prostate cancers.66,67,68,69,70,71Each center has developed a unique technique for this modality using either a template or a freehand placement technique. Nonetheless, each is but a modification of the basic “Seattle” model because all are transperineal image-guided interstitial implantations. The following section describes an HDR prostate brachytherapy technique developed at University of California, San Francisco (UCSF) that is a hybrid of template and freehand styles. It also makes use of an advanced treatment-planning algorithm with inverse planning simulated annealing (IPSA).

UCSF Technique and Outcomes

Preoperative Evaluation

All patients have a preoperative consultation with the radiation oncologist, the urologist, and the anesthesiologist. The known tumor locations in the prostate are reviewed, with extra attention given during procedure to ensure these locations are adequately covered. This extra attention in the pretreatment phase minimizes the need to adjust the catheters after the implant.

Table 8.4 Eligibility and Exclusion Criteria for Radiation Therapy Oncology Group 0321

Eligibility

Exclusion

Clinical T1c–T3b, N0, M0

No nodes, no local organ invasion, no metastases

Zubrod 0–1

Zubrod >1

No prior pelvic RT

Prior pelvic RT

HT <120 d

HT >120 d

No prostate radical surgery

Prior prostate radical surgery

Physically and mentally capable

Major medical or psychiatric illness

No TURP defect

TURP defect

Clinical Combinations of Risk Factor Groups for Protocol

T1c–T2c, Gleason 2–6, PSA >10 but <20

or

T3a–T3b, Gleason 2–6, PSA <20

or

T1c–T3b, Gleason 7–10, PSA <20

RT, radiation therapy; HT, hormonal therapy; TURP, transurethral resection of prostate; PSA, prostate-specific antigen.

Implant Procedure

Anesthesia

The procedure is most often performed with either epidural anesthesia or spinal anesthesia. Epidural anesthesia is preferred at UCSF as it can be titrated for postoperative pain control. Spinal anesthesia with long-lasting morphine (Duramorph) also works well for patients with single 23-hour overnight hospital stay. In patients who need general anesthesia, postoperative pain is controlled with patient control analgesic (PCA).

Preparation of the Catheter Entry Site

After giving the induction anesthesia, the patient is placed in the low dorsal lithotomy position using Allen's stirrups. The perineum is shaved and the posterior edge of the pubic symphysis is palpated and marked on the skin. The distance between the mark and the anus represents the space available for inserting the catheters. If the patient has a very short perineum, the catheter entry points must be closer. Typically 16 catheters are used for the implants. Four columns of four entrance points are marked on the perineum (see Fig. 8.33). The entrance points are separated into groups on either side of the median raphe. The midline space was created to minimize any chance of piercing the bulb of the penis and the urethra during the implant. After one becomes familiar with entry point selection, the perineum is not routinely marked.

The number of catheters used to cover the prostate, as reported by various authors, is between 6 and 22.72,73 Using too few catheters will lead to a less conformal dose distribution and increase dose heterogeneity. The use of too many catheters may cause unnecessary trauma for the patient. Charra-Brunaud et al. investigated this problem from a dosimetric perspective74 and found that, for an average size prostate, 15 to 21 catheters provide adequate coverage. A further increase in the number decreased the high-dose volume, but at a lower rate.

 

Figure 8.33 The perineum is shaved and the catheter entry points are marked in four columns on the skin between the pubic symphysis and the anus. The columns are positioned to each side of the central raphe with care to avoid central entrance sites that may compromise the penile bulb or urethra.

Transrectal Ultrasound

After the patient is prepped and draped, the TRUS probe is secured to a brachytherapy stand. The brachytherapy stand provides a sterile and stable imaging platform (see Fig. 8.34). This technique was adapted from the permanent seed implant technique. To obtain the best TRUS image of the prostate, the probe must be parallel to the posterior border of the prostate. The probe should apply light pressure to the anterior rectal wall to obtain an artifact-free image of the prostate without causing significant distortion of the prostate. A brachytherapy stand with microadjustment control is very useful for alignment of the probe with the prostate. Occasionally, the air trapped between the probe and the rectum causes distortion of the image. The air is released by inserting a straight urinary catheter into the air pocket.

Figure 8.34 The perineum is prepped and draped in a sterile manner. A disposable condom covers the ultrasound probe as it is gently inserted through the anus. The probe is secured to the stepper with a retaining band and connected to the ultrasound unit with the white cable. Transparent draping over the ultrasound probe facilitates manipulation of the controls of the stepper and the probe during the implant without compromising the sterile technique.

Figure 8.35 Transrectal ultrasound images of a prostate implant. A: Anterior catheters. Catheters around the urethra are generally inserted first because they are best seen before the posterior catheters are inserted. B: Posterior catheters are inserted. C: Posterior catheters can be advanced into the seminal vesicles to cover the base of the prostate and seminal vesicles or to provide additional margins.

Catheter Insertion

Sixteen gauge plastic catheters with metal obturators are assembled. Before starting the procedure, a Foley catheter is inserted into the bladder. This allows visualization of the urethra on TRUS and helps to prevent accidental puncturing of the urethra during the implant. Instead of keeping all the catheters parallel to one other, the freehand technique emphasizes that the positioning of the catheter be based on the target volume seen on the ultrasound. The goals are as follows:

1. Place the catheters 1 to 2 mm (usually 12) around the prostate capsule, and four catheters half-way between the outer ring of catheters and the urethra.

2. Maintain an even spacing of catheters on each level of the axial ultrasound images.

3. Maintain the relative position of catheters at each level from the skin to the base of the prostate, avoiding crossover of catheters.

4. The posterior row of catheters is advanced into the inferior portion of the seminal vesicles. These catheters should be near the posterior border or the center of the seminal vesicle.

For each implant, each catheter is inserted transperineally at the marked entrance points. Once the catheter is inserted through the skin, it is advanced at 5-mm intervals using the brachytherapy stand from prostate apex to the base, taking great care to avoid puncturing of the vascular structures, urethra, bulb, or crus of the penis. The two most anterior medial catheters are placed first, followed by lateral posterior catheters (see Fig. 8.35). The two medial anterior catheters are most likely to pierce the urethra and the bladder neck, so they must be guided with the greatest care under direct ultrasound image guidance. As more catheters are inserted, the locations of these catheters become less visible, making further adjustment difficult. Because of the variation of the diameter of the prostate at each level, the catheters often diverge as they traverse the gland from the apex to the base (see Fig. 8.36).

Gold Marker Seeds

Gold marker seeds are placed at the base and the apex of prostate before the posterior two rows of catheters are inserted. The apical seed is implanted just posterior to the urethra and the base seed is implanted at the inferiormost space between the bladder wall and the seminal vesicles. The needle depth is confirmed on the sagittal view using the seeds as fiduciary markers (see Fig. 8.37). The seeds also mark the TRUS-identified prostate apex and base, which can later be compared with CT images. The base marker seed can also be used to assess catheter movement between HDR fractions.

Cystoscopy

Most published series have reported urethral morbidity; therefore, every effort should be made to avoid placing catheters too close to the urethra.72,75,76,77,78,79,80,81,82,83,84 As recommended by Mate et al. a retroflexed cystoscopy is performed after all catheters are inserted.73 To view the bladder neck, the flexible cystoscope is advanced superiorly and deflected off the dome of the bladder (see Fig. 8.38). Once the bladder neck is visualized, the anterior catheters are advanced until they cause tenting of the bladder neck mucosa. The catheters are not advanced into the bladder. However, the posterior catheters are routinely advanced into the inferior portion of the seminal vesicles (see Fig. 8.39). This is done after the cystoscopy using ultrasound guidance to improve the coverage of the base of the prostate and to anticipate potential interfraction catheter movement.

Figure 8.36 A computer reconstruction of the contours and catheters. The prostate contours are red hoops, the white surface is bladder, and the pink surface is rectum. The catheters are in green, dwell positions are in purple and the prescription isodose is the blue surface cloud.

Figure 8.37 Two saggittal ultrasound images of the prostate. The ¥ marks the hyperechoic shadow caste by the marker seed and the needle tip; SV marks the seminal vesicle.

Securing the Catheters

The implanted catheters are secured with a “dental putty” technique. A friction collar is placed on each catheter before beginning the procedure. After the catheters are inserted, the friction collar is advanced to approximately 1 cm from the skin. Two sutures are then placed on the perineum, one across each group of the catheters. Care must be taken not to puncture the catheters subcutaneously. Once placed, the suture needles are removed for safety. The sutures are secured anterior to the catheters until needed. These sutures are later used to tie the hardened putty that holds the catheters against the perineum (see Fig. 8.40). The obturators are left in place in the catheters until after the sutures are inserted to help prevent accidental piercing or cutting of the catheter by the suture needle. Once the obturators are removed, a perforated grid is made from unheated Aquaplast mask material and placed over the catheters so as to maintain their spacial relationship (see Fig. 8.41). The grid temporarily holds the catheters while the dental putty is applied. Aquaplast works well for this purpose because the HDR compatible catheters closely fit in the perforations. The catheters are separated into two groups by dividing them at the median raphe. By securing the catheters in two groups, each group is allowed to move independently. This decreases the chance of the catheters being pulled out.

Figure 8.38 A: A flexible cystoscope can be retroflexed in the bladder to visualize the bladder neck. B: This retroflexed cystoscopy image of the bladder neck demonstrates tips of catheter tips that cause tenting of the bladder mucosa.

Figure 8.39 Ultrasounds of seminal vesicles shows catheters in close proximity to the bladder.

 

Figure 8.40 With the ultrasound probe still in place to check for catheter movement, each catheter receives a friction collar that is pulled down to the level of the skin. Skin sutures are passed laterally to these catheters for securing putty blocks when they are formed.

Figure 8.41 The catheters are sorted and held in a pattern using two unheated rectangles of Aquaplast grid, approximately 3 × 6 cm in size.

The putty used is commercial dental molding putty, with high viscosity, which is used to make dental impressions (Reprosil Type I). This is an adaptation of the technique described in surface mould application and intracavitary brachytherapy.85,86,87,88,89,90,91 A variety of different commercial products are available for this purpose. The putty is first applied around the friction collars and then gently molded around the catheters with pressure. This removes air pockets from around the catheters and friction collars. Finally, the superior surface of the putty is molded against the perineum to create a custom fit (see Fig. 8.42). The goals during the application of putty are as follows:

1. Fill in the free space between the catheters, the patient, and the Aquaplast grid.

2. Mold the putty to conform to the patient's perineum.

3. Put each group of catheters into a small block that can be secured using one to two sutures.

With some practice, one quickly becomes a master of this technique. The same technique can be used to secure any volume implant on an irregular surface.

The final size of each group of eight catheters, including putty, is approximately 2 cm × 3 cm × 1.5 cm. The friction collars are sandwiched between the putty, so the friction holds the catheters. This friction is tight enough to keep the catheter in place yet loose enough to allow adjustment of the catheters after the putty hardens. This particular type of putty hardens 3 minutes after its two components are mixed together. Once the putty is hardened, the grid is removed. The putty is then tightly secured against the perineum using the two sutures placed earlier. The final result is shown in Figure 8.43. Figure 8.44 is an illustration of the steps of this procedure. The customized fit provided by this technique improves patient comfort and minimizes catheter displacement between treatments.

 

Figure 8.42 The putty is applied around and between the catheters and the friction collars and molded into a block shape with all catheters generously covered.

Treatment Planning

Simulation

For three-dimensional (3D)-treatment planning, the patient undergoes a CT or MRI of the pelvis. Slice thickness <3 mm is used to minimize error.92 The metal obturators are removed before scanning to decrease image distortion or scatter. Only the plastic CT-/MRI-compatible catheters are left during scanning. This improves the quality of image. The scan is reviewed before moving the patient off the table to ensure the following:

Figure 8.43 When the putty has set, the Aquaplast mask material may be removed and the retaining sutures tied around the central portion of each putty block.

 

Figure 8.44 An illustration of securing the catheters using putty. I. The catheters are implanted through the skin. II. Friction collars are applied to each catheter. III. The temporary Aquaplast grid is slid over the catheters to hold them apart. The space between the Aquaplast and the friction collars is filled in with dental putty, molding the putty against patient's skin. IV. Previously placed silk sutures secure the putty and catheters to the skin.

1. The catheters are deep enough to cover the planned target volume (PTV).

2. The Foley catheter balloon is pulled down toward the bladder neck.

3. The end of each catheter is included on the scan.

4. All fiducial markers and the volumes of interest are included in the scan.

5. The identity of each catheter is evident.

Occasionally, an obturator has to be reinserted to advance a catheter before the scan is repeated. Any marker/contrast has the potential to degrade the quality of the CT scan or MR image. At UCSF, if contrast is used in the Foley catheter balloon or bladder, it is of ≤30% concentration. Marker seeds are routinely <2-mm length and do not significantly distort. Radiopaque catheters are not used. Dummy markers used during CT simulation were found to produce artifacts that made contouring more difficult. The air column in the catheter provides good enough contrast with the soft tissue allowing identification of the ends of the catheters on CT scans. Once the scan is completed, images are then transferred to the planning system.

Contouring Volumes

The importance of proper contouring cannot be overemphasized. If the physician does not personally contour all the structures, then she/he must review every slice contoured. At UCSF, the OAR are contoured before contouring the PTV and the urethra. The OAR contoured include the bladder, the rectum, and the bulb of the penis. The contouring of the OAR is started on the image that most clearly shows the structure; this usually means starting near the middle of the structure and then contouring superiorly and then inferiorly. Most treatment-planning systems allow previous contours to be copied to the current slice. The copied contour provides a good starting point for the new contour. This approach improves the consistency of the contour between slices.

Contouring of the prostate apex and the base is challenging. The following three methods are used to outline the apex of prostate:

1. The position of the urethra relative to the center of the prostate is followed. Because the urethra moves anteriorly immediately after it exits the urogenital diaphragm, the apex of the prostate is usually just superior to this point.

2. The sphincter muscles become more prominent just before they merge with the urogenital diaphragm. The apex of the prostate can be outlined by following the medial edge of the muscle from rectum toward the pubic symphysis.

3. The marker seeds inserted during the procedure confirm the location of the apex. If the seed is located near a slice identified by one of the methods, this confirms the location of the apex.

 

The base of the prostate is difficult to see because of volume averaging and its complex shape. Both tenting and deflating the bladder can cause the bladder wall to appear thicker. The following three methods are used to outline the base of prostate:

1. The Foley catheter balloon marks the inside wall of the bladder.

2. Marker seed is placed at the base.

3. The cystoscopy findings are used to evaluate the shape of the bladder neck.

An example of the UCSF contour is shown in Figure 8.45. The other useful method of identifying the base and apex of the prostate is using a sagittal reconstruction (see Fig. 8.46). Because the implant catheters tend to move inferiorly, the medial portion of the seminal vesicles is routinely included in the PTV as a margin. The outline of the PTV should include the prostate and any region of known extracapsular extension. If there is known seminal vesicles extension, the catheters should be inserted into the seminal vesicles and the PTV should include the seminal vesicles. After insertion of the catheters, contouring is the second and final opportunity to ensure the tumor volume is properly treated.

Localization of Catheters

The catheters are visualized as air columns in the tissue (see Fig. 8.47) as markers are not routinely placed in the catheters for CT/MRI. Besides identifying the path of each catheter, the center of the last dwell position must be accurately located. It is important to develop a common policy on how the last dwell position is identified to ensure the last dwell position is consistently identified. The policy is based on the size of the source, catheter construction, thickness of CT scan slice, and which part (tip or middle) of the source/dwell position is being digitized. A clear policy for catheter reconstruction ensures the dose displayed is the dose delivered.

Optimization

Optimization of the implant involves two steps, selective activation of dwell positions and the determination of relative dwell time. At UCSF between 1997 and 2001 an optimization technique based on the commercially available software was used. Only dwell positions within the PTV were activated. The prescription dose to a dose point at the center of urethra and at the base of the prostate was calculated. Geometric optimization based on volume was used to calculate the relative dwell times. The prescription dose was selected on the basis of the isodose distribution. The plan that minimized the hot spot (150% isodose volume) and dose to the bladder and rectum while covering the implanted volume was selected. The bladder and rectal doses were kept below the prescription dose and the 150% isodose line was kept away from the urethra. This often required manual adjustment of the dwell times.93 Since 2001, this process has been completely automated with a mathematical algorithm-based optimization system called IPSA.94

Figure 8.45 Computed tomography scan images of an implant. The upper three panels show the apex region, and the lower three panels show the base of the prostate. The planned target volume is marked in red, the rectum in yellow, the bladder in green, and the urethra in pink. The left medial border of the muscle is marked in blue in the upper middle and right panel.

Figure 8.46 Sagittal reconstruction of computed tomography scan. The urethra (U) with Foley catheter and a posterior catheter are clearly shown. Apical marker seed (A) and base marker seed (B) are marked on the scan.

 

Figure 8.47 Transverse images of an implant. A: Computed tomography scan image: Air columns in the catheters show up clearly on computed tomography scan allowing identification of the catheters. B: Magnetic resonance image of the same patient: Zonal anatomy of the prostate and other soft tissue structures are shown better on a magnetic resonance image.

Figure 8.48 Conformal dose distribution can be delivered to the prostate using a modern brachytherapy treatment system. A steep dose falloff outside of the implant volume minimizes dose to nearby normal bladder and rectal tissues. The prescription dose is represented as the yellow isodose line in A and the blue cloud in B.

The software selectively activates dwell positions inside the target volume and then identifies the combination of dwell times that best conform to dose constraints of target volumes and critical organs. After contouring the volume of interest, dose constraints are given to dose calculation points within each volume. For each contoured volume, there are two types of dose calculation points. One set of dose calculation points is located near the surface of the contour and the other set is located near the dwell positions. The adjustment dose to the first set of dose points controls the target coverage and conformality (see Fig. 8.48), and adjustment of dose to the second set of dose points controls the dose homogeneity. An example of dose constraints used is listed in Table 8.5.

Dmin and Dmax represent the lower and the upper range of acceptable doses. If the dose goes below or above the range, the penalty increases at rates Mminand Mmax, respectively. Adjustment of Mmin and Mmax sets the priority among different structures. Once the dose constraints are set, IPSA rapidly finds the dwell time combination with the least amount of penalty using the simulated annealing algorithm.

Table 8.5 Dose Constraints for Inverse Planning Simulated Annealing High Dose Rate Prostate Brachytherapy Treatment Planning

 

Dmin

Mmin

Dmax

Mmax

Targetsurface

950

100

1,425

100

Targetinside

950

100

1,425

70

Urethrasurface

950

100

1,140

60

Urethrainside

950

100

1,140

60

Bladdersurface

0

0

475

40

Rectumsurface

0

0

475

40

Key: Dmin—minimum acceptable dose; Dmax—maximum acceptable dose; Mmin—penalty for not achieving minimum dose to structure; Mmax—penalty for not staying with maximum dose to structure.

 

Once an optimized treatment plan is generated, it is the physician's responsibility to evaluate the plan and decide if it is acceptable. Various normal structures dose–volume limits have been described in the literature.73,95 At UCSF, the rectal and bladder volumes are kept below the prescription dose, and urethral volume below the 150% isodose volume. This has worked well with 45 Gy EBRT followed by 6 Gy × 3 using one implant.93 The RTOG is currently testing an external beam dose of 45 Gy followed by 9.5 Gy × 2 using one implant, which is the current standard at UCSF in a multi-institutional phase II study. Normal tissue limits used in this study are as follows:

1. Bladder and rectal volumes receiving 75% of prescription dose or 7.12 Gy must be <1 cc (V75% <1 cc)

2. Urethral volume receiving 125% of the prescription dose or 11.87 Gy must be <1 cc (V125% <1 cc).

Once the treatment plan is generated, a simple hand calculation is routinely performed to compare the results with the IPSA to the in-house nomogram. The nomogram was constructed on the basis of the treated patients. The calculation is based on the dose, current source activity, volume, and treatment time. The nomogram allows for a quick check to make sure the total treatment time is within reason.

Treatments

Although it is possible to use catheters of the same length and therefore the same indexer length for all treatments, at UCSF the catheters are routinely trimmed so that the indexer length differs between patients. This minimizes the chance of using the wrong treatment plan. Although this requires more work, once the data is entered correctly, the afterloader is used to double-check the connection before each fraction. Most patients stay in the hospital overnight and are brought down for the second treatment the next morning. Before the second treatment, the implant is inspected for displacement. If the catheter has to be adjusted, the CT and planning are repeated before the second treatment. After the second treatment, the implant is removed and the patient is usually discharged by noon.

Implant Removal

To remove the implant, each catheter is slowly pulled to within 2 cm below the skin, and then all catheters are removed at once. Once all the catheters are removed, pressure is applied to the implant site using gauze for a few minutes until the bleeding stops. Because most patients at UCSF have epidural pain control, additional medication for pain control during removal is not routinely needed.

Postoperatively, sitz baths are recommended in the first 1 to 2 days. Most patients do not require any additional medication. All patients are reminded of the expected short-term side effects, which include urinary urgency and frequency. These are evaluated at regular follow-up appointments.

Chapter 8 HDR Case Studies

 

Case 1

A 59-year-old man presented with T3b, Gleason 8, adenocarcinoma of prostate, and pretreatment PSA of 5.2. TRUS showed extracapsular extension and bilateral seminal vesicle invasion (see Fig. 8.49). Eight out of eight biopsies were positive, including both seminal vesicles. The patient had hormonal therapy and pelvic radiation to 45 Gy, and HDR brachytherapy of 19 Gy in 2 fractions. At the time of the implant, the posterior catheters were advanced into the seminal vesicles. This case illustrates the ability to cover extracapsular and deliver full dose to the seminal vesicles with HDR boost.

Figure 8.49 Implant with the posterior catheters advanced into the seminal vesicles.

These two cases illustrate the flexibility of inverse planning (IPSA) and HDR brachytherapy. In both of the images shown in Figure 8.50 and Figure 8.51 the 100% isodose line is in red, and 150% and 50% lines are in yellow and green, respectively.

Case 2

This is a similar intermediate risk group patient with a dominant let periferal zone lesion seen on MRI spectroscopy. A: The MRI spectroscopy identified a dominant intraprostatic lesion and is marked in orange at the left PZ. Using inverse planning, the preexisting high-dose region (150%) was directed to this lesion. The minimum dose to the lesion was escalated to 150% without increasing the dose to the urethra, the bladder, and the rectum.96 B: In this case, inverse planning with CT imaging was used to decrease the dose to the urethra. The 100% isodose line tightly conforms to the prostate and the 150% isodose line breaks up around the catheters.

Figure 8.50 The dominant intraprostatic lesion, as identified by magnetic resonance spectroscopy, is marked in orange. MRI-based dosimetry shows 100% isodose line in red, 150% in yellow. The PTV is in blue.

Figure 8.51 Computed tomography scan image where inverse planning was used to decrease the dose to the urethra. One hundred percent isodose line is in red, and 150% and 50% isodose lines are in yellow and green, respectively.

Case 3

In another similar risk group patient excellent dose conformance to the PTV is seen. Inverse planning decreased urethral dose optimally.

 

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