high dose rate brachytherapy in the treatment of prostate cancer

BRACHYTHERAPY 0889-8588/99 $8.00 + .OO

HIGH DOSE RATE BRACHYTHERAPY IN THE

TREATMENT OF PROSTATE CANCER

Rodney R. Rodriguez, MD, PhD, D. Jeffrey Demanes, MD, and Gillian A. Altieri, CMD

Prostate cancer is the most common malignancy of the male genitourinary tract.14 The number of new cases of prostate cancer in the United States in 1998 is estimated to be 184,500, with 39,200 men dying of their disease.14 The use of external beam radiation therapy (EBRT) as definitive treatment for localized prostate cancer is well estab1ished.l. 2o In the last two decades, interstitial radioactive implantation has been used in the treatment of prostate cancer in an attempt to improve local control rates. The goal of brachytherapy in the treatment of localized prostate cancer is to increase the dose to tumor-bearing structures while reducing the dose to normal dose-limiting structures.

Prostate brachytherapy has been delivered by either permanent low dose rate (LDR) or temporary high dose rate (HDR) implants. It is usually combined with EBRT, although permanent implants are now routinely used as monotherapy in selected patients.19 Procedures for both permanent and temporary prostate implantation have evolved from inaccurate, open retropubic techniques4, 9, lo* 26 to highly accurate, closed transrectal ultrasound-guided implantation^.^, 11, 12, 13,

A variety of radioactive isotopes have been used in prostate brachytherapy for both LDR and HDR techniques. Two isotopes, iodine-125

22, 24

From the California Endocurietherapy Cancer Center (RRR, DJD, GAA), and the Depart- ment of Radiation Oncology, Summit Medical Center (RRR, DJD), Oakland, California

HEMATOLOGY /ONCOLOGY CLINICS OF NORTH AMERICA

VOLUME 13 NUMBER 3 * JUNE 1999 503

504 RODRIGUEZ et a1

125) and palladium-103 (I'd-103) are used for LDR permanent implants in the form of small pellets or seeds. Low dose rate temporary implants utilize iridium-192 (Ir-192) in the form of a wire or seeds embedded in a nylon ribbon. The Ir-192 used in HDR temporary prostate implants comes in the form of a single source welded to the end of a thin, flexible stainless-steel cable. Both the LDR 1-125 and Pd-103 seeds and the temporary LDR Ir-192 sources are manually loaded. Iridium-192 in HDR brachytherapy is loaded by a computer-controlled unit called a remote afterloader.

The development of HDR remote afterloading opened a new era for prostate brachytherapy. For the first time since the discovery of radium in the early 1900s, the HDR remote afterloader enabled radiation oncologists to control the amount of radiation administered both to tumor-bearing structures and to normal tissues. In addition, its complete radiation safety and use as an out-patient procedure make HDR brachytherapy a very powerful technological tool for treating prostate cancer.

BASICS OF HIGH DOSE RATE BRACHYTHERAPY

High dose rate brachytherapy has been used for more than 34 years to treat cancer of the cervix and endometrium.* High dose rate remote afterloading replaces manually loaded LDR sources in which the radiation dose delivered to the prostate and surrounding normal structures is very difficult or impossible to control. The afterloader is able to move the radiation source in specified steps, called dweZZ positions, within the catheters. These dwell positions can be programmed to occur at different spacings, from 2.5 mm to 1.0 cm apart (Fig. 1). In addition, the amount of time the source spends in these dwell positions can be controlled. The dosimetrist can choose from a variety of calculation methods the one that best suits the implantation. For the treatment of prostate cancer, the best method is geometric optimization on v o l ~ m e . ~ The computer software analyzes the relationship of the implant catheters to one another and determines the amount of dwell time the source must spend in each position to achieve a uniform dose distribution around and within the implant. The dosimetrist can adjust individual dwell times to shape the prescribed isodose value to the prostate (conformal brachytherapy). In addition, if doses to the normal structures, such as the bladder, rectum, and urethra, are too high, the dwell times can be reduced in the positions that contribute to the high doses, thus lowering these doses to acceptable levels. The result is a treatment, delivered in a matter of minutes, that accurately achieves the shape and doses desired by the physician (Fig. 2).

Treatments are delivered on an outpatient basis. The fractionated HDR dose is delivered in a matter of minutes, compared with hours or days in conventional LDR treatments (Table 1). The short treatment time adds to the patient's comfort. No residual radiation remains in the patient. When all the treatment fractions have been given, the implanted

HIGH DOSE RATE BRACHYTHERAPY IN THE TREATMENT OF PROSTATE CANCER 505

Figure 1. High dose rate (HDR) stepping source. Bar represents 1.7 mm. (Courtesy of Nucletron Corporation, Columbia, MD.)

catheters are removed. After a brief observation time to ensure the patient is stable and urinating properly, the patient can be discharged.

Another benefit of the HDR system is that radiation exposure to hospital staff and family members is eliminated. The radiation treatments are delivered in a specially designed and shielded treatment room. When the treatment is finished, the radiation source retracts into the afterloader’s safe.

Table 1. BRACHYTHERAPY DOSE RATES AND TREATMENT TIMES ~ ~

Dose Rate Description Range Treatment Time

Low Dose Rate (LDR) 0.3-1.0 Gy/hr 30-70 hours Medium Dose Rate (MDR) 1.0-20 Gy/hr 1-20 hours High Dose Rate (HDR) >20.0 Gy/hr (>0.33 Gy/min) 10 minutes (fractionated)

Courtesy of Nucletron Corporation, Columbia, MD.

506 RODRIGUEZ et a1

Figure 2. A -0, Autoradiograph images of varying radiation distributions possible with HDR brachytherapy technology. (Courtesy of Nucletron Corporation, Columbia, MD.)

Patient Selection

Patients suitable for treatment of localized prostate carcinoma by a combination of EBRT and HDR brachytherapy are those with stages T1 through T3, Gleason scores of 2 to 10, and prostatic specific antigen (PSA) values less than 20. Patients with higher PSA values are also candidates if their metastatic work-up is negative and/or if the tumor is confined to the transitional zone. (These patients often have higher PSAs despite prostate-confined disease.)

Staging

All patients receive a digital rectal examination and PSA testing. Sextant biopsies from the bilateral prostate apex, midgland, and base are obtained by transrectal ultrasound (TRUS) and placed in separately labeled jars for pathologic evaluation. The TRUS examination should measure prostatic volume, evaluate the capsule and seminal vesicles, and identify and accurately delineate any hypoechoic regions. A bone scan is indicated only if the PSA is greater than 10 ng/ml. A pelvic MR imaging scan or endorectal coil MR imaging is performed only if there is a high risk of positive seminal vesicles and/or gross extracapsular disease. Evaluation of pelvic lymph nodes is undertaken only if there is a high suspicion of lymph-node metastases.


Treatment Protocol

External beam radiation therapy can be delivered either before, during, or after HDR brachytherapy.2, 3, 11, 12, 13, 17, 18, 24 External beam doses range from 36 to 50 Gy. Table 2 shows the EBRT doses given at California Endocurietherapy Cancer Center (CET), Oakland, California; Royal Oak, Michigan; Seattle, Washington; Kiel, Germany and Goteborg, Sweden.

The transperineal closed implantations are performed with the patient under spinal anesthesia with intrathecal Duramorph (Elkins-Sinn, Cherry Hill, NJ) using TRUS and cystoscopic guidance. During TRUS examination the prostate volume, width, height, and length, the location of hypoechoic regions, and possible extracapsular extension or seminal vesicle involvement are evaluated (Fig. 3) . Transrectal ultrasound guidance is used to place trocars into the prostate, using the fixed template method? 12, 16, 18, 24 or the Syed free-style template technique.22, 26

The initial placement of the first four trocars can be verified by fluoroscopy (Fig. 4). Trocars are inserted from anterior to posterior so as to prevent unnecessary TRUS shadowing. The urethra is visualized using a radiopaque 18 French 5-mL balloon Foley catheter in the bladder. Whichever technique is used for placing the trocars into the prostate, both the urethra and the anterior rectal wall must be carefully avoided. Under TRUS guidance, two gold seeds are placed in the prostate base and one in the prostate apex as markers to verify the final placement of the trocars and determine the number of dwell positions to activate along the length of the catheters in order to cover the prostate ade- quately Cystoscopy is performed before implantation to evaluate any anatomical variations such as trilobar hypertrophy and/or an elevated bladder neck that would indicate postimplantation obstruction. In addition, a preimplantation cystoscopy is used to evaluate the extent of transurethral resection (TUR) defects, because patients receiving HDR brachytherapy have often undergone a TUR. Postimplantation flexible fiberoptic cystoscopy is performed to ensure that no trocars are penetrat- ing into the bladder and that only tenting of the bladder mucosa is

Fluoroscopy and radiographs are also used for postimplantation visualization. Anteroposterior and lateral radiographs verify the depth and overall quality of the implantation (Fig. 5). Figure 5C shows a

seen.11, 12. 18.22

Table 2. PUBLISHED EXTERNAL BEAM RADIATION THERAPY SCHEMES

Group EBRT (Gy) Daily (Gy)

Oakland, California 36.0 1.8

Seattle, Washington (1989-95) 50.4 1.8 Seattle, Washington (1995-present) 45.0 1.8 Kiel, Germany 50.4 1.8 Goteborg, Sweden 50.4 1.8

Royal Oak, Michigan 46.0 2.0

508 RODRIGUEZ et a1

Figure 3. A, Transrectal ultrasound (TRUS) prostate volumetric analysis, transverse (left) and longitudinal (right). 13, TRUS transverse image of hypoechoic lesion in the right midgland (dofs and arrow).

Illustration continued on opposite page

HIGH DOSE R A E BRACHYTHERAI'Y IN THE TREATMENT OF PROSTATE CANCER 509

Figure 3 (Continued). C, TRUS longitudinal image of a left midgland hypoechoic lesion (dots and arrow).

510 RODRIGUEZ et a1

Figure 4. A, AP fluoroscopic image and TRUS transverse image (B) of the first four free- hand placed trocars (arrows) in midline position.


transverse TRUS image of a completed TRUS-guided, fluoroscopically aided complex transperineal implantation of the prostate. This technique also allows the implantation to be performed on patients with seminal vesicle involvement (Fig. 6).

Various methods are used to obtain data needed for the dosimetric calculations. The most common method is the use of postimplant simulation/localization radiographs, in which digitized images of the catheter and nearby structures are entered manually into the treatment planning computer. Intraoperative dosimetry is used in some centers where the HDR brachytherapy treatment is given intraoperatively.6, 11, 23

Other groups utilize preplanned dosimetry to deliver the HDR treatment intraoperatively.2 Computerized tomographs (CT) are also used to determine the location of the trocars and their relationship to nearby struc- ture@ (Fig. 7).

Dose Prescription

Dose prescription depends upon the imaging method used. If ultrasound images are used to determine the periphery of the prostate, the target volume is defined as the TRUS volume plus 5 mm beyond the periphery." If the prostate is outlined on CT images, the target volume is the same as the prostate volume.*7* l8 The prescribed dose can also be delivered to a reference point assumed to be the minimum dosage-point in the implanted volume.6

Dose limits for normal structures vary according to the amount of the external beam dose (Table 3). The two structures that are susceptible to high radiation doses are the urethra and rectum. (The bladder lies superiorly to the prostate, and any dwell positions at the tips of the catheters that come too near the bladder can be turned off or deleted without affecting the dosimetric integrity of the implant.) As mentioned earlier, the HDR system allows the adjustment of dwell times so that the doses to these structures are reduced, while still giving the prescribed dose to the prostate. Figure 8 shows a set of isodose curves for whole- organ conformal HDR brachytherapy delivering a dose of 6 Gy to the 100% isodose line. Patients with TUR defects can also be treated with

Table 3. MAXIMUM NORMAL TISSUE DOSE AS A PERCENTAGE OF PRESCRIBED HIGH DOSE RATE DOSE

EBRT Urethra Bladder Group (GY) (%)

Oakland, California 36 a 2 0 <75 Royal Oak, Michigan 45 <112 NR Seattle, Washington 45 < n o NR Eel, Germany 50 NR NR Goteborg, Sweden 50 80 NR

Rectum ("4

<65 87

NR NR 60

NR = not reported.

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Figure 5. AP fluoroscopic image (A) and lateral fluoroscopic image (6). Illustration continued on opposite page


Figure 5 (Continued). TRUS transverse image (C) of completed implant.

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Figure 6. TRUS transverse (A) and longitudinal (B) images showing trocars (arrow) in seminal vesicles (sv).


Figure 7. CT image showing trocars (black dots) placed by TRUS guidance.

SC.1e I. 1.00

t tX

Figure 8. lsodose curves for whole-organ conformal HDR treatment. A = transverse; 6 = AP; C = lateral.

, + X

le 1:

plane 2: Y - IS ’

600

540

300

Figure 9. lsodose curve for whole-organ conformal treatment of a prostate cancer patient with a transurethral resection (TUR) defect. Note “donut hole”, created by adjusting the dwell times of the central trocars, sparing the defect and urethra.

HDR brachytherapy. Figure 9 depicts a set of isodose curves for such a patient, exhibiting a “donut hole” (toroidal) contour in the center of the prostate corresponding to the TUR defect.

High Dose Rate Fractionation

21, 24, 25 In addition, the number of implantations performed also varies. Table 4 shows the published EBRT and HDR fractionation schemes for several medical groups that have performed large numbers of HDR brachytherapy prostate implantations. The CET protocol for disease stages Tla through T3b is for 36 Gy EBRT. After the completion of EBRT, the patient undergoes two implantations, one week apart. Each implantation is treated twice at 6 Gy/fraction.

A variety of HDR fractionation schemes exist.2, 12, 16, 17,

Tumor-Specific Boosting Technique

Patients with TRUS-documented, biopsy-proven hypoechoic regions, with palpable, biopsy-positive gross disease, or with gross disease within the prostate visible with endorectal coil MR imaging are candidates for a tumor-specific boost dose of radiation in addition to the whole-prostate conformal HDR treatment.21 These areas are carefully


Table 4. PUBLISHED EXTERNAL BEAM RADIATION THERAPY AND HIGH DOSE RATE DOSE SCHEMES

Number Interval EBRT of Between

Group (GY) HDR Fractionation Implants Implants

Oakland, California 36 *6.0 X 3 (2 fx/implant) 2 1 week Royal Oak, Michigan 46 5.5 x 3 3 1 week

6.0 X 3 (1 fx/implant) 6.5 X 3

Seattle, Washington 50 4.0 X 4 (4 fx/implant) 1

Seattle, Washington 45 5.5 x 3 (3 fx/implant) 1 (1989-1995)

(1996-present) Kiel, Germany 50 15.0 X 2 (1 fx/implant) 2 1 week Goteburg, Sweden 50 10.2 x 2 (1 fx/implant) 2 2 weeks

*6.0 x 3 indicates 6.0 Gy delivered 3 times for total dose of 24.0 Gy. Fx = fractions.

delineated on the TRUS intraoperative examination (see Fig. 3) and on the tumor-specific boost planning diagram (Fig. 10). With HDR, it is possible to add 0.5 to 0.75 Gy/fraction to the gross disease as a concurrent boost. The experienced dosimetrist develops an understanding of how much to reduce the bladder, urethral, and rectal doses in the whole- gland treatment plan so that when the boost doses are added to the whole-gland plan, the composite bladder, urethral, and rectal doses do not exceed the allowed total. Table 5 shows the treatment schemes developed at CET. All HDR fractions are given on a twice-daily fractionation schedule with a minimum of 6 hours between fractions. The dose fractionation schedules are based on the linear quadratic equation model used in the past to treat cervical and endometrial carcinoma^.'^

RESULTS OF COMBINING EBRT AND HDR BRACHYTHERAPY

The Seattle Experience

Between October 1989 and August 1995, 104 patients were treated at the Seattle Prostate Institute in Seattle, Washington.'* Disease stages

Table 5. DOSE MODIFICATION FACTORS FOR TUMOR SPECIFIC BOOST

Factor Modification

Gleason score 2 7 TRUS hypoechoic lesion Palpable nodule Extracapsular extension

Increase dose 0.5-0.75 Gy/fraction Increase dose 0.5-0.75 Gy/fraction Increase dose 0.75 Gy/fraction Increase dose 0.75 Gy/fraction

TRUS = transrectal ultrasound.

518 RODRIGUEZ et a1

ANTERIOR

RIGHT

5

0

POSTERIOR

B

2

0 13

0 - LEFT

RT. KILT. INF INF.

15

0

Figure 10. A, Location of right midgland hypoechoic lesion seen on transverse and longitudinal TRUS images. B, Planning diagrams for boost treatment of right midgland hypoechoic lesion.

Illustration continued on opposite page


I " " " ' ' 1 . ' ' ' ~ ' ' ' " ' 1 ' " ' - v P1.m 3: x - o ' LG" t X Plane I' V - O c C

SC.1. 1: 1.00 5 Scale 1 1.00 15 -

ll Figure 10 (Continued). C, lsodose curves for tumor-specific boost of a right midgland hypoechoic lesion. Note catheters not involved in the boost have been deactivated. A = transverse; 6 = AP; C = lateral.

treated were Tlb to T3c. Gleason scores were 3 through 9 with a median PSA of 8.1 ng/mL. With a median follow-up of 45 months, the reported freedom from PSA progression was 84%. The level of genitourinary (GU) morbidity was very acceptable. Only 6.7% of the patients developed urethral strictures that were managed conservatively, and 1.9% developed moderately severe urinary frequency and dysuria that resolved with symptomatic treatment. Only one patient (1%) had prostatic urethral necrosis, but this patient had had a TUR of the prostate 2 years before his HDR treatments. No patients have developed chronic incontinence. Late gastrointestinal (GI) complications were also minimal. Only 2 patients (2%) had transient rectal bleeding and proctitis which resolved without treatment. No other GI complications were observed.

The Royal Oak Experience

The series from William Beaumont Hospital in Royal Oak, Michigan,16, l7 includes 59 patients with disease stages T2b to T3c, Glea- son scores of 2 to 10, and a mean PSA of 17.25 ng/mL. With a mean follow-up of 19 months, the center reports a PSA normalization (<1.5 ng/mL) of 86%. Acute and chronic morbidity was scored using Radia-

520 RODRIGUEZ et a1

tion Therapy Oncology Group (RTOG) guidelines. Only 7% of the patients had acute grade 3 toxicity. No chronic GI toxicity was seen.

The Kiel Experience

Kovacs et al"-13 in Kiel, Germany, have reported on 171 patients treated between 1986 and 1996. Sixty-one (36%) of these patients received androgen suppression 6 months before irradiation, which was termi- nated before beginning irradiation. Thirteen (8%) patients continued androgen suppression after radiotherapy. Thirteen percent of the patients had pretreatment PSA levels of 4 ng/mL, 46% had levels less than or equal to 20 ng/mL, and 40% had levels greater than 20 ng/mL. Prostate- specific antigen progression was defined as the PSA level never reaching or falling below 1 ng/mL prior to an increase or as a PSA increase to twice the nadir level after reaching or falling below 1 ng/mL. With a median follow-up of 55 months, PSA progression occurred in 11% of patients with stage Tlb to T2b disease and in 15% of patients with stage T3 disease. As scored on the RTOG/EORTC criteria, 13 patients (5%) experienced grade 1 GU morbidity, 14 patients (7%) experienced grade 2 GU morbidity, and 3 patients (2%) developed dysurial cystitis (grade 3 morbidity). Nine cases (5%) of incontinence occurred in patients with previous TURPS. Late morbidity characterized as proctitis occurred as follows: 12 patients (7%) experienced grade 1 morbidity, 10 patients (6%) experienced grade 2 morbidity, and 5 patients (3%) experienced grade 3 morbidity. Other late complications consisted of one case of osteoradio- necrosis of both pubic rami in an osteoporotic patient.

The Swedish Experience

Borghede et a F in Goteberg, Sweden, treated 50 patients with disease stages Tlb to T3b between July 1988 and June 1994. Tumors were classified according to the World Health Organization (WHO) classification system and included 14 grade 1, 13 grade 2, and 6 grade 3 tumors. Pretreatment PSA values were as follows: 5 patients, 0 to 4 ng/ mL; 25 patients, 5 to 10 ng/mL; 12 patients, 11 to 20 ng/mL; and 8 patients, greater than 20 ng/mL. With a mean follow-up of 45 months, the reported clinical and biopsy-verified overall local control rate was 96% (48 of 50 patients). For disease stages T1 and T2, the local control rate was 97% (37 of 38 patients), and for stage T3 disease it was 92% (11 of 12 patients). Eighty-four percent of all patients (42 of 50) had PSA values of less than 1.0 ng/mL. Acute dysuria occurred in 4 of the patients (ti%), and chronic dysuria occurred in 2 of the patients (4%). chronic macroscopic hematuria occurred in one patient (2%). The inci- dence of RTOG acute grade 3 urinary frequency occurred in 4 patients YO), and 1 patient (2%) experienced chronic urinary frequency. No urethral strictures or incontinence were seen. Chronic GI bleeding was


seen in one patient (2%), and this was self-limited. No chronic diarrhea or fecal incontinence was seen. In addition, no grade 3 or 4 toxicity was seen. Sexual function was preserved in 88% of the patients.

The California Endocurietherapy Cancer Center (CET) Experience

The group at CET in Oakland, Califomia,22 treated 353 patients between September 1991 and January 1998. Disease stages treated ranged from Tlb to T3c, and Gleason scores ranged from 2 to 9. With a median follow-up of 36 months, the results of the first 110 patients showed that 85% of the patients had a PSA value of less than 1.5 ng/ mL. Chronic urinary incontinence was seen in 4 patients (4%). Three of these patients had preradiation TURPS. One patient (1%) had persistent chronic rectal bleeding which resolved with conservative measures. Sex- ual potency was preserved in 75% of all patients.

SUMMARY

Because the HDR brachytherapy treatments are delivered within minutes and on an outpatient basis, HDR brachytherapy is very well tolerated by patients and offers complete radiation safety. Published studies2,11,12,13,16,17,18,U, 24,25 h ave shown high local clinical and biochemi- cal control rates. Chronic complications have been acceptably low. Very low rates of urinary incontinence and high sexual potency rates have been reported. Gastrointestinal morbidity has been minimal.

The development of Ir-192 HDR afterloading brachytherapy and refinements in the dosimetry have ushered in a new era in prostate brachytherapy. The control of the radiation dose and the ability to shape the radiation treatment envelope using a stepping source have allowed a giant step forward in radiation oncology technology. It is now possible to deliver tumoricidal doses of radiation conformally to the prostate while minimizing the dose to the bladder, urethra, and rectum. At present, HDR afterloaded brachytherapy is the optimal whole-organ and tumor-specific conformal radiation therapy for prostate cancer.

References

1. Bagshaw M, Cox RS, Ramback JE: Radiation therapy for localized prostate cancer: Justification by long-term follow-up. Urol Clin North Am 177874302, 1990

2. Borghede G, Hedelin H, Holmang S, et al: Combined treatment with temporary short- term high dose rate iridium 192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma. Radiother 0 x 0 1 44237-294, 1997

3. Borghede G, Hedelin H, Holmang S, et al: Irradiation of localized prostatic carcinoma with a combination of high dose rate iridium 192 brachytherapy with three target definitions and dose levels inside the prostate gland. Radiother Oncol44:245-250,1997

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4. Brindle JS, Martinez AA, Schray M, et al: Pelvic lymphadenectomy and transperineal interstitial implantation of Ir-192 combined with external beam radiotherapy for bulky Stage C prostatic carcinoma. Int J Radiat Oncol Biol Phys 171063-1066, 1989

5. Edmundsen GK Geometry based optimization for stepping source implants. In Marti- nez AA, Orton CG, Mould RF: Brachytherapy HDR and LDR Remote Afterloading State of the Art. 184-192, 1989

6. Edmundsen GK, Rizzo NR, Teahan M, et al: Concurrent treatment planning for outpatient high dose rate prostate template implants. Int J Radiat Oncol Biol Phys 271215-1223, 1993

7. Holm H H Transperineal iodine-125 seed implantation in prostate cancer guided by transperineal ultrasonography. J Urol30283-290, 1983

8. J o s h C A High activity source afterloading in gynecologic cancer and its future prospects. Ulrich Henschke Memorial Lecture, Endocurietherapy/Hyperthermia On-

9. Kahn K, Crawford ED, Johnson E L Transperineal percutaneous iridium 192 implants of the prostate. Int J Radiat Oncol Biol Phys 9:1391-1395, 1983

10. Kahn K, Thompson W, Bush S, et al: Transperineal percutaneous iridium-192 interstitial template implants of the prostate: Results and complications in 321 patients. Int J Radiat Oncol Biol Phys 22:935-939, 1992

11. Kovacs G, Wirth B, Bertermann H, et a1 Prostate preservation by combined external beam and HDR brachytherapy in nodal negative prostate cancer patients: An interme- diate analysis after ten years experience [abstract]. Int J Radiat Oncol Biol Phys 36(suppl):198, 1996

12. Kovacs G, Galalae R, Loch T: HDR brachytherapy for prostate cancer: German Experi- ence [abstract]. In Ninth International Brachytherapy Conference and Third National Conference Towards the Millenium, Palm Springs, September 3-6, 1997, pp 84-85

13. Kovacs G, Galalae R, Loch T Complications of brachytherapy of carcinoma of the prostate: HDR brachytherapy [abstract]. In Ninth International Brachytherapy Confer- ence and Third National Conference Towards the Millennium, Palm Springs, Septem- ber 3 4 , 1997, pp 89-90

14. Landis SH, Murray T, Bolden S, et al: Cancer Statistics 1998. CA Cancer J Clin 486-29, 1998

15. Martinez A, Orton C, Mould R Brachytherapy HDR and LDR. In Proceedings of Brachytherapy Remote Afterloading; State of the Art Meeting, May 4-6, Dearborn, Michigan, 1989, pp 121-137

16. Martinez A, Gonzalez J, Stromberg J: Conformal prostate brachytherapy: Initial experience of a Phase 1/11 dose escalation trial. Int J Radiat Biol Phys 33:1019-1027, 1995

17. Mate T, Kovacs G, Martinez A: High dose rate brachytherapy of the prostate. In Nag S (ed): High Dose Rate Brachytherapy: A Textbook. Armonk, NY, Futura Publishers,

18. Mate T, Gottesman J, Hatton J, et al: High dose rate afterloading iridium-192 prostate brachytherapy: Feasibility report. Int J Radiat Oncol Biol Phys 41:525-533, 1998

19. Nag S, Beyer D, Friedland J, et al: American Brachytherapy Society Recommendations for Transperineal Permanent Brachytherapy of Prostate Cancer, in press

20. Perez C, Pilspich M, Zinuska F Tumor control in definitive irradiation of localized carcinoma of the prostate. Int J Radiat Oncol Biol Phys 12523-532, 1986

21. Puthawala A, Syed A, Tansey L: Temporary iridium-192 implant in the management of carcinoma of the prostate: An analysis of treatment results and complications in the first one hundred patients. Endocurietherapy/Hyperthermia Oncology 1:2534, 1985

22. Rodriguez R, Demanes DJ: HDR brachytherapy: Ultimate in conformal radiotherapy for treatment of prostate cancer. In Zamboglou N (ed): New Developments in Intersti- tial Remote Controlled Brachytherapy. Munich, W. Zuckschwerd und Verlag, 1997,

23. Stromberg J, Martinez A, Benson R Improved local control and survival for surgically staged patients with locally advanced prostate cancer treated with up-front low dose rate indium-192 prostate implantation and external beam irradiation. Int J Radiat Oncol Biol Phys 28:67-75, 1993

24. Stromberg J, Martinez A, Gonzalez J: Ultrasound-guided high dose rate conformal

cology 5~69-81, 1989

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brachytherapy boost in prostate cancer: Treatment description and preliminary results of a phase 1/11 clinical trial. Int J Radiat Oncol Biol Phys 33:161-171, 1995

25. Stromberg J, Martinez A, Honvitz E, et al: Conformal high dose rate iridium-192 boost brachytherapy in localized advanced prostate cancer: Superior prostate specific antigen response compared to external beam. In Ninth International Brachytherapy Conference, Palm Springs, September 3-6, 1997, p 75

26. Syed A, Puthawala A, Austin P: Temporary iridium-192 implant in the management of carcinoma of the prostate. Cancer 69:2515-2524, 1992

27. Whitmore W, Hilaris B, Grabstald H Retropubic implantation of iodine-125 in the treatment of prostate carcinoma. J Urol 108:918-920,1972

Address reprint requests to Rodney R. Rodriguez, PhD, MD

Medical Director California Endocurietherapy Cancer Center

3012 Summit St, Suite 2675 Oakland, CA 94609

e-mail [email protected]

high dose rate brachytherapy in the treatment of prostate cancer

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