Brachytherapy: Current Status and Future Strategies — Can High Dose Rate Replace Low Dose Rate and External Beam Radiotherapy?

Brachytherapy delivers the most conformal high dose radiotherapy possible to the prostate, using either a low dose rate (LDR) or high dose rate (HDR) technique. It may be used either alone as monotherapy or in combination with external beam radiotherapy (EBRT) as a local boost. Comparative efficacy studies, including one randomised controlled trial, consistently show higher cancer control rates when brachytherapy is used compared with EBRT alone, with even some evidence of improvement in survival. There are now extensive mature data supporting the use of LDR as monotherapy for patients with low-risk and selected intermediate-risk disease, with most series reporting long-term disease control rates of over 90% after high-quality implants. HDR is most commonly combined with EBRT to treat intermediate- and high-risk disease, with disease control rates of over 90% reported. The low alpha/beta ratio of prostate cancer combined and the ability to optimally sculpt dose distribution provides the biological and dosimetric rationale for HDR. HDR enables more consistent implant quality than LDR, with evidence of lower acute and late toxicity. Many dose and fractionation schedules of HDR in combination with EBRT have been investigated, but a single fraction of 10–15 Gy is commonly combined with EBRT to a dose of 40–50 Gy to treat intermediate- and high-risk disease. High disease control rates are also reported with HDR as monotherapy, particularly in patients with low- and intermediate-risk disease. Although older series have delivered four to six fractions of HDR, there is growing evidence to support the delivery of HDR in three or even two fractions. Single-fraction HDR monotherapy is now being investigated and if early data are confirmed with longer follow-up, may well become the treatment of choice for many men with localised prostate cancer.     

Brachytherapy boost techniques for locally advanced prostate cancer

Brachytherapy boosts in combination with external-beam radiation therapy allow a highly conformal dose of radiation to be delivered to the prostate in a safe, efficient manner. Several types of brachytherapy boost techniques are used currently. Techniques based on transrectal ultrasound (TRUS) guidance clearly provide the most accurate method of radioactive source placement with reduced toxicity. Temporary implants employing remote afterloading systems with high-dose-rate (HDR) brachytherapy offer the added advantage of further optimizing dose distribution after needle placement. Novel brachytherapy programs using intraoperative real-time dosimetric analyses provide additional options for performing truly conformal dose escalation. Results with these newer boost techniques appear to be as good as or better than other forms of therapy in comparably staged patients. Until standardized methods of reporting treatment data are uniformly applied and longer follow-up is obtained with other treatment modalities, brachytherapy boosts combined with external-beam radiation should be considered an acceptable treatment option for patients with locally advanced prostate cancer. The challenge for the future will be to determine which treatment approach is optimal given certain critical pretreatment prognostic factors. In addition, the role of adjuvant androgen deprivation in controlling this malignancy will be critical and awaits the results of several recently initiated or completed randomized trials.     

Rectal bleeding after high-dose-rate brachytherapy combined with hypofractionated external-beam radiotherapy for localized prostate cancer: impact of rectal dose in high-dose-rate brachytherapy on occurrence of grade 2 or worse rectal bleeding

PURPOSE: To evaluate the incidence of Grade 2 or worse rectal bleeding after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiotherapy (EBRT), with special emphasis on the relationship between the incidence of rectal bleeding and the rectal dose from HDR brachytherapy. METHODS AND MATERIALS: The records of 100 patients who were treated by HDR brachytherapy combined with EBRT for > or =12 months were analyzed. The fractionation schema for HDR brachytherapy was prospectively changed, and the total radiation dose for EBRT was fixed at 51 Gy. The distribution of the fractionation schema used in the patients was as follows: 5 Gy x 5 in 13 patients; 7 Gy x 3 in 19 patients; and 9 Gy x 2 in 68 patients. RESULTS: Ten patients (10%) developed Grade 2 or worse rectal bleeding. Regarding the correlation with dosimetric factors, no significant differences were found in the average percentage of the entire rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose from EBRT between those with bleeding and those without. The average percentage of the entire rectal volume receiving 10%, 30%, 50%, 80%, and 90% of the prescribed radiation dose from HDR brachytherapy in those who developed rectal bleeding was 77.9%, 28.6%, 9.0%, 1.5%, and 0.3%, respectively, and was 69.2%, 22.2%, 6.6%, 0.9%, and 0.4%, respectively, in those without bleeding. The differences in the percentages of the entire rectal volume receiving 10%, 30%, and 50% between those with and without bleeding were statistically significant. CONCLUSIONS: The rectal dose from HDR brachytherapy for patients with prostate cancer may have a significant impact on the incidence of Grade 2 or worse rectal bleeding.     

Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

PURPOSE: Several investigations have revealed that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy. METHODS AND MATERIALS: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the alpha/beta ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on computed tomography images. The number of patients in each fractionation group was as follows: 13 in the 5-Gy group; 19 in the 7-Gy group, and 38 in the 9-Gy group. The tumor stage was T1 in 10 patients, T2 in 36 patients, and T3 in 24 patients. The Gleason score was 2-6 in 11 patients, 7 in 34 patients, and 8-10 in 25 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 14 months (range 3-42 months). The toxicities were graded based on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. RESULTS: The main symptoms of acute GU toxicity were dysuria and increase in urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 39 patients (56%), and Grade 2-4, 31 patients (44%). One patient who developed acute urinary obstruction was classified as having Grade 4 toxicity. Comparison of the distribution of the grade of acute GU toxicity among the different fractionation groups revealed no statistically significant differences among the groups. The urethral dose in HDR brachytherapy was evaluated using the following DVH parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. The V30-110 values in the patients with Grade 2-4 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. On the other hand, there were no significant differences in the V120-150 values between patients with Grade 0-1 and Grade 2-4 toxicity. Regarding the influence of the number of needles implanted for the radiation therapy, patients with 11 needles or less showed a significantly higher incidence of Grade 2-4 acute GU toxicity compared with those with 12 needles or more (p < 0.05). CONCLUSIONS: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer when considered from the viewpoint of acute toxicity. Increase in the fraction dose or reduction in the number of fractions in HDR brachytherapy did not affect the severity of acute GU toxicity, and the volume of urethra receiving an equal or lower radiation dose than the prescribed dose was more closely associated with the grade severity of acute GU toxicity than that receiving a higher than the prescribed dose.     

3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer.

PURPOSE: To evaluate treatment outcome of 3D conformal high dose rate (HDR) brachytherapy and external beam irradiation (EBRT) combined with temporary androgen deprivation for patients with localized prostate cancer. PATIENTS AND METHODS: Between January 1997 and September 1999 we treated 102 patients with stage T1-3 N0 M0 prostate cancer. Stage T1-2 was found in 71, T3 in 31 patients. Median pretreatment PSA level was 15.3 ng/ml. After ultrasound-guided transrectal implantation of four afterloading needles, CT based 3D brachytherapy planning was performed. All patients received four HDR implants using a reference dose per implant of 5 or 7Gy. Time between each implant was 14 days. After brachytherapy EBRT followed up to 39.6 or 45.0 Gy. All patients received temporary androgen deprivation, starting 2-19 months before brachytherapy, ending 3 months after EBRT. RESULTS: Median follow-up was 2.6 years (range 2.0-4.1 years). Actuarial biochemical control rate was 87% at 2 years and 82% at 3 years. In 14 patients we noted biochemical failure, in five patients clinical failure. Overall survival was 90%, disease specific survival 98.0% at 3 years. Acute grade 3 toxicity occurred in 4%, late grade 3 toxicity in 5%. One patient developed a prostatourethral-rectal fistula as late grade 4 toxicity. The conformal quality of 300 HDR implants was analyzed using dose volume histograms. CONCLUSIONS: 3D conformal HDR brachytherapy and EBRT combined with temporary androgen deprivation is an effective treatment modality for prostate cancer with minimal associated toxicity and encouraging biochemical control rates after a median follow-up of 2.6 years.     

Current results of brachytherapy for soft tissue sarcoma

Perioperative brachytherapy results in a better local control rate than surgery alone for extremity soft tissue sarcoma. Brachytherapy enables the delivery of a high radiation dose to a limited volume of tissue, allows the reduction of radiation treatment time, enables direct visualization of the tumor bed and surrounding critical structures, and costs less than external beam radiotherapy. The literature seems to regard the effectiveness of brachytherapy as comparable to that of external beam radiotherapy, and the side effect profile is acceptable. Traditional low-dose-rate brachytherapy methods require extended periods of patient isolation, but recent technologic advances may obviate this necessity. Newer high-dose-rate (HDR) brachytherapy delivery methods allow for the fractionation of radiation delivery and outpatient treatment in some cases. Furthermore, with HDR brachytherapy, the radiation dose distribution can be tailored around critical anatomic structures. Although the application of HDR brachytherapy to soft tissue sarcoma is relatively new, it seems to result in a satisfactory local control rate and may replace traditional low-dose-rate techniques.     

High dose rate brachytherapy in the treatment of prostate cancer.

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, 22, 24, 25 have shown high local clinical and biochemical 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.     

Needle displacement during HDR brachytherapy in the treatment of prostate cancer

Purpose: We used clinical patient data to examine implant displacement between high dose rate (HDR) brachytherapy fractions for prostate cancer to determine its impact on treatment delivery.

Materials and Methods: We analyzed the verification films taken prior to each fraction for 96 consecutive patients treated with HDR brachytherapy boosts as part of their radiation therapy for definitive treatment of organ-confined prostate cancer at our institution. Patients were treated with 18–24 Gy in 4 fractions of HDR delivered in 40 hours followed by 36–39.6 Gy external beam radiation to the prostate. We determined the mean and maximum displacement distances of marker seeds placed in the prostate and of the implanted needles between HDR fractions.

Results: Mean and maximum displacement distances between fractions were documented up to 7.6 mm and 28.5 mm, respectively, for the implant needles and 3.6 mm and 11.4 mm, respectively, for the gold marker seeds. All displacement of implant needles occurred in the caudal direction. At least 1 cm caudal displacement of needles occurred prior to 15.5% all fractions. Manual adjustment of needles was required prior to 15% of fractions, and adjustment of the CLP only was required in 24%. Most of the displacement for both the marker seeds and needles occurred between the first and second fractions.

Conclusions: There is significant caudal displacement of interstitial implant needles between HDR fractions in our prostate cancer patients. Obtaining verification films and making adjustments in the treatment volume prior to each fraction is necesary to avoid significant inaccuracies in treatment delivery.     

High dose rate brachytherapy for prostate cancer: Standard of care and future direction

High dose rate brachytherapy is a highly conformal method of radiation dose escalation for prostate cancer and one of several treatment options for men with localised disease. The large doses per fraction exploit the low alpha/beta ratio of prostate cancer cells so that biological radiation dose delivered is substantially greater than that achieved with conventional external beam delivery. This review article presents contemporary data on the rationale for high dose rate brachytherapy including treatment technique and future directions.     

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.     

High dose rate interstitial brachytherapy in soft tissue sarcoma: technical aspects and results.

BACKGROUND: Radiation is essential for function preservation in the management of soft tissue sarcoma (STS). One of the advantages of brachytherapy is that it allows for specific localization of radiation dose to the tumor bed. We examined the results of our clinical experiences with immediate postoperative high dose rate (HDR) brachytherapy and external beam radiation treatment (EBRT) for STS. METHODS: A total of 17 patients (11 primary and six recurrent) between 1995 and 1999 were included in this review. The inclusion criteria for HDR and EBRT were as follows: (1) high-grade tumor, (2) low-grade tumor of > or = 10 cm, (3) recurrent tumor, (4) tumor abutting or invading critical structures and (5) positive margin. The catheters (six French) were placed parallel to the long axis of the tumor with a 1-1.5 cm spacing in between. If necessary, muscle or gel-foam was placed over the critical structures to maintain a minimum space of 0.5 cm from the catheters. On postoperative day 6, patients received HDR (2-3 Gy/fraction x6, twice daily). Three weeks later, patients received EBRT (total 36-60 Gy). The follow-up duration was between 13 and 60 months (median 31 months). RESULTS: There was no local failure within the radiation field in any of the patients. One patient required wound revision for delayed healing after brachytherapy. During EBRT, most patients experienced only mild erythema (grade 1 or 2 skin reaction). In long-term follow-up, there were no patients with neuropathy or significant fibrosis. CONCLUSIONS: Our results suggest that immediate postoperative HDR with a total dose of 12-18 Gy over 3 days is an effective treatment combined with EBRT in the management of STS.     

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.     

Technology Insight: Combined external-beam radiation therapy and brachytherapy in the management of prostate cancer

External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity.     

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

PURPOSE: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. METHODS AND MATERIALS: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. RESULTS: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. CONCLUSION: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.     

Patient-reported Outcomes and Health-related Quality of Life in Prostate Cancer Treated with a Single Fraction of High Dose Rate Brachytherapy Combined with Hypofractionated External Beam Radiotherapy

AimsHigh dose rate (HDR) brachytherapy offers a highly conformal approach to radiotherapy delivery, enabling dose escalation. We report our experience using a combined HDR boost and external beam radiotherapy (EBRT) approach and its associated toxicity and effect on quality of life.Materials and methodsPatients with intermediate- or high-risk prostate cancer were treated with a single fraction HDR boost and EBRT between July 2008 and March 2010. Patient-reported toxicity data were collected at baseline and regular intervals after radiotherapy using International Prostate Symptom Score and Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic scales (LENT-SOMA) questionnaires; health-related quality of life data were captured by the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.ResultsNinety-five patients received an HDR boost of 12.5 Gy followed by EBRT delivered as 37.5 Gy in 15 fractions over 3 weeks. The International Prostate Symptom Score peaked 6 weeks after radiotherapy (median value: 9). The LENT-SOMA bladder/urethra mean baseline score was 0.35 and peaked 6 weeks after radiotherapy (mean = 0.59). Difficulties with urinary flow and frequency were the most common reported symptoms. LENT-SOMA rectum/bowel mean scores at baseline were 0.24 and peaked after 6 months (mean = 0.37). Bowel urgency was the most common reported toxicity. EPIC urinary scores returned to baseline values at 6 months and bowel median scores recovered after 24 months. There were no statistically significant associations between patient or dosimetric parameters and patient-reported outcomes.ConclusionA combined HDR boost and hypofractionated EBRT regimen offers a well-tolerated method of dose escalation with acceptable levels of patient-reported toxicity.     

Acute genitourinary toxicity after high dose rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Second analysis to determine the correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

PURPOSE: We have been treating localized prostate cancer with high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiation therapy (EBRT) at our institution. We recently reported the existence of a correlation between the severity of acute genitourinary (GU) toxicity and the urethral radiation dose in HDR brachytherapy by using different fractionation schema. The purpose of this study was to evaluate the role of the urethral dose in the development of acute GU toxicity more closely than in previous studies. For this purpose, we conducted an analysis of patients who had undergone HDR brachytherapy with a fixed fractionation schema combined with hypofractionated EBRT. METHODS AND MATERIALS: Among the patients with localized prostate cancer who were treated by 192-iridium HDR brachytherapy combined with hypofractionated EBRT at Gunma University Hospital between August 2000 and November 2004, we analyzed 67 patients who were treated by HDR brachytherapy with the fractionation schema of 9 Gy x two times combined with hypofractionated EBRT. Hypofractionated EBRT was administered at a fraction dose of 3 Gy three times weekly, and a total dose of 51 Gy was delivered to the prostate gland and seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography-guided HDR brachytherapy. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on computed tomography images. The tumor stage was T1c in 13 patients, T2 in 31 patients, and T3 in 23 patients. The Gleason score was 2-6 in 12 patients, 7 in 34 patients, and 8-10 in 21 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 11 months (range 3-24 months). The toxicities were graded based on the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity criteria. RESULTS: The main symptoms of acute GU toxicity were dysuria and increase in the urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 42 patients (63%); Grade 2-3, 25 patients (37%). The urethral dose in HDR brachytherapy was determined using the following dose-volume histogram (DVH) parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. In addition, the D5 (dose covering 5% of the urethral volume), D10, D20, and D50 of the urethra were also estimated. The V30-V150 values in the patients with Grade 2-3 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. The D10 and D20, but not D5 and D50, values were also significantly higher in the patients with Grade 2-3 acute GU toxicity than in those with Grade 0-1 toxicity. Regarding the influence of the number of needles implanted, there was no correlation between the number of needles implanted and the severity of acute GU toxicity or the V30-V150 values and D5-D50 values. CONCLUSIONS: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer, when considered from the viewpoint of acute toxicity. However, because the urethral dose was closely associated with the grade of severity of the acute GU toxicity, the urethral dose in HDR brachytherapy must be kept low to reduce the severity of acute GU toxicity.     

High-dose irradiation for prostate cancer via a high-dose-rate brachytherapy boost: results of a phase I to II study

OBJECTIVE: To evaluate outcomes of intermediate- and high-risk prostate cancer patients on a prospective dose-escalation study of pelvic external-beam radiation therapy (EBRT) combined with high-dose-rate (HDR) brachytherapy boost. METHODS: From November 1991 to April 2003, 197 patients were treated for intermediate- and high-risk disease features. All patients had prostate-specific antigen>10 ng/ml, Gleason score>or=7, or clinical stage>or=T2b, and all received pelvic EBRT (46 Gy) while receiving either two or three HDR boost treatments. HDR dose fractionation increased progressively and was divided into two dose levels. The mean prostate biologic equivalency dose was 88.2 Gy for the low-dose group and 116.8 Gy for the high-dose group (alpha/beta=1.2). Clinical failure was either local failure or distant metastasis; clinical event-free survival (cEFS) was defined as patients who lived free of clinical failure. RESULTS: Median follow-up was 4.9 years. The 5-year rates were as follows: biologic failure (BF), 18.6%, clinical failure (CF), 9.8%, cEFS 84.8%, cause-specific survival (CSS), 98.3%, and overall survival (OS), 92.9%. Five-year biochemical failure (68.7% vs. 86%, p<0.001), CF (6.1% vs. 15.6%, p=0.04), cEFS (75.5% vs. 91.7%, p=0.003), CSS (95.4% vs. 100%, p=0.02), and OS (86.2% vs. 97.8%, p=0.002) were significantly better for the high-dose group. Multivariate analysis showed that high-dose group (p=0.01, HR 0.35) and Gleason score (p=0.01, HR 1.84) were significant variables for cEFS. Multivariate analysis showed that high-dose group (p=0.01, HR 0.14) and age (p=0.03, HR 1.09 per year) were significant variables for overall survival. CONCLUSION: There is a strong dose-response relationship for intermediate- to high-risk prostate cancer patients. Improved locoregional control with higher radiation doses alone can significantly decrease biochemical and clinical failures.     

The use of magnetic resonance imaging for image-guided brachytherapy

Progress has been made in the delivery of brachytherapy, from low-dose rate (LDR) to high-dose rate (HDR) treatments, allowing for dose optimisation, conformal treatments, improved radiation protection, and improved accuracy and efficiency. Image-guided brachytherapy, incorporating spatial and temporal changes, is now possible with advanced imaging and treatment technology. This report reviews the evidence for the benefits of image-guided brachytherapy using magnetic resonance imaging (MRI), mainly for cervix and prostate cancer, but also possibilities for other tumour sites. It also emphasises the need for a dedicated MRI unit for brachytherapy.