Salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy

PURPOSE: To determine the toxicity and clinical outcome of salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy. METHODS AND MATERIALS: Twenty-one patients underwent (103)Pd salvage brachytherapy (median minimum peripheral dose, 90Gy) after local failure after external beam radiation (median dose, 66.6Gy) from 1/21/1998 to 4/5/2005. The median age was 72 years. Six patients had prior transurethral resection of the prostate. The median Gleason score was 7 and the median preimplant prostate-specific antigen was 3.8. Twelve patients received concurrent androgen ablation with prostate brachytherapy. Biochemical failure was defined as three consecutive rises in prostate-specific antigen scored at the call date, initiation of hormone therapy, or clinical failure. Toxicity was defined according to the National Cancer Institute common toxicity criteria and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. RESULTS: With a median followup of 36 months, the actuarial 3-year and 5-year overall survival rates were 81% and 81%, and the biochemical failure-free survival rates were 94% and 38%, respectively. There was no significant difference in biochemical failure-free survival (p=0.98) and overall survival (p=0.13) for patients who had androgen ablation. Four patients developed biochemical failure and 1 patient developed distant metastasis at 59 months from treatment. Four patients had Grade 2 genitourinary adverse events, 2 patients had Grade 1 genitourinary adverse events, and 1 patient had a Grade 2 gastrointestinal adverse event. There were no Grade 3 or higher adverse events. All three deaths were secondary to other medical comorbidities. CONCLUSIONS: Salvage prostate brachytherapy after external beam radiation failure can be safely performed with acceptable biochemical control. This treatment option should be considered for patients who have prolonged life expectancy after localized external beam radiation failure.     

Feasibility and preliminary outcome of salvage combined HDR brachytherapy and external beam radiotherapy (EBRT) for local recurrences after radical prostatectomy

PURPOSE: Feasibility of combined fractionated intensity modulated brachytherapy (IMBT) and external beam radiotherapy (EBRT) as well as the effect of local dose escalation was investigated in a non-randomized retrospective observation trial for histologically-proven macroscopic local recurrences of prostate cancer after radical prostatectomy. METHODS AND MATERIALS: Thirty-five patients with transrectal ultrasound (TRUS) detectable tumors were treated. Applied dose per IMBT fraction was 15 Gy, prescribed on the target (TRUS visible tumor) surface. For the first 21 patients, two fractions of IMBT were delivered in 2 weeks interval, complementary to 30 Gy EBRT to the small pelvis. Further, as second step of dose escalation, 14 patients were treated with 2 x 15 Gy IMBT combined with 40 Gy EBRT. The total treatment time was 4 and 5 weeks, respectively. RESULTS: PSA was decreased in 34 out of 35 patients post-therapeutically. After a mean follow-up of 27 months, 32 out of 35 patients are alive. However, in 67% of the patients, we observed postimplant PSA elevation with or without detectable local and/or systemic progress. The mean duration of biochemical non-evidence of disease (bNED) after radiation was 12 months for all patients (31% in the 30 Gy group and 42% in the 40 Gy group). No RTOG/EORTC grade III or IV side effects were registered during/after radiotherapy. CONCLUSION: Combined EBRT and IMBT-boost of TRUS detectable recurrences of prostate cancer after radical prostatectomy seems to be a feasible method of salvage treatment. These early results need to be confirmed by further prospective randomized trials and by longer follow-up in all dose groups.     

Prostate preservation by combined external beam and HDR brachytherapy in nodal negative prostate cancer

Purpose

The combined external beam- and high-dose rate brachytherapy (HDR-BT) of localized prostate cancer was introduced at Kiel University in 1986. The aim of this intermediate analysis was to judge the Kiel method of localized prostate cancer radiation treatment after ten years experience.

Patients and Methods

In the past ten years 174 patients with histological proven localized prostate cancer were subjected to combined tele-/HDR-brachytherapy. Local staging in all of the cases by transrectal ultrasound, nodal staging in the majority of the cases by CT or MRI. Average age of the patients was 68.2 years (44–84). According to AJCC/UICC staging T1B, T2, T3 was found in 2, 113 and 59 cases, respectively. Highly differentiated tumors (G1) were found in 27, moderately differentited (G2) in 87, poorly differentiated (G3) in 60 cases. The mean follow-up was 47.1 months with the median of 51.7 months. Total prescribed dose 50 Gy on the small pelvis and 70 Gy on the prostate capsule due to the integration of two, 15 Gy each, HDR-brachytherapy fractions in 6 weeks.

Results

Ten patients died of prostate cancer and 18 of intercurrent diseases resulting in a 5 years overall survival rate of 83% and tumor specific survival rate of 94%. Twenty-one patients showed a clinical progression, of these 14 systemic, 5 local and 2 both systemic and local. Additional 16 patients had PSA elevation only. The 5-years biochemical and/or clinical progression-free survival in the cohort was 79% and 73% for the T3 tumors. Side effects were 27 cases of proctitis/colitis and 20 cases of dysuria/cystitis.

Conclusion

The integrated HDR-BT combined with external beam radiation treatment is a method with excellent tumor control rates at five years superior to those of external beam treatment alone or external beam combined with iodine-125 implants. This form of radiotherapy would appear to be particularly well-suited to treatment of advanced localized (T3) tumors.

     

Locally recurrent breast cancer: pulse dose rate brachytherapy for repeat irradiation following lumpectomy-- a second chance to preserve the breast

PURPOSE: To perform and assess the effectiveness of local excision of recurrent tumor followed by postoperative pulse dose rate (PDR) brachytherapy. MATERIALS AND METHODS: From 1994 to 2000, 17 patients who had small recurrent breast carcinomas after initially undergoing breast-conserving therapy (BCT), which included postoperative radiation therapy, were treated with local tumor excision and PDR brachytherapy. Recurrences occurred at a median time of 50 months (range, 11-208 months) after primary treatment. Eight patients underwent a combination of PDR brachytherapy (total dose range, 12.5-28.0 Gy) and external-beam radiation therapy (EBT) (total dose range, 12-30 Gy). Nine patients underwent radiation therapy with 40.2-50.0-Gy PDR brachytherapy only. The prescribed radiation dose was 0.5-1.0 Gy per pulse. Patients were examined for local tumor control and treatment-related side effects. RESULTS: Twelve of 17 patients had no local tumor at a median follow-up time of 59 months (range, 20-84 months); two of these patients showed signs of having distant disease. One patient died after a cerebral stroke without evidence of tumor. Four women treated with combined EBT and brachytherapy had secondary local tumor recurrences 4, 8, 8, and 11 months after therapy and had to undergo mastectomy. Despite having undergone radiation therapy previously, patients had side effects limited to moderate (grade 1-2) fibrosis. CONCLUSION: Local tumor excision combined with PDR brachytherapy for small local-regional tumor recurrences after primary BCT is feasible and well tolerated and might obviate mastectomy. Preliminary experiences are encouraging. Further studies are required for appropriate patient selection.     

Combined External Beam and Intraluminal Radiotherapy for Irresectable Klatskin Tumors

BACKGROUND: In most cases of proximal cholangiocarcinoma, curative surgery is not possible. Radiotherapy can be used for palliative treatment. We report our experience with combined external beam and intraluminal radiotherapy of advanced Klatskin's tumors. PATIENTS AND METHODS: 30 patients were treated for extrahepatic proximal bile duct cancer. Our schedule consisted of external beam radiotherapy (median dose 30 Gy) and a high-dose-rate brachytherapy boost (median dose 40 Gy) delivered in four of five fractions, which could be applied completely in twelve of our patients. 15 patients in the brachytherapy and nine patients in the non-brachytherapy group received additional low-dose chemotherapy with 5-fluorouracil. RESULTS: The brachytherapy boost dose improved the effect of external beam radiotherapy by increasing survival from a median of 3.9 months in the non-brachytherapy group to 9.1 months in the brachytherapy group. The effect was obvious in patients receiving a brachytherapy dose above 30 Gy, and in those without jaundice at the beginning of radiotherapy (p < 0.05). CONCLUSIONS: The poor prognosis in patients with advanced Klatskin's tumors may be improved by combination therapy, with the role of brachytherapy and chemotherapy still to be defined. Our results suggest that patients without jaundice should be offered brachytherapy, and that a full dose of more than 30 Gy should be applied.     

High-dose-rate brachytherapy combined with long-term hormonal therapy for high-risk prostate cancer: results of a retrospective analysis

Purpose High-dose-rate (HDR) brachytherapy combined with hormonal therapy (HTx), without the addition of external beam radiation therapy (EBRT) for high-risk prostate cancer was evaluated retrospectively. Materials and Methods Between May 1995 and April 2002, 35 patients with prostate cancer [Stage≥T2b (UICC 1997) or tumor grading=3 or prostate-specific antigen (PSA) level≥20 ng/mL] were treated with HDR brachytherapy combined with HTx. Most patients (74%) had two or more of these factors. All patients received Iridium-192 HDR brachytherapy with a total dose of 54 Gy/9 fractions/5 days (48 Gy/8 fractions/5 days for the first 6 cases) in one implant session. The median neoadjuvant HTx [luteinizing hormone-releasing hormone (LH-RH) agonist and antiandrogen] period was 7 months. The median adjuvant HTx (ATH) (LH-RH agonist) period was 40 months, and median follow-up was 57 months (range, 23–117 months). Results The 5-year actuarial biochemical control, local control, and disease-free rates were 62%, 96%, and 76% respectively. No patients experienced local and/or regional relapse without distant progression. The 5-year actuarial cause-specific survival and overall survival rates were 89% and 87%, respectively. The acute and late toxicity were moderate and well tolerated. Conclusion HDR brachytherapy plus long-term HTx is at least as effective as conventional EBRT plus long-term HTx.     

3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Preliminary results.

BACKGROUND: Evaluation of feasibility, tolerance and efficiency for a new 3D interstitial HDR brachytherapy technique combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. PATIENTS AND METHODS: Between January 1997 and August 1998 we treated 35 patients with stage cT1-3 N0 M0 prostate cancer. Thirty-two patients with a follow-up of 12 to 28 months (median: 18 months) were evaluated. After ultrasound-guided transrectal implantation of 4 non-parallel needles, CT based 3D brachytherapy treatment planning ("Offenbach system") was performed. All patients received 4 fractions brachytherapy using a fractional dose of 5 or 7 Gy. Time between each fraction was 14 days. After brachytherapy 3D external irradiation followed up to 39.6 or 45.0 Gy. All patients received androgen deprivation, starting 2 to 19 months before brachytherapy, ending 3 months after 3D external radiotherapy. RESULTS: Posttreatment PSA levels dropped to < 1.5 ng/ml in 29/32 patients (91%). In 25 patients PSA levels were < 0.5 ng/ml, in 4 patients 0.5 to 1.5 ng/ml. In 2 patients we noted biochemical relapse. Transrectal implantation was very well tolerated. Grade 3 acute urinary toxicity occurred in 1 patient. We noted no Grade 2 or higher acute gastrointestinal toxicity. One patient developed a Grade 3 late urinary toxicity. No patient showed late gastrointestinal side effects. All 140 dose-volume histograms for 3D HDR brachytherapy were analyzed. CONCLUSIONS: The new 3D HDR brachytherapy technique, combined with 3D external irradiation and androgen deprivation, is a feasible, so far well-tolerated and effective treatment in the short-time follow-up of median 18 months.     

The feasibility of a second lumpectomy and breast brachytherapy for localized cancer in a breast previously treated with lumpectomy and radiation therapy for breast cancer

PURPOSE: With accumulating evidence supporting partial-breast irradiation, we conducted a Phase I/II study to evaluate the role of a second conservative surgery and brachytherapy for patients presenting with a local recurrence/new primary in a breast who has previously undergone a lumpectomy and external radiation therapy for breast cancer. METHODS AND MATERIALS: Fifteen patients with a localized lesion in the breast have undergone a second lumpectomy and received low-dose-rate brachytherapy on protocol. The first 6 patients received a dose of 30Gy. With no unacceptable acute toxicity observed, the brachytherapy dose was increased to 45Gy. Three patients received adjuvant chemotherapy and 8 patients are on antiestrogen therapy. RESULTS: The median time interval between the primary breast cancer diagnosis and the second cancer event in the ipsilateral breast is 94 months (range, 28-211). With a median followup of 36 months after brachytherapy, the 3-year Kaplan-Meier overall survival, local disease-free survival and mastectomy-free survival are 100% and 89%, respectively. There was no Grade 3/4 fibrosis or necrosis observed. All patients had baseline asymmetry due to the breast volume deficit from the second lumpectomy. With breast asymmetry as a given, the cosmetic result observed in all patients has been good to excellent. CONCLUSIONS: Early results suggest low-complication rates, high rate of local control and freedom from mastectomy. Additional studies are needed to establish whether a second lumpectomy and breast brachytherapy are an acceptable alternative to mastectomy for patients presenting with a localized cancer in a previously irradiated breast.     

High-dose-rate brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience

PurposeTreatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT.Patients and MethodsSix men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound–guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36 Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30 Gy, received 24 Gy in four fractions.ResultsMedian age was 67.5 (56–74) years. At a median followup of 26 (14–60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19 ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3–5 toxicity.ConclusionTransperineal ultrasound–guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.     

Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects

INTRODUCTION: The neurohistological findings in patients treated with targeted beta emitters such as (131)I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a (131)I-labeled monoclonal antibody (mAb) injected into surgically created resection cavities during brain tumor resections. METHODS: Directed tissue samples of the cavity walls were obtained because of suspected tumor recurrence from 28 patients. Samples and clinical follow-up were evaluated on all patients (Group A) based on total radiation dose received and a subset of these (n=18; Group B, proximal therapy subset) who had received external beam therapy within 相似文献   

Secondary bladder cancer during long-term follow-up after iodine-125 permanent seed implantation for localized prostate cancer

IntroductionBrachytherapy for prostate cancer treatment may induce secondary bladder cancer during long-term follow-ups. This study reviews the risk and tumor characteristics of secondary bladder cancer after brachytherapy.MethodsThis single-institution retrospective study included 1162 patients treated with low-dose-rate permanent seed implantation brachytherapy with iodine-125, with or without external beam radiation therapy, for localized prostate cancer. We calculated and compared the rates of secondary bladder cancer among patients treated with brachytherapy and radical prostatectomy (n = 218) before and after a propensity score-matching analysis. Possible risk factors for secondary bladder cancer, such as patient age and external beam radiation therapy administration, were analyzed.ResultsOf 1162 patients with a median follow-up period of 11.4 (range: 0.7–15.5) years, 26 presented with urothelial carcinomas and 1 with adenocarcinoma at a median of 8.9 (range: 2.9–14.0) years after brachytherapy, although the incidence rates of secondary bladder cancer after brachytherapy were not significantly different from those after radical prostatectomy. No significant risk factors for secondary bladder cancer were identified. The initial symptoms of secondary bladder cancer were gross hematuria (74%) and microscopic hematuria with positive urine cytology (15%). Among 26 cases of secondary urothelial carcinoma, 54% were high-grade and 46% were invasive. After brachytherapy, invasive urothelial carcinoma occurred later than noninvasive urothelial carcinoma (p = 0.01).ConclusionsConsidering the aggressive malignancy of secondary bladder cancer, cystoscopy and urine cytology should be performed for further investigation of the causes of gross or microscopic hematuria and rule out secondary bladder cancer in cases followed longer than 3 years after brachytherapy.     

Transperineal Low-Dose Rate Iridium-192 Interstitial Brachytherapy in Cervical Carcinoma Stage IIB

PURPOSE: To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. PATIENTS AND METHODS: 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MV linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. RESULTS: At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival was 48% in patients aged less than 45 years as compared to 80% in patients of more than 45 years (p = 0.009). Dose to the cervical point was a prognostic indicator with 5- and 10-year disease free survival of 47% in patients who received < 35 Gy in comparison to 80% in patients who had > 35 Gy (p = 0.03). There was no difference in local control and survival in patients with minimal and moderate parametrial involvement. Bulky disease (> 4 cm) at presentation and a longer gap between external radiation and brachytherapy showed a trend towards inferior local control. CONCLUSIONS: Interstitial brachytherapy after external beam irradiation in patients with cervical carcinoma Stage IIB results in acceptable local control, survival and complication rates. Increased dose to the cervical disease results in improved local control and survival and should therefore be considered while optimizing brachytherapy treatment plans. Comparison of the results with those of standard intracavitary therapy remains to be proven in a randomized trial.     

High-dose-rate interstitial brachytherapy in recurrent and previously irradiated head and neck cancers--preliminary results

PURPOSE: Although high-dose-rate brachytherapy (HDRBT) offers significant advantages over low dose rate brachytherapy, there are scant data on improved local control (LC) and treatment-related complications in patients with recurrent head and neck (H&N) cancers. We report our preliminary results in patients with recurrent H&N cancers treated with interstitial HDRBT. METHODS AND MATERIALS: Thirty patients with recurrent H&N cancers were treated with HDRBT between September 2003 and October 2005. Seventy-seven percent (23/30) of the patients had either local or regional recurrence in the area of previous external beam radiation therapy. The treatment sites were oral cavity/oropharynx (11/30), neck (10/30), face/nasal cavity (6/30), and parotid bed (3/30). Whereas 18 patients underwent surgical resection followed by HDRBT, 3 patients were treated with combined external beam radiation and HDRBT, and the remaining 9 were treated with HDRBT alone. The dose and fractionation schedules used were 3.4Gy twice per day (b.i.d.) to 34Gy for postoperative cases, 4Gy b.i.d. to 20Gy when combined with 40-50Gy external beam, and 4Gy b.i.d. to 40Gy for definitive treatment. HDRBT was initiated 5 days after catheter placement to allow for tissue healing. RESULTS: With a median followup of 12 months, 6 local recurrences were observed 1-10 months after the procedure. The 2-year LC and overall survival outcomes for the entire group were 71% and 63%, respectively. Patients treated with surgical resection and HDRBT had an improved 2-year LC compared to the patients treated with HDRBT+/-external beam radiation alone (88% vs. 40%, p=0.05). Six Grade II and four Grade III complications were noted in five patients, all observed in the postoperative HDRBT group. CONCLUSION: The preliminary results of HDRBT indicate an acceptable LC and morbidity in recurrent H&N cancers. A planned surgical resection followed by HDRBT is associated with improved tumor control in these high-risk patients. Based on these encouraging results, prospective clinical trials are warranted using HDRBT in recurrent H&N cancers to decrease late toxicity.     

Combined modality treatment with high-dose-rate brachytherapy boost for locally advanced prostate cancer

PURPOSE: This is a retrospective review of our experience using high-dose-rate (HDR) brachytherapy boost for prostate cancer. METHODS AND MATERIALS: During the study period, we recommended external beam radiotherapy (45 Gy) and HDR boost (18 Gy in three fractions) combined with hormonal therapy (HT) for 2 months before and during radiotherapy to patients with at least one of the following risk features: pretreatment prostate-specific antigen>10, Gleason score (GS)>or=7, and clinical T3 disease. Additional HT for 2 years after radiotherapy was recommended for patients with GS>7. To patients whose risk of positive nodes exceeded 15%, we recommended whole pelvic radiotherapy. We administered HDR via single implant, and all fractions were given within 24h. RESULTS: This report is based on our initial 64 patients treated with HDR boost. The median follow-up was 50 months (range 25-68 months). The 4-year estimates of overall and disease-free survival were 98% and 92%, respectively. One patient experienced late grade 4 gastrointestinal toxicity. CONCLUSIONS: HDR brachytherapy is an effective means of delivering conformal prostate radiotherapy, and may be used with whole pelvic radiotherapy and HT.     

Preliminary toxicity and prostate-specific antigen response of a Phase I/II trial of neoadjuvant hormonal therapy, 103Pd brachytherapy, and three-dimensional conformal external beam irradiation in the treatment of locally advanced prostate cancer

PURPOSE: Standard therapies for locally advanced prostate cancer have resulted in suboptimal disease control rates. A Phase I/II trial was designed for patients with positive seminal vesicle biopsies, prostate-specific antigen (PSA) >15 ng/ml, Gleason score > or =8 or clinical classification T2c-T3 to improve local control and to test the tolerance of the prostate to high-dose radiation by using neoadjuvant hormonal therapy, 103Pd brachytherapy, and conformal three-dimensional external beam radiation therapy (EBRT). This article outlines treatment-related morbidity and PSA response to this regimen and analyzes the effect of escalating doses of brachytherapy. METHODS AND MATERIALS: Forth-three patients with T1c-T3 prostate cancer were enrolled in a Phase I/II trial from March 1994 through September 1997. Follow-up ranged from 12 to 64 months (median, 32 months). Pretreatment PSA ranged from 2.1 to 202 ng/ml (median, 16 ng/ml). Seventy-seven percent (33 of 43) of patients had high-grade tumors (score > or =7). Seventy-four percent (32 of 43) had stage > or =T2c. A total of 21 (49%) patients had positive seminal vesicle biopsies. Treatment consisted of hormonal therapy for 3 months with leuprolide and flutamide followed by a 103Pd implant and, 2 months later, 59.4 Gy of three-dimensional EBRT. Hormonal therapy was continued for 9 months. The planned 103Pd dose was escalated from 57 Gy (13 patients) to 77 Gy (13 patients) to 86 Gy (17 patients). RESULTS: The actuarial freedom from PSA failure (PSA>0.5 ng/ml) at 4 years was 74%. There were no significant differences found when analyzing patients by presenting PSA or seminal vesicle status. There was a trend toward improved outcome with higher doses delivered to the prostate via the implant. Patients receiving doses > or =65 Gy (31 patients) had a freedom from PSA failure rate at 4 years of 89.5%, compared with 52.5% for those receiving doses <65 Gy (10 patients; p=0.08). The last PSA values for those patients free from PSA failure were < or =0.1 ng/ml in 25 (69%), >0.1-0.2 ng/ml in 5 (14%), and >0.2-0.5 ng/ml in 6 (17%). The actuarial freedom from developing Grade 2 proctitis was 75% at 4 years. There was a trend toward increased proctitis with increasing prostate implant doses. Patients with doses < or =70 Gy (n=12) had a 92% freedom from Grade 2 proctitis compared with 67.5% for those with doses delivered to 90% of the gland from a dose-volume histogram of >70 Gy (n=29) (p=0.15). There were no cases of Grade 3 or 4 proctitis. The 3-year actuarial preservation of sexual potency rate was 43%. CONCLUSIONS: The preliminary results from this regimen show an improvement in PSA control for this group of locally advanced prostate cancer patients over more standard therapies. To maximize control while minimizing toxicity, doses of 65-70 Gy of 103Pd should be used when 59.4 Gy of three-dimensional EBRT is delivered. Longer follow-up will be needed to further substantiate these findings.     

Favorable clinical outcomes of three-dimensional computer-optimized high-dose-rate prostate brachytherapy in the management of localized prostate cancer

PURPOSE: To report PSA relapse-free survival and toxicity outcomes of prostate cancer patients who have undergone three-dimensional computer-optimized high-dose-rate (HDR) brachytherapy with external beam radiotherapy as definitive treatment. METHODS AND MATERIALS: One hundred five patients consecutively treated between 1998 and 2004 are reported. All patients were treated with HDR boost with lr 192 (5.5-7.0 Gy), based upon postimplant CT three-dimensional treatment planning using an in-house treatment plan optimization algorithm. Three-dimensional conformal external beam radiotherapy (45-50.4 Gy) was also administered 3 weeks after the HDR procedure. Toxicity was measured using National Cancer Institutes Common Toxicity Criteria and International Prostate Symptom Score indices. RESULTS: With a median followup of 44 months (8-79 months), the 5-year PSA relapse-free survival outcomes for low, intermediate and high-risk patients were 100%, 98%, and 92%, respectively, Median urinary toxicity, and 93% of patients denied rectal problems at the time of last followup. Erectile dysfunction was noted in 47% patients at the time of last followup, but overall 80% were able to achieve vaginal penetration when those who responded to sildenafil were included. CONCLUSION: Computer-optimized three-dimensional HDR prostate brachytherapy provides excellent disease control for even high risk localized prostate cancer. Significant toxicity has been minimal.     

Effect and toxicity of endoluminal high-dose-rate (HDR) brachytherapy in centrally located tumors of the upper respiratory tract.

AIM: To assess effect and toxicity of high-dose-rate afterloading (HDR) alone or in combination with external beam radiotherapy (EBRT) in centrally located tumors of the upper respiratory tract. PATIENTS AND METHODS: From 1987 to 1996, 55 patients were treated. Twenty-one patients (group A1: 17 non-small-cell lung cancer [NSCLC], A2: 4 metastases from other malignancies) were treated using HDR alone due to a relapse after external beam irradiation. In 34 previously untreated and inoperable patients (group B1: 27 NSCLC, B2: 7 metastases from other malignancies) HDR was given as a boost after EBRT (30 to 60 Gy, median 50). HDR was carried out with a 192Ir source (370 GBq). The brachytherapy dose (group A: 5 to 27 Gy, median 20; B: 10 to 20 Gy, median 15) was prescribed to 1 cm distance from the source axis. A distanciable applicator was used in 39/55 patients. RESULTS: In group A1, a response rate (CR, PR) of 53% (group B1: 77%) was reached. The median survival (Kaplan-Meier) was 5 months in group A1 (B1: 20 months). The 1-, 3- and 5-year local progression free survival rates (Kaplan-Meier) were 66% (15%), 52% (0%), and 37% (0%) in group B1 (group A1). Prognostic favorable factors in group B1 were a tumor diameter < 20 mm, the lack of radiological mediastinal involvement, a complete remission, and a Karnofsky performance status > 70. Grade-1 or 2 toxicity (RTOG/EORTC) occurred in 0% in group A and in 6% in group B. We observed no Grade-3 or 4 toxicity. Complications caused by persistent or progressive local disease occurred in 3 patients in group A (fatal hemorrhage, tracheomediastinal fistula, hemoptysis) and in 2 patients in group B (fatal hemorrhage, hemoptysis). CONCLUSIONS: HDR brachytherapy is an effective treatment with moderate side effects. In combination with external beam irradiation long-term remissions can be reached in one third of the patients.     

Interstitial High-Dose-Rate Brachytherapy in the Treatment of Base of Tongue Carcinoma

BACKGROUND AND PURPOSE:. To date none of the studies examined the feasibility and efficacy of interstitial high-dose-rate (HDR) brachytherapy in the treatment of carcinoma of the tongue base. Therefore the aim of this study was to contribute to this issue. PATIENTS AND METHODS:. Between 1992 and 2000 37 patients (mean age 55 years) with T1-4 and N0-3 carcinoma of the base of tongue were presented. Neck dissection was carried out in twelve cases (32%). 30 patients with advanced stage received brachytherapy boost after 50-66.5 Gy (mean, 60 Gy) locoregional external beam irradiation (EBI) and 7 patients with early stage (T1-2, N0) were managed locally with wide tumor excision and sole brachytherapy. 4 of them underwent neck dissection and the others were subjected to 50 Gy regional EBI. The mean dose of boost and sole brachytherapy was 18 Gy and 28 Gy, respectively. RESULTS:. The median follow-up time for surviving patients was 51 months. The 7 sole brachytherapy patients are living with no evidence of disease. For patients treated with EBI and brachytherapy boost, the 5-year actuarial rate of local, locoregional recurrence-free and overall survival was 60%, 52% and 46%, respectively. For all patients in univariate analysis larger tumor size (T4 vs. T1-3) was significant negative predictor of local (RR: 7.23) and locoregional control (RR: 3.87), but nodal involvement was not. Delayed soft tissue ulceration and osteoradionecrosis occurred in 4 (13%) EBI and brachytherapy treated patients. None of the sole brachytherapy patients experienced severe late radiation toxicity. CONCLUSION:. EBI combined with interstitial HDR brachytherapy boost result in acceptable local tumor control with low incidence of late side effects in patients with advanced disease. Fractionated sole HDR brachytherapy following tumor excision is a feasible treatment option for patients with early stage cancer and gives excellent local results.     

Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma

PURPOSE: To study the efficacy of reirradiation as salvage treatment in patients with locally recurrent nasopharyngeal carcinoma. PATIENTS AND METHODS: Between 1993 and 2000, 20 consecutive patients (twelve males and eight females) with nasopharyngeal cancer, previously irradiated in different Hungarian institutions, were reirradiated for biopsy-proven locally recurrent tumor. Histologically, 85% of the patients had WHO type III, 5% type II, and 10% type I disease. Stages I-IV (AJCC 1997 staging system) were assigned to five (25%), seven (35%), five (25%), and three (15%) patients, respectively; none of them had distant metastases, and only eight (40%) displayed regional dissemination. The median time period between termination of primary treatment and local recurrence was 30 (range, 10-204) months.Brachytherapy was the method most frequently used: in ten cases alone (especially for rT1 tumors), and in eight cases in combination with external beam therapy. Two patients with locally advanced disease underwent external beam therapy only. The median dose in the event of brachytherapy alone was 20 Gy (4 x 5 Gy or 5 x 4 Gy, range, 16-36 Gy), and the dose range for exclusive external irradiation was 30-40 Gy. In cases of combined irradiation, a median 20-Gy brachytherapy (range, 16-40 Gy) was associated with 30-40 Gy of external irradiation. Radiotherapy was supplemented by neck dissection (six patients), nasopharyngectomy (one patient), or chemotherapy (eleven patients). RESULTS: 16 patients were reirradiated once, three twice, and one patient three times, with a median equivalent dose for tumor effect of 36 Gy (mean, 44 Gy; range, 19-117 Gy; the estimated alpha/beta-ratio was 10 Gy). The median equivalent dose of reirradiation for late effect on normal tissue (with an estimated 70% delivery of the tumor dose) amounted to 30 Gy (mean, 37 Gy; range, 13-101 Gy, estimated alpha/beta-ratio 3 Gy). After a median follow-up of 37 (range, 12-72) months, the overall survival was 60% (12/20). Seven of the twelve surviving patients are currently tumor-free. After primary irradiation, xerostomy occurred in all patients as an unavoidable side effect of treatment. Following reirradiation, a severe (grade 3 or higher) late toxicity (CTC criteria, version 2) has been observed in two tumor-free patients (10%) so far (necrosis of soft palate and paresis of glossopharyngeal nerve). CONCLUSION: Retreatment of nasopharyngeal carcinoma with radiotherapy (preferably a combined modality), can result in longterm local control and survival in a substantial proportion of patients, at the price of an acceptable morbidity.