Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients.

PURPOSE: Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. MATERIALS AND METHODS: The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. RESULTS: For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. CONCLUSION: This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.

Phase II trial of concurrent sunitinib and image-guided radiotherapy for oligometastases.

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060.

Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity.

Current research in prostate brachytherapy focuses on five key concepts covered in this review. Transrectal ultrasound-guided prostate brachytherapy assisted by intraoperative treatment planning is the most advanced form of image-guided radiation delivery. Prostate brachytherapy alone for low-risk prostate cancer achieves lower prostate-specific antigen (PSA) nadirs than intensity-modulated radiotherapy (IMRT) or protons while maintaining durable biochemical control in about 90% of patients without late failures seen in surgically treated patients. As an organ-conserving treatment option, seed implant results in a lower rate of erectile dysfunction and urinary incontinence than surgery that has been validated in several recent prospective studies. Combined IMRT and seed implant has emerged as a rational and highly effective approach to radiation-dose escalation for intermediate- and high-risk prostate cancer. Preliminary results suggest that seed implantation may play a role in improving outcomes for historically poor-prognosis locally advanced and recurrent prostate cancers.

Young men have equivalent biochemical outcomes compared with older men after treatment with brachytherapy for prostate cancer.

PURPOSE: To evaluate retrospectively the biochemical outcomes of young men treated with low-dose-rate brachytherapy for prostate cancer. METHODS AND MATERIALS: From 1990 to 2005, 1,665 men with clinically localized prostate cancer were treated with low-dose-rate brachytherapy +/- hormone therapy (HT) +/- external beam radiotherapy and underwent > or = 2 years of follow-up. Patients were stratified on the basis of age: < or = 60 (n = 378) and >60 years (n = 1,287). Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine the association of variables with freedom from biochemical failure (FFbF). RESULTS: Median follow-up was 68 months (range, 24-180) for men < or = 60 years and 66 months (range, 24-200) for men >60. For the entire group, the actuarial 5- and 8-year FFbF rates were 94% and 88%, respectively. Men < or = 60 demonstrated similar 5- and 8-year FFbF (95% and 92%) compared with men >60 (93% and 87%; p = 0.071). A larger percent of young patients presented with low-risk disease; lower clinical stage, Gleason score (GS), and pretreatment PSA values; were treated after 1997; did not receive any HT; and had a high biologic effective dose (BED) of radiation (all ps <0.001). On multivariate analysis, PSA (p = 0.001), GS (p = 0.005), and BED (p < 0.001) were significantly associated with FFbF, but age was not (p = 0.665). CONCLUSION: Young men achieve excellent 5- and 8-year biochemical control rates that are comparable to those of older men after prostate brachytherapy. Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer.

Do high radiation doses in locally advanced prostate cancer patients treated with 103Pd implant plus external beam irradiation cause increased urinary, rectal, and sexual morbidity?

PURPOSE: To investigate the morbidity of higher radiation doses in prostate cancer patients. METHODS AND MATERIALS: Five hundred eighty-five men treated with seed implantation and external beam irradiation were followed a median of 5 years (range, 2-11). Hormonal therapy (HT) of 9 months duration was used in 504 (86.2%) patients. The biologic effective dose (BED) was calculated using an alpha/beta of 2. Urinary incontinence (UI) and symptoms (IPSS) were prospectively collected. Rectal morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) scale. Two BED dose groups of 220 Gy (n=136) were used. Comparisons of means were made by Student's t test, and the associations were tested by chi-square analysis (Pearson). RESULTS: Urinary retention developed in 36 (6.2%) and was not associated with BED or IPSS. Retention occurred more often with prostate volume >50 cc (17%, p=0.001). The median change in urinary symptoms (IPSS) was 1. Sixty-one percent with high BED were more likely to have increased postimplant symptoms compared with 39% with lower BED (p=0.025; odds ratio [OR], 1.107; 95% confidence interval [CI], 1.10-1.21). UI occurred in 25 patients (4.3%) and was only associated with a postimplant transurethral resection of the prostate (TURP) (n=25), 16% vs. 2.3% for no TURP (p=0.001; OR, 8; 95% CI, 2.4-27). Of the 373 patients initially potent, 204 (54.7%) maintained potency. Impotence was only associated with age at implant (p=0.001) and HT (p=0.004). Sixty-two (10.6%) patients had Grade 1-2 and 4 patients had Grade 3-4 (0.7%, 2 ulcers and 2 fistulas) rectal complications. Three of the Grade 3/4 complications occurred with a dose 220 Gy does not seem to increase morbidity.

Local control following permanent prostate brachytherapy: effect of high biologically effective dose on biopsy results and oncologic outcomes.

PURPOSE: To determine factors that influence local control and systemic relapse in patients undergoing permanent prostate brachytherapy (PPB). METHODS AND MATERIALS: A total of 584 patients receiving PPB alone or PPB with external beam radiation therapy (19.5%) agreed to undergo prostate biopsy (PB) at 2 years postimplantion and yearly if results were positive or if the prostate-specific antigen (PSA) level increased. Short-term hormone therapy was used with 280 (47.9%) patients. Radiation doses were converted to biologically effective doses (BED) (using alpha/beta = 2). Comparisons were made by chi-square analysis and linear regression. Survival was determined by the Kaplan-Meier method. RESULTS: The median PSA concentration was 7.1 ng/ml, and the median follow-up period was 7.1 years. PB results were positive for 48/584 (8.2%) patients. Positive biopsy results by BED group were as follows: 22/121 (18.2%) patients received a BED of < or =150 Gy; 15/244 (6.1%) patients received >150 to 200 Gy; and 6/193 (3.1%; p < 0.001) patients received >200 Gy. Significant associations of positive PB results by risk group were low-risk group BED (p = 0.019), intermediate-risk group hormone therapy (p = 0.011) and BED (p = 0.040), and high-risk group BED (p = 0.004). Biochemical freedom from failure rate at 7 years was 82.7%. Biochemical freedom from failure rate by PB result was 84.7% for negative results vs. 59.2% for positive results (p < 0.001). Cox regression analysis revealed significant associations with BED (p = 0.038) and PB results (p = 0.002) in low-risk patients, with BED (p = 0.003) in intermediate-risk patients, and with Gleason score (p = 0.006), PSA level (p < 0.001), and PB result (p = 0.038) in high-risk patients. Fifty-three (9.1%) patients died, of which eight deaths were due to prostate cancer. Cause-specific survival was 99.2% for negative PB results vs. 87.6% for positive PB results (p < 0.001). CONCLUSIONS: Higher radiation doses are required to achieve local control following PPB. A BED of >200 Gy with an alpha/beta ratio of 2 yields 96.9% local control rate. Failure to establish local control impacts survival.

Does neoadjuvant hormonal therapy improve urinary function when given to men with large prostates undergoing prostate brachytherapy?

PURPOSE: We evaluated the effect of neoadjuvant hormonal therapy on urinary function in men with a prostate volume of 50 cc or greater undergoing prostate brachytherapy. MATERIALS AND METHODS: A total of 395 men with 50 cc or greater glands were treated with 3 months of neoadjuvant hormonal therapy (204) or implantation alone (191). Urinary function was assessed by the International Prostate Symptom Score, the urinary retention incidence and subsequent transurethral prostate resection. RESULTS: Median patient age was 67 years and median followup was 6 years. Mean prostate volume in neoadjuvant hormonal therapy cases was 72.9 cc, which decreased to 54.3 cc after 3 months (p <0.001). Mean prostate volume in cases without hormonal therapy was 60.6 cc (p <0.001). Urinary retention occurred in 16 of 191 men (8.4%) without vs 25 of 204 (12.3%) with hormonal therapy (p = 0.207). The median duration of urinary retention was 42 days (range 2 to 243). There were no significant associations of urinary retention with prostate size, prostate or urethral dose, or pre-implantation International Prostate Symptom Score. Of patients without hormonal therapy retention occurred in 3 of 12 (25%) with a pre-implantation International Prostate Symptom Score of 15 or greater and in 13 of 168 (7.7%) with a score of less than 15 (OR 4.0, 95% CI 1-16, p = 0.04). In contrast, there was no difference in the retention rate in patients with hormonal therapy with an initial score of 15 or greater vs less than 15 (2 of 25 or 8% vs 11 of 102 or 10.8%, p = 0.614). Transurethral prostate resection was done in 11 of 191 men (5.8%) without vs 12 of 204 (5.9%) with hormonal therapy (p = 0.958). There was no difference in biochemical failure in the 2 groups. CONCLUSIONS: Neoadjuvant hormonal therapy has its greatest benefit in patients receiving brachytherapy who have a large prostate and an International Prostate Symptom Score of 15 or greater.

Outcomes for patients with high-grade prostate cancer treated with a combination of brachytherapy, external beam radiotherapy and hormonal therapy.

OBJECTIVE: To assess the outcomes for patients with Gleason score 8-10 prostate cancer treated with brachytherapy, external beam radiotherapy (EBRT) and hormonal therapy (HT). PATIENTS AND METHODS: In all, 181 patients with Gleason scores 8-10 prostate cancer were treated from 1994 to 2006 with a (103)Pd implant (prescription dose 100 Gy), 45 Gy of EBRT and 9 months of HT. The median (range) follow-up was 65 (24-150) months; freedom from biochemical failure (FBF) rates were calculated using the Phoenix definition. RESULTS: The 8-year actuarial FBF, freedom from distant metastases, prostate-cancer specific survival and overall survival were 73%, 80%, 87% and 79%, respectively. The pretreatment prostate-specific antigen (PSA) level significantly affected FBF, with 8-year rates of 72%, 82% and 58% for patients with PSA level of 10-20 and >20 ng/mL, respectively (P = 0.006). The PSA level had no significant effect on rates of distant metastases. The Gleason score had the most significant affect on FBF in a multivariate analysis, and was the only factor to significantly affect rates of distant metastases; the 8-year FBF rates were 84%, 55% and 30% for scores of 8, 9 and 10, respectively (P = 0.003). The corresponding freedom from distant metastases and prostate-cancer specific survival rates were 86%, 76%, 30% (P < 0.001) and 92%, 80%, 62.5% (P = 0.003), respectively. CONCLUSIONS: The 8-year outcomes after this regimen showed favourable biochemical and distant control, as well disease-specific survival rates for patients with Gleason scores of 8-10. This treatment approach should be considered as a viable option for this subset of patients with high-risk disease.

Phase 1 study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response.

BACKGROUND: To determine the safety and maximum-tolerated dose of concurrent sunitinib and image-guided radiotherapy (IGRT) followed by maintenance sunitinib in oligometastastic patients. METHODS: Eligible patients had 1 to 5 sites of metastatic cancer measuring

Radiation dose predicts for biochemical control in intermediate-risk prostate cancer patients treated with low-dose-rate brachytherapy.

PURPOSE: To evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (FFbF) in patients with intermediate-risk prostate cancer. METHODS AND MATERIALS: From a prospectively collected database of 2250 men treated at Mount Sinai Hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen [PSA] level 10-20 ng/mL, Gleason score 7, or Stage T2b) were identified who had a minimum follow-up of 24 months and postimplant CT-based dosimetric analysis. Biologically effective dose (BED) values were calculated to compare doses from different isotopes and treatment regimens. Patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. Patient- and treatment-related factors were analyzed with respect to FFbF. The median follow-up was 60 months (range, 24-167 months). Biochemical failure was defined according to the Phoenix definition. Univariate analyses were used to determine whether any variable was predictive of FFbF. A two-sided p value of <0.05 was considered significant. RESULTS: Overall, the actuarial FFbF at 10 years was 86%. Dose (BED <150 Gy(2) vs. >or=150 Gy(2)) was the only significant predictor of FFbF (p < 0.001). None of the other variables (PSA, external-beam radiotherapy, Gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year FFbF. CONCLUSIONS: Radiation dose is an important predictor of FFbF in intermediate-risk prostate cancer. Treatment should continue to be individualized according to presenting disease characteristics until results from Radiation Therapy Oncology Group trial 0232 become available.

There is no correlation between erectile dysfunction and dose to penile bulb and neurovascular bundles following real-time low-dose-rate prostate brachytherapy.

PURPOSE: We evaluated the relationship between the onset of erectile dysfunction and dose to the penile bulb and neurovascular bundles (NVBs) after real-time ultrasound-guided prostate brachytherapy. METHODS AND MATERIALS: One hundred forty-seven patients who underwent prostate brachytherapy met the following eligibility criteria: (1) treatment with 125I brachytherapy to a prescribed dose of 160 Gy with or without hormones without supplemental external beam radiation therapy, (2) identification as potent before the time of implantation based on a score of 2 or higher on the physician-assigned Mount Sinai Erectile Function Score and a score of 16 or higher on the abbreviated International Index of Erectile Function patient assessment, and (3) minimum follow-up of 12 months. Median follow-up was 25.7 months (range, 12-47 months). RESULTS: The 3-year actuarial rate of impotence was 23% (34 of 147 patients). An additional 43% of potent patients (49 of 113 patients) were using a potency aid at last follow-up. The penile bulb volume receiving 100% of the prescription dose (V(100)) ranged from 0-0.05 cc (median, 0 cc), with a dose to the hottest 5% (D(5)) range of 12.5-97.9 Gy (median, 40.8 Gy). There was no correlation between penile bulb D(5) or V(100) and postimplantation impotency on actuarial analysis. For the combined right and left NVB structures, V(100) range was 0.3-5.1 cc (median, 1.8 cc), and V(150) range was 0-1.5 cc (median, 0.31 cc). There was no association between NVB V(100) or V(150) and postimplantation impotency on actuarial analysis. CONCLUSION: Penile bulb doses are low after real-time ultrasound-guided prostate brachytherapy. We found no correlation between dose to either the penile bulb or NVBs and the development of postimplantation impotency.

Prognostic significance of 5-year PSA value for predicting prostate cancer recurrence after brachytherapy alone and combined with hormonal therapy and/or external beam radiotherapy.

PURPOSE: To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment. METHODS AND MATERIALS: Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years. RESULTS: The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was 0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer. CONCLUSION: The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse.

Distant and local recurrence in patients with biochemical failure after prostate brachytherapy.

PURPOSE: To analyze the patterns of failure after the brachytherapy management of localized prostate cancer. METHODS AND MATERIALS: From 1990 to 2008, 2869 patients underwent prostate brachytherapy and 213 experienced a prostate-specific antigen (PSA) failure by the Phoenix definition. Of these 213 patients, 33.5% were low, 18.5% intermediate, and 58% high risk. RESULTS: Of the 119 patients biopsied, 36 (30%) had a least one positive posttreatment biopsy. In univariate and multivariate analyses, PSA doubling time was the most predictive of a positive biopsy. Patients with doubling times < or =3, >3-6, > or =6-10, and >10 months had positive biopsy rates of 9%, 18%, 36%, and 42%, respectively (p=0.01). The actuarial rate of remaining free from distant metastases at 10 years was 73%. Patients with PSA doubling times of < or =3, >3-6, >6-10, and >10 months had freedom from distant metastases rates of 0%, 74%, 78%, and 94.5% at 10 years, respectively (p<0.0001). In multivariate analysis, PSA doubling time and time to PSA failure were the most significant predictors of developing distant metastases. CONCLUSIONS: About one third of patients harbor a component of local failure and one fourth demonstrate clinical metastases. PSA doubling time can be used to help predict the source of a rising PSA.

Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer.

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.

Stereotactic radiosurgery for thoracic malignancies.

Radiosurgery for lung cancer is a novel and promising concept that warrants thorough review. Stereotactic body radiotherapy enables the selective delivery of an intense dose of high-energy radiation to destroy a tumor with precise targeting. The radiobiology and physics behind the use of radiosurgery are presented, followed by a discussion of promising retrospective and prospective clinical data that has been reported from Japan, Europe, and the United States. The article closes with a discussion of multidisciplinary approaches that include radiosurgery which are on the therapeutic horizon.

Adjuvant radiotherapy improves overall survival for patients with lymph node-positive head and neck squamous cell carcinoma.

BACKGROUND: Although adjuvant radiotherapy (RT) is often recommended for locally advanced squamous cell carcinoma of the head and neck (HNSCC), its effect on overall or cancer-specific survival has not been clearly demonstrated. In the current study, the frequency and effect of adjuvant RT on overall survival was investigated in patients with resected lymph node-positive head and neck cancer. METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients were selected with lymph node-positive HNSCC (American Joint Committee on Cancer and SEER stage 3/4) who were treated either with surgery alone or surgery and RT and were diagnosed between 1988 and 2001. A total of 8795 patients who met the inclusion criteria for analysis comprised the study population, with a median follow-up of 4.3 years for patients still alive at the time of last follow-up. RESULTS: Adjuvant RT was utilized in 84% of patients. Adjuvant RT improved the 5-year overall survival (43.2% [95% confidence interval (95% CI), 41.9-44.4%] for surgery + RT vs 33.4% [95% CI, 30.7-36.0%] for surgery alone; P < .001) and cancer-specific survival (50.9% for surgery + RT vs 42.1% for surgery) on univariate analysis. On multivariate analysis, adjuvant RT (hazards ratio [HR] of 0.78; 95% CI, 0.71-0.86 [P < .001]) remained a significant predictor of improved survival. The significant benefit of radiation on overall survival was noted for lymph node-positive patients with both primary tumors localized to the involved organ (HR of 0.81; 95% CI, 0.71-0.94 [P = .007]) and more locally invasive primary tumors (HR of 0.77; 95% CI, 0.68-0.87 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the largest reported analysis of adjuvant RT in patients with locally advanced HNSCC published to date, adjuvant RT resulted in an approximately 10% absolute increase in 5-year cancer-specific survival and overall survival for patients with lymph node-positive HNSCC compared with surgery alone. Despite combined surgery and adjuvant RT, outcomes in this high-risk population remain suboptimal, emphasizing the need for continued investigation of innovative treatment approaches.

TGFB1 single nucleotide polymorphisms are associated with adverse quality of life in prostate cancer patients treated with radiotherapy.

PURPOSE: To investigate whether the presence of single nucleotide polymorphisms (SNPs) located within TGFB1 might be predictive for the development of adverse quality-of-life outcomes in prostate cancer patients treated with radiotherapy. METHODS AND MATERIALS: A total of 141 prostate cancer patients treated with radiotherapy were screened for SNPs in TGFB1 using DNA sequencing. Three quality-of-life outcomes were investigated: (1) prospective decline in erectile function, (2) urinary quality of life, and (3) rectal bleeding. Median follow-up was 51.3 months (range, 12-138 months; SD, 24.4 months). RESULTS: Those patients who possessed either the T/T genotype at position -509, the C/C genotype at position 869 (pro/pro, codon 10) or the G/C genotype at position 915 (arg/pro, codon 25) were significantly associated with the development of a decline in erectile function compared with those who did not have these genotypes: 56% (9 of 16) vs. 24% (11 of 45) (p = 0.02). In addition, patients with the -509 T/T genotype had a significantly increased risk of developing late rectal bleeding compared with those who had either the C/T or C/C genotype at this position: 55% (6 of 11) vs. 26% (34 of 130) (p = 0.05). CONCLUSIONS: Possession of certain TGFB1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy for prostate cancer. Therefore, identification of patients harboring these genotypes may represent a means to predict which men are most likely to suffer from poor quality-of-life outcomes after radiotherapy for prostate cancer.

(125)I monotherapy using D90 implant doses of 180 Gy or greater.

PURPOSE: The purpose of this study was to characterize the oncologic results and toxicity profile of patients treated with (125)I implants using the dose delivered to 90% of the gland from the dose-volume histogram (D90) of greater than 144 Gy. METHODS AND MATERIALS: From June 1995 to Feb 2005, a total of 643 patients were treated with (125)I monotherapy for T1-T2 prostate cancer with a D90 of 180 Gy or greater (median, 197 Gy; range, 180-267 Gy). Implantations were performed using a real-time ultrasound-guided seed-placement method and intraoperative dosimetry to optimize target coverage and homogeneity by using modified peripheral loading. We analyzed biochemical disease-free survival (bDFS) of 435 patients who had a minimum 2-year prostate-specific antigen follow-up (median follow-up, 6.7 years; range, 2.0-11.1 years). RESULTS: Five-year bDFS rates for the entire cohort using the American Society for Therapeutic Radiology and Oncology and Phoenix definitions were 96.9% and 96.5%, respectively. Using the Phoenix definition, 5-year bDFS rates were 97.3% for low-risk patients and 92.8% for intermediate/high-risk patients. The positive biopsy rate was 4.1%. The freedom rate from Grade 2 or higher rectal bleeding at 5 years was 88.5%. Acute urinary retention occurred in 10.7%, more commonly in patients with high pretreatment International Prostate Symptom Scores (p < 0.01). In patients who were potent before treatment, 73.4% remained potent at 5 years after implantation. CONCLUSIONS: Patients with a minimum D90 of 180 Gy had outstanding local control based on prostate-specific antigen control and biopsy data. Toxicity profiles, particularly for long-term urinary and sexual function, were excellent and showed that D90 doses of 180 Gy or greater performed using the technique described were feasible and tolerable.

Brachytherapy for the treatment of prostate cancer.

Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. Largely due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. The reason that brachytherapy results are reproducible in several different practice settings is because numerous implant quality factors have been defined over the last 20 years, which can be applied objectively to judge the success of the intervention both during and after the procedure. In addition, recent long-term follow-up studies have clarified that the secondary cancer incidence of brachytherapy is not clinically meaningful. In terms of future directions, the study of radiation repair genetics may allow for the counseling physician to better estimate any given patients risk for side effects, thereby substantially reducing the therapeutic uncertainties faced by patients choosing a prostate cancer intervention.

Effect of low dose-rate prostate brachytherapy on the sexual health of men with optimal sexual function before treatment: analysis at > or = 7 years of follow-up.

OBJECTIVE: To evaluate the effect of low-dose rate prostate brachytherapy on the sexual health of men with > or = 7 years of prospective evaluation and optimum sexual function before treatment. PATIENTS AND METHODS: In all, 223 patients with T1b to T3a prostate cancer and a median (range) age of 66 (50-82) years were treated with permanent seed implantation from November 1990 to March 1998. They were followed for a median (range) of 8.2 (7-14.1) years using prospective quality-of-life measures. Erectile function (EF) was assessed using a physician-assigned score and beginning in June 2000; the validated International Index of EF (IIEF-5) was used as a complementary method to quantify late EF. No adjustment was made to differentiate sexual function with or with no pharmacological intervention for EF. Pearson's chi-square test and Student's t-test were used to compare the groups. RESULTS: Of the 223 men, 131 (59%) had optimal EF before their brachytherapy; of these, 51 (40%) at the last follow-up evaluation were using either a phosphodiesterase type 5 inhibitor (44, 86%), yohimbine (two, 4%) or alprostadil (five, 10%). The age at implantation was highly predictive of current EF; 23 of 25 (92%) men aged 50-59 years had a current EF of > or = 2; those aged 60-69 and 70-78 years had an EF of > or =2 in 48/75 (64%) and 18/31 (58%) (P = 0.01). A current IIEF-5 score of > or = 16 also correlated highly with age at implant, i.e. 50-59, 16/25 (64%); 60-69, 20/75 (27%) and 70-78 years, 6/31 (19%) (P < 0.001). CONCLUSION: Patients aged <60 years and with optimal EF before low-dose rate prostate brachytherapy have a very high probability of long-term EF.