Randomized, double-blinded, placebo-controlled crossover trial of treating erectile dysfunction with sildenafil after radiotherapy and short-term androgen deprivation therapy: results of RTOG 0215.

INTRODUCTION: Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. AIM: The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. METHODS: In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. MAIN OUTCOME MEASURES: The primary end point was improved erectile function, as measured by the IIEF. RESULTS: The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤ 120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. CONCLUSIONS: This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer.

Salvage permanent perineal radioactive-seed implantation for treating recurrence of localized prostate adenocarcinoma after external beam radiotherapy.

OBJECTIVE: To assess our experience with salvage permanent perineal radioactive-seed implantation (SPPI) as a possible therapeutic option for recurrent prostate adenocarcinoma, as salvage therapies for recurrences after definitive external beam radiotherapy (EBRT) for localized adenocarcinoma of the prostate are associated with significant morbidity and biochemical failure. PATIENTS AND METHODS: We retrospectively analysed on patients who had SPPI for localized recurrent prostate adenocarcinoma from 1996 to 2007 after primary treatment with EBRT. Excluded were patients who had other primary treatment or had no follow-up. Primary outcomes were time to biochemical relapse-free survival, using the Phoenix definition of a prostate-specific antigen (PSA) nadir +2 ng/mL, and cancer-specific survival. Secondary outcomes were the International Prostate Symptom Score (IPSS), the International Index of Erectile Function-5 score (IIEF-5), and complications based on Common Terminology Criteria for Adverse Events (version 3). RESULTS: In all, 37 patients had SPPI during this period; after applying inclusion and exclusion criteria, 24 remained for analysis. At the time of salvage therapy, the median time to the diagnosis of local recurrence was 49 months, the median PSA level was 3.36 ng/mL, the median PSA doubling time was 20 months, and all patients were clinically re-staged at or=8 in three (not recorded in two). The median follow-up after SPPI was 30 months; the cancer-free survival was 96% (one death) and biochemical relapse-free survival was 88% (three patients). The PSA level was higher than the levels before SPPI at 3 months in all three failures, but lower in all 21 patients considered relapse-free. Complications included one urethral stricture, one grade 3 rectal haemorrhage and five grade 2 gross haematuria that resolved with conservative management. Insufficient data were available to assess the IPSS or IIEF-5 scores. CONCLUSION: With a short-term follow-up SPPI appears to provide excellent prostate cancer control with an acceptable rate of complications for patients with local recurrence of prostate cancer after EBRT. An extended follow-up is necessary to determine the long-term durability and safety of SPPI.

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

PURPOSE: Treatment 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 METHODS: Six 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 36Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30Gy, received 24Gy in four fractions. RESULTS: Median 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 0.19ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3-5 toxicity. CONCLUSION: Transperineal 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.

Proposed rectal dose constraints for patients undergoing definitive whole pelvic radiotherapy for clinically localized prostate cancer.

PURPOSE: Although several institutions have reported rectal dose constraints according to threshold toxicity, the plethora of trials has resulted in multiple, confusing dose-volume histogram recommendations. A set of standardized, literature-based constraints for patients undergoing whole pelvic radiotherapy (RT) for prostate cancer would help guide the practice of prostate RT. The purpose of this study was to develop these constraints, demonstrate that they are achievable, and assess the corresponding rectal toxicity. METHODS AND MATERIALS: An extensive literature search identified eight key studies relating dose-volume histogram data to rectal toxicity. A correction factor was developed to address differences in the anatomic definition of the rectum across studies. The dose-volume histogram constraints recommended by each study were combined to generate the constraints. The data from all patients treated with definitive intensity-modulated RT were then compared against these constraints. Acute rectal toxicity was assessed. RESULTS: A continuous, proposed rectal dose-constraint curve was generated. Intensity-modulated RT not only met this constraint curve, but also was able to achieve at least 30-40% lower dose to the rectum. The preliminary clinical results were also positive: 50% of patients reported no acute bowel toxicity, 33% reported Grade 1 toxicity, and 17% reported Grade 2 toxicity. No patients reported Grade 3-4 acute rectal toxicity. CONCLUSIONS: In this study, we developed a set of proposed rectal dose constraints. This allowed for volumetric assessment of the dose-volume relationship compared with single dose-volume histogram points. Additional research will be performed to validate this threshold as a class solution for rectal dose constraints.

Inverse planning simulated annealing for magnetic resonance imaging-based intracavitary high-dose-rate brachytherapy for cervical cancer.

PURPOSE: To develop a technique using exclusively magnetic resonance imaging (MRI) to perform dwell position identification, targets and organs at risk delineation, and to apply inverse planning dose optimization to high-dose-rate brachytherapy for cervical cancer. METHODS AND MATERIALS: We included 15 consecutive women treated with high-dose-rate (HDR) brachytherapy for cervical cancer. All patients underwent MRI after placement of tandem and ring applicator containing a gadodiamide-filled dummy marker. This technique allowed direct visualization of the source pathway and precise definition of the intra-applicator source positions. For each patient, we delineated gross target volume (GTV), high-risk clinical target volume (HR-CTV), and organs at risk on MRI, according to the European Gynecological GEC-ESTRO Working Group definitions. We performed inverse planning simulated annealing (IPSA) and analyzed the dose-volume histograms with the following endpoints: D(90), D(100), and V(100) for GTV and HR-CTV; D0.1 cc, D1 cc, D2 cc for bladder, rectum, and bowel; and dose at Point A. RESULTS: The intra-applicator source pathway was easily visualized on MRI using the gadodiamide-filled marker. IPSA provided excellent target coverage. The mean D(90) and V(100) for HR-CTV were 103+/-5% and 92+/-3%, respectively. IPSA provided excellent bladder sparing. D1 cc and D2 cc of bladder were 73+/-10% and 67+/-10%, respectively. CONCLUSIONS: We developed a novel technique that allows direct visualization of the intra-applicator source pathway on MRI. Using this technique, we successfully performed inverse planning directly from MRI.

Daily electronic portal imaging of implanted gold seed fiducials in patients undergoing radiotherapy after radical prostatectomy.

PURPOSE: The aim of this study was to measure interfraction prostate bed motion, setup error, and total positioning error in 10 consecutive patients undergoing postprostatectomy radiotherapy. METHODS AND MATERIALS: Daily image-guided target localization and alignment using electronic portal imaging of gold seed fiducials implanted into the prostate bed under transrectal ultrasound guidance was used in 10 patients undergoing adjuvant or salvage radiotherapy after prostatectomy. Prostate bed motion, setup error, and total positioning error were measured by analysis of gold seed fiducial location on the daily electronic portal images compared with the digitally reconstructed radiographs from the treatment-planning CT. RESULTS: Mean (+/- standard deviation) prostate bed motion was 0.3 +/- 0.9 mm, 0.4 +/- 2.4 mm, and -1.1 +/- 2.1 mm in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) axes, respectively. Mean set-up error was 0.1 +/- 4.5 mm, 1.1 +/- 3.9 mm, and -0.2 +/- 5.1 mm in the LR, SI, and AP axes, respectively. Mean total positioning error was 0.2 +/- 4.5 mm, 1.2 +/- 5.1 mm, and -0.3 +/- 4.5 mm in the LR, SI, and AP axes, respectively. Total positioning errors >5 mm occurred in 14.1%, 38.7%, and 28.2% of all fractions in the LR, SI, and AP axes, respectively. There was no significant migration of the gold marker seeds. CONCLUSIONS: This study validates the use of daily image-guided target localization and alignment using electronic portal imaging of implanted gold seed fiducials as a valuable method to correct for interfraction target motion and to improve precision in the delivery of postprostatectomy radiotherapy.

Radiotherapy in the management of clinically localized prostate cancer: evolving standards, consensus, controversies and new directions.

Major advances have been made in the definitive use of various forms of radiotherapy (RT) in the management of clinically localized prostate cancer (PCa). Despite tremendous gains, the radiation oncology community continues to struggle with several key questions. In general, the areas of controversy pertain to how to improve the therapeutic ratio of RT. Specifically, key issues include dose escalation; the relative benefit of alternative forms of RT (ie, brachytherapy and protons); target localization; the use, timing, and duration of androgen deprivation; and the need for pelvic nodal irradiation. Multiple efforts have been made to address each of these issues; however, there is no consensus on how to resolve them. This review is an evidence-based critique of the available treatment approaches considered for the optimal use of radiotherapy as definitive management of clinically localized PCa.

Radiotherapy in the management of common genitourinary malignancies.

A continued role for radiation therapy in the multidisciplinary management of genitourinary malignancies seems certain. Treatment outcomes continue to improve, accompanied by diminishing rates of toxicity. With continued technologic advances in the delivery of radiation, including the use of adaptive radiotherapy, the discovery and application of novel treatment agents, and the combined efforts of urologists, medical oncologists, and radiation oncologists, patients who have genitourinary malignancies have an excellent chance of cure.

3D inverse treatment planning for the tandem and ovoid applicator in cervical cancer.

PURPOSE: Three-dimensional treatment planning systems and inverse planning optimization for brachytherapy are becoming commercially available. Guidelines for target delineation and dose constrictions have not been established using this new software. In this study we describe a method of target delineation for the tandem and ovoids applicator. We then compare inverse planning dose distributions with the traditional methods of prescribing dose. METHODS AND MATERIALS: Target and organ-at-risk volumes were defined using systematic guidelines on 15 patients treated in our department with high-dose-rate brachytherapy for cervical cancer using tandem and ovoids. High-dose-rate distributions were created according to three different dose optimization protocols: inverse planning simulated annealing (IPSA), point A, and point A with a normalization of 2 cc of the bladder receiving 80% of the dose (bladder-sparing method). An uniform cost function for dose constraints was applied to all IPSA generated plans, and no manual optimization was allowed for any planning method. RESULTS: Guidelines for target and structure-at-risk volumes, as well as dose constraint cost functions, were established. Dose-volume histogram analysis showed that the IPSA algorithm indicated no difference in tumor coverage compared with point A optimization while decreasing dose to the bladder and rectum. The IPSA algorithm provided better target volume coverage compared with bladder-sparing method with equivalent doses to the bladder and rectum. CONCLUSION: This study uses a systematic approach for delineating target and organ-at-risk volumes and a uniform cost function for generating IPSA plans for cervical cancer using tandem and ovoids. Compared with conventional dose prescription methods, IPSA provides a consistent method of optimization that maintains or improves target coverage while decreasing dose to normal structures. Image-guided brachytherapy and inverse planning improve brachytherapy dosimetry.

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.

A comparison between tandem and ovoids and interstitial gynecologic template brachytherapy dosimetry using a hypothetical computer model.

PURPOSE: To evaluate the dose distribution within the clinical target volume between two gynecologic brachytherapy systems---the tandem and ovoids and the Syed-Neblett gynecologic template---using a hypothetical computer model. METHODS AND MATERIALS: Source positions of an intracavitary system (tandem and ovoids) and an interstitial system (GYN template) were digitized into the Nucletron Brachytherapy Planning System. The GYN template is composed of a 13-catheter implant (12 catheters plus a tandem) based on the Syed-Neblett gynecologic template. For the tandem and ovoids, the dwell times of all sources were evenly weighted to produce a pear-shaped isodose distribution. For the GYN template, the dwell times were determined using volume optimization. The prescribed dose was then normalized to point A in the intracavitary system and to a selected isodose line in the interstitial system. The treated volume in the two systems was kept approximately the same, and a cumulative dose-volume histogram of the treated volume was then generated with the Nucletron Brachytherapy Planning System to use for comparison. To evaluate the dose to a hypothetical target, in this case the cervix, a 2-cm-long, 3-cm-diameter cylinder centered along the tandem was digitized as the clinical target volume. The location of this hypothetical cervix was based on the optimal application of the brachytherapy system. A visual comparison of clinical target coverage by the treated volume on three different orthogonal planes through the treated volume was performed. The percentage dose-volume histograms of the target were generated for comparison. Multiple midline points were also placed at 5-mm intervals away from the tandem in the plane of the cervix to simulate the location of potential bladder and rectal dose points. Doses to these normal structures were calculated for comparison. RESULTS: Although both systems covered the hypothetical cervix adequately, the interstitial system had a better coverage of the region lateral to the cervix. Smaller volumes of the vagina and uterine fundus received the full dose from the interstitial implant. The cumulative dose-volume histograms revealed larger high-dose regions within the treatment volume for the intracavitary system. The volumes receiving > or = 180% of the prescription dose were 31 cc and 17 cc for the intracavitary system and interstitial system, respectively. The isodose lines showed that most of this difference results from the high-dose region around the tandem. The percentage dose-volume histograms showed that a larger percentage of cervix received a higher dose in the intracavitary system. Fifty-two percent of the target volume received 200% or higher of the prescription dose with tandem and ovoids, compared with only 20% with the template system. Analysis of dose points outside of the 100% isodose lines showed a slightly more rapid dose drop-off with the interstitial system compared to the intracavitary system. Point doses at 20, 25, and 30 mm from the tandem in the interstitial system were 100%, 69%, and 51% of prescribed dose, and from the intracavitary system were 101%, 76%, and 58%, respectively. CONCLUSIONS: Our dosimetric analysis revealed a better coverage in the parametrial regions, but underdosage of the central cervical region, for the interstitial system. On the other hand, because of the increased distance of source to dose point, there is a more rapid dose drop-off outside the treated volume with the interstitial system, which has the potential to improve tissue sparing. Based on this analysis, we caution against using a radiotherapy system with a homogeneous central dose distribution when treating cervical cancer with an intact uterus. We recommend differential loading of the implant catheters with the majority of dose delivered from the tandem when using an interstitial GYN template with remote afterloader.

Longitudinal assessment of changes in sexual function and bother in patients treated with external beam radiotherapy or brachytherapy, with and without neoadjuvant androgen ablation: data from CaPSURE.

PURPOSE: To evaluate the effects of external beam radiotherapy (EBRT), with or without brachytherapy (BT) boost or brachytherapy monotherapy with and without short-term androgen ablation (<==6 months; STAD) on sexual function (SF) and sexual bother (SB) in men treated for localized prostate cancer. METHODS AND MATERIALS: A total of 992 men with newly diagnosed prostate cancer enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor database were studied to assess treatment-related changes in SF and SB. Six treatment subgroups (EBRT - STAD, EBRT + STAD, BT - STAD, BT + STAD, EBRT + BT - STAD, EBRT + BT + STAD) were compared. RESULTS: The greatest reported changes in SF occurred during the first 2 posttreatment years. Patients receiving BT reported greater SF and the least change in SF overall; those receiving EBRT + BT reported the greatest decline in SF. SF scores associated with STAD were initially lower than in patients without STAD; however by 1 year no statistically significant difference in SF or SB was noted. CONCLUSION: Each treatment for prostate cancer can negatively affect SF and SB. Initial differences among treatment subgroups exist, but diminish with time. SF changes associated with EBRT +/- BT were statistically significant and those for BT were not. STAD appeared to confer only temporary and recoverable impairment of erectile function.

Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma.

OBJECTIVES: We performed a retrospective review of the efficacy and morbidity of radical pleurectomy/decortication and intraoperative radiotherapy followed by external beam radiation therapy with or without chemotherapy for diffuse malignant pleural mesothelioma. METHODS: A total of 32 patients with diffuse malignant pleural mesothelioma were initially evaluated between January 1995 and September 2000. Three patients were excluded from analysis because of unresectable disease. Two patients died postoperatively, and one patient had recurrent disease previously treated at an outside institution. Of the remaining 26 patients included in the analysis, 24 received intraoperative radiotherapy. External beam radiation therapy was generally started 1 to 2 months after resection and delivered by means of 3-dimensional conformal radiation therapy or with inverse treatment planning intensity-modulated radiation therapy. When given, chemotherapy consisted of 2 to 3 cycles of cyclophosphamide, doxorubicin (Adriamycin), and cisplatin initiated 1 to 2 months after completion of radiation. RESULTS: At the time of data analysis, 5 of 26 patients were alive. The median follow-up was 9.7 months (range, 2-67.6 months). The median overall survival and progression-free interval from the time of the operation were 18.1 and 12.2 months, respectively. The Kaplan-Meier estimates of overall survival and freedom from progression at 1 year were 64% and 50%, respectively. The site of failure was mostly locoregional. However, there were 4 abdominal failures and 1 contralateral lung failure. CONCLUSIONS: Radical pleurectomy/decortication with aggressive radiotherapy with or without chemotherapy might offer an alternative treatment option to those who cannot tolerate extrapleural pneumonectomy.

Computer-assisted, atlas-based segmentation for target volume delineation in whole pelvic IMRT for prostate cancer.

The purpose of this study is to evaluate whether computer-assisted segmentation is clinically feasible in target volume delineation for prostate cancer patients treated with whole pelvic IMRT. An atlas was created, comprised of 44 clinically node-negative prostate cancer patients. Three regions of interest (ROIs) were chosen for analysis: prostate, pelvic lymph nodes, and rectum. For a separate tester set of 15 patients with previously contoured ROIs by three experienced physicians, atlas-assisted contours were compared to manual contours by calculating a volumetric overlap index. In the tester set patients, the average overlap between the manually drawn and atlas-based contours for the prostate, pelvic lymph nodes, and rectum was 60%, 51%, and 64%, respectively. The volume differences were significant in the rectum and pelvic lymph nodes (p = 0.049 and p = 0.016, respectively); this was not true for the prostate. A subset analysis based on physician-specific atlases showed that the average overlap index for the pelvic lymph nodal volume increased from 51% to 60%, while the other ROIs had no significant changes. Despite significant inter-physician differences, atlas-based segmentation for pelvic lymph node delineation serves as an initial guideline for physicians, potentially improving both consistency and efficiency in contouring.

High-dose-rate brachytherapy boost for prostate cancer: comparison of two different fractionation schemes.

PURPOSE: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy × 3 fractions (patient group 1) and 950 cGy × 2 fractions (patient group 2). METHODS AND MATERIALS: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy × 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy × 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score ≥7, and/or clinical stage T3 disease. RESULTS: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. CONCLUSIONS: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost.

PURPOSE: Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. PATIENTS AND METHODS: A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. RESULTS: With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir < or =0.5 ng/mL, 91% vs. 59%, respectively). CONCLUSION: We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or CPBRTB.

Phase II trial of combined high-dose-rate brachytherapy and external beam radiotherapy for adenocarcinoma of the prostate: preliminary results of RTOG 0321.

PURPOSE: To estimate the rate of late Grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) after treatment with external beam radiotherapy and prostate high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: Each participating institution submitted computed tomography-based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined Stage T1c-T3b prostate cancer were eligible for the present study. All patients were treated with 45 Gy in 25 fractions using external beam radiotherapy and one HDR implant delivering 19 Gy in two fractions. All AEs were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Late GU/GI AEs were defined as those occurring >9 months from the start of the protocol treatment, in patients with ≥18 months of potential follow-up. RESULTS: A total of 129 patients from 14 institutions were enrolled in the present study. Of the 129 patients, 125 were eligible, and AE data were available for 112 patients at analysis. The pretreatment characteristics of the patients were as follows: Stage T1c-T2c, 91%; Stage T3a-T3b, 9%; prostate-specific antigen level ≤10 ng/mL, 70%; prostate-specific antigen level >10 but ≤20 ng/mL, 30%; and Gleason score 2-6, 10%; Gleason score 7, 72%; and Gleason score 8-10, 18%. At a median follow-up of 29.6 months, three acute and four late Grade 3 GU/GI AEs were reported. The estimated rate of late Grade 3-5 GU and GI AEs at 18 months was 2.56%. CONCLUSION: This is the first prospective, multi-institutional trial of computed tomography-based HDR brachytherapy and external beam radiotherapy. The technique and doses used in the present study resulted in acceptable levels of AEs.

High-dose rate brachytherapy using inverse planning simulated annealing for locoregionally advanced cervical cancer: a clinical report with 2-year follow-up.

PURPOSE: We present clinical outcomes of image-guided brachytherapy using inverse planning simulated annealing (IPSA) planned high-dose rate (HDR) brachytherapy boost for locoregionally advanced cervical cancer. METHODS AND MATERIALS: From February 2004 through December 2006, 51 patients were treated at the University of California, San Francisco with HDR brachytherapy boost as part of definitive radiation for International Federation of Gynecology and Obstetrics Stage IB1 to Stage IVA cervical cancer. Of the patients, 46 received concurrent chemotherapy, 43 with cisplatin alone and 3 with cisplatin/5-fluorouracil. All patients had IPSA-planned HDR brachytherapy boost after whole-pelvis external radiation to a total tumor dose of 85 Gy or greater (for alpha/beta = 10). Toxicities are reported according to National Cancer Institute CTCAE v3.0 (Common Terminology Criteria for Adverse Events version 3.0) guidelines. RESULTS: At a median follow-up of 24.3 months, there were no toxicities of Grade 4 or greater and the frequencies of Grade 3 acute and late toxicities were 4% and 2%, respectively. The proportion of patients having Grade 1 or 2 gastrointestinal and genitourinary acute toxicities was 48% and 52%, respectively. Low-grade late toxicities included Grade 1 or 2 vaginal, gastrointestinal, and hormonal toxicities in 31%, 18%, and 4% of patients, respectively. During the follow-up period, local recurrence developed in 2 patients, regional recurrence developed in 2, and new distant metastases developed in 15. The rates of locoregional control of disease and overall survival at 24 months were 91% and 86%, respectively. CONCLUSIONS: Definitive radiation by use of inverse planned HDR brachytherapy boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease.

Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610.

PURPOSE: Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate neoadjuvant androgen deprivation therapy (ADT) in combination with external-beam radiotherapy (EBRT) in men with locally advanced prostate cancer. This report summarizes long-term follow-up results. MATERIALS AND METHODS: Between 1987 and 1991, 456 assessable patients (median age, 70 years) were enrolled. Eligible patients had bulky (5 x 5 cm) tumors (T2-4) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system. Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT, or they received EBRT alone. Study end points included overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), disease-free survival (DFS), and biochemical failure (BF). RESULTS: Ten-year OS estimates (43% v 34%) and median survival times (8.7 v 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P = .12). There was a statistically significant improvement in 10-year DSM (23% v 36%; P = .01), DM (35% v 47%; P = .006), DFS (11% v 3%; P < .0001), and BF (65% v 80%; P < .0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events. CONCLUSION: The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.

Advances in the treatment of localized prostate cancer: the role of anatomic and functional imaging in men managed with radiotherapy.

Radiation therapy is an active modality in the management of local and regional prostate cancer, but can be curative only if all existing disease is encompassed within the treatment portal. In addition to the ability to deliver sufficient radiation dose, accurate targeting is critical to achieve better treatment outcomes. Failure to accommodate daily variations in setup and organ motion potentially limits the efficacy of sophisticated conformal techniques (three-dimensional conformal radiotherapy and intensity-modulated radiotherapy). Increased use of various online and real-time imaging techniques is an important step toward enhancing treatment accuracy. The incorporation of functional imaging techniques into treatment planning is another important step. The addition of biologic and metabolic information regarding the location and extent of disease combined with real-time online imaging will allow us to better determine where, how, and with what to treat appropriate targets and improve cure rates.