Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol.

INTRODUCTION: A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer. METHODS: We are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events. ETHICS AND DISSEMINATION: The RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets. TRIAL REGISTRATION NUMBER: NCT02603341.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

Patterns of failure in patients with head and neck carcinoma of unknown primary treated with radiation therapy.

BACKGROUND: The purpose of this study was to examine patterns of failure and the relationship to radiation doses in patients with head and neck carcinoma of unknown primary (HNCUP). METHODS: We reviewed 85 patients with HNCUP treated with curative-intent radiation therapy (RT) during 1995 to 2012. RESULTS: There have been no failures in the pharyngeal axis. Relapse at initial neck sites of disease developed in 7 patients (8.2%). The median dose to these sites was 70 Gy (range, 63-70 Gy). Failure at neck sites without initial disease occurred in 4 patients (4.7%). The median dose was 54 Gy (range, 50-58.8 Gy). There were no contralateral failures in a small cohort of patients receiving unilateral treatment (n = 6). Percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months was 7.4%, and 2.5% at 3 years. Esophageal stricture developed in 5 patients (5.9%). CONCLUSION: RT for HNCUP produces excellent locoregional control rates with acceptably low levels of late toxicity. Doses prescribed to sites of eventual failure did not vary significantly from those sites that were treated and remain in control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E426-E431, 2016.

Phase II trial of bevacizumab + cetuximab + cisplatin with concurrent intensity-modulated radiation therapy for patients with stage III/IVB head and neck squamous cell carcinoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and tolerability of the addition of 2 monoclonal antibodies, bevacizumab and cetuximab, to 2 cycles of high-dose cisplatin administered concurrently with intensity-modulated radiation therapy (IMRT) for head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with newly diagnosed stage III/IVB (M0) HNSCC received cetuximab (400 mg/m(2) loading dose, followed by 250 mg/m(2) weekly), bevacizumab (15 mg/kg, days 1 and 22), and cisplatin (50 mg/m(2) , days 1, 2, 22, and 23) concurrently with IMRT (70 Gy). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety and tolerability. RESULTS: Among 30 patients enrolled in this study, the primary tumor site was the oropharynx in 24 patients (p16 immunohistochemistry was positive in 17, negative in 1, and not done in 6 of the oropharyngeal tumors). Median age was 57 years (range, 38-77 years) and 27 patients had clinical stage IVA disease. All patients completed the full planned dose of radiation therapy. The most common ≥ grade 3 adverse events were lymphopenia, mucositis (functional), and dysphagia. With a median follow-up of 33.8 months, 2-year PFS was 88.5% (95% confidence interval [CI] = 68.1-96.1) and 2-year OS was 92.8% (95% CI = 74.2-98.1). CONCLUSION: The addition of bevacizumab and cetuximab to 2 cycles of cisplatin, given concurrently with IMRT, was well-tolerated and was associated with favorable efficacy outcomes in this patient population. © 2015 Wiley Periodicals, Inc. Head Neck 38: E566-E570, 2016.

Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia outcomes.

OBJECTIVES: To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). METHODS: A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. RESULTS: The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs. 24.4 Gy; P<0.001). CONCLUSIONS: Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes.

Gastrointestinal stromal tumors, version 2.2014.

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

Soft tissue sarcoma, version 2.2014.

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

Using a novel dose QA tool to quantify the impact of systematic errors otherwise undetected by conventional QA methods: clinical head and neck case studies.

Recent studies have demonstrated that per-beam planar intensity-modulated radiation therapy (IMRT) quality assurance (QA) passing rates may not predict clinically relevant patient dose errors. This work is to evaluate the effect of dose variations introduced in dynamic multi-leaf collimator (DMLC) modeling and delivery processes on clinically relevant metrics for IMRT. Ten head and neck (HN) IMRT plans were randomly selected for this study. The conventional per-beam IMRT QA was performed for each plan by 2 different methods: (1) with gantry angle of 0 (gantry pointing downward) for all IMRT fields and (2) with gantry at specific angles as designed in the IMRT plan. For each patient, a batch analysis was done for each scenario and then imported to the 3DVH (Sun Nuclear Corp.) for processing. A "corrected DVH" was generated and compared to the DVH from the treatment plan. Their differences represented errors introduced from the combination of the treatment planning system (TPS) dose calculation algorithm and beam-delivery. The dose metrics from the two scenarios were compared with the corresponding calculated doses, and then their differences were analyzed. Although all per-beam planar IMRT QA had high Gamma passing rates 99.3 ± 1.3% (92.3-100%) for "2%/3 mm" criteria, there were significant errors in some of the calculated clinical dose metrics. Such as, for all the plans studied, there were as much as 3.2%, 5.7%, 5.6%, 2.3%, 4.1%, and 23.8% errors found in max cord dose, max brainstem dose, mean parotid dose, larynx dose, oral cavity dose, and PTV(D95) dose, respectively. The differences in errors for clinical metrics obtained between the two scenarios (zero gantry angle vs. true gantry angles) can also be significant: max cord dose (2.9% vs. 0.2%), max brainstem dose (3.8% vs. 0.4%), mean parotid dose (2.3% vs. 4.5%), mean larynx dose (3.9% vs. 2.0%), mean oral cavity dose (1.6% vs. 3.9%), and PTV(D95) dose (-0.4% vs. -2.6%). However, in the two scenarios, a strong and clear correlation between the dose differences for each of the organ structures was observed. This study confirms that conventional IMRT QA performance metrics are not predictive of dose errors in PTV and organs-at-risk. The clinically-relevant-dose QA has allowed us to predict the patient dose-volume relationships.

Soft tissue sarcoma, version 2.2012: featured updates to the NCCN guidelines.

The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.

Confirmation of skin doses resulting from bolus effect of intervening alpha-cradle and carbon fiber couch in radiotherapy.

In this study, we verified the treatment planning calculations of skin doses with the incorporation of the bolus effect due to the intervening alpha-cradle (AC) and carbon fiber couch (CFC) using radiochromic EBT2 films. A polystyrene phantom (25 × 25 × 15 cm(3)) with six EBT2 films separated by polystyrene slabs, at depths of 0, 0.1, 0.2, 0.5, 1, 1.4 cm, was positioned above an AC, which was ~1 cm thick. The phantom and AC assembly were CT scanned and the CT-images were transferred to the treatment planning system (TPS) for calculations in three scenarios: (A) ignoring AC and CFC, (B) accounting for AC only, (C) accounting for both AC and CFC. A single posterior 10 × 10 cm(2) field, a pair of posterior-oblique 10 × 10 cm(2) fields, and a posterior IMRT field (6 MV photons from a Varian Trilogy linac) were planned. For each radiation field configuration, the same MU were used in all three scenarios in the TPS. Each plan for scenario C was delivered to expose a stack of EBT2 films in the phantom through AC and CFC. In addition, in vivo EBT2 film measurement on a lung cancer patient immobilized with AC undergoing IMRT was also included in this study. Point doses and planar distributions generated from the TPS for the three scenarios were compared with the data from the EBT2 film measurements. For all the field arrangements, the EBT2 film data including the in vivo measurement agreed with the doses calculated for scenario (C), within the uncertainty of the EBT2 measurements (~4%). For the single posterior field (a pair of posterior-oblique fields), the TPS generated doses were lower than the EBT2 doses by 34%, 33%, 31%, 13% (34%, 31%, 31%, 11%) for scenario A and by 27%, 25%, 22%, 8% (25%, 21%, 21%, 6%) for scenario B at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. For the IMRT field, the 2D dose distributions at each depth calculated in scenario C agree with those measured data. When comparing the central axis doses for the IMRT field, we found the TPS generated doses for scenario A (B) were lower than the EBT2 data by 35%, 34%, 31%, 16% (29%, 26%, 23%, 10%) at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. There were no significant differences for the depths of 1.0 and 1.4 cm for all the radiation fields studied. TPS calculation of doses in the skin layers accounting for AC and CFC was verified by EBT2 film data. Ignoring the presence of AC and/or CFC in TPS calculation would significantly underestimate the doses in the skin layers. For the clinicians, as more hypofractionated regimens and stereotactic regimens are being used, this information will be useful to avoid potential serious skin toxicities, and also assist in clinical decisions and report these doses accurately to relevant clinical trials/cooperative groups, such as RTOG.

Percutaneous endoscopic gastrostomy in oropharyngeal cancer patients treated with intensity-modulated radiotherapy with concurrent chemotherapy.

BACKGROUND: The clinical benefit of routine placement of prophylactic percutaneous endoscopic gastrostomy (pPEG) tubes was assessed in patients with oropharyngeal cancer (OPC) who are undergoing intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy. METHODS: From 1998 through 2009, 400 consecutive patients with OPC who underwent chemoradiation were included. Of these, 325 had a pPEG and 75 did not (nPEG). Weight and albumin change from baseline to mid-IMRT, end of IMRT, 1 month post-IMRT, and 3 months post-IMRT were evaluated. The treating physicians prospectively recorded acute and late toxicities. RESULTS: Significantly lower absolute weight loss at end of IMRT (6.80 kg vs 8.38 kg, P = .007), 1 month post-IMRT (9.06 kg vs 11.33 kg, P = .006), and 3 months post-IMRT (11.10 kg vs 13.09 kg, P = .044) was noted in the pPEG versus nPEG groups. This benefit in reduction of percent weight loss was consistently significant only among patients with BMI < 25. Significant differences were noted in hospital admission rate (15.1% vs 26.7%, P = .026) and volume of nonchemotherapy hydration (8.9 liters vs 17.2 liters, P = .004). There were no differences in percent albumin change, acute dysphagia, acute mucositis, acute xerostomia, chronic dysphagia, radiation treatment duration, and overall survival. Multivariate analysis noted age >55 years (P < .001), female sex (P < .001), and T3/4 category disease (P < .001) were significantly associated with prolonged PEG use. CONCLUSIONS: Although pPEG reduced absolute and percent weight loss and need for hospitalizations in our cohort of patients with OPC undergoing chemoradiation, no differences were noted in radiation treatment duration, toxicity, and overall survival. Prolonged PEG use correlated with age >55 years, female sex, and T3/T4 tumors.

Time course and predictors for cancer-related fatigue in a series of oropharyngeal cancer patients treated with chemoradiation therapy.

BACKGROUND: Cancer-related fatigue (CRF) is a highly prevalent and underestimated symptom in cancer patients. This study aims to analyze CRF solely in a cohort of oropharyngeal cancer patients who underwent treatment with radiotherapy (RT). METHODS: In January 2008 to June 2010, 87 consecutive oropharyngeal carcinoma patients underwent definitive RT. Concurrent chemotherapy was used for 94% of patients. The median prescription dose to the planning target volume of the gross or clinical tumor volume was 70 Gy for definitive cases (n = 84) and 66 Gy for postoperative cases (n = 3), both delivered over 6.5 weeks. A normalized 12-point numeric rating scale assessed CRF from patient visits before, during, and after RT. RESULTS: The median follow-up of living patients was 14 months. Fatigue peaked 1-2 weeks post-RT and remained higher than baseline for up to 2 years post-RT in 50% of patients. The average fatigue score at the time of completion of therapy or maximum thereafter up to 1 year post-RT was significantly worse than baseline. Patients who experienced pain had a trend toward significance with association for a higher maximum difference in fatigue from baseline. Karnofsky performance status score, weight change, and mood disorders did not correlate with CRF. CONCLUSIONS: Fatigue was a common treatment-related symptom in this uniform cohort of patients with oropharyngeal cancer. RT was highly correlated with worsening of CRF. Pain control has the potential to help mitigate CRF in patients experiencing pain, and will need to be confirmed using larger datasets.

Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: an update of the Memorial Sloan-Kettering Cancer Center experience.

PURPOSE: To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC). METHODS AND MATERIALS: Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%. The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based. RESULTS: Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia ≥Grade 2 was 11% and 29%, respectively. CONCLUSIONS: Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.

Intensity-modulated radiation therapy in oropharyngeal carcinoma: effect of tumor volume on clinical outcomes.

PURPOSE: To analyze the effect of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) on treatment outcomes in patients treated with definitive intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC). METHODS AND MATERIALS: Between September 1998 and April 2009, a total of 442 patients with squamous cell carcinoma of the oropharynx were treated with IMRT with curative intent at our center. Thirty patients treated postoperatively and 2 additional patients who started treatment more than 6 months after diagnosis were excluded. A total of 340 patients with restorable treatment plans were included in this present study. The majority of the patients underwent concurrent platinum-based chemotherapy. The pGTV and nGTV were calculated using the original clinical treatment plans. Cox proportional hazards models and log-rank tests were used to evaluate the correlation between tumor volumes and overall survival (OS), and competing risks analysis tools were used to evaluate the correlation between local failure (LF), regional failure (RF), distant metastatic failure (DMF) vs. tumor volumes with death as a competing risk. RESULTS: Median follow-up among surviving patients was 34 months (range, 5-67). The 2-year cumulative incidence of LF, RF and DF in this cohort of patients was 6.1%, 5.2%, and 12.2%, respectively. The 2-year OS rate was 88.6%. Univariate analysis determined pGTV and T-stage correlated with LF (p < 0.0001 and p = 0.004, respectively), whereas nGTV was not associated with RF. On multivariate analysis, pGTV and N-stage were independent risk factors for overall survival (p = 0.0003 and p = 0.0073, respectively) and distant control (p = 0.0008 and p = 0.002, respectively). CONCLUSIONS: In this cohort of patients with OPC treated with IMRT, pGTV was found to be associated with overall survival, local failure, and distant metastatic failure.

Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer.

PURPOSE: To compare concurrent cisplatin (CDDP) and radiation (RT) with cetuximab (C225) and RT for locally advanced head-and-neck cancer (LAHNC). METHODS AND MATERIALS: This study retrospectively compared 174 consecutive, newly diagnosed LAHNC patients definitively treated from March 1, 2006, to April 1, 2008, with single-agent CDDP/RT (n = 125) or C225/RT (n = 49). We excluded patients who received additional concurrent, induction, or adjuvant systemic therapy; weekly cisplatin; prior head-and-neck radiotherapy; or primary surgical resection. Outcomes were analyzed by the Kaplan-Meier method, Cox model, and competing-risks analysis tools. RESULTS: The C225/RT patients were older and had decreased creatinine clearance. At a median follow-up of 22.5 months for living patients, the 2-year locoregional failure rate was 5.7% for CDDP/RT and 39.9% for C225/RT (p < 0.0001). The 2-year failure-free survival (FFS) and overall survival (OS) rates were 87.4% vs. 44.5% (p < 0.0001) and 92.8% vs. 66.6% (p = 0.0003), respectively, in favor of CDDP/RT. When the Cox proportional hazards model was used for multivariate analysis, treatment with CDDP/RT predicted for improved locoregional control (p < 0.0001), FFS (p < 0.0001), and OS (p = 0.01). Late Grade 3 or 4 toxicity or feeding tube dependence 9 months after completion of RT was observed in 21% of patients in the CDDP/RT cohort and 24% in the C225/RT cohort (p = 0.66). CONCLUSIONS: In this study of LAHNC patients, CDDP/RT achieved better locoregional control, FFS, and OS than C225/RT. Although the results were upheld on multivariate analysis, they must be interpreted cautiously because of the retrospective nature of the study and significant differences in patient selection. There was no statistically significant difference in late Grade 3 or 4 effects or feeding tube dependence.

Complications of radiation therapy to the hand after soft tissue sarcoma surgery.

PURPOSE: Radiation has been shown to improve local control after resection of soft tissue sarcomas. However, it may also result in major complications in the hand, given the compact nature of functional tissues and limited tissue volumes in the hand. The purpose of this investigation was to describe the hand-specific complications of radiation therapy for patients with soft tissue sarcoma of the hand (STSH). METHODS: We performed a retrospective chart review of 55 consecutive patients with STSH treated by a single surgeon between 1993 and 2006. We identified 26 patients who were treated with external beam radiation, brachytherapy, or both, either preoperatively or postoperatively, and reviewed their clinical course. RESULTS: After a median follow-up of 7 years, 29 treatment-related complications occurred in 19 patients who had received radiation, whereas 3 of the 29 patients treated with surgery alone developed complications. All patients who received brachytherapy and 14 of the 21 treated with external beam radiation alone developed complications. There were 5 early minor, 2 early major, 3 late minor, and 19 late major complications. CONCLUSIONS: Patients with STSH who underwent radiation therapy had a high rate of complications. The complication rate in our series was higher in patients who had brachytherapy catheters placed adjacent to finger joints. A better understanding of predictors of complications will help to determine the optimal timing and type of radiation therapy to treat patients with STSH. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

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.