Long-Term Outcomes of NRG Oncology/RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Anal Canal Cancer.

PURPOSE: A multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer. METHODS AND MATERIALS: T2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0 = 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3 = 45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3. RESULTS: Of 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy-5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction. CONCLUSIONS: Dose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.

Precision Medicine: Genomic Profiles to Individualize Therapy.

Precision medicine is the application of genotypic and Omics biomarkers to determine the most appropriate, outcome-driven therapy for individual patients. To determine the best choice of therapy, institutions use significant information technology-enabled data from imaging, electronic medical records, sensors in the clinic/hospitals, and wearable sensors to determine treatment response. With genomic profiling, targets to affect a disease course are continuing to be developed. As clonal mutational prevalence continues to be understood, information can be communicated to patients to inform them that resistance is common, requiring collection of more genetic mutations from patients with further biopsies or blood collection.

Curative treatment of esophageal cancer; an evidenced based review.

BACKGROUND: In 2013, roughly 18,000 cases of esophageal cancer will be diagnosed in the United States with more than 15,000 people dying from the disease. Worldwide, an estimated 482,300 new esophageal cancer cases were diagnosed with 406,800 deaths in 2008. Squamous cell carcinoma (SCC) and adenocarcinoma (AC) account for >90% of all esophageal cancer cases. METHODS: The authors will examine the role of radiation therapy, chemotherapy, and surgery in the curative management of esophageal cancer by examining randomized control data, single arm phase II trials, several recently published meta-analyses, as well as retrospective data where there is no clinical trial data available. The role of positron emission tomography (PET) will be reviewed as well. RESULTS: Current data support the role of neoadjuvant chemoradiotherapy followed by surgical resection for locally advanced esophageal cancer with 3-year overall survival ranging from 30% to 60%. The benefit of adjuvant chemoradiation therapy is limited to margin positive and/or node positive patients. There is emerging data questioning the survival benefit of surgical resection after chemoradiotherapy. External beam radiation therapy alone results in very few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. PET scanning is vital in staging and has become a strong predictor of response and survival. CONCLUSIONS: Preoperative or definitive concurrent chemoradiotherapy is the established standard of care for locally advanced cancers of the esophagus. While preoperative chemotherapy is supported by level 1 evidence, the true benefit of induction chemotherapy before chemoradiotherapy has not been established in a prospective randomized control trial. The role of surgery in the management of SCC is still a hotly debated subject, however, it is still recommended for AC. There is no data to support adjuvant chemotherapy after preoperative chemoradiotherapy. The benefit of neoadjuvant chemotherapy seems to be limited AC. Radiation without chemotherapy is palliative and never curative. PET continues to be integrated into treatment decisions and predicts for response and survival after therapy.

Mucosa-associated lymphoid tissue lymphoma and concurrent adenocarcinoma of the prostate.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is a rare disease that characteristically follows an indolent course. It is believed that infection or chronic inflammation may be triggers for malignant transformation in the prostate, but it is of unknown etiology. Reports of MALT lymphomas of the prostate with other concurrent primary prostate cancers are even more limited. We present the unique case of a 67-year-old male with concurrent adenocarcinoma of the prostate and primary MALT lymphoma of the prostate. The patient was treated with standard therapy for prostate adenocarcinoma, which would also treat a primary MALT lymphoma. He has been disease-free for over one year for both his primary malignancies. This case confirms that MALT lymphoma can arise concurrently with adenocarcinoma of the prostate.

Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer.

OBJECTIVE: Patients with early-stage invasive ductal breast cancer were prospectively evaluated using MammoSite RTS balloon brachytherapy (RTS Cytyc Corp, Marlborough, MA) as the sole modality for delivering accelerated partial breast irradiation to the lumpectomy bed with breast-conserving surgery. This report presents the 5-year results of the treated patients. METHODS: From May 2000 to October 2001, 70 patients were enrolled in this prospective study. Forty-three patients completed accelerated partial breast irradiation with MammoSite brachytherapy following lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years (mean 65.2 months). Criteria for entry into the study were unifocal invasive ductal carcinoma, tumor size < or = 2 cm, age > or = 45 years, absence of extensive intraductal component, cavity size > or = 3 cm in 1 dimension, node-negative, and final margins negative per National Surgical Adjuvant Breast and Bowel Project definition. A minimum balloon-to-skin surface distance of 5 mm was required. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose-rate brachytherapy. Data on infection, seromas, cosmetic outcome, and toxicities were collected at 3 and 6 months and at yearly intervals. Local recurrences, both true recurrences in the lumpectomy bed and failures outside the initially treated target volume (elsewhere failures), were recorded. Contralateral breast failure rates were noted. RESULTS: The catheter was not implanted in 16 of the 70 enrolled patients due to cavity size not amenable to balloon placement (n = 10), ineligible by criteria (n = 4), and skin spacing (n = 2). Fifty-four patients were implanted and 43 were successfully treated with MammoSite balloon brachytherapy. Reasons for catheter explantation in 11 patients were poor cavity conformance in 7, inadequate skin spacing in 2, positive node in 1 and age less than 45 years in 1. Of the 43 patients who completed treatment, the infection rate was 9.3%. Seroma formation occurred in 32.6% of patients, of which 12% were symptomatic requiring aspiration. Asymptomatic fat necrosis was identified in 4 of the 43 patients, noted from time of catheter removal at 11, 14, 42, and 63 months. Good-excellent cosmetic outcomes were achieved in 83.3% of the 36 patients with more than 5 years of follow-up. Cosmetic outcomes were improved, with increased skin spacing having statistical significance at skin spacing > or = 7 mm. The only serious adverse events were 2 infections: mastitis and abscess. Seven of the 43 treated patients have been discontinued from follow-up. None had a local recurrence recorded at last visit. Reasons for exit from the study were death from metastatic disease (n = 3), lost to follow-up (n = 2), and placed in hospice for other medical conditions (n = 2). No local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. No contralateral cancers have developed. CONCLUSIONS: MammoSite balloon brachytherapy as a sole modality for delivering radiation to the tumor bed has been successful in achieving excellent local control in this initial clinical study of patients with early-stage invasive ductal breast cancer. This has been achieved with minimal toxicities and good-excellent cosmetic outcomes in 83.3%. Accelerated partial breast irradiation using the MammoSite balloon in a carefully selected group of patients has demonstrated 5-year local recurrence results comparable to those achieved with conventional whole breast radiation therapy and interstitial catheter brachytherapy as reported at 5-year data points in studies of these treatment modalities. Poor cavity conformance and inadequate skin distance were the main factors limiting use of the MammoSite device. Extended follow-up will be required to determine the long-term efficacy of this treatment modality.

Lay patient navigator program implementation for equal access to cancer care and clinical trials: essential steps and initial challenges.

BACKGROUND: Disparities in cancer detection, treatment, and outcomes among racial/ethnic minorities and low-income patients are well documented. One way to reduce these disparities is to use patient navigators to address barriers to care. However, little information about optimal characteristics of navigator programs or considerations for those interested in setting up such programs is available. METHODS: The design and implementation of a patient navigator program for underserved cancer patients in an urban, nonacademic community hospital setting is described. The program, which used lay navigators, was conceived as a component of the Urban Latino African American Cancer (ULAAC) Disparities Project in South Los Angeles, a National Cancer Institute (NCI)-sponsored project to improve cancer care and clinical trial access for minority and low-income patients. RESULTS: Careful initial planning, including input from a community advisory committee, was essential to smooth program implementation. Thirty-one volunteers completed navigator training in the program's first year of operation. Of 135 patients offered navigation services, 75 (56%) accepted, and preliminary feedback from patients, navigators, and providers suggests high levels of satisfaction with navigation. Standardized templates used by navigators and staff to record key information are proving helpful for monitoring quality and outcomes (such as effectiveness in addressing specific barriers to care) and continually improving the program. CONCLUSIONS: The ULAAC program represents a viable model for developing lay navigator programs in community hospitals. Preliminary assessments suggest that the program has a positive effect on minority and low-income cancer patients' experience with care and reduces barriers to care. Additional time and research are needed, however, to fully assess the impact on care and outcomes.

Preliminary results and evaluation of MammoSite balloon brachytherapy for partial breast irradiation for pure ductal carcinoma in situ: a phase II clinical study.

BACKGROUND: This report presents the preliminary results and evaluation of the MammoSite balloon catheter (MammoSite Radiation Therapy System; Cytyc Corporation, Marlboro, MA) as the sole method of delivering partial breast irradiation to the lumpectomy bed with breast-conserving surgery in patients with pure ductal carcinoma in situ (DCIS). METHODS: Twelve institutions are participating in this phase II clinical study. A total of 133 patients have been enrolled and 100 patients have successfully completed the prescribed radiation therapy. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose rate brachytherapy. Patients who met the following criteria were selected for enrollment into the study: age 45 years or older, unicentric pure DCIS, mammographic lesion of 3 cm or less, negative margins as defined by 1 mm or more, postoperative final gross pathologic size of tumor of 5 cm or less, clinically node negative, and a postlumpectomy mammogram showing the absence of any residual suspicious microcalcifications. The placement of the MammoSite catheter was performed either at the time of the lumpectomy or postlumpectomy. The minimum distance from the balloon surface to the surface of the skin is greater than 5 mm. Data collection points are at time of enrollment, time of implant, 3 months, 6 months, and then yearly at 1- to 5-year follow-up visits. Data collected are local control rates, cosmetic outcome using the Harvard Scale, toxicities, serious adverse events, disease-free survival, cause-specific survival, and contralateral breast failure. The Van Nuys Prognostic Index scores were calculated for each patient. Local recurrence is defined as either invasive or noninvasive recurrence within the target volume. Ipsilateral elsewhere recurrence is defined as either an invasive or noninvasive recurrence occurring outside of the target volume in the previously treated breast. This recurrence is classified as a new primary tumor. RESULTS: The mean follow-up period was 9.5 months (range, 1-24 mo). The MammoSite catheter was explanted for the following reasons: inadequate skin distance (5.1%; 6 of 117), poor cavity conformance (5.1%; 6 of 117), positive margins (2.6%; 3 of 117), final histology (.85%; 1 of 117), and physician decision (.85%; 1 of 117). Of the patients in whom the MammoSite was explanted because of skin spacing or cavity conformance, 50% were at sites of new users (institutions that have placed fewer than 10 Mammosite catheters). Cosmetic results were rated as excellent in 63%, good in 35%, and fair in 2% in the 86 patients with a follow-up visit. Two patients were diagnosed with an ipsilateral local recurrence, 1 outside of the target volume and 1 true recurrence/marginal miss. One patient was diagnosed at 8 months and the other was diagnosed at 11 months. Both of these ipsilateral failures were DCIS. The Van Nuys Prognostic Index of these 2 patients was 9 and 8, respectively. Data collected showed the mean age at placement was 60.8 y, mean tumor size was 10.6 mm, mean actual closest surgical margin was 6.8 mm (range, .1-40 mm), a re-excision rate of 35%, postlumpectomy placement was 71%, and the mean skin-to-balloon surface distance was 13 mm with 89% > or =7 mm. No serious adverse events were reported. The infection rate was 4.0%. CONCLUSIONS: Accelerated partial breast irradiation delivered with the MammoSite balloon was clinically successful in patients entered into a phase II clinical study with pure DCIS, with results comparable with other studies reported in the literature that have evaluated use of the MammoSite balloon brachytherapy for delivery of radiation therapy in early breast cancers. Inadequate skin distance and poor cavity conformance were the main factors limiting the use of the MammoSite device. Cosmetic results were good to excellent in 98%. There have been 2 ipsilateral breast recurrences.

Gene expression in tumor-adjacent normal tissue is associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation.

Recurrence is a significant clinical problem for patients with rectal cancer treated with adjuvant chemoradiation. Previous studies have suggested that determining intratumoral gene expression of key genes may be helpful in predicting clinical outcome of patients with gastrointestinal malignancies undergoing chemotherapy. The role of molecular predictors for prediction of recurrence in the setting of adjuvant chemoradiotherapy is not well established. The present study was designed to identify a genetic profile that would be associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation therapy. A retrospective study with a longitudinal cohort and a cross-sectional cohort of 67 patients with locally advanced rectal cancer who underwent cancer resection, followed by 5-fluorouracil (5-FU) plus pelvic radiation was conducted. Total RNA was extracted from formalin-fixed, paraffin-embedded, laser-captured-microdissected tissue. We determined mRNA levels of genes involved in the 5-FU pathway (thymidylate synthase, dihydropyrimidine dehydrogenase), DNA-repair (excision-repair cross-complementing factor 1, Rad51), angiogenesis/radiation sensitivity [vascular endothelial growth factor (VEGF)] and radio-sensitivity [epidermal growth factor receptor (EGFR)] in tumor tissue and tumor-adjacent normal tissue by quantitative reverse transcriptase-polymerase chain reaction. In univariate analysis, only intratumoral gene expression level of VEGF (P = 0.055) was associated with recurrence, whereas elevated mRNA expression levels of thymidylate synthase (P = 0.008), VEGF (P = 0.023) and EGFR (P = 0.004) in tumor-adjacent normal tissue were significantly associated with recurrence. Multivariate analysis using recursive partitioning indicated that distinct groups of recurrence could be defined by elevated mRNA expression levels of VEGF, EGFR in tumor-adjacent normal tissue, and Rad51 in tumor tissue. These data suggest that the genetic profile of the tumor-adjacent normal tissue may be associated with treatment failure, indicating that tumor microenvironment may be more important in the development of recurrence of rectal tumors than formerly expected.

Optimization of MammoSite therapy.

PURPOSE: Radiation source anisotropy causes about 10% of a spherically shaped planning target volume surrounding a MammoSite balloon to receive less than the prescribed dose. The principal dose-limiting factor for MammoSite therapy is the dose to the overlying skin. Additional limiting factors potentially include the dose to portions of the heart and lung. The goal of optimization is to deliver the prescribed dose to as much of the planning target volume as possible while avoiding toxicity to adjacent organs. METHODS AND MATERIALS: An experimental CT-based high-dose-rate brachytherapy treatment planning system was used to investigate optimization strategies for MammoSite treatment. This system implements a linear optimization of high-dose-rate dwell times on the basis of constraints assigned to points of interest and a set of potential dwell positions. RESULTS: The cylindrical symmetry of the MammoSite catheter limits the optimization process to creating spherical, ellipsoidal, or egg-shaped isodose distributions whose major axis is oriented along the catheter axis. If the dose to a limiting structure, such as skin, is not an issue, the use of multiple dwell positions can compensate for source anisotropy and create a more spherical isodose surface enclosing the planning target volume compared with a single dwell position. When skin becomes a dose-limiting factor, the catheter axis orientation, source anisotropy, dwell position, and dwell weighting can be exploited to limit the skin dose while simultaneously preserving the prescribed dose to as much of the target volume as possible. CONCLUSION: Optimization of MammoSite therapy using multiple dwell positions within the balloon is both possible and practical.

MammoSite radiation therapy system.

The MammoSite Radiation Therapy System (RTS) has become the most widely used brachytherapy method used in the treatment of breast cancer, due to its ease of use, short learning curve, and requirement of only one interstitial path through the breast skin. The dosimetry is simple, one source position in the middle of the MammoSite balloon catheter. The data on long-term complications, however are not available, though developing. Trials for DCIS are being developed, as well as a comparison trial to standard external beam radiation as well as other forms of accelerated partial breast irradiation (APBI).

Use of high-dose-rate brachytherapy in the management of locally recurrent rectal cancer.

INTRODUCTION: Locally recurrent rectal cancer is associated with poor quality of life and has justified aggressive surgical and adjuvant approaches to control the disease. This study was designed to evaluate the use of fractionated perioperative high-dose-rate brachytherapy in association with wide surgical excision (debulking). Our hypothesis is that this combined therapy can help control locally recurrent rectal cancer. METHODS: Patients with biopsy-proven locally recurrent rectal cancer that could not be completely removed surgically were considered candidates for this procedure. All patients had abdominal exploration, aggressive tumor debulking, and placement of afterloading brachytherapy catheters. Patients underwent simulation on postoperative Day 3 and received 1,200 to 2,500 (mean, 1,888) cGy of fractionated high-dose-rate brachytherapy between postoperative Days 3 and 5. All patients had involvement of the lateral pelvic sidewall and/or the sacrum. RESULTS: Twenty-seven patients (18 males) aged 32 to 79 years underwent therapy. Follow-up ranged from 18 to 93 (mean, 50) months and was available in 27 patients. Ten patients (37 percent) were alive at the time of this report. Nine patients are without evidence of disease. Five patients (18 percent) died of non-cancer-related causes without evidence of recurrent disease. Five complications potentially related to treatment (3 abscesses, 2 fistulas) occurred in five patients. CONCLUSION: High-dose radiation brachytherapy delivers high-dose, highly controlled, focused radiation to specific sites of disease, thereby minimizing injury to normal tissues. The results in this series suggest increased local control, better palliation, and increased salvage of patients.

The use of linear programming in optimization of HDR implant dose distributions.

The introduction of high dose rate brachytherapy enabled optimization of dose distributions to be used on a routine basis. The objective of optimization is to homogenize the dose distribution within the implant while simultaneously satisfying dose constraints on certain points. This is accomplished by varying the time the source dwells at different locations. As the dose at any point is a linear function of the dwell times, a linear programming approach seems to be a natural choice. The dose constraints are inherently linear inequalities. Homogeneity requirements are linearized by minimizing the maximum deviation of the doses at points inside the implant from a prescribed dose. The revised simplex method was applied for the solution of this linear programming problem. In the homogenization process the possible source locations were chosen as optimization points. To avoid the problem of the singular value of the dose at a source location from the source itself we define the "self-contribution" as the dose at a small distance from the source. The effect of varying this distance is discussed. Test cases were optimized for planar, biplanar and cylindrical implants. A semi-irregular, fan-like implant with diverging needles was also investigated. Mean central dose calculation based on 3D Delaunay-triangulation of the source locations was used to evaluate the dose distributions. The optimization method resulted in homogeneous distributions (for brachytherapy). Additional dose constraints--when applied--were satisfied. The method is flexible enough to include other linear constraints such as the inclusion of the centroids of the Delaunay-triangulation for homogenization, or limiting the maximum allowable dwell time.

Radiation medicine innovations for the new millenium.

PURPOSE OF THE STUDY: To review technological advances in the field of radiation oncology in the management of benign and malignant diseases. BASIC PROCEDURES: We reviewed major advances in the field of radiation oncology in the past decade with special emphasis on reduction of treatment related toxicities, and technological improvements in planning and delivery of radiation. Modalities reviewed include computerized three-dimensional conformal treatment planning, stereotactic radiosurgery, intensity-modulated radiation therapy, ultrasound-guided transperineal permanent brachytherapy of the prostate, and high-dose rate brachytherapy. MAIN FINDINGS: There have been major technological advances as evidenced by a decrease in treatment-related toxicities and better target definition resulting in higher local control rates. PRINCIPAL CONCLUSIONS: Significant improvements in technique and equipment have firmly positioned radiotherapy as major artillery in the fight against both benign and malignant diseases.

Initial clinical experience with the MammoSite breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We present the results of the initial clinical testing of the MammoSite balloon breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. METHODS AND MATERIALS: Seventy patients were enrolled in a multicenter prospective trial testing the applicator for safety and performance. Fifty-four patients were implanted, and 43 patients were ultimately eligible for and received brachytherapy as the sole radiation modality after lumpectomy. Patients were staged T1N0M0 with negative pathologic margins and age >45 years. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using 192Ir high-dose-rate brachytherapy. A minimum skin-to-balloon surface distance of 5 mm was required for treatment. Device performance, complications, and cosmesis were assessed. RESULTS: Computed tomography imaging post-balloon inflation showed 8, 14, and 21 patients with 5-6 mm, 7-9 mm, and >10 mm of skin spacing, respectively. Two patients were explanted because of inadequate skin spacing and 7 because of suboptimal conformance of the surgical cavity to the applicator balloon. One patient was explanted because of positive nodal status and another because of age. The most common side effects related to device placement included mild erythema, drainage, pain, and echymosis. No severe side effects related to implantation, brachytherapy, or explantation occurred. Side effects related to radiation therapy were generally mild with erythema, pain, and dry desquamation being the most common. At 1 month, 88% of patients were evaluated as having good-to-excellent cosmetic results. CONCLUSIONS: The MammoSite balloon breast brachytherapy applicator performed well clinically. All eligible patients completed treatment. Side effects were mild to moderate and self-limiting. Skin-balloon surface distance and balloon-cavity conformance were the main factors limiting the initial use of the device.

Breast-conserving therapy for ductal carcinoma in situ: a 20-year experience with excision plus radiation therapy.

BACKGROUND: Breast conservation therapy is a practical alternative to mastectomy for the treatment of ductal carcinoma in situ (DCIS). The role of radiation therapy after excision for DCIS has been debated, however, its value in reducing recurrence has been proven by multiple prospective randomized trials and is well accepted. METHODS: We examined a prospective database of 260 patients treated for DCIS with excision and radiation from 1979 to 2002. Two different treatment regimens were examined for local recurrence-free survival. Patients treated with radiation therapy 4 days per week were compared with patients treated 5 days per week. The total doses were similar for both groups; boost types differed. Local recurrence as a function of other factors, including nuclear grade, comedonecrosis, and margin width was evaluated. RESULTS: The median time to local recurrence was 61 months for patients treated 4 days per week compared with 52 months for patients treated 5 days per week (P = not significant). There was no statistical difference in the Kaplan-Meier detailing the probability of local recurrence-free survival for patients treated 4 days per week versus patients treated 5 days per week. Overall, cosmetic results between the two groups were equivalent. CONCLUSIONS: The comparison of two different radiation treatment regimens shows no difference in local disease-free survival or cosmetic result.

Postoperative radiotherapy in 423 patients with pT3N0 prostate cancer.

PURPOSE: To evaluate the treatment outcome in pT3N0 patients with adenocarcinoma of the prostate treated with an elective course of postoperative irradiation (RT). METHODS AND MATERIALS: During a 22-year period, a total of 423 pT3N0 prostate cancer patients were treated at a single medical center with prostatic fossa RT, which was the only adjuvant therapy given. The patient characteristics were as follows: median age 66 years; Stage pT3aN0 in 296 (70%) and pT3bN0 in 127 (30%); Gleason score 2-4 in 12 (2.8%), 5-6 in 157 (37.1%), 7 in 151 (35.7%), and 8-10 in 100 (23.6%); and the median and mean preoperative prostate-specific antigen (PSA) level was 10 and 15.9 ng/mL, respectively. Radiotherapy consisted of a median dose of 48 Gy delivered to the prostatic fossa and its immediate vicinity. The median follow-up was 7 years. RESULTS: The 5- and 10-year actuarial survival rate was 92% and 73%, respectively, and the 5- and 10-year disease-free survival rate (PSA <0.05 ng/mL) was 69% and 51%, respectively. In multivariate analysis, the Gleason score was the most important predictor for survival (p = 0.00005), and pathologic stage and Gleason score were independently predictive of disease-free survival (p = 0.00007 and 0.0003, respectively). The worst prognostic category was represented by pT3bN0, Gleason score 7-10 patients who had a 5.3 times greater risk of tumor recurrence than those with pT3aN0, Gleason score 2-6. A high (>25 ng/mL) preoperative PSA level was also a predictor of tumor recurrence (p = 0.03). A total of 43 patients (10.2%) developed clinical recurrence. This included 30 patients (7%) with distant metastases alone and 13 (3%) with local recurrence, which included 2 patients who also had distant disease. An additional 88 patients (20%) had PSA elevation (>0.05 ng/mL). This treatment program was well tolerated, with acute toxicity common (62%) but of no clinical significance. No late or severe toxicity was recorded. CONCLUSION: Adjuvant radiotherapy, as given in this study, appears to substantially reduce the expected incidence of local tumor recurrence in pT3N0 prostate cancer patients. The treatment outcome was poor in pT3bN0 and Gleason score 7-10 patients, with >80% showing evidence of clinical or PSA recurrence at 10 years after therapy. This group should be the target of a prospective trial of systemic therapy.