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Purpose: The possibility that prostate cancers have a low alpha/ß ratio led to a schedule including a hypofractionated boost. The purpose of this study was to analyze the outcomes of this regimen. Patients and Methods: Between 2002 and 2007, 125 patients with localized prostate cancer were treated. Median follow-up was 33 months. Radiation therapy was delivered to a planning target volume including the prostate and seminal vesicles with a 1-1.5 cm margin to block edge using a 6-field technique to 45 Gy in 25 fractions. This was followed by a 2.5-Gy/fraction intensity-modulated radiation therapy boost to the prostate alone to a total dose of 75 Gy in 61 low-risk patients and 77.5 Gy to the prostate and seminal vesicles in 64 high- and intermediate-risk patients. Results: There have been 2 (1.6%) biochemical failures, 1 death from prostate cancer, and 1 death in a patient with no evidence of disease. Rates of acute genitourinary and gastrointestinal toxicity (grade 1 and 2) for the whole group were 31.2% and 16%, respectively. Rates of chronic genitourinary and gastrointestinal toxicity (grade 1 and 2) for the whole group were 30.4% and 27.2%, respectively. There were 2 patients (1.6%) with grade 3 gastrointestinal toxicity at 12 and 18 months' follow-up. They had radiation proctitis requiring laser cauterization. Conclusion: The preliminary results of this novel schedule were excellent. Given that the alpha/ß ratio is still in question, this technique addresses concerns regarding low and high ratios. This technique is a suitable alternative method of dose escalation in the treatment of localized prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: This phase I/II, multi-institutional trial explored the tolerance and efficacy of stepwise increasing hypofractionation (HPFX) radiation therapy regimens for fraction sizes up to 4.3 Gy in localized prostate cancer., Methods and Materials: Three escalating dose-per-fraction schedules were designed to yield similar predicted tumor control while maintaining equivalent predicted late toxicity. HPFX levels I, II, and III were carried out sequentially and delivered schedules of 64.7 Gy/22 fx/2.94 Gy, 58.08 Gy/16 fx/3.63 Gy, and 51.6 Gy/12 fx/4.3 Gy, respectively with next level escalations contingent upon acceptable gastrointestinal (GI) toxicity. The primary endpoints were biochemical control and toxicity., Results: A total of 347 patients were recruited by 5 institutions with 101, 111, and 135 patients treated on HPFX levels I, II, and III with median follow-ups of 100, 85.5, and 61.7 months, respectively (83.2 months combined). The National Comprehensive Cancer Network low- or intermediate-risk group distribution was 46% and 54%, respectively. Sixteen percent of patients, primarily intermediate risk, received 6 months of androgen deprivation therapy. The 8-year nadir + 2 actuarial biochemical control rates for HPFX levels I, II, and III were 91.1% ± 3.0%, 92.7% ± 2.7%, and 88.5% ± 4.6%, respectively (Kaplan-Meier log rank, 0.903). Among clinical covariates, only Gleason score reached near significance in multivariate analysis (P = .054). Twenty-six patients failed biochemically (crude incidence of 7.5%), and there were 5 cause-specific deaths. GI and genitourinary toxicities were acceptable and similar across the 3 HPFX levels. The combined actuarial cumulative incidence of grade 2+ GI and genitourinary toxicities at 7 years were 16.3% ± 2.1% and 22.1% ± 2.4%, respectively., Conclusions: HPFX employing fraction sizes extending into the 3.6 to 4.3 Gy/fraction range can be delivered with excellent oncologic outcomes. Such schedules, positioned between moderate and ultra-HPFX, may provide additional options for patients wishing to avoid prolonged treatment schedules associated with conventionally fractionated radiation therapy for prostate cancer., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective: This multi-institutional phase I/II trial explored patient-assessed tolerance of increasingly hypofractionated (HPFX) radiation for low/intermediate risk prostate cancer., Methods: 347 patients enrolled from 2002 to 2010. Three increasing dose-per-fraction schedules of 64.7 Gy/22 fx, 58.08 Gy/16 fx and 51.6 Gy/12 fx were each designed to yield equivalent predicted late toxicity. Three quality of life (QoL) surveys were administered prior to treatment and annually upto 3 years., Results: Bowel QoL data at 3years revealed no significant difference among regimens (p=0.469). Bowel QoL for all regimens declined transiently, largely recovering by three years, with only the 22 fraction decrement reaching significance. Bladder outcomes at 3 years were comparable (p=0.343) although, for all patients combined, a significant decline was observed from the baseline (p=0.008). Spitzer quality of life data revealed similarly excellent, 3-year means (p=0.188). International erectile function data also revealed no significant differences at 3 years although all measures except intercourse satisfaction worsened post-treatment., Conclusions: Three-year QoL changes for bowel, bladder and SQLI were modest and similar for 3 HPFX regimens spanning 2.94-4.3 Gy per fraction. These favorable patient-scored outcomes demonstrate the safety and tolerability of such regimens and may be leveraged to support further implementation of mild to moderately hypofractionated radiotherapy in the setting of low and intermediate-risk prostate cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Soy isoflavones sensitize prostate cancer cells to radiation therapy by inhibiting cell survival pathways activated by radiation. At the same time, soy isoflavones have significant antioxidant and anti-inflammatory activity, which may help prevent the side effects of radiation. Therefore, we hypothesized that soy isoflavones could be useful when given in conjunction with curative radiation therapy in patients with localized prostate cancer. In addition to enhancing the efficacy of radiation therapy, soy isoflavones could prevent the adverse effects of radiation. We conducted a pilot study to investigate the effects of soy isoflavone supplementation on acute and subacute toxicity (≤6 mo) of external beam radiation therapy in patients with localized prostate cancer. Forty-two patients with prostate cancer were randomly assigned to receive 200 mg soy isoflavone (Group 1) or placebo (Group 2) daily for 6 mo beginning with the first day of radiation therapy, which was administered in 1.8 to 2.5 Gy fractions for a total of 73.8 to 77.5 Gy. Adverse effects of radiation therapy on bladder, bowel, and sexual function were assessed by a self-administered quality of life questionnaire at 3 and 6 mo. Only 26 and 27 patients returned completed questionnaires at 3 and 6 mo, respectively. At each time point, urinary, bowel, and sexual adverse symptoms induced by radiation therapy were decreased in the soy isoflavone group compared to placebo group. At 3 mo, soy-treated patients had less urinary incontinence, less urgency, and better erectile function as compared to the placebo group. At 6 mo, the symptoms in soy-treated patients were further improved as compared to the placebo group. These patients had less dripping/leakage of urine (7.7% in Group 1 vs. 28.4% in Group 2), less rectal cramping/diarrhea (7.7% vs. 21.4%), and less pain with bowel movements (0% vs. 14.8%) than placebo-treated patients. There was also a higher overall ability to have erections (77% vs. 57.1%). The results suggest that soy isoflavones taken in conjunction with radiation therapy could reduce the urinary, intestinal, and sexual adverse effects in patients with prostate cancer.

Objectives: It is unclear whether postoperative salvage radiation therapy (SRT) and early adjuvant radiotherapy (ART) after radical prostatectomy lead to equivalent long-term tumor control. We studied a group of patients undergoing ART by comparing them with a matched control group undergoing SRT after biochemical failure., Methods: Using a multi-institutional database of 2299 patients, 449 patients with pT3-4N0 disease were eligible for inclusion, including 211 patients receiving ART and 238 patients receiving SRT. Patients were matched in a 1:1 ratio according to preoperative prostate-specific antigen Gleason score, seminal vesicle invasion, surgical margin status, and follow-up from date of surgery., Results: A total of 192 patients were matched (96:96). The median follow-up was 94 months from surgery and 73 months from RT completion. There was a significant reduction in biochemical failure with ART compared with SRT. The 5-year freedom from biochemical failure (FFBF) from surgery was 75% after ART, compared with 66% for SRT (hazard ratio [HR] = 1.6, P = .049). The 5-year FFBF from the end of RT was 73% after ART, compared with 50% after SRT (HR = 2.3, log rank [LR] P = .0007). From the end of RT, SRT and Gleason score >or=8 were independent predictors of diminished FFBF. From the date of surgery, Gleason score >or=8 was a significant predictor of FFBF., Conclusions: Early ART for pT3-4N0 prostate cancer significantly reduces the risk of long-term biochemical progression after radical prostatectomy compared with SRT. Gleason score >or=8 was the only factor on multivariate analysis associated with metastasic progression.

Purpose: From the randomized study Southwest Oncology Group 8794 we evaluated the effect of seminal vesicle involvement on outcomes and whether those patients benefited from post-prostatectomy adjuvant radiation therapy., Materials and Methods: Southwest Oncology Group study 8794 randomized high risk patients (with seminal vesicle positive disease and/or capsular penetration and/or positive margins) to radiation vs observation after prostatectomy. A total of 431 subjects with pathologically advanced prostate cancer were randomized., Results: Median followup was 12.2 years. Of the patients 139 had seminal vesicle involvement with or without capsular penetration and/or positive margins. Compared to the 286 patients with seminal vesicle negative disease there was poorer 10-year biochemical failure-free survival (33% for seminal vesicle negative and 22% for seminal vesicle positive, p = 0.04), metastasis-free survival (70% and 56%, respectively, p = 0.005) and overall survival (10-year overall survival 74% and 61%, respectively, p = 0.02) for those with seminal vesicle positive disease. Patients with seminal vesicle positive disease who received adjuvant radiation compared to observation realized an improvement in 10-year biochemical failure-free survival from 12% to 36% (p = 0.001), in 10-year overall survival from 51% to 71% (p = 0.08) and in metastasis-free survival from 47% to 66% (p = 0.09), respectively., Conclusions: Although seminal vesicle involvement is a negative prognostic factor, long-term control is possible especially if patients are given adjuvant radiation therapy. This therapy appears to be effective in patients with seminal vesicle involvement.

Background: Few intervention studies have been conducted to help couples manage the effects of prostate cancer and maintain their quality of life. The objective of this study was to determine whether a family-based intervention could improve appraisal variables (appraisal of illness or caregiving, uncertainty, hopelessness), coping resources (coping strategies, self-efficacy, communication), symptom distress, and quality of life in men with prostate cancer and their spouses., Methods: For this clinical trial, 263 patient-spouse dyads were stratified by research site, phase of illness, and treatment; then, they were randomized to the control group (standard care) or the experimental group (standard care plus a 5-session family intervention). The intervention targeted couples' communication, hope, coping, uncertainty, and symptom management. The final sample consisted of 235 couples: 123 couples in the control group and 112 couples in the experimental group. Data collection occurred at baseline before randomization and at 4 months, 8 months, and 12 months., Results: At 4-month follow-up, intervention patients reported less uncertainty and better communication with spouses than control patients, but they reported no other effects. Intervention spouses reported higher quality of life, more self-efficacy, better communication, and less negative appraisal of caregiving, uncertainty, hopelessness, and symptom distress at 4 months compared with controls, and some effects were sustained to 8 months and 12 months., Conclusions: Men with prostate cancer and their spouses reported positive outcomes from a family intervention that offered them information and support. Programs of care need to be extended to spouses who likely will experience multiple benefits from intervention., (2007 American Cancer Society)

Purpose: Despite the high prevalence of prostate cancer, little information is available on the quality of life of men and their spouses during the phases of illness. This study assessed patients' and spouses' quality of life, appraisal of illness, resources, symptoms, and risk for distress across three phases of prostate cancer: newly diagnosed, biochemical recurrence, and advanced., Patients and Methods: The sample consisted of 263 patient/spouse dyads. A stress-appraisal conceptual model guided the selection of variables which were then assessed with established instruments. Study variables were examined for phase effects (differences in dyads across three phases), role effects (patients v spouses), and phase-by-role interactions (differences within dyads across phases) using analysis of variance (ANOVA)., Results: More phase effects than role effects were found, indicating that the psychosocial experiences of patients and their spouses were similar, but differed from dyads in other phases. Dyads in the advanced phase were at highest risk for distress. These patients had the lowest physical quality of life, and their spouses had the lowest emotional quality of life of all participants. Dyads in the biochemical recurrence and advanced phases had more negative appraisals of illness and caregiving, greater uncertainty, and more hopelessness compared with dyads in the newly diagnosed phase. Spouses, in contrast to patients, had less confidence in their ability to manage the illness and perceived less support across all phases of illness., Conclusion: Phase-specific programs of care are needed to assist both men with prostate cancer and their spouses to manage the effects of illness.

Teletherapy with high linear energy transfer radiations (LET), perhaps more than with low LET types, requires careful beam collimation to limit effects to normal structures. Intensity modulated techniques may also hold promise in this regard. Accordingly, a remote computer-controlled, high-resolution multileaf collimator (MLC) is placed into service at the Gershenson Radiation Oncology Center's fast neutron therapy center of the Karmanos Cancer Institute, Detroit, Michigan. Prior to clinical application the basic radiological properties of the fast neutron MLC are studied. Complicating the evaluation is the mixed neutron and gamma radiation field environment encountered with fast neutron beams. As a reference the MLC performance is compared to an existing multirod collimator (MRC) used at the facility for more than ten years. The MLC aggregate transmission is found to be about 4%, slightly outperforming the MRC. The measured gamma component for a closed collimator is 1.5 times higher for the MLC, compared with the MRC. The different materials used for attenuation, steel and tungsten, respectively account for the difference. The geometry for the MRC is double focused whereas that for the MLC is single focused. The resulting penumbrae agree between the focused axis of the MLC and both axes of the MRC. Penumbra differences between the focused and unfocused axes were not observable at small field sizes and a maximum of about 1 cm for a 25 x 25 cm2 field at 2.5 cm depth in water. For a 10 x 10 cm2 field the focused penumbra is 9 mm, and the unfocused is 12 mm. The many benefits of the fully automatic MLC over the semimanual MRC are considered to justify this compromise.

Purpose: This study investigates the enhanced conformality of neutron dose distributions obtainable through the application of intensity modulated neutron radiotherapy (IMNRT) to the treatment of prostate adenocarcinoma., Methods and Materials: An in-house algorithm was used to optimize individual segments for IMNRT generated using an organ-at-risk (OAR) avoidance approach. A number of beam orientation schemes were investigated in an attempt to approach an optimum solution. The IMNRT plans were created retrospectively for 5 patients previously treated for prostate adenocarcinoma using fast neutron therapy (FNT), and a comparison of these plans is presented. Dose distributions and dose-volume histograms (DVHs) were analyzed and plans were evaluated based on percentage volumes of rectum and bladder receiving 95%, 80%, and 50% (V(95), V(80), V(50)) of the prescription dose, and on V(60) for both the femoral heads and GM(muscle) group., Results: Plans were normalized such that the IMNRT DVHs for prostate and seminal vesicles were nearly identical to those for conventional FNT plans. Use of IMNRT provided reductions in rectum V(95) and V(80) of 10% (2-27%) and 13% (5-28%), respectively, and reductions in bladder V(95) and V(80) of 12% (3-26%) and 4% (7-10%), respectively. The average decrease in V(60) for the femoral heads was 4.5% (1-18%), with no significant change in V(60) for the GM(muscle) group., Conclusions: This study provides the first analysis of the application of intensity modulation to neutron radiotherapy. The IMNRT technique provides a substantial reduction in normal tissue dose in the treatment of prostate cancer. This reduction should result in a significant clinical advantage for this and other treatment sites.

Purpose: In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature., Materials and Methods: Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions., Results: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes., Conclusions: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Purpose: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy., Materials and Methods: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment., Results: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published., Conclusions: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.

Purpose: The object of this study was to evaluate the duration of response to intermittent androgen deprivation (IAD) in patients with nonmetastatic recurrent or localized prostate cancer., Patients and Methods: One hundred ten patients received IAD from February 1992 to February 2005. One hundred three patients were treated after failure of primary radiation therapy and/or prostatectomy, with the remaining 7 patients treated primarily with IAD. The median duration of treatment cycle was 6 months. Patients were considered resistant to hormone therapy if the prostate-specific antigen (PSA) level increased, with castrate levels of testosterone. At the time of initial diagnosis, the median Gleason score was 7 (range, 4-9), and tumor stages were as follows: T1/T2 (n = 73), T3 and T4 N1 (n = 34), and other (n = 3). The median PSA at the initiation of IAD was 8.25 ng/mL., Results: The median follow-up after beginning IAD was 45.5 months. Patients received a median of 2 cycles (range, 1-9 cycles). Ninety-four of 110 patients (85.5%) remained responsive to IAD. Sixteen patients (14.5%) progressed to become refractory to primary hormone treatment. Patients with a higher tumor stage (T3 and T4) were significantly more likely to develop resistance. The median time to become refractory to hormone therapy was 47.9 months (range, 9.4-93.4 months). Five patients were put on secondary continuous hormone treatment, and 3 of them developed resistance at a median of 9 months. One patient was put on a secondary IAD and was still responding at the last follow-up., Conclusion: With 85.5% of the original patient population still responding to the primary hormone therapy at 45.5 months of follow-up, IAD appears to be a viable option for patients with biochemical failure after local radiation therapy. A pattern of shortening time between cycles and an increasing nadir PSA level with each successive cycle is consistent with the gradual development of hormone resistance.

The electromechanical properties of a 120-leaf, high-resolution, computer-controlled, fast neutron multileaf collimator (MLC) are presented. The MLC replaces an aging, manually operated multirod collimator. The MLC leaves project 5 mm in the isocentric plane perpendicular to the beam axis. A taper is included on the leaves matching beam divergence along one axis. The 5-mm leaf projection width is chosen to give high-resolution conformality across the entire field. The maximum field size provided is 30 x 30 cm2. To reduce the interleaf transmission a 0.254-mm blocking step is included. End-leaf steps totaling 0.762 mm are also provided allowing opposing leaves to close off within the primary radiation beam. The neutron MLC also includes individual 45 degrees and 60 degrees automated universal tungsten wedges. The automated high-resolution neutron collimation provides an increase in patient throughput capacity, enables a new modality, intensity modulated neutron therapy, and limits occupational radiation exposure by providing remote operation from a shielded console area.

Background: New cancer therapeutic strategies must be investigated that enhance prostate cancer treatment while minimizing associated toxicities. We have previously shown that genistein, the major isoflavone found in soy, enhanced prostate cancer radiotherapy in vitro and in vivo. In this study, we investigated the cellular and molecular interaction between genistein and radiation using PC-3 human prostate cancer cells., Methods: Tumor cell survival and progression was determined by clonogenic analysis, flow cytometry, EMSA analysis of NF-kappaB, and western blot analysis of cyclin B1, p21WAF1/Cip1, and cleaved PARP protein., Results: Genistein combined with radiation caused greater inhibition in PC-3 colony formation compared to genistein or radiation alone. Treatment sequence of genistein followed by radiation and continuous exposure to genistein showed optimal effect. Cell cycle analysis demonstrated a significant dose- and time-dependent G2/M arrest induced by genistein and radiation that correlated with increased p21WAF1/Cip1 and decreased cyclin B1 expression. NF-kappaB activity was significantly decreased by genistein, yet increased by radiation. Radiation-induced activation of NF-kappaB activity was strongly inhibited by genistein pre-treatment. A significant and striking increase in cleaved PARP protein was measured following combined genistein and radiation treatment, indicating increased apoptosis., Conclusion: A mechanism of increased cell death by genistein and radiation is proposed to occur via inhibition of NF-kappaB, leading to altered expression of regulatory cell cycle proteins such as cyclin B and/or p21WAF1/Cip1, thus promoting G2/M arrest and increased radiosensitivity. These findings support the important and novel strategy of combining genistein with radiation for the treatment of prostate cancer.

Background and Purpose: To implement an on-line correction scheme based on implanted markers to reduce treatment margins in external beam radiation therapy (EBRT) of carcinoma of the prostate. In turn reduction in treatment margins reduces irradiated volumes and offers the possibility of reduced normal tissue complications or escalated target dose., Patients and Methods: Five or six gold markers were implanted in 10 patients treated for prostate carcinoma using EBRT. All patients were enlisted in an IRB-approved protocol. Before each fraction two portal images were obtained using a low dose (2MU). Positions of the markers were calculated from these images using an in-house developed program. Corrections were applied with a threshold of 2mm displacement. After correction the procedure was repeated., Results: Overall systematic errors were reduced from 7.45, 1.29, and 5.12 mm to 0.65, 0.11, and 0.46 mm in, respectively, the antero-posterior, lateral, and cranio-caudal directions. Likewise, the overall SD were reduced from 5.99, 5.34, and 4.44 mm to 2.82, 2.64, and 2.22 mm, respectively. All reductions were highly significant (P < 0.01) using a t-test for systematic and an F-test for random errors. On an individual level all but three patients showed significant improvements in all directions for the random errors. All patients improved in at least one direction. Systematic errors were significantly lower in all patients. Simulated correction schemes using this data suggest that margin reduction using off-line reduction does not benefit substantially from on-line corrections in the first few fractions., Conclusions: Use of marker-based correction improves the patient position. Factors influencing the accuracy were: (1) number of seeds usable for correction, (2) distribution of markers throughout the volume of interest, and (3) objective instructions for patient realignment.

Transfecting genes into tumors, to upregulate major histocompatibility complex (MHC) class I and class II molecules and inhibit MHC class II associated invariant chain (Ii), induces a potent anti-tumor immune response when preceded by tumor irradiation, in murine RM-9 prostate carcinoma. The transfected genes are cDNA plasmids for interferon-gamma (pIFN-gamma), MHC class II transactivator (pCIITA), an Ii reverse gene construct (pIi-RGC), and a subtherapeutic dose of adjuvant IL-2 (pIL-2). Responding mice rejected challenge with parental tumor and demonstrated tumor-specific cytotoxic T lymphocytes (CTLs). We have extended our investigation to determine the relative roles of each one of the four plasmids pIFN-gamma, pCIITA, pIi-RGC, and pIL-2 in conjunction with radiation for the induction of a curative immune response. Upregulation of MHC class I with pIFN-gamma or class II with pCIITA, separately, does not lead to a complete response even if supplemented with pIL-2 or pIi-RGC. An optimal and specific antitumor response is achieved in more than 50% of the mice when, after tumor irradiation, tumor cells are converted in situ to a MHC class I+/class II+/Ii- phenotype with pIFN-gamma, pCIITA, pIi-RGC, and pIL-2. We demonstrate further that both CD4+ helper T cells and CD8+ cytotoxic T cells are essential for induction of an antitumor response because in vivo depletion of either subset abrogates the response. The radiation contributes to the gene therapy by causing tumor debulking and increasing the permeability of tumors to infiltration of inflammatory cells.

This study investigates the influence of multileaf collimator (MLC) leaf width on intensity modulated radiation therapy (IMRT) plans delivered via the segmented multileaf collimator (SMLC) technique. IMRT plans were calculated using the Corvus treatment planning system for three brain, three prostate, and three pancreas cases using leaf widths of 0.5 and 1 cm. Resulting differences in plan quality and complexity are presented here. Plans calculated using a 1 cm leaf width were chosen over the 0.5 cm leaf width plans in seven out of nine cases based on clinical judgment. Conversely, optimization results revealed a superior objective function result for the 0.5 cm leaf width plans in seven out of the nine comparisons. The 1 cm leaf width objective function result was superior only for very large target volumes, indicating that expanding the solution space for plan optimization by using narrower leaves may result in a decreased probability of finding the global minimum. In the remaining cases, we can conclude that we are often not utilizing the objective function as proficiently as possible to meet our clinical goals. There was often no apparent clinically significant difference between the two plans, and in such cases the issue becomes one of plan complexity. A comparison of plan complexity revealed that the average 1 cm leaf width plan required roughly 60% fewer segments and over 40% fewer monitor units than required by 0.5 cm leaf width plans. This allows a significant decrease in whole body dose and total treatment time. For very complex IMRT plans, the treatment delivery time may affect the biologically effective dose. A clinically significant improvement in plan quality from using narrower leaves was evident only in cases with very small target volumes or those with concavities that are small with respect to the MLC leaf width. For the remaining cases investigated in this study, there was no clinical advantage to reducing the MLC leaf width from 1 to 0.5 cm. In such cases, there is no justification for the increased treatment time and whole body dose associated with the narrower MLC leaf width.

Objective: We have shown previously that pretreatment with genistein potentiated cell killing induced by radiation in human PC-3 prostate carcinoma cell line in vitro. We tested this approach in vivo using an orthotopic prostate carcinoma model of PC-3 cells in nude mice., Methods: Established prostate tumors were pretreated with p.o. genistein at a dose of 5 mg/d for 2 days followed by tumor irradiation with 5 Gy photons. One day after radiation, genistein was resumed and given every other day for 4 weeks., Results: Genistein combined with radiation caused a significantly greater inhibition of primary tumor growth (87%) compared with genistein (30%) or radiation (73%) alone. The number of metastatic lymph nodes was also significantly decreased following genistein and radiation. Paradoxically, genistein alone increased the size of lymph nodes associated with heavy tumor infiltration. Genistein-treated prostate tumors were large with necrosis, apoptotic cells, and giant cells and have a lower proliferation index than in control tumors. Following radiation, areas of tumor destruction replaced by fibrotic tissue and inflammatory cells as well as giant cells were observed, which are typical of radiation effect. After radiation and genistein treatment, an increase in giant cells, apoptosis, inflammatory cells, and fibrosis was observed with decreased tumor cell proliferation consistent with increased tumor cell destruction. Long-term therapy with genistein after prostate tumor irradiation significantly increased survival., Conclusions: Genistein combined with prostate tumor irradiation led to a greater control of the growth of the primary tumor and metastasis to lymph nodes than genistein or radiation alone, resulting in greater survival.

Immunological control or cure of tumors depends on initiating a robust T helper cell response to MHC class II epitopes of tumor-associated antigens. T helper cells regulate the potency of cytotoxic T lymphocyte and antibody responses. We have developed a novel approach to stimulate T helper cells by converting tumor cells into MHC class II molecule-positive, antigen presenting cells. Furthermore, using antisense methods, we suppress expression of the Ii protein, that normally blocks the antigenic peptide binding site of MHC class II molecules during synthesis in the endoplasmic reticulum. In such gene-engineered tumor cells, the MHC class II molecules pick up antigenic peptides, which have been transported into the endoplasmic reticulum for binding to MHC class I molecules. All nucleated cells create such "surveys of self" to detect viral or malignant transformation. Our method extends that survey of self to MHC class II endogenous tumor-associated antigens. Simultaneous presentation of tumor antigens by both MHC class I and II generates a robust and long-lasting antitumor immune response. Injecting murine tumors with genes, which induce MHC class II molecules and suppress Ii protein, cures a significant number of animals with renal and prostate tumors. We have developed analogous human gene vectors that are suitable for most patients and cancers, because they are monomorphic and active in all HLA-DR alleles. We review our findings, and analyze remaining issues for preclinical study and the design of clinical trials.

To circumvent the toxicity caused by systemic injection of cytokines, cytokine cDNA genes encoding the human interleukin IL-2 cDNA (Ad-IL-2) and murine interferon IFN-gamma gene (Ad- IFN-gamma) were inserted into adenoviral vectors. These constructs were used for intratumoral gene therapy of murine renal adenocarcinoma Renca tumors. Treatment with three doses of Ad-IL-2 or Ad- IFN-gamma, given a day apart, was more effective than single-dose gene therapy. We found that tumor irradiation enhanced the therapeutic efficacy of Ad-IL-2 and Ad-IFN-gamma intratumoral gene therapy. Tumor irradiation, administered 1 day prior to three doses of Ad-IL-2 treatment, was more effective than radiation or Ad-IL-2 alone, resulting in tumor growth arrest in all mice, increased survival and a consistent increase in complete tumor regression response rate. Complete responders rejected Renca tumor challenge and demonstrated specific cytotoxic T-cell activity, indicative of specific tumor immunity. The effect of radiation combined with three doses of Ad-IFN-gamma was less pronounced and did not lead to tumor immunity. Histological observations showed that irradiation of the tumor prior to gene therapy increased tumor destruction and inflammatory infiltrates in the tumor nodules. These findings demonstrate that tumor irradiation improves the efficacy of Ad-IL-2 gene therapy for induction of antitumor immune response.

In locally advanced pancreatic cancer, the utilization of chemotherapy and radiotherapy is increasing, although in view of the reported long-term results of several contemporary trials, further improvements are certainly needed. Encouraging results using the combination of cisplatin, cytarabine, caffeine, and continuous infusion (CI) 5-fluorouracil (5-FU) (PACE) for the treatment of advanced pancreatic carcinoma prompted a phase II study using PACE followed by external beam radiotherapy with CI of 5-FU (PACE-RT) for localized disease. Forty-one patients were treated with PACE-RT as adjuvant therapy after surgical resection (21 patients), or as primary therapy for locally advanced, unresectable disease (20 patients), with reevaluation for resection after completion of treatment. PACE consisted of cisplatin 100 mg/m2 IV on day 1, cytarabine 2 g/m2 IV every 12 hours x 2 doses, and caffeine 400 mg/m2 subcutaneously after each cytarabine dose; and days 3 to 21, 5-FU 250 mg/m2/d given by CI. Cycles were repeated every 28 days. After 2 cycles of PACE, radiation therapy was given concurrently with 5-FU at 200 mg/m2/d. In the adjuvant setting, the tumor bed and the draining lymph node basin received 50.4 Gy and 45 Gy, respectively. In the neoadjuvant setting, the primary and regional lymph nodes were to receive 39.6 Gy followed by a neutron boost of 8 NGy to the gross tumor volume. Photon therapy was delivered at 1.8 Gy per fraction and neutron therapy at 0.8 NGy per fraction, 5 days a week. All patients were evaluable for toxicity and survival. The most common toxicity was myelosuppression, with grade III to IV neutropenia occurring in 59% of the patients. The median survival times in the locally advanced and adjuvant patients were 13.4 and 18.1 months, with 1-year survival rates of 52% and 65%, respectively. Nine of 20 patients receiving PACE-RT for unresectable carcinoma had sufficient tumor regression to meet clinical criteria for exploration; three were resected with curative intent. The survival of these three patients undergoing resection after neo-adjuvant therapy was 22.4, 24.3 and 40 months. The treatment program was active, but only moderately well tolerated. Modification of this regimen with newer, less toxic drugs may provide better results and reduced toxicity.

The aim of this paper is to study the correction of prostate motion and position during external beam therapy. The correction was performed using a commercially available ultrasound-based repositioning tool. Electronic portal imaging with the use of fiducial markers was used to assess efficacy and accuracy. Patients undergoing radiation treatment for adenocarcinoma of the prostate were enrolled in a positioning study. Fifteen patients had five to six gold fiducial markers implanted in their prostate. These patients were positioned daily in a standard manner and then were repositioned every other day using an ultrasound-based correction system. Every fraction of a patients' treatment was imaged. This yielded 156 image pairs with and 119 pairs without repositioning available for analysis. This group of patients with markers had the following residual positions measured after the use of ultrasound repositioning. A mean error of -0.4 mm (LL), -2.6 mm (CC), and +2.5 mm (AP) with a standard deviation of 4.3, 5.4, and 5.7 mm. In two directions the improvements of treatment using the ultrasound correction were smaller than the precision of this experiment. They were no larger than 0.81 mm (LAT), and 0.95 mm (CC). In the AP direction a significant improvement was found of 1.6 mm. A highly significant correlation (p < 0.001) was found between the residual errors in the cranio-caudal direction and the shifts performed on the basis of the ultrasound measurements (Spearman ranking R = 0.53). We presented a method to objectively estimate improvements by a correction scheme. This method applied to ultrasound-based adjustment showed significant improvement in one direction and no measurable improvement in two other directions.

Purpose: To improve the outcome of radiotherapy for prostate carcinoma bone tumors, we investigated bone tumor irradiation with photons or neutrons followed by interleukin 2 (IL-2) therapy in a tumor model., Methods and Materials: Implantation of PC-3 cells in nude mouse femur cavity induced a bone tumor that progressed to the formation of a palpable tumor, at the hip joint, by Day 20. Established bone tumors were irradiated with photons or neutrons, and a day later, mice were treated with IL-2 therapy for 3 weekly cycles., Results: PC-3 bone tumors responded to radiation with photons or neutrons in a dose-dependent manner. Combination of photon or neutron radiation with IL-2 therapy increased tumor growth delay, compared to that with photons or neutrons alone. Radiation alone or combined with IL-2 significantly increased mouse survival compared to that with IL-2 or no treatment. After combined therapy, a complete inhibition of bone tumor growth was observed in 45% to 50% of the mice. Histologically, the combined therapy resulted in greater tumor destruction associated with fibrosis, new bone formation, and inflammatory infiltrates than that observed with each modality alone., Conclusions: The efficacy of tumor irradiation with neutrons or photons was enhanced by IL-2 therapy for the treatment of prostate carcinoma bone tumors.

Our goal was to convert murine RM-9 prostate carcinoma cells in vivo into antigen-presenting cells capable of presenting endogenous tumor antigens and triggering a potent T-helper cell-mediated immune response essential for the generation of a specific antitumor response. We showed that generating the major histocompatibility complex (MHC) class I+/class II+/Ii- phenotype, within an established subcutaneous RM-9 tumor nodule, led to an effective immune response limiting tumor growth. This phenotype was created by intratumoral injection of plasmid cDNAs coding for interferon gamma, MHC class II transactivator, and an antisense reverse gene construct (RGC) for a segment of the gene for Ii protein (-92,97). While this protocol led to significant suppression of tumor growth, there were no disease-free survivors. Nevertheless, irradiation of the tumor nodule on the day preceding initiation of gene therapy yielded 7 of 16 mice that were disease-free in a long-term follow up of 57 days compared to 1 of 7 mice receiving radiotherapy alone. Mice receiving radiotherapy and gene therapy rejected challenge with parental RM-9 cells and demonstrated specific cytotoxic T-cell activity in their splenocytes but not the mouse cured by radiation alone. These data were reproduced in additional experiments and confirmed that tumor irradiation prior to gene therapy resulted in complete tumor regression and specific tumor immunity in more than 50% of the mice. Increasing the number of plasmid injections after tumor irradiation induced tumor regression in 70% of the mice. Administering radiation before this novel gene therapy approach, that creates an in situ tumor vaccine, holds promise for the treatment of human prostate carcinoma.

The purpose of this study was to summarize the progress made using fast neutron irradiation in the treatment of prostate cancer at Wayne State University between 1991 and the year 2001. The results of three Phase II studies and one Phase III st udy involving nearly 700 patients is summarized in this paper. The Phase II studies weredose finding studies looking at doses of 15, 9, 10, and 11 nGy, respectively. The randomized protocol was a study of sequence looking at the results of treating patients with neutron first versus neutron radiation last. The results demonstrated that the best combination of tumor control probabilities and normal tissue complications was found in a mix of approximately 50% neutrons and 50% photons. Thus, the standard doses become 10 nGy and 40 Gy of photons. The randomized trial demonstrated that the sequence has significant importance and the disease-free survival was 93% for patients treated with neutrons first versus 73% for patients treated with neutrons last. There was no difference in the rate of acute or chronic complications. Finally, an analysis was performed demonstrating which patients may best benefit from the use of neutron irradiation. It was shown that patients with one, two, or three adverse risk factors had a significant improvement in disease-free survival when part of the treatment included neutron radiation versus standard photon radiation alone. Neutron radiation can be delivered safely with effort to see that it is superior to that which can be achieved by conformal photon irradiation by itself. Future work will be done to expand the role of neutron radiation in other clinical disease sites.

A computer controlled multileaf collimator (MLC) is being designed to replace the multirod collimator (MRC) at present used to shape the d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron. The computer controlled MLC will improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. The existing MRC uses tungsten rods, while the new MLC will use steel as the leaf material. In the current study the attenuation and activation characteristics of steel are compared with those of tungsten to ensure that (a) the attenuation achieved in the MLC is at least equivalent to that of the existing MRC, and (b) that the activation of the steel will not result in a significant change in the activation levels within the treatment room. The latter point is important since personnel exposure (particularly to the radiation therapy technologists) from induced radioactivity must be minimized. Measurement of the neutron beam attenuation in a broad beam geometry showed that a 30 cm thick steel leaf yielded 2.5% transmission. This compared favorably with the 4% transmission obtained with the existing MRC. Irradiation of steel and tungsten samples at different depths in a 30 cm steel block indicated that the activation of steel should be no worse than that of tungsten.

Purpose: Five-year results from the 1989 patterns of care study (PCS) for prostate cancer are now ready for analysis. The PCS was initiated to determine national averages for treatments and examine outcomes prospectively; the 1989 prostate study is the first to have collected pre- and post-treatment serum PSA data., Methods and Materials: Six hundred patients treated with radiotherapy with curative intent for prostate cancer at 71 separate institutions in the year 1989 made up the study population. Three hundred ninety-one cases were fully analyzable. Pretreatment patient and tumor characteristics were as follows: of the 391 analyzable, 255 had pretreatment PSA values obtained, and 245 had a Gleason's sum (GS) reported. Three hundred fifty-eight were Caucasian, 24 African-American, and 3 Hispanic (also 6 unknown). One hundred three patients had PSA < 10, 60 had PSA 10-19, and 92 presented with PSA >20. Ninety-seven patients were from Radiation Therapy Oncology Group (RTOG), Community Cancer Centers (CCC), or teaching institutions; 141 patients were from other hospital-based, nonteaching institutions; and 153 were from freestanding radiation oncology facilities. Seventy-one patients were T1, 203 T2, and 100 T3/4. Twenty-four out of 391 patients also received neoadjuvant hormone therapy. Survival curves were constructed using Kaplan-Meier methods, and differences between groups were tested for significance using the log-rank test. For cumulative incidence curves, Gray's test was used to investigate failure distributions between groups. The variables entering Cox model for multivariate analysis included age, race, T stage, pretreatment PSA, and GS. A patient was considered a PSA failure if the treating radiation oncologist reported it as such., Results: With a median follow-up of 5.7 years, the 5-year biochemical no evidence of disease (bNED) and overall survival were 56% and 79% respectively for Stage T1, 52% and 81% for T2, and 36% and 63% for Stages T3 and T4 combined. As expected, higher pretreatment PSA, GS, and T stage were all prognostic of poorer outcome. On univariate analysis, bNED survival was adversely impacted by T stage (p = 0.009), pretreatment PSA (p = 0.0035), and by the GS (p = 0.0038). Cause-specific failure was significantly lower for higher T stage (p = 0.014), GS (p = 0.001), and also pretreatment PSA (p = 0.0004). Overall survival was significantly lower in patients with higher T stage (p = 0.047) or GS (p = 0.0191), but not pretreatment PSA (p = 0.284). On multivariate analysis, pretreatment PSA was found to be statistically significant in association with bNED survival, and GS was associated with overall survival, cause-specific survival, and distant metastasis. Few late complications were reported: 13/391 and 13/391 Grade 2-3 gastrointestinal (GI) and genitourinary (GU) complications respectively, with two patients having required surgery with or without a permanent colostomy., Conclusion: For a representative cross-section of institutions in the United States, radiotherapy achieved high rates of bNED and CSS in selected groups of prostate cancer patients. When studied retrospectively, increased pretreatment PSA was a strong predictor of both biochemical failure and death due to prostate cancer. New strategies for patients with high-stage, high-grade tumors and/or pretreatment PSA >20 deserve testing.

We have shown previously that genistein, the major isoflavone in soybean, inhibited the growth of human prostate cancer cells in vitro by affecting the cell cycle and inducing apoptosis. To augment the effect of radiation for prostate carcinoma, we have now tested the combination of genistein with photon and neutron radiation on prostate carcinoma cells in vitro. The effects of photon or neutron radiation alone or genistein alone or both combined were evaluated on DNA synthesis, cell growth, and cell ability to form colonies. We found that neutrons were more effective than photons for the killing of prostate carcinoma cells in vitro, resulting in a relative biological effectiveness of 2.6 when compared with photons. Genistein at 15 microM caused a significant inhibition in DNA synthesis, cell growth, and colony formation in the range of 40-60% and potentiated the effect of low doses of 200-300 cGy photon or 100-150 cGy neutron radiation. The effect of the combined treatment was more pronounced than with genistein or radiation alone. Our data indicate that genistein combined with radiation inhibits DNA synthesis, resulting in inhibition of cell division and growth. Genistein can augment the effect of neutrons at doses approximately 2-fold lower than photon doses required to observe the same efficacy. These studies suggest a potential of combining genistein with radiation for the treatment of localized prostate carcinoma.

We have shown that implantation of human prostate carcinoma PC-3 cells in the prostates of nude mice led to the formation of prostate tumors with metastases to para-aortic lymph nodes. We found that day 6 prostate tumors were responsive to systemic injections of interleukin 2 (IL-2) therapy. We have now investigated the combination of primary tumor irradiation and IL-2 for metastatic prostate cancer in this preclinical tumor model. The effect of neutron radiation was compared with that of photon radiation. Advanced prostate tumors (approximately 0.4 cm) were irradiated, and a day later, mice were treated with systemic IL-2 for three weekly cycles. In separate experiments, mice were either sacrificed on day 30 to assess prostate tumor size and tumor histology or followed for survival. A dose-dependent inhibition of prostate tumor growth was caused either by photons or neutrons, but neutrons were more effective than photons with a relative biological effectiveness of 2. The tumor inhibition obtained with 250 cGy neutrons and 500 cGy photons was significant (>75%) and was further increased (> or = 90%) by addition of IL-2 therapy. In survival studies, the combination of radiation and IL-2 showed a significant survival advantage compared with untreated mice (P < or = 0.005) or radiation alone (P < or = 0.003) and an increase in median survival compared with IL-2 alone. Histologically, the combined regimen resulted in a greater degree of tumor destruction, inflammatory response, and vascular damage than that observed with each modality alone. After this combined treatment, no tumor was histologically detected in the para-aortic lymph nodes of these mice, and the lymph nodes were significantly smaller. These findings showed that primary tumor irradiation, either with neutrons or photons, enhanced IL-2 therapeutic effect for the treatment of advanced prostate cancer. This combined modality induced an antitumor response that controlled the growth of prostate tumors and their metastases.

Recent advances in combined modality treatment of locally advanced head and neck cancer have improved local and regional disease control and survival with better functional outcome. However, the local and regional failure rate after radiation therapy is still high for tumors that respond poorly to cisplatin-based neoadjuvant chemotherapy. This clinical observation suggests a common biological mechanism for resistance to cisplatin and photon irradiation. In this report, we investigated the molecular basis underlying cisplatin resistance in head and neck squamous carcinoma (HNSCC) cells and asked if fast neutron radiation enhances cisplatin cytotoxicity in cisplatin-resistant cells. We found that cisplatin sensitivity correlates with caspase induction, a cysteine proteinase family known to initiate the apoptotic cell death pathway, suggesting that apoptosis may be a critical determinant for cisplatin cytotoxicity. Neutron radiation effectively enhanced cisplatin cytotoxicity in HNSCCs including cisplatin-resistant cells, whereas photon radiation had little effect on cisplatin cytotoxicity. Interestingly, neutron-enhanced cisplatin cytotoxicity was associated neither with apoptosis nor with cell cycle regulation, as determined by caspase activity assay, annexin V staining, and flow cytometric analysis. Taken together, the present study provides a molecular insight into cisplatin resistance and may also provide a basis for more effective multimodality protocols involving neutron radiation for patients with locally advanced head and neck cancer.

Increased consumerism, patient empowerment, and autonomy are creating a health care revolution. In recent years, the public has become better informed and more sophisticated. An extraordinary amount of treatment advice from books, the media, and the Internet is available to patients today, although much of it is confusing or conflicting. Consequently, the traditional, paternalistic doctor-patient relationship is yielding to a more consumerist one. The new dynamic is based on a participatory ethic and a change in the balance of power. This shared decision-making creates a true partnership between professionals and patients, in which each contributes equally to decisions about treatment or care. Evidence suggests that in diseases such as prostate cancer, where there may be a number of appropriate treatment options for a particular patient, shared decision-making may lead to improved clinical and quality-of-life outcomes. This article explores the evolving relationship between the physician and patient, the pros and cons of shared decision-making, and the use of video technology in the clinical setting. The authors review the use of medical decision aids, including a video-based educational program called CHOICES, in the treatment of prostate cancer and other diseases.