Influence of vascular comorbidities and race on erectile dysfunction after prostate cancer radiotherapy.

INTRODUCTION: Vascular comorbidities (VC) (hypertension, diabetes, and hyperlipidemia) are known factors related to erectile dysfunction (ED) in men. However, no data are yet available for the effects of VC on ED incidence after prostate cancer radiotherapy (XRT). AIM: To investigate the influence of VC on post-XRT ED incidence and to further characterize ED incidence by racial groups. MAIN OUTCOME MEASURES: ED incidence. METHODS: We reviewed 732 charts of patients (267 Caucasian and 465 African American [AA]) who received prostate XRT (external beam radiotherapy and/or brachytherapy) with or without hormone therapy between 1999 and 2010. The number of pre-XRT VC (0, 1, 2, or 3) was determined by medical history and medication list. ED (defined by use of erectile aids or by documentation of moderate or high sexual dysfunction on patient history) was determined pre-XRT as well as 1, 2, and 4 years post-XRT. RESULTS: ED incidence progressively increased from 22% pre-XRT to 58% 4 years post-XRT (P < 0.01). Additionally, ED incidence significantly increased with number of VC-4-year incidence between patients with 1 vs. 0 (P = 0.02), 2 vs. 0 (P < 0.01), 3 vs. 0 (P < 0.01), 3 vs. 1 (P < 0.01), and 3 vs. 2 (P = 0.04) VC (2 vs. 1 VC was nonsignificant). Compared with the Caucasian patients, ED incidences were slightly higher for the AA group with 0, 1, 2, and 3 comorbidities at 4 years follow-up (but statistically nonsignificant). CONCLUSIONS: The number of VCs have a significant effect on development of post-XRT ED. Pre- and post-XRT ED appear to be independent of race when number of VCs are considered. Our results can be used to guide physicians in counseling patients on the incidence of ED by number of VC and as preliminary data for prospective efforts aimed at reducing post-XRT ED.

Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer.

PURPOSE: The objective of this study was to determine whether limiting the doses delivered to the penile bulb (PB) and corporal bodies with intensity modulated radiation therapy (IMRT) preserves erectile function compared with standard IMRT in men with prostate cancer. METHODS AND MATERIALS: A total of 117 patients with low- to intermediate-risk, clinical T1a-T2c prostate adenocarcinoma were enrolled in a single-institution, prospective, single-blind, phase 3 randomized trial. All received definitive IMRT to 74 to 80 Gy in 37 to 40 fractions and standard IMRT (s-IMRT) or erectile tissue-sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the penile bulb and corporal bodies to ≤15 Gy and ≤7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function and phosphodiesterase type 5 inhibitor (PDE5) medication records. RESULTS: Sixty-two patients received ETS-IMRT, and 54 received s-IMRT; 1 patient did not receive radiation therapy. Before treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, P = .53). Of 85 evaluable patients with International Index of Erectile Function and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (P = .86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (P = .54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-year 91.8% vs 90.7%, respectively, P = .77), with a median follow-up of 7.4 years. There were no differences in acute or late gastrointestinal or genitourinary toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, although power was limited by attrition and unplanned dosimetric crossover. CONCLUSIONS: ETS-IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.

Associations Between Social Determinants of Health and Psychoneurologic Symptom Clusters in Women With Gynecologic Cancers: A Longitudinal Study.

OBJECTIVES: To evaluate the associations between social determinants of health (SDOH) and psychoneurologic symptom (PNS) clusters in women with gynecologic cancers during cancer treatment. SAMPLE & SETTING: 67 women with gynecologic cancers who received radiation therapy were assessed at baseline, six to eight weeks after treatment, and six months after treatment at oncology clinics in Georgia. METHODS & VARIABLES: Fatigue, pain, sleep disturbances, cognitive impairment, and depressive symptoms were measured to determine a PNS cluster score. Associations between SDOH and PNS cluster scores were assessed using mixed-effect models. RESULTS: Larger mean PNS cluster scores were reported in individuals with less education, lower income, and unemployment, as well as in those living in more disadvantaged neighborhoods. IMPLICATIONS FOR NURSING: Individual- and community-level SDOH and their interactions were associated with more PNS clusters. Studying SDOH at multiple levels depicts how various social disadvantages can exacerbate poor health outcomes.

Exploring the Anal Microbiome in HIV Positive and High-Risk HIV Negative Women.

This exploratory study sought to characterize the anal microbiome and explore associations among the anal microbiome, risk factors for anal cancer, and clinical factors. A pilot sample of 50 HIV infected and high-risk HIV negative women were recruited from the former Women's Interagency HIV Study. Microbiome characterization by 16S rRNA gene sequencing and datasets were analyzed using QIIME 2™. Composition of the anal microbiome and its associations with anal cancer risk factors and clinical factors were analyzed using linear decomposition model and permutational multivariate analysis of variance. Composition of the anal microbiome among HIV positive and high-risk negative women was dominated by Bacteroides, Prevotella, and Campylobacter. The overall taxonomic composition and microbial diversity of the anal microbiome did not significantly differ by HIV status. However, the abundance of Ruminococcus 1 belonging to the Rumincoccaceae family was associated with HIV status (q = .05). No anal cancer risk factors were associated with the anal microbiome composition. Clinical factors marginally associated with the anal microbiome composition included body mass index (BMI; p = .05) and hepatitis C virus (HCV; p = .05). Although HIV and risk factors for anal cancer were not associated with the composition of the anal microbiome in this pilot sample, other clinical factors such as BMI and HCV, may be worth further investigation in a larger study. Future research can build on these findings to explore the role of the microbiome and HIV comorbidities in women.

Follow-Up to High-Resolution Anoscopy After Abnormal Anal Cytology in People Living with HIV.

Current expert recommendations suggest anal cytology followed by high-resolution anoscopy (HRA) for biopsy and histological confirmation may be beneficial in cancer prevention, especially in people living with HIV (PLWH). Guided by the social ecological model, the purpose of this study was to examine sociodemographic and clinical variables, individual-level factors (depression, HIV/AIDS-related stigma, and health beliefs) and interpersonal-level factors (social support) related to time to HRA follow-up after abnormal anal cytology. We enrolled 150 PLWH from a large HIV community clinic, with on-site HRA availability, in Atlanta, GA. The median age was 46 years (interquartile range of 37-52), 78.5% identified as African American/Black, and 88.6% identified as born male. The average length of follow-up to HRA after abnormal anal cytology was 380.6 days (standard deviation = 317.23). Only 24.3% (n = 39) of the sample had an HRA within 6 months after an abnormal anal cytology, whereas 57% of the sample had an HRA within 12 months. HIV/AIDS-related stigma [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.33-0.90] and health motivation (OR 0.80, 95% CI 0.67-0.95) were associated with time to HRA follow-up ≤6 months. For HRA follow-up ≤12 months, we found anal cytology [high-grade squamous intraepithelial lesions/atypical squamous cells of undetermined significance cannot exclude HSIL (HSIL/ASCUS-H) vs. low-grade squamous intraepithelial lesions (LSIL) OR = 0.05, 95% CI 0.00-0.70; atypical squamous cells of undetermined significance (ASCUS) vs. LSIL OR = 0.12, 95% CI 0.02-0.64] and health motivation (OR = 0.86, 95% CI 0.65-0.99) were associated. Findings from this study can inform strategies to improve follow-up care after abnormal anal cytology at an individual and interpersonal level in efforts to decrease anal cancer morbidity and mortality.

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

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

Comparisons of Depression, Sexual Function, and Quality of Life Between Women With Gynecological Cancers and Race-Matched Healthy Controls.

BACKGROUND: Although higher incidence and mortality of gynecological cancer (GynCa) are documented in black compared with white women, few studies have documented quality of life (QOL) or healthy control comparisons. OBJECTIVE: This study compared depression, sexual function, and QOL between patients with GynCa and race-matched healthy controls. METHODS: Patients with GynCa and healthy controls completed the Patient Health Questionnaire-9, Female Sexual Function Index, and Functional Assessment of Cancer Therapy-General measures at baseline; GynCa patients were assessed again at 6 months post-radiation therapy (RT). RESULTS: Analyses included 84 participants (51% white, 49% black), including 28 GynCa patients and 56 controls with similar marital status. Compared with healthy controls, patients were younger, had a higher body mass index, and had more depression (P = .01); 82% of the patients and 71% of the healthy controls met criteria for sexual dysfunction at baseline (P = .29). Patients pre-RT had greater sexual dysfunction and lower QOL (P = .001) than controls did; patients at 6-month post-RT showed improved sexual function scores compared with pre-RT, with similar results to controls. White GynCa patients reported less sexual desire (P = .02), more pain (P = .05), and lower total Female Sexual Function Index scores (P = .01) than did black GynCa patients. Both black and white GynCa patients reported lower total QOL than their race-matched controls did (P = .07 and P = .002). CONCLUSIONS: Women with GynCa reported more depression and lower QOL than did healthy controls pre-RT. Among GynCa patients, white women had more sexual dysfunction than black women did. IMPLICATIONS FOR PRACTICE: The differences in sexual dysfunction between white and black women with GynCa suggest developing guidelines directing routine sexual assessment and rehabilitation in women treated for GynCa.

Characterizing Pain Experiences: African American Patients With Multiple Myeloma Taking Around-the-Clock Opioids.

BACKGROUND: Despite known disparities by race, studies to date have not focused on pain characterization among African American patients with multiple myeloma. OBJECTIVES: This study aimed to characterize the pain experience, beliefs about pain and pain control, and additional symptoms among African American patients with multiple myeloma taking around-the-clock opioids. METHODS: This study employed secondary analysis of baseline data from a completed longitudinal study of opioid adherence. Descriptive statistics were used to characterize the sample, pain experience, beliefs regarding pain and pain control, and related symptoms. FINDINGS: Participants (N = 34) experienced everyday pain and additional symptoms, and half experienced depression. Pain management barriers included dislike of pills, fear of addiction, and bothersome side effects from pain and medication. Additional larger studies can incorporate multilevel factors contributing to high symptom burden.

Dairy intake and 1,25-dihydroxyvitamin D levels in men at high risk for prostate cancer.

OBJECTIVE: Dairy food intake has been associated with prostate cancer in previous work, but the mechanism by which this occurs is unknown. Dairy calcium may suppress circulating levels of potentially cancer-protective 1,25-hydroxyvitamin D (1,25(OH)2D). We examined the associations of dairy, milk, calcium, and vitamin D intake with plasma 1,25(OH)2D levels among 296 men (194 black, 102 non-black) enrolled in a high risk program for prostate cancer from 10/96 to 10/07. METHODS: All participants completed diet and health history questionnaires and provided plasma samples, which were assessed for levels of 25-hydroxyvitamin D and 1,25(OH)2D. We used multivariate linear regression to examine associations with 1,25(OH)2D. RESULTS: After adjustment for age, race, energy intake, BMI, and alcohol intake, we observed no associations for any of our variables of interest with 1,25(OH)2D, or any meaningful differences in estimates by race or vitamin D status. CONCLUSION: Our findings, in a sample including a large proportion of black participants, do not confirm previous findings showing an inverse association between calcium intake and 1,25(OH)2D levels. As such, they suggest that future work should explore other mechanisms by which dairy foods and calcium might increase prostate cancer risk.

Prostate cancer early detection program recruitment methods and show rates in men at high risk.

PURPOSE: Men with a family history of prostate cancer and black men are at higher risk for prostate cancer. Recruitment and retention of these men at high risk into early detection programs is challenging. We report a comprehensive analysis of recruitment methods, show rates and participant factors from the Prostate Cancer Risk Assessment Program, a prospective, longitudinal prostate cancer screening study. MATERIALS AND METHODS: Men 35 to 69 years old were eligible for recruitment if they had a family history of prostate cancer, were black or had a BRCA1/2 mutation. Recruitment methods were analyzed using standard statistical methods with respect to participant demographics and presentation to the first program appointment. RESULTS: Of 707 men recruited 64.9% presented to the initial program appointment. More men were recruited via radio than via referral or other methods (chi-square = 298.13, p <0.0001). Men recruited by radio were more likely to be black (p <0.001), less educated (p = 0.003) and not married or partnered (p = 0.007), and have no prostate cancer family history (p <0.001). Men recruited by referral had a higher income (p = 0.007) and were more likely to attend the initial program visit than those recruited by radio or other methods (chi-square = 27.08, p <0.0001). CONCLUSIONS: This comprehensive analysis shows that radio led to higher recruitment of black men with lower socioeconomic status. However, these men at high risk have a lower presentation rate for prostate cancer screening. Targeted motivational measures must be studied to improve the show rate for prostate cancer risk assessment in these men at high risk.

Pilot Study of Vaginal Microbiome Using QIIME 2™ in Women With Gynecologic Cancer Before and After Radiation Therapy.

OBJECTIVES: To characterize the vaginal microbiome using QIIME 2™ (Quantitative Insights Into Microbial Ecology 2) in women with gynecologic cancer. SAMPLE & SETTING: 19 women with gynecologic cancer before and after radiation therapy at a comprehensive cancer center in Atlanta, Georgia. METHODS & VARIABLES: This pilot study analyzed vaginal microbiome communities using a microbiome analysis pipeline, beginning with 16S rRNA gene sequencing and processing through use of a bioinformatics pipeline to downstream microbial statistical analysis. RESULTS: The findings showed the methods to be robust, and most women with gynecologic cancer showed depletion of Lactobacillus. Compared to those pre-radiation therapy, women post-radiation therapy showed higher abundances of Mobiluncus, Atopobium, and Prevotella but lower abundances of Lactobacillus, Gardnerella, and Peptostreptococcus, which are associated with bacterial vaginosis. IMPLICATIONS FOR NURSING: This study presents the fundamentals of human microbiome data collection and analysis methods to inform nursing science. Assessing the vaginal microbiome provides a potential pathway to develop interventions to ameliorate dysbiosis of the vaginal microbiome.

Research Agenda of the Oncology Nursing Society: 2019-2022.

PROBLEM STATEMENT: To define the Oncology Nursing Society Research Agenda for 2019-2022. DESIGN: Multimethod, consensus-building approach by members of the Research Agenda Project Team. DATA SOURCES: Expert opinion, literature review, surveys, interviews, focus groups, town hall, and review of research priorities from other cancer care organizations and funding agencies. ANALYSIS: Content analysis and descriptive statistics were used to synthesize research priority themes that emerged. FINDINGS: Three priority areas for scientific development were identified. IMPLICATIONS FOR NURSING: The Research Agenda can be used to focus oncology nurses' research, scholarship, leadership, and health policy efforts to advance quality cancer care, inform research funding priorities, and align initiatives and resources across the ONS enterprise.

Pretreatment quality of life predicts for locoregional control in head and neck cancer patients: a radiation therapy oncology group analysis.

PURPOSE: To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional control (LRC) and/or overall survival (OS). METHODS AND MATERIALS: HRQOL questionnaires, using a validated instrument, the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), version 2, were completed by patients before the start of treatment. OS and LRC were the outcome measures analyzed using a multivariate Cox proportional hazard model. RESULTS: Baseline FACT-H&N data were available for 1,093 patients and missing for 417 patients. No significant difference in outcome was found between the patients with and without baseline FACT-H&N data (p = 0.58). The median follow-up time was 27.2 months for all patients and 49 months for surviving patients. Multivariate analyses were performed for both OS and LRC. Beyond tumor and nodal stage, Karnofsky performance status, primary site, cigarette use, use of concurrent chemotherapy, and altered fractionation schedules, the FACT-H&N score was independently predictive of LRC (but not OS), with p = 0.0038. The functional well-being component of the FACT-H&N predicted most significantly for LRC (p = 0.0004). CONCLUSIONS: This study represents, to our knowledge, the largest analysis of HRQOL as a prognostic factor in locally advanced head and neck cancer patients. The results of this study have demonstrated the importance of baseline HRQOL as a significant and independent predictor of LRC in patients with locally advanced head and neck cancer.

Gender differences in pretreatment quality of life in a prospective lung cancer trial.

The purpose of this analysis was to assess the impact of pretreatment factors on quality of life (QOL) in patients with locally advanced nonsmall cell lung cancer (NSCLC). In particular, this study focused on the possible interaction between gender-specific baseline health-related QOL and Karnofsky performance score (KPS) in a prospective randomized lung cancer trial. QOL information, using validated instruments (Functional Assessment of Cancer Therapy-Lung [FACT-L], version 2, and Functional Living Index-Cancer [FLIC]), was prospectively collected in patients with locally advanced NSCLC treated on Radiation Therapy Oncology Group (RTOG) trial 89-01. Between April 1990 and April 1994, 70 eligible patients participated in a phase III trial comparing a regimen containing sequential chemotherapy and radiation therapy versus sequential chemotherapy plus surgery. Of these 70 patients, 46 underwent pretreatment FLIC and 49 underwent pretreatment FACT-L. There was a significant interaction between gender and KPS using FLIC (P = 0.009), which also showed a trend toward significance with FACT (P = 0.09). Significant KPS-by-gender interactions were noted for FACT-L in the physical well-being and additional concerns-lung subscales (P = 0.012 and P = 0.0003, respectively). The results of both the FLIC and FACT-L demonstrated significantly lower scores corresponding to lower KPS values (P = 0.009 and P = 0.016, respectively). Results of this randomized study incorporating prospective QOL measurements suggested that in patients with locally advanced NSCLC, analyzing QOL data by either gender or performance status alone may not accurately reflect how these factors depend upon each another. Understanding the interaction between gender and performance status could lead to better prognosticators and potentially could tailor interventions for specific groups of patients with lung cancer.

Feasibility of using administrative claims data for cost-effectiveness analysis of a clinical trial.

OBJECTIVE: This study was performed retrospectively to determine if Medicare claims data could be used to evaluate the cost effectiveness, from a payer perspective, of different radiation treatment schedules evaluated in a national clinical trial. METHODS: Medicare costs from all providers and all places of service were obtained from the Centers for Medicare & Medicaid Services for patients treated in the period 1992-1996 on Radiation Therapy Oncology Group 90-03, and combined with data on outcomes from the trial. RESULTS: Of the 1,113 patients entered, Medicare cost data and clinical outcomes were available for 187 patients. Significant differences in tolerance of treatment and outcome were noted between patients with Medicare data included in the study and patients without Medicare data, and non-Medicare patients excluded from it. Ninety-five percent confidence ellipses on the incremental cost-effectiveness scatterplots crossed both axes, indicating non-significant differences in cost effectiveness between radiation treatment schedules. CONCLUSIONS: Claims data permit estimation of cost effectiveness, but Medicare data provide inadequate representation of results applicable to patients from the general population.

Sociodemographic Predictors of Anal Cancer Screening and Follow-up in Human Immunodeficiency Virus-Infected Individuals.

BACKGROUND: Anal cancer in the United States is generally rare; however, human immunodeficiency virus (HIV)-infected individuals are 28 times more likely to be given a diagnosis of anal cancer than the general population. OBJECTIVE: The aim of this study was to examine the rates and sociodemographic predictors of anal cancer screening and follow-up anoscopy in a sample of HIV-infected individuals. METHODS: Data for this study (n = 200) were derived from a retrospective chart review of randomly selected HIV-infected individuals. Data analyses included Pearson's correlation coefficient statistic to examine bivariate associations and logistic regression modeling for prediction of anal Papanicolaou test screening and follow-up anoscopy. RESULTS: Screening rates and follow-up after an abnormal anal Pap test were low. Women were less likely to be screened for anal cancer (odds ratio [OR], 0.244; P = .007). Men who have sex with men were almost 4 times more likely to be screened for anal cancer (OR, 3.7; P = .02). Men who have sex with men were 6 times more likely to have follow-up after an abnormal anal Pap test compared with heterosexual men or women of any sexual orientation (OR, 6.88; P = .002). CONCLUSIONS: High-risk groups for anal cancer should be targeted for preventative measures as part of a cancer prevention plan to decrease the personal and clinical burden associated with anal cancer. IMPLICATIONS FOR PRACTICE: Cancer prevention is a multistep process that requires screening and follow-up efforts, where healthcare providers play a vital role in these efforts. Findings from this study can inform strategies to improve screening and follow-up rates in HIV-infected individuals.

Attrition in NRG Oncology's Radiation-Based Clinical Trials.

PURPOSE: To determine individual, organizational, and protocol-specific factors associated with attrition in NRG Oncology's radiation-based clinical trials. METHODS AND MATERIALS: This retrospective analysis included 27,443 patients representing 134 NRG Oncology's radiation-based clinical trials .trials with primary efficacy results published from 1985-2011. Trials were separated on the basis of the primary endpoint (fixed time vs event driven). The cumulative incidence approach was used to estimate time to attrition, and cause-specific Cox proportional hazards models were used to assess factors associated with attrition. RESULTS: Most patients (69%) were enrolled in an event-driven trial (n = 18,809), while 31% were enrolled in a fixed-time trial (n = 8634). Median follow-up time for patients enrolled in fixed-time trials was 4.1 months and 37.2 months for patients enrolled in event-driven trials. Fixed time trials with a duration < 6 months had a 5 month attrition rate of 4.3% (95% confidence interval [CI]: 3.4%, 5.5%) and those with a duration ≥ 6 months had a 1 year attrition rate of 1.6% (95% CI: 1.2, 2.1). Event-driven trials had 1- and 5-year attrition rates of 0.5% (95% CI: 0.4%, 0.6%) and 13.6% (95% CI: 13.1%, 14.1%), respectively. Younger age, female gender, and Zubrod performance status >0 were associated with greater attrition as were enrollment by institutions in the West and South regions and participation in fixed-time trials. CONCLUSIONS: Attrition in clinical trials can have a negative effect on trial outcomes. Data on factors associated with attrition can help guide the development of strategies to enhance retention. These strategies should focus on patient characteristics associated with attrition in both fixed-time and event-driven trials as well as in differing geographic regions of the country.

Racial differences in CYP3A4 genotype and survival among men treated on Radiation Therapy Oncology Group (RTOG) 9202: a phase III randomized trial.

PURPOSE: Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4 *1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02. METHODS AND MATERIALS: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) +/- 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression using American Society for Therapeutic Radiology and Oncology consensus guidelines. RESULTS: There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression. CONCLUSIONS: The samples analyzed support previously reported observations about the distribution of CYP3A4 *1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out.

Four-week course of radiation for breast cancer using hypofractionated intensity modulated radiation therapy with an incorporated boost.

PURPOSE: Standard radiation for early breast cancer requires daily treatment for 6 to 7 weeks. This is an inconvenience to many women, and for some a barrier for breast conservation. We present the acute toxicity of a 4-week course of hypofractionated radiation. METHODS AND MATERIALS: A total of 75 patients completed radiation on a Phase II trial approved by the hospital institutional review board. Eligibility criteria were broad to include any patient normally eligible for standard radiation: age >or=18 years, invasive or in situ cancer, American Joint Committee on Cancer Stage 0 to II, breast-conserving surgery, and any systemic therapy not given concurrently. The median age was 52 years (range, 31-81 years). Of the patients, 15% had ductal carcinoma in situ, 67% T1, and 19% T2; 71% were N0, 17% N1, and 12% NX. Chemotherapy was given before radiation in 44%. Using photon intensity-modulated radiation therapy and incorporated electron beam boost, the whole breast received 45 Gy and the lumpectomy bed 56 Gy in 20 treatments over 4 weeks. RESULTS: The maximum acute skin toxicity by the end of treatment was Grade 0 in 9 patients (12%), Grade 1 in 49 (65%) and Grade 2 in 17 (23%). There was no Grade 3 or higher skin toxicity. After radiation, all Grade 2 toxicity had resolved by 6 weeks. Hematologic toxicity was Grade 0 in most patients except for Grade 1 neutropenia in 2 patients, and Grade 1 anemia in 11 patients. There were no significant differences in baseline vs. 6-week posttreatment patient-reported or physician-reported cosmetic scores. CONCLUSIONS: This 4-week course of postoperative radiation using intensity-modulated radiation therapy is feasible and is associated with acceptable acute skin toxicity and quality of life. Long-term follow-up data are needed. This radiation schedule may represent an alternative both to longer 6-week to 7-week standard whole-breast radiation and more radically shortened 1-week, partial-breast treatment schedules.

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer.

PURPOSE: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. RESULTS: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. CONCLUSION: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.