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This longitudinal study examined associations among HPV, inflammation and fatigue in head and neck cancer (HNC) patients receiving intensity-modulated radiation therapy (IMRT). Consented patients were followed pre-, one-month and three-month post-IMRT. Fatigue was assessed by the Multidimensional Fatigue Inventory-20. Plasma interleukin-1receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor2 (sTNFR2) were determined using Magnetic Luminex Screening Assay; acute phase proteins (CRP) were determined using a standard turbidimetric assay. Mixed effect modeling and path analysis were used to examine the associations. Ninety-four patients with newly diagnosed, locally advanced non- metastatic HNC were enrolled from 2012 to 2015; majority received concurrent chemoradiotherapy (CRT). Fifty-three percent of them were HPV+. HPV+ patients were more likely to be male, have no history of tobacco use, have higher BMI, be diagnosed with oropharyngeal cancer, and receive CRT. HPV+ patients had significant lower fatigue, and lower inflammation as represented by CRP (p

Acupuncture, a component of the centuries old traditional Chinese medicine paradigm (1), has shown promise among patients with cancer for treatment of toxicities such as nausea, fatigue, and pain (2). To build a strong evidence base for acupuncture in survivorship care, large randomized controlled trials are needed to establish the efficacy of acupuncture for symptom management in cancer (2). While acupuncture has been found to be more effective than standard care or usual care in many large RCTs for chronic pain in noncancer populations, the large effect seen in the sham acupuncture (SA) group introduces great uncertainty in evaluating and interpreting the efficacy of acupuncture in the randomized setting (3). Indeed, a recent meta-analysis found that SA was much more effective than sham oral pharmaceutical placebos for migraine prophylaxis (4). Although the response to SA has led skeptics to consider the acupuncture effect no more than placebo, it remains quite possible that the sham interventions being studied are non-inert or acting via a different mechanism (5). Further evaluation of the contribution of the placebo effect to acupuncture is essential to addressing these methodological challenges about efficacy and to advancing the science of the field. Response expectancy is defined as, “expectations held by the individual about one’s own emotional and physiological response” to a treatment and is a critical component of the placebo response (6). Expectancy can be based upon a prior stimulus (eg, prior acupuncture or a similar intervention), the environment (eg, confidence in the practitioner), or learned conditioning (7). Evaluation of the association of expectancy with response to acupuncture has yielded mixed results (8), but a large study in noncancer pain populations found Baseline expectancy predicted treatment response (9). Despite the growing recognition of the importance of evaluating expectancy and elucidating the nonspecific effect of acupuncture, prior research has not used a validated instrument to evaluate response expectancy in the context of acupuncture. In addition, the majority of acupuncture studies evaluating response expectancy to date have measured expectancy only once at Baseline, when expectancy can change over time (10). Thus, this study aims to evaluate the association between response expectancy as measured by the Acupuncture Expectancy Scale (AES) (11,12), and treatment response to real and sham electroacupuncture (EA) for the treatment of aromatase inhibitor (AI)-associated arthralgia among women with breast cancer (13). The specific research questions of the study were: 1) Does Baseline expectancy predict pain reduction in the EA or SA groups? and 2) Does expectancy change with respect to responder status over the course of treatment in the EA or SA groups?

The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research.

PurposeThe Radiation Therapy Oncology Group (RTOG) conducted a randomized, placebo-controlled trial evaluating the efficacy of GM-CSF in reducing mucosal injury and symptom burden from curative radiotherapy for head and neck (H&N) cancer.MethodsEligible patients with H&N cancer receiving radiation encompassing ≥50% of the oral cavity or oropharynx received subcutaneous GM-CSF or placebo. Quality of life (QoL) was assessed using the RTOG-modified University of Washington H&N Symptom Questionnaire at baseline 4, 13, 26, and 48weeks from radiation initiation.ResultsOf 125 eligible patients, 114 were evaluable for QoL (58 GM-CSF, 56 placebo). Patient demographics, clinical characteristics, and baseline symptom scores were well balanced between the treatment arms. At the end of the acute period (13weeks), patients in both arms reported negative change in total symptom score indicating increase in symptom burden relative to baseline (mean -18.4 GM-CSF, -20.8 placebo). There was no difference in change in total symptom score (p>0.05) or change in mucous, pain, eating, or activity domain scores (p>0.01) between patients in the GM-CSF and placebo arms. Analysis limited to patients treated per protocol or with an acceptable protocol deviation also found no difference in change in total symptom score (p>0.05) or change in domain scores (p>0.01) between treatment arms. Provider assessment of acute mucositis during treatment did not correlate with patient-reported mucous domain and total symptom scores (p>0.05).ConclusionGM-CSF administered concurrently during head and neck radiation does not appear to significantly improve patient-reported QoL symptom burden.

We identified a standard core set of patient-reported symptoms and health-related quality-of-life (HRQOL) domains to be assessed in head and neck (H&N) cancer clinical trials. The core symptom and HRQOL domain scores were used to guide recommendations by a working group of experts as part of a National Cancer Institute Symptom Management and HRQOL Clinical Trials Planning Meeting. A PubMed search was conducted using the search terms of "health-related quality of life" and "head & neck cancer," limited to publications from January 1, 2000, to December 31, 2010. Fifty-four articles were used to guide the choice of recommendations. Twenty-nine symptoms and nine domains were identified, from which 12 H&N-specific core symptoms and HRQOL domains were recommended: swallowing, oral pain, skin changes, dry mouth, dental health, opening mouth/trismus, taste, excess/thick mucous/saliva, shoulder disability/motion, voice/hoarseness, social domain, and functional domain. This core set of 12 H&N-specific, patient-reported symptoms and HRQOL domains should be assessed in future H&N cancer clinical trials.

Importance Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined. Objectives To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected. Design, Setting, and Participants Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013. Interventions One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year. Main Outcomes and Measures Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events. Results Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo ( P = .49); an absolute difference of 5% (95% CI, −9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners. Conclusions and Relevance Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients. Trial Registration clinicaltrials.gov Identifier:NCT00931528

The purpose of the present study was to systematically compare the psychological and screening profiles of first-degree relatives (FDRs) of prostate cancer patients versus non-FDRs. FDRs (n = 56) and non-FDRs (n = 100), recruited through prostate cancer index cases and newspaper advertisements, completed questionnaires via mail. FDRs reported feeling at greater risk for prostate cancer, estimated that they were at higher average lifetime risk for the disease, agreed more strongly that prostate cancer is inherited, and that less can be done to prevent the development of the disease. Increased age, but not FDR status, was associated with more frequent screening behavior. Taken together, the results indicate that FDRs are characterized by greater perceived vulnerability to prostate cancer and lower expectations about disease prevention. Yet, they are no more likely to be screened than non-FDRs. These findings underscore the importance of developing, and evaluating, evidence-based health communication protocols to promote screening adherence among at-risk patients.

EPIDEMIOLOGY, SCREENING, AND EARLY DETECTION

Cancer and cancer therapies impair sexual health in a multitude of ways. The promotion of sexual health is therefore vital for preserving quality of life and is an integral part of total or holistic cancer management. Nursing, to provide holistic care, requires research that is meaningful to patients as well as the profession to develop educational and interventional studies to promote sexual health and coping. To obtain meaningful research data instruments that are reliable, valid, and pertinent to patients' needs are required. Several sexual functioning instruments were reviewed for this study and found to be lacking in either a conceptual foundation or psychometric validation. Without a defined conceptual framework, authors of the instruments must have made certain assumptions regarding what women undergoing cancer therapy experience and what they perceive as important. To check these assumptions before assessing women's sexuality after cancer therapies in a larger study, a pilot study was designed to compare what women experience and perceive as important regarding their sexuality with what is assessed in several currently available research instruments, using the focus group technique. Based on the focus group findings, current sexual functioning questionnaires may be lacking in pertinent areas of concern for women treated for breast or gynecologic malignancies. Better conceptual foundations may help future questionnaire design. Self-regulation theory may provide an acceptable conceptual framework from which to develop a sexual functioning questionnaire.

This study assessed changes in gene expression and their association with fatigue in head and neck cancer (HNC) patients receiving Intensity-Modulated Radiotherapy (IMRT). Consented patients were investigated pre- and 1-month post-IMRT. Fatigue was assessed by Multidimensional Fatigue Inventory-20. RNA was isolated from peripheral blood mononuclear cells and analyzed on Illumina Whole Genome BeadChips microarray. Forty non-metastatic HNC patients were enrolled; 70% received chemoIMRT. 1076 genes demonstrated expression changes from pre- to post-IMRT that were significantly correlated with changes in fatigue; 323 (30%) were up-regulated and 753 (70%) were down-regulated from pre- to post-IMRT. Gene enrichment analysis was performed using MetaCore/Cytoscape (FDR 0.01). Among top 200 genes, the top two biological pathways in up-regulated genes were related to IL6 regulation and Legionellosis in innate immune response. The top two biological pathways in down-regulated genes were related to thymic T cell selection and IL12 regulation in acquired immune response. Among top 200 up-regulated genes, the top network of transcription factors/receptors, such as RAGE, AP-1, and CREB1, was significantly over-represented for genes involved in body’s response to treatment-related stimuli. The second most significant network, including TLR, NFkB and its family, was significantly over-represented for genes involved in body’s immune and defense system. These findings suggest that fatigue is associated with expression changes in genes related to inflammation and immune response. Future large studies are needed to verify these findings.

Overview: Just as clinical trial design and rigor have evolved with improvements in methods and processes, so too have methods for capturing patient data in clinical trials. Substantial evidence suggests that standard physician reporting of symptoms for which we lack objective diagnostics (e.g., pain) is often discordant with patient self-report. Current reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTC[AE]) for symptom capture relies on a filtering system, from patient to physician to medical record to medical record abstraction to data entry, with each step requiring interpretation and the possibility of error. In contrast, patient-reported outcomes (PROs) eliminate the filter and rely on direct report. Furthermore, the lack of validation and training in use of the CTC(AE) creates an inadequate data capture system. Inadequacies might be observed as underreporting or overreporting symptom prevalence and severity compared with patient self-report. Inaccuracies in symptom reporting can lead to missing important prognostic information, lack of understanding of patient adherence with therapies, and lack of information for patient decision making. They can also lead to opportunities lost in terms of labeling claims and comparative effectiveness analyses. New developments in patient-reported outcome (PRO) reporting, including the PRO-CTC(AE) and models for incorporation of PROs in clinical trials, might facilitate routine PRO reporting complementary to CTC(AE) in clinical trials. In addition, the cadre of validated PRO instruments already in existence allows for more in-depth, hypothesis-driven evaluations. For standard toxicity reporting, the time has come for mandatory routine PRO symptom reporting complementary to the CTC(AE).

Background As breast cancer patients increasingly use complementary and alternative medicine (CAM), clinical trials are needed to guide appropriate clinical use. We sought to identify socio-demographic, clinical and psychological factors related to willingness to participate (WTP) and to determine barriers to participation in an acupuncture clinical trial among breast cancer patients. Methods We conducted a cross-sectional survey study among post-menopausal women with stage I-III breast cancer on aromatase inhibitors at an urban academic cancer center. Results Of the 300 participants (92% response rate), 148 (49.8%) reported WTP in an acupuncture clinical trial. Higher education (p = 0.001), increased acupuncture expectancy (p

In this article, we address statistical techniques appropriate for examining longitudinal changes in cancer symptom clusters. When the cluster structure is not pre-determined, researchers may examine symptom clusters either at each time point or use composite scores to examine the symptom clusters across time points. When the cluster structures are pre-determined, the statistical techniques depend on the research assumptions or purposes. Multilevel modeling, generalized estimating equations, latent growth curve modeling, and multivariate repeated-measure analysis of variance are good choices for exploring whole cluster changes over time. Alternately, confirmatory factor analysis and path analysis are appropriate techniques for examining changes in symptom relationships within clusters over time. Each technique is described, with examples and strengths and weaknesses.

This study's purpose is to develop a quantitative ultrasound technology to evaluate radiation-induced vaginal fibrosis. Radiation therapy (RT) is an important treatment modality for most gynecologic (GYN) malignancies. However, vaginal fibrosis is a common chronic side-effect, affecting 80% of women post vaginal or pelvic RT. Vaginal fibrosis leads to pain, sexual dysfunction, and poor quality of life.The authors propose a novel ultrasound approach that combines conventional B-mode imaging with Nakagami parameter imaging to quantitatively evaluate post-RT vaginal injury. From the B-mode image, vaginal wall thickness and echo intensity were calculated to capture the anatomy and echogenicity of the vaginal wall. From Nakagami imaging, two statistical parameters, Nakagami probability density function (PDF) and Nakagami shape, were computed to measure the concentration and arrangement of vaginal tissue microstructures. This novel ultrasound imaging concept was investigated in a pilot study of 12 patients, who were previously diagnosed and treated for endometrial cancer. The 12 participants were stratified into two groups: (1) the control group consisted of 6 patients who received surgery (hysterectomy) alone and (2) the post-RT group consisted of 6 patients who received surgery plus radiotherapy, with a follow-up time of 12-38 months. Each participant underwent one transvaginal ultrasound study (6 MHz). Three transverse images of the anterior vaginal wall were acquired in a 2 cm step from the apex (vaginal cuff) to the introitus (vagina opening). The vaginal wall thickness, echo intensity, Nakagami PDF, and Nakagami parameter were calculated to evaluate radiation-induced vaginal fibrosis.Both B-mode and Nakagami methods showed significant differences in parameters between the post-RT and nonirradiated vaginal walls. Compared with the control group, the vaginal wall thickness of the post-RT group increased by 153.2% (p = 0.002), the echo intensity increased by 11.6% (p = 0.017), the Nakagami PDF increased by 72.3% (p0.001), and the Nakagami shape valued increased by 33.0% (p = 0.028).Vaginal fibrosis appears to be associated with a thickened vaginal wall, higher echogenicity, as well as increased Nakagami PDF and shape parameters. This pilot study shows the authors' quantitative ultrasound approach combining B-mode and Nakagami imaging is a promising imaging method to evaluate vaginal fibrosis. This imaging method may be useful as physicians try to address vaginal toxicities and sexual dysfunction in women after radiotherapy for GYN malignancies.

Introduction We describe the development and validation of the Patient-Reported Outcomes Measurement Information System® Sexual Function and Satisfaction (PROMIS® SexFS; National Institutes of Health) measures, version 1.0, for cancer populations. Aim To develop a customizable self-report measure of sexual function and satisfaction as part of the U.S. National Institutes of Health PROMIS Network. Methods Our multidisciplinary working group followed a comprehensive protocol for developing psychometrically robust patient-reported outcome measures including qualitative (scale development) and quantitative (psychometric evaluation) development. We performed an extensive literature review, conducted 16 focus groups with cancer patients and multiple discussions with clinicians, and evaluated candidate items in cognitive testing with patients. We administered items to 819 cancer patients. Items were calibrated using item-response theory and evaluated for reliability and validity. Main Outcome Measures The PROMIS SexFS measures, version 1.0, include 81 items in 11 domains: Interest in Sexual Activity, Lubrication, Vaginal Discomfort, Erectile Function, Global Satisfaction with Sex Life, Orgasm, Anal Discomfort, Therapeutic Aids, Sexual Activities, Interfering Factors, and Screener Questions. Results In addition to content validity (patients indicate that items cover important aspects of their experiences) and face validity (patients indicate that items measure sexual function and satisfaction), the measure shows evidence for discriminant validity (domains discriminate between groups expected to be different) and convergent validity (strong correlations between scores on PROMIS and scores on conceptually similar older measures of sexual function), as well as favorable test–retest reliability among people not expected to change (interclass correlations from two administrations of the instrument, 1 month apart). Conclusions The PROMIS SexFS offers researchers a reliable and valid set of tools to measure self-reported sexual function and satisfaction among diverse men and women. The measures are customizable; researchers can select the relevant domains and items comprising those domains for their study.

Purpose : To assess institutional and patient compliance with quality of life (QL) instruments in RTOG clinical trials. To assess feasibility of using the Functional Assessment Cancer Therapy (FACT), Sexual Adjustment Questionnaire (SAQ), and Changes in Urinary Function (CUF) QL instruments in a prostate clinical trial and to compare patient self-report of symptoms to medical professional ratings of the same symptoms using the RTOG acute toxicity rating scales. Methods and Materials : Three self-assessment QL instruments, the FACT, the SAQ, and CUF, were to be administered to patients on a Phase II locally advanced prostate trial at specified time points. Specific instructions for both data managers and for patients on when, how, and why to fill out the questionnaires were included. Results : Sixty-seven percent (24 out of 36) of patients accrued to RTOG 90-20 completed both the initial FACT and SAQ. Eighty-five percent completed FACT at end of RT and 73% at 3 months. Eighty-one percent completed SAQ at end of treatment, while 69% completed this form at 3 months. Compliance drops off thereafter. Seventy-five percent of patients who had their symptom of dysuria rated by a medical professional as 0 on the RTOG toxicity rating scale self-reported the same. Only 56% of patient self-reports on FACT regarding diarrhea were in agreement with the medical professional's RTOG rating of 0 toxicity. The measures were determined to be in moderate agreement when the patient evaluated a symptom as a 1 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG toxicity rating scale. There was moderate agreement in 13% of patients with dysuria and 31% of patients with diarrhea. Low agreement occurred when the patient evaluated a symptom as a 2 or 3 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG scale. Low agreement occurred in 13% of both patients reporting dysuria and diarrhea. Differences between how medical professionals and patients were able to rate erectile function make direct comparisons difficult, but the trend towards significant discrepancies is still noteworthy. Conclusions : Quality of life assessments are necessary and attainable in RTOG clinical trials. Compliance rates for both institutional and patient participation were acceptable at initial and 3 month follow-up. Reasons for noncompliance were predominantly institution related and not patient related. Strategies to address both institution and patient compliance have been developed and implemented within the RTOG. Serious disagreement between patient self-reports of symptoms on the FACT QL scale and medical professional ratings on the RTOG acute toxicity rating scales of the same symptoms was 13% at 3 months follow-up. This warrants continued use of QL self-assessments in clinical trials.

The purpose of this article is to review the late effects of cancer therapy on the female reproductive tract. The anatomic sites detailed are the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is discussed. Clinical syndromes are presented. Tolerance doses of irradiation for late effects are rarely presented in the literature and are reviewed where available. Management strategies for surgical, radiotherapeutic, and chemotherapeutic late effects are discussed. Endpoints for evaluation of therapeutic late effects have been formulated utilizing the symptoms, objective, management, and analytic (SOMA) format. Late effects on the female reproductive tract from cancer therapy should be recognized and managed appropriately. A grading system for these effects is presented. Endpoints for late effects and tolls for the evaluation need to be further developed.

Screening for prostate cancer has improved early detection of the disease and may impact on mortality rates. Since all reported screening programs to date have originated in urology practices, we undertook such an effort in our department of radiation oncology where a comprehensive prostate cancer program exists. Four annual prostate cancer screening programs were conducted by our department of radiation oncology between 1990–1993. Examiners and supportive personnel included the attending staff, house staff, rotating medical students, and nurses from the department of radiation oncology. Urologists were encouraged, but not required, to assist. Eligible subjects included men ≧ 50 years old and men ≧ 40 if a family history of prostate cancer in a first degree relative was documented. The screening protocol consisted of directed history, measurement of serum prostate specific antigen (PSA), followed by digital rectal examination (DRE) performed by attending physicians. Needle biopsies were carried out on men with abnormal DRE, elevated PSA (>4 ng/mL), or both. Complete follow-up was obtained by contacting participants and their primary physicians. During the 4-year period, 442 men were screened (annual range: 91–202) and a total of 11 cancers were diagnosed. All patients diagnosed with cancer had negative metastatic work-up. Among those screened, 20% (90/442) had abnormal DRE alone, 8.8% (39/442) had elevated PSA alone, while 9.2% (41/442) had both abnormal DRE and elevated PSA. Adenocarcinoma was diagnosed in 1% (1/90) of patients with abnormal DRE alone, 18% (7/39) of those with abnormal PSA alone, and in 7% (3/41) of men with both abnormalities. Among those with cancer, 63% (7/11) opted for definitive irradiation, 27% (3/11) chose prostatectomy and one patient chose observation. Among those who selected radiotherapy, 86% (6/7) were treated in our department. Prostate screening can be conducted by a radiation oncology practice and provides a valuable contribution to the community. Our screening program succeeded in diagnosing patients with organ-confined disease. These data extend the evidence of Catalona et al. [N Engl J Med 324:1156–1161, 1991] which suggest that rectal examination can no longer be regarded as the sole or most useful means of detecting prostate cancer. Most (63%) of the patients diagnosed through this effort opted for definitive treatment by radiotherapy. The majority (86%) of patients selecting irradiation were treated at our center. Although screening for prostate cancer is feasible, controlled clinical trials comparing screened to unscreened samples are needed to determine the effect of earlier detection on morbidity and survival. © 1995 Wiley-Liss, Inc.

Purpose In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods and Materials Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such as proton beam therapy, and the international harmonization of clinical trial QA. Results Four recommendations were made: ( 1 ) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); ( 2 ) to establish a case QA repository; ( 3 ) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and ( 4 ) to explore the feasibility of consolidating clinical trial QA in the United States. Conclusion Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based.

Objective To evaluate erectile function after high-dose radiotherapy for prostate cancer using the International Index of Erectile Function, Expanded Prostate Cancer Index Composite, and stamp test. Methods Men with favorable and intermediate-risk prostate cancer were assigned to receive prostate intensity-modulated radiotherapy (IMRT) versus an erectile tissue-sparing IMRT technique in a Phase III randomized, prospective study. The stamp test and International Index of Erectile Function and Expanded Prostate Cancer Index Composite questionnaires were completed at baseline and 6 months, 1 year, and 2 years after IMRT. The Sexual Health Inventory for Men scores were abstracted from the International Index of Erectile Function questionnaire. A partner questionnaire, designated IIEF-P, modeled after the International Index of Erectile Function questionnaire but from the perspective of the partner, was also collected. Results The data from 94 men who were enrolled in the trial and who had completed ≥1 questionnaire or 1 stamp test were analyzed. The median age of the patient population was 62.5 years. The median radiation dose was 76 Gy (range 74-80). At 6 months and 1 year after high-dose IMRT, a positive stamp result correlated significantly with the median Expanded Prostate Cancer Index Composite sexual summary, sexual function, and bother subscale scores. Additionally, 6 months after IMRT, the stamp test correlated with the median International Index of Erectile Function, International Index of Erectile Function sexual function domain, and Sexual Health Inventory for Men scores. Robust concordance for the International Index of Erectile Function and Sexual Health Inventory for Men scores was appreciated between responding patient and partner pairs. Conclusion Nocturnal tumescence, as indicated by a positive stamp test, correlated well with established quality of life questionnaires after IMRT. The stamp test should strongly be considered as an objective measure of erectile function in future studies of erectile dysfunction in patients with prostate cancer.

The Radiation Therapy Oncology Group (RTOG) has embarked on seven phase II or phase III multicentre clinical trials involving a quality of life component. Each quality of life trial used questionnaires or examinations that have been tested for reliability and validity by independent investigators. Each trial includes questionnaires that examine the patient's physical, functional, social, and emotional status, and that measure a specific quality of life issue pertinent to the patient's diagnosis or treatment. Two trial designs have been implemented for studies with quality of life endpoints. One design involves companion trials to the primary treatment study pertaining solely to the quality of life endpoint. The second design integrates the quality of life component into the primary trial design. The RTOG has found a need for education of individuals and institutions expected to administer and obtain the quality of life data. Once the data have been collected several methods for the analysis of the quality of life data are available. However, there is no one best method for analysing quality of life data, thus more than one method should be used in order to provide insight into the data.

The purposes of this exploratory pilot were to describe perceived barriers to participation in cervical cancer prevention research, and identify culturally-appropriate communication strategies to recruit Asian women into cancer prevention research. This thematic analysis of transcripts, from focus groups and in-depth interviews, was conducted in English, Vietnamese, and Mandarin Chinese, at a community clinic in Philadelphia, Pennsylvania. Thirty participants were either Vietnamese (35%) or Chinese (65%). Mean age was 36.8 (SD 9.9 years). Reasons for non-participation were: lack of time, inconvenience, mistrust of institutions and negative experiences, lack of translated materials, feeling intimidated by English, and the lack of translation of key words or terms. Enhancers of participation were: endorsement by a spouse, monetary compensation, and a personalized approach that offers a benefit for Asian women. To increase participation, first one must remove language barriers and, preferably, use specific dialects. Second, one must specify if benefits are indirectly or directly related to the family or cultural group. Asian research participants in our study consistently expressed that a significant motivator was their desire to be of help, in some way, to a family member or to the Asian community in general.

Purpose To investigate patients’ willingness to participate (WTP) in a randomized controlled trial (RCT) comparing intensity-modulated radiotherapy (IMRT) with proton beam therapy (PBT) for prostate cancer (PCa). Methods and Materials We undertook a qualitative research study in which we prospectively enrolled patients with clinically localized PCa. We used purposive sampling to ensure a diverse sample based on age, race, travel distance, and physician. Patients participated in a semi-structured interview in which they reviewed a description of a hypothetical RCT, were asked open-ended and focused follow-up questions regarding their motivations for and concerns about enrollment, and completed a questionnaire assessing characteristics such as demographics and prior knowledge of IMRT or PBT. Patients’ stated WTP was assessed using a 6-point Likert scale. Results Forty-six eligible patients (33 white, 13 black) were enrolled from the practices of eight physicians. We identified 21 factors that impacted patients’ WTP, which largely centered on five major themes: altruism/desire to compare treatments, randomization, deference to physician opinion, financial incentives, and time demands/scheduling. Most patients (27 of 46, 59%) stated they would either “definitely” or “probably” participate. Seventeen percent (8 of 46) stated they would “definitely not” or “probably not” enroll, most of whom (6 of 8) preferred PBT before their physician visit. Conclusions A substantial proportion of patients indicated high WTP in a RCT comparing IMRT and PBT for PCa.

BACKGROUND It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma. METHODS From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years. RESULTS The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients. CONCLUSIONS Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).

Background The objective of this study was to validate a simple predictive model for survival of patients with advanced cancer. Methods Previous studies with training and validation datasets developed a model predicting survival of patients referred for palliative radiotherapy using three readily available factors: primary cancer site, site of metastases and Karnofsky performance score (KPS). This predictive model was used in the current study, where each factor was assigned a value proportional to its prognostic weight and the sum of the weighted scores for each patient was survival prediction score (SPS). Patients were also classified according to their number of risk factors (NRF). Three risk groups were established. The Radiation Therapy and Oncology Group (RTOG) 9714 data was used to provide an additional external validation set comprised of patients treated among multiple institutions with appropriate statistical tests. Results The RTOG external validation set comprised of 908 patients treated at 66 different radiation facilities from 1998 to 2002. The SPS method classified all patients into the low-risk group. Based on the NRF, two distinct risk groups with significantly different survival estimates were identified. The ability to predict survival was similar to that of the training and previous validation datasets for both the SPS and NRF methods. Conclusions The three variable NRF model is preferred because of its relative simplicity.

Existing studies of medication adherence treat “nonadherence” as a monolithic concept. The goal of this study was to isolate correlates of intentional versus unintentional nonadherence for analgesic treatment for cancer pain. Patients were recruited from outpatient oncology clinics in the middle Atlantic region, ≥18 years old, and diagnosed with solid tumors, and had an active prescription of at least one around-the-clock analgesic. The Morisky Medication Adherence Scale (MMAS) was used to assesses “unintentional” (forgetfulness/carelessness) and “intentional” (stopping use of medication if feeling better or worse) dimensions of analgesic nonadherence. A visual analog scale was used to assess the percentage of analgesic doses taken in the preceding month. A majority of participants (85.5%) took prescribed analgesics in the index period. However, 51% reported taking only up to 60% of the analgesic doses prescribed to them. Stopping taking analgesics when feeling better was the most commonly reported nonadherence behavior (74%); those reporting “intentional” nonadherence when feeling better were more likely to report not using analgesics in the index week (100% vs. 67.7%; p = .029) and agree that pain medication can keep you from knowing what is going on in your body (p = .029) and were less likely to need stronger pain medication (33.3% vs. 81.5%; p = .003). “Unintentional” nonadherence, i.e., forgetfulness/carelessness, though associated with many analgesic beliefs, was not associated with measures of analgesic use in the index period. These preliminary data indicate that different heuristics underlie intentional versus unintentional nonadherence to analgesia and that intentional and unintentional nonadherence behaviors may have different implications for pain treatment outcomes.

Purpose We investigated the impact of race, in conjunction with gender and partner status, on locoregional control (LRC) and overall survival (OS) in three head and neck trials conducted by the Radiation Therapy Oncology Group (RTOG). Methods and Materials Patients from RTOG studies 9003, 9111, and 9703 were included. Patients were stratified by treatment arms. Covariates of interest were partner status (partnered vs. non-partnered), race (white vs. non-white), and sex (female vs. male). Chi-square testing demonstrated homogeneity across treatment arms. Hazards ratio (HR) was used to estimate time to event outcome. Unadjusted and adjusted HRs were calculated for all covariates with associated 95% confidence intervals (CIs) and p values. Results A total of 1,736 patients were analyzed. Unpartnered males had inferior OS rates compared to partnered females (adjusted HR = 1.22, 95% CI, 1.09–1.36), partnered males (adjusted HR = 1.20, 95% CI, 1.09–1.28), and unpartnered females (adjusted HR = 1.20, 95% CI, 1.09–1.32). White females had superior OS compared with white males, non-white females, and non-white males. Non-white males had inferior OS compared to white males. Partnered whites had improved OS relative to partnered non-white, unpartnered white, and unpartnered non-white patients. Unpartnered males had inferior LRC compared to partnered males (adjusted HR = 1.26, 95% CI, 1.09–1.46) and unpartnered females (adjusted HR = 1.30, 95% CI, 1.05–1.62). White females had LRC superior to non-white males and females. White males had improved LRC compared to non-white males. Partnered whites had improved LRC compared to partnered and unpartnered non-white patients. Unpartnered whites had improved LRC compared to unpartnered non-whites. Conclusions Race, gender, and partner status had impacts on both OS and locoregional failure, both singly and in combination.

Previous studies by our group and others have demonstrated the importance of sociodemographic factors in cancer-related outcomes. The identification of these factors has led to novel approaches to the care of the high-risk cancer patient, specifically in the adoption of clinical interventions that convey similar benefits as favorable sociodemographic characteristics. This study examined the importance of marital status and race as prognostic indicators in men with prostate cancer. This report is a meta-analysis of 3,570 patients with prostate cancer treated in three prospective RTOG clinical trials. The Kaplan–Meier method was used to estimate the survival rate and the cumulative incidence method was used to analyze biochemical failure rate. Hazard ratios were calculated for all covariates using either the Cox or Fine and Gray’s proportional hazards model or logistic regression model with associated 95% confidence intervals and p values. Hazard ratio (HR) for overall survival (OS) for single status compared to married status was 1.36 (95% CI, 1.2 to 1.53). OS HR for non-White compared to White patients was 1.05 (CI 0.92 to 1.21). In contrast, the disease-free survival (DFS) HR and biochemical failure (BF) HR were both not significantly different neither between single and married patients nor between White patients and non-White patients. Median time to death for married men was 5.68 years and for single men was 4.73 years. Median time for DFS for married men was 7.25 years and for single men was 6.56 years. Median time for BF for married men was 7.81 years and for single men was 7.05 years. Race was not associated with statistically significant differences in this analysis. Congruent with our previous work in other cancer sites, marital status predicted improved prostate cancer outcomes including overall survival. Prostate cancer is the most common visceral cancer in men in the USA. The stratification of prostate cancer risk is currently modeled solely on pathologic prognostic factors including PSA and Gleason Score. Independent of these pathologic prognostic factors, our paper describes the central sociodemographic factor of being single as a negative prognostic indicator. Single men are at high risk of poorer outcomes after prostate cancer treatment. Intriguingly, in our group of patients, race was not a significant prognostic factor. The findings in this paper add to the body of work that describes important sociodemographic prognostic factors that are currently underappreciated in patients with cancer. Future steps will include the validation of these findings in prospective studies, and the incorporation of clinical strategies that identify and compensate for sociodemographic factors that predict for poorer cancer outcomes.

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.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.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, p0.0001). Men recruited by radio were more likely to be black (p0.001), less educated (p = 0.003) and not married or partnered (p = 0.007), and have no prostate cancer family history (p0.001). 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, p0.0001).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.

Purpose Timely recruitment and retention of human subjects remains a leading problem in oncology clinical trials even among the national oncology clinical trial cooperative groups. The Radiation Therapy Oncology Group (RTOG) developed an exploratory survey to assess member attitudes, beliefs, and practices (ABPs) towards clinical trials that might influence patient accrual to clinical trials. Methods The survey was developed using Survey Monkey© and emailed to principal investigators (PIs) and research associates (RAs) at 267 RTOG member institutions. Survey items were selected based on a review of the literature. PI and RA responses were matched by institution to determine whether responses varied due to job responsibilities and/or institutional practices. Principal component analysis was used to achieve variable reduction in further describing respondents' ABPs. Results PIs and RAs reported similar recruitment concerns [ κ = 0.55, 95% CI (0.51, 0.60)]. Five components related to recruitment concerns were identified: presentation of trials to patients, barriers and recruitment risks, staff involvement, access for underrepresented populations, and familial involvement (patient). Nearly one of four (24%) respondents perceived that patients did not understand what randomization means. Staff issues included nearly a third of respondents not having a formal mechanism at their institution for eligibility screening, and similarly, about one of three respondents felt that unrepresented patient populations would benefit from translated consent forms. Conclusions Findings of this survey inform RTOG strategies for addressing opportunities for improvement, including clinician/patient education and a best practices tool box that in the future would include successful mechanisms for eligibility screening and recruitment.

Radiation Therapy Oncology Group 97-14 concluded that a single fraction of radiation was as effective in relieving pain as multiple fractions in the treatment of patients with bone metastases. A statistically significant higher retreatment rate, however, was noted in patients undergoing a single fraction treatment. The purpose of the analysis was to determine whether multiple fraction treatment is cost-effective in treating patients with bone metastasis, by preventing further retreatment.A Markov model was used to evaluate the cost-effectiveness of 30 Gy in 10 fractions in comparison with 8 Gy in 1 fraction. Transition probabilities, cost, and utilities were obtained from the clinical trial. Costs and outcomes were not discounted because of the short time line for the study.The expected mean cost and quality-adjusted survival in months for patients receiving 8 Gy in 1 fraction and 30 Gy in 10 fractions was 998 US dollars and 7.26 months and 2316 US dollars and 9.53 months, respectively. The incremental cost-effectiveness ratio was 6973 US dollars/quality-adjusted life year. The results were sensitive to the utility of the posttreatment state for both single and multiple fraction treatments.Single fraction treatment was the less expensive treatment in the treatment of patients with bone metastasis treated on Radiation Therapy Oncology Group 97-14.

Background Few studies have examined vitamin D insufficiency in African American men although they are at very high risk. We examined the prevalence and correlates of vitamin D insufficiency among African American men in Philadelphia. Methods Participants in this cross-sectional analysis were 194 African American men in the Philadelphia region who were enrolled in a risk assessment program for prostate cancer from 10/96–10/07. All participants completed diet and health history questionnaires and provided plasma samples, which were assessed for 25-hydroxyvitamin D (25(OH)D) concentrations. We used linear regression models to examine associations with 25(OH)D concentrations and logistic regression to estimate odds ratios (OR) for having 25(OH)D ≥ 15 ng/mL. Results Mean 25(OH)D was 13.7 ng/mL, and 61% of men were classified as having vitamin D insufficiency (25(OH)D 400 vs. 0 IU/day), milk consumption (OR 5.9, 95% CI 2.2, 16.0 for ≥ 3.5 vs. Conclusion The problem of low vitamin D status in African American men may be more severe than previously reported. Future efforts to increase vitamin D recommendations and intake, such as through supplementation, are warranted to improve vitamin D status in this particularly vulnerable population.

BACKGROUND: Arthralgia is common in postmenopausal breast cancer survivors (BCS) who are receiving aromatase inhibitors (AIs). The objective of this study was to evaluate the perceived onset, characteristics, and risk factors for AI-related arthralgia (AIA). METHODS: In a cross-sectional survey of postmenopausal BCS who were receiving adjuvant AI therapy at a university-based oncology clinic, patient-reported attribution of AIs as a cause of joint pain was used as the primary outcome. Multivariate logistic regression analyses were performed to evaluate risk factors. RESULTS: Among 300 survey respondents, 139 (47%) attributed AI as a cause of their current arthralgia. Of those patients, 74% recognized the onset of AIA within 3 months of starting medication, and 67% rated joint pain as moderate or severe in the previous 7 days. In multivariate logistic regression analyses, the time since last menstrual period (LMP) was the only significant predictor of AIA. Controlling for covariates, the women who had their LMP within 5 years had the highest probability of reporting AIA (73%), whereas those who had their LMP ≥10 years previously had the lowest probability of reporting AIA (35%; adjusted odds radio, 3.39; 95% confidence interval, 1.21-9.44; P = .02). Wrists/hands, ankles/feet, elbows, and knees appeared to be associated more strongly with AI-related symptoms than non-AI–related joint symptoms (all P < .01). CONCLUSIONS: AIA was common, began within the first 3 months of therapy in most patients, and appeared to be related inversely to the length of time since cessation of menstrual function. These findings suggest that estrogen withdrawal may play a role in the mechanism of this disorder. Cancer 2009. © 2009 American Cancer Society.

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.Medicare costs from all providers and all places of service were obtained from the Centers for MedicareMedicaid 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.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.Claims data permit estimation of cost effectiveness, but Medicare data provide inadequate representation of results applicable to patients from the general population.

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. 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. 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. 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.

To determine if physician prediction of survival duration (PSD) is accurate for patients with metastatic breast or prostate cancer.Radiation Therapy Oncology Group 9714 (RTOG 9714) was a randomized comparison of radiotherapy schedules for treatment of bone metastases. The treating physician assigned a baseline Karnofsky Performance Score (KPS) and predicted survival duration at study entry. Patients completed the Functional Assessment of Cancer Therapy (FACT). These three were compared to actual survival time.Eight hundred ninety-eight patients were eligible and analyzable. Actual median survival was 9.3 months. The median PSD was 12 months. PSD, KPS, and FACT were all moderately correlated with actual survival. Patients with higher KPS had a longer survival time (882 patients, Spearman's rho = 0.259, p0.0001). The median survival of the 618 expired patients is 6.5 months (PSD was 12 months). The PSD was within 1 month of actual survival in 61 (10%), with 177 (29%) patients surviving more than 1 month longer than predicted and 375 (61%) surviving more than 1 month less than predicted. A univariate analysis of actual overall survival was performed, dividing the PSD into 4 groups. For predicted survivals of 6 months or less, less than 6 to less than 12 months, 12 months, and more than 12 months, median actual survivals were 7.0, 7.2, 9.7. and 13.5 months (p0.0001).KPS, FACT scores, and PSD all are correlated with actual survival. Physicians on this study were able to predict which patients would have longer survival times, although prediction of survival was optimistic compared to actual survival by an average of 3 months.

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.

128 Background: Neurocognitive functional decline is a common sequalae of cranial irradiation (CI) that significantly impacts quality of life. Preclinical studies and randomized clinical trials show that following traumatic brain injury and cerebrovascular accidents, premenopausal women demonstrate decreased mortality and improved neurocognitive function, with these benefits presumed to be derived from progesterone. We hypothesized that progesterone may serve similar role in neuroprotection following cranial irradiation. Methods: Adult non-tumor bearing wild type C57BL/6 male mice were treated with two separate fractionated radiation therapy regimen (9 Gy and 15 Gy) to the brain. Cohorts of these mice were administered progesterone (16mg/kg daily) as a pretreatment for 3 days and concurrent with the radiotherapy for a total of 14 days with tapering during the last two days. The animals were then tested using different behavioral measures for cognitive function including morris water maze (MWM) for assessing spatial and related forms of learning and memory, elevated plus maze (EPM), , and spontaneous locomotor activity (SLA) tests. Mice were tested for cognitive function on day 10 and after 30 days of treatment for short and long-term effects of (CI) on memory function. Results: All irradiated mice showed statistically significant decline in MWM, EPM, and SLA measures. There were no significant differences in the 9 Gy versus 15 Gy cohorts. Progesterone administration produced a statistically significant group effect (F (4, 25) = 8.553; P(4, 25) = 8.613; P(4, 25)= 7.993; P

27 Background: The considerable interest in short UHR 5-12 fractions(fr) in management of CaP is based on potential radiobiological advantages, patient convenience & resource allocation benefits. Prior to comparison with standard RT regimens (SRTR), a study was undertaken whose primary objective was to demonstrate that 1-year health-related quality of life (HRQOL) for at least one UHR arm was not significantly lower than baseline as measured by the Bowel & Urinary domains EPIC instrument(EPIC B&U). Secondary objectives included acute & late GI & GU toxicity. Methods: RTOG 0938 is a randomized phase II study of CaP patients(pts), (Gleason score 2-6, stage T1-2a & PSA < 10 ng/mL) receiving 36.25 Gy (5 fr of 7.25 Gy in 2 wks), or 51.6 Gy (12 fr of 4.3 Gy in 2.5 wks). Pts were stratified according to RT technique – Cyberknife vs IMRT/VMAT or protons. A change in EPIC bowel domain score (baseline to 1-year) > 5 points & in EPIC urinary domain score > 2 points were felt to be clinically significant. The frequency for > 5 point change in bowel score (FREQE-B) in ≤ 35% of pts was considered acceptable, with the frequency ≥ 55% unacceptable. Similarly, the frequency for > 2 point change in urinary score (FREQE-U) in ≤ 40% was considered acceptable, with the frequency ≥ 60% unacceptable. A sample size of 156 pts was needed for 95% power with one-sided significance level of 0.025 to preserve an overall level of 0.05. Results: 240 pts were enrolled to ensure adequacy of data for analysis. The compliance for HRQOL completion was good ( > 80%). The 1 year FREQE-B for 5 fr was 23.5% (p < 0.001) & 12 fr was 23.1% (p < 0.001). The 1 year FREQE-U for 5 fr was 35.3% (p < 0.001) & 12 fr was 34.7% (p < 0.001). Conclusions: This study confirms that based on changes in EPIC B&U (baseline to 1-year), acute & late toxicity, both the 5 & 12 fr regimens are well tolerated. These UHR need to be compared to current SRTR in the context of a RCT with efficacy & toxicity endpoints. Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, UG1CA189867 from the National Cancer Institute (NCI). Clinical trial information: NCT01434290. [Table: see text]

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA < 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.

Patient-Reported Outcomes in NRG Oncology/RTOG 0938, a Randomized Phase 2 Study Evaluating 2 Ultrahypofractionated Regimens (UHRs) for Prostate Cancer H. Lukka, P. Stephanie, D. Bruner, J.P. Bahary, C.A.F. Lawton, J.A. Efstathiou, R. Kudchadker, L. Ponsky, S.A. Seaward, I.S. Dayes, D.D. Gopaul, J.M. Michalski, G. Delouya, I.D. Kaplan, E.M. Horwitz, M. Roach, III, W.H. Pinover, D.C. Beyer, H.M. Sandler, and L.A. Kachnic; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON, Canada, NRG Oncology Statistics and Data Management Center, Philadelphia, PA, Emory University, Atlanta, GA, Hopital Notre-Dame du CHUM, Montreal, QC, Canada, Medical College of Wisconsin, Milwaukee, WI, Massachusetts General Hospital, Harvard Medical School, Boston, MA, MD Anderson Cancer Center, Houston, TX, United States, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, Kaiser Permanente Northern California, Santa Clara, CA, United States, McMaster University, Hamilton, ON, Canada, Grand River Regional Cancer Centre, Kitchener, ON, Canada, Washington University School of Medicine, St. Louis, MO, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada, Beth Israel Deaconess Medical Center, Boston, MA, Fox Chase Cancer Center, Philadelphia, PA, University of California, San Francisco, San Francisco, CA, Abington Memorial Hospital, Abington, PA, United States, Foundation for Cancer Research and Education, Phoenix, AZ, Cedars-Sinai Medical Center, Los Angeles, CA, Boston Medical Center, Boston, MA