Deborah Watkins Bruner

Palliative radiotherapy for bone metastases: An ASTRO evidence-based guideline

PURPOSE To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. METHODS AND MATERIALS A systematic search of the National Library of Medicines PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. RESULTS The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. CONCLUSIONS Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use and provide consensus views concerning contemporary controversies or unanswered questions that warrant prospective trial evaluation.

Relative risk of prostate cancer for men with affected relatives: systematic review and meta-analysis.

An increased risk of prostate cancer associated with a family history of prostate cancer has been documented in multiple published reports. Risk has been shown to vary by degree of relationship and age of onset of disease in the affected relative. Several studies, using various designs, have estimated the relative risk (RR) for these associations. The purpose of our study was to identify and summarize published reports on the relationship between risk of prostate cancer and family history, which is defined as having a father, brother, any first‐ or second‐degree relative or other relative affected with prostate cancer. A Medline and manual search from 1982 to 2000 identified 24 studies that reported RR and confidence intervals (CI) and satisfied inclusion criteria. Pooled RR estimates based upon a weighted average model were as follows: any affected family member RR = 1.93, CI 1.65–2.26; affected first‐degree relative RR = 2.22, CI 2.06–2.40; affected second‐degree relative RR = 1.88, CI 1.54–2.30; father with prostate cancer RR = 2.12, CI 1.82–2.51; and brother with prostate cancer RR = 2.87, CI 2.21–3.73). Statistical comparison of pooled data demonstrated that the RR is significantly higher for affected brother than for affected father (p < 0.03). A sensitivity analysis demonstrated that these results are robust with respect to population bias. This meta‐analysis confirms that risk of prostate cancer is associated with family history of disease and improves the quantification of this risk.

Patterns and Risk Factors Associated with Aromatase Inhibitor Related Arthralgia Among Breast Cancer Survivors

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).

Patient-Reported Outcomes Assessment in Cancer Trials: Taking Stock, Moving Forward

To evaluate and improve the use of cancer trial end points that reflect the patients own perspective, the National Cancer Institute organized an international conference, Patient-Reported Outcomes Assessment in Cancer Trials (PROACT), in 2006. The 13 preceding articles in this special issue of the Journal were commissioned in preparation for or in response to the PROACT conference, which was cosponsored by the American Cancer Society. Drawing from these articles and also commentary from the conference itself, this concluding report takes stock of what has been learned to date about the successes and challenges in patient-reported outcome (PRO) assessment in phase III, phase II, and symptom management trials in cancer and identifies ways to improve the scientific soundness, feasibility, and policy relevance of PROs in trials. Building on this synthesis of lessons learned, this article discusses specific administrative policies and management procedures to improve PRO data collection, analysis, and dissemination of findings; opportunities afforded by recent methodologic and technologic advances in PRO data collection and analysis to enhance the scientific soundness and cost efficiency of PRO use in trials; and the importance of better understanding the usefulness of PRO data to the full spectrum of cancer decision makers, including patients and families, health providers, public and private payers, regulatory agencies, and standards-setting organizations.

Late injury of cancer therapy on the female reproductive tract

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.

Quality of life study in prostate cancer patients treated with three-dimensional conformal radiation therapy: Comparing late bowel and bladder quality of life symptoms to that of the normal population☆

PURPOSE The goals of this study were twofold. First, differences were quantified for symptoms that impact bowel and bladder quality of life (QOL) in prostate cancer patients treated with three-dimensional conformal radiotherapy (3DCRT) alone to the prostate vs. whole pelvis with prostate boost. Second, bowel and bladder QOL measures for these patients were compared to those of the normal population of men with a similar age distribution. MATERIAL AND METHODS Two health status surveys evaluating bowel and bladder functioning, along with the AUA Symptom Problem Index and the BPH Impact Index, were mailed to 195 prostate cancer patients treated with 3DCRT between 12/92 and 11/95 at Fox Chase Cancer Center by a single clinician (GH). No patient received hormonal management as part of his treatment. Ninety-five patients had pretreatment PSA levels <10 ng/ml, T1/T2A tumors with Gleason scores 2-6, and no perineural invasion. They were treated to the prostate alone and are referred to as Group I. The remaining 100 patients had one or more of the following characteristics: pretreatment PSA levels > or =10 ng/ml, T2B/T3 tumors, Gleason scores 7-10, or perineural invasion. These patients were treated to the whole pelvis followed by a boost to the prostate and are referred to as Group II. Frequencies were tabulated, and differences in percentages for the two groups were evaluated using the two-tailed Fishers Exact Test. Overall percentages were compared to those for equivalent measures reported by Litwin (1999) based on a normal population of men with a mean age of 73 years (range 47-86). Comparisons to the normal population were also evaluated using two-tailed Fishers Exact p values. RESULTS The mailing yielded a high response rate of 71% (n = 139, 66 in Group I and 73 in Group II). The mean age was 67 (range 49-82), and the median ICRU dose levels for Groups I and II were 73 and 76 Gy, respectively. Responses relating to bladder symptoms were similar for Groups I and II, except for the degree of bother associated with trouble in urination over the last month. Percentages for no bother at all were 66% and 56% for Groups I and II, respectively. Observed differences in bowel functioning related to rectal urgency over the past year (22% vs. 40% for Groups I and II, p = 0.03), the use of pads for protection against bowel incontinence (0% vs. 10% for Groups I and II, p = 0.01), and bowel satisfaction (88% vs. 72% for Groups I and II, p = 0.03). There was no significant difference in the degree of bother bladder symptoms cause men treated with radiotherapy as compared to men without cancer. Few patients reported bowel dysfunction bother as a big problem, but patients do tend to have more very small to moderate bother from bowel dysfunction than the normal population (55% vs. 33%, p < 0.001). CONCLUSION This is the first long-term study of QOL in men treated with high-dose 3DCRT for prostate cancer. It demonstrates that these men enjoy QOL related to bladder function similar to that of the normal population. Few patients report bother from bowel symptoms as a big problem but tend to have more very small to moderate bother than the normal population. Treatment of prostate cancer patients to the whole pelvis may result in decreased QOL as defined by rectal urgency, the use of pads for bowel incontinence, and satisfaction with bowel functioning. However, regardless of field size, men are generally satisfied with their bowel and bladder functioning three to six years post treatment.

Issues and Challenges With Integrating Patient-Reported Outcomes in Clinical Trials Supported by the National Cancer Institute–Sponsored Clinical Trials Networks

PURPOSE The objective of this report is to provide a historical overview of and the issues and challenges inherent in the incorporation of patient-reported outcomes (PROs) into multinational cancer clinical trials in the cancer cooperative groups. METHODS An online survey of 12 cancer cooperative groups from the United States, Canada, and Europe was conducted between June and August of 2006. Each of the cooperative groups designated one respondent, who was a member of one of the PRO committees within the cooperative group. RESULTS There was a 100% response rate, and all of the cancer clinical trial cooperative groups reported conducting PRO research. PRO research has been conducted in the cancer cooperative groups for an average of 15 years (range, 6 to 30 years), and all groups had multidisciplinary committees focused on the design of PRO end points and the choice of appropriate PRO measures for cancer clinical trials. The cooperative groups reported that 5% to 50% of cancer treatment trials and an estimated 50% to 75% of cancer control trials contained PRO primary and secondary end points. There was considerable heterogeneity among the cooperative groups with respect to the formal and informal policies and procedures or cooperative group culture towards PROs, investigator training/mentorship, and resource availability for the measurement and conduct of PRO research within the individual cooperatives. CONCLUSION The challenges faced by the cooperative groups to the incorporation of PROs into cancer clinical trials are varied. Some common opportunities for improvement include the adoption of standardized training/mentorship mechanisms for investigators for the conduct of PRO assessments and data collection and the development of minimal criteria for PRO measure acceptability. A positive cultural shift has occurred in most of the cooperative groups related to the incorporation of PROs in clinical trials; however, financial and other resource barriers remain and need to be addressed.

The impact on quality of life by radiation late effects

The Radiation Therapy Oncology Group (RTOG) is developing an improved scoring system for the late effects of radiation therapy. There is a need to assess the impact of treatment on long-term survival. The RTOG Late Effects Toxicity Grading Scale documents the absence or the degree to which a symptom or sign is present. The scale in itself does not, however, score the impact of symptoms on survival. This Late Effects Scale in conjunction with quality-of-life assessments will provide the information necessary to assess the impact of treatment toxicities on normal daily living. Neither documentation of late effects nor their impact on quality of survival is an end in itself. These scales are only instruments that should serve to direct us toward our higher goal of designing interventional studies concerned with the quality of survival or rehabilitation. The development of the Late Effects Toxicities Grading Scale is a beginning.

Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study.

The objective of the current study was to examine whether emotional well‐being predicted survival in a large sample of patients with head and neck cancer who were participating in multicenter clinical trials.

Prevalence and correlates of vitamin D status in African American men

BackgroundFew 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.MethodsParticipants 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.ResultsMean 25(OH)D was 13.7 ng/mL, and 61% of men were classified as having vitamin D insufficiency (25(OH)D <15 ng/mL). Even among men with vitamin D intake ≥ 400 IU/day, 55% had 25(OH)D concentrations <15 ng/mL. In multivariate models, 25(OH)D concentrations were significantly associated with supplemental vitamin D intake (OR 4.3, 95% confidence interval (CI) 1.5, 12.4) for >400 vs. 0 IU/day), milk consumption (OR 5.9, 95% CI 2.2, 16.0 for ≥ 3.5 vs. <1 time per week), and blood collection in the summer. Additionally, 25(OH)D concentrations increased with more recreational physical activity (OR 1.3, 95% CI 1.1, 1.6 per hour). A significant inverse association of body mass index with 25(OH)D concentrations in bivariate analyses was attenuated with adjustment for season of blood collection.ConclusionThe 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.