Barriers to cancer clinical trial participation have been the subject of frequent study, but the rate of trial participation has not changed substantially over time. Studies often emphasize ...patient-related barriers, but other types of barriers may have greater impact on trial participation. Our goal was to examine the magnitude of different domains of trial barriers by synthesizing prior research.
We conducted a systematic review and meta-analysis of studies that examined the trial decision-making pathway using a uniform framework to characterize and quantify structural (trial availability), clinical (eligibility), and patient/physician barrier domains. The systematic review utilized the PubMed, Google Scholar, Web of Science, and Ovid Medline search engines. We used random effects to estimate rates of different domains across studies, adjusting for academic vs community care settings.
We identified 13 studies (nine in academic and four in community settings) with 8883 patients. A trial was unavailable for patients at their institution 55.6% of the time (95% confidence interval CI = 43.7% to 67.3%). Further, 21.5% (95% CI = 10.9% to 34.6%) of patients were ineligible for an available trial, 14.8% (95% CI = 9.0% to 21.7%) did not enroll, and 8.1% (95% CI = 6.3% to 10.0%) enrolled. Rates of trial enrollment in academic (15.9% 95% CI = 13.8% to 18.2%) vs community (7.0% 95% CI = 5.1% to 9.1%) settings differed, but not rates of trial unavailability, ineligibility, or non-enrollment.
These findings emphasize the enormous need to address structural and clinical barriers to trial participation, which combined make trial participation unachievable for more than three of four cancer patients.
Women have more adverse events (AEs) from chemotherapy than men, but few studies have investigated sex differences in immune or targeted therapies. We examined AEs by sex across different treatment ...domains.
We analyzed treatment-related AEs by sex in SWOG phase II and III clinical trials conducted between 1980 and 2019, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events. Symptomatic AEs were defined as those aligned with the National Cancer Institute's Patient-Reported Outcome-Common Terminology Criteria for Adverse Events; laboratory-based or observable/measurable AEs were designated as objective (hematologic
nonhematologic). Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 14 objective AE categories were examined.
In total, N = 23,296 patients (women, 8,838 37.9%; men, 14,458 62.1%) from 202 trials experiencing 274,688 AEs were analyzed; 17,417 received chemotherapy, 2,319 received immunotherapy, and 3,560 received targeted therapy. Overall, 64.6% (n = 15,051) experienced one or more severe (grade ≥ 3) AEs. Women had a 34% increased risk of severe AEs compared with men (odds ratio OR = 1.34; 95% CI, 1.27 to 1.42;
< .001), including a 49% increased risk among those receiving immunotherapy (OR = 1.49; 95% CI, 1.24 to 1.78;
< .001). Women experienced an increased risk of severe symptomatic AEs among all treatments, especially immunotherapy (OR = 1.66; 95% CI, 1.37 to 2.01;
< .001). Women receiving chemotherapy or immunotherapy experienced increased severe hematologic AE. No statistically significant sex differences in risk of nonhematologic AEs were found.
The greater severity of both symptomatic AEs and hematologic AEs in women across multiple treatment modalities indicates that broad-based sex differences exist. This could be due to differences in AE reported, pharmacogenomics of drug metabolism/disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving immunotherapy, suggesting that studying AEs from these agents is a priority.
Summary Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer ...opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Neuropathy is a debilitating toxicity associated with various chemotherapy agents. We evaluated the association between common comorbid conditions and the development of peripheral neuropathy in ...patients treated with taxane-based chemotherapy.
We examined the Southwest Oncology Group database to identify phase II and III trials that included taxane therapy from 1999 to 2011. We linked the Southwest Oncology Group clinical records to Medicare claims data according to Social Security number, sex, and date of birth. The following disease conditions potentially associated with peripheral neuropathy were evaluated: diabetes, hypothyroidism, hypercholesterolemia, hypertension, varicella zoster, peripheral vascular disease, and autoimmune diseases. Multivariate logistic regression was used to model the odds of experiencing grade 2 to 4 neuropathy.
A total of 1,401 patients from 23 studies were included in the analysis. Patients receiving paclitaxel were more likely to experience grade 2 to 4 neuropathy compared with docetaxel (25% v 12%, respectively; OR, 2.20; 95% CI, 1.52 to 3.18; P < .001). The inclusion of a platinum agent was also associated with greater neuropathy (OR, 1.68; 95% CI, 1.18 to 2.40; P = .004). For each increase in age of 1 year, the odds of neuropathy increased 4% (P = .006). Patients with complications from diabetes had more than twice the odds of having neuropathy (OR, 2.13; 95% CI, 1.31 to 3.46; P = .002) compared with patients with no diabetes. In contrast, patients with autoimmune disease were half as likely to experience neuropathy (OR, 0.49; 95% CI, 0.24 to 1.02; P = .06). The other conditions were not associated with neuropathy.
We found that in addition to drug-related factors, age and history of diabetes were independent predictors of the development of chemotherapy-induced peripheral neuropathy. Interestingly, we also observed that a history of autoimmune disease was associated with reduced odds of neuropathy. Patients with diabetic complications may choose to avoid paclitaxel or taxane plus platinum combination therapies if other efficacious options exist.
Abstract
Background
Patient participation in clinical trials is vital for knowledge advancement and outcomes improvement. Few adult cancer patients participate in trials. Although patient ...decision-making about trial participation has been frequently examined, the participation rate for patients actually offered a trial is unknown.
Methods
A systematic review and meta-analysis using 3 major search engines was undertaken. We identified studies from January 1, 2000, to January 1, 2020, that examined clinical trial participation in the United States. Studies must have specified the numbers of patients offered a trial and the number enrolled. A random effects model of proportions was used. All statistical tests were 2-sided.
Results
We identified 35 studies (30 about treatment trials and 5 about cancer control trials) among which 9759 patients were offered trial participation. Overall, 55.0% (95% confidence interval CI = 49.4% to 60.5%) of patients agreed to enroll. Participation rates did not differ between treatment (55.0%, 95% CI = 48.9% to 60.9%) and cancer control trials (55.3%, 95% CI = 38.9% to 71.1%; P = .98). Black patients participated at similar rates (58.4%, 95% CI = 46.8% to 69.7%) compared with White patients (55.1%, 95% CI = 44.3% to 65.6%; P = .88). The main reasons for nonparticipation were treatment choice or lack of interest.
Conclusions
More than half of all cancer patients offered a clinical trial do participate. These findings upend several conventional beliefs about cancer clinical trial participation, including that Black patients are less likely to agree to participate and that patient decision-making is the primary barrier to participation. Policies and interventions to improve clinical trial participation should focus more on modifiable systemic structural and clinical barriers, such as improving access to available trials and broadening eligibility criteria.
Studies of dietary ω-3 fatty acid intake and prostate cancer risk are inconsistent; however, recent large prospective studies have found increased risk of prostate cancer among men with high blood ...concentrations of long-chain ω-3 polyunsaturated fatty acids (LCω-3PUFA 20:5ω3; 22:5ω3; 22:6ω3. This case-cohort study examines associations between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial.
Case subjects were 834 men diagnosed with prostate cancer, of which 156 had high-grade cancer. The subcohort consisted of 1393 men selected randomly at baseline and from within strata frequency matched to case subjects on age and race. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between fatty acids and prostate cancer risk overall and by grade. All statistical tests were two-sided.
Compared with men in the lowest quartiles of LCω-3PUFA, men in the highest quartile had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Associations were similar for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response.
This study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA. The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LCω-3PUFA intake should consider its potential risks.
Purpose
Patients with cancer experience acute and chronic symptoms caused by their underlying disease or by the treatment. While numerous studies have examined the impact of various treatments on ...symptoms experienced by cancer patients, there are inconsistencies regarding the symptoms measured and reported in treatment trials. This article presents a systematic review of the research literature of the prevalence and severity of symptoms in patients undergoing cancer treatment.
Methods
A systematic search for studies of persons receiving active cancer treatment was performed with the search terms of “multiple symptoms” and “cancer” for studies involving patients over the age of 18 years and published in English during the years 2001 to 2011. Search outputs were reviewed independently by seven authors, resulting in the synthesis of 21 studies meeting criteria for generation of an Evidence Table reporting symptom prevalence and severity ratings.
Results
Data were extracted from 21 multi-national studies to develop a pooled sample of 4,067 cancer patients in whom the prevalence and severity of individual symptoms was reported. In total, the pooled sample across the 21 studies was comprised of 62 % female, with a mean age of 58 years (range 18 to 97 years). A majority (62 %) of these studies assessed symptoms in homogeneous samples with respect to tumor site (predominantly breast and lung cancer), while 38 % of the included studies utilized samples with mixed diagnoses and treatment regimens. Eighteen instruments and structured interviews were including those measuring single symptoms, multi-symptom inventories, and single symptom items drawn from HRQOL or health status measures. The MD Anderson Symptom Inventory was the most commonly used instrument in the studies analyzed (
n
= 9 studies; 43 %), while the Functional Assessment of Cancer Therapy, Hospital Anxiety and Depression Subscale, Medical Outcomes Survey Short Form-36, and Symptom Distress Scale were each employed in two studies. Forty-seven symptoms were identified across the 21 studies which were then categorized into 17 logical groupings. Symptom prevalence and severity were calculated across the entire cohort and also based upon sample sizes in which the symptoms were measured providing the ability to rank symptoms.
Conclusions
Symptoms are prevalent and severe among patients with cancer. Therefore, any clinical study seeking to evaluate the impact of treatment on patients should consider including measurement of symptoms. This study demonstrates that a discrete set of symptoms is common across cancer types. This set may serve as the basis for defining a “core” set of symptoms to be recommended for elicitation across cancer clinical trials, particularly among patients with advanced disease.
To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events ...(PRO-CTCAE).
To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items.
A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit.
Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30).
A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median range intraclass correlation coefficient, 0.76 0.53-.96). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median range r=0.43 0.10-.56; all P≤.006).
Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.
The National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be ...assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO).
We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001-2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment.
We recommend that a core set of 12 symptoms--specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea--be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients.
This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies.
IMPORTANCE: Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors and often result in therapy discontinuation. Small studies suggest that acupuncture may decrease ...aromatase inhibitor–related joint symptoms. OBJECTIVE: To determine the effect of acupuncture in reducing aromatase inhibitor–related joint pain. DESIGN, SETTING, AND PATIENTS: Randomized clinical trial conducted at 11 academic centers and clinical sites in the United States from March 2012 to February 2017 (final date of follow-up, September 5, 2017). Eligible patients were postmenopausal women with early-stage breast cancer who were taking an aromatase inhibitor and scored at least 3 on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain). INTERVENTIONS: Patients were randomized 2:1:1 to the true acupuncture (n = 110), sham acupuncture (n = 59), or waitlist control (n = 57) group. True acupuncture and sham acupuncture protocols consisted of 12 acupuncture sessions over 6 weeks (2 sessions per week), followed by 1 session per week for 6 weeks. The waitlist control group did not receive any intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52. MAIN OUTCOMES AND MEASURES: The primary end point was the 6-week BPI-WP score. Mean 6-week BPI-WP scores were compared by study group using linear regression, adjusted for baseline pain and stratification factors (clinically meaningful difference specified as 2 points). RESULTS: Among 226 randomized patients (mean SD age, 60.7 8.6 years; 88% white; mean SD baseline BPI-WP score, 6.6 1.5), 206 (91.1%) completed the trial. From baseline to 6 weeks, the mean observed BPI-WP score decreased by 2.05 points (reduced pain) in the true acupuncture group, by 1.07 points in the sham acupuncture group, and by 0.99 points in the waitlist control group. The adjusted difference for true acupuncture vs sham acupuncture was 0.92 points (95% CI, 0.20-1.65; P = .01) and for true acupuncture vs waitlist control was 0.96 points (95% CI, 0.24-1.67; P = .01). Patients in the true acupuncture group experienced more grade 1 bruising compared with patients in the sham acupuncture group (47% vs 25%; P = .01). CONCLUSIONS AND RELEVANCE: Among postmenopausal women with early-stage breast cancer and aromatase inhibitor–related arthralgias, true acupuncture compared with sham acupuncture or with waitlist control resulted in a statistically significant reduction in joint pain at 6 weeks, although the observed improvement was of uncertain clinical importance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01535066
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