SWOG S1820: A pilot randomized trial of the Altering Intake, Managing Bowel Symptoms Intervention in Survivors of Rectal Cancer.

BACKGROUND: Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention for bowel dysfunction in survivors of rectal cancer. METHODS: Ninety-three posttreatment survivors were randomized to the AIMS-RC group (N = 47) or the Healthy Living Education attention control group (N = 46) after informed consent and completion of a prerandomization run-in. Outcome measures were completed at baseline and at 18 and 26 weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self-efficacy, and positive/negative affect. RESULTS: Most participants were White and college educated, with a mean age of 55.2 years and median time since surgery of 13.1 months. There were no statistically significant differences in total bowel function score by group, with the AIMS-RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p = .01) and the frequency subscale of the bowel function index (p = .03). The AIMS-RC group reported significantly higher acceptability of the study. CONCLUSIONS: SWOG S1820 did not provide evidence of benefit from the AIMS-RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS-RC intervention.

Baseline characteristics and recruitment for SWOG S1820: altering intake, managing bowel symptoms in survivors of rectal cancer (AIMS-RC).

PURPOSE: Many survivors of rectal cancer experience persistent bowel dysfunction. There are few evidence-based symptom management interventions to improve bowel control. The purpose of this study is to describe recruitment and pre-randomization baseline sociodemographic, health status, and clinical characteristics for SWOG S1820, a trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention. METHODS: SWOG S1820 aimed to determine the preliminary efficacy, feasibility, and acceptability of AIMS-RC, a symptom management intervention for bowel health, comparing intervention to attention control. Survivors with a history of cancers of the rectosigmoid colon or rectum, within 6-24 months of primary treatment completion, with a post-surgical permanent ostomy or anastomosis, and over 18 years of age were enrolled. Outcomes included total bowel function, low anterior resection syndrome, quality of life, motivation for managing bowel health, self-efficacy for managing symptoms, positive and negative affect, and study feasibility and acceptability. RESULTS: The trial completed accrual over a 29-month period and enrolled 117 participants from 34 institutions across 17 states and one US Pacific territory. At baseline, most enrolled participants reported self-imposed diet adjustments after surgery, persistent dietary intolerances, and bowel discomfort post-treatment, with high levels of constipation and diarrhea (grades 1-4). CONCLUSIONS: SWOG S1820 was able to recruit, in a timely manner, a study cohort that is demographically representative of US survivors of rectal cancer. Baseline characteristics illustrate the connection between diet/eating and bowel symptoms post-treatment, with many participants reporting diet adjustments and persistent inability to be comfortable with dietary intake. GOV REGISTRATION DATE: 12/19/2019. GOV IDENTIFIER: NCT#04205955.

Impact of treatment experience on patient knowledge of colony-stimulating factors among patients receiving cancer chemotherapy: evidence from S1415CD-a large pragmatic trial.

PURPOSE: Primary prophylactic granulocyte colony-stimulating factors (PP-CSFs) are prescribed alongside chemotherapy regimens that carry a significant risk of febrile neutropenia (FN). As part of S1415CD, a prospective, pragmatic trial evaluating the impact of automated orders to improve PP-CSF prescribing, we evaluated patients' baseline knowledge of PP-CSF and whether that knowledge improved following the first cycle of chemotherapy. METHODS: Adult patients with breast, colorectal, or non-small-cell lung cancer initiating chemotherapy were enrolled in S1415CD between January 2016 and April 2020. Eight questions assessing knowledge of CSF indications, risks, benefits, and out-of-pocket costs were included in a baseline survey and in a follow-up survey at the end of the first cycle of chemotherapy. Responses were stratified by the trial arm and whether chemotherapy was low, intermediate, or high FN risk. RESULTS: Of the 3605 eligible patients, 3580 (99.3%) completed the baseline survey, and 3420 (95.5%) completed the follow-up survey. At baseline, 803 (22.4%) patients responded "Don't know" to all 8 questions, and all patients averaged 2.75 correct questions. At follow-up, knowledge increased by 0.34 in the high-FN-risk group (p < 0.001) but declined for the other FN-risk groups. In multivariate analysis, receiving a high-FN-risk regimen and younger age were significantly associated with knowledge improvement. CONCLUSION: Chemotherapy patients had poor knowledge of PP-CSF that improved only modestly among recipients of high-FN-risk chemotherapy. Further efforts to inform patients about the risks, benefits, and costs of PP-CSF may be warranted, particularly for those in whom prophylaxis is indicated. TRIAL REGISTRATION: NCT02728596, April 6, 2016.

Antiviral therapy use and related outcomes in patients with cancer and viral infections: results from SWOG S1204.

PURPOSE: Information is limited about adherence to practice guidelines in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection receiving anticancer treatment. METHODS: Newly diagnosed adult cancer patients were enrolled in a multicenter, prospective cohort study (SWOG S1204) during 2013-2017 to evaluate the prevalence of HBV, HCV, or HIV in patients initiating anticancer treatment. At 6 months, records of virus-positive patients were reviewed for antiviral therapy use; anticancer treatment dose reduction; and HBV reactivation (elevated viral load). Categorical variables were compared using chi-square or Fisher's exact test. RESULTS: Of 3055 enrolled patients with viral testing, 230 had chronic or past HBV, HCV, or HIV with 6-month follow-up data (chronic HBV, 15 patients; past HBV, 158; HCV, 49; HIV, 30). Twenty percent (3/15) of chronic HBV and 11% (17/158) of past HBV patients were co-infected with HCV and/or HIV. Rates of antiviral therapy use by 6 months were as follows: chronic HBV, 85% (11/13); past HBV receiving anti-B cell therapy, 60% (3/5); past HBV receiving systemic anticancer therapy without anti-B cell therapy, 8% (8/105); HCV, 6% (2/35); and HIV, 90% (19/21). Among patients with available data, anticancer treatment dose was reduced in 1 of 145 patients with past HBV and 1 of 42 with HCV. HBV reactivation occurred in 1 of 15 patients with chronic HBV; this patient was not receiving antiviral therapy. CONCLUSION: Many patients with cancer and viral infections either do not receive guideline-recommended antiviral treatment or receive antiviral treatment that is not recommended in guidelines. Further education is needed to improve adherence to guidelines.

Successes and challenges of implementing a cancer care delivery intervention in community oncology practices: lessons learned from SWOG S1415CD.

BACKGROUND: Cancer Care Delivery (CCD) research studies often require practice-level interventions that pose challenges in the clinical trial setting. The SWOG Cancer Research Network (SWOG) conducted S1415CD, one of the first pragmatic cluster-randomized CCD trials to be implemented through the National Cancer Institute (NCI) Community Oncology Program (NCORP), to compare outcomes of primary prophylactic colony stimulating factor (PP-CSF) use for an intervention of automated PP-CSF standing orders to usual care. The introduction of new methods for study implementation created challenges and opportunities for learning that can inform the design and approach of future CCD interventions. METHODS: The order entry system intervention was administered at the site level; sites were affiliated NCORP practices that shared the same chemotherapy order system. 32 sites without existing guideline-based PP-CSF standing orders were randomized to the intervention (n = 24) or to usual care (n = 8). Sites assigned to the intervention participated in tailored training, phone calls and onboarding activities administered by research team staff and were provided with additional funding and external IT support to help them make protocol required changes to their order entry systems. RESULTS: The average length of time for intervention sites to complete reconfiguration of their order sets following randomization was 7.2 months. 14 of 24 of intervention sites met their individual patient recruitment target of 99 patients enrolled per site. CONCLUSIONS: In this paper we share seven recommendations based on lessons learned from implementation of the S1415CD intervention at NCORP community oncology practices representing diverse geographies and patient populations across the U. S. It is our hope these recommendations can be used to guide future implementation of CCD interventions in both research and community settings. TRIAL REGISTRATION: NCT02728596 , registered April 5, 2016.

Peripheral Zone Inflammation Is Not Strongly Associated With Lower Urinary Tract Symptom Incidence and Progression in the Placebo Arm of the Prostate Cancer Prevention Trial .

BACKGROUND: Intraprostatic inflammation has been associated with lower urinary tract symptom (LUTS) progression. However, prior studies used tissue removed for clinical indications, potentially skewing inflammation extent or biasing the association. We, therefore, evaluated inflammation and LUTS incidence and progression in men who underwent biopsy of the prostate peripheral zone irrespective of indication. MATERIALS AND METHODS: We developed nested case-control sets in men in the placebo arm of the Prostate Cancer Prevention Trial who were free of clinical BPH and had a protocol-directed year 7 biopsy. Cases had baseline IPSS <15 and year 7 IPSS of 8-14 (low, N = 47), 15-19 (incident moderate, N = 42), or ≥20 (incident high, N = 44). Controls had baseline and year 7 IPSS <8 (N = 41). For progression from IPSS <8, cases had baseline to year 7 IPSS slope >75th percentile (N = 46) and controls had a slope <25th percentile (N = 45). For progression from IPSS = 8-14, cases had a slope >75th percentile (N = 46) and controls had a slope <25th percentile (N = 46). We reviewed three H&E-stained biopsy cores per man to determine prevalence of ≥1 core with inflammation and mean extent (%) of tissue area with inflammation. RESULTS: Inflammation prevalence in low cases (64%) was similar to controls (66%), but higher in moderate (69%) and high (73%) cases (P-trend = 0.4). Extent did not differ across LUTS categories (P-trend = 0.5). For progression from IPSS < 8, prevalence (65%, P = 0.9) and extent (2.5%, P = 0.8) in cases did not differ from controls (64%, 2.7%). For progression from IPSS 8-14, prevalence in cases (52%) was lower than in controls (78%, P = 0.009), while extent was higher in cases (5.3%) than controls (3.6%), especially in men with ≥1 core with inflammation (10.1% versus 4.6%, P = 0.06). CONCLUSION: Peripheral zone intraprostatic inflammation is not strongly associated with LUTS incidence or progression. Prostate 76:1399-1408, 2016. © 2016 Wiley Periodicals, Inc.

Stepwise development of a cancer care delivery research study to evaluate the prevalence of virus infections in cancer patients.

BACKGROUND: SWOG initiated a cancer care delivery research study of virus infection rates among newly diagnosed cancer patients. This study will inform viral screening guidelines in oncology clinics. METHODS: In a first step 'vanguard' phase, we evaluated the feasibility of multiple study procedures. Site investigators were surveyed to obtain feedback on study implementation. RESULTS: Much higher enrollment occurred at sites where all physicians participated and viral testing was performed as routine practice. These procedures will be required going forward. Additional protocol changes based on site investigator input were implemented. CONCLUSION: This multistep protocol design process illustrates how cancer care delivery research studies can adapt to real-world strategies and procedures that exist at community clinics where the predominance of cancer patients are treated.

A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.

BACKGROUND: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. METHODS: The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 µg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function. RESULTS: Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E. CONCLUSIONS: Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00241865 .

Moving a randomized clinical trial into an observational cohort.

BACKGROUND: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute (NCI) and conducted by the Southwest Oncology Group (SWOG). A total of 35,533 men were assigned randomly to one of the four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, and placebo + placebo). The independent Data and Safety Monitoring Committee (DSMC) recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. PURPOSE: A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-Up (CFU) study. METHODS: The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada, and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants. RESULTS: At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of 31 December 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site institutional review boards (IRBs). However, from this cohort, we estimate that an additional 580 prostate cancer cases and 215 Gleason 7 or higher grade cancers will be identified. Over 109,000 individual items have been mailed to participants. Active SELECT ancillary studies have continued. The substantial SELECT biorepository is available to researchers; requests to use the specimens are reviewed for feasibility and scientific merit. As of April 2012, 12 proposals had been approved. LIMITATIONS: The accrual goal of the follow-up study was not met, limiting our power to address the study objectives satisfactorily. The CFU study is also dependent on a number of factors including continued funding, continued interest of investigators in the biorepository, and the continued contribution of the participants. Our experience may be less pertinent to investigators who wish to follow participants in a treatment trial or participants in prevention trials in other medical areas. CONCLUSIONS: Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up.

Risk prediction of hepatitis B or C or HIV among newly diagnosed cancer patients.

BACKGROUND: Screening for viral infection in cancer patients is inconsistent. A mechanism to readily identify cancer patients at increased risk of existing or prior viral infection could enhance screening efforts while reducing costs. METHODS: We identified factors associated with increased risk of past or chronic hepatitis virus B, hepatitis virus C, or HIV infection before initiation of systemic cancer therapy. Data were from a multicenter prospective cohort study of 3051 patients with newly diagnosed cancer (SWOG-S1204) enrolled between 2013 and 2017. Patients completed a survey with questions pertaining to personal history and behavioral, socioeconomic, and demographic risk factors for viral hepatitis or HIV. We derived a risk model to predict the presence of viral infection in a random set of 60% of participants using best subset selection. The derived model was validated in the remaining 40% of participants. Logistic regression was used. RESULTS: A model with 7 risk factors was identified, and a risk score with 4 levels was constructed. In the validation cohort, each increase in risk level was associated with a nearly threefold increased risk of viral positivity (odds ratio = 2.85, 95% confidence interval = 2.26 to 3.60, P < .001). Consistent findings were observed for individual viruses. Participants in the highest risk group (with >3 risk factors), comprised of 13.4% of participants, were 18 times more likely to be viral positive compared with participants with no risk factors (odds ratio = 18.18, 95% confidence interval = 8.00 to 41.3, P < .001). CONCLUSIONS: A risk-stratified screening approach using a limited set of questions could serve as an effective strategy to streamline screening for individuals at increased risk of viral infection.

Universal Viral Screening of Patients with Newly Diagnosed Cancer in the United States: A Cost-efficiency Evaluation.

Recommendations for universal screening of patients with cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are inconsistent. A recent multisite screening study (S1204) from the SWOG Cancer Research Network found that a substantial number of patients with newly diagnosed cancer had previously unknown viral infections. The objective of this study was to determine the cost-efficiency of universal screening of patients with newly diagnosed cancer. We estimated the cost-efficiency of universal screening of new cancer cases for HBV, HCV, or HIV, expressed as cost per virus detected, from the health care payer perspective. The prevalence of each virus among this cohort was derived from S1204. Direct medical expenditures included costs associated with laboratory screening tests. Costs per case detected were estimated for each screening strategy. Secondary analysis examined the cost-efficiency of screening patients whose viral status at cancer diagnosis was unknown. Among the possible options for universal screening, screening for HBV alone ($581), HCV alone ($782), HBV and HCV ($631) and HBV, HCV, and HIV ($841) were most efficient in terms of cost per case detected. When screening was restricted to patients with unknown viral status, screening for HBV alone ($684), HBV and HCV ($872), HBV and HIV ($1,157), and all three viruses ($1,291) were most efficient in terms of cost per newly detected case. Efficient viral testing strategies represent a relatively modest addition to the overall cost of managing a patient with cancer. Screening for HBV, HCV, and HIV infections may be reasonable from both a budget and clinical standpoint. SIGNIFICANCE: Screening patients with cancer for HBV, HCV, and HIV is inconsistent in clinical practice despite national recommendations and known risks of complications from viral infection. Our study shows that while costs of viral screening strategies vary by choice of tests, they present a modest addition to the cost of managing a patient with cancer.

Intervention Nonadherence in the TrACER (S1415CD) Study: A Pragmatic Randomized Trial of a Standardized Order Entry for CSF Prescribing.

PURPOSE: We conducted a pragmatic, cluster-randomized trial to test whether a guideline-based standing order entry (SOE) improves use of primary prophylactic CSF (PP-CSF) prescribing for patients receiving myelosuppressive chemotherapy. We investigated variability in adherence to the intervention. METHODS: We conducted a cluster-randomized trial among 32 oncology clinics from the NCI Community Oncology Research Program. Clinics were randomized 3:1 to a guideline-based PP-CSF SOE or usual care. Among SOE sites, automated orders for PP-CSF were included for regimens at high risk for febrile neutropenia (FN) and an alert not to use PP-CSF for low FN risk. A secondary 1:1 randomization was done among intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for patients receiving intermediate risk-regimens. Providers were allowed to override the SOE. RESULTS: Overall, PP-CSF use among patients receiving high FN risk treatment was high and not different between arms; however, rates of PP-CSF use varied widely by site, ranging from 48.6% to 100%. Among those receiving low FN risk regimens, PP-CSF use was low and not different between arms; however, PP-CSF use ranged from 0% to 19.4% across sites. In the intermediate-risk substudy, PP-CSF was five-fold higher among sites randomized to SOE; however, there was considerable variability in adherence to intervention assignment: PP-CSF use ranged from 0% to 75% among sites randomized to SOE. Despite an alert to not prescribe, PP-CSF prescribing ranged from 0% to 33%. CONCLUSION: In this randomized pragmatic trial aimed at improving PP-CSF prescribing, there was substantial variability in site adherence to the intervention assignment. Although the ability to opt out of the intervention is a feature of pragmatic trials, planning to estimate nonadherence is critical to ensure adequate power.

A Pragmatic Cluster-Randomized Trial of a Standing Order Entry Intervention for Colony-Stimulating Factor Use Among Patients at Intermediate Risk for Febrile Neutropenia.

PURPOSE: Primary prophylactic colony-stimulating factors (PP-CSFs) are prescribed to reduce febrile neutropenia (FN) but their benefit for intermediate FN risk regimens is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) PP-CSF intervention, we conducted a substudy to evaluate the effectiveness of SOE for patients receiving intermediate-risk regimens. METHODS: TrACER was a cluster randomized trial where practices were randomized to usual care or a guideline-based SOE intervention. In the primary study, sites were randomized 3:1 to SOE of automated PP-CSF orders for high FN risk regimens and alerts against PP-CSF use for low-risk regimens versus usual care. A secondary 1:1 randomization assigned 24 intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for intermediate-risk regimens. Clinicians were allowed to over-ride the SOE. Patients with breast, colorectal, or non-small-cell lung cancer were enrolled. Mixed-effect logistic regression models were used to test differences between randomized sites. RESULTS: Between January 2016 and April 2020, 846 eligible patients receiving intermediate-risk regimens were registered to either SOE to prescribe (12 sites: n = 542) or an alert to not prescribe PP-CSF (12 sites: n = 304). Rates of PP-CSF use were higher among sites randomized to SOE (37.1% v 9.9%, odds ratio, 5.91; 95% CI, 1.77 to 19.70; P = .0038). Rates of FN were low and identical between arms (3.7% v 3.7%). CONCLUSION: Although implementation of a SOE intervention for PP-CSF significantly increased PP-CSF use among patients receiving first-line intermediate-risk regimens, FN rates were low and did not differ between arms. Although this guideline-informed SOE influenced prescribing, the results suggest that neither SOE nor PP-CSF provides sufficient benefit to justify their use for all patients receiving first-line intermediate-risk regimens.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Change in plasma α-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation.

BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV1)] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGAex). We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV1 decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4-mL/y attenuated FEV1 decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564). CONCLUSIONS: Greater response to vitE supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.

Effects of a Guideline-Informed Clinical Decision Support System Intervention to Improve Colony-Stimulating Factor Prescribing: A Cluster Randomized Clinical Trial.

Importance: Colony-stimulating factors are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia. Research suggests that 55% to 95% of colony-stimulating factor prescribing is inconsistent with national guidelines. Objective: To examine whether a guideline-based standing order for primary prophylactic colony-stimulating factors improves use and reduces the incidence of febrile neutropenia. Design, Setting, and Participants: This cluster randomized clinical trial, the Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER), involved 32 community oncology clinics in the US. Participants were adult patients with breast, colorectal, or non-small cell lung cancer initiating cancer therapy and enrolled between January 2016 and April 2020. Data analysis was performed from July to October 2021. Interventions: Sites were randomized 3:1 to implementation of a guideline-based primary prophylactic colony-stimulating factor standing order system or usual care. Automated orders were added for high-risk regimens, and an alert not to prescribe was included for low-risk regimens. Risk was based on National Comprehensive Cancer Network guidelines. Main Outcomes and Measures: The primary outcome was to find an increase in colony-stimulating factor use among high-risk patients from 40% to 75%, a reduction in use among low-risk patients from 17% to 7%, and a 50% reduction in febrile neutropenia rates in the intervention group. Mixed model logistic regression adjusted for correlation of outcomes within a clinic. Results: A total of 2946 patients (median [IQR] age, 59.0 [50.0-67.0] years; 2233 women [77.0%]; 2292 White [79.1%]) were enrolled; 2287 were randomized to the intervention, and 659 were randomized to usual care. Colony-stimulating factor use for patients receiving high-risk regimens was high and not significantly different between groups (847 of 950 patients [89.2%] in the intervention group vs 296 of 309 patients [95.8%] in the usual care group). Among high-risk patients, febrile neutropenia rates for the intervention (58 of 947 patients [6.1%]) and usual care (13 of 308 patients [4.2%]) groups were not significantly different. The febrile neutropenia rate for patients receiving high-risk regimens not receiving colony-stimulating factors was 14.9% (17 of 114 patients). Among the 585 patients receiving low-risk regimens, colony-stimulating factor use was low and did not differ between groups (29 of 457 patients [6.3%] in the intervention group vs 7 of 128 patients [5.5%] in the usual care group). Febrile neutropenia rates did not differ between usual care (1 of 127 patients [0.8%]) and the intervention (7 of 452 patients [1.5%]) groups. Conclusions and Relevance: In this cluster randomized clinical trial, implementation of a guideline-informed standing order did not affect colony-stimulating factor use or febrile neutropenia rates in high-risk and low-risk patients. Overall, use was generally appropriate for the level of risk. Standing order interventions do not appear to be necessary or effective in the setting of prophylactic colony-stimulating factor prescribing. Trial Registration: ClinicalTrials.gov Identifier: NCT02728596.

Association of symptomatic benign prostatic hyperplasia and prostate cancer: results from the prostate cancer prevention trial.

This study examined the association between symptomatic benign prostatic hyperplasia (BPH) and prostate cancer risk in 5,068 placebo-arm participants enrolled in the Prostate Cancer Prevention Trial (1993-2003). These data include 1,225 men whose cancer was detected during the 7-year trial--556 detected for cause (following abnormal prostate-specific antigen or digital rectal examination) and 669 detected not for cause (without indication), as well as 3,843 men who had biopsy-proven absence of prostate cancer at the trial end. Symptomatic BPH was assessed hierarchically as self-report of surgical or medical treatment, moderately severe symptoms (International Prostate Symptom Score >14), or physician diagnosis, and analyses were completed by BPH status at baseline (prevalent) or BPH prior to cancer diagnosis or study end (prevalent plus incident). Controlled for age, race, and body mass index, neither prevalent (risk ratio = 1.03, 95% confidence interval: 0.92, 1.14) nor prevalent plus incident (risk ratio = 0.96, 95% confidence interval: 0.87, 1.06) symptomatic BPH was associated with prostate cancer risk. This lack of association was consistent across subgroups defined by type of BPH-defining event (treatment, symptoms, or physician diagnosis), prompt for prostate cancer diagnosis, and prostate cancer grade. This study provides the strongest evidence to date that BPH does not increase the risk of prostate cancer.

Patient-Reported Outcomes and Long-Term Nonadherence to Aromatase Inhibitors.

BACKGROUND: Nonadherence to aromatase inhibitors (AIs) is common and increases risk of breast cancer (BC) recurrence. We analyzed factors associated with nonadherence among patients enrolled in S1105, a randomized trial of text messaging. METHODS: At enrollment, patients were required to have been on an adjuvant AI for at least 30 days and were asked about financial, medication, and demographic factors. They completed patient-reported outcomes (PROs) representing pain (Brief Pain Inventory), endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms), and beliefs about medications (Treatment Satisfaction Questionnaire for Medicine; Brief Medication Questionnaire). Our primary endpoint was AI nonadherence at 36 months, defined as urine AI metabolite assay of less than 10 ng/mL or no submitted specimen. We evaluated the association between individual baseline characteristics and nonadherence with logistic regression. A composite risk score reflecting the number of statistically significant baseline characteristics was examined. RESULTS: We analyzed data from 702 patients; median age was 60.9 years. Overall, 35.9% patients were nonadherent at 36 months. Younger patients (younger than age 65 years) were more nonadherent (38.8% vs 28.6%, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.05 to 2.16; P = .02). Fourteen baseline PRO scales were each statistically significantly associated with nonadherence. In a composite risk model categorized into quartile levels, each increase in risk level was associated with a 46.5% increase in the odds of nonadherence (OR = 1.47, 95% CI =1.26 to 1.70; P < .001). The highest-risk patients were more than 3 times more likely to be nonadherent than the lowest-risk patients (OR = 3.14, 95% CI = 1.97 to 5.02; P < .001). CONCLUSIONS: The presence of multiple baseline PRO-specified risk factors was statistically significantly associated with AI nonadherence. The use of these assessments can help identify patients for targeted interventions to improve adherence.

SWOG S1820: Altering Intake, Managing Symptoms for bowel dysfunction in survivors of Rectal Cancer (The AIMS-RC intervention trial).

OBJECTIVE: To describe the study protocol of SWOG S1820, a trial of the Altering Intake, Managing Symptoms intervention for bowel dysfunction in survivors of Rectal Cancer (AIMS-RC). DESIGN: SWOG S1820 is a multi-site, randomized trial of 94 post-treatment survivors of rectal cancer, comparing the intervention and attention control arms. SETTING: Affiliated institutions of the National Cancer Institute (NCI)-supported National Community Oncology Research Program (NCORP) and the National Clinical Trial Network (NCTN). PARTICIPANTS: Survivors of rectal cancer who are between 6 and 24 months after treatment completion. INTERVENTION: AIMS-RC is a 17-week, 10 session telephone coaching program to help survivors of rectal cancer track their symptoms and improve their diets for better health and bowel function. It includes telephone-based coaching, resource manual, and personalized text/email messaging for motivation in between the telephone sessions. MAIN OUTCOME MEASURES: Bowel function, low anterior resection syndrome score, quality of life (QOL), dietary quality, motivation, self-efficacy, positive/negative affect, feasibility, adherence, retention, acceptability. ANALYSIS: Thirty-seven participants per arm (74 total) provide 80% power to detect this 0.5 standard deviation effect size, based on a two-sample t-test with a 1-sided alpha = 0.1. A total of 94 randomized participants will be accrued to account for 7% ineligibility and 15% attrition at 6 months.

Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial.

The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994-2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a structured supplement-use questionnaire. Cancer was detected in 1,703 men; 127 cancers were high-grade (Gleason score 8-10). There were no associations of any nutrient or supplement with prostate cancer risk overall. Risk of high-grade cancer was associated with high intake of polyunsaturated fats (quartile 4 vs. quartile 1: odds ratio = 2.41, 95% confidence interval (CI): 1.33, 4.38). Dietary calcium was positively associated with low-grade cancer but inversely associated with high-grade cancer (for quartile 4 vs. quartile 1, odds ratios were 1.27 (95% CI: 1.02, 1.57) and 0.43 (95% CI: 0.21, 0.89), respectively). Neither dietary nor supplemental intakes of nutrients often suggested for prostate cancer prevention, including lycopene, long-chain n-3 fatty acids, vitamin D, vitamin E, and selenium, were significantly associated with cancer risk. High intake of n-6 fatty acids, through their effects on inflammation and oxidative stress, may increase prostate cancer risk.