Home-based versus supervised group exercise in men with prostate cancer on androgen deprivation therapy: A randomized controlled trial and economic analysis.

INTRODUCTION: Differences between health outcomes, participation/adoption, and cost-effectiveness of home-based (HOME) interventions and supervised group-based training (GROUP) in men with prostate cancer (PC) on androgen deprivation therapy (ADT) are currently unknown. The objective of this study was to assess the clinical efficacy, adherence, and cost-effectiveness of HOME versus GROUP in men on ADT for PC. MATERIALS AND METHODS: This was a multicentre, 2-arm non-inferiority randomized controlled trial and companion cost-effectiveness analysis. Men with PC on ADT were recruited from August 2016 to March 2020 from four Canadian centres and randomized 1:1 to GROUP or HOME. All study participants engaged in aerobic and resistance training four to five days weekly for six months. Fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F)] and functional endurance [6-min walk test (6MWT)] at six months were the co-primary outcomes. Secondary outcomes included quality of life, physical fitness, body composition, blood markers, sedentary behaviour, and adherence. Between-group differences in primary outcomes were compared to margins of 3 points for FACT-F and 40 m for 6MWT using a Bayesian analysis of covariance (ANCOVA). Secondary outcomes were compared with ANCOVA, Costs included Ministry of Health costs, program costs, patient out-of-pocket, and time costs. TRIAL REGISTRATION: #NCT02834416. RESULTS: Thirty-eight participants (mean [standard deviation (SD)] age, 70 [9.0] years) were enrolled (GROUP n = 20; HOME n = 18). There was an 89.8% probability that HOME was non-inferior to GROUP for both fatigue and functional endurance and a 9.5% probability that HOME reduced fatigue compared to GROUP (mean [SD] change, 12.1 [8.1] vs 3.6 [6.1]; p = 0.040) at six months. Adherence was similar among study arms. HOME was cost-saving (mean difference: -$4122) relative to GROUP. DISCUSSION: A HOME exercise intervention appears non-inferior to GROUP for fatigue and functional endurance and requires fewer resources to implement. HOME appears to ameliorate fatigue more than GROUP, but has comparable effects on other clinically relevant outcomes. Although limited by sample size and attrition, these results support further assessment of home-based programs.

Preference-based versus randomized controlled trial in prostate cancer survivors: Comparison of recruitment, adherence, attrition, and clinical outcomes.

Introduction: Patients' unwillingness to be randomized to a mode of exercise may partly explain their poor recruitment, adherence, and attrition in randomized controlled trials (RCTs) of exercise in oncology. It is unknown whether a preference-based trial can improve recruitment, adherence, retention, and clinical outcomes compared to a RCT of the same exercise interventions. Objective: We assessed the effects of a 2-arm exercise preference trial on adherence and clinical outcomes compared to a similar 2-arm RCT in men with prostate cancer (PC). Methods: This was a two-arm preference-based trial of group-based training (GROUP) or home-based training (HOME). PC survivors on androgen deprivation therapy (ADT) who declined randomization to the RCT but chose to participate in a preference trial were recruited in four Canadian centers. All study participants engaged in aerobic and resistance training, 4-5 days weekly for 6 months, aiming for 150 minutes/week of moderate-to-vigorous physical activity. The primary outcomes were changes from baseline to 6 months in fatigue and functional endurance. Secondary outcomes were quality of life, physical fitness, body composition, blood markers, and adherence. Linear mixed models were used to assess the effects of HOME versus GROUP on primary outcomes. In pooled preference and RCT data, the selection effect (i.e., difference between those who were and were not willing to be randomized) and treatment effect (i.e., difference between GROUP and HOME) were estimated using linear regression. Results and conclusion: Fifty-four participants (mean [SD] age, 70.2 [8.6] years) were enrolled (GROUP n=17; HOME n=37). Comparable effects on primary and secondary outcomes were observed following GROUP or HOME in the preference-based trial. Adherence was similar between preference and RCT participants. However, attrition was higher in the RCT (50.0% vs. 27.8%, p= 0.04). Compared to GROUP, HOME was more effective in ameliorating fatigue (mean difference: +5.2, 95%CI=1.3 to 9.3 p=0.01) in pooled preference and RCT data. A preference-based trial results in comparable observed effects on clinical outcomes and adherence and lower attrition compared with a RCT of the same exercise interventions in PC survivors on ADT. Given the appeals of preference-based trials to study participants, additional studies are warranted. Clinical trial registration: clinicaltrials.gov, identifier (NCT03335631).

Remote, proactive, telephone based management of toxicity in outpatients during adjuvant or neoadjuvant chemotherapy for early stage breast cancer: pragmatic, cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of remote proactive management of toxicities during chemotherapy for early stage breast cancer. DESIGN: Pragmatic, cluster randomised trial. SETTING: 20 cancer centres in Ontario, Canada, allocated by covariate constrained randomisation to remote management of toxicities or routine care. PARTICIPANTS: All patients starting adjuvant or neoadjuvant chemotherapy for early stage breast cancer at each centre. 25 patients from each centre completed patient reported outcome questionnaires. INTERVENTIONS: Proactive, standardised, nurse led telephone management of common toxicities at two time points after each chemotherapy cycle. MAIN OUTCOME MEASURES: The primary outcome, cluster level mean number of visits to the emergency department or admissions to hospital per patient during the whole course of chemotherapy treatment, was evaluated with routinely available administrative healthcare data. Secondary patient reported outcomes included toxicity, self-efficacy, and quality of life. RESULTS: Baseline characteristics of participants were similar in the intervention (n=944) and control arms (n=1214); 22% were older than 65 years. Penetration (that is, the percentage of patients who received the intervention at each centre) was 50-86%. Mean number of visits to the emergency department or admissions to hospital per patient was 0.91 (standard deviation 0.28) in the intervention arm and 0.94 (0.40) in the control arm (P=0.94); 47% (1014 of 2158 patients) had at least one visit to the emergency department or a hospital admission during chemotherapy. Among 580 participants who completed the patient reported outcome questionnaires, at least one grade 3 toxicity was reported by 48% (134 of 278 patients) in the intervention arm and by 58% (163 of 283) in the control arm. No differences in self-efficacy, anxiety, or depression were found. Compared with baseline, the functional assessment of cancer therapy trial outcome index decreased by 6.1 and 9.0 points in the intervention and control participants, respectively. CONCLUSIONS: Proactive, telephone based management of toxicities during chemotherapy did not result in fewer visits to the emergency department or hospital admissions. With the rapid rise in remote care because of the covid-19 pandemic, identifying scalable strategies for remote management of patients during cancer treatment is particularly relevant. TRIAL REGISTRATION: ClinicalTrials.gov NCT02485678.

A Community Hospital-Based Study: A Prespecified Neutrophil Count with Adjuvant mFOLFOX6 Associated with Increased Delays, Increased G-CSF Use, and Reduced Dose Intensity.

PURPOSE: To look at how the absolute neutrophil count (ANC) is used by community oncologists as the main factor in ordering adjuvant mFOLFOX6 for colorectal cancer. This study reports on how this decision impacts chemotherapy delays, effects received dose intensity (RDI), and increases the use of granulocyte-colony-stimulating factor (G-CSF). METHODS: A retrospective chart review was conducted for all patients receiving adjuvant mFOLFOX6 for colorectal cancer at a two-site community hospital in Toronto, Ontario, Canada, between July 2013 and March 2019. Seven physicians treated 140 patients, who made 1636 clinic visits to receive 1461 cycles of prescribed chemotherapy. RESULTS: The mean ANC per physician associated with a decision to give chemotherapy ranged from 1.05×109/L (95% CI 0.98-1.13×109/L) to 1.5x109/L with a decision to delay if the ANC was lower. Subsequent cycles were then supported by G-CSF with very similar ANC decision levels for dose delay. Physicians were more likely to prescribe chemotherapy with higher pretreatment ANC, r=0.3 (p<0.000). G-CSF was used in 24.6% of cycles and usage had grown to 44.2% by the 12th cycle; physician use ranged from 0.36% to 54.2% of cycles. Secondary prophylaxis was the indication in 94.7% of cases. There was an inverse relationship between the frequency of G-CSF use and the RDI of continuous infusion 5FU, r=-0.26 (p<0.001). There were delays for 8.8% of visits for cycles not supported by G-CSF and, surprisingly, 15.9% of visits for cycles supported by G-CSF. Neutropenia caused 61.6% of delays for chemotherapy cycles not supported by G-CSF and 44.1% for cycles supported by G-CSF. CONCLUSION: Physicians required a pretreatment ANC of 1.05-1.5×109/L before prescribing mFOLFOX6 chemotherapy. When ANC was low, a dose delay and secondary prophylaxis with G-CSF failed to consistently achieve the much sought after ANC. This then caused more delay, reduced RDI and increased expense for both patients and the system. Fewer delays, less G-CSF and increased RDI would have resulted with reduced reliance on ANC and adoption of chemotherapy dose reduction.

A structured group exercise program for patients with metastatic cancer receiving chemotherapy and CTNNB1 (ß-catenin) as a biomarker of exercise efficacy.

INTRODUCTION: Exercise can improve the symptoms of cancer. However, is it a cancer treatment? We tested the feasibility of group exercise for metastatic cancer patients while on chemotherapy. A biomarker for exercise efficacy in colorectal cancer (CRC), ß-catenin, was tested. METHODS: Patients undergoing palliative chemotherapy were eligible for a pre-post, single-arm study comprising an indefinite, weekly group exercise intervention using strength and aerobic training. The Functional Assessment of Chronic Illness Therapy (FACIT) and Piper Fatigue Scale (PFS) questionnaires were administered, and aerobic capacity assessed using the 6-minute walk test. Selection bias, as measured by invitation rate, as well as participation, compliance, and attrition rates, was measured. CRC patients had surgical sections stained for ß-catenin and correlated to survival. The statistical analysis was primarily exploratory and hypothesis generating. RESULTS: Of the 124 eligible patients, 53 (43%) patients were invited and 35 (28%) patients participated. The median number of classes attended was 16, the compliance rate was 73.1% (95% confidence interval [CI] 67.0-79.4), and the modified attrition rate was 24%. There were no injuries. No significant improvements were seen in the FACIT or PFS at 30 weeks. Aerobic capacity significantly improved at 30 weeks. Participation of CRC patients in the exercise pilot vs nonparticipation was not associated with a change in survival (hazard ratio [HR] =0.98, 95% CI 0.32-2.97). For all CRC patients, strong nuclear staining for ß-catenin, compared to weak, suggested a lower risk of mortality (HR =0.54, 95% CI 0.14-1.96). However, CRC participants in the exercise program with weak nuclear staining for ß-catenin had a trend to lower mortality (HR =0.39, 95% CI 0.025-6.1). CONCLUSION: Exercise for patients with metastatic cancer receiving chemotherapy is feasible and safe. ß-Catenin is a potential biomarker for exercise anticancer effect in CRC.

FOLFOX chemotherapy can safely be given to neutropenic patients with early-stage colorectal cancer for higher dose intensity and fewer visits.

PURPOSE: How does giving adjuvant FOLFOX chemotherapy to patients with early-stage colorectal cancer (ESCRC) regardless of the day-before absolute neutrophil counts (ANC) effect chemotherapy-induced febrile neutropenia (CIFN) rates, received dose intensity (RDI), and chemotherapy cycle delay? Does an ANC level predict future neutropenia? METHODS: A retrospective chart review was conducted on all patients receiving adjuvant chemotherapy for ESCRC at a mid-sized community hospital in Toronto, Ontario, Canada between April 2005 and May 2014. All patients were under one medical oncologist. Day-before CBC data were collected along with other patient characteristics. CIFN was confirmed by hospital records. Inclusion criteria were met by 132 patients. Overall, 1074 cycles of chemotherapy were analyzed. RESULTS: Six episodes of CIFN were observed. There was a significant difference in the average day-before ANC between patients who developed CIFN (1.4 × 10(9)/L, 95 % CI 0.76-2.0 × 10(9)/L) and those who did not (2.9 × 10(9)/L, 95 % CI 2.8-3.0 × 10(9)/L, p = 0.03). The RDI for oxaliplatin was 0.95 and for 5-fluorouracil (5-FU) was 0.96. A total of 170 cycles were given at day-before ANC <1.5 × 10(9)/L (range 0.1 × 10(9)/L-1.4 × 10(9)/L), and 24 were delayed for 1 week for hematologic reasons. Cycles given with grade 2 neutropenia predicted higher grades of neutropenia with a sensitivity of 0.22 (95 % CI 0.12-0.38). CONCLUSIONS: Adjuvant FOLFOX chemotherapy may be given in the setting of low day-before ANC to patients with ESCRC. The benefits include higher RDI and a reduced number of clinic visits for the patient.

Full-dose chemotherapy in early stage breast cancer regardless of absolute neutrophil count and without G-CSF does not increase chemotherapy-induced febrile neutropenia.

PURPOSE: Does giving full-dose adjuvant chemotherapy to patients with early stage breast cancer (ESBC) regardless of the day-before absolute neutrophil count (ANC) lead to an increased incidence of chemotherapy-induced febrile neutropenia (CIFN)? What factors may predispose patients to CIFN? METHODS: This was a retrospective chart review conducted on all patients receiving adjuvant chemotherapy for ESBC at a mid-sized community hospital in Toronto, Ontario, Canada between September 2005 and August 2011. Day-before CBC data were collected along with other patient characteristics. CIFN was confirmed by hospital records. One hundred fifty-four patients met the inclusion criteria. Overall, 830 cycles of chemotherapy were analyzed. Univariate and multivariate logistic regression analyses were used to identify risk factors for CIFN. RESULTS: Twenty-two episodes of CIFN were observed. There was no significant difference in day-before ANC between patients who developed CIFN relative to those who did not. The day-before ANC was <1.5 × 10(9)/L for 88 cycles of chemotherapy. ANC analyzed as a continuous variable showed that the odds ratio (OR) for CIFN was 0.97 (95 % CI 0.82-1.13, p = NS). The pseudo R (2) statistic, which is a measure of variability accounted for by a regression model, was only 0.0008, indicating that ANC explained less than 1 % of the variability in the risk of CIFN. The most significant predictor of CIFN was the chemotherapy regimen, with docetaxel (Taxotere)/cyclophosphamide demonstrating the highest risk (OR 7.1, 95 % CI 1.4-34.9, p = 0.016). CONCLUSIONS: Full-dose adjuvant chemotherapy may be given to patients with ESBC regardless of the day-before ANC, without significantly increasing the risk of CIFN. The chemotherapy regimen is the most significant predictor for CIFN.