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Despite remarkable improvements in screening, diagnosis, and targeted therapies, cancer remains the second leading cause of death in the United States. It is increasingly clear that diet and lifestyle practices play a substantial role in cancer development and progression. As such, various dietary compositions have been proposed for reducing cancer risk and as potential adjuvant therapies. In this article, we critically assess the preclinical and human trials on the effects of the ketogenic diet (KD, i.e., high-fat, moderate-to-low protein, and very-low carbohydrate content) for cancer-related outcomes. The mechanisms underlying the hypothesized effects of KD, most notably the Warburg Effect, suggest that restricting carbohydrate content may impede cancer development and progression via several pathways (e.g., tumor metabolism, gene expression). Overall, although preclinical studies suggest that KD has antitumor effects, prolongs survival, and prevents cancer development, human clinical trials are equivocal. Because of the lack of high-quality clinical trials, the effects of KD on cancer and as an adjunctive therapy are essentially unknown. We propose a set of research recommendations for clinical studies examining the effects of KD on cancer development and progression.

Background The rates of physical inactivity and related cancer incidence and mortality are disproportionately high in the Deep South region in the United States, a rural, medically underserved region with a large African American population compared with the rest of the nation. Given this region’s lower rates of literacy and internet access, interactive voice response (IVR) system–automated telephone-based interventions have the potential to help overcome physical activity intervention barriers (literacy, internet access, costs, and transportation) but have yet to be extended to rural, underserved populations, such as in the Deep South. Thus, extensive formative research is being conducted to develop and beta test the Deep South IVR System–Supported Active Lifestyle intervention in preparation for dissemination in rural Alabama counties. Objective This paper aims to describe the design and rationale of an ongoing efficacy trial of the Deep South IVR System–Supported Active Lifestyle intervention. Methods A two-arm randomized controlled trial will be conducted to compare a 12-month physical activity intervention versus a wait-list control condition in 240 underactive adults from 6 rural Alabama counties. The Deep South IVR System–Supported Active Lifestyle intervention is based on the Social Cognitive Theory and includes IVR-automated physical activity–related phone counseling (daily in months 0-3, twice weekly in months 4-6, and weekly in months 7-12) and support from local rural county coordinators with the University of Alabama O’Neal Comprehensive Cancer Center Community Outreach and Engagement Office. The primary outcome is weekly minutes of moderate- to vigorous-intensity physical activity (7-day physical activity recall; accelerometry) at baseline, 6 months, 12 months, and 18 months. Rural Active Living Assessments will be conducted in each rural county to assess walkability, assess recreational amenities, and inform future environment and policy efforts. Results This study was funded in March 2019 and approved by the institutional review board of the University of Alabama at Birmingham in April 2019. As of February 2020, start-up activities (hiring and training staff and purchasing supplies) were completed. Study recruitment and assessments began in September 2020 and are ongoing. As of February 2021, a total of 43 participants have been enrolled in Dallas County, 42 in Sumter County, and 51 in Greene County. Conclusions IVR-supported phone counseling has great potential for addressing physical activity barriers (eg, culture, literacy, cost, or transportation) and reducing related rural health disparities in this region. Trial Registration ClinicalTrials.gov NCT03903874; https://clinicaltrials.gov/ct2/show/NCT03903874. International Registered Report Identifier (IRRID) DERR1-10.2196/29245

This narrative review of web-delivered weight management, diet quality, and physical activity interventions for cancer survivors relies on a systematic search of PubMed, Psych Info, and EBSCOhost which identified 19 unique web-delivered lifestyle interventions for cancer survivors. The sample sizes for these studies ranged from 11–492. Intervention duration ranged from 1–12 months; however, most interventions were 6–12 weeks in length. Ten studies were randomized controlled trials (RCTs), two were two-arm quasi RCTs, and seven employed a single-arm pre/post-test design. Many (N= 15) of the interventions were well-grounded in behavioral theory, which may have led to favorable behavior change. Most studies (15-of-19) targeted and reported increases in physical activity, while only a few targeted and reported improvements in diet quality (36.9% and 15.8%, respectively) and weight management (26.3% and 10.5%, respectively). A notable limitation was that most studies were conducted among populations that were primarily White and female. Future directions for Internet-based lifestyle interventions for cancer survivors include increasing: (a) focus on multiple behavior change, (b) representation of male and minority populations to improve generalizability of findings, (c) extended intervention duration and follow-up to evaluate long-term efficacy of web-based lifestyle interventions, and (d) sample size to allow for adequate statistical power.

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RESULTS:When RT was performed during survivorship, significant differences between the RT and control groups were found for changes in muscle size (0.38kg [95% CI 0.06, 0.71], p = 0.02; I 2 = 50.7%, p = 0.01) and fat mass (-0.55kg [95% CI -0.97, -0.13], p = 0.01; I 2 = 71.3%, p = <0.001). When RT was performed during treatment, there was a significant difference between RT and control groups for changes in muscle size (0.86kg [95% CI 0.25, 1.47], p = 0.005; I 2 = 0.0%, p = 0.63), however there was no difference between groups for changes in fat mass (-0.00kg [95% CI -0.82, 0.81], p = 0.99; I 2 = 0.0%, p = 0.62). CONCLUSION: Modest improvements in body composition were observed following RT in cancer survivors on treatment and throughout survivorship. These changes are smaller than those observed following similar programs in the general population. The reason for these differences warrants further investigation.

BACKGROUND Internet-based lifestyle programs are increasingly being used to deliver health behavior change interventions to cancer survivors. However, little is known about website use in this population or its associations with healthy lifestyle changes. OBJECTIVE To describe lifestyle intervention website use (logins, time on website, and clicks) among cancer survivors, as well as patterns of use by participant characteristics. Additionally, associations were explored between website use and changes in healthy lifestyle knowledge and practice. METHODS Thirty-five cancer survivors participated in a single-arm pilot test of the SurvivorSHINE website. Knowledge and practices related to healthful diet and physical activity behaviors were measured at baseline and follow-up. Website use (e.g., time spent on the website, frequency of logins, webpage visits, and clicks) were collected from the SurvivorSHINE administrative site during a 2-week intervention period. Patterns of use were examined by participants’ gender and race. Associations between website use and changes in healthy lifestyle knowledge, physical activity, diet, and weight were explored. Independent t-tests were used to compare website use between males and females, and Non-Hispanic Whites (NHW) and Blacks (NHB). Pearson correlations were used to examine associations between website use and behavior change. RESULTS Participants logged into the SurvivorSHINE website an average of 3.2 times (SD = 2) over the 2-week period and spent a total average of 94 minutes (SD = 56 minutes). Examining website activity, 1905 clicks were logged. The user profile (344 clicks) and the home sections (301 clicks) were the most visited components. No associations were observed between the frequency of logins or the total time on the website and improvements in knowledge-related to healthy lifestyles, nor in changes in body weight or dietary intake. However, the total time on the website was positively correlated with improvements in accelerometer-measured physical activity (r = 0.74, p = 0.02), as well as self-reported physical activity (r = 0.35, p = 0.047). CONCLUSIONS Cancer survivors demonstrated clear interest in a diet and exercise website as evidenced by their frequency of logins, clicks on numerous features, and total viewing time. Moreover, increased website usage was correlated with improvements in physical activity. CLINICALTRIAL NCT00303875, NCT00630591 INTERNATIONAL REGISTERED REPORT RR2-10.1007/s13187-021-02026-x