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      Effect of Exercise on Chemotherapy-Induced Peripheral Neuropathy Among Patients Treated for Ovarian Cancer : A Secondary Analysis of a Randomized Clinical Trial

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          Abstract

          This secondary analysis compared the effect of a 6-month aerobic exercise intervention vs attention control for chemotherapy-induced peripheral neuropathy (CIPN) among participants in the Women’s Activity and Lifestyle Study in Connecticut trial who received chemotherapy for ovarian cancer.

          Key Points

          Question

          What is the effect of exercise on chemotherapy-induced peripheral neuropathy (CIPN)?

          Findings

          In this secondary analysis of a randomized clinical trial of 134 patients with ovarian cancer, the self-reported CIPN score was 1.6 points lower in those who were randomized to the exercise intervention compared with the attention control group, indicating significant improvement in CIPN symptoms.

          Meaning

          Findings of this secondary analysis suggest that exercise is a promising treatment for CIPN and incorporating exercise program referrals into the standard oncology care may reduce CIPN symptoms and increase quality of life for survivors of ovarian cancer.

          Abstract

          Importance

          Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common and severe adverse effects of chemotherapy, is associated with worse quality of life among survivors of ovarian cancer. Currently, there is no effective treatment for CIPN.

          Objective

          To evaluate the effect of a 6-month aerobic exercise intervention vs attention-control on CIPN among women treated for ovarian cancer in the Women’s Activity and Lifestyle Study in Connecticut (WALC) to provide evidence to inform the guidelines and recommendations for prevention or treatment of CIPN.

          Design, Setting, and Participants

          This prespecified secondary analysis evaluated the Women’s Activity and Lifestyle Study in Connecticut (WALC), a multicentered, open-label, population-based, phase 3 randomized clinical trial of an aerobic exercise intervention vs attention control for CIPN in patients who were diagnosed with ovarian cancer. Only WALC participants who received chemotherapy were included in this analysis. Participants were randomized 1:1 to either a 6-month aerobic exercise intervention or to attention control. All analyses were conducted between September 2022 and January 2023.

          Interventions

          The exercise intervention consisted of home-based moderate-intensity aerobic exercise facilitated by weekly telephone counseling from an American College of Sports Medicine/American Cancer Society–certified cancer exercise trainer. Attention control involved weekly health education telephone calls from a WALC staff member.

          Main Outcomes and Measure

          Change in CIPN was the primary outcome in this secondary analysis. This outcome was represented by CIPN severity, which was self-measured by participants at baseline and 6 months using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity scale, with a score range of 0 to 44. A mixed-effects model was used to assess the 6-month change in CIPN between the exercise intervention and attention control arms.

          Results

          Of the 134 participants (all females; mean [SD] age, 57.5 [8.3] years) included in the analysis, 69 were in the exercise intervention arm and 65 were in the attention control arm. The mean (SD) time since diagnosis was 1.7 (1.0) years. The mean (SD) baseline CIPN scores were 8.1 (5.6) in the exercise intervention arm and 8.8 (7.9) in the attention control arm ( P = .56). At 6 months, the self-reported CIPN score was reduced by 1.3 (95% CI, −2.3 to −0.2) points in the exercise intervention arm compared with an increase of 0.4 (95% CI, −0.8 to 1.5) points in the attention control arm. The between-group difference was −1.6 (95% CI, −3.1 to −0.2) points. The point estimate was larger among the 127 patients with CIPN symptoms at enrollment (−2.0; 95% CI, −3.6 to −0.5 points).

          Conclusions and Relevance

          Findings of this secondary analysis of the WALC trial indicate that a 6-month aerobic exercise intervention vs attention control significantly improved self-reported CIPN among patients who were treated for ovarian cancer. While replication of the findings in other studies is warranted, incorporating referrals to exercise programs into standard oncology care could reduce CIPN symptoms and increase quality of life in patients with ovarian cancer.

          Trial Registration

          ClinicalTrials.gov Identifier: NCT02107066

          Related collections

          Most cited references52

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          Is Open Access

          Cancer statistics, 2023

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.
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            Social cognitive theory: an agentic perspective.

            The capacity to exercise control over the nature and quality of one's life is the essence of humanness. Human agency is characterized by a number of core features that operate through phenomenal and functional consciousness. These include the temporal extension of agency through intentionality and forethought, self-regulation by self-reactive influence, and self-reflectiveness about one's capabilities, quality of functioning, and the meaning and purpose of one's life pursuits. Personal agency operates within a broad network of sociostructural influences. In these agentic transactions, people are producers as well as products of social systems. Social cognitive theory distinguishes among three modes of agency: direct personal agency, proxy agency that relies on others to act on one's behest to secure desired outcomes, and collective agency exercised through socially coordinative and interdependent effort. Growing transnational embeddedness and interdependence are placing a premium on collective efficacy to exercise control over personal destinies and national life.
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              Ovarian cancer statistics, 2018

              In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                1 August 2023
                August 2023
                1 August 2023
                : 6
                : 8
                : e2326463
                Affiliations
                [1 ]Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut
                [2 ]Yale Cancer Center, New Haven, Connecticut
                [3 ]Dana-Farber Cancer Institute, Boston, Massachusetts
                [4 ]Wayne State University, Detroit, Michigan
                [5 ]Yale School of Medicine, New Haven, Connecticut
                [6 ]Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
                Author notes
                Article Information
                Accepted for Publication: June 20, 2023.
                Published: August 1, 2023. doi:10.1001/jamanetworkopen.2023.26463
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2023 Cao A et al. JAMA Network Open.
                Corresponding Author: Anlan Cao, MBBS, Department of Chronic Disease Epidemiology, Yale School of Public Health, 60 College St, New Haven, CT 06520-803 ( anlan.cao@ 123456yale.edu ).
                Author Contributions: Drs Irwin and Ferrucci had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Ligibel, Schwartz, Esserman, Irwin, Ferrucci.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Cao.
                Critical review of the manuscript for important intellectual content: All authors.
                Statistical analysis: Cao, Li, Esserman.
                Obtained funding: Irwin.
                Administrative, technical, or material support: Cartmel, Harrigan, Gogoi, Schwartz, Ferrucci.
                Supervision: Gogoi, Esserman, Irwin, Ferrucci.
                Conflict of Interest Disclosures: Dr Cartmel reported receiving grants from National Cancer Institute during the conduct of the study. Dr Esserman reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Ferrucci reported receiving grants from National Cancer Institute during the conduct of the study. No other disclosures were reported.
                Funding/Support: This study was supported by grants NCI 5R01CA138556 and P30 CA016359 from the National Cancer Institute at the NIH, grant UL1TR000142 from the National Center for Advancing Translational Science at the NIH, and grant P30AG021342 from the Yale Claude D. Pepper Older Americans Independence Center.
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Data Sharing Statement: See Supplement 3.
                Additional Contributions: Certain data were collected from the Connecticut Tumor Registry located in the Connecticut Department of Public Health. We thank all of the study participants and physicians; Rajni Mehta, MPH, Director of the Rapid Case Ascertainment Shared Resource, Yale Cancer Center; and the following Connecticut hospitals: Charlotte Hungerford Hospital, Bridgeport Hospital, Danbury Hospital, Hartford Hospital, Middlesex Hospital, New Britain General Hospital, Bradley Memorial Hospital, Yale/New Haven Hospital, St Francis Hospital and Medical Center, St Mary’s Hospital, Hospital of St Raphael, St Vincent’s Medical Center, Stamford Hospital, William W. Backus Hospital, Windham Hospital, Eastern Connecticut Health Network, Griffin Hospital, Bristol Hospital, Johnson Memorial Hospital, Day Kimball Hospital, Greenwich Hospital, Lawrence and Memorial Hospital, Milford Hospital, New Milford Hospital, Norwalk Hospital, Sharon Hospital, and Waterbury Hospital. None of these groups and individuals were financially compensated for their contributions.
                Article
                zoi230766
                10.1001/jamanetworkopen.2023.26463
                10394582
                37526937
                1c7fa90f-9dfc-4123-9374-e0b7a6dfb69a
                Copyright 2023 Cao A et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 14 April 2023
                : 20 June 2023
                Categories
                Research
                Original Investigation
                Online Only
                Oncology

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