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Literature search | The systematic literature search identified 1062 records. We used an automated tool (Rayyan) to identify duplicate records in the eligibility process of this systematic review; after eliminating duplicates, 776 records remained. The records excluded after screening by title and abstract were 766, and only ten full-text articles were assessed for eligibility. Four studies without a control group and two studies where efficacy was not determined by MSCs therapy were excluded. Finally, four studies were included in this systematic review [ | PMC10374120 | ||
Flow diagram of the study identification process. | PMC10374120 | |||
Study characteristics and quality assessment | UC | Four studies were included in this systematic review, three were RCTs, and one was non-RCTs. The included studies involved a total of 358 patients. The studies of Wang et al. (2013) and Yang et al. (2018) were conducted in China, Álvaro-Gracia et al. (2017) in Spain, and Shadmanfar et al. (2018) was conducted in Iran; only one study was multi-center (Álvaro-Gracia et al.). The study of Álvaro-Gracia et al. (2017) was divided into three subgroups according to the dosage, and the study of Yang et al. 2018 was divided into two subgroups according to the response or non-response of MSCs treatment, the route of administration was intravenous for 75% of the studies and intra-articular for 25% of these. The tissue sources of MSCs were: 50% umbilical cord (UC), 25% bone marrow (BM), and 25% adipose tissue (AT). Finally, the treatment assignments were masked in 50% of the studies. The included studies’ overall characteristics are shown in | PMC10374120 | |
Risk of bias assessment of included RCTs–Cochrane RoB tool 2.0. | PMC10374120 | |||
Risk of bias assessment in the non-RCTs of Wang, 2013 –ROBINS-I tool. | PMC10374120 | |||
Overall characteristics of the included studies. | Rheumatoid Arthritis | RHEUMATOID ARTHRITIS | UC-MSCs, Umbilical Cord-derived Mesenchymal Stem Cells; DMARDs, Rheumatoid Arthritis with Disease-Modifying Drugs; Ad-MSCs, Adipose-derived Mesenchymal Stem Cells; BM-MSCs, Bone marrow-derived Mesenchymal Stem Cells; IV, Intravenous infusion; IA, Intra-articular injection. | PMC10374120 |
GRADE assessment | pain | ADVERSE EVENTS, ADVERSE EVENT | We use the GRADE approach to assess evidence for each important outcome and present the summary findings for all combinations of MSCs therapy and control interventions in the included RCTs and non-RCTs. These treatments were evaluated as clinical activity, measures of response by the ACR scale, and safety of therapy with MSCs. The grade of certainty of evidence for clinical activity outcome measures was considered high to low. The quality of evidence was downgraded for risk of bias, inconsistency, and imprecision of the results. Due to the few studies (n < 10) in the meta-analysis, the publication bias could not be excluded because the test power is usually too low to distinguish chance from real asymmetry. The certainty of evidence for DAS28-ESR outcomes was high (outcome measures were reported in one RCT). Certainty of the subscales of WOMAC as pain, function, stiffness outcomes was moderate (outcome measures were reported in one RCT); certainty for VAS, DAS28, and HAQ outcomes was high to low (outcome measures were reported in two RCTs). Certainty of evidence for measure of response outcomes as patients reaching ACR 20,50,70 was considered high to low (outcome measures were reported in two RCTs). Certainty of evidence for the safety of treatments: Adverse events (serious and non-serious adverse events) were low with inconsistency (1 level) and imprecision (1 level).The evidence was downgraded for inconsistency and imprecision from 1 to 2 levels. None of the outcomes were upgraded based on risk of bias (see | PMC10374120 |
GRADE assessment. | Rheumatoid Arthritis, Osteoarthritis | RHEUMATOID ARTHRITIS, DISEASE, OSTEOARTHRITIS | UC-MSCs, Umbilical Cord-derived Mesenchymal Stem Cells; Ad-MSCs, Adipose-derived Mesenchymal Stem Cells; BM-MSCs, Bone marrow-derived Mesenchymal Stem Cells; DMARDs, Rheumatoid Arthritis with Disease-Modifying Drugs; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; VAS, Visual Analogue Scale; DAS28, Disease Activity Score-28; HAQ, Health Assessment Questionnaire; DAS28-ESR, Disease Activity Score-28 Erythrocyte Sedimentation Rate (ESR); ACR 20/50/70, Percentage of patients achieving ACR20/50/70 responses; CI, Confidence Interval; SD, Standard Deviation. | PMC10374120 |
Outcomes | PMC10374120 | |||
Safety evaluation | ADVERSE EVENTS | Overall, MSCs therapy was safe and well tolerated in all studies, as no serious adverse events (non-SAEs) were observed during or after MSCs administration. Wang et al. [ | PMC10374120 | |
Forest Plot of the incidence of adverse events in the MSCs therapy group and control group. | PMC10374120 | |||
Forest Plot of the incidence of non-serious adverse events in MSCs therapy group and control group. | PMC10374120 | |||
Forest Plot of the incidence of serious adverse events in MSCs therapy group and control group. | ADVERSE EVENTS | In the L’Abbé plot for the rate of adverse events ( | PMC10374120 | |
L’Abbé plot for the incidence of adverse events in the MSCs therapy group and control group. | deaths, gastrointestinal tract bleeding | MALIGNANCIES | Decreased total protein and globulin levels and increased albumin and hemoglobin levels after DMARDs plus UC-MSCs administration in comparison with the control group had shown in the study of Wang et al.; the function of the liver could be estimated based on this elevation in levels of albumin and hemoglobin and based on the decreased incidence of gastrointestinal tract bleeding. Álvaro-Gracia et al. not reported abnormal laboratory values nor relevant vital sign abnormalities, malignancies, or deaths. The study of Yang et al. was not found significant abnormalities in a routine blood test, liver, and kidney function analysis, urine analysis, or electrocardiography. | PMC10374120 |
Sensitivity analyses | The small number of RCTs in each safety meta-analysis made it impossible the conduct sensitivity analyses. | PMC10374120 | ||
Publication bias | Publication bias was evaluated at the outcome level with the funnel plot ( | PMC10374120 | ||
Funnel plot, using data from 3 trials of adverse events in MSCs therapy group and control group. | PMC10374120 | |||
Summary of active RA clinical trials with MSC therapy that included a control group. | PMC10374120 | |||
Discussion | rheumatoid arthritis, tumor necrosis, TNF-α, toxicity, swollen joints, inflammation, UC, pain, RA | RHEUMATOID ARTHRITIS, TUMOR NECROSIS, ADVERSE EVENTS, INFLAMMATION, INFLAMMATORY DISEASE | Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments during the last decades, owing to their potential applications such as anti-inflammatory, uncommon immunomodulatory competence, self-renewal, and multipotency properties. Many ongoing clinical trials are investigating the safety and efficacy of MSCs therapies to treat inflammatory diseases, which have shown positive clinical outcomes, with improved swollen joints, pain level, and quality of life. Furthermore, few RCT or non-RCT of MSCs conducted on rheumatoid arthritis (RA) patients have also shown some positive performance without serious adverse events. In this study, we presented a summary of active RA clinical trials with MSCs therapy that included a control group (Our Systematic Review and Meta-analysis are the first work that substantially summarizes the safety of systemic MSCs administration isolated from the umbilical cord (UC), adipose tissue (AT), and bone marrow (BM) in the treatment of rheumatoid arthritis. This work did not find serious adverse events per system organ class, during or after MSCs administration, and provided initial safety and efficacy assessment for MSCs; in general, infusions of MSCs were safe and well tolerated in the included studies. Serum levels of cellular mediators that drive inflammation in RA, such as interleukin-6 and tumor necrosis factor alfa (TNF-α), decreased after the first MSCs treatment without evidence of toxicity at the dosage concentration in a period studied.Due to the great variability in evaluating the clinical efficacy between the studies included, it was impossible to perform a meta-analysis for these outcomes; however, a comprehensive summary was performed, in which the HAQ and DAS28 scores decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed. However, studies did not show improvement beyond 12 months without continuous treatment administration.Currently, the most well-known sources of MSCs are BM, AT, and UC; although MSCs can be isolated from any human tissue, there exist restrictions such as the availability of source tissues and invasiveness of the isolation procedures and different donor’s features [ | PMC10374120 |
Conclusion | RA | EVENTS | The evidence of effect is inconclusive for the efficacy outcomes, although the data showed a trend toward clinical efficacy. Our findings could suggest that MSCs therapy could be considered in treating RA when first-line treatment of RA as conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) treatments have failed, and a biologic DMARDs is not feasible. Overall, a favorable safety profile and no life-threatening events were observed in subjects with RA. However, due to the methodological limitations of the included studies and the considerable heterogeneity between there, several high-quality, large sample sizes and extended follow-up RCTs should be performed to confirm the trend toward clinical efficacy observed in this study. | PMC10374120 |
Supporting information | PMC10374120 | |||
PRISMA 2020 checklist. | (DOCX)Click here for additional data file. | PMC10374120 | ||
Search strategies for each database. | (DOCX)Click here for additional data file.We want to thank BioXcellerator, BioXscience, and BioXtech for their administrative assistance and critical review of the manuscript. | PMC10374120 | ||
References | PMC10374120 | |||
Introduction | COVID-19Tetracyclines, coronavirus disease 2019 | VIRUS, CORONAVIRUS DISEASE 2019 | Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the development of vaccines and therapeutic agents has mitigated its severity and mortality. mRNA vaccines, such as BNT162b2 and mRNA-1273In addition to vaccines, antiviral agents, and neutralizing antibodies, which are specific to the SARS-CoV-2 virus, repurposed immunomodulatory agents, such as dexamethasone, balicitinib, tocilizumab, and sarilumab, have been shown to mitigate the severity and mortality of COVID-19Tetracyclines exhibit anti-viral and anti-inflammatory activities through multiple mechanisms | PMC10447520 |
Results | PMC10447520 | |||
Disposition of patients | This open-label, multicenter, parallel-group, randomized controlled trial was conducted between September 1, 2020 and March 31, 2022 at four institutes in Osaka, Japan. The last entry was on September 22, 2021, when the delta variant of SARS-CoV-2 was prevalent in Japan. Twenty-three hospitalized patients who provided informed consent and were screened were randomized into three groups: a control group (n = 7), demeclocycline 150 mg daily group (n = 8), and demeclocycline 300 mg daily group (n = 8) (Fig. Flow diagram. | PMC10447520 | ||
Baseline characteristics of patients | The baseline characteristics of the 20 patients in the mITT population were similar across groups (Table Baseline clinical characteristics (mITT population).mITT: modified intention-to-treat. | PMC10447520 | ||
Preventing the exacerbation of COVID-19 | respiratory failure, exacerbations | RESPIRATORY FAILURE | Kaplan–Meier estimates of the cumulative incidence of dexamethasone treatment due to COVID-19 exacerbations by day 8 were 42.9% in the control group (95% CI 7.6% to 75.7%), 14.3% in the demeclocycline 150 mg group (95% CI 0.5% to 49.1%), and 40.0% in the demeclocycline 300 mg group (95% CI 3.1% to 78.6%) (Fig. (Kaplan–Meier estimates of the cumulative incidence of continuous oxygen therapy due to respiratory failure in COVID-19 by day 8 were 16.7% in the control group (95% CI 0.5% to 54.9%) and 0.0% in the demeclocycline treatment groups (Fig. Average changes in oxygen saturation measured by pulse oximetry (SpONegative conversion of saliva SARS-CoV-2 RNA levels on day 8.Changes in and change rates of T cells from day 1 to day 8 of the study treatment.Demeclocycline150 mgDemeclocycline300 mg | PMC10447520 |
SARS-CoV-2 viral RNA level | Saliva SARS-CoV-2 RNA turned negative on day 8 in 42.9% (3/7) of patients in the demeclocycline 150 mg group and 50.0% (2/4) in the demeclocycline 300 mg group, in contrast to only 16.7% (1/6) in the control group (as shown in Table | PMC10447520 | ||
T cell and cytokine responses after treatment | BLOOD | T cell and cytokine responses were analyzed from blood samples collected at baseline (prior to the study treatment on day 1) and on day 8. Blood samples collected on day 8 were obtained prior to the administration of dexamethasone, if applicable. Due to the administration of dexamethasone prior to blood sample collection on day 8, samples were not obtained from two patients in the control group, one in the demeclocycline 150 mg group, and two in the demeclocycline 300 mg group. Furthermore, a blood sample from one patient in the demeclocycline 300 mg group was not obtained due to patient withdrawal.The average change rates of CD8Changes in HLA-DRIn contrast to CD8An analysis of the relationship between the change rates of T cells (CD4Relationships between change rates of T cells and cytokines in demeclocycline treatment groups (n = 9). ( | PMC10447520 | |
B cell and antibody responses after treatment | The average change rates of CD19At the initiation of the study treatment, SARS-CoV-2 antibodies in three patients were positive. The durations from symptom onset to the initiation of the study treatment for these patients were seven, eleven, and thirteen days, respectively. Among patients whose antibodies were negative at treatment initiation, there was a 75.0% (3/4) positivity rate for SARS-CoV-2 antibodies in the control group, 83.3% (5/6) in the demeclocycline 150 mg group, and 100% (2/2) in the demeclocycline 300 mg group on day 8 of the study treatment. These results suggest that B cell counts and SARS-CoV-2 antibodies slightly increased in each group. | PMC10447520 | ||
COVID-19 symptoms | cough | On day 1, the most prevalent symptom among each group was cough, with a prevalence of 57.1% (4/7) in the control group, 71.4% (5/7) in the demeclocycline 150 mg group, and 83.3% (5/6) in the demeclocycline 300 mg group (as shown in Supplementary Fig. | PMC10447520 | |
Safety | ADVERSE EVENTS, ADVERSE EVENT | Treatment-emergent adverse events (TEAEs) were reported by one (14.3%), one (14.3%), and three (50.0%) patients in the control, demeclocycline 150 mg, and demeclocycline 300 mg groups, respectively (as shown in Table Adverse events (safety analysis population) over 29 days. | PMC10447520 | |
Discussion | diabetes mellitus, hypertension, pneumonia, Hypertension | PNEUMONIA, DISEASE, DIABETES MELLITUS, HYPERTENSION, HYPERTENSION | In the present study, the administration of low-dose demeclocycline for patients with mild-to-moderate COVID-19 was well tolerated and demonstrated potential in mitigating the exacerbation of COVID-19. The number of CD4Patients with mild-to-moderate COVID-19 were recruited in the present study. Immunological responses varied based on the severity of the disease. In the RECOVERY trial, no clear benefit of the dexamethasone treatment was observed among patients with COVID-19 who did not require oxygen support. However, the mortality rate was lower among patients receiving oxygen support who were administered dexamethasone than in the group receiving standard careIn the present study, a significant increase was observed in the population of CD4A plethora of immunomodulatory agents, such as dexamethasone, balicitinib, tocilizumab, and sarilumab, are utilized to treat patients with severe COVID-19. However, there are currently no therapeutic agents that have been specifically developed to support antiviral T cell responses in patients with early and mild COVID-19. The findings of our previous preclinical studies demonstrated that tetracyclines enhanced antigen-specific T cell responsesThe most frequent coexisting conditions in the present study were hypertension (20.0%) and diabetes mellitus (20.0%). Patients with hypertension were 2/7 (28.6%) in the control group and 2/7 (28.6%) in the demeclocycline 150 daily group. Patients with diabetes mellitus were also 2/7 (28.6%) in the control group and 2/7 (28.6%) in the demeclocycline 150 daily group. Hypertension and diabetes mellitus were reported to be at increased risk of developing severe COVID-19The present study had a number of limitations that need to be addressed. We did not conduct an analysis of SARS-CoV-2-specific T cells, which is crucial for understanding the immunological response to SARS-CoV-2 in patients with COVID-19. Furthermore, due to the small cohort size, it was challenging to evaluate clinical responses to the demeclocycline treatment. During the course of this clinical study, we encountered significant difficulties in both patient enrollment and study treatment completion. To minimize the effects of T cell responses, patients who had been vaccinated against COVID-19 were excluded from the study, and the concurrent use of corticosteroids, including dexamethasone, was prohibited during study treatment. Since the majority of Japanese citizens had rapidly received COVID-19 vaccines, there were a limited number of eligible COVID-19 patients who had not been vaccinated. Furthermore, all of the COVID-19 patients enrolled in this study were diagnosed with pneumonia via chest imaging and were generally indicated for dexamethasone treatments when demeclocycline treatments were terminated. We estimated that 8 patients were needed in each three groups, and actually, a total of 23 patients were randomized for the present study. However, the discontinuation of the study treatment, attributed to the administration of dexamethasone, resulted in a reduction in the cohort of patients assessed for T cell responses. Contrary to our hypothesis of CD8In summary, the present study suggests that patients with mild-to-moderate COVID-19 treated with low-dose demeclocycline exhibited T cell responses that were favorable for recovery from COVID-19. However, further studies with larger sample sizes are needed to confirm and expand upon these results. | PMC10447520 |
Methods | PMC10447520 | |||
Study design | The present study was an open-label, multicenter, parallel-group, randomized controlled clinical trial involving patients diagnosed with mild-to-moderate COVID-19. Participants with mild-to-moderate COVID-19 were planned to be randomly assigned in a 1:1:1 ratio to one of three groups: a control group (normal treatment), a group receiving 150 mg of demeclocycline once daily, and a group receiving 300 mg of demeclocycline (150 mg twice daily). Individuals allocated to the demeclocycline groups received a daily dose of 150 mg once daily or 150 mg twice daily for a period of 14 days.This clinical trial was conducted in accordance with the guidelines set forth in the Declaration of Helsinki. The study protocol received approval from the Certified Review Board of Osaka University (CRB5180007) and each individual participating institution. Written informed consent was obtained from patients prior to their inclusion in the study. This study was registered with the Japan Registry of Clinical Trials as jRCTs051200049 ( | PMC10447520 | ||
Patients | SARS-CoV-2 infection | SARS-COV-2 INFECTION | We prospectively identified patients aged between 20 and 75 years with SARS-CoV-2 infection confirmed by a positive reverse transcription-polymerase chain reaction (RT-PCR) or SARS-CoV-2 antigen tests that were approved by the Ministry of Health, Labour and Welfare in Japan. Inclusion criteria were mild-to-moderate COVID-19 without the need for oxygen support. Exclusion criteria were an SpO | PMC10447520 |
Treatment | Patients in the demeclocycline 150 mg daily group and demeclocycline 300 mg daily group (administered as 150 mg twice daily) received the study drug orally in the form of demeclocycline 150 mg capsules for a period of 14 days. The concurrent use of corticosteroids, including dexamethasone, immunosuppressants, and immunostimulants, or biologics, such as vaccines and antibody drugs, was prohibited during the study treatment, except for sotrovimab or casirivimab plus imdevimab. If a patient required the administration of dexamethasone due to the exacerbation of COVID-19, the study treatment was discontinued. | PMC10447520 | ||
Randomization | The patients were randomly assigned to one of three groups; control, demeclocycline 150 mg daily, demeclocycline 300 mg daily groups. The allocation ratio was set at 1:1:1. We used stratified randomization by institute with permuted blocks (block size = 3). In this study, an open-label design was applied. The reason for this design was that the primary endpoint was the enhancement of the T cell response, which is an objective measure devoid of evaluator bias. The statistician, who was responsible for this study, generated the allocation list confidentially and implementation was managed via the electronic data capture system (Datatrak Enterprise Cloud | PMC10447520 | ||
Outcomes and assessments | SECONDARY | The primary and secondary outcomes of the present study included changes from baseline (day 1, prior to the study treatment) in T cells, cytokines, and SARS-CoV-2 RNA on day 8. The primary outcome was the change rate of peripheral CD8Clinical outcomes included the change in oxygen saturation measured by pulse oximetry (SpO | PMC10447520 | |
Sample size and statistical analyses | ADVERSE EVENTS, SECONDARY | We estimated that 8 patients were needed in each group to detect a 15% difference in the change rate of CD8Efficacy analyses were performed on the mITT population, where patients without receiving the study treatment at any time, without any observations on efficacy/safety, or with eligibility violations were excluded from all randomized patients.The primary outcome, a difference in the change rate of CD8Regarding secondary outcomes, differences in the change in or change rate of T cells (CD8The safety assessment was based on adverse events reported during this trial. We calculated the number and percentage of all adverse events, which were coded according to Medical Dictionary for Regulatory Activities (MedDRA) terms.All analyses were conducted with SAS Version 9.4 software (SAS Institute, Inc., Cary, NC). | PMC10447520 | |
Supplementary Information | The online version contains supplementary material available at 10.1038/s41598-023-41051-2. | PMC10447520 | ||
Acknowledgements | This work was funded by Shionogi & Co., Ltd., Strategic Global Partnership & X (Cross)- Innovation Initiative, Graduate School of Medicine, Osaka University and Osaka University Hospital, Grant for Research and Development against Covid-19, and JSPS KAKENHI Grant Number 21K08153 (KI). The clinical study was supported by Shionogi & Co., Ltd. The quantification of lymphocytes and cytokines was supported by Strategic Global Partnership & X (Cross)-Innovation Initiative, Graduate School of Medicine, Osaka University and Osaka University Hospital, Grant for Research and Development against Covid-19. Preparation of the study report was supported by JSPS KAKENHI Grant Number 21K08153. We thank the teams in the Department of Medical Innovation, Osaka University Hospital, Yukio Tanaka for project management, Yasue Imagawa for data management, Takashi Hirota for programming, Sayuri Tsurumura and Miho Tarui for study monitoring, Manabu Yamaji, Megumi Asayama, and Tsubasa Nagata for drafting the protocol, Etsushi Iida, Mayuko Ouchi, and Yoshiaki Yamagishi for drafting a clinical study report, and Yukiko Shiromoto and Keisuke Sawada for the study audit. | PMC10447520 | ||
Author contributions | T.M. | K.I. and H.K. conceptualized the study. K.I., H.K., and T.Y. were involved in finalizing the protocol of the study. T.N., N.Y., T.K., K.H., T.M., K.T., K.M., A.O., S.G., K.A., M.M., and H.K. were involved in the clinical care of patients. S.O. and T.Y. were involved in data curation and the formal analysis of data. Y.T. and A.K. supervised the study. K.I., S.O., and T.Y. prepared the original draft of the manuscript. All authors were involved in writing, reviewing, and editing of the manuscript. | PMC10447520 | |
Data availability | The authors declare that the primary data supporting the results of the present study are available within the article and its supplementary information files. Additional data may be obtained from the corresponding author upon reasonable request. | PMC10447520 | ||
Competing interests | The authors declare no competing interests. | PMC10447520 | ||
References | PMC10447520 | |||
Abstract | PMC10417098 | |||
Background | lung cancer, NSCLC, skin toxicity | LUNG CANCER, SKIN TOXICITIES, SKIN TOXICITY, NSCLC | Dacomitinib significantly improves progression‐free survival and overall survival (OS) compared with gefitinib in patients with non–small‐cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. | PMC10417098 |
Methods | NSCLC, skin toxicity | SKIN TOXICITY, NSCLC | We performed a single‐arm, prospective, open‐label, multi‐institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR‐activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. | PMC10417098 |
Results | L858R, Skin toxicities, paronychia, rash | MAY, PARONYCHIA, SKIN TOXICITY, SKIN TOXICITIES | In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32–83 years), 20 were male, and 36 had a performance status of 0–1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%–56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression‐free survival was 6.8 months (95% CI, 4.0–8.6 months) and median OS was 21.6 months (95% CI, 17.0 months–not reached). | PMC10417098 |
Conclusion | SKIN TOXICITY | Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.We evaluated whether comprehensive prophylaxis reduces dacomitinib‐induced skin toxicity and improves treatment continuation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration.
| PMC10417098 | |
INTRODUCTION | lung cancer, NSCLC | LUNG CANCER, SKIN TOXICITY, NSCLC | The current standard of care for patients with advanced or metastatic non–small‐cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐activating mutations is treatment with EGFR‐tyrosine kinase inhibitors (TKIs). A meta‐analysis of randomized controlled trials with first‐generation EGFR‐TKIs (gefitinib or erlotinib) showed prolonged progression‐free survival (PFS) relative to chemotherapy in first‐line settings.In the ARCHER1042 study, preemptive treatment with doxycycline reduced skin toxicity of dacomitinib treatment. | PMC10417098 |
METHODS | PMC10417098 | |||
Study design and patient selection | SQUAMOUS CELL CARCINOMA, BRAIN METASTASES, ONCOLOGY, RECURRENT NSCLC, INTERSTITIAL LUNG DISEASE | This multi‐institutional phase II trial employed a single‐arm, prospective, and open‐label design. The study protocol has been previously reported and registered in the Japan Registry of Clinical Trials (jRCTs071190015, Figure The key eligibility criteria were as follows: patients with advanced or recurrent NSCLC excluding squamous cell carcinoma, harboring EGFR‐activating mutations, aged ≥20 years, a performance status (PS) of ≤2 based on the Eastern Cooperative Oncology Group scale, and adequate organ function. The main exclusion criteria were symptomatic brain metastases and interstitial lung disease. | PMC10417098 | |
Treatments | NSCLC, toxicities, diarrhea, Cancer | ADVERSE EVENT, DISEASE PROGRESSION, ADVERSE EVENTS, INTERSTITIAL PNEUMONITIS, SKIN TOXICITIES, NSCLC, EVENTS, SKIN TOXICITY, CANCER | Patients can participate in the study regardless of prior treatment for NSCLC. If the patients have received prior therapy, the following periods must have elapsed before study entry and adverse events: at least 2 weeks after cytotoxic chemotherapy administration and 4 weeks after chest irradiation. If the patient received EGFR‐TKI treatment, skin toxicities must have recovered to Grade <2 based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scale for eligibility. All adverse events were graded according to CTCAE, version 5.0.Eligible patients received dacomitinib and comprehensive prophylaxis for skin toxicity. Dacomitinib was started at 45 mg/day and tolerated for up to two dose reductions (30 and 15 mg/day). The preemptive strategy consisted of five agents: minocycline (100 mg orally, once daily); skin moisturizer containing heparinoid (twice daily for the face, neck, chest, back, and extremities); a medium topical steroid (class IV, twice daily for the face); a very strong topical steroid (class II, twice daily for the neck, chest, back, and extremities); and sunscreen (sun protection factor ≥ 25, protection factor UVA 4–8, and UVA and UVB protection). We provided patient guidance for medicine use and evaluated their adherence to the prophylactic treatment using a patient diary.Treatments were discontinued when the following events occurred: (1) disease progression; (2) severe adverse events (interstitial pneumonitis of any grade or non‐hematological toxicities of Grade 4); (3) requirement for threefold dose reduction of dacomitinib administration; and (4) discontinuation of dacomitinib treatment for ≥3 weeks. Severe adverse events led to the interruption of dacomitinib treatment, which could restart after recovery. In the case of diarrhea or skin toxicities, dacomitinib administration was restarted after improvement to Grade ≤1. In the case of other adverse events, dacomitinib was restarted after recovery with Grade ≤2. | PMC10417098 |
Endpoints | toxicity, rash, pruritus, paronychia, palmar‐plantar erythrondysesthesia syndrome, eczema | SKIN INFECTION, PARONYCHIA, ERYTHEMA MULTIFORME, SKIN TOXICITIES, ECZEMA | The primary endpoint was the incidence of skin toxicities ranked as Grade ≥2 during the initial 8 weeks of dacomitinib treatment. Dermatologic toxicity was defined as acneiform rash, dry skin, pruritus, paronychia, palmar‐plantar erythrondysesthesia syndrome, maculopapular rash, erythema multiforme, skin infection, and eczema. Secondary endpoints included the incidence of dose reduction of dacomitinib, PFS, and safety. | PMC10417098 |
Statistical analysis | NSCLC, skin toxicity, skin toxicities | SKIN TOXICITIES, SKIN TOXICITY, NSCLC | We planned to include 40 patients with NSCLC in this trial. The sample size was calculated using a one‐sample binomial test. In the ARCHER1042 trial, the incidence of Grade ≥2 skin toxicity during 8 weeks of dacomitinib initiation was 46% in the placebo group and 23% in the doxycycline prophylaxis group, respectively.Regarding the primary endpoint, the incidence of Grade ≥2 skin toxicities in the initial 8 weeks of dacomitinib treatment was calculated, and a 90% confidence interval (CI) was estimated based on the Wald method. The 95% CI was calculated for the incidence of dose reduction with dacomitinib. The survival curve of PFS was estimated using the Kaplan–Meier method, and the 95% CI of the median PFS and yearly PFS rates were estimated using the Brookmeyer and Crowley method and Greenwood method, respectively. SAS version 9.4 (SAS Institute, Cary, NC, USA) was used for all statistical analyses. | PMC10417098 |
Ethics considerations | This study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol and all amendments were reviewed and approved by the ethical review board of the Clinical Research Network Fukuoka Certified Review Board (CRB7180004). All patients provided written informed consent before enrollment. | PMC10417098 | ||
RESULTS | PMC10417098 | |||
Patients | NSCLC | MAY, NEUROENDOCRINE CARCINOMA, NSCLC | A total of 41 patients with EGFR‐mutated NSCLC were enrolled between May 2019 and April 2021 from 14 institutions. The data cut‐off date was April 30, 2022. The baseline patient characteristics are summarized in Table Baseline patient characteristics (Abbreviations: EGFR, epidermal growth factor receptor; LCNEC, large‐cell neuroendocrine carcinoma; TKIs, tyrosine kinase inhibitors.Body surface area was calculated using the Du Bois formula.One patient each had L861Q, exon20 insertion, and G719X compounded with S768I. | PMC10417098 |
Medication adherence | Of the 41 enrolled patients, more than 90% were perfectly compliant with prophylactic minocycline administration throughout the study period. Adherence to the topical medications was lower than that to the oral prophylaxis; nevertheless, more than 80% of the patients were compliant with the topical medications (skin moisturizer containing heparinoid and topical steroids) in 80% of the days during the study period. Sunscreen was recommended for use on outings, and perfect adherence was observed throughout >70% of the period (Figure Adherence pattern for prophylaxis medication during the 8 weeks of the study period. Adherence to prophylaxis medication was evaluated every 2 weeks for 8 weeks. The respective numbers of patients who were 100% compliant with prophylaxis at weeks 2, 4, 6, and 8 with each treatment were as follows: (A) minocycline: 38, 37, 33, and 32; (B) skin moisturizer: 37, 34, 29, and 31; (C) medium topical steroid: 35, 33, 29, and 29; (D) very strong topical steroid: 34, 31, 30, and 30; (E) sunscreen: 16, 21, 22, and 21. Eight patients discontinued dacomitinib treatments before the end of week 8. | PMC10417098 | ||
Primary endpoint | toxicities, Skin toxicities | SKIN | Skin toxicities (Grade ≥2) occurred in 43.9% (90% CI, 31.2%–56.7%) of the enrolled patients during the initial 8 weeks of dacomitinib therapy, which did not meet the primary endpoint (Skin toxicities in the initial 8 weeks of treatment ( | PMC10417098 |
Dacomitinib treatment in the initial 8 weeks | DISEASE PROGRESSION | During the 8 weeks after the start of dacomitinib therapy, nine patients (22.2%) discontinued treatment with dacomitinib. Disease progression was the most common cause (five patients). Among the patients who discontinued dacomitinib within the 8 weeks, the median treatment duration was 22 days (range: 8–52 days) (Table | PMC10417098 | |
Dose modification and safety | acneiform rash, paronychia, rash, skin toxicities | ADVERSE EVENTS, ADVERSE EVENT, PARONYCHIA, SKIN TOXICITIES | Due to skin toxicities, eight patients (19.5%; 95% CI, 7.4%–31.6%) underwent dose reduction. Of the eight patients, seven reduced the dacomitinib dosage once and one reduced the dose twice. The reasons for dose reduction mainly included acneiform rash (six patients), maculopapular rash (three patients), and paronychia (two patients).In addition to skin toxicities, severe non‐hematological adverse events (Grade ≥3) occurred in 12 patients (29.3%) (Table Adverse events other than skin toxicities in the initial 8 weeks of treatment (Number of evaluated population = 40 patients.Number of evaluated population = 37 patients. | PMC10417098 |
Efficacy and long‐term safety | The median PFS was 6.8 months (95% CI, 4.0–8.6 months) and median OS was 21.6 months (95% CI, 17.0 months to not reached) (Figures Progression‐free survival after enrollment in the study. The median progression‐free survival time was 6.8 months and median follow‐up time was 6.2 months.Overall survival after enrollment in the study. The median overall survival time was 21.6 months and median follow‐up time was 15.3 months. | PMC10417098 | ||
DISCUSSION | toxicity, infections, rash, paronychia, keratinization, skin toxicities, cutaneous toxicity, skin toxicity | SKIN, INFECTIONS, PARONYCHIA, SKIN TOXICITIES, SKIN TOXICITY | This was a prospective interventional study with prophylactic treatment to reduce skin toxicity associated with dacomitinib treatment. A total of 41 patients participated, and skin toxicities of Grade ≥2 were observed in 18/41 patients (43.9%; 90% CI, 31.2%–56.7%) during the initial 8 weeks of treatment. The primary endpoint failed to achieve statistical significance because the upper limit of the 90% CI exceeded the pre‐planned threshold of 46%.The representative skin toxicities with Grade ≥2 in this study were acneiform rash (26.8%) and paronychia (12.2%), which were less than the rates of 33% and 42% in the overall population of the ARCHER1050 study.Cohort I in ARCHER1042, which was used as the basis for the statistical design of this study, consisted mostly of non‐Asians, accounting for 97.3% of the enrolled participants. The enzymatic activity of the main metabolizing enzyme of dacomitinib, CYP2D6, is known to differ across races. Asians have a high frequency (41%) of a reduced function allele, CYP2D6*10, which is rarely present in Caucasians.Cutaneous side effects induced by EGFR‐TKIs are due to the inhibition of EGFR in basal keratinocytes and hair follicles. Disturbance of terminal keratinocyte differentiation and keratinization of the follicular epithelium results in occlusion of the follicular orifice, causing an acne‐like skin rash.Individuals of Asian descent, owing to their comparably thinner stratum corneum,Adherence to both oral and topical prophylaxis medications was good, with perfect compliance in 80% of the patients throughout the 8 weeks. Adherence to treatment is crucial for improving quality of life and obtaining optimal outcomes.Skin problems are a challenge in continuing treatment with EGFR inhibitors; 90% of patients develop skin problems, 76% require treatment interruption, 60% require dose reduction, and 32% require treatment discontinuation.Response rates were similar to those of other trials in both patients previously treated with EGFR‐TKI and EGFR‐TKI‐naïve patients.The most established prophylaxis for cutaneous toxicity is oral tetracyclines, which prevent and overcome infections.This study has some limitations. First, the study had an open‐label, single‐arm design, which could have introduced bias. We tried to educate the patients uniformly using an instruction guide, and we evaluated medication adherence based on patient diaries. Second, previously treated patients were enrolled. Ideally, medication adherence and skin toxicity evaluation should be limited to EGFR‐TKI‐naive patients. In the analyses of the association between skin toxicities and patients' characteristics, no significant correlation was observed. Third, since adherence was good at 8 weeks in this study, concurrently prophylaxis must continue during ongoing EGFR‐TKI therapy. Further study is awaited about long‐term adherence and toxicity management.This study prospectively evaluated the efficacy of comprehensive prophylaxis for dacomitinib‐related skin toxicity in the Japanese population. Although no significant differences were observed, the study may have been effective considering the racial differences in skin toxicity. The prevention of skin toxicity and patient education are important for the maintenance of quality of life and continuity of treatment. | PMC10417098 |
AUTHOR CONTRIBUTIONS | PMC10417098 | |||
FUNDING INFORMATION | This research was funded by Pfizer. Inc. | PMC10417098 | ||
CONFLICT OF INTEREST STATEMENT | Tadaaki | Shigeru Tanzawa recieved personal fees as honoraria from Astrazeneca K.K, Lily Japan, Chugai Pharmaceutical and Taiho Pharmaceutical. Tadaaki Yamada recieved commercial research grants from Pfizer, Ono Pharmaceutical, Janssen Pharmaceutical K.K, AstraZeneca, and Takeda Pharmaceutical Company Limited, payment for lectures from Eli Lilly and participated on advisory Board. Koichi Takayama recieved lecture fee from Pfizer Inc. | PMC10417098 | |
ETHICAL APPROVAL | This study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol and all amendments were reviewed and approved by the ethical review board of the Clinical Research Network Fukuoka Certified Review Board (CRB7180004). All patients provided written informed consent before enrollment. | PMC10417098 | ||
CLINICAL TRIAL REGISTRATION | The study protocol has been previously reported and registered in the Japan Registry of Clinical Trials (jRCTs071190015). | PMC10417098 | ||
Supporting information |
Figure S1.
Click here for additional data file.
Table S1.
Click here for additional data file. | PMC10417098 | ||
ACKNOWLEDGMENTS | We thank the patients who participated in this study and their families and site staff. We also thank the contributors of this study (Nobuhiko Seki, Noriyuki Ebi, Kohei Yoshimine, Masafumi Yamaguchi, Takashi Yokoi, Kazutoshi Komiya, Kazuo Kasahara, Akira Nakao, and Shinsuke Shiotsu) and the Clinical Research Support Center Kyushu (Akiko Ouraji, Yoshiaki Nishiyama) for managing the present study. | PMC10417098 | ||
DATA AVAILABILITY STATEMENT | The datasets analyzed during the current study are available from the corresponding author on reasonable request. | PMC10417098 | ||
REFERENCES | PMC10417098 | |||
Abstract | PMC10469755 | |||
Background | cancer | CANCER | Most physical activity (PA) interventions in young adult cancer survivors (YACS) have focused on short‐term outcomes without evaluating longer‐term outcomes and PA maintenance. This study examined the effects of an mHealth PA intervention at 12 months, after 6 months of tapered contacts, relative to a self‐help group among 280 YACS. | PMC10469755 |
Methods | sedentary behaviors | YACS participated in a 12‐month randomized trial that compared self‐help and intervention groups. All participants received an activity tracker, smart scale, individual videochat session, and access to a condition‐specific Facebook group. Intervention participants also received lessons, tailored feedback, adaptive goal setting, text messages, and Facebook prompts for 6 months, followed by tapered contacts. Accelerometer‐measured and self‐reported PA (total [primary outcome], moderate‐to‐vigorous [MVPA], light, steps, sedentary behaviors) were collected at baseline, 6, and 12 months. Generalized estimating equation analyses evaluated group effects on outcomes from baseline to 12 months. | PMC10469755 | |
Results | From baseline to 12 months, there were no between‐ or within‐group differences in accelerometer‐measured total PA min/week, while increases in self‐reported total PA were greater in the intervention versus self‐help group (mean difference = +55.8 min/week [95% CI, 6.0–105.6], | PMC10469755 | ||
Conclusion | cancer, Cancer | CANCER, CANCER | The intervention was not more effective than the self‐help group at increasing accelerometer‐measured total PA over 12 months. Both groups maintained PA from 6 to 12 months. Digital approaches have potential for promoting sustained PA participation in YACS, but additional research is needed to identify what strategies work for whom, and under what conditions.The IMproving Physical Activity after Cancer Treatment trial tested whether an mHealth physical activity intervention for young adult cancer survivors was more effective than a self‐help group at improving total amount of physical activity and other health outcomes over 12 months among 280 participants around the United States. The intervention was not more effective at increasing accelerometer‐measured total physical activity over 12 months relative to a self‐help group that only received digital tools. However, increases in self‐reported total physical activity were significantly greater in the intervention group, and both groups maintained levels of accelerometer‐measured total and moderate‐to‐vigorous physical activity from 6 to 12 months.
| PMC10469755 |
INTRODUCTION | cancer | CANCER, CHRONIC DISEASE | Young adult cancer survivors (YACS), diagnosed between ages 18–39, are at increased risk for morbidity and developing chronic disease,Previous digital PA interventions have shown potential among YACS, but most studies are limited by small sample sizes and short duration (8–12 weeks).We recently completed the IMPACT trial, the longest randomized controlled trial of a PA intervention among YACS to date. | PMC10469755 |
METHODS | PMC10469755 | |||
Study Design | sedentary behaviors | SECONDARY | The IMPACT trial was a 12‐month, 2‐arm randomized controlled trial of an mHealth intervention designed specifically for YACS compared with a self‐help condition. The study protocol and primary (total PA) and secondary (MVPA, light PA, steps, sedentary behaviors) outcomes at 6 months (primary time point) have been previously reported. | PMC10469755 |
Participants and Sample | RECRUITMENT | Participants were YACS, ages 18–39, who were post‐treatment, within 10 years of diagnosis, and not meeting PA recommendations of ≥150 min/week of MVPA (as measured by accelerometer). Details on participant recruitment and the study sample ( | PMC10469755 | |
Procedures and study conditions | The intervention and self‐help conditions have been previously described in detail. | PMC10469755 | ||
Active intervention delivery to the intervention group occurred during months 1–6, with tapered contacts from months 7–12. Intervention components were designed using social cognitive theory | PMC10469755 | |||
Self‐help | Along with the initial videochat session, self‐help participants had continued access to the digital tools for the duration of the study (i.e., months 1–12), including the condition‐specific Facebook group. Throughout months 1–12, study interventionists monitored Facebook group activity and posted when new cohorts of participants were added but did not encourage engagement with specific prompts or provide any additional contacts. | PMC10469755 | ||
Measures | PA was measured at baseline, 6, and 12 months using accelerometers (ActiGraph GT3X+, Pensacola, FL) and self‐reported with a modified version of the Godin Leisure Time Exercise Questionnaire, | PMC10469755 | ||
Statistical analyses | sedentary behaviors | EVENTS | Descriptive analyses were conducted to summarize participants' baseline characteristics by condition. Fisher's exact tests compared the groups on reported medical events. Wilcoxon rank sum tests compared the groups on days of activity tracking and Facebook engagement. To evaluate intervention effects relative to the self‐help group, we used an intention‐to‐treat approach including data from all participants. We conducted repeated measures analyses using generalized estimating equation (GEE) analyses to compare the effects of the intervention and self‐help groups on total PA min/week over the course of the 12‐month study. Based on examination of spaghetti plots showing the trajectory of accelerometer‐measured and self‐reported activity over time from baseline to 6 to 12 months, it appeared that the general activity trends over time were often non‐linear. Therefore, time was treated as categorical to allow the longitudinal model to accommodate non‐linear trends over time. The longitudinal analyses modeled accelerometer‐measured and self‐reported PA outcomes (total, MVPA, light, steps, sedentary behaviors) by group, time as a 3‐level category (i.e., baseline as reference, month 6, and month 12), and the interaction between group and time. These models estimated activity changes over time from baseline to 12 months and 6 to 12 months within groups, as well as differences in changes over time from baseline to 12 months and 6 to 12 months between groups. As prespecified in the study protocol, adjusted models included education, time since diagnosis, age, and wear time (accelerometer‐measured outcomes only) as covariates. | PMC10469755 |
RESULTS | PMC10469755 | |||
Participant characteristics and adherence | Of 280 participants randomized, 242 completed accelerometer assessments (86.4%) at 12 months, of which 236 (84.3%) provided valid accelerometer data (6 malfunctioning accelerometers); 246 (87.9%) completed valid self‐report PA questionnaires (Figure Consolidated standards of reporting trials diagram of participant flow. During months 7–12 (182 days), intervention participants tracked activity on a median (IQR) of 161 (52.5, 180.0) or 88.5% of days, which was significantly higher than self‐help participants (119.5 [11.5, 177.0], 65.7%) ( | PMC10469755 | ||
Total physical activity | Table Changes in physical activity and sedentary behavior within and between intervention and self‐help groups in the IMPACT Trial.Abbreviations: CI, confidence interval; PA, physical activity; SD, standard deviation.Unadjusted means. Baseline sample: Adjusted for education, time since diagnosis, age, and wear time (accelerometer only).Within‐group improvement occurred between baseline and 6 months at Within‐group improvement occurred between baseline and 12 months at Changes in accelerometer‐measured and self‐reported total physical activity by group over 12 months. Unadjusted means, with error bars showing 95% confidence intervals. | PMC10469755 | ||
Moderate‐to‐vigorous physical activity ( | Over 12 months, both groups increased accelerometer‐measured MVPA (+22.5 min/week; 95% CI, 8.76–36.2 in intervention vs. +13.9 min/week, 95% CI, 2.97–24.9 in self‐help), with no between‐group difference (Changes in accelerometer‐measured and self‐reported moderate‐to‐vigorous physical activity by group over 12 months. Unadjusted means, with error bars showing 95% confidence intervals. The proportion of YACS meeting PA guidelines at 12 months based on accelerometer data was 8.5% in the intervention versus 5.0% in the self‐help group, with no differences in relative risk (1.76 [95% CI, 0.68–4.56]; | PMC10469755 | ||
Light physical activity, steps, and sedentary behavior | From baseline to 12 months, there were no between‐ or within‐group differences in accelerometer‐measured light PA (There were no between‐group (Analyses with participants who completed measures at all time points yielded similar results. When removing outliers in models of accelerometer‐measured total PA, between‐group differences in change from 6 to 12 months became significant favoring the self‐help group (−175.6 min/week, 95% CI, −308.9, −42.3; | PMC10469755 | ||
DISCUSSION | theory‐based, cancer | CANCER, RECRUITMENT, ADVERSE EFFECTS | While PA is well‐recognized as beneficial for cancer survivors, little research has examined longer‐term PA change and maintenance among YACS. The IMPACT intervention offered a mobile PA intervention to YACS who are at risk for adverse effects from cancer decades following their treatment. Following a 6‐month active intervention, tapered contacts and access to a moderated Facebook group did not result in greater increases in accelerometer‐measured total PA min/week in the intervention group at 12 months relative to a self‐help group. However, change in self‐reported total PA min/week from baseline to 12 months was significantly greater in the intervention versus self‐help group. Among both groups, levels of accelerometer‐ and self‐reported total PA were maintained between 6 and 12 months. Further, both groups improved accelerometer‐measured and self‐reported MVPA over 12 months and maintained improvements from 6 to 12 months. Intervention participants (48%) were more likely to report meeting PA guidelines than self‐help participants (33%) at 12 months. Overall, both digital approaches could be promising for promoting sustained PA participation and long‐term health benefits in YACS, but additional research is needed to identify what strategies work for whom, and under what conditions.The lack of intervention effect on accelerometer‐measured total PA at 12 months is similar to prior studies with cancer survivors, which observed PA improvements in both intervention and control groups, resulting in a lack of effects.Other home or web‐based interventions among survivors have reported significant intervention effects on PA at 12 months, but were based on self‐reported outcomes.At 12 months, there was no intervention effect on accelerometer‐measured MVPA, though intervention participants were more likely to report meeting MVPA guidelines than self‐help participants. The between‐group differences in self‐reported MVPA increases over 12 months approached significance. MVPA increases in the self‐help group were consistent with earlier definitions of contamination in home‐based trials (>60 min/week)For some intervention participants, having continued access to goal setting prompted by text message, a Facebook group with moderated prompts, bimonthly lessons and tailored feedback (i.e., theory‐based intervention components designed to promote behavioral capability, self‐regulation, self‐efficacy, and social support) may have promoted successful PA maintenance from 6 to 12 months. Among cancer survivors, self‐regulatory (e.g., goal setting, self‐monitoring, behavioral feedback)The decline in steps from 6 to 12 months within the intervention group may reflect decreases in light PA, which was also observed in a trial of PA maintenance following an intervention among survivors with activity trackers, group sessions, and a phone call.To our knowledge, this is the first study among YACS to evaluate digital intervention strategies to support PA adoption and maintenance over 12 months. Strengths of the study included the randomized controlled design, nationwide recruitment, remote delivery, strong retention, multiple measures of PA and sedentary behavior, and an active comparison group that facilitated evaluation of the sustained effects of access to digital tools and a Facebook group alone. Findings should also be considered in the context of limitations. The correlation between accelerometer‐ and self‐reported PA was significant but small, indicating bias in self‐reported PA measurement, which is reflected in the differing proportions of YACS meeting PA guidelines by measurement type. Since participants were not blinded to group assignment, intervention participants may have had higher social desirability bias to report higher levels of PA. Intervention participants received tapered contacts in months 7–12, which precluded the examination of intervention effects in the absence of continued contact. Given the relatively homogeneous study sample with respect to race, sex, and education, study findings may not be generalizable more broadly to YACS. Finally, the study focused on promotion of aerobic activity without emphasis on strength training, which is another component of the PA guidelines for cancer survivors.This study contributes to the growing evidence that mHealth interventions with activity trackers may be effective for promoting and maintaining PA among cancer survivors. Findings suggest that a theory‐based intervention designed to enhance strategies offered by digital tools was more effective than a self‐help group at 12 months for self‐reported total PA and possibly self‐reported MVPA, but not accelerometer‐measured total PA or MVPA. Overall, both digital approaches have potential for dissemination to widely reach and promote PA maintenance and related health benefits among YACS. Additional research is needed to elucidate for whom, and under what contexts, specific intervention strategies work best. | PMC10469755 |
AUTHOR CONTRIBUTIONS | PMC10469755 | |||
FUNDING INFORMATION | Diabetes, Digestive, Cancer | KIDNEY DISEASES, DIABETES, CANCER | National Cancer Institute (R01CA204965; P30CA016086); National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056350); University of North Carolina at Chapel Hill (University Cancer Research Fund); National Center for Advancing Translational Sciences (UL1TR002489). | PMC10469755 |
CONFLICT OF INTEREST STATEMENT | None. | PMC10469755 |
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