Let's TOC Fertility: A stepped wedge cluster randomized controlled trial of the Telehealth Oncofertility Care (TOC) intervention in children, adolescent and young adult cancer survivors.

INTRODUCTION: Children, adolescent, and young adult cancer survivors experience overall increased risks of infertility that are preventable through effective fertility preservation services prior to starting cancer treatment. Oncofertility care is the evidence-based practice of informing newly diagnosed cancer patients about their reproductive risks and supporting shared decision-making on fertility preservation services. Despite longstanding clinical guidelines, oncofertility care delivery continues to be limited and highly variable across adult and pediatric oncology settings. MATERIALS AND METHODS: We describe the design of a stepped wedge cluster randomized clinical trial to evaluate the effectiveness of the multi-component Telehealth Oncofertility Care (TOC) intervention conducted in 20 adult and pediatric oncology clinics across three health systems in Southern California. Intervention components are: 1) electronic health record-based oncofertility needs screen and referral pathway to a virtual oncofertility hub; 2) telehealth oncofertility counseling through the hub; and 3) telehealth oncofertility financial navigation through the hub. We hypothesize the intervention condition will be associated with increased proportions of patients who engage in goal-concordant oncofertility care (i.e., engagement in reproductive risk counseling and fertility preservation services that meet the patient's fertility goals) and improved patient-reported outcomes, compared to the usual care control condition. We will also evaluate intervention implementation in a mixed-methods study guided by implementation science frameworks. DISCUSSION: Our overall goal is to speed implementation of a scalable oncofertility care intervention at cancer diagnosis for children, adolescent and young adult cancer patients to improve their future fertility and quality of life. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05443737.

Implementation of state health insurance benefit mandates for cancer-related fertility preservation: following policy through a complex system.

BACKGROUND: A myriad of federal, state, and organizational policies are designed to improve access to evidence-based healthcare, but the impact of these policies likely varies due to contextual determinants of, reinterpretations of, and poor compliance with policy requirements throughout implementation. Strategies enhancing implementation and compliance with policy intent can improve population health. Critically assessing the multi-level environments where health policies and their related health services are implemented is essential to designing effective policy-level implementation strategies. California passed a 2019 health insurance benefit mandate requiring coverage of fertility preservation services for individuals at risk of infertility due to medical treatments, in order to improve access to services that are otherwise cost prohibitive. Our objective was to document and understand the multi-level environment, relationships, and activities involved in using state benefit mandates to facilitate patient access to fertility preservation services. METHODS: We conducted a mixed-methods study and used the policy-optimized exploration, preparation, implementation, and sustainment (EPIS) framework to analyze the implementation of California's fertility preservation benefit mandate (SB 600) at and between the state insurance regulator, insurer, and clinic levels. RESULTS: Seventeen publicly available fertility preservation benefit mandate-relevant documents were reviewed. Interviews were conducted with four insurers; 25 financial, administrative, and provider participants from 16 oncology and fertility clinics; three fertility pharmaceutical representatives; and two patient advocates. The mandate and insurance regulator guidance represented two "Big P" (system level) policies that gave rise to a host of "little p" (organizational) policies by and between the regulator, insurers, clinics, and patients. Many little p policies were bridging factors to support implementation across levels and fertility preservation service access. Characterizing the mandate's functions (i.e., policy goals) and forms (i.e., ways that policies were enacted) led to identification of (1) intended and unintended implementation, service, and patient outcomes, (2) implementation processes by level and EPIS phase, (3) actor-delineated key processes and heterogeneity among them, and (4) inner and outer context determinants that drove adaptations. CONCLUSIONS: Following the midstream and downstream implementation of a state health insurance benefit mandate, data generated will enable development of policy-level implementation strategies, evaluation of determinants and important outcomes of effective implementation, and design of future mandates to improve fit and fidelity.

Acupuncture vs Massage for Pain in Patients Living With Advanced Cancer: The IMPACT Randomized Clinical Trial.

Importance: Pain is challenging for patients with advanced cancer. While recent guidelines recommend acupuncture and massage for cancer pain, their comparative effectiveness is unknown. Objective: To compare the effects of acupuncture and massage on musculoskeletal pain among patients with advanced cancer. Design, Setting, and Participants: A multicenter pragmatic randomized clinical trial was conducted at US cancer care centers consisting of a northeastern comprehensive cancer center and a southeastern cancer institute from September 19, 2019, through February 23, 2022. The principal investigator and study statisticians were blinded to treatment assignments. The duration of follow-up was 26 weeks. Intention-to-treat analyses were performed (linear mixed models). Participants included patients with advanced cancer with moderate to severe pain and clinician-estimated life expectancy of 6 months or more. Patient recruitment strategy was multipronged (eg, patient database queries, mailings, referrals, community outreach). Eligible patients had English or Spanish as their first language, were older than 18 years, and had a Karnofsky score greater than or equal to 60 (range, 0-100; higher scores indicating less functional impairment). Interventions: Weekly acupuncture or massage for 10 weeks with monthly booster sessions up to 26 weeks. Main Outcomes and Measures: The primary end point was the change in worst pain intensity score from baseline to 26 weeks. The secondary outcomes included fatigue, insomnia, and quality of life. The Brief Pain Inventory (range, 0-10; higher numbers indicate worse pain intensity or interference) was used to measure the primary outcome. The secondary outcomes included fatigue, insomnia, and quality of life. Results: A total of 298 participants were enrolled (mean [SD] age, 58.7 [14.1] years, 200 [67.1%] were women, 33 [11.1%] Black, 220 [74.1%] White, 46 [15.4%] Hispanic, and 78.5% with solid tumors). The mean (SD) baseline worst pain score was 6.9 (1.5). During 26 weeks, acupuncture reduced the worst pain score, with a mean change of -2.53 (95% CI, -2.92 to -2.15) points, and massage reduced the Brief Pain Inventory worst pain score, with a mean change of -3.01 (95% CI, -3.38 to -2.63) points; the between-group difference was not significant (-0.48; 95% CI, -0.98 to 0.03; P = .07). Both treatments also improved fatigue, insomnia, and quality of life without significant between-group differences. Adverse events were mild and included bruising (6.5% of patients receiving acupuncture) and transient soreness (15.1% patients receiving massage). Conclusions and Relevance: In this randomized clinical trial among patients with advanced cancer, both acupuncture and massage were associated with pain reduction and improved fatigue, insomnia, and quality of life over 26 weeks; however, there was no significant different between the treatments. More research is needed to evaluate how best to integrate these approaches into pain treatment to optimize symptom management for the growing population of people living with advanced cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT04095234.

Intervening on women's health for rural young breast cancer survivors: A study protocol.

INTRODUCTION: From diagnosis to post-treatment, many young breast cancer survivors (YBCS) experience infertility, limited contraception choices, concern about pregnancy safety, and menopausal symptoms. Clinical guidelines recommend oncofertility care (counseling and/or clinical services that meet fertility, contraception, pregnancy health and/or menopausal symptom management needs) throughout the cancer care continuum. However, significant oncofertility care gaps exist in rural, community oncology settings. MATERIALS AND METHODS: We describe the design of an interrupted time series, effectiveness-implementation hybrid clinical trial that evaluates a multi-component intervention to improve YBCS engagement in oncofertility care. The intervention is comprised of 1) oncology clinic-based oncofertility needs screen; 2) a women's health survivorship care plan in Spanish and English; 3) remote patient navigation; and 4) telehealth oncofertility consultation. During the pre-intervention period (12 months), usual care will be delivered. During the intervention period (15 months), the multi-component intervention will be implemented at two rural oncology clinics with largely Latina, Spanish-speaking populations. The primary outcome of YBCS (n = 135) engagement in oncofertility care will be collected from medical record review. We will also collect validated patient-reported outcomes. Informed by the Exploration Preparation Implementation Sustainment (EPIS) implementation science framework, we will integrate qualitative and quantitative data to explore whether and how the intervention was effective, acceptable, appropriate, and delivered with fidelity. DISCUSSION: Our overall goal is to speed implementation of a scalable oncofertility care intervention for YBCS in underserved areas to reduce disparities and improve reproductive health and quality of life. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05414812.

Development, Usability Testing, and Implementation Assessment of Cancer Related Infertility Score Predictor, an Online Cancer Related Infertility Risk Counseling Tool.

Purpose: Oncofertility counseling of female cancer patients lacks efficient access to tailored and valid infertility risk estimates to support shared decision-making on fertility preservation treatments. The objective was to develop, conduct user-centered design, and plan clinic-based implementation of the Cancer Related Infertility Score Predictor (CRISP), a web-based tool to support infertility risk counseling. Methods: Using a mixed methods design, literature review was undertaken to abstract data on infertility, primary ovarian insufficiency, and amenorrhea risks of common cancer treatments. The CRISP website was programmed to take user input about patient ages and cancer treatments and generate a risk summary. Using user experience methodology and semistructured interviews, usability testing and implementation assessment were conducted with 12 providers recruited from 5 medical centers in Southern California. Results: The web-based CRISP tool encompasses infertility risk data for 60 treatment regimens among 10 cancer types. Usability testing demonstrated that the tool is intuitive and informed minor modifications, including adding crowd-sourced submission of additional cancer treatments. Participants rated the tool as credible, advantageous over current provider methods to ascertain infertility risks, and useful for tailoring treatment planning and counseling patients. A key barrier was lack of information on some cancer treatments. Fit within clinical workflow was feasible, particularly with electronic health record integration. Conclusions: The novel, web-based CRISP tool is a feasible, acceptable, and appropriate tool to address provider knowledge gap about cancer related infertility risks and use for patient counseling. CRISP has significant potential to support tailored oncofertility counseling in the heterogeneous young cancer patient population.

A Multicomponent Telehealth Intervention to Improve Oncofertility Care Delivery Among Young Cancer Patients: A Pilot Study.

Purpose: Oncofertility care for pediatric, adolescent, and young adult cancer patients remains under-implemented across adult and pediatric oncology settings. We pilot tested an electronic health record (EHR)-enabled multicomponent oncofertility intervention (including screening, referral, and fertility consult) in an adult academic oncology program and systematically assessed intervention fit to pediatric and community oncology programs. Methods: Using surveys (n = 33), audits (n = 143), and interviews (n = 21) guided by implementation science frameworks, we pilot tested the EHR-enabled intervention for oncofertility care in young cancer patients at an adult oncology program and evaluated implementation outcomes. We interviewed health care providers from seven regional oncology and fertility programs about intervention fit to their clinical contexts. Results: We recruited 33 health care providers from an adult oncology setting and 15 health care providers from seven additional oncology and fertility settings. At the adult oncology setting, the intervention was found to be appropriate, acceptable, and feasible and improved the screening of fertility needs (from 30% pre- to 51% post-intervention); yet, some patients did not receive appropriate referrals to fertility consults. Providers across all settings suggested content and context modifications, such as adding options to the intervention or allowing the screening component to pop up at a second visit, to improve and adapt the intervention to better fit their clinical care contexts. Conclusions: We found that the EHR-enabled intervention increased the rate of goal-concordant oncofertility care delivery at an adult oncology program. We also identified facilitators, barriers, and needed adaptations to the intervention required for implementation and scaling-up across diverse oncology settings.

Acupuncture versus massage for pain in patients living with advanced cancer: a protocol for the IMPACT randomised clinical trial.

INTRODUCTION: Pain, comorbid fatigue and sleep disturbances are common and distressing symptoms for patients with advanced cancer, negatively impacting their quality of life. Clinical guidelines recommend non-pharmacological interventions, including acupuncture and massage, for pain management in adult patients with cancer in adjunct to conventional care. However, high-quality evidence about the comparative effectiveness and long-term durability of these therapies for symptom management is limited. METHODS AND ANALYSIS: We describe the design of a two-arm, parallel group, multicentre randomised controlled trial that investigates the use of acupuncture versus massage for musculoskeletal pain among 300 patients with diverse types of advanced cancer. The primary aim is to evaluate the long-term effectiveness (26 weeks from randomisation) of acupuncture vs massage for pain (primary outcome) and comorbid symptoms (fatigue, sleep disturbance and quality of life). The secondary aim is to identify patient-level demographic characteristics (eg, sex, race, age), clinical factors (eg, insomnia, pain severity) and psychological attributes that are associated with a greater reduction in pain for either acupuncture or massage. Patients will receive weekly acupuncture or massage treatments for 10 weeks, followed by monthly booster sessions up to 26 weeks. The primary endpoint will be the change in worst pain intensity score from baseline to 26 weeks. We will collect validated patient-reported outcomes at multiple time points over 26 weeks. ETHICS AND DISSEMINATION: The Institutional Review Board at Memorial Sloan Kettering Cancer Center in New York approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. Our findings will help patients and healthcare providers make informed decisions about incorporating non-pharmacological treatments to manage pain for patients with advanced cancer. TRIAL REGISTRATION NUMBER: NCT04095234.

Effectiveness of Electroacupuncture or Auricular Acupuncture vs Usual Care for Chronic Musculoskeletal Pain Among Cancer Survivors: The PEACE Randomized Clinical Trial.

IMPORTANCE: The opioid crisis creates challenges for cancer pain management. Acupuncture confers clinical benefits for chronic nonmalignant pain, but its effectiveness in cancer survivors remains uncertain. OBJECTIVE: To determine the effectiveness of electroacupuncture or auricular acupuncture for chronic musculoskeletal pain in cancer survivors. DESIGN, SETTING, AND PARTICIPANTS: The Personalized Electroacupuncture vs Auricular Acupuncture Comparative Effectiveness (PEACE) trial is a randomized clinical trial that was conducted from March 2017 to October 2019 (follow-up completed April 2020) across an urban academic cancer center and 5 suburban sites in New York and New Jersey. Study statisticians were blinded to treatment assignments. The 360 adults included in the study had a prior cancer diagnosis but no current evidence of disease, reported musculoskeletal pain for at least 3 months, and self-reported pain intensity on the Brief Pain Inventory (BPI) ranging from 0 (no pain) to 10 (worst pain imaginable). INTERVENTIONS: Patients were randomized 2:2:1 to electroacupuncture (n = 145), auricular acupuncture (n = 143), or usual care (n = 72). Intervention groups received 10 weekly sessions of electroacupuncture or auricular acupuncture. Ten acupuncture sessions were offered to the usual care group from weeks 12 through 24. MAIN OUTCOMES AND MEASURES: The primary outcome was change in average pain severity score on the BPI from baseline to week 12. Using a gatekeeping multiple-comparison procedure, electroacupuncture and auricular acupuncture were compared with usual care using a linear mixed model. Noninferiority of auricular acupuncture to electroacupuncture was tested if both interventions were superior to usual care. RESULTS: Among 360 cancer survivors (mean [SD] age, 62.1 [12.7] years; mean [SD] baseline BPI score, 5.2 [1.7] points; 251 [69.7%] women; and 88 [24.4%] non-White), 340 (94.4%) completed the primary end point. Compared with usual care, electroacupuncture reduced pain severity by 1.9 points (97.5% CI, 1.4-2.4 points; P < .001) and auricular acupuncture reduced by 1.6 points (97.5% CI, 1.0-2.1 points; P < .001) from baseline to week 12. Noninferiority of auricular acupuncture to electroacupuncture was not demonstrated. Adverse events were mild; 15 of 143 (10.5%) patients receiving auricular acupuncture and 1 of 145 (0.7%) patients receiving electroacupuncture discontinued treatments due to adverse events (P < .001). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial among cancer survivors with chronic musculoskeletal pain, electroacupuncture and auricular acupuncture produced greater pain reduction than usual care. However, auricular acupuncture did not demonstrate noninferiority to electroacupuncture, and patients receiving it had more adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02979574.

Theory-Guided Development of Fertility Care Implementation Strategies for Adolescent and Young Adult Cancer Survivors.

Purpose: Oncofertility care at cancer diagnosis remains underimplemented across oncology and fertility care settings, with limited tools to scale up effective implementation strategies. Using implementation science theory, we systematically assessed factors that influence oncofertility care implementation and mapped scalable strategies, particularly electronic health record (EHR)-enabled ones, that fit adult and pediatric oncology care contexts. Methods: Using purposeful sampling, we recruited health care providers and female, reproductive-aged survivors of adolescent and young adult (AYA) cancers (AYA survivors) from a comprehensive cancer center and a freestanding children's hospital to semistructured interviews and focus groups. Using thematic analysis combining inductive codes with deductive codes using the Consolidated Framework for Implementation Research (CFIR), we characterized barriers and facilitators to care and designed responsive strategies. Two coders independently coded each transcript. Results: We recruited 19 oncology and fertility providers and 9 cancer survivors. We identified barriers and facilitators to oncofertility care in the CFIR domains of individual, inner setting, outer setting, and process, allowing us to conceptualize oncofertility care to encompass three core components (screening, referral, and fertility preservation counseling) and map five strategies to these components that fit an adult and a children's context and bridge oncology and fertility practices. The strategies were screening using a best practice advisory, referral order, telehealth fertility counseling, provider audit and feedback, and provider education. All but provider education were EHR tools with embedded efficiencies. Conclusion: An implementation science approach systematically assessed oncofertility care and mapped strategies to provide a theory-based approach and scalable EHR tools to support wider dissemination.

Psychosocial stress and ovarian function in adolescent and young adult cancer survivors.

STUDY QUESTION: Is psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)? SUMMARY ANSWER: We observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors. WHAT IS KNOWN ALREADY: Psychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: AYA survivor participants were ages 15-35 at cancer diagnosis and ages 18-40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3-7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: The median age of participants was 34.0 years (range 19-41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0-36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures. LIMITATIONS, REASONS FOR CAUTION: Our analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress. WIDER IMPLICATIONS OF THE FINDINGS: The lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans. STUDY FUNDING/COMPETING INTEREST(S): NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Beyond Premature Ovarian Insufficiency: Staging Reproductive Aging in Adolescent and Young Adult Cancer Survivors.

CONTEXT: Although stages of reproductive aging for women in the general population are well described by STRAW+10 criteria, this is largely unknown for female adolescent and young adult cancer survivors (AYA survivors). OBJECTIVE: This work aimed to evaluate applying STRAW + 10 criteria in AYA survivors using bleeding patterns with and without endocrine biomarkers, and to assess how cancer treatment gonadotoxicity is related to reproductive aging stage. DESIGN: The sample (n = 338) included AYA survivors from the Reproductive Window Study cohort. Menstrual bleeding data and dried-blood spots for antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) measurements (Ansh DBS enzyme-linked immunosorbent assays) were used for reproductive aging stage assessment. Cancer treatment data were abstracted from medical records. RESULTS: Among participants, mean age 34.0 ±â€…4.5 years and at a mean of 6.9 ±â€…4.6 years since cancer treatment, the most common cancers were lymphomas (31%), breast (23%), and thyroid (17%). Twenty-nine percent were unclassifiable by STRAW + 10 criteria, occurring more frequently in the first 2 years from treatment. Most unclassifiable survivors exhibited bleeding patterns consistent with the menopausal transition, but had reproductive phase AMH and/or FSH levels. For classifiable survivors (48% peak reproductive, 30% late reproductive, 12% early transition, 3% late transition, and 7% postmenopause), endocrine biomarkers distinguished among peak, early, and late stages within the reproductive and transition phases. Gonadotoxic treatments were associated with more advanced stages. CONCLUSIONS: We demonstrate a novel association between gonadotoxic treatments and advanced stages of reproductive aging. Without endocrine biomarkers, bleeding pattern alone can misclassify AYA survivors into more or less advanced stages. Moreover, a large proportion of AYA survivors exhibited combinations of endocrine biomarkers and bleeding patterns that do not fit the STRAW + 10 criteria, suggesting the need for modified staging for this population.

Personalized electro-acupuncture versus auricular-acupuncture comparative effectiveness (PEACE): A protocol of a randomized controlled trial for chronic musculoskeletal pain in cancer survivors.

INTRODUCTION: Chronic pain is a leading cause of disability and remains under-treated in nearly half of patients with cancer. The opioid crisis has highlighted an urgent public health need for effective nonpharmacological pain management. Electroacupuncture (EA) and Battlefield Acupuncture (BFA) represent nonpharmacological modalities used in clinical practice to manage pain; however, their effectiveness has not been rigorously evaluated in oncology settings. METHODS: We describe the design of a 3-arm, parallel, single-center, multisite randomized controlled trial that investigates EA and BFA versus usual-care wait-list control (WLC) for chronic musculoskeletal pain among 360 patients with diverse cancer types across various stages. The primary aim is to compare effects of EA and BFA versus WLC on pain, physical function, and co-morbid symptoms. The secondary aim is to examine the interaction between patient outcome expectancy and acupuncture modality (EA vs BFA) on pain reduction. The tertiary aim is to evaluate the association between genetic polymorphisms and responses to acupuncture. Patients will be randomized in a 2:2:1 ratio to EA:BFA:WLC. Acupuncture groups will receive weekly treatments over 10 weeks. WLC will receive usual care over the same evaluation period as the acupuncture groups. The primary endpoint will be the change in average pain intensity score from baseline to week 12. We will collect validated patient-reported outcomes and blood/saliva samples at multiple timepoints over 24 weeks. DISCUSSION: Our findings will advance nonpharmacological pain management in oncology and inform personalized treatment approaches that integrate individuals' expectations and genetic biomarkers to deliver "precision" acupuncture to cancer patients with chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02979574.

Genetic predictors to acupuncture response for hot flashes: an exploratory study of breast cancer survivors.

OBJECTIVE: Because hot flashes are a common symptom experienced by women with breast cancer, we sought to explore genetic predictors associated with response to acupuncture for the treatment of hot flashes. METHODS: Using data from our completed randomized controlled trial (Clinicaltrials.gov identifier: NCT01005108) on hot flashes among breast cancer survivors who provided biomarker collection (N = 108), we extracted and assayed DNA for single nucleotide polymorphisms in genes involved in neurotransmission, thermoregulation, and inflammation (ADORA1, COMT, TCL1A, and TRPV1). For our primary outcome we classified individuals with a 50% or more reduction in their hot flash composite score at the end of treatment as responders. We used Fisher exact test to identify individual and combined single nucleotide polymorphisms associated with treatment response. RESULTS: Among women (N = 57) who received acupuncture treatment (electro or sham), we found that women who were carriers of at least one of these six genotypes (ADORA1 rs41264025-GA or rs16851029-GG or rs12744240-GT, COMT rs6269-GA, TCL1A rs2369049-GG, and TRPV1 rs8065080-TT) were more likely to respond to acupuncture for hot flashes than noncarriers (70.3% vs 37.5%, P = 0.035). These six genotypes were not associated with response in women (N = 51) who received pharmacological hot flash treatment (gabapentin or placebo pill; 37.5% vs 37.5%, P = 1.0). CONCLUSIONS: In this exploratory, proof of concept study, we identified six genotypes that may predict response to acupuncture for hot flashes in breast cancer survivors. If confirmed by future studies, these findings may inform the development of personalized acupuncture for managing hot flashes.

What makes one respond to acupuncture for insomnia? Perspectives of cancer survivors.

OBJECTIVE: Like any therapy, acupuncture is effective for some patients, while not helpful for others. Understanding from a patients' perspective what makes one respond or not to acupuncture can help guide further intervention development. This study aimed to identify factors that influence the perception of acupuncture's therapeutic effect among cancer survivors with insomnia. METHOD: We conducted post-treatment semi-structured interviews with cancer survivors who were randomized to the acupuncture group in a clinical trial for the treatment of insomnia. Survivors were categorized into Responders and Non-Responders to acupuncture treatment based on the change in the Insomnia Severity Index with a reduction of eight points or greater as the cut-off for the response. An integrated approach to data analysis was utilized by merging an a priori set of codes derived from the key ideas and a set of codes that emerged from the data through a grounded theory approach. Codes were examined for themes and patterns. RESULTS: Among 28 cancer survivors interviewed, 18 (64%) were classified as Responders. Participants perceived the ability to respond to acupuncture as dependent on treatment that effectively: (1) alleviated co-morbidities contributing to insomnia, (2) supported sleep hygiene practices, and (3) provided a durable therapeutic effect. Acupuncture treatment that did not address one of these themes often detracted from positive treatment outcomes and diminished perceived benefit from acupuncture. SIGNIFICANCE OF RESULTS: We identified patient-perceived contributors to response to acupuncture, such as co-morbid medical conditions, adequate support for sleep hygiene practices, and temporary therapeutic relief. Addressing these factors may improve the overall effectiveness of acupuncture for insomnia.

Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors.

BACKGROUND: Arthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA). METHODS: We performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants. RESULTS: Among 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00-2.20], had a more recent transition into menopause (<10 years) (5-10 years AOR 1.55, 95% CI 1.09-2.22; <5 years AOR 1.78, 95% CI 1.18-2.67), were within one year of starting AIs (AOR 1.61, 95% CI 1.08-2.40), and those who received chemotherapy (AOR 1.38, 95% CI 1.02-1.88) were significantly more likely to report AIAA. Additionally, SNP rs11648233 (HSD17B2) was significantly associated with higher odds of AIAA (AOR 2.21, 95% CI 1.55-3.16). CONCLUSIONS: Time since menopause and start of AIs, prior chemotherapy, and SNP rs11648233 within the HSD17B2 gene in the estrogen pathway were significantly associated with patient-reported AIAA. These findings suggest that clinical and genetic factors involved in estrogen withdrawal increase the risk of AIAA in postmenopausal breast cancer survivors.

What if Acupuncture Were Covered by Insurance for Pain Management? A Cross-Sectional Study of Cancer Patients at One Academic Center and 11 Community Hospitals.

OBJECTIVE: In response to the national opioid crisis, governmental and medical organizations have called for broader insurance coverage of acupuncture to improve access to nonpharmacologic pain therapies, especially in cancer populations, where undertreatment of pain is prevalent. We evaluated whether cancer patients would be willing to use insurance-covered acupuncture for pain. DESIGN AND SETTING: We conducted a cross-sectional survey of cancer patients with pain at one academic center and 11 community hospitals. METHODS: We used logistic regression models to examine factors associated with willingness to use insurance-covered acupuncture for pain. RESULTS: Among 634 cancer patients, 304 (47.9%) reported willingness to use insurance-covered acupuncture for pain. In univariate analyses, patients were more likely to report willingness if they had severe pain (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.03-2.45) but were less likely if they were nonwhite (OR = 0.59, 95% CI = 0.39-0.90) or had only received high school education or less (OR = 0.46, 95% CI = 0.32-0.65). After adjusting for attitudes and beliefs in multivariable analyses, willingness was no longer significantly associated with education (adjusted OR [aOR] = 0.78, 95% CI = 0.50-1.21) and was more negatively associated with nonwhite race (aOR = 0.49, 95% CI = 0.29-0.84). CONCLUSIONS: Approximately one in two cancer patients was willing to use insurance-covered acupuncture for pain. Willingness was influenced by patients' attitudes and beliefs, which are potentially modifiable through counseling and education. Further research on racial disparities is needed to close the gap in utilization as acupuncture is integrated into insurance plans in response to the opioid crisis.

Efficacy of a web-based women's health survivorship care plan for young breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivorship care plans (SCP) have limited content addressing women's health issues. This trial tested if young breast cancer survivors who receive a web-based, women's health SCP were more likely to improve on at least one of the four targeted issues (hot flashes, fertility-related concerns, contraception, and vaginal symptoms) compared to attention controls. METHODS: A randomized controlled trial recruited female survivors ages 18-45 at diagnosis, 18-50 at enrollment, completed primary cancer treatment, and had a significant women's health issue: moderate or higher fertility-related concerns; ≥ 4 hot flashes/day with ≥ 1 of moderate severity; ≥ 1 moderate vaginal atrophy symptoms; or not contracepting/using less effective methods. Survivors underwent stratified, block randomization with equal allocation to intervention and control groups. The intervention group accessed the online SCP; controls accessed curated resource lists. In intention-to-treat analysis, the primary outcome of improvement in at least one issue by 24 weeks was compared by group. RESULTS: 182 participants (86 intervention, 96 control), mean age 40.0 ± 5.9 and 4.4 ± 3.2 years since diagnosis, were randomized. 61 intervention group participants (70.9%) improved, compared to 55 controls (57.3%) (OR 1.82, 95% CI 0.99-3.4, p = 0.057). The following issue-specific improvements were observed in the intervention versus control arms: fertility-related concerns (27.9% vs. 14.6%, OR 2.3, 95% CI 1.1-4.8); hot flashes (58.5% vs. 55.8%, OR 1.1, 95% CI 0.57-2.2); vaginal symptoms (42.5% vs. 40.7%, OR 1.1, 95% CI 0.6-2.0); contraception (50% vs. 42.6%, OR 1.4, 95% CI 0.74-2.5). CONCLUSIONS: In young breast cancer survivors, a novel, web-based SCP did not result in more change in the primary outcome of improvement in at least one of the four targeted women's health issues, than the attention control condition. The intervention was associated with improved infertility concerns, supporting efficacy of disseminating accessible, evidence-based women's health information to this population.

Utilization of integrative medicine differs by age among pediatric oncology patients.

PURPOSE: Coping with symptoms related to cancer treatment is challenging for pediatric patients with cancer and their caregivers. Additionally, caring for pediatric patients requires specialized expertise to incorporate age-appropriate interventions to improve outcomes. Despite the increase in pediatric inpatient integrative medicine (IM) therapies, there is a paucity of knowledge about whether the utilization of IM therapies differs by patient age. METHODS: We conducted a retrospective analysis on IM utilization among pediatric inpatients between 2008 and 2016 in a tertiary urban cancer center using electronic medical records. Multivariable logistic regression models examined the relationship between age and specific type of IM utilization, adjusting for specific demographic factors. RESULTS: Between 2008 and 2016, the pediatric inpatient IM service had 20 686 visits and treated 1877 unique patients. A significant age difference (P < 0.001) by modality was noted: dance therapy (mean age ± standard deviation: 5.9 ± 5.3 years), music therapy (8.0±7.0 years), mind-body therapies (13.0 ± 7.7 years), massage (14.5 ± 7.8 years), and acupuncture (20.0 ± 7.9 years). In multivariable analysis, the association between age and use of specific IM therapies remained significant (P < 0.001 for all). CONCLUSION: Specific types of inpatient IM therapy usage significantly differed by the age of pediatric patients with cancer; therefore, designing and providing age-appropriate IM interventions with consideration for developmental stage are needed to ensure that the most appropriate and effective therapies are provided to children with cancer.

Understanding the Use of Acupuncture for Insomnia Among Cancer Survivors: A Qualitative Study.

OBJECTIVE: To understand cancer survivors' perceptions regarding the use of acupuncture for the treatment of cancer-related insomnia. DESIGN: Semistructured interviews with cancer survivors participating in a randomized controlled trial comparing the effectiveness of Cognitive Behavioral Therapy for Insomnia (CBT-I) and acupuncture for the treatment of insomnia. Interviews were conducted before randomization into either treatment option, and structured to elicit participants' experiences with insomnia as well as their beliefs and understanding surrounding acupuncture for the treatment of insomnia. An integrated approach was used for data analysis. SUBJECTS: Sixty-three cancer survivors with DSM-V diagnosed insomnia. RESULTS: Participants shared a broad lack of understanding regarding acupuncture for the treatment of insomnia. Specifically, individuals in this study expressed confusion surrounding what symptoms or medical conditions acupuncture could be used to treat, how acupuncture works, and how long the effects of acupuncture last. CONCLUSIONS: This study identified three specific gaps in knowledge, including treatment target, mechanism, and durability, surrounding the use of acupuncture for insomnia in cancer survivors. Addressing these gaps by providing appropriate and timely education surrounding the use of acupuncture to treat insomnia is essential to increase the evidence-informed utilization of acupuncture and to better meet patients' needs among cancer survivors.

Barriers to physical activity: a study of academic and community cancer survivors with pain.

PURPOSE: Despite the numerous benefits of physical activity (PA) for patients with cancer, many cancer survivors report challenges to participating in PA. The objectives of this study were (1) to assess barriers to PA and (2) to examine participant characteristics associated with modifiable barriers to PA among cancer survivors with pain. METHODS: We conducted a cross-sectional survey study at one academic medical center and 11 community hospitals. Participants completed the 12-item Physical Activity Barriers After Cancer (PABAC) instrument (Cronbach's alpha = 0.75). Multivariable regression models examined participant characteristics associated with PABAC scores with a higher score indicating more barriers to PA. RESULTS: Among 662 survivors, 67% had moderate or severe pain (rating 4 or greater on a scale of 0 to 10). Seventy-five percent of survivors did not meet the American Cancer Society PA recommendations on average, and these individuals had higher mean PABAC scores (beta coefficient (ß) = 2.02, 95% confidence interval (CI) 0.96-3.09, p < 0.001). In adjusted analyses, cancer survivors who were non-white (ß = 1.55, 0.28-2.82, p = 0.02), treated at a community hospital (ß = 1.07, 0.09-2.05, p = 0.03), had surgery (ß = 1.69, 0.69-2.69, p = 0.001), or within 12 months of diagnosis (ß = 1.15, 0.20-2.10, p = 0.02) reported greater barriers to PA. CONCLUSIONS: The majority of cancer survivors with pain are not adequately participating in PA. Key demographic and clinical characteristics are associated with survivors' barriers. IMPLICATIONS FOR CANCER SURVIVORS: Efforts to overcome specific barriers are needed to promote PA after a cancer diagnosis.