Impact of the Integrative Oncology Scholars Program on Oncology Providers' Key Knowledge of Dietary Supplements and Antioxidants for Providing Evidence-based Oncology Care.

Dietary supplements are commonly used among cancer survivors. Oncology providers rarely receive training about dietary supplements. We evaluated whether e-learning modules could improve oncology providers' dietary supplement knowledge. Oncology providers participated in the National Cancer Institute funded Integrative Oncology Scholars (IOS) program. We used posttest readiness assurance tests (RAT) to measure knowledge acquisition from modules. One cohort completed a pre and posttest RAT to assess change in knowledge. Multivariate linear regression models adjusted for gender, race, profession, and years in practice were used to determine if these characteristics were associated with posttest RAT performance and change in pre to posttest RAT scores. Scholars (N = 101) included 86% (N = 87) females; age 44 ± 10 years; 72% (N = 73) Non-Hispanic White; years in practice mean range 11-15 ± 10. There were 37 physicians, 11 physician assistants, 23 nurses, 21 social workers, 2 psychologists, 4 pharmacists, and 2 physical therapists. The posttest dietary supplement and antioxidant RAT scores for all Scholars were 67 ± 18% and 71 ± 14%. In adjusted models there were no significant associations between dietary supplement and antioxidant posttest RAT scores with Scholar characteristics. Change in RAT scores for dietary supplement and antioxidants were 25% ± 23 and 26% ± 27 (P < 0.0001). In adjusted models, there were no significant predictors of change in dietary supplement RATs. For antioxidant RATs, profession was associated with change in scores (P = 0.021). Improvement in Scholar's test scores demonstrate the IOS program can significantly increase oncology providers' knowledge of dietary supplements and antioxidants.

Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study.

BACKGROUND: Oxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. METHODS: Patients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.

How to Make Evidence-Based Integrative Medicine a Part of Everyday Oncology Practice.

Integrativety oncology (IO) is a "patient-centered, evidence-informed field of comprehensive cancer care that utilizes mind-body practices, natural products, and lifestyle modifications from different traditions alongside conventional cancer treatments." There is an urgent need to educate oncology health care providers on the fundamentals of evidence-based IO to meet the needs of people with cancer. In this chapter, we aim to provide oncology professionals with actionable guidance on the basis of the Society for Integrative Oncology (SIO)-American Society of Clinical Oncology (ASCO) guidelines on integrative medicine use during oncology visits to help alleviate symptoms and side effects in people with cancer during and after treatment.

Neighborhood attributes and cardiovascular disease risk in breast cancer survivors: The Pathways Study.

BACKGROUND: Breast cancer survivors are at a higher risk of cardiovascular disease (CVD) morbidity and mortality compared with the general population. The impact of objective social and built neighborhood attributes on CVD risk in a cohort of female breast cancer survivors was examined. METHODS: The 3975 participants came from the Pathways Study, a prospective cohort of women with invasive breast cancer from an integrated health care system in northern California. Women diagnosed with breast cancer from 2006 through 2013 were enrolled on average approximately 2 months after diagnosis. Their baseline addresses were geocoded and appended to neighborhood attributes for racial/ethnic composition, socioeconomic status (SES), population density, urbanization, crime, traffic density, street connectivity, parks, recreational facilities, and retail food environment. Incident CVD events included ischemic heart disease, heart failure, cardiomyopathy, or stroke. Cox proportional hazards models estimated associations of neighborhood attributes with CVD risk, which accounted for clustering by block groups. Fully adjusted models included sociodemographic, clinical, and behavioral factors. RESULTS: During follow-up through December 31, 2018, 340 participants (8.6%) had CVD events. A neighborhood racial/ethnic composition measure, percent of Asian American/Pacific Islander residents (lowest quintile hazard ratio [HR], 1.85; 95% CI, 1.03-3.33), and crime index (highest quartile HR, 1.48; 95% CI, 1.08-2.03) were associated with the risk of CVD events independent of individual SES, hormone receptor status, treatment, cardiometabolic comorbidities, body mass index, and physical activity. CONCLUSIONS: With the application of a socio-ecological framework, how residential environments shape health outcomes in women with breast cancer and affect CVD risk in this growing population can be understood.

Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study.

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements. OBJECTIVES: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk. METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the 6-y study examination. RESULTS: We observed a total of 110 dietary supplement-metabolite associations that met the criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity, and number of medications (adjusted P < 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n = 15), including positive associations with oxalate, tartronate, threonate, and isocitrate, which were each in turn protective for the risk of incident diabetes. Vitamin C was also associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid related compounds including α-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamine or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with γ-glutamylvaline, levels of which were positively associated with the risk of diabetes. CONCLUSIONS: Our data point to potential metabolite changes associated with vitamin C and B vitamins, which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding the health effects of dietary supplements and identify potential biological mediators.

Effects of acupuncture to decrease adverse events in patients with high-risk non-muscle invasive bladder cancer receiving induction intravesical BCG therapy: Study protocol for a randomized, controlled pilot and feasibility study.

Background: Treatment-related serious adverse events (SAEs) are common in patients receiving intravesical Bacillus Calmette-Guerin (BCG) for the treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC). Here we describe the protocol of a randomized, attention/waitlist-controlled feasibility pilot study testing the use of acupuncture to decrease SAEs and treatment interruptions in this population. The primary objectives are to evaluate the feasibility and efficacy of conducting pre-procedure acupuncture in a Urology Clinic. Methods: A total of 45 patients will be recruited and randomized in a 2:1 ratio (treatment arm: attention/waitlist control). Eligibility criteria include 1) age 18 years or older, 2) English-speaking, 3) high-risk NMIBC, 4) no acupuncture in the previous 3 months, and 5) willing and able to participate in trial activities. Patients in the treatment arm will receive acupuncture prior to weekly BCG for a total of six weeks. Methods were developed to train and monitor research acupuncturists and included online and in-person training, study manuals, and monthly meetings throughout the study period. Feasibility assessments include evaluation of the recruitment, retention and protocol adherence to acupuncture treatment, and measurement of CTCAE v5.0 adverse events specific to acupuncture, and clinic staff surveys regarding the intervention impact on clinic workflow. Efficacy measures will be compared between treatment and control groups including: EORTC-QLQ-NMIBC-24, EORTC-QLQ-C30, CTCAE v5.0, medication journal, healthcare utilization, current use of complementary, alternative, and integrative therapies, and acupuncture expectancy and treatment preference. Trial results will inform the design of a multi-center trial to expand testing of the protocol to a larger patient cohort.

Comparison of Acupuncture vs Sham Acupuncture or Waiting List Control in the Treatment of Aromatase Inhibitor-Related Joint Pain: A Randomized Clinical Trial.

Importance: Aromatase inhibitors (AIs) have proven efficacy for the treatment of hormone-sensitive breast cancer; however, arthralgias (pain and stiffness) contribute to nonadherence with therapy for more than 50% of patients. Objective: To examine the effect of acupuncture in reducing AI-related joint pain through 52 weeks. Design, Setting, and Participants: A randomized clinical trial was conducted at 11 sites in the US from May 1, 2012, to February 29, 2016, with a scheduled final date of follow-up of September 5, 2017, to compare true acupuncture (TA) with sham acupuncture (SA) or waiting list control (WC). Women with early-stage breast cancer were eligible if they were taking an AI and scored 3 or higher on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain). Analysis was conducted for data received through May 3, 2021. Interventions: Participants were randomized 2:1:1 to the TA (n = 110), SA (n = 59), or WC (n = 57) group. The TA and SA protocols were composed of 6 weeks of intervention at 2 sessions per week (12 sessions overall), followed by 6 additional weeks of intervention with 1 session per week. Participants randomized to WC received no intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52. Main Outcomes and Measures: In this long-term evaluation, the primary end point was the 52-week BPI-WP score, compared by study group using linear regression, adjusted for baseline pain and stratification factors. Results: Among 226 randomized women (mean [SD] age, 60.7 [8.6] years; 87.7% White; mean [SD] baseline BPI-WP score, 6.7 [1.5]), 191 (84.5%) completed the trial. In a linear regression, 52-week mean BPI-WP scores were 1.08 (95% CI, 0.24-1.91) points lower in the TA compared with the SA group (P = .01) and were 0.99 (95% CI, 0.12-1.86) points lower in the TA compared with the WC group (P = .03). In addition, 52-week BPI pain interference scores were statistically significantly lower in the TA compared with the SA group (difference, 0.58; 95% CI, 0.00-1.16; P = .05). Between 24 and 52 weeks, 12 (13.2%) of TA, 6 (11.3%) of SA, and 5 (10.6%) of WC patients reported receipt of acupuncture. Conclusions and Relevance: In this randomized clinical trial, women with AI-related joint pain receiving 12 weeks of TA had reduced pain at 52 weeks compared with controls, suggesting long-term benefits of this therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01535066.

Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline.

PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other health care providers on integrative approaches to managing pain in patients with cancer. METHODS: The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included pain intensity, symptom relief, and adverse events. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 227 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: Among adult patients, acupuncture should be recommended for aromatase inhibitor-related joint pain. Acupuncture or reflexology or acupressure may be recommended for general cancer pain or musculoskeletal pain. Hypnosis may be recommended to patients who experience procedural pain. Massage may be recommended to patients experiencing pain during palliative or hospice care. These recommendations are based on an intermediate level of evidence, benefit outweighing risk, and with moderate strength of recommendation. The quality of evidence for other mind-body interventions or natural products for pain is either low or inconclusive. There is insufficient or inconclusive evidence to make recommendations for pediatric patients. More research is needed to better characterize the role of integrative medicine interventions in the care of patients with cancer.Additional information is available at https://integrativeonc.org/practice-guidelines/guidelines and www.asco.org/survivorship-guidelines.

Integrative Oncology Education: An Emerging Competency for Oncology Providers.

A growing number of cancer patients use complementary and alternative therapies during and after conventional cancer treatment. Patients are often reluctant to discuss these therapies with their oncologist, and oncologists may have limited knowledge and confidence on how to advise patients on the appropriate use. Integrative oncology is a patient-centered, evidence-informed field that utilizes mind-body practices, lifestyle modifications and/or natural products interwoven with conventional cancer treatment. It prioritizes safety and best available evidence to offer appropriate interventions alongside conventional care. There are few opportunities for oncologists to learn about integrative oncology. In this commentary, we highlight the Integrative Oncology Scholars (IOS) program as a means to increase competency in this growing field. We provide an overview of several integrative oncology modalities that are taught through this program, including lifestyle modifications, physical activity, and mind-body interventions. We conclude that as more evidence is generated in this field, it will be essential that oncology healthcare providers are aware of the prevalent use of these modalities by their patients and cancer centers include Integrative Oncology trained physicians and other healthcare professionals in their team to discuss and recommend evidence-based integrative oncology therapies alongside conventional cancer treatments to their patients.

Helping Patients Eat Better During and Beyond Cancer Treatment: Continued Nutrition Management Throughout Care to Address Diet, Malnutrition, and Obesity in Cancer.

Cancer patients and survivors are at risk of poor clinical outcomes due to poor nutritional intake following cancer diagnosis. During cancer treatment, treatment toxicities can affect eating patterns and can lead to malnutrition resulting in loss of lean body mass and excessive weight loss. Following treatment and throughout survivorship, patients are at risk of not meeting national nutrition guidelines for cancer survivors, which can affect recurrence and survival. Obesity, which is highly prevalent in cancer patients and survivors, can affect clinical outcomes during treatment by masking malnutrition and is also a risk factor for cancer recurrence and poorer survival in some cancers. Appropriate and effective nutritional education and guidance by trained clinicians are needed throughout the cancer continuum. This article presents an overview of recommendations and guidelines for nutrition and weight management and provides recent examples of behavioral theory-based targeted lifestyle interventions designed to increase adherence to recommendation by cancer patients and survivors.

Integrative Oncology Scholars Program: A Model for Integrative Oncology Education.

OBJECTIVES: Oncology providers are often confronted by patients who use complementary or alternative therapies, but have limited knowledge or confidence on how to advise patients on appropriate use. Despite this, there are few opportunities for oncology providers to learn about complementary or alternative therapies, while at the same time there is a high demand for integrative oncology (IO) training. To address a gap in IO educational opportunities, and particularly for nonphysicians, we created the Integrative Oncology Scholars (IOS) Program. The program's goal is to train 100 IO leaders and facilitate partnerships between them and complementary practitioners. DESIGN: Four iterations of a year-long National Cancer Institute-funded educational program that combines in-person team-based learning and eLearning to teach the evidence, application, and philosophy supporting IO. SETTINGS: In-person sessions take place at the University of Michigan, and eLearning is implemented using a Canvas website (Instructure, Inc., Salt Lake City, UT). SUBJECTS: Nurses, social workers, physician assistants, psychologists, physicians, pharmacists, and physical/occupational therapists with active oncology practices. Educational intervention: Four cohorts of 25 oncology providers per year will learn the evidence base for complementary and alternative approaches to a wide number of oncology topics, including symptom control, dietary supplements commonly used by cancer patients, diet, and the utility of specific integrative approaches for common oncology side-effects such as fatigue. OUTCOME MEASURES: A mixed methods approach will be used to evaluate overall IOS Program progress and individual scholar's impact on IO research, education, and clinical endeavors. RESULTS: The first cohort of 25 IOS has been recruited and their education will begin in Summer 2018. Scholars come from 13 states and represent 23 different healthcare systems. CONCLUSIONS: The IOS Program has the potential to increase the number of trained IO providers, educators, and researchers in the United States.

Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927).

PURPOSE: Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results. METHODS: We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I-III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0-10). RESULTS: Among the 249 participants, 139 had BMI < 30 kg/m2 (56%) and 110 had BMI ≥ 30 kg/m2 (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p = 0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p = 0.28; interaction p = 0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p = 0.005 and p = 0.01, respectively). CONCLUSIONS: In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.

Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial.

Importance: Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors and often result in therapy discontinuation. Small studies suggest that acupuncture may decrease aromatase inhibitor-related joint symptoms. Objective: To determine the effect of acupuncture in reducing aromatase inhibitor-related joint pain. Design, Setting, and Patients: Randomized clinical trial conducted at 11 academic centers and clinical sites in the United States from March 2012 to February 2017 (final date of follow-up, September 5, 2017). Eligible patients were postmenopausal women with early-stage breast cancer who were taking an aromatase inhibitor and scored at least 3 on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain). Interventions: Patients were randomized 2:1:1 to the true acupuncture (n = 110), sham acupuncture (n = 59), or waitlist control (n = 57) group. True acupuncture and sham acupuncture protocols consisted of 12 acupuncture sessions over 6 weeks (2 sessions per week), followed by 1 session per week for 6 weeks. The waitlist control group did not receive any intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52. Main Outcomes and Measures: The primary end point was the 6-week BPI-WP score. Mean 6-week BPI-WP scores were compared by study group using linear regression, adjusted for baseline pain and stratification factors (clinically meaningful difference specified as 2 points). Results: Among 226 randomized patients (mean [SD] age, 60.7 [8.6] years; 88% white; mean [SD] baseline BPI-WP score, 6.6 [1.5]), 206 (91.1%) completed the trial. From baseline to 6 weeks, the mean observed BPI-WP score decreased by 2.05 points (reduced pain) in the true acupuncture group, by 1.07 points in the sham acupuncture group, and by 0.99 points in the waitlist control group. The adjusted difference for true acupuncture vs sham acupuncture was 0.92 points (95% CI, 0.20-1.65; P = .01) and for true acupuncture vs waitlist control was 0.96 points (95% CI, 0.24-1.67; P = .01). Patients in the true acupuncture group experienced more grade 1 bruising compared with patients in the sham acupuncture group (47% vs 25%; P = .01). Conclusions and Relevance: Among postmenopausal women with early-stage breast cancer and aromatase inhibitor-related arthralgias, true acupuncture compared with sham acupuncture or with waitlist control resulted in a statistically significant reduction in joint pain at 6 weeks, although the observed improvement was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT01535066.

Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement of the SIO Clinical Practice Guideline.

Purpose The Society for Integrative Oncology (SIO) produced an evidence-based guideline on use of integrative therapies during and after breast cancer treatment that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. ASCO considered the guideline for endorsement. Methods The SIO guideline addressed the use of integrative therapies for the management of symptoms and adverse effects, such as anxiety and stress, mood disorders, fatigue, quality of life, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Interventions of interest included mind and body practices, natural products, and lifestyle modifications. SIO systematic reviews focused on randomized controlled trials that were published from 1990 through 2015. The SIO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. Results The ASCO Expert Panel determined that the recommendations in the SIO guideline-published in 2017-are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline with a few added discussion points. Recommendations Key recommendations include the following: Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-l-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy because of a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related adverse effects. Additional information is available at: www.asco.org/supportive-care-guidelines .

Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715).

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes. Acetyl-L-carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients in this trial. Methods: S0715 was a randomized, double-blind, multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer. CIPN was measured by the 11-item neurotoxicity (NTX) component of the FACT-Taxane scale at weeks 12, 24, 36, 52, and 104. We examined NTX scores over two years using linear mixed models for longitudinal data. Individual time points were examined using linear regression. Regression analyses included stratification factors and the baseline score as covariates. All statistical tests were two-sided. Results: Four-hundred nine subjects were eligible for evaluation. Patients receiving ALC had a statistically significantly (P = .01) greater reduction in NTX scores (worse CIPN) of -1.39 points (95% confidence interval [CI] = -2.48 to -0.30) than the placebo group. These differences were particularly evident at weeks 24 (-1.68, 95% CI = -3.02 to -0.33), 36 (-1.37, 95% CI = -2.69 to -0.04), and 52 (-1.83, 95% CI = -3.35 to -0.32). At 104 weeks, 39.5% on the ALC arm and 34.4% on the placebo arm reported a five-point (10%) decrease from baseline. For both treatment groups, 104-week NTX scores were statistically significantly different compared with baseline (P < .001). Conclusions: For both groups, NTX scores were reduced from baseline and remained persistently low. Twenty-four weeks of ALC therapy resulted in statistically significantly worse CIPN over two years. Understanding the mechanism of this persistent effect may inform prevention and treatment strategies. Until then, the potential efficacy and harms of commonly used supplements should be rigorously studied.