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INTRODUCTION: As pharmacological strategies remain limited for relieving fatigue and associated cognitive symptoms, integrative modalities such as traditional Chinese medicine (TCM) could be explored as therapeutic strategies in cancer survivors. Here, we evaluate and report the efficacy and safety of a TCM concoction, modified Xiang Bei Yang Rong Tang (XBYRT), on quality of life (QOL), cancer-related fatigue (CRF), and cognitive symptoms, compared to placebo. METHODS: In a single-centered, randomized, double-blinded, placebo-controlled pilot trial conducted from 2019 to 2022, fatigued cancer survivors ≥21 years old were recruited to receive the XBYRT intervention or placebo (5% diluted) once daily for the duration of 8 weeks. Patient-reported outcomes for QOL, CRF, cognition, blood samples for biomarker testing, and adverse events were collected at baseline (T0), 4 weeks (T1), 8 weeks (T2), and 10 weeks (T3) after baseline. Linear regression was performed to evaluate differences between groups at T2 and T3. RESULTS: A total of 1502 patients were screened, with 672 patients considered eligible. Of the eligible, 15 XBYRT and 13 placebo subjects with similar mean ages (58.5 vs 58.4) were recruited. Both groups were predominantly Chinese (93% vs 62%), breast cancer patients (87% vs 62%), and diagnosed with stage 2 cancer (60% vs 46%). Although no significant difference was found in QOL between groups, the XBYRT group exhibited improved emotional fatigue at T3 (P = .045) and higher BDNF levels at T2 (P = .047) and T3 (P = .029). After baseline adjustment, XBYRT was associated with better perceived cognitive impairment at T2 (P = .011) and T3 (P = .017), as well as overall perceived cognitive function at T3 (P = .028). XBYRT is well tolerated, with grade 3 adverse events reported in three XBYRT (20%) and two placebo (15%) subjects. CONCLUSION: In this pilot study, XBYRT as an integrative therapy is safe and generates encouraging improvements in cognitive and fatigue symptoms. Difficulties with recruitment limited the generalizability of trial findings, thus findings should be verified through a larger, multi-centered trial.

Brain-derived neurotrophic factor (BDNF) improves cognitive function by stimulating neurogenesis and neuroplasticity. We hypothesize that higher plasma BDNF levels are protective against cognitive toxicity among adolescent and young adult cancer patients (15-39 years old). In a prospective, longitudinal study, we recruited 74 newly diagnosed cancer and 118 age-matched non-cancer controls who completed the Cambridge Neuropsychological Test Automated Battery (CANTAB), Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) and blood draws. Plasma BDNF was quantified using an enzyme-linked immunosorbent assay. Genomic DNA from buffy coat was genotyped for BDNF Val66Met. Most cancer participants were diagnosed with breast (24%) and head/neck (22%) cancers. After adjusting for sociodemographic variables (age, gender, race, marital status, education years), cancer participants had lower BDNF levels (ng/mL) at baseline (median: 10.7 vs 21.6, p

BackgroundThere is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study.MethodsNewly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF]).ResultsWe recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p

PurposeThe purpose of this study is to investigate how different cancer-related symptoms influence work outcomes among cancer survivors.MethodsA literature search was performed in PubMed, EMBASE, CINAHL, PsycINFO, and Scopus to identify studies published between 1st January 1999 and 30th October 2020 that investigated the impact of specific cancer-related symptoms on work outcomes among cancer survivors who have completed primary antineoplastic treatment. Study findings were extracted and grouped by symptoms and work outcomes, allowing comparison of associations between these outcomes.ResultsSeventy-three articles representing 68 studies were eligible for inclusion. From these studies, 27 cancer-related symptoms, 9 work outcomes, and 68 unique associations between specific symptoms and work outcomes were identified. Work status (return to work and employment rates) was most commonly studied, and symptom burden was mainly measured from the patient's perspective. Higher symptom burden was generally associated with trends of poorer work outcomes. Significant associations were reported in most studies evaluating body image issues and work status, oral dysfunction and work status, fatigue and work ability, and depression and work ability.ConclusionSeveral cancer-related symptoms were consistently associated with inferior work outcomes among cancer survivors. Body image issues and oral dysfunction were shown to be associated with poorer employment rates, while fatigue and depression were linked to lower levels of work performance.Implications for cancer survivorsFailure to return to work and decreased productivity post-cancer treatment can have negative consequences for cancer survivors and society at large. Findings from this review will guide the development of work rehabilitation programs for cancer survivors.Protocol registrationPROSPERO identifier CRD42020187754.

PurposeCurrently, limited information is available on care provided to breast cancer survivors in Singapore. This study aims to assess the quality of post-treatment cancer survivorship care among breast cancer survivors on the basis of compliance with international guidelines up to 5 years post-primary treatment.MethodsThis study analyzed a cohort of 189 nonmetastatic breast cancer survivors recruited from the National Cancer Centre Singapore, Changi General Hospital, and KK Women's and Children's Hospital between November 2011 and September 2015. Data were retrieved from electronic medical records in 6-month intervals. Adherence to guidelines was assessed in four areas: (1) recurrent cancer surveillance, (2) monitoring and detecting late effects, (3) health care resource utilization, and (4) preventive care. Descriptive statistics, Kaplan-Meier, and regression analyses were conducted.ResultsAnnual surveillance mammogram adherence rates were ≥ 83% consistently. The most common new diagnosis was osteoporosis at an incidence rate of 102 (95% CI, 77.6 to 135) cases per 1,000 person-years. Overall, ≤ 10.1% of survivors had an emergency department or hospitalization visit. Oncologist services were overutilized, with a median of 6 (interquartile range: 4-10) visits in the first 6 months before reducing to a median of 2 (interquartile range: 1-3) visits biannually 3 years post-treatment. Bone mineral density test utilization rate adhered to guidelines for 92.2% of aromatase inhibitor recipients but only for 36.4% of premenopausal tamoxifen recipients.ConclusionOverall, adherence rates to surveillance and osteoporosis preventive care were high. Extensive utilization of oncologist services up to 5 years post-primary treatment could be reversed with strategies to engage and coordinate survivorship care with primary care providers, leveraging their strengths to improve adherence to health promotion and chronic disease management.

The purpose of this study is to elucidate how patient-reported cognitive symptoms manifest from variations in hormone levels or precursors such as dehydroepiandrosterone (DHEA) and its sulfated form [collectively termed as DHEA(S)] and to investigate their association in breast cancer survivors. Levels of estradiol and DHEA(S) were compared between early-stage breast cancer patients with and without cancer-related cognitive impairment (CRCI) during adjuvant chemotherapy. Data were analyzed from 242 patients (mean age ± SD = 50.8 ± 9.2 years) who had completed FACT-Cog v.3.0, blood draws and questionnaires. Regression model was used to fit the magnitude of change in each respective biomarker levels against overall cognitive impairment status while adjusting for clinically important covariates. There was reduction in mean plasma levels of estradiol and DHEAS during and towards the end of chemotherapy (p-values

PurposeTo identify subgroups of female breast cancer patients with distinct self-reported employment interference (EI) profiles and determine which demographic, clinical, and symptom characteristics, and quality of life outcomes were associated with subgroup membership.MethodsWomen with breast cancer (n = 385) were assessed for changes in EI over ten times, from prior to, through 12 months after breast cancer surgery. Latent profile analysis (LPA) was used to identify subgroups of patients with distinct EI profiles.ResultsThree distinct EI profiles (i.e., None - 26.2% (n = 101), Low - 42.6% (n = 164), High - 31.2% (n = 120)) were identified. Compared to the None and Low groups, patients in the High group were more likely to be younger. Higher proportions in the High group were non-White, pre-menopausal prior to surgery, had more advanced stage disease, had received an axillary lymph node dissection, had received neoadjuvant chemotherapy, had received adjuvant chemotherapy, and had a re-excision or mastectomy on the affected breast within 6 months after surgery. In addition, these patients had lower quality of life scores. Compared to the None group, the High group had higher levels of trait and state anxiety, depressive symptoms, fatigue and sleep disturbance and lower levels of cognitive function.ConclusionsThis study provides new knowledge regarding EI profiles among women in the year following breast cancer surgery. The non-modifiable risk factors (e.g., younger age, being non-White, having more advanced stage disease) can inform current screening procedures. The potentially modifiable risk factors can be used to develop interventions to improve employment outcomes of breast cancer patients.

Cytokines facilitate the peripheral immune and cerebral response, through their ability to modulate the expression of brain derived neurotrophic factor (BDNF). Cytokines and BDNF are implicated in cancer-related cognitive impairment (CRCI), but their relationship has not been clearly defined for this condition. The aim of this study was to evaluate the associations of cytokines and BDNF among early stage breast cancer (ESBC) patients with different CRCI trajectories. This was a multicenter longitudinal study involving 136 ESBC patients. CRCI was assessed using the FACT-Cog (V3) questionnaire. Plasma cytokines and BDNF levels were quantified at three time points throughout chemotherapy. The associations between cytokines and BDNF were analyzed using linear mixed models, with interaction terms for CRCI status. All cytokines analyzed showed inverse associations with BDNF levels. There was a significant interaction between IL-6 and the persistent impairment trajectory, which would impact on BDNF levels (p = 0.026). The inverse associations with BDNF were more pronounced for IFN-γ, IL-1β, IL-4, IL-8, and GM-CSF in patients with persistent CRCI. The coefficient values for IL-2, IL-4, and TNF-α also indicate that there was a greater magnitude of decrease in BDNF level for every unit of cytokine increase in patients with acute and persistent CRCI, compared to patients without CRCI. The differential associations between cytokines and BDNF may be indicative of probable susceptibility to the elevation of cytokines. Further research is required to elucidate the specific associations of cytokines and BDNF, along with their contributions to acute and persistent CRCI.

The Oncology Pharmacy Team (OPT), consisting of specialty-trained pharmacists and/or pharmacy technicians, is an integral component of the multidisciplinary healthcare team (MHT) involved with all aspects of cancer patient care. The OPT fosters quality patient care, safety, and local regulatory compliance. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on five key areas: 1) oncology pharmacy practice as a pharmacy specialty; 2) contributions to patient care; 3) oncology pharmacy practice management; 4) education and training; and 5) contributions to oncology research and quality initiatives to involve the OPT. This position statement advocates that: 1) the OPT be fully incorporated into the MHT to optimize patient care; 2) educational and healthcare institutions develop programs to continually educate OPT members; and 3) regulatory authorities develop certification programs to recognize the unique contributions of the OPT in cancer patient care.

BackgroundCancer-related fatigue (CRF) is a debilitating condition which commonly affects cancer survivors. The management of CRF remains a challenge due to the lack of effective pharmacological interventions. Traditional Chinese medicine (TCM) could be a potential therapeutic option for CRF. The modified Xiang Bei Yang Rong Tang (XBYRT) is a TCM herbal decoction, formulated to improve fatigue symptoms in cancer survivors. This clinical trial aims to evaluate the efficacy and safety of XBYRT in improving CRF and quality of life (QOL) of cancer survivors.MethodsThis is a single centre, randomized, double-blind, placebo-controlled, parallel trial. Eighty cancer survivors will be recruited and randomized to receive the XBYRT or placebo decoction, in a ratio of 1:1. Participants will consume the XBYRT/placebo decoction daily for 8 weeks and undergo assessments at baseline and 4, 8 and 10 weeks after baseline. The participants will be assessed for patient-reported outcomes (PRO), blood biomarkers and adverse events at each time point. The primary outcome is the overall health and QOL status, at 8 weeks follow-up. The secondary outcomes are the effects of XBYRT on fatigue levels, cancer-related cognitive impairment and QOL, as assessed by PRO. The incidence of adverse events and the effects of the XBYRT decoction on blood biomarkers associated with CRF will also be evaluated.DiscussionEfficacy and safety outcomes from this trial will provide important clinical data to guide future large-scale randomized controlled trials, and the evaluation of the objective blood biomarkers can help to delineate the biological mechanisms of CRF.Trial registration numberClinicalTrials.gov NCT04104113 . Registered on 26 September 2019.

PURPOSE: A breast cancer diagnosis has a substantial economic impact. Study aims were to evaluate for inter-individual differences in cancers level of interference with employment and identify phenotypic and symptom characteristics associated with higher levels of interference. METHODS: Patients (n = 387) were enrolled prior to breast cancer surgery and followed for 12 months. Interference with employment was measured using a 0 (no problem) to 10 (severe problem) numeric rating scale. Hierarchical linear modeling (HLM) was used to evaluate for inter-individual differences in trajectories of employment interference and characteristics associated with employment interference at enrollment and over 12 months. RESULTS: Patients mean age was 55.0 (±11.7) years and the majority underwent breast conservation surgery (80.6%). Mean employment interference score was 3.2 (±3.7). Unconditional model for employment interference demonstrated a decreasing linear trend (-.076/month). Younger age, lower income, higher pain intensity, and having an axillary lymph node dissection were associated with higher pre-surgical interference scores. Having a sentinel lymph node biopsy was associated with ongoing employment interference scores. Higher sleep disturbance scores were associated with both initial and ongoing employment interference scores. Receipt of chemotherapy, use of complementary or alternative therapies, and re-excision or mastectomy following surgery were significant time varying covariates. CONCLUSION: This study is the first to use HLM to describe inter-individual differences in the trajectories of cancers interference with employment and associated factors prior to and for 12 months following breast cancer surgery. Patients with the identified risk factors warrant ongoing assessments of employment interference and appropriate referrals.

ObjectiveCancer-related cognitive impairment (CRCI) among adolescent and young adult (AYA) cancer patients with noncentral nervous system (CNS) cancers has not been well studied. In this study, we aimed to describe CRCI-associated trends and characteristics among AYA cancer patients.MethodsIn a longitudinal cohort of AYA cancer patients without CNS disease, CRCI was evaluated over 1 year using the Functional Assessment of Cancer Therapy-Cognitive Function Instrument, a self-reported cognitive outcome measure. CRCI prevalence was quantified using the previously established minimal clinically important difference. CRCI-associated longitudinal trends and factors were evaluated with mixed-effects model analysis.ResultsNinety-one patients (mean age = 28.4 ± 6.7 years) were included. Approximately one-third (34.1%) experienced CRCI at least once during the study follow-up. Female gender (P = .02), Indian ethnicity (P

Purpose: With an increasing focus on developing survivorship services tailored for adolescent and young adult (AYA) cancer survivors, incorporation of viewpoints from both survivors and health care professionals (HCPs) is important. This study aims to explore the perceptions of current and prospective survivorship services from both groups in Singapore to propose service design and delivery strategies. Methods: Focus group discussions with 23 AYA cancer survivors between the ages of 16 and 39 years at diagnosis and 18 HCPs were conducted in National Cancer Centre Singapore (NCCS) and Singapore Cancer Society (SCS). All focus group discussions were transcribed verbatim. Deductive thematic analysis was performed according to the components of a design thinking model: empathizing with AYA survivors, defining care gaps, proposing services, and implementation strategies. Results: AYA survivors preferred age-specific services that are aligned with their personal goals. Current survivorship care failed to address the needs of survivors' dependents (caregivers and children) and to consider the utility of each service temporally. Prospective services should clarify disease disclosure obligation in job search and introduce a care navigator. Key implementation strategies included (1) training HCPs on communication techniques with AYA, (2) selecting engagement platforms that complement survivors' information-seeking behavior, (3) improving outreach to survivors through appropriate branding and publicity, and (4) consolidating services from multiple providers. Conclusions: The design of survivorship care services for AYA survivors should be systematic in its conceptualization process and employ implementation strategies. The coordination of the wide spectrum of services warrants a concerted effort by cancer centers, community partners, and the government.

A decline in cognitive function following cancer treatment is one of the most commonly reported post-treatment symptoms among patients with cancer and those in remission, and include memory, processing speed, and executive function. A clear understanding of cognitive impairment as a result of cancer and its therapy can be obtained by delineating structural and functional changes using brain imaging studies and neurocognitive assessments. There is also a need to determine the underlying mechanisms and pathways that impact the brain and affect cognitive functioning in cancer survivors. Exosomes are small cell-derived vesicles formed by the inward budding of multivesicular bodies, and are released into the extracellular environment via an exocytic pathway. Growing evidence suggests that exosomes contribute to various physiological and pathological conditions, including neurological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication, and neurogenesis. In this review, we summarize the relationship between exosomes and cancer-related cognitive impairment. Unraveling exosomes' actions and effects on the microenvironment of the brain, which impacts cognitive functioning, is critical for the development of exosome-based therapeutics for cancer-related cognitive impairment.

The International Society of Oncology Pharmacy Practitioners organized a workshop to create learning opportunities on biosimilars in pharmacy practice on 10 October 2019. The topics that were covered included (i) the development and testing of biosimilars, (ii) the challenges of bringing biosimilars to market, and (iii) real-world data on patient safety and perceptions during biosimilar implementation. The development of biosimilars can take up to eight years and the extensiveness of the process depends on several factors, such as the complexity of the production process and regulatory requirements. Compared to generic products of small-molecule drugs, there is a higher barrier to market entry for biosimilars, explaining the small number of biosimilars in the market. Appraisal of biosimilars for inclusion in hospital formularies is also different from the review process of originator biologics, where the former is usually institution-led and has fewer restrictions on use. When several biosimilar products are available, factors that should be considered besides cost are licensed indications, supply chain confidence, clinical data, and product attributes. Real-world data have shown that biosimilars are well-tolerated and have safety data that are comparable to that of the originator product. Oncology pharmacists from the United Kingdom, Kenya, and Canada also presented their respective experiences with biosimilar use. Different countries at varying stages of biosimilar implementation faced distinct challenges. Nevertheless, resources to assist biosimilar implementation can potentially be shared between different regions. International Society of Oncology Pharmacy Practitioners is well-positioned to foster professional cooperation at an international level to drive biosimilar implementation.

Introduction: We conducted a randomized controlled trial evaluating the efficacy and tolerability of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with early breast cancer receiving neo/adjuvant weekly paclitaxel. Methods: Patients were recruited from the National Cancer Centre Singapore and randomized (1:1) to receive either cryotherapy or usual care. Cryotherapy was applied as frozen gloves and socks on all extremities from 15 min before paclitaxel until 15 min post-infusion every cycle. Efficacy was measured by patient-reported outcomes (Patient Neurotoxicity Questionnaire [PNQ] and EORTC QLQ-CIPN20) and electrophysiological assessments. The primary endpoint was PNQ severity at 2 weeks after 12 cycles of weekly paclitaxel. Results: A total of 46 patients were recruited, of which 8 dropped out before paclitaxel treatment, leaving 38 evaluable. There was no significant difference in PNQ severity between cryotherapy and usual care at 2 weeks after paclitaxel treatment (sensory: p = 0.721; motor: p = 1.000). A benefit was observed at 3 months post-paclitaxel based on PNQ (sensory: 14.3 vs. 41.2%, p = 0.078; motor: 0 vs. 29.4%, p = 0.012) and CIPN20 (sensory: β = -3.6, 95%CI = -10.5-3.4, p = 0.308; motor: β = -7.3, 95%CI = -14.6-0, p = 0.051). Additionally, cryotherapy subjects have lower CIPN20 autonomic score (β = -5.84, 95%CI = -11.15 to -0.524, p = 0.031) and higher sympathetic skin response hand amplitudes (β = 0.544, 95%CI = 0.108-0.98, p = 0.014), suggesting possible autonomic benefits from cryotherapy. Temporary interruption with cryotherapy occurred in 80.9% of the subjects due to cold intolerance. Conclusions: There is insufficient evidence that cryotherapy prevents sensory neuropathy which may be due to the high rates of cryotherapy interruption in this study. The autonomic benefits of cryotherapy should be further investigated with appropriate outcome measures. Clinical Trial Registration: ClinicalTrials.gov: NCT03429972.

Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients' self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25-0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24-0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individuals specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology.

Cancer-related fatigue (CRF) is subjective and has wide inter-individual variability. Given that leptin is commonly associated with fatigue syndrome, its use as a potential biomarker for CRF is being investigated. The primary objective of this study was to evaluate the association between leptin and CRF in early-stage breast cancer patients receiving chemotherapy. In a prospective cohort study, patients completed assessments at baseline (T1), during chemotherapy (T2) and after chemotherapy (T3). Levels of plasma leptin and adipokines were measured using a Luminex bead-immunoassay and CRF was measured using the Multi-Dimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Data were analysed longitudinally using a generalised estimating equation incorporating clinically relevant parameters and pro-inflammatory adipokines. The analysis included 136 patients (mean age ± SD = 51.5 ± 8.8 years; 69.1% receiving anthracycline-based chemotherapy). More patients experienced CRF at T3 (23.8%) than at T2 (13.8%) compared to baseline. An increase was observed in the median plasma leptin level at T2, followed by a decrease at T3 (T1: 4.07 ng/mL, T2: 4.95 ng/mL and T3: 3.96 ng/mL). In the multivariate model, the change in leptin levels over time was significantly associated with the total MFSI-SF score (β = -0.15, P = 0.003) after adjusting for the tumour necrosis factor-α (TNF-α) level, anxiety, depression, insomnia, age, menopausal status and type of chemotherapy. This is the first study to report leptin as a biomarker that predicts the onset of CRF over time. Future studies are required to validate the findings.

CONTEXT:Financial toxicity (FT) is used to describe the financial distress/hardship associated with cancer and its treatment. OBJECTIVES:The aim of this review was to explore the relationship between FT and symptom burden. METHOD:A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE, EMBASE, and CINAHL (from January 2000 to January 2018) and accepted quantitative, mixed-methods and qualitative studies. Data were extracted and appraised by two reviewers. Owing to significant heterogeneity in the included studies, a narrative synthesis was performed. RESULTS:Nine studies involving 11,544 cancer survivors were included. Of these nine studies, eight were of high quality. The relationships between FT and psychological symptoms and physical symptoms were examined in eight and three studies, respectively. Six studies reported a positive relationship between FT and depression. Three studies found a positive association between FT and anxiety. Limited evidence was found for an association between FT and stress, fear of recurrence, spiritual suffering, pain, and overall symptom burden. CONCLUSIONS:A relatively clear association exists between FT and psychological symptoms. Clinicians should regularly screen for, assess, and manage emotional distress that may be attributed to FT. Although the causal pathway is not known, future intervention studies aimed at minimizing or preventing FT should evaluate psychological symptoms as secondary outcomes. Little is known about the relationships between FT and physical symptoms. Future research should overcome methodological limitations by incorporating longitudinal data collection, use of mixed-methods approaches, and homogeneity of samples.