Intervention For Cancer Survivors Research Articles

An Electrochemical and Raman Scattering Dual Detection Biosensor for Rapid Screening and Biomolecular Profiling of Cancer Biomarkers

Detecting circulating biomarkers sensitively and quantitatively is paramount for cancer screening, diagnosis, and treatment selection. Particularly, screening of a panel of circulating protein biomarkers followed by mapping of individual biomarkers could assist better diagnosis and understanding of the cancer progression mechanisms. Herein, we present a miniaturized biosensing platform with dual readout schemes (electrochemical and Surface enhanced Raman scattering (SERS)) for rapid cancer screening and specific biomarker expressional profiling to support cancer management. Our approach utilizes a controlled nanomixing phenomena under alternative current electrohydrodynamic condition to improve the isolation of cancer-associated circulating proteins (i.e., Epidermal growth factor receptor (EGFR), BRAF, Programmed death-ligand 1 (PD-L1)) with antibody functionalized sensor surface for rapid and efficient isolation of the targets and subsequent labelling with SERS nanotags. The method employs Differential Pulse Voltammetry (DPV) for rapidly screening for the presence of the circulating proteins on biosensor surface irrespective of their type. Upon positive DPV detection, SERS is applied for sensitive read-out of individual biomarkers biomarker levels. In a proof-of-concept study, we demonstrate the dual detection biosensor for analysing circulating BRAF, EGFR and PDL-1 proteins and successfully screened both ensemble and individual biomarker expressional levels as low as 10 pg (1 ng/mL). Our findings clearly indicate the potential of the proposed method for cancer biomarker analysis which may drive the translation of this dual sensing concept in clinical settings.

Bias Reduction through Analysis of Competing Events (BRACE) Correction to Address Cancer Treatment Selection Bias in Observational Data.

Cancer treatments can paradoxically appear to reduce the risk of noncancer mortality in observational studies, due to residual confounding. Here we introduce a method, Bias Reduction through Analysis of Competing Events (BRACE), to reduce bias in the presence of residual confounding. BRACE is a novel method for adjusting for bias from residual confounding in proportional hazards models. Using standard simulation methods, we compared BRACE with Cox proportional hazards regression in the presence of an unmeasured confounder. We examined estimator distributions, bias, mean squared error (MSE), and coverage probability. We then estimated treatment effects of high versus low intensity treatments in 36,630 prostate cancer, 4,069 lung cancer, and 7,117 head/neck cancer patients, using the Veterans Affairs database. We analyzed treatment effects on cancer-specific mortality (CSM), noncancer mortality (NCM), and overall survival (OS), using conventional multivariable Cox and propensity score (adjusted using inverse probability weighting) models, versus BRACE-adjusted estimates. In simulations with residual confounding, BRACE uniformly reduced both bias and MSE. In the absence of bias, BRACE introduced bias toward the null, albeit with lower MSE. BRACE markedly improved coverage probability, but with a tendency toward overcorrection for effective but nontoxic treatments. For each clinical cohort, more intensive treatments were associated with significantly reduced hazards for CSM, NCM, and OS. BRACE attenuated OS estimates, yielding results more consistent with findings from randomized trials and meta-analyses. BRACE reduces bias and MSE when residual confounding is present and represents a novel approach to improve treatment effect estimation in nonrandomized studies.

Diet/Nutrition: Ready to Transition from a Cancer Recurrence/Prevention Strategy to a Chronic Pain Management Modality for Cancer Survivors?

Evidence for the relationship between chronic pain and nutrition is mounting, and chronic pain following cancer is gaining recognition as a significant area for improving health care in the cancer survivorship population. This review explains why nutrition should be considered to be an important component in chronic pain management in cancer survivors by exploring relevant evidence from the literature and how to translate this knowledge into clinical practice. This review was built on relevant evidence from both human and pre-clinical studies identified in PubMed, Web of Science and Embase databases. Given the relationship between chronic pain, inflammation, and metabolism found in the literature, it is advised to look for a strategic dietary intervention in cancer survivors. Dietary interventions may result in weight loss, a healthy body weight, good diet quality, systemic inflammation, and immune system regulations, and a healthy gut microbiota environment, all of which may alter the pain-related pathways and mechanisms. In addition to being a cancer recurrence or prevention strategy, nutrition may become a chronic pain management modality for cancer survivors. Although additional research is needed before implementing nutrition as an evidence-based management modality for chronic pain in cancer survivors, it is already critical to counsel and inform this patient population about the importance of a healthy diet based on the data available so far.

Acoustic Array Biochip Combined with Allele-Specific PCR for Multiple Cancer Mutation Analysis in Tissue and Liquid Biopsy.

Regular screening of point mutations is of importance to cancer management and treatment selection. Although techniques like next-generation sequencing and digital polymerase chain reaction (PCR) are available, these are lacking in speed, simplicity, and cost-effectiveness. The development of alternative methods that can detect the extremely low concentrations of the target mutation in a fast and cost-effective way presents an analytical and technological challenge. Here, an approach is presented where for the first time an allele-specific PCR (AS-PCR) is combined with a newly developed high fundamental frequency quartz crystal microbalance array as biosensor for the amplification and detection, respectively, of cancer point mutations. Increased sensitivity, compared to fluorescence detection of the AS-PCR amplicons, is achieved through energy dissipation measurement of acoustically "lossy" liposomes binding to surface-anchored dsDNA targets. The method, applied to the screening of BRAF V600E and KRAS G12D mutations in spiked-in samples, was shown to be able to detect 1 mutant copy of genomic DNA in an excess of 104 wild-type molecules, that is, with a mutant allele frequency (MAF) of 0.01%. Moreover, validation of tissue and plasma samples obtained from melanoma, colorectal, and lung cancer patients showed excellent agreement with Sanger sequencing and ddPCR; remarkably, the efficiency of this AS-PCR/acoustic methodology to detect mutations in real samples was demonstrated to be below 1% MAF. The combined high sensitivity and technology-readiness level of the methodology, together with the ability for multiple sample analysis (24 array biochip), cost-effectiveness, and compatibility with routine workflow, make this approach a promising tool for implementation in clinical oncology labs for tissue and liquid biopsy.

Topology preserving stratification of tissue neoplasticity using Deep Neural Maps and microRNA signatures

BackgroundAccurate cancer classification is essential for correct treatment selection and better prognostication. microRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression, and their dyresgulation is a common disease mechanism in many cancers. Through a clearer understanding of miRNA dysregulation in cancer, improved mechanistic knowledge and better treatments can be sought.ResultsWe present a topology-preserving deep learning framework to study miRNA dysregulation in cancer. Our study comprises miRNA expression profiles from 3685 cancer and non-cancer tissue samples and hierarchical annotations on organ and neoplasticity status. Using unsupervised learning, a two-dimensional topological map is trained to cluster similar tissue samples. Labelled samples are used after training to identify clustering accuracy in terms of tissue-of-origin and neoplasticity status. In addition, an approach using activation gradients is developed to determine the attention of the networks to miRNAs that drive the clustering. Using this deep learning framework, we classify the neoplasticity status of held-out test samples with an accuracy of 91.07%, the tissue-of-origin with 86.36%, and combined neoplasticity status and tissue-of-origin with an accuracy of 84.28%. The topological maps display the ability of miRNAs to recognize tissue types and neoplasticity status. Importantly, when our approach identifies samples that do not cluster well with their respective classes, activation gradients provide further insight in cancer subtypes or grades.ConclusionsAn unsupervised deep learning approach is developed for cancer classification and interpretation. This work provides an intuitive approach for understanding molecular properties of cancer and has significant potential for cancer classification and treatment selection.

Fertility Preservation in Young Breast Cancer Patients: a Concept Analysis

The purpose of this study was to clarify and analyze the concept of fertility preservation in young breast cancer patients.As the reproductive age of women increases and the number of young cancer patients increases, there is an uncertainsituation in which young cancer patients diagnosed with breast cancer may lose fertility in the course of cancer treatment.Fertility preservation is a widely used concept It is necessary to clarify the meaning and concept of fertility preservationin young breast cancer patients in order to reduce confusion in the selection of cancer treatment and fertility preservation.For this study the process of Walker & Avant’s analysis was used. Eleven studies from electronic data bases met criteriafor selection. Fertility preservation can be defined by the following attributes 1)basic human desire 2)voluntary choiceaccording to the individual’s point of view 3)change of perception through consultation. The antecedents of fertilitypreservation consisted of: 1)Appropriateness of providing information 2)differences in individual values 3)socioenvironmentalfactors. The consequences occurring as a result of fertility preservation were: 1)improvement distress and2)enhancement of quality of life. Results of this analysis provides a theoretical framework for oncology medical staff tobetter understand fertility preservation in young breast cancer patients, to improve quality of life.

"For Years I lived in a Cage. Now the Cage Is Open and I Am Just Learning to Fly." Perspectives of Cancer Survivors on Psychological Resilience.

Transitioning from treatment to survivorship engenders several challenges that cancer survivors must learn to manage. These challenges are commonly associated with struggling to manage reentry into postcancer life. Thus, balance is restored after cancer, and postcancer experiences should be considered along with all previous life experiences. This balancing process surrounding cancer causes some cancer survivors' life to deteriorate, whereas other cancer survivors begin a psychological resilience process. The aim of this study was to investigate the way that psychological resilience is experienced by cancer survivors. The present descriptive qualitative design study was conducted from August 2019 through January 2020. A total of 12 cancer survivors were sampled from the follow-up clinics of a hospital. Data were collected through semistructured, pilot-tested, face-to-face interviews using an interview guide. Three main themes were clarified based on the descriptive analysis of the data on cancer survivors' experiences: "fight vs lose," "balancing uncertainties," and "learned to fly." The results demonstrate the importance and influence of psychological resilience in the overall cancer experience. This study provides insight into the subjective psychological resilience process of cancer survivors. Nurses may use this knowledge in fostering effective strategies enabling cancer survivors to develop psychological resilience. The results offer a promising resource for nurses to assess and address the risk and protective factors of cancer survivors to identify unique needs and to provide individualized care. In this context, nurses can develop novel approaches and interventions for cancer survivors in accordance with Kumpfer's resilience framework.

Identification of RAS mutant biomarkers for EGFR inhibitor sensitivity using a systems biochemical approach.

SUMMARYMutations can be important biomarkers that influence the selection of specific cancer treatments. We recently combined mathematical modeling of RAS signaling network biochemistry with experimental cancer cell biology to determine why KRAS G13D is a biomarker for sensitivity to epidermal growth factor receptor (EGFR)-targeted therapies. The critical mechanistic difference between KRAS G13D and the other most common KRAS mutants is impaired binding to tumor suppressor Neurofibromin (NF1). Here, we hypothesize that impaired binding to NF1 is a ‘‘biophysical biomarker’’ that defines other RAS mutations that retain therapeutic sensitivity to EGFR inhibition. Both computational and experimental investigations support our hypothesis. By screening RAS mutations for this biophysical characteristic, we identify 10 additional RAS mutations that appear to be biomarkers for sensitivity to EGFR inhibition. Altogether, this work suggests that personalized medicine may benefit from migrating from gene-based and allele-based biomarker strategies to biomarkers based on biophysically defined subsets of mutations.

Emerging from the haze: Feasibility pilot of a virtual multi-dimensional psycho-educational cognitive rehabilitation intervention for cancer survivors with decreased perceived cognitive function after cancer therapy.

276 Background: Standardized, effective cognitive rehabilitation interventions that can be widely disseminated are urgently needed for cancer-related cognitive impairment. The purpose of this single-arm pilot study was to test the feasibility/acceptability of virtual delivery of a cognitive rehabilitation intervention for participants in virtual groups. Study aims included: (1) Recruit 30 participants and achieve a 70% retention rate; (2) Demonstrate feasibility/acceptability of measures assessing determinants of behavior change (missing data <25%; reliability >.70); and (3) Explore interventional impact on perceived cognitive function (PCF), determinants of behavior change, and loneliness. Methods: Adult cancer survivors reporting impaired cognitive function following primary treatment were enrolled from two cancer centers and affiliates. Two cohorts (N=37) attended six weekly sessions and completed pre-/post- patient reported outcome questionnaires designed to measure PCF, loneliness, and determinants of behavior change for exercise, sleep, and mindfulness. Results: Participant retention rate was 85%. Measures of determinants of behavior change were reliable ( r >.70) across all three behaviors. Post-intervention scores for PCF, determinants of behavior change, and loneliness ratings significantly improved (Table). Inverse correlation between changes in loneliness, PCF ( r= -.376 to -.452, p <.05) and exercise intention ( r = -0.544, p =.001) were noted. Conclusions: Virtual delivery of cognitive rehabilitation interventions may be feasible and acceptable to cancer survivors reporting impairment in cognitive function after primary treatment. Loneliness may be an important predictor of both issues with cognitive function and intention to change behavior. [Table: see text]

Cancer survivors\u2019 views on digital support for smoking cessation and alcohol moderation: a survey and qualitative study

BackgroundDigital interventions may provide low-threshold support for smoking cessation (SC) and alcohol moderation (AM) to the growing population of cancer survivors. The objective was to explore preconditions of successful AM and SC digital interventions for cancer survivors.MethodsUsing a multi-method approach we conducted a survey (n = 240), a qualitative study consisting of four focus groups (n = 15) and semi-structured interviews with Dutch cancer survivors (n = 8). To help interpretation of our results we interviewed experts in the field of eHealth and cancer survivors (n = 6) and we organized an expert meeting (n = 7). Qualitative data were analysed using the Framework approach and were double-coded by two coders.ResultsSurvey results show the majority of drinkers had not previously considered AM (n = 158, 84.9%), often because they deemed their alcohol use to be non-problematic. All current smokers in the survey had considered SC before. In focus groups and interviews it became clear that SC efforts did not always stem from their own willingness to quit smoking, but originated from a wish to please their social environment. Main themes to be addressed in digital SC and AM that emerged from the interviews and focus groups, centred on the different ways of identification as cancer survivors, need for autonomy, differential beliefs about SC and AM, and the importance of a positive, non-patronizing tone-of-voice. Several specific preferences for digital interventions were formulated, although some cancer survivors prefer no support or face-to-face contact.ConclusionsCancer survivors are a diverse group with diverse preferences for AM and SC support. Digital AM and SC interventions for cancer survivors are perceived to be of value by some, especially when they incorporate a positive, non-judgemental and non-patronizing tone-of-voice, address concerns specifically relevant to cancer survivors, offer possibilities for personalization, and emphasize autonomy throughout. To encourage AM specifically, problem recognition and awareness of the health benefits of AM should be improved.

Effects of tandem cognitive behavioral therapy and healthy lifestyle interventions on health-related outcomes in cancer survivors: a systematic review.

PurposeHealthy lifestyle (HL) behaviors and cognitive behavioral therapy (CBT) have been individually shown to improve adverse effects of cancer treatment. Little is known about how such programs in tandem affect health-related outcomes. This review evaluates extant literature on tandem CBT/HL interventions on health-related outcomes in cancer survivors.MethodsA comprehensive search of PubMed, PsychINFO, CINAHL, and Embase databases revealed numerous studies involving CBT and HL tandem interventions in cancer survivors in the last 20 years. Studies meeting the inclusion criteria were examined and assessed by the authors.ResultsThe 36 studies included 5199 participants. Interventions involved the use of CBT in combination with a HL condition (stress reduction, increasing physical activity, etc.). These tandem conditions were compared against no intervention, usual care, and/or CBT alone or HL alone. Interventions were delivered by a variety of interventionists, and over different durations. The most common HL target outcomes were stress, and insomnia. Most studies (31 of 36) reported a reduction in adverse treatment and/or cancer-related effects.ConclusionFindings were biased with the overrepresentation of breast cancer survivors, and underrepresentation of minority groups, and those with advanced cancer. Thus, this review highlights the need for further research to test tandem interventions against CBT alone and HL alone, and toward identifying the most efficacious interventions for dissemination and implementation across diverse groups of cancer survivors.Implications for cancer survivorsTandem CBT/HL interventions can improve health-related outcomes for cancer survivors when compared to usual care, but there is a paucity of knowledge to suggest differential outcomes when compared to CBT or HL alone.

Programmatic Costs of the Telehealth Ostomy Self-Management Training: An Application of Time-Driven Activity-Based Costing

ObjectivesProgrammatic cost assessment of novel clinical interventions can inform their widespread dissemination and implementation. This study aimed to determine the programmatic costs of a telehealth Ostomy Self-Management Training (OSMT) intervention for cancer survivors using Time-Driven Activity-Based Costing (TDABC) methodology. MethodsWe demonstrated a step-by-step application of TDABC based on a process map with core OSMT intervention activities and associated procedures and determined resource use and costs, per unit procedure. We also assessed per-patient costs from a payer perspective and provided estimates of total hours and costs by personnel, activity, and procedure. ResultsThe per-patient cost of the OSMT was $1758. Personnel time accounted for 91% of the total cost. Site supervisor and information technology technician time were the most expensive personnel resources. Telehealth technical and communication equipment accounted for 8% of the total cost. Intervention coordination and monitoring efforts represented most of the total time cost (62%), followed by the intervention delivery (35%). The procedures with the highest cost were communication via phone or virtual meetings (24%), email exchanges (18%), and telehealth session delivery (18%). ConclusionsFuture efforts to replicate, disseminate, and implement the OSMT intervention should anticipate funding for nonclinical components of the intervention, including coordination and monitoring, and consider how these activities can be performed most efficiently. For institutions without established telemedicine programs, selection of videoconferencing platforms and adequate staffing for participant technical support should be considered. Our step-by-step application of TDABC serves as a case study demonstrating how interventionists can gather data on resource use and costs of intervention activities concurrently with their collection of trial data.

An Audio-Recorded Hypnosis Intervention for Chronic Pain Management in Cancer Survivors: A Randomized Controlled Pilot Study

ABSTRACT This pilot study evaluated the feasibility, acceptability, and potential efficacy of a 4-week hypnosis audio-recording intervention in cancer survivors with chronic pain. Forty participants were randomly assigned to treatment (n = 21) or wait-list (n = 19) conditions. Pain intensity ratings were lower at Week 4 for both groups. The effect size for pain reduction in the treatment group was d = 0.25 from baseline to 4 weeks, and the interaction effect (Time x Group) was F = .024; η2 p = .001. The small interaction effect may be due to the availability of only one recording and large variability in dose. Qualitative data indicated that the intervention’s benefits included participation in self-care, improved relaxation, and an opportunity to focus on oneself in a positive way. Further efficacy testing of an audio-recording intervention in a fully powered clinical trial is warranted.

Abstract 192: MutAnt: Mutation annotation machine learning algorithm for pathogenicity evaluation of single nonsynonymous nucleotide substitutions in cancer cells

Abstract With the wealth of next-generation sequencing (NGS) produced over the last decade, distinguishing between pathogenic and neutral single nucleotide missense mutations is essential to understanding disease pathogenesis and cancer treatment selection and optimization. Current experimental methods, such as overexpression assays, siRNA, knock-out models, and studies in cultured cells or model organisms, can help uncover the phenotype of a set of mutations in genes but are not optimal for the identification of pathogenic mutations in thousands of potential candidates. In this study, we present a new mutation annotation tool, MutAnt, for the prediction of mutation pathogenicity that achieves superior performance by integrating state-of-the-art machine learning techniques with feature selection and hyperparameter tuning. To develop MutAnt, a supervised machine learning algorithm was trained to classify pathogenic and neutral single nonsynonymous nucleotide substitutions. The training dataset was based on ClinVar v20190102, the CancerGenomeInterpreter database of validated pathogenic mutations, and benign mutations from the database of Cancer Passenger Mutations (dbCPM). The Boruta algorithm with Shapley values was used for feature selection, and the Bayesian optimization was applied for the model hyperparameter tuning. Diverse validation methods were utilized in the development of MutAnt, such as cross-validation; the Database of Curated Mutations (DoCM); holdout on new mutations documented in the latest released version of ClinVar database, which contains validated disease-associated single nucleotide polymorphisms (SNPs) not previously annotated in existing algorithms; mutations with high allele frequency; test dataset III from VariBench; and correlation with the mean function score in a saturation genome editing experiment for the BRCA gene. MutAnt exhibited a stronger performance than other methods on all of the tested validation strategies, which was demonstrated by its accuracy (high f1-score, 0.95 to 0.99) and sensitivity-specificity value (ROC-AUC value, 0.97 to 0.99) in classifying mutations in each validation dataset. Furthermore, the present approach allowed for the prediction of novel mutations that are not covered by extensive population studies with higher accuracy than other methods. This was demonstrated by its prediction of the clinically relevant BRCA variants in the saturation genome editing experiment. In conclusion, MutAnt outperformed all compared mutation annotation algorithms in this study for the classification of clinically relevant benign and pathogenic mutations in the ClinVar dataset. Importantly, this approach allows prediction of novel mutations, subsequently allowing for the selection of targeted therapies for a broader set of patients. Citation Format: Aleksandr Sarachakov, Viktor Svekolkin, Zoia Antysheva, Jessica H. Brown, Alexander Bagaev, Nathan Fowler. MutAnt: Mutation annotation machine learning algorithm for pathogenicity evaluation of single nonsynonymous nucleotide substitutions in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 192.

Abstract LB059: Dual methylation and mutation analysis from a single input of plasma cfDNA without sample splitting

Abstract Genomic and epigenetic changes are known to be the underlying mechanism of cancer development. Assessing the genomic (mutation) and epigenetic (methylation) changes has become increasingly important for cancer detection and treatment selection, especially in the field of cfDNA-based liquid biopsy. Targeted Next-Generation Sequencing (NGS) enables in-depth analysis of specific genomic regions that is essential for the clinical application of liquid biopsy. However, current targeted NGS assays are complicated, lengthy, and inefficient. Two major hurdles of existing targeted NGS methods make them impractical for the clinical setting. First, there is no comprehensive, end to end, kit solution available for targeted methylation sequencing (TMS) from sample to sequencing ready library. Second, the low yield of cfDNA from clinical blood samples presents a major challenge for multi-modal analyses on one sample. Thus, an assay that is capable of both methylation and mutation analysis would be optimal for clinical research and future diagnostic assays.Here, we report the performance of Point-n-Seq, a kit solution that can provide in-depth DNA analysis with highly flexible and customizable focused panels to enable both methylation and mutation analysis without sample splitting. Custom panels of 10 to 1000s of markers can be designed with >99% first-pass success rate. We conducted both performance validation and multi-center, multi-operator, reproducibility studies. With spike-in titration of cancer cell-line gDNA with known mutation and methylation profile, we achieved a reliable detection level down to 0.003% of tumor DNA with a linear relationship between the measured and expected fractions.In a pilot study, we designed a colorectal cancer (CRC) TMS panel covering 560 methylation markers and a mutation panel with >350 hotspot mutations in 22 genes. From only 1ml of plasma from late stage CRC patients, we detected cancer-specific methylation signals in all samples tested, and hotspot mutations with clinical implications. Next, a tumor-informed mutation panel covering approximately 100 personalized mutations for each patient was compared to the tumor-independent CRC methylation panel to analyze 23 stage I and II CRC patient plasma samples. The initial results showed that tumor-independent TMS assay achieved a comparable or superior limit of detection compared to the personalized tumor-informed approach. Moreover, to further improve assay sensitivity, metrics for cfDNA size can be integrated into the analysis of the same workflow without sample splitting. The Point-n-Seq kit, with a highly streamlined workflow and dual methylation and mutation analysis, provides a highly sensitive and robust non-invasive method for cancer detection, monitoring and treatment guidance. Citation Format: Grace Q. Zhao, Yun Bao, Heng Wang, Vanita S. Natu, Jayashree Joshi, Yingmin Wang, Elena Arzumanyan, Wanping Wang, Jianmin Wang, John Coller, Shengrong Lin. Dual methylation and mutation analysis from a single input of plasma cfDNA without sample splitting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB059.

Early Cost-effectiveness Analysis of Risk-Based Selection Strategies for Adjuvant Treatment in Stage II Colon Cancer: The Potential Value of Prognostic Molecular Markers.

To explore the potential value of consensus molecular subtypes (CMS) in stage II colon cancer treatment selection, we carried out an early cost-effectiveness assessment of a CMS-based strategy for adjuvant chemotherapy. We used a Markov cohort model to evaluate three selection strategies: (i) the Dutch guideline strategy (MSS+pT4), (ii) the mutation-based strategy (MSS plus a BRAF and/or KRAS mutation or MSS plus pT4), and (iii) the CMS-based strategy (CMS4 or pT4). Outcomes were number of colon cancer deaths per 1,000 patients, total discounted costs per patient (pp), and quality-adjusted life-years (QALY) pp. The analyses were conducted from a Dutch societal perspective. The robustness of model predictions was assessed in sensitivity analyses. To evaluate the value of future research, we performed a value of information (VOI) analysis. The Dutch guideline strategy resulted in 8.10 QALYs pp and total costs of €23,660 pp. The CMS-based and mutation-based strategies were more effective and more costly, with 8.12 and 8.13 QALYs pp and €24,643 and €24,542 pp, respectively. Assuming a threshold of €50,000/QALY, the mutation-based strategy was considered as the optimal strategy in an incremental analysis. However, the VOI analysis showed substantial decision uncertainty driven by the molecular markers (expected value of partial perfect information: €18M). On the basis of current evidence, our analyses suggest that the mutation-based selection strategy would be the best use of resources. However, the extensive decision uncertainty for the molecular markers does not allow selection of an optimal strategy at present. Future research is needed to eliminate decision uncertainty driven by molecular markers.

Mindfulness-Based Interventions in Cancer Survivors: A Systematic Review of Participants’ Adherence to Home Practice

BackgroundAlthough mindfulness-based interventions (MBIs) have demonstrated efficacy for alleviating psychological distress in cancer survivors, little is known about the extent to which participants adhere to assigned home practice. The purpose of this systematic review was to summarize and appraise the literature on rates and correlates of adherence to mindfulness home practice among cancer survivors.MethodsFour databases (PubMed, Psychology and Behavioral Sciences, PsycInfo, and CINAHL) were searched for studies published before October 15, 2020. Articles were included if they evaluated the benefits of an MBI program for adults with cancer.ResultsTwenty-one studies (N=1811 participants) meeting the inclusion criteria were identified (randomized controlled trials (n=13), non-randomized controlled designs (n=2), single-group studies (n=6)). The pooled adherence rate for participants’ home practice was 60% of the assigned amount, which equated to 27 min per day during the intervention period. There was some evidence for a relationship between home practice of mindfulness techniques and improvements in mood, stress, anxiety, depression, and fear of cancer recurrence (correlation coefficients ranged from 0.33 to 0.67). Factors including marital status, mood disturbance at baseline, intervention modality, and personality traits were evaluated in relation to adherence to home practice, but the current literature was inadequate to evaluate whether a relationship exists.ConclusionAdherence to mindfulness home practice among cancer survivors is suboptimal, and most of the correlates of adherence studied to date are non-modifiable. More research is warranted to scrutinize the role of home practice in mindfulness-based interventions, including assessment of modifiable factors influencing adherence to improve benefits for this population.

Can COV Direct: Effectiveness of a tele-medicine self- care interventions for cancer survivors during COVID 19 pandemic.

1583 Background: Good mental health improves the overall quality of life. Anxiety and depression in post-treatment cancer survivors is common and can affect adversely on the individual. CanCovDirect is a novel, tele-medicine self-care intervention for cancer survivors. We practiced a randomized controlled superiority trial to compare CanCovDirect with usual standard care (SC) in this population.Methods: Individuals completing cancer treatment within the past 3 years who had symptoms with or without anxiety or depression were recruited from clinical and community settings in Northern Kerala. We allocated the participants using block randomization (CanCovDirect plus SC or to SC alone). Assessments of anxiety and depression severity (Centre for Epidemiological Studies-Depression scale [CES-D]; primary outcome) and secondary outcomes anxiety symptoms (Hospital Anxiety and Depression Scale) health-related quality of life (Short Form Survey-12 mental and physical component summaries), were conducted at baseline, as well as 3 and 6 months (primary time point). Analyses of outcomes were adjusted for covariates using linear regression. Results: Participants recruited between June 2020 and November 2020 were randomly assigned to CanCovDirect (n = 152) or SC (n = 152). Among 350 participants randomly assigned, 304 (86.85%) completed the primary outcome at 6 months. CanCovDirect participants reported less severe anxiety and depressive symptoms on the CES-D than SC participants at 6 months, adjusted effect size (ES) 1.68 (95% CI, 1.28 to 2.05). CanCovDirect participants also had significantly greater quality of life compared with SC. Exploratory analysis suggested that types of cancer was a modifier of the primary outcome (interaction term P value =.04); the intervention was effective in women (ES, 0.62; 95% CI, −0.45 to 0.89). Conclusions: CanCovDirect is an essential method of managing mild-moderate depression and anxiety symptoms in cancer survivors.

A dual target sequencing solution to assess genomic and epigenomic alterations in cell-free DNA with no sample splitting.

3043 Background: Assessing the genomic and epigenomic changes on plasma cell-free DNA (cfDNA) using next-generation sequencing (NGS) has become increasingly important for cancer detection and treatment selection guidance. However, two major hurdles of existing targeted NGS methods make them impractical for the clinical setting. First, there is no comprehensive, end to end, kit solution available for targeted methylation sequencing (TMS), let alone one that analyzes both mutation and methylation information in one assay. Second, the low yield of cfDNA from clinical blood samples presents a major challenge for conducting multi-omic analysis. Thus, an assay that is capable of both genomic and epigenomic analysis would be advantageous for clinical research and future diagnostic assays. Methods: Here, we report the performance of Point-n-SeqTM dual analysis, a kit solution that can provide in-depth DNA analysis with highly flexible and customizable focused panels to enable both genomic and epigenomic analysis without sample splitting. With custom panels of tens to thousands of markers designed with > 99% first-pass success rate, we conducted both performance validation and multi-center, multi-operator, reproducibility studies. Using spike-in titration of cancer cell-line gDNA with known mutation and methylation profiles, Point-n-Seq assay achieved a reliable detection level down to 0.003% of tumor DNA with a linear relationship between the measured and expected fractions. Benchmarked with conventional targeted sequencing and methylation sequencing, Point-n-Seq solution also demonstrated improved performance, speed and shortened hands-on time. Results: In a pilot clinical study, a colorectal cancer (CRC) TMS panel covering 560 methylation markers and a mutation panel with > 350 hotspot mutations in 22 genes were used in the dual assay. Using 1ml of plasma from late-stage CRC patients, cancer-specific methylation signals were detected in all samples tested, and oncogenic mutations. In an early-stage cohort (33 stage I/II CRC patient ), comparison of the analysis between tumor-informed, personalized-mutation panels (̃100 private SNVs) for each patient and the tumor-independent CRC methylation panels were conducted. The initial results showed that tumor-independent TMS assay achieved a comparable detection compared to the personalized tumor-informed approach. Moreover, cfDNA size information (fragmentome) is also integrated into the analysis of the same Point-n-Seq workflow to improve the assay sensitivity. Conclusions: Point-n-Seq dual analysis is poised to advance both research and clinical applications of early cancer detection, minimal residual disease (MRD), and monitoring.

The GET FIT trial (NCT01635413): A randomized controlled trial of strength training versus Tai Ji Quan for fall prevention among female cancer survivors.

12059 Background: Women with cancer are significantly more likely to fall than women without cancer but there are not yet any evidence-based fall prevention strategies that specifically target cancer survivors. The GET FIT trial compares the efficacy of two distinct types of exercise, strength training vs. tai ji quan, to prevent falls in women finished with chemotherapy. Methods: We conducted a 3 group, single-blind, parallel design, randomized controlled trial in older, inactive women cancer survivors treated with chemotherapy. Women were randomly assigned to 1 of 3 intervention groups: 1) strength training, 2) tai ji quan or 3) a placebo control group (stretching) that trained 2x/week for 6 months. Additional follow-up occurred 6 months after formal training stopped. The primary outcome was fall rate across 6-and 12 months; secondary outcomes, reflective of training fidelity, were maximal leg strength (by 1-repetition maximum) and dynamic postural control (by computerized dynamic posturography), collected at 0, 3, and 6 months. Results: 442 women (mean age 62.4 + 6.3 yrs.) were enrolled and randomly assigned to study groups. Over the 6 months prior to enrollment, 21% of the sample (n = 94) reported at least one fall (of which, 37% (n = 35) reported two or more falls)), and 12% (n = 51) reported at least one injurious fall. Retention across the 12 months study period was 88%, while adherence to the study interventions over 6 months averaged 73%, 71%, and 74% for the strength, tai ji quan and stretching (control) groups, respectively. 26% of the sample (n = 99 of 382) reported at least one fall during the intervention and 27% (n = 102) reported falls during follow up. Using regression models, there were no significant differences in the odds of having at least one fall during the intervention period (1-6 months) or across the entire follow-up period (1-12 months) between the control and either the strength or tai ji quan groups. At 6 months, the strength group showed a greater increase from baseline in maximal leg strength (+14.3 kg, 95% CI: 11.4-17.1) than the control group (+7.5 kg, 95% CI: 4.6-10.4, p = 0.002). Whereas, the tai ji quan group showed a greater increase in dynamic postural control (+2.42%, 95% CI: 1.36-3.48) compared to the control group (+0.35%, 95% CI: -0.69-1.38, p = 0.007). Conclusions: Despite evidence for fidelity of strength and tai ji quan training to improve muscle strength and postural control, respectively, neither program significantly lowered fall rates over a placebo control group. It is possible that the dose of exercise was too low and/or the sample was not at high risk of falls. The etiology of fall risk in women cancer survivors needs to be better understood as it may differ from risk factors in older adults. Future trials should consider patient-centered, tailored fall-prevention interventions for cancer survivors based on identified fall risk factors. Clinical trial information: NCT01635413.