Arti Parganiha

Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival

The disruption of the circadian timing system (CTS), which rhythmically controls cellular metabolism and proliferation, accelerated experimental cancer progression. A measure of CTS function in cancer patients could thus provide novel prediction information for outcomes, and help to identify novel specific therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS biomarker, which was monitored using a wrist watch accelerometer for 2 days in 436 patients with metastatic colorectal cancer. The relative percentage of activity in-bed versus out-of-bed (Iu2009<u2009O) constituted the tested CTS measure, whose prognostic value for overall survival (OS) and progression-free survival (PFS) was determined in a pooled analysis of three patient cohorts with different treatment exposures. Median OS was 21.6 months [17.8–25.5] for patients with Iu2009<u2009O above the median value of 97.5% as compared to 11.9 months [10.4–13.3] for those with a lower Iu2009<u2009O (Log-rank pu2009<u20090.001). Multivariate analyses retained continuous Iu2009<u2009O as a joint predictor of both OS and PFS, with respective hazard ratios (HR) of 0.954 (pu2009<u20090.001) and 0.970 (pu2009<u20090.001) for each 1% increase in Iu2009<u2009O. HRs had similar values in all the patient subgroups tested. The circadian physiology biomarker Iu2009<u2009O constitutes a robust and independent quantitative predictor of cancer patient outcomes, that can be easily and cost-effectively measured during daily living. Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms.

The difference between in bed and out of bed activity as a behavioral marker of cancer patients: A comparative actigraphic study.

The current study was conducted to provide normative data on actigraphic dichotomy index (Iu2009<u2009O) (the percentage of in bed activity counts that are less than the median of out of bed counts) in healthy population and to assess whether the Iu2009<u2009O could be an effective index in discriminating the circadian motor activity of cancer patients from healthy controls. In this retrospective study, we recovered 408 actigraphic records from two databases: healthy controls (nu2009=u2009182; 79 males; mean age 38.7u2009±u200912.6) and patients with metastatic colorectal cancer (nu2009=u2009226; 149 males; mean age 58.4u2009±u200911.4). Beside the usual actigraphic sleep parameters (time in bed, sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency, number of awakenings, and mean motor activity), we also computed the dichotomy index and number of actigraphic wake parameters, namely, diurnal motor activity, diurnal total sleep time, number of sleep episodes, and the mean duration of the longest diurnal sleep episode. Using the Youden index, we calculated the cut off value that performed the best for Iu2009<u2009O and actigraphic wake parameters. Finally, we created Receiver Operator Characteristic curves to test the efficacy of each actigraphic parameter to discriminate cancer patient from healthy controls. Mean Iu2009<u2009O was 99.5% (SD, 0.48%) in the healthy group, as compared to 96.6% (SD, 3.6%) in the cancer group (pu2009<u20090.0001). Important age-related effects appeared unlikely after performing both the main analysis with age as a covariate, and a subset analysis in 104 subjects matched for age and sex. In the main analysis, all actigraphic parameters, except total sleep time, significantly differentiated the two groups of participants. However, the Iu2009<u2009O was the one that clearly performed best. Here, we provide the first large dataset on Iu2009<u2009O in healthy subjects, we confirm the relevance of this circadian index for discriminating advanced stage colorectal cancer patients from healthy subjects, and we lay the grounds for further investigations of this circadian index in patients with other chronic diseases.

Worsening of rest-activity circadian rhythm and quality of life in female breast cancer patients along progression of chemotherapy cycles

ABSTRACT Chemotherapy and its associated side effects can induce the disruption of circadian rest-activity rhythm and may have negative consequences on health-related quality of life (HRQoL) of cancer patients. In the current study, repeated-measures cross-sectional design was implemented to determine the status of circadian rest-activity rhythm and to assess the HRQoL of newly diagnosed female breast cancer patients those were planned to receive six cycles of chemotherapy. Rest activity and HRQoL were assessed in twenty-five patients during chemotherapy cycles 1st (C1), 3rd (C3), and 6th (C6) immediately after they reported to the outdoor ward of the Regional Cancer Center, Pt. J.N.M. Medical College, Dr. B.R. Ambedkar Memorial Hospital, Raipur, India. Wrist actigraphs for consecutive spans of 3–4 days were used to record the rest-activity rhythm, and its parameters were computed with the help of Cosinor Rhythmometry. Quality of life (QoL) parameters were assessed using EORTC QLQ-C30 and QLQ-BR23. Results revealed that average scores of all rhythm parameters, such as MESOR, amplitude, acrophase, rhythm quotient, circadian quotient, peak activity, dichotomy index, and autocorrelation coefficient; and all functional scales of QLQ-C30, such as physical, role, emotional, cognitive, and social, and global quality of life statistically significantly decreased with the increasing number of chemotherapy cycles (C1 to C3 and C6). Scores of symptom scales of QLQ-C30, such as fatigue, pain, dyspnoea, insomnia, appetite loss, and diarrhea increased significantly from C1 to C6. Among the QLQ-BR23 scales, scores of sexual functioning, sexual enjoyment, breast symptoms, and arm symptoms significantly decreased, whereas scores of systemic therapy side effects, and upset by hair loss significantly increased across the chemotherapy cycles. We conclude that rest-activity rhythm disrupted and HRQoL of breast cancer patients worsened along the increasing number of chemotherapy cycles. We suggest that along with the treatment protocol, level of disruption of these parameters should be assessed and managed with the proper interventions that prominently include timing of the chemotherapy administration. The latter is pivotal for maintenance of these parameters, which are likely to enhance the physiological ability of patients for better treatment responses and may improve the overall QoL and survival of the patients.

Monitoring of rest-activity rhythm in cancer patients paves the way for the adoption of patient-specific chronotherapeutic approach

Abstract The status and phases of the circadian timing system (CTS) can be ascertained through measuring several biological functions. Of those measurements, rest-activity rhythm is considered as a reliable circadian biomarker to evaluate the function of CTS among oncology population. Its amenable non-invasive monitoring over longitudinal time scale makes it more appropriate and convenient. Its use as reference rhythm for timing the medications is widely accepted in cancer and sleep clinics. Current mini review highlights the present knowledge on different actigraphy devices used for the measurement of circadian rest-activity rhythm. Further, this review presents recent data dealing with the status of circadian rest-activity rhythm in cancer patients and discusses its association with health-related patients’ quality of life. Application of this concept supports that the interventions with abilities to reverse CTS dysfunction in cancer patients might prolong their survival with improved and acceptable level of health-related quality of life.

Circadian rhythm characteristics of salivary alpha-amylase – a potential stress marker, in breast cancer in- and out-patients: a follow-up study

ABSTRACT Salivary alpha-amylase has been implemented as renewed non-invasive biomarker of interest to measure the levels of stress in humans. In the current clinical study, two-factor repeated-measures cross-sectional design was implemented to determine the salivary alpha-amylase levels and its rhythm characteristics in newly diagnosed female breast cancer in- and out-patients. Alpha-amylase levels were determined using the Salimetrics® salivary alpha-amylase assay kit. Rhythm characteristics of alpha-amylase were computed using the Cosinor Rhythmometry technique. Results showed that the levels of alpha-amylase significantly increased from/to the increasing number of chemotherapy cycle in patients of both group; however the levels were higher in in-patients. Further, results revealed significant differences in rhythm characteristics of alpha-amylase characterized by higher MESOR, lower amplitude, and advanced acrophase in in-patients as compared to out-patients. Current findings indicate that patients of both the groups were associated with progression under stress levels across the number of chemotherapy cycle; however, the levels of stress were higher in in-patients as compared to out-patients. Higher level of stress in cancer in-patients could be attributed to the possible effect of hospitalization and/or relative social isolation.

Circadian clock, cell cycle, and breast cancer: an updated review

Abstract Some key elements are common to two fundamental periodic regulatory processes; the circadian cycle and the cell cycle. Underlying mechanisms of coordination between the two processes are critical for proper cellular functioning and physiology. Disruption in the mechanisms of one process may affect the role of other that may direct critical physiological changes and may cause severe diseases like cancer, etc. More or less persuasive evidences evolve from the breast cancer research. In this mini review, we highlighted the molecular coordination’s of the elements of circadian cycle and the cell cycle and their altered expressions associated with the genesis and progression of breast cancer.

Hospitalization-induced exacerbation of the ill effects of chemotherapy on rest-activity rhythm and quality of life of breast cancer patients: a prospective and comparative cross-sectional follow-up study

ABSTRACT Chemotherapy administration may result in the disruption of circadian rhythms and impairment of quality of life (QoL) of cancer patients. Nevertheless, we have little knowledge on the long-term consequences of chemotherapy and the effects of hospitalization. In the present study, we employed the two-factor repeated-measure cross-sectional design to determine the effects of chemotherapy and hospitalization on rest-activity (RA) rhythm and QoL of breast cancer patients. Initially, we randomly selected 39 inpatients and 42 outpatients, scheduled to receive six cycles of chemotherapy, from the Regional Cancer Center (RCC), Raipur, India. Finally, 30 patients in each group were included in the current study. We monitored circadian RA rhythm and QoL using wrist actigraphy and QLQ-C30 and QLQ-BR23, respectively, during the 1st (C1), 3rd (C3) and 6th (C6) chemotherapy cycles. Results revealed that with the progression of chemotherapy cycles (from C1 to C6), all rhythm parameters, namely mesor, amplitude, acrophase, rhythm quotient (RQ), circadian quotient (CQ), peak activity (PA), dichotomy index and autocorrelation coefficient, significantly decreased in both cancer in- and outpatients. In both groups of patients and during C1–C6, all functional and global QoL measures of QLQ-C30 and QLQ-BR23 significantly decreased and the symptoms significantly increased, except constipation, body image, sexual functioning and future perspectives in outpatients. The hospitalization exacerbated the problems associated with the RA rhythm and the QoL of the patients. In conclusion, the current study highlighted the negative consequences of hospitalization among inpatients, irrespective of the stage of cancer. We, therefore, recommend that cancer patients should be administered with chemotherapy as outpatients. The proposed protocol might have a covert bearing on the expression of better physiological state leading to satisfactory treatment outcomes.

Relevance of circadian coordination for the outcome of patients with advanced gastro-intestinal (GI) cancer

15043 Background: Experimental cancer progression is controlled by the circadian timing system whose function can be assessed through non-invasive continuous rest-activity (RA) monitoring. Here, we investigated the relevance of I<O, a critical RA rhythm parameter that compares the relative amounts of activity in bed (I) and out of bed (O), for predicting tumor response, progression-free survival (PFS) and overall survival (OS) in an international cohort of 584 cancer patients (pts). Methods: RA rhythm was monitored for ≥ 48 h using a wrist-worn accelerometer (Ambulatory Monitoring Inc., Ardsley, NY, USA) before chemotherapy delivery (12 centers in 4 countries). A comprehensive database was constructed including pts history and characteristics, treatment received, its tolerability and efficacy. Main items were verified in pt charts and updated for 372 GI pts. This process is ongoing for the remaining pts. Univariate and multivariate analyses (SPSS 15.0) determined the relationship between I<O (range: 50%, ...