Subjective sleep and overall survival in chemotherapy-naïve patients with metastatic colorectal cancer
Abstract
Backround Sleep disorders are prevalent in patients with advanced cancer. Their impact on clinical outcomes is not well understood.Methods A post-hoc analysis was conducted in 361 chemo-naïve patients with metastatic colorectal cancer completing twice the EORTC QLQ-C30 questionnaire within a randomized international phase III trial. The study assessed the effect on overall survival (OS) of subjective sleep complaint, used as a normal or a time-dependent covariate (TDC), using a multivariate Cox proportional hazard model. Prognostic analysis was conducted on the whole study population and separately in each treatment arm (conventional FOLFOX2, or chronomodulated chronoFLO4).Results Sleep problems were reported by 202 patients (56%) at baseline and by 188 (52%) on treatment. Sleep problems at baseline were independently associated with a higher risk of earlier death (HR: 1.36; p = 0.011), progression (HR: 1.43; p = 0.002) and poor treatment response (RR: 0.58; p = 0.016). TDC analysis confirmed the independent prognostic effect of sleep problems on OS (HR: 1.37; p = 0.008), while on treatment this effect was only observed using univariate analysis. The negative prognostic value of sleep problems on OS at baseline, on treatment, and as a TDC was greatest on chronoFLO4 compared to FOLFOX2.Conclusions Subjective sleep problems are associated with poor clinical outcomes in metastatic colorectal cancer patients and affect chronotherapy effectiveness. There is a need for a well-tuned circadian timing system in order to increase chronotherapy activity. Prospective studies are needed for determining the impact of therapeutic approaches on sleep disorders upon quality of life and survival of cancer patients.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Untreated cancer-related insomnia may contribute to poorer treatment response, increased risk of cancer recurrence, and reduced survival.
“Untread cancer-related insomnia may also contribute to poorer treatment response, increased risk of cancer recurrence, and reduced survival. 9-11”
From Digital Cognitive-Behavioral Therapy for Insomnia in Cancer Survivors: Protocol for a Pragmatic Clinical Trial (2024) · cites this paper as [9]
The Results section (page not supplied) links baseline sleep complaints in patients with metastatic colorectal cancer to lower objective response, earlier disease progression, and shorter survival. It does not assess cancer recurrence or establish that the sleep problems were untreated insomnia. The reported associations also do not establish that insomnia caused the poorer outcomes. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., Filiberti, A., Flechtner, H., Fleishman, S. B., Haes, J. C. J. M. D., et al. (1993) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/85.5.365 · Cited by 16,005 · see citing works
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421 · see citing works
Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies
Cappuccio, F. P., D'Elia, L., Strazzullo, P., & Miller, M. A. (2010) · Sleep · doi:10.1093/sleep/33.5.585 · Cited by 2,224 · see citing works
Night-Shift Work and Risk of Colorectal Cancer in the Nurses' Health Study
Schernhammer, E. S., Laden, F., Speizer, F. E., Willett, W. C., Hunter, D. J., Kawachi, I. I., Fuchs, C. S., & Colditz, G. A. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.11.825 · Cited by 837 · see citing works
Quinten, C., Coens, C., Mauer, M. E. L., Comte, S., Sprangers, M. A. G., Cleeland, C. S., Osoba, D., Bjordal, K., & Bottomley, A. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70200-1 · Cited by 663 · see citing works
The Prognostic Significance of Patient-Reported Outcomes in Cancer Clinical Trials
Gotay, C. C., Kawamoto, C. T., Bottomley, A., & Efficace, F. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.3439 · Cited by 645 · see citing works
Palesh, O. G., Roscoe, J. A., Mustian, K. M., Roth, T., Savard, J., Ancoli-Israel, S., Heckler, C., Purnell, J. Q., Janelsins, M. C., & Morrow, G. R. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.5011 · Cited by 557 · see citing works
Self-citationCircadian Timing in Cancer Treatments
Lévi, F., Okyar, A., Dulong, S., Innominato, P. F., & Clairambault, J. (2010) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094626 · Cited by 478 · see citing works
Self-citationKöhne, C.-H., Cunningham, D., Costanzo, F. D., Glimelius, B. L. G., Blijham, G. H., Aranda, E., Scheithauer, W., Rougier, P. R., Palmer, M. K., Wils, J. A., et al. (2002) · Annals of Oncology · doi:10.1093/annonc/mdf034 · Cited by 463 · see citing works
Mormont, M., Waterhouse, J. M., Bleuzen, P., Giacchetti, S., Jami, A., Bogdan, A., Lellouch, J., Misset, J. L., Touitou, Y., & Lévi, F. (2000) · PubMed · Cited by 428 · see citing works
Self-citationLéger, D., & Bayon, V. (2010) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2010.01.003 · Cited by 376 · see citing works
Koller, M. T., Aaronson, N. K., Blazeby, J. M., Bottomley, A., Dewolf, L., Fayers, P. M., Johnson, C. A., Ramage, J. K., SCOTT, N. W., & West, K. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2007.05.029 · Cited by 302 · see citing works
Innominato, P. F., Focan, C., Gorlia, T., Moreau, T., Garufi, C., Waterhouse, J. M., Giacchetti, S., Coudert, B. P., Iacobelli, S., Genet, D., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4747 · Cited by 246 · see citing works
Self-citationFoster, F., & Wulff, K. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1670 · Cited by 243 · see citing works
Giacchetti, S., Bjarnason, G. A., Garufi, C., Genet, D., Iacobelli, S., Tampellini, M., Smaaland, R., Focan, C., Coudert, B. P., Humblet, Y., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.1440 · Cited by 237 · see citing works
Self-citationHowell, D., Oliver, T. K., Keller-Olaman, S., Davidson, J. R., Garland, S. N., Samuels, C. H., Savard, J., Harris, C. A., Aubin, M., Olson, K. L., et al. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt506 · Cited by 236 · see citing works
Palesh, O. G., Aldridge-Gerry, A. A., Zeitzer, J. M., Koopman, C., Neri, E., Giese‐Davis, J., Jo, B., KRAEMER, H. C., Nouriani, B., & Spiegel, D. (2014) · SLEEP · doi:10.5665/sleep.3642 · Cited by 235 · see citing works
Self-citationPatient Self-Reports of Symptoms and Clinician Ratings as Predictors of Overall Cancer Survival
Quinten, C., Maringwa, J. T., Gotay, C. C., Martinelli, F., Coens, C., Reeve, B. B., Flechtner, H., Greimel, E., King, M. T., Osoba, D., et al. (2011) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djr485 · Cited by 226 · see citing works
The circadian timing system in clinical oncology
Innominato, P. F., Roche, V., Palesh, O. G., Ulusakarya, A., Spiegel, D., & Lévi, F. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.916990 · Cited by 213 · see citing works
Self-citationQuinten, C., Martinelli, F., Coens, C., Sprangers, M. A. G., Ringash, J. G., Gotay, C. C., Bjordal, K., Greimel, E., Reeve, B. B., Maringwa, J. T., et al. (2013) · Cancer · doi:10.1002/cncr.28382 · Cited by 206 · see citing works
Sleep-Wake as a Biological Rhythm
Lavie, P. (2001) · Annual Review of Psychology · doi:10.1146/annurev.psych.52.1.277 · Cited by 186 · see citing works
Chronotherapy and the molecular clock: Clinical implications in oncology☆
Innominato, P. F., Lévi, F., & Bjarnason, G. A. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.06.002 · Cited by 165 · see citing works
Self-citationPalesh, O. G., Peppone, Innominato, Janelsins, Jeong, M., Sprod, L. K., Savard, J., Rotatori, R. M., Telli, Mustian, et al. (2012) · Nature and Science of Sleep · doi:10.2147/nss.s18895 · Cited by 160 · see citing works
Self-citationEfficace, F., Bottomley, A., Coens, C., Steen, K. V., Conroy, T., Schöffski, P., Schmoll, H., Cutsem, E. V., & Köhne, C. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.07.025 · Cited by 143 · see citing works
Innominato, P. F., Giacchetti, S., Bjarnason, G. A., Focan, C., Garufi, C., Coudert, B. P., Iacobelli, S., Tampellini, M., Durando, X., Mormont, M., et al. (2012) · International Journal of Cancer · doi:10.1002/ijc.27574 · Cited by 129 · see citing works
Self-citationSleep Disruption in Breast Cancer Patients and Survivors
Palesh, O. G., Aldridge-Gerry, A. A., Ulusakarya, A., Ortiz‐Tudela, E., Capuron, L., & Innominato, P. F. (2013) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2013.0179 · Cited by 120 · see citing works
Self-citationSleep/Wake Patterns of Individuals With Advanced Cancer Measured by Ambulatory Polysomnography
Parker, K. P., Bliwise, D. L., Ribeiro, M. H. L., Jain, S. R., Vena, C. I., Kohles-Baker, M. K., Rogatko, A., Xu, Z., & Harris, W. B. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.2135 · Cited by 116 · see citing works
Zhang, X., Giovannucci, E. L., Wu, K., Gao, X., Hu, F., Ogino, S., Schernhammer, E. S., Fuchs, C. S., Redline, S., Willett, W. C., et al. (2013) · Sleep · doi:10.5665/sleep.2626 · Cited by 115 · see citing works
Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival
Lévi, F., Dugué, P., Innominato, P. F., Karaboué, A., Dispersyn, G., Parganiha, A., Giacchetti, S., Moreau, T., Focan, C., Waterhouse, J. M., et al. (2014) · Chronobiology International · doi:10.3109/07420528.2014.924523 · Cited by 112 · see citing works
Self-citationDetermining the level of sleepiness in the American population and its correlates
Ohayon, M. M. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.06.008 · Cited by 111 · see citing works
as the Sleep Disturbance Expert Panel on behalf of the Cancer Journey Advisory Group of the Canadian Partnership Against Cancer, Howell, D., Oliver, T. K., Keller-Olaman, S., Davidson, J. R., Garland, S. N., Samuels, C. H., Savard, J., Harris, C. A., Aubin, M., et al. (2013) · Supportive Care in Cancer · doi:10.1007/s00520-013-1823-6 · Cited by 100 · see citing works
Efficace, F., Innominato, P. F., Bjarnason, G. A., Coens, C., Humblet, Y., Tumolo, S., Genet, D., Tampellini, M., Bottomley, A., Garufi, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.3117 · Cited by 94 · see citing works
Self-citationVagal regulation, cortisol, and sleep disruption in women with metastatic breast cancer
Palesh, O., Zeitzer, J. M., Conrad, A., Giese-Davis, J., Mustian, K. M., Popek, V., Nga, K., & Spiegel, D. (2008) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.27280 · Cited by 87 · see citing works
Self-citationFatigue and Other Variables During Adjuvant Chemotherapy for Colon and Rectal Cancer
Berger, A. M., Grem, J. L., Visovsky, C. M., Marunda, H. A. T., & Yurkovich, J. M. (2010) · Oncology nursing forum · doi:10.1188/10.onf.e359-e369 · Cited by 65 · see citing works
The circadian rest‐activity rhythm, a potential safety pharmacology endpoint of cancer chemotherapy
Ortiz‐Tudela, E., Iurisci, I., Beau, J., Karaboué, A., Moreau, T., Rol, M. A., Madrid, J. A., Lévi, F., & Innominato, P. F. (2013) · International Journal of Cancer · doi:10.1002/ijc.28587 · Cited by 58 · see citing works
Self-citationFatigue in colorectal cancer patients: prevalence and associated factors
Mota, D. D. C. D. F., Pimenta, C. A. D. M., & Caponero, R. (2012) · Revista Latino-Americana de Enfermagem · doi:10.1590/s0104-11692012000300010 · Cited by 55 · see citing works
Innominato, P. F., Mormont, M., Rich, T. A., Waterhouse, J. M., Lévi, F., & Bjarnason, G. A. (2009) · Integrative Cancer Therapies · doi:10.1177/1534735409355293 · Cited by 47 · see citing works
Self-citationInnominato, P. F., Giacchetti, S., Moreau, T., Smaaland, R., Focan, C., Bjarnason, G. A., Garufi, C., Iacobelli, S., Tampellini, M., Tumolo, S., et al. (2011) · Chronobiology International · doi:10.3109/07420528.2011.597532 · Cited by 46 · see citing works
Self-citationFatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer
Innominato, P. F., Giacchetti, S., Moreau, T., Bjarnason, G. A., Smaaland, R., Focan, C., Garufi, C., Iacobelli, S., Tampellini, M., Tumolo, S., et al. (2013) · Cancer · doi:10.1002/cncr.28072 · Cited by 44 · see citing works
Self-citationPsychosocial correlates of sleep quality and architecture in women with metastatic breast cancer
Aldridge-Gerry, A. A., Zeitzer, J. M., Palesh, O. G., Jo, B., Nouriani, B., Neri, E., & Spiegel, D. (2013) · Sleep Medicine · doi:10.1016/j.sleep.2013.07.012 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [1]1. Palesh O, Peppone L, Innominato PF, et al. Prevalence, Putative Mechanisms and Management of Sleep Problems During Chemotherapy. Nature and Science of Sleep. 2012;4: 151162.
Cited by
Sorted by citations
Cancer and stress: NextGen strategies
Cui, B., Peng, F., Lu, J., He, B., Su, Q., Luo, H., Deng, Z., Jiang, T., Su, K., Huang, Y., et al. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.11.005 · Cited by 152 · see citing works
Garland, S. N. (2021) · Sleep · doi:10.1093/sleep/zsab202 · Cited by 7 · see citing works
Clara, M. I., Van Straten, A., Canavarro, M. C., & Allen Gomes, A. (2024) · Acta Medica Portuguesa · doi:10.20344/amp.21094 · Cited by 5 · see citing works
- Authors
- Innominato, P. F., Spiegel, D., Ulusakarya, A., Giacchetti, S., Bjarnason, G. A., Lévi, F., & Palesh, O.
- Affiliations
- Inserm (FR)
- Stanford Medicine (US)
- Sunnybrook Health Science Centre (CA)
- Corresponding author
- Innominato, Pasquale F.
- ORCID
- Venue
- Sleep Medicine
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 16
- Issue
- 3
- Pages
- 391-398
- ISSN
- 1389-9457 (ISSN-L)
- OpenAlex
- W2067058194
- Cited by
- 88
- References
- 40
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 14 · 2023: 7 · 2022: 9 · 2021: 13 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 6 · 2016: 1 · 2014: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Sleep Medicine (publishedVersion)
- PubMed (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- Funders
- Association Internationale pour la Recherche sur le Temps Biologique et la Chronotherapie (ARTBC International), Paul Brousse Hospital, Villejuif, France
- Topics
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- sleep disorders, metastatic colorectal cancer, subjective sleep complaints, overall survival, prognostic factors, chronotherapy, chemotherapy-naive patients, circadian timing, EORTC QLQ-C30
- MeSH terms
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Female, Fluorouracil, Humans, Male, Middle Aged, Organoplatinum Compounds, Prognosis, Quality of Life, Surveys and Questionnaires, Sleep Wake Disorders, Colorectal Neoplasms, Survival Rate, Proportional Hazards Models, Chronotherapy, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
