2023+ESMO临床实践指南：成人癌症患者失眠（英文版）.pdf

SPECIAL ARTICLEInsomnia in adult patients with cancer:ESMO Clinical Practice Guideline5L.Grassi1y,R.Zachariae2,3y,R.Caruso1,L.Palagini4,R.Campos-Rdenas5,M.B.Riba6,7,M.Lloyd-Williams8,9,D.Kissane10,G.Rodin11,D.McFarland12,13,C.I.Ripamonti14&D.Santini15,on behalf of the ESMO Guidelines Committee?1Institute of Psychiatry,Department of Neuroscience and Rehabilitation,University of Ferrara,Ferrara,Italy;2Unit for Psychooncology and Health Psychology(EPoS),Department of Oncology,Aarhus University Hospital,Aarhus;3Danish Center for Breast Cancer Late Effects(DCCL),Aarhus University Hospital,Aarhus,Denmark;4Sleep Clinic,Department of Clinical and Experimental Medicine,Azienda Ospedaliero Universitaria Pisana,University of Pisa,Pisa,Italy;5Department of Psychiatry,Hospital Clnico Universitario Lozano Blesa,University of Zaragoza,Zaragoza,Spain;6Department of Psychiatry,University of Michigan,Ann Arbor;7University ofMichigan Rogel Cancer Center,University of Michigan,Ann Arbor,USA;8Academic Palliative and Supportive Care Studies Group(APSCSG),Primary Care and MentalHealth,University of Liverpool,Liverpool;9Department of Supportive and Palliative Care,Liverpool John Moores University,Liverpool,UK;10Department of Psychiatry,Monash University and Monash Medical Centre,Monash Health,Clayton,Australia;11Department of Supportive Care,Princess Margaret Cancer Centre,Toronto,Canada;12Department of Psychiatry,University of Rochester,Rochester;13Wilmont Cancer Institute,University of Rochester Medical Center,Rochester,USA;14Schoolof Speciality in Palliative Medicine,Department of Medical and Surgical Specialties,Radiological Sciences and Public Health,University of Brescia,Brescia;15MedicalOncology A,Policlinico Umberto I,Sapienza University of Rome,Rome,ItalyAvailable online XXXKey words:insomnia,cancer,oncology,psychiatry,psycho-oncologyINTRODUCTIONSleep disturbance is a common problem in patients withcancer,regardless of cancer type,stage and phase oftreatment.1Sleep disorders can be identified using thecriteria of the World Health Organization InternationalClassification of Diseases 11th edition(ICD-11)(updatedchapter on Sleepewake disorders),2the American Psychi-atric Association Diagnostic and Statistical Manual ofMental Disorders fifth edition e Text Revision(DSM-5-TR)3and the American Academy of Sleep Medicine(AASM)In-ternational Classification of Sleep Disorders(ICSD)thirdedition.4The three classification systems describe a series of dis-orders and conditions,including sleepewake disorders(insomnia),sleep-related breathing disorders,parasomnias,sleep-related movement disorders and circadian rhythmsleepewake disorders(see Supplementary Table S1,avail-ableathttps:/doi.org/10.1016/j.esmoop.2023.102047).Insomnia is by far the most frequent and clinically signifi-cant problem in patients with cancer.1,5Sleep health isimportant in oncology at many different levels,includinginfluences on the immune system,neuroendocrinologicalfunction,cognitive function,general well-being and qualityof life(QoL).6It is therefore mandatory for cancer cliniciansto regularly screen their patients for insomnia.Further-more,it is necessary to distinguish episodic from persistentinsomnia,to assess the specific dimensions of insomnia andthe negative consequences for patients,and to treat thedisorder according to evidence-based guidelines.7This Clinical Practice Guideline(CPG)presents an up-to-date,evidence-based approach to assessing and managinginsomnia disorder in patients with cancer and cancer sur-vivors.The authors followed the levels of evidence andgrades of recommendation as detailed in the Methodologysection.DEFINITION,INCIDENCE AND PREVALENCEInsomnia is defined as difficulties falling asleep and/ormaintaining sleep that cause distress and have a negativeimpact on daily functioning.Insomnia is the most commonsleep disorder,with a prevalence that is estimated to be6%-10%in the general population and three times greaterin patients with cancer and cancer survivors.1,5Moreover,up to 95%of patients with cancer report sleep disturbancesduring the disease and treatment trajectory,as well as insurvivorship and near the end of life.8Variations ininsomnia symptoms may be associated more with differentcancer treatments than cancer site.Symptoms often peakfollowing diagnosis,but may develop or worsen duringcancer treatment.9Insomnia frequently follows a chroniccourse,is strongly correlated with depressive symptomsand fatigue10and is associated with hyperarousal,11painand work-related worries.12Caregivers of patients withcancer may also experience poor quality of sleep,which inturn is associated with a reduced ability to cope withemotional problems.13In summary,disturbed sleep remains*Correspondence to:ESMO Guidelines Committee,ESMO Head Office,ViaGinevra 4,CH-6900 Lugano,SwitzerlandE-mail:clinicalguidelinesesmo.org(ESMO Guidelines Committee).5Approved by the ESMO Guidelines Committee:September 2023.yCo-primary authors.2059-7029/2023 The Author(s).Published by Elsevier Ltd on behalf ofEuropean Society for Medical Oncology.This is an open access article under theCC BY-NC-ND license(http:/creativecommons.org/licenses/by-nc-nd/4.0/).Volume xxx-Issue xxx-2023https:/doi.org/10.1016/j.esmoop.2023.1020471a neglected problem in oncology,with respect to not onlyscreening,but also providing adequate management.CONSEQUENCESInsomnia has been associated with an increased risk ofmental and physical health problems,including irritability,anxiety,depression,impaired QoL and greater disability andmortality,both in the general population and specifically inoncology.14Decades of research into the causes of chronic insomniahave identified physiological,cognitive and emotionalarousal as key factors.Hyperarousal and increased mentaland physiological stress-reactivity have been hypothesisedto contribute to the maintenance of insomnia by interactingwith negative cognitions,dysfunctional beliefs about sleepand negative sleep-related behaviours.The allostatic loadtheory suggests that sleep loss is both a precipitant of stressand a consequence of it,with evidence to suggest thatinsomnia-related stress may lead to persistent dysregulationof multiple biological systems15and various adverse cancer-related outcomes.Furthermore,stressors and challengesrelated to cancer and its treatment can cause insomnia orworsen existing insomnia,which then exacerbates comorbidmedical conditions such as pain,psychiatric conditions,daytime fatigue and somnolence,sleep-disordered breath-ing and napping-associated pain increase.16Thus a delete-rious feedback loop may be created which maintains orexacerbates insomnia and cancer-related comorbid condi-tions,including depression,anxiety,post-traumatic stressdisorder symptoms,daytime fatigue and pain.Symptoms of insomnia,depression and fatigue canmaintain and amplify each other in patients with cancer viamultiple mechanisms.Insomnia may lead to depression bydysregulating multiple systems involved in mood disorders.It is associated with a marked decrease in T cells andincreased levels of proinflammatory markers,such asC-reactive protein,interleukin-6 and tumour necrosis factor,and may promote a state of chronic inflammation whichcontributes to depression.However,the role of insomnia inmodulating the onset and outcome of cancer remainsunclear.17Cancer-related fatigue is a syndrome characterised byphysical,mentalandemotionalsymptoms,includinggeneralised weakness,diminished concentration or atten-tion,reduced motivation to engage in usual activities andemotional lability,similar to the symptoms that characterisedepression.18The aetiology of cancer-related fatigue maybe best explained by a multifactorial model that considersnot only the biological mechanisms but also psychologicaland behavioural factors,including insomnia,which has beenidentified as one of seven factors most commonly associ-ated with cancer-related fatigue.Several biological mecha-nisms may explain the bidirectional associations amongcancer-related insomnia,depression and fatigue,includingcytokine and hypothalamicepituitaryeadrenal axis dysre-gulation.18Treatment of insomnia is therefore recom-mended,not only in patients undergoing active cancertreatment,but also in long-term cancer survivors and pa-tients undergoing palliative care.Persistent insomnia in cancer may become a perpetu-ating factor in a vicious cycle of fatigue,depression andother cancer-related symptoms.These are promoted byinsomnia-related dysregulations of the immune and endo-crine systems,in combination with the effects of cancertreatment and the cancer itself.Insomnia can have signifi-cant consequences in patients with cancer,including anincreased risk of infection,persistent symptoms afterchemotherapy(ChT)and poorer recovery from depressionand anxiety,leading to reduced overall well-being andQoL.19Assessing insomnia and providing efficacious in-terventions can help to alleviate symptoms and late effects,as well as improving mental health,physical health and QoLin patients with cancer and cancer survivors.RISK FACTORSThe currently accepted risk factor model for insomnia is thediathesisestress model,commonly known as the 3-Pmodel,which describes predisposing,precipitating andperpetuating factors relevant to the development andmaintenance of persistent insomnia.In patients with can-cer,the 3-P model is useful for understanding the interac-tion between the general and cancer-specific factorsinvolved in cancer-related insomnia(see SupplementaryTable S2,available at https:/doi.org/10.1016/j.esmoop.2023.102047).Predisposing factors for insomnia are genetic,physio-logical and psychological factors that confer differentialsusceptibility to individuals in their sleep-related responsesto stress.Such factors include advanced age,female sex,ananxiety-prone personality,tendency to ruminate and afamily or personal history of insomnia and/or anxiety ordepression.Circadianrhythmdisruptioncouldalsocontribute to the development of insomnia in thesepatients.Precipitating factors include physiological,environmentaland psychological stressors which may interact with pre-disposing factors to produce acute insomnia symptoms.Patients with cancer and cancer survivors are exposed todifferent types of precipitating factors for insomnia alongthe cancer trajectory.These include stress and distressrelated to the cancer diagnosis and cancer treatments,suchas ChT,radiotherapy and hormone therapy.Cancer itself,aswell as surgery,hospitalisation,symptoms and varioustreatment-relatedside-effects,maydisruptcircadianrhythms and contribute to insomnia.In some cancers(e.g.breastcancer),antihormonaltreatmentsmayinducemenopausal symptoms contributing to the development ofsleep disorders.Perpetuating factors include behavioural,cognitive andenvironmental factors that contribute to the maintenanceand exacerbation of insomnia.Perpetuating factors com-mon to all patients with cancer include maladaptive be-haviours and beliefs that patients use to cope with sleepdifficulties.DetrimentalbehavioursincludespendingESMO OpenL.Grassi et al.2https:/doi.org/10.1016/j.esmoop.2023.102047Volume xxx-Issue xxx-2023extended time in bed,taking frequent and long naps,following an irregular sleep schedule and being physicallyinactive.Catastrophising about harms related to theinability to sleep and the daytime consequences of poorsleep may increase mental and physiological arousal thatdelays sleep onset and causes frequent,prolonged awak-enings in patients with cancer.20While the precipitating factors of insomnia are likely todiffer between patients with cancer and the general pop-ulation,most of the predisposing and perpetuating factorsof primary insomnia are similar to those of insomnia inpatients with cancer and in cancer survivors with comorbidinsomnia.As the recommended behavioural treatments forinsomnia target the perpetuating factors,the treatmentsthat are efficacious in patients with insomnia as the primarydiagnosis are also likely to be efficacious for treatinginsomnia in cancer settings.DIAGNOSISThe diagnosis of insomnia is similar across the nosologicalsystems,although some details differ between systems(seeSupplementary Table S1,available at https:/doi.org/10.1016/j.esmoop.2023.102047).In the DSM-5-TR,insomnia disorder is diagnosed as acomplaint of dissatisfaction with sleep quantity or quality,associated with one or more of the three main symptoms(i.e.difficulties falling asleep,staying asleep and earlyawakening),with sleep difficulty occurring?3 nights perweek,lasting?3 months,persisting despite adequate op-portunities for sleep and causing significant impairmentin daily life.Insomnia can be episodic(symptoms lasting?1 month but 3 months),persistent(symptoms lasting?3 months)or recurrent(at least two episodes within thespace of 1 year).In this framework,insomnia is considereda 24-hour sleepewake disorder,characterised by bothnocturnal and diurnal symptoms.The insomnia criteria in ICD-11 are the same as in DSM-5-TR,but ICD-11 specifies the symptoms secondary to sleepdifficulties(e.g.fatigue or malaise;attention,concentrationor memory impairment;mood disturbance or irritability).ICD-11 also classifies insomnia as short term(lasting5 is indicative of poor SQ.While the PSQI captures abroaderspectrum ofsleep than an insomnia severity scale,itmay be less relevant in the daily clinical oncology setting.Further,the numerous items increase patient burden,thescoring is rather cumbersome and the index is not intendedas a screening instrument for insomnia.L.Grassi et al.ESMO OpenVolume xxx-Issue xxx-2023https:/doi.org/10.1016/j.esmoop.2023.1020473There is agreement among sleep researchers that it canbe useful for insomnia sufferers to monitor their sleep overtime on a night-by-night basis using diaries to identifymaladaptive sleep patterns and track treatment effects.34The Consensus Sleep Diary(CSD)35was developed by anexpert panel and asks patients to record their sleep,including the time they went to bed,the time they tried tofall asleep,how long it took them to fall asleep,how manytimes they woke up,how long these awakenings lasted,thetime of their final awakening,the time they got out of bedand the perceived quality of their sleep.Objective measures of sleep such as polysomnography oractigraphy are not routinely required for insomnia diagnosisand evaluation but can be considered as a part of detailedexploration of sleep according to the patients clinical con-dition.16Table 1 describes the most important tools toassess insomnia disorders in patients with cancer.Algo-rithms for the screening and management of insomnia areTable 1.Examples of the most frequently used psychometric and nonpsychometric validated tools to assess insomnia disorders in patients with cancerMeasuresDescriptionScalesISI28The ISI is a self-report seven-item scale investigating sleep over the past 14 days(difficulties falling asleep,difficulties maintainingsleep,early morning awakenings,satisfaction or dissatisfaction