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The Complexity of Symptoms and Problems Experienced in Children with Cancer: A Review of the Literature

Open AccessPublished:August 12, 2008DOI:https://doi.org/10.1016/j.jpainsymman.2008.03.009

      Abstract

      To adequately help children with cancer, care providers need to understand the complexity of symptoms and problems associated with the illness that children are experiencing, which can enable them to better tailor patient care individually to each child. In this integrative literature review, we identified the types of symptoms and problems that children with cancer can experience during treatment and rehabilitation; the terms/expressions they use to describe their symptoms and problems; how children's symptoms and problems vary during the course of their illness; and how they vary and co-vary with age, gender or race. Of the 1175 titles identified, 110 articles met the inclusion criteria and were included in the review. Seventy-eight were research-based. A total of 219 distinct symptoms or problems were identified in the literature either as the main problem or a symptom of the main problem. There is significant evidence that children and adolescents experience numerous and complex symptoms, and problems during and after treatment for cancer. Children use many different expressions to talk about their symptom experiences. However, few articles looked at how children's symptoms and problems varied during the course of their illness or the variations in symptom severity and degree of bother, or examined the relationship between children's symptom experience and age, gender, or race. Most instruments that were used to measure symptoms were interviewer-administered questionnaires, often adaptations from adult versions, and in younger children, symptoms were often obtained from adult informants. The insights gained from this review can be helpful to researchers and clinicians who wish to better understand how symptoms and problems are experienced from the children's own perspective. However, more research is needed: to better understand differences in symptom experiences among different age groups; to identify differences among children from distinct cultural, ethnic, or socio-economic backgrounds; to clarify how symptoms and problems interfere with daily life; and to refine assessment methods that allow even younger children to communicate their symptom experiences in an age-adjusted manner.

      Key Words

      Introduction

      The past decades have seen remarkable progress in the treatment and prognosis of childhood cancer,
      • Patenaude A.F.
      • Last B.
      Cancer and children: where are we coming from, where are we going?.
      yet its diagnosis and treatment remains a difficult experience for the child and the family. Childhood cancer is associated with multiple physical, psychosocial, and behavioral symptoms, and problems owing to the illness itself, its treatment and uncertain prognosis, and medical procedures. Treatment usually involves multiple hospitalizations and interference with the child's normal development, activities, and social interactions over a long period of time; problems can continue long after children overcome the actual illness.
      • Bruce M.
      A systematic and conceptual review of posttraumatic stress in childhood cancer survivors and their parents.
      Unfortunately, clinicians often are not aware of cancer patients' symptoms. Consequently, symptoms remain underdiagnosed and undertreated.
      • Camp L.D.
      A comparison of nurses' recorded assessments of pain with perceptions of pain as described by cancer patients.
      • Grossman S.A.
      • Sheidler V.R.
      • Sweeden K.
      • et al.
      Correlation of patient and caregiver ratings of cancer pain.
      To adequately help children with cancer, health care providers need to elicit, understand, and communicate with the child about his or her experiences of symptoms and problems from the child's own perspective. This can be difficult, because less developed verbal and cognitive skills or adults' communication styles may prevent children from reporting and engaging in communication about distressing experiences with their care providers. Because children vary widely in their symptom and problem experiences, self-awareness and distress, clinicians cannot automatically anticipate what children are experiencing, and consequently, what care is in their best interest. Particularly for younger children, it is difficult in a “traditional” conversation to talk about difficult topics. Children with cancer are, therefore, at a particular risk that their symptoms and problems remain underdiagnosed and undertreated.
      To overcome these problems, our research team developed SISOM, an interactive assessment and communication tool to provide children with a “voice.”
      • Ruland C.M.
      • Starren J.
      • Vatne T.M.
      Participatory design with children in the development of a support system for patient-centered care in pediatric oncology.
      SISOM is the Norwegian acronym for Si det SOM det er, meaning: “Tell it as it is,” or Selvrapportering Innen Symptomer Og Mestring, meaning: Self-Reporting on Symptoms and Management. SISOM is designed to help children aged seven to 12 years with cancer to report their symptoms/problems in a child-friendly, age-adjusted manner, and assist clinicians (nurses and physicians) in addressing and integrating children's reported symptoms and problems into patient care.
      The interactivity and graphical and audiovisual functionalities made possible by the computer provide entirely different possibilities than questionnaires to capture children's experiences of symptoms and problems from the child's own perspective, and in a manner adapted to their developmental stage. SISOM uses spoken text, sound, animations, and intuitively meaningful metaphors and pictures to express or depict symptoms and problems that even younger children who cannot read can respond to.
      To define the symptoms and problems to be represented in SISOM, we conducted a systematic review of the literature to identify the breadth and depth of physical, psychosocial, and behavioral symptoms and problems children with cancer can experience, and the language and concepts they use to express and communicate their symptoms from their own perspective. Although a few earlier reviews have provided some insights into the symptoms and problems of children with cancer and their families,
      • Docherty S.L.
      Symptom experiences of children and adolescents with cancer.
      • Eiser C.
      • Hill J.J.
      • Vance Y.H.
      Examining the psychological consequences of surviving childhood cancer: systematic review as a research method in pediatric psychology.
      • Pickard A.
      • Topfer L.-A.
      • Feeny D.
      A structured review of studies on health-related quality of life and economic evaluation in pediatric acute lymphoblastic leukemia.
      • Vance Y.H.
      • Eiser C.
      The school experience of the child with cancer.
      these reviews have only included some symptoms or aspects of the children's illness experiences, and no known review to date has addressed the full scope of symptoms and problems of children with cancer, including the perspective of children themselves. Therefore, the insights gained from our review could be helpful to researchers and clinicians who wish to better understand symptoms and problems from the children's own perspective, which can help them improve communication and better tailor patient care individually to each child.
      Thus the purpose of our review was to summarize the state of knowledge on the following questions:
      • 1.
        What is the range of symptoms and problems experienced by children with cancer reported in the literature?
      • 2.
        How do children describe their symptoms and problems? What are the terms/expressions they use?
      • 3.
        How do children's symptoms and problems vary during the course of their illness?
      • 4.
        What are the relationships between children's symptom experiences and age, gender, or race?

      Methods

      Search Strategy and Data Sources

      For this review, we performed two systematic searches. To define the content of SISOM, the first search was conducted for the time period 1990–August 2004 (Search 1). To update the review for the purpose of this paper with the most recent publications, we performed an additional search (Search 2) from September 2004 to October 25, 2007.
      For Search 1, the following electronic databases were searched: Clinical Evidence, National Guideline Clearinghouse; MEDLINE (1966–August 2004); CINAHL (1982–August 2004); EMBASE (1988–August 2004); PsycINFO (1872–August 2004); ERIC (1966–June 2004); in 2004 and February/March 2005, Cochrane Library (2005, Issue 1, all databases); in February 2005, Digital Dissertations (1861–2004) and SUMSearch.
      Detailed search strategies were developed for each electronic database based on the search strategy developed for MEDLINE. In each database, every term was searched in the database thesaurus and as free text/key word. The following terms were the central search terms used; further synonyms and modifications were added in each database to fit and utilize each database/thesaurus:
      • Child∗, adolescen∗, infant∗, young adult∗
      • Leukemi∗, leukaemi∗, [Childhood Neoplasms, MeSH] [Childhood Leukemia, EMBASE]
      • Chemotherap∗, radiotherap∗, radiat∗
      • Symptom∗, problem∗, consequenc∗, side effect∗, adverse effect∗, secondary effect∗, sequel∗, iatrogenic, deleterious
      In CINAHL, additional searches were conducted replacing the words symptom∗, problem∗, etc. as search terms with several specific symptoms/problems and their synonyms.
      The inclusion criteria were children zero to 18 years who received treatment for leukemia; with symptoms described during and after treatment for up to three years from diagnosis; English and Scandinavian language articles; and all types of research designs and qualitative research with at least 12 subjects. Studies were also included if chemotherapy was one of the interventions for some of the participants. All types of symptoms and side effects (physical, psychological, psychosocial, emotional, behavioral, and functional) in children and adolescents with leukemia during treatment and follow-up were reviewed.
      Exclusion criteria for the articles were: children who had surgery-related symptoms, cranial radiation, and symptoms related to long-term effects of treatment or illness. Case studies were excluded except for one where the symptom was rare but with a poor outcome. Studies were excluded if participating children were not clearly separated from the adults with cancer. Testing of drugs and treatment methods concerning children with leukemia were mostly outside the scope of this review unless symptoms and side effects were reported and discussed.
      In Search 2, the search criteria were extended to include all cancer diagnoses and with no limitations regarding treatment, but restricted to articles that included symptoms and problems obtained through children's self-report or included children's own perceptions. This was attributed to our particular interest in the children's own perspective about their symptom experiences, and because the first search had already provided an exhaustive and broad range of symptom and problem descriptions. Except for these alterations in the search strategy, the inclusion and exclusion criteria from the first search remained unchanged. The following terms were the central search terms used in the second search, and further synonyms and modifications were added in each database to fit and utilize each database/thesaurus:
      • Child∗, adolescen∗, infant∗, young adult∗
      • Cancer∗, neoplasm∗
      • Symptom∗, problem∗, consequenc∗, side effect∗, adverse effect∗, secondary effect∗, sequel∗
      • Self report∗, self assess∗, self concept∗

      Data Abstraction

      The search in the online databases yielded 1094 titles for Search 1 and an additional 81 for Search 2. From the two searches combined, 1015 were excluded after the abstract had been read, as they did not meet criteria. A further 160 were retrieved in full text, and of these, 50 were not used after the article had been read, as they did not meet the criteria. One hundred and ten articles were retained (Figure 1).
      References from the articles were scanned for other relevant articles, and pediatric cancer experts contacted for symptom information. Agreement between two reviewers was greater than 90%, with consensus reached on whether the articles met the inclusion or exclusion criteria. On those studies where disagreement occurred, a second review was undertaken until consensus was reached.

      Results

      Types of Cancer and Demographic Data

      A total of 5059 children or adolescents with cancer participated in the reviewed studies.
      The most common cancer in children and adolescents was leukemia although other types of cancer were reported. These included acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), Hodgkin's and non-Hodgkin's lymphoma, solid tumors, Wilms' tumor, and other tumors. The breakdown on gender was nearly always reported and in those studies where reporting age was applicable, age ranged from one to 20 years. Fifty-two had mixed age samples, 19 had children 12 years or younger, and seven sampled only adolescents. Children and adolescents were in remission or on therapy in most studies. The largest sample was 496
      • Wu E.
      • Robison L.L.
      • Jenney M.E.M.
      • et al.
      Assessment of health-related quality of life of adolescent cancer patients using the Minneapolis-Manchester Quality of Life Adolescent Questionnaire.
      and the smallest was seven.
      • Haase J.E.
      • Rostad M.
      Experiences of completing cancer therapy: children's perspectives…including commentary by Steeves RH.
      In the research-based studies, gender was fairly evenly distributed. From studies in which it would have been appropriate to report race, only one-third did so. Of those studies that included race, approximately 74% of the children or adolescents were Caucasian, 9% African American, 9% Hispanic, and 7% others (Asian and others). Family socioeconomic status (SES) was difficult to estimate overall as it was measured in different ways. Parents' education was used most frequently, followed by the Hollingshead Index, family income, and occupational prestige. Hollingshead 4 Factor Index of Social Status, however, combines education, income, gender, and marital status to produce the index factor.

      Duncan GJ, Magnuson K. Off with Hollingshead: socioeconomic resources, parenting, and child development. Evanston, IL: Northwestern University, 2001. Available at: www.northwestern.edu/ipr/publications/papers/2004/duncan/hollingshead.pdf. Accessed December 18, 2007.

      Overall, SES was either not reported or not measured in approximately 60% of the research studies. In general, it appears that children came from upper-lower to middle-class families, but with the difficulties in measurement of the concept of SES, this is a tenuous conclusion.
      Treatment status at the time of the study was reported in all studies. Forty-two percent of the children were undergoing chemotherapy, 26% were off treatment, and 12% were in remission, but a number of studies also combined children at different treatment/illness stages. The setting for research was not reported in 38% of the studies. Of those studies that did report settings, many studies collected data from several settings. Most were carried out in inpatient or outpatient settings or both, and also in patients' homes or in the community. In studies where it would have been appropriate to report the response rate, 45% did so. The response rate ranged from 31% to 100%, with a mean of 88%.

      Types of Studies

      A total of 110 articles were identified that described symptoms in children and adolescents with cancer. Seventy-eight articles were research studies (Table 1).
      Table 1Type of Studies and Reference Number of Author(s)
      Type of ReviewReference Number
      Systematic reviews (n=4)
      • Docherty S.L.
      Symptom experiences of children and adolescents with cancer.
      ,
      • Eiser C.
      • Hill J.J.
      • Vance Y.H.
      Examining the psychological consequences of surviving childhood cancer: systematic review as a research method in pediatric psychology.
      ,
      • Pickard A.
      • Topfer L.-A.
      • Feeny D.
      A structured review of studies on health-related quality of life and economic evaluation in pediatric acute lymphoblastic leukemia.
      ,
      • Vance Y.H.
      • Eiser C.
      The school experience of the child with cancer.
      General reviews of the literature (n=21)
      • Bruce M.
      A systematic and conceptual review of posttraumatic stress in childhood cancer survivors and their parents.
      ,
      • Bradlyn A.S.
      • Harris C.V.
      • Spieth L.E.
      Quality of life assessment in pediatric oncology: a retrospective review of phase III reports.
      ,
      • Challinor J.
      • Miaskowski C.
      • Moore I.
      • et al.
      Review of research studies that evaluated the impact of treatment for childhood cancers on neurocognition and behavioral and social competence: nursing implications.
      ,
      • Chin E.A.
      A brief overview of the oral complications in pediatric oncology patients and suggested management strategies.
      ,
      • Colby-Graham M.F.
      • Chordas C.
      The childhood leukemias.
      ,
      • Sencer S.F.
      • Kelly K.M.
      Complementary and alternative therapies in pediatric oncology.
      ,
      • Collins J.J.
      Cancer pain management in children.
      ,
      • Coniglio S.J.
      • Blackman J.A.
      Developmental outcome of childhood leukemia.
      ,
      • DuHamel K.N.
      • Redd W.H.
      • Vickberg S.M.
      Behavioral interventions in the diagnosis, treatment and rehabilitation of children with cancer.
      ,
      • Edwards J.L.
      • Gibson F.
      • Richardson A.
      • et al.
      Fatigue in adolescents with and following a cancer diagnosis: developing an evidence base for practice.
      ,
      • Friebert S.E.
      • Shurin S.B.
      Acute lymphocytic leukemia: treatment and ongoing care.
      ,
      • Hockenberry M.
      Symptom management research in children with cancer.
      ,
      • Hockenberry M.J.
      • Coody D.K.
      • Bennett B.S.
      Childhood cancers: incidence, etiology, diagnosis, and treatment.
      ,
      • Hockenberry-Eaton M.
      • Benner A.
      Patterns of nausea and vomiting in children: nursing assessment and intervention.
      ,
      • Hydzik C.A.
      Late effects of chemotherapy: implications for patient management and rehabilitation.
      ,
      • Langeveld N.E.
      • Stam H.
      • Grootenhuis M.A.
      • et al.
      Quality of life in young adult survivors of childhood cancer.
      ,
      • Moore I.M.
      Central nervous system toxicity of cancer therapy in children.
      ,
      • Mulhern R.K.
      • Butler R.W.
      Neurocognitive sequelae of childhood cancers and their treatments.
      ,
      • Sala A.
      • Pencharz P.
      • Barr R.D.
      Children, cancer, and nutrition–a dynamic triangle in review.
      ,
      • Van Dongen-Melman J.
      Developing psychosocial aftercare for children surviving cancer and their families.
      ,
      • Woodgate R.
      • McClement S.
      Symptom distress in children with cancer: the need to adopt a meaning-centered approach.
      Instrument development (n=11)
      • Calaminus G.
      • Weinspach S.
      • Teske C.
      • et al.
      Quality of life in children and adolescents with cancer. First results of an evaluation of 49 patients with the PEDQOL questionnaire.
      ,
      • Collins J.J.
      • Byrnes M.E.
      • Dunkel I.J.
      • et al.
      The measurement of symptoms in children with cancer.
      ,
      • Collins J.J.
      • Devine T.D.
      • Dick G.S.
      • et al.
      The measurement of symptoms in young children with cancer: the validation of the Memorial Symptom Assessment Scale in children aged 7–12.
      ,
      • Eiser C.
      • Havermans T.
      • Craft A.
      • et al.
      Validity of the Rotterdam Symptom Checklist in paediatric oncology.
      ,
      • Hockenberry-Eaton M.
      • Manteuffel B.
      • Bottomley S.
      Development of two instruments examining stress and adjustment in children with cancer.
      ,
      • Hockenberry M.J.
      • Hinds P.S.
      • Barrera P.
      • et al.
      Three instruments to assess fatigue in children with cancer: the child, parent and staff perspectives.
      ,
      • Marchese V.G.
      • Chiarello L.A.
      • Lange B.J.
      Strength and functional mobility in children with acute lymphoblastic leukemia.
      ,
      • Tuffrey C.
      • Muir K.R.
      • Walker D.A.
      Development of a treatment tolerability scale for use with young patients receiving intensive treatment for cancer.
      ,
      • Tucker C.L.
      • Slifer K.J.
      • Dahlquist L.M.
      Reliability and validity of the brief behavioral distress scale: a measure of children's distress during invasive medical procedures.
      ,
      • Varni J.W.
      • Burwinkle T.M.
      • Katz E.R.
      • et al.
      The PedsQL in pediatric cancer: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module.
      ,
      • Bhatia S.
      • Jenney M.E.
      • Bogue M.K.
      • et al.
      The Minneapolis-Manchester Quality of Life Instrument: reliability and validity of the adolescent form.
      Experimental, quasi-experimental, RCTs (n=12)
      • Chen C.
      • Wang R.
      • Cheng S.
      • et al.
      Assessment of chemotherapy-induced oral complications in children with cancer.
      ,
      • Dahlquist L.M.
      • Pendley J.S.
      • Landthrip D.S.
      • et al.
      Distraction intervention for preschoolers undergoing intramuscular injections and subcutaneous port access.
      ,
      • Delbecque-Boussard L.
      • Gottrand F.
      • Ategbo S.
      • et al.
      Nutritional status of children with acute lymphoblastic leukemia: a longitudinal study.
      ,
      • Kingma A.
      • van Dommelen R.I.
      • Mooyaart E.L.
      • et al.
      Slight cognitive impairment and magnetic resonance imaging abnormalities but normal school levels in children treated for acute lymphoblastic leukemia with chemotherapy only.
      ,
      • Noll R.B.
      • Gartstein M.A.
      • Vannatta K.
      • et al.
      Social, emotional, and behavioral functioning of children with cancer.
      ,
      • Precourt S.
      • Robaey P.
      • Lamothe I.
      • et al.
      Verbal cognitive functioning and learning in girls treated for acute lymphoblastic leukemia by chemotherapy with or without cranial irradiation.
      ,
      • Reinders-Messelink H.A.
      • Schoemaker M.M.
      • Snijders T.A.
      • et al.
      Analysis of handwriting of children during treatment for acute lymphoblastic leukemia.
      ,
      • Sawyer M.
      • Antoniou G.
      • Toogood I.
      • et al.
      Childhood cancer: a 4-year prospective study of the psychological adjustment of children and parents.
      ,
      • Shore S.
      • Shephard R.J.
      Immune responses to exercise in children with cancer.
      ,
      • Stehbens J.A.
      • MacLean W.E.
      • Kaleita T.A.
      • et al.
      Effects of CNS prophylaxis on the neuropsychological performance of children with acute lymphoblastic leukemia: nine months postdiagnosis.
      ,
      • Waber D.P.
      • Tarbell N.J.
      • Fairclough D.
      • et al.
      Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.
      ,
      • Zeltzer L.
      • Dolgin M.J.
      • LeBaron S.
      • et al.
      A randomized, controlled study of behavioral intervention for chemotherapy distress in children with cancer.
      Descriptive research studies–physical symptoms (n=14)
      • Ammann R.A.
      • Hirt A.
      • Luthy A.R.
      • et al.
      Identification of children presenting with fever in chemotherapy-induced neutropenia at low risk for severe bacterial infection.
      ,
      • Brown R.T.
      • Madan-Swain A.
      • Pais R.
      • et al.
      Cognitive status of children treated with central nervous system prophylactic chemotherapy for acute lymphocytic leukemia.
      ,
      • Hedstrom M.
      • Haglund K.
      • Skolin I.
      • et al.
      Distressing events for children and adolescents with cancer: child, parent, and nurse perceptions.
      ,
      • Kadan-Lottick N.
      • Marshall J.A.
      • Baron A.E.
      • et al.
      Normal bone mineral density after treatment for childhood acute lymphoblastic leukemia diagnosed between 1991 and 1998.
      ,
      • Lo L.H.
      • Hayman L.L.
      Parents associated with children in measuring acute and delayed nausea and vomiting.
      ,
      • Skolin I.
      • Hursti U.K.
      • Wahlin Y.B.
      Parents' perception of their child's food intake after the start of chemotherapy.
      ,
      • Tyc V.L.
      • Mulhern R.K.
      • Jayawardene D.
      • et al.
      Chemotherapy-induced nausea and emesis in pediatric cancer patients: an analysis of coping strategies.
      ,
      • Tyc V.L.
      • Vallelunga L.
      • Mahoney S.
      • et al.
      Nutritional and treatment-related characteristics of pediatric oncology patients referred or not referred for nutritional support.
      ,
      • Van Cleve L.
      • Bossert E.
      • Beecroft P.
      • et al.
      The pain experience of children with leukemia during the first year after diagnosis.
      ,
      • Van der Sluis I.
      • van den Heuvel-Eibrink M.
      • Hablen K.
      • et al.
      de Muinck Keizer-Schrama SMP. Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia.
      ,
      • Van-Dongen-Melman J.E.
      • Hokken-Koelega A.C.
      • Hahlen K.
      • et al.
      Obesity after successful treatment of acute lymphoblastic leukemia in childhood.
      ,
      • Weekes D.P.
      • Kagan S.H.
      • James K.
      • et al.
      The phenomenon of hand holding as a coping strategy in adolescents experiencing treatment-related pain.
      ,
      • Zernikow B.
      • Meyerhoff U.
      • Michel E.
      • et al.
      Pain in pediatric oncology – children's and parents' perspectives.
      ,
      • Jurbergs N.
      • Long A.
      • Hudson M.
      • et al.
      Self-report of somatic symptoms in survivors of childhood cancer: effects of adaptive style.
      Descriptive research studies–psychological symptoms (n=20)
      • Anderson V.
      • Smibert E.
      • Ekert H.
      • et al.
      Intellectual, educational, and behavioural sequelae after cranial irradiation and chemotherapy.
      ,
      • de Oliveira B.M.
      • Viana M.B.
      • Zani C.L.
      • et al.
      Clinical and laboratory evaluation of compliance in acute lymphoblastic leukaemia.
      ,
      • Grootenhuis M.A.
      • Last B.F.
      Children with cancer with different survival perspectives: defensiveness, control strategies, and psychological adjustment.
      ,
      • Hockenberry-Eaton M.
      • Dilorio C.
      • Kemp V.
      The relationship of illness longevity and relapse with self-perception, cancer stressors, anxiety, and coping strategies in children with cancer.
      ,
      • Levi R.B.
      • Drotar D.
      Health-related quality of life in childhood cancer: discrepancy in parent-child reports.
      ,
      • Madan-Swain A.
      • Brown R.T.
      • Foster M.A.
      • et al.
      Identity in adolescent survivors of childhood cancer.
      ,
      • Michalowski M.
      • Ketzer C.
      • Daudt L.
      • et al.
      Emotional and behavioral symptoms in children with acute leukemia.
      ,
      • Moore I.M.
      • Espy K.A.
      • Kaufmann P.
      • et al.
      Cognitive consequences and central nervous system injury following treatment for childhood leukemia.
      ,
      • Moore I.M.
      • Challinor J.
      • Pasvogel A.
      • et al.
      Behavioral adjustment of children and adolescents with cancer: teacher, parent, and self-report.
      ,
      • Mullis R.L.
      • Mullis A.K.
      • Kerchoff N.F.
      The effect of leukemia and its treatment on self-esteem of school-age children.
      ,
      • Noll R.B.
      • Bukowski W.M.
      • Davies W.H.
      • et al.
      Adjustment in the peer system of adolescents with cancer: a two-year study.
      ,
      • Ritchie M.A.
      Self-esteem and hopefulness in adolescents with cancer.
      ,
      • Sawyer M.
      • Antoniou G.
      • Toogood I.
      • et al.
      A comparison of parent and adolescent reports describing the health-related quality of life of adolescents treated for cancer.
      ,
      • Trask P.C.
      • Paterson A.G.
      • Trask C.L.
      • et al.
      Parent and adolescent adjustment to pediatric cancer: associations with coping, social support, and family function.
      ,
      • Varni J.W.
      • Katz E.R.
      • Colegrove Jr., R.
      • et al.
      Perceived social support and adjustment of children with newly diagnosed cancer.
      ,
      • Varni J.W.
      • Katz E.R.
      • Colegrove Jr., R.
      • et al.
      Perceived physical appearance and adjustment of children with newly diagnosed cancer: a path analytic model.
      ,
      • von Essen L.
      • Enskar K.
      • Kreuger A.
      • et al.
      Self-esteem, depression and anxiety among Swedish children and adolescents on and off cancer treatment.
      ,
      • Phipps S.
      • Long A.
      • Hudson M.
      • et al.
      Symptoms of post-traumatic stress in children with cancer and their parents: effects of informant and time from diagnosis.
      ,
      • Ozono S.
      • Saeki T.
      • Mantani T.
      • et al.
      Factors related to posttraumatic stress in adolescent survivors of childhood cancer and their parents.
      ,
      • Stoppelbein L.A.
      • Greening L.
      • Elkin D.
      Risk of posttraumatic stress symptoms: a comparison of child survivors of pediatric cancer and parental bereavement.
      Descriptive research studies–physical and psychological symptoms (n=5)
      • Wu E.
      • Robison L.L.
      • Jenney M.E.M.
      • et al.
      Assessment of health-related quality of life of adolescent cancer patients using the Minneapolis-Manchester Quality of Life Adolescent Questionnaire.
      ,
      • Barrera M.
      • Boyd-Pringle L.A.
      • Sumbler K.
      • Saunders F.
      Quality of life and behavioral adjustment after pediatric bone marrow transplantation.
      ,
      • Hockenberry-Eaton M.
      • Kemp V.
      • DiIorio C.
      Cancer stressors and protective factors: predictors of stress experienced during treatment for childhood cancer.
      ,
      • Kvist S.B.M.
      • Rajantie J.
      • Kvist M.
      • et al.
      Perceptions of problematic events and quality of care among patients and parents after successful therapy of the child's malignant disease.
      ,
      • Landolt M.A.
      • Vollrath M.
      • Niggli F.K.
      Health-related quality of life in children with newly diagnosed cancer: a one year follow-up study.
      Qualitative studies (n=12)
      • Davies B.
      • Whitsett S.F.
      • Bruce A.
      • et al.
      A typology of fatigue in children with cancer.
      ,
      • Hinds P.S.
      • Hockenberry-Eaton M.
      • Gilger E.
      • et al.
      Comparing patient, parent, and staff descriptions of fatigue in pediatric oncology patients.
      ,
      • Hinds P.S.
      • Hockenberry-Eaton M.
      Developing a research program on fatigue in children and adolescents diagnosed with cancer.
      ,
      • Hockenberry-Eaton M.
      • Hinds P.S.
      • Alcoser P.
      • et al.
      Fatigue in children and adolescents with cancer.
      ,
      • Hockenberry-Eaton M.
      • Hinds P.
      • O'Neill J.B.
      • et al.
      Developing a conceptual model for fatigue in children.
      ,
      • Hockenberry-Eaton M.
      • Hinds P.S.
      Fatigue in children and adolescents with cancer: evolution of a program of study.
      ,
      • Stewart J.L.
      Getting used to it:” children finding the ordinary and routine in the uncertain context of cancer.
      ,
      • Woodgate R.L.
      • Degner L.F.
      Nothing is carved in stone!: uncertainty in children with cancer and their families.
      ,
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      ,
      • Woodgate R.L.
      • Degner L.F.
      A substantive theory of keeping the spirit alive: the spirit within children with cancer and their families.
      ,
      • Woodgate R.L.
      A different way of being: adolescents' experiences with cancer.
      ,
      • Woodgate R.L.
      Life is never the same: childhood cancer narratives.
      Pilot studies (n=3)
      • Bossert E.A.
      • Van Cleve L.
      • Savedra M.C.
      Children with cancer: the pain experience away from the health care setting.
      ,
      • Cheng K.K.F.
      • Molassiotis A.
      • Chang A.M.
      An oral care protocol intervention to prevent chemotherapy-induced oral mucositis in paediatric cancer patients: a pilot study.
      ,
      • Hinds P.S.
      • Gattuso J.S.
      • Fletcher A.
      • et al.
      Quality of life as conveyed by pediatric patients with cancer.
      Expert opinion (n=5)
      • Dychkowski L.
      Returning to school after a diagnosis of cancer: the challenges facing school nurses in the management of students with cancer.
      ,
      • Hanigan M.J.
      • Walter G.A.
      Nutritional support of the child with cancer.
      ,
      • Lilley L.L.
      Side effects associated with pediatric chemotherapy: management and patient education issues.
      ,
      • VanDenburgh K.
      Childhood cancer in the classroom: information for the school nurse.
      ,
      • White N.C.
      Educational related problems for children with cancer.
      Book (n=1)
      • Varni J.W.
      • Blount R.L.
      • Quiggins D.L.
      Oncologic disorders.
      Case study (n=1)
      • Weitzman S.
      • Manson D.
      • Wilson G.
      • et al.
      Fever and respiratory distress in an 8-year-old boy receiving therapy for acute lymphoblastic leukemia.
      RCTs=randomized controlled trials.
      From the 110 studies, four were systematic reviews; 21 were more general reviews; 11 were instrument development; 51 were research studies that used quantitative studies with experimental, quasi-experimental, or descriptive designs; 13 used qualitative methods; and 10 were pilot studies, expert opinion, books, or a case study. Qualitative methods included interviews, one of which came from a quantitative study,
      • Van Cleve L.
      • Bossert E.
      • Beecroft P.
      • et al.
      The pain experience of children with leukemia during the first year after diagnosis.
      with open-ended, semi-structured, structured, or mixed-type interviews. Subjects were children, adolescents, families, teachers, and hospital staff. Observation and participant observation methods were employed in five studies.
      • Weekes D.P.
      • Kagan S.H.
      • James K.
      • et al.
      The phenomenon of hand holding as a coping strategy in adolescents experiencing treatment-related pain.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      • Woodgate R.L.
      • Degner L.F.
      A substantive theory of keeping the spirit alive: the spirit within children with cancer and their families.
      • Woodgate R.L.
      A different way of being: adolescents' experiences with cancer.
      • Woodgate R.L.
      Life is never the same: childhood cancer narratives.
      Eight studies used focus groups conducted with children and adolescents, parents, siblings, or hospital staff.
      • Hockenberry M.J.
      • Hinds P.S.
      • Barrera P.
      • et al.
      Three instruments to assess fatigue in children with cancer: the child, parent and staff perspectives.
      • Hinds P.S.
      • Hockenberry-Eaton M.
      • Gilger E.
      • et al.
      Comparing patient, parent, and staff descriptions of fatigue in pediatric oncology patients.
      • Hinds P.S.
      • Hockenberry-Eaton M.
      Developing a research program on fatigue in children and adolescents diagnosed with cancer.
      • Hockenberry-Eaton M.
      • Hinds P.S.
      • Alcoser P.
      • et al.
      Fatigue in children and adolescents with cancer.
      • Hockenberry-Eaton M.
      • Hinds P.
      • O'Neill J.B.
      • et al.
      Developing a conceptual model for fatigue in children.
      • Hockenberry-Eaton M.
      • Hinds P.S.
      Fatigue in children and adolescents with cancer: evolution of a program of study.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      • Woodgate R.L.
      A different way of being: adolescents' experiences with cancer.
      Four studies used the narrative method to uncover symptoms.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      • Woodgate R.L.
      • Degner L.F.
      A substantive theory of keeping the spirit alive: the spirit within children with cancer and their families.
      • Woodgate R.L.
      A different way of being: adolescents' experiences with cancer.
      • Woodgate R.L.
      Life is never the same: childhood cancer narratives.
      Seven studies focused on how children described symptoms in their own words.
      • Hinds P.S.
      • Hockenberry-Eaton M.
      • Gilger E.
      • et al.
      Comparing patient, parent, and staff descriptions of fatigue in pediatric oncology patients.
      • Hinds P.S.
      • Hockenberry-Eaton M.
      Developing a research program on fatigue in children and adolescents diagnosed with cancer.
      • Hockenberry-Eaton M.
      • Hinds P.S.
      • Alcoser P.
      • et al.
      Fatigue in children and adolescents with cancer.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      • Woodgate R.L.
      A different way of being: adolescents' experiences with cancer.
      • Woodgate R.L.
      Life is never the same: childhood cancer narratives.
      • Hinds P.S.
      • Gattuso J.S.
      • Fletcher A.
      • et al.
      Quality of life as conveyed by pediatric patients with cancer.
      Audiotaping was used in nine qualitative studies
      • Hedstrom M.
      • Haglund K.
      • Skolin I.
      • et al.
      Distressing events for children and adolescents with cancer: child, parent, and nurse perceptions.
      • Hinds P.S.
      • Hockenberry-Eaton M.
      • Gilger E.
      • et al.
      Comparing patient, parent, and staff descriptions of fatigue in pediatric oncology patients.
      • Hockenberry-Eaton M.
      • Hinds P.S.
      • Alcoser P.
      • et al.
      Fatigue in children and adolescents with cancer.
      • Stewart J.L.
      Getting used to it:” children finding the ordinary and routine in the uncertain context of cancer.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      • Woodgate R.L.
      A different way of being: adolescents' experiences with cancer.
      • Woodgate R.L.
      Life is never the same: childhood cancer narratives.
      • Bossert E.A.
      • Van Cleve L.
      • Savedra M.C.
      Children with cancer: the pain experience away from the health care setting.
      • Hinds P.S.
      • Gattuso J.S.
      • Fletcher A.
      • et al.
      Quality of life as conveyed by pediatric patients with cancer.
      and one quantitative study.
      • Van Cleve L.
      • Bossert E.
      • Beecroft P.
      • et al.
      The pain experience of children with leukemia during the first year after diagnosis.
      Quantitative approaches relied heavily on questionnaires or surveys covering physical and psychological domains, biophysical measures, biomarkers, and motor behavior. Questionnaires were used by children and also other individual's perceptions of the child or adolescent, including parents, siblings, hospital staff, and teachers. Three studies conducted chart reviews to identify documented symptoms.
      • Ammann R.A.
      • Hirt A.
      • Luthy A.R.
      • et al.
      Identification of children presenting with fever in chemotherapy-induced neutropenia at low risk for severe bacterial infection.
      • Tyc V.L.
      • Mulhern R.K.
      • Jayawardene D.
      • et al.
      Chemotherapy-induced nausea and emesis in pediatric cancer patients: an analysis of coping strategies.
      • de Oliveira B.M.
      • Viana M.B.
      • Zani C.L.
      • et al.
      Clinical and laboratory evaluation of compliance in acute lymphoblastic leukaemia.
      Biophysical and biochemical parameters were used to identify symptom-related outcomes. There were nine studies that used biophysical parameters. These included tests for biomarkers, stress, bone mineral density, exercise, anthropometric measures, height and weight, body mass index (BMI), body composition, and motor behavior.
      • Marchese V.G.
      • Chiarello L.A.
      • Lange B.J.
      Strength and functional mobility in children with acute lymphoblastic leukemia.
      • Delbecque-Boussard L.
      • Gottrand F.
      • Ategbo S.
      • et al.
      Nutritional status of children with acute lymphoblastic leukemia: a longitudinal study.
      • Reinders-Messelink H.A.
      • Schoemaker M.M.
      • Snijders T.A.
      • et al.
      Analysis of handwriting of children during treatment for acute lymphoblastic leukemia.
      • Shore S.
      • Shephard R.J.
      Immune responses to exercise in children with cancer.
      • Kadan-Lottick N.
      • Marshall J.A.
      • Baron A.E.
      • et al.
      Normal bone mineral density after treatment for childhood acute lymphoblastic leukemia diagnosed between 1991 and 1998.
      • Van der Sluis I.
      • van den Heuvel-Eibrink M.
      • Hablen K.
      • et al.
      de Muinck Keizer-Schrama SMP. Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia.
      • Van-Dongen-Melman J.E.
      • Hokken-Koelega A.C.
      • Hahlen K.
      • et al.
      Obesity after successful treatment of acute lymphoblastic leukemia in childhood.
      • de Oliveira B.M.
      • Viana M.B.
      • Zani C.L.
      • et al.
      Clinical and laboratory evaluation of compliance in acute lymphoblastic leukaemia.
      • Hockenberry-Eaton M.
      • Kemp V.
      • DiIorio C.
      Cancer stressors and protective factors: predictors of stress experienced during treatment for childhood cancer.
      Two studies used videotaping.
      • Tucker C.L.
      • Slifer K.J.
      • Dahlquist L.M.
      Reliability and validity of the brief behavioral distress scale: a measure of children's distress during invasive medical procedures.
      • Varni J.W.
      • Burwinkle T.M.
      • Katz E.R.
      • et al.
      The PedsQL in pediatric cancer: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module.
      There were 60 quantitative studies where instruments were used. Validity was reported for 10 (9%) and reliability estimates for 21 (19%). Of the latter, 16 studies had lower than acceptable internal consistency, i.e., less than 0.70. Twenty-five (23%) studies stated that good psychometrics existed for validity and reliability but did not report it. A total of 60 different instruments were used in the studies.

      Types of Symptoms and Problems Reported in the Literature Experienced by Children and Adolescents with Cancer

      In the first search, a total of 219 distinct symptoms or problems were identified in the literature either as the main problem or a symptom of the main problem. The second search did not reveal new symptoms or problems; however, we identified a few new synonyms or wordings for earlier identified symptoms.
      Thirty-six percent were psychological or emotional symptoms or problems, 31% physiological, 22% were both physical and psychological, and 11% were school-related or behavioral. The specific symptoms that were identified in both searches are categorized in Table 2 under the headings of physical, psychological/emotional, school-related, or physical and psychological.
      Table 2Symptom Descriptors by Type in the Literature Review
      Physical
      • Bleeding
      •  Bruising
      •  Petechia
      •  Purpura
      •  Bleeding gums and nose
      •  Hemorrhagic cystitis
      • CNS
      •  Numbness/tingling hands and feet
      •  Seizures
      •  Sensation, loss of
      •  Deep tendon reflex loss
      •  Handwriting problems
      •  Paresthesias
      •  Foot drop
      •  Ataxia
      •  Paraplegia
      •  Dizziness
      • ENT
      •  Ototoxicity
      •  Photosensitivity
      •  Ptosis
      •  Transient papilledema
      • GI symptoms
      •  Appetite, lack of (anorexia) or increased
      •  Taste, changes/alterations
      •  Constipation (paralytic ileus)
      •  No bowel movement
      •  Diarrhea
      •  Stomach
      •  Nausea
      •  Vomiting
      •  Emesis
      • Hair loss (alopecia)
      • Infection
      •  Fever
      •  Pneumonia
      •  Herpes zoster
      •  Candida
      •  Septicemia
      • Malaise
      • Malnutrition
      •  Weight loss
      • Mobility
      •  Decreased
      •  Limping
      • Nephrotoxicity
      • Obesity (adiposity)
      • Oral symptoms
      •  Mouth sores (mucositis, stomatitis, gingivitis)
      •  Mouth, dry (xerostomia)
      •  Deepening of the voice
      •  Oral debris
      •  Dry lips
      •  Swallowing, difficulty
      • Pain (intensity, location, pattern)
      •  Uncomfortable
      •  Annoying
      •  Feeling sore
      •  Pain, treatment-related
      •  Pain, procedure-related
      •  Headache
      • Respiratory distress
      •  Cough
      •  Dyspnea
      • Skin changes
      •  Itching
      • Speech, impairment
      •  Dysphasia
      • Strength, decreased
      • Sweating
      • Swelling, arms and feet
      • Psychological, emotional
      • Adherence/noncompliance
      •  Noncompliance with medication
      •  Drug intake issues by mother and child
      • Fear
      •  Apprehensive
      •  Afraid
      • Alienation
      • Anxiety
      •  General
      •  Social
      •  Procedure-related
      •  Treatment-related
      •  Separation
      •  Nervous, feeling
      • Behavior problems
      • Communication problems
      • Developmental, impairment
      • Dying (think of)
      • Embarrassment
      • Family function, positive or negative
      • Food aversions (peculiar combinations of food)
      • Hopelessness/hopefulness
      • Identity formation (foreclosure)
      • Independence, loss of
      • Integrity, loss of
      • Isolation
      •  Social and physical
      •  Loneliness
      •  Confinement
      • Learning disabilities
      • Loss, sense of
      • Mental
      •  Concentration (decreased)
      •  Confusion
      •  Mental work, increased
      •  Uneasy (mental, secondary to disheartening thoughts)
      • Mood
      •  Attitude (negative)
      •  Aggressive
      •  Bad tempered
      •  Bad
      •  Bored
      •  Cranky
      •  Defensive
      •  Sad (dysphoria)
      •  Indecisive
      •  Irritable
      •  Joy
      •  Miserable
      •  Mood bad
      •  Dysphoria
      •  Upset
      •  Withdrawn
      • Mistrust, feelings of
      • Nausea and vomiting, anticipatory
      • Neurocognitive deficits
      •  Attentional
      •  Poor eye/hand coordination
      •  Engagement
      •  Executive functions
      •  Processing and fluid abilities, slowness
      •  Secondary deficits (knowledge-based, crystallized abilities)
      •  Impaired short- and long-term memory
      •  Verbal processing
      • Peer relationships
      •  Rejection
      •  Acceptance
      • Physical appearance
      • Post-traumatic stress disorder
      • Respect, lack of
      • Self-concept
      •  Self-doubt
      •  Self-worth
      • Sleep
      •  A lot
      •  Inadequate
      •  Altered
      •  Insomnia
      • Stigma
      • Stress (cancer stressors)
      • Somatization (internalizing/externalizing)
      Both physical and psychological
      • Quality of life domains:
      • Academic functioning
      • Autonomy
      • Acute and chronic pain
      • Body image
      • Eating and sleeping
      • Cognition
      • Emotional functioning
      • Fatigue
      •  Mental exhaustion
      •  Lethargy
      •  Typical
      •  Treatment-related
      •  Energy, lack of, complete loss
      •  Energy expenditure (increased)
      •  Inactivity
      •  Tired (physical, regular, or chronic)
      •  Drowsy (somnolence)
      •  Malaise
      • Physical functioning
      •  Self-care functioning
      •  Mobility
      • Play
      •  Hard to move or run
      •  Weak
      •  Tire easily
      •  Not able to play
      • Psychological functioning
      •  Intellectual/neuropsychological functioning
      • Social functioning (friends/family)
      •  Satisfaction (life, self and abilities)
      •  Relations with family (siblings/parents)
      •  Recreation and leisure functioning
      •  Social support
      • Work functioning
      •  Impact of treatment on daily activities
      •  Employment issues
      • Sexual issues
      •  Sexual performance
      •  Sexual functioning
      •  Fertility
      •  Childbearing ability
      •  Potential risk to offspring
      •  Birth control
      •  Sperm banking
      •  Artificial insemination
      •  Reproductive counseling
      • Satisfaction with medical care
      School-related
      • Anxiety (school-related)
      • Athletic competence (exercise tolerance)
      • Behavioral problems
      • Neurocognitive deficits
      • Decrease in academic performance
      •  Mathematics, reading, spelling problems
      •  Hard to think
      •  Learning problems
      •  Study skills affected
      •  Leadership issues
      • Peer relationships
      •  Social reputation
      •  Social acceptance
      •  Social competence
      •  Social desirability
      •  Emotional well-being
      •  Acceptance/rejection
      •  Loneliness
      • School-related
      •  Integration into school
      •  Play restrictions
      •  Absenteeism
      •  Phobia
      •  Avoidance
      CNS, central nervous system; ENT, ear, nose and throat; GI, gastrointestinal.
      Many of the symptoms named specifically by children were overlapping or similar to words described in the literature and have been placed in Table 3 to reflect the depth and diversity of symptoms and the language children and adolescents used to describe their symptoms but were not used in the descriptive statistics mentioned earlier.
      Table 3Symptom Descriptors Given by Children
      Physical
      • GI symptoms
      •  Sick/ache
      •  Feel bad (stomach)
      •  Sick stomach
      • Pain
      •  Sick feeling
      •  Hurting feeling
      •  Hurting
      •  Yucky
      •  Crappy
      •  Shitty
      •  Feel sore
      •  Aching
      •  Annoying
      •  Comes and goes
      •  Annoying
      •  Hating chemotherapy
      •  Hate getting the poke
      • Play
      •  Hard to move/run
      •  Can't run fast or anything
      •  Not able to play
      •  Can't hang out with friends
      Psychological
      • Fear
      •  Scared
      •  Afraid I won't wake up
      •  Afraid, think about dying
      • Anxious
      • Isolation
      •  Feeling imprisoned
      • Lacking a sense of the future
      • Life, restrictions on
      • Mental uneasiness
      • Mood
      •  All in your mind
      •  Yucky feeling
      •  Can't be bothered
      •  Tired of everything that has happened
      •  Not myself, don't feel like normal self
      •  Son of a bitch
      •  Grumpy
      •  Changes everything
      •  Crying
      •  Depressed
      •  Feeling alone inside
      •  Feeling sorry
      •  Hard to think
      •  Mind shuts off
      •  Mad
      •  Changes
      •  Roller coaster
      •  Not going to let it (cancer) take control
      •  Sad
      •  Heart is sad
      •  Uncertainty
      •  When your counts are down–really bad
      •  Worrying
      •  Feel like I wish it was all over you know? But not very often
      • Missing out on things
      •  Miss my friends
      •  You miss school
      • Sleep
      •  Nightmares
      •  Sleepy
      •  Difficult to fall asleep
      • Stigma
      •  Name calling
      •  “Cancer kid”
      •  “Baldy”
      Physical and psychological
      • Fatigue
      •  Body is heavy
      •  Mind a blur
      •  Shutdown
      •  Feel like laying around
      •  Feeling drained
      •  Wearing away of body, wearing you out
      •  Wearing away of body and mind
      •  Tired, can't read well anymore, can't keep eyes open
      •  See a dull face in the mirror
      •  Lifestyle changes 100%
      •  Like a vegetable
      •  Wiped out
      •  Shut down
      •  Hard to move/run
      •  Feel like laying around
      •  Feel like hit by a truck
      •  Like jet lag
      GI, gastrointestinal.
      The most frequent symptoms studied were psychological, e.g., anxiety, fear, cognitive issues, mood, uncertainty, and fatigue, which also has physical elements. Pain was investigated in several studies and a few were related to painful procedures. Symptoms investigated in 10- to 18-year-olds were both physical and psychological, but had more psychological or school-related issues, e.g., anxiety, peer-related issues, self-concept, and somatization.

      How Do Symptoms Vary Over Time?

      There is little discussion in the literature about change in symptoms over time. Differences in home vs. hospitalized or outpatient visits has received little attention in terms of comparison of symptoms. In this review, about an equal number of studies explored children's symptom experience while undergoing treatment or after therapy/in remission. It was difficult to categorize some studies because of the different subdiagnoses and treatment plans, and also the lack of specific information in the articles. However, symptoms described while undergoing chemotherapy focused more on physical aspects, and a few were related to both physical and psychological aspects. Symptoms described after therapy or in remission focused primarily on psychological, behavioral, or school-related domains. A few studies had samples in which some children were undergoing therapy and some were in remission. Another difficulty was that some symptoms, e.g., fatigue and quality of life, fall into both domains. However, there were a few studies that included data collection over time in inpatient, outpatient, home, and school settings.
      Woodgate et al.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      described the childhood cancer course in four-and-a-half- to 18-year-olds in three settings: inpatient, outpatient, and home, for approximately 80 weeks. Families had difficulty, however, separating symptoms from the overall cancer experience. Categories, definitions, and characteristics of the experience were developed, and the central phenomenon was “getting through the rough spots.” These were described as “hell on earth,” “scary,” or “devastating.” Some characteristics may be viewed as symptoms or problems, e.g., uncertainty, sadness, roller coaster experience, limitations, restrictions, extra work and losses. How the symptoms varied over time was unclear.
      In Varni et al.,
      • Varni J.W.
      • Katz E.R.
      • Colegrove Jr., R.
      • et al.
      Perceived social support and adjustment of children with newly diagnosed cancer.
      adolescents (eight to 13 years of age) were assessed for perceived social support and perceived self-esteem at the time of diagnosis and nine months later. Greater support predicted significantly lower psychological distress and higher self-esteem, and classmate support was the most consistent predictor of adaptation to cancer.

      Relationship Between Children's Symptom Experiences and Age, Gender, or Race

      It is difficult to answer the question about the association between age and symptoms. Very few of the research studies with samples of children and adolescents had a breakdown of symptom by age. Not all studies provided the age range of the children. A few examined age and gender differences. Eiser et al.
      • Eiser C.
      • Havermans T.
      • Craft A.
      • et al.
      Validity of the Rotterdam Symptom Checklist in paediatric oncology.
      provided data on a small sample of children and reported that, in children less than 7.3 years, illness had a greater impact on physical function; boys were more active than girls. Ritchie
      • Ritchie M.A.
      Self-esteem and hopefulness in adolescents with cancer.
      studied adolescents' self-esteem and hopefulness and found that there were no interaction effects between gender and stage of adolescence with respect to perceived level of self-esteem and amount of hopefulness. In Van Dongen Melman et al.,
      • Van-Dongen-Melman J.E.
      • Hokken-Koelega A.C.
      • Hahlen K.
      • et al.
      Obesity after successful treatment of acute lymphoblastic leukemia in childhood.
      gender and age were not related to obesity after treatment for ALL.
      Hockenberry-Eaton et al.
      • Hockenberry-Eaton M.
      • Hinds P.S.
      • Alcoser P.
      • et al.
      Fatigue in children and adolescents with cancer.
      explored symptom descriptors between seven- and 12-year-olds (n=14) and 13- to 16-year-olds (n=15). They studied fatigue and used focus groups and audio-taping. Play, tiredness, and mood changes were apparent in both age groups, but there were more symptoms in adolescents.
      Cancer symptoms described in children's words were assigned attributes of the symptom in different age groups: preschool, school age, and adolescence.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      For the symptom sick stomach, e.g., a preschool child said “it makes me sick,” a school age child said “I feel a little better than gross,” and an adolescent said “You feel bad, but you know in what way. When you are feeling ill like vomiting or nausea, I guess the word for feeling bad is nausea or you have a headache like those are the words to describe it because you know exactly what is wrong with you.”
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      , p. 806 The investigators stated that “Children's cancer symptoms were expressed as overall feeling states with assigned meanings.”
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      , p. 812
      Hinds et al.
      • Hinds P.S.
      • Hockenberry-Eaton M.
      • Gilger E.
      • et al.
      Comparing patient, parent, and staff descriptions of fatigue in pediatric oncology patients.
      studied fatigue and believed that conceptually seven- to 12-year-old children described physical symptoms of fatigue, and adolescents 13 to 18 years merged mental and physical tiredness. For example, they concluded that fatigue in seven- to 12-year-old children included a profound sense of tiredness, difficulty with movement and play, and produced anger and sadness. Fatigue could be acute, episodic, or chronic. In adolescents, fatigue was seen as a complex, changing state of exhaustion, both physical and mental, or a combination of the two. Fatigue resulted in symptoms, such as not being involved with your friends, school, or sport; anger; not wanting to be bothered by others; and just wanting to lie down. They also found that this changing state of fatigue could be acute, episodic, or chronic.
      In the Varni et al.
      • Varni J.W.
      • Katz E.R.
      • Colegrove Jr., R.
      • et al.
      Perceived social support and adjustment of children with newly diagnosed cancer.
      adolescent study, older age was significantly correlated with depressed symptoms. Males had significantly more externalizing behavior problems than females, and females received significantly greater parental support and friend support.
      However, there were few studies that examined age and gender differences in symptom experiences during the course of their illness and none that looked at racial differences and symptoms.

      Terms and Expressions Children and Adolescents Use to Communicate Symptoms

      In Table 3, children's and adolescent's actual use of words to describe symptoms are shown. The actual words children used are more descriptive in nature. Most of these words come from seven studies,
      • Hinds P.S.
      • Hockenberry-Eaton M.
      • Gilger E.
      • et al.
      Comparing patient, parent, and staff descriptions of fatigue in pediatric oncology patients.
      • Hinds P.S.
      • Hockenberry-Eaton M.
      Developing a research program on fatigue in children and adolescents diagnosed with cancer.
      • Hockenberry-Eaton M.
      • Hinds P.S.
      • Alcoser P.
      • et al.
      Fatigue in children and adolescents with cancer.
      • Woodgate R.L.
      • Degner L.F.
      • Yanofsky R.
      A different perspective to approaching cancer symptoms in children.
      • Woodgate R.L.
      • Degner L.F.
      A substantive theory of keeping the spirit alive: the spirit within children with cancer and their families.
      • Woodgate R.L.
      A different way of being: adolescents' experiences with cancer.
      • Woodgate R.L.
      Life is never the same: childhood cancer narratives.
      where the emphasis was on eliciting children's own words to express their symptoms, with the emphasis on hearing the voice of the child.

      Discussion

      This literature review, based on 110 articles published between 1990 and 2007, is the first comprehensive review that includes an entire range of symptoms and problems reported in the literature in children with cancer, including children's illness experiences from their own perspective, and the language and terms they use to communicate their symptoms. It, therefore, can contribute to a better understanding of the breadth and depth of symptoms children and adolescents experience. Although a few earlier reviews exist,
      • Docherty S.L.
      Symptom experiences of children and adolescents with cancer.
      • Eiser C.
      • Hill J.J.
      • Vance Y.H.
      Examining the psychological consequences of surviving childhood cancer: systematic review as a research method in pediatric psychology.
      • Pickard A.
      • Topfer L.-A.
      • Feeny D.
      A structured review of studies on health-related quality of life and economic evaluation in pediatric acute lymphoblastic leukemia.
      • Vance Y.H.
      • Eiser C.
      The school experience of the child with cancer.
      they focused only on selected symptoms, or were limited to short follow-up periods. Whereas most symptoms and problems located in our search were psychological, this review provides significant evidence that children and adolescents experience a large number of complex psychological, physical, school-related, and behavioral symptoms and problems during and after treatment for cancer.
      However, this review also revealed some knowledge gaps, and thus suggestions, for further research. For example, symptom experiences were generally explored with little distinction as to whether they were elicited from children or adolescents. There may be differences in symptoms associated with age and gender, but not enough studies have addressed the issue to draw conclusions. Most research studies used mixed samples, rarely compared younger children and adolescents, and may, therefore, have missed important information. This is unfortunate, because smaller children are at a different cognitive developmental stage and have different perceptions about the world than adolescents, and thus, may experience their symptoms and problems differently. From the few studies that included only younger children or adolescents or distinguished between age groups, it appears that physical symptoms are experienced similarly by children and adolescents, but that adolescents have far more psychological or school-related problems and symptoms. Thus, more studies are needed to better tease out differences in symptom experiences among different age groups.
      There is also a paucity of information on background data, such as race, gender, family structure, and SES. Few studies have addressed symptom differences associated with these factors. Much of what we know about symptoms comes from Caucasian samples. Children from different cultural, geographical, and socioeconomic backgrounds may experience symptoms and problems differently, respond in other ways to similar events, or may have different support structures. Knowledge about such differences would be important information for clinicians that could help them adjust patient care individually to each child. Therefore, more studies are needed to explore differences in symptom experiences in children from different cultural, ethnic, or socioeconomic backgrounds.
      Very few studies have addressed how symptoms and problems change during different stages in children's illness trajectories, or variations in symptom severity and degree of bother. Symptoms may be predominantly physical during active chemotherapy in the early stages of treatment, but more psychological in later stages. Symptoms and problems may be acute, episodic, or chronic. There is also little research about which other variables co-vary with symptom experience. That symptom experiences vary widely during different stages of the illness has been found in adult cancer patients.
      • Hickok J.T.
      • Morrow G.R.
      • Roscoe J.A.
      • et al.
      Occurrence, severity, and longitudinal course of twelve common symptoms in 1129 consecutive patients during radiotherapy for cancer.
      It is, therefore, highly likely that children experience similar variations as well. Such variations may be even more profound in children, because while being sick over an extended period of time, they simultaneously go through their own developmental process. Thus, more longitudinal studies should be conducted to better understand how symptoms and problems vary over time. Also, we need to know more about how much bother and interference in their lives symptoms cause and how children would assign priority to symptom alleviation.
      A number of instruments have been used to elicit symptoms and problems for children and adolescents with cancer: over 20 psychological scales, more than 15 physical scales, a dozen containing both physical and psychological instruments, some school-related symptom measurement tools, and various parent, school, and health care provider tools. These instruments were primarily used for research purposes, rarely to support patient care.
      Most of the instruments were interviewer-administered questionnaires. Especially, for lower age groups, younger children rarely served as their own informants. Text-based questionnaires require a certain level of cognitive development and reading ability that younger children still lack. Parents, care providers or teachers often serve as proxy informants about the child's symptoms rather than the child itself. This can be problematic for several reasons. Adults may not be the best proxies for reporting a child's individual symptom experiences. Children may wish to protect their parents from being worried about them and, therefore, keep troublesome problems to themselves. Even if children are interviewed directly and the questions are read out loud to them, younger children often still have difficulty answering, partially because the language is difficult, and partially because they may not be motivated to respond to sensitive questions in an examination-like situation. Also, many assessment instruments for children are adaptations from adult versions, and not particularly developed for children's cognitive and emotional developmental stage. Thus, better assessment methods are needed that allow children to report their symptoms in a child-friendly, age-adjusted manner.
      However, a few number of studies have interviewed, observed, or audio- or videotaped children directly. Thus, we know that children and adolescents use somewhat different terminology to express their symptoms than adults, and the words they use are much more graphic. Although this can give some important indications that can help clinicians better understand and communicate with children about their symptoms and problems, much more research is needed on children's own words, expressions, thoughts, beliefs and perceptions, and their understanding of symptom concepts.
      The studies reviewed on symptoms and problems in children and adolescents with cancer were primarily focused on describing symptoms and problems, and in a few instances, on the children's verbal expressions they use. We did not find studies that discussed “best practices” on how to elicit symptoms from children in best possible ways, beyond aspects of validity and reliability. Given that younger children have limited verbal and reading skills, it is surprising that there are so few instruments out there that use graphical representations, symbols, or spoken text to help children report their symptoms and problems from their own perspective and in an age-adjusted manner. The interactivity and graphical and audio-visual functionalities made possible by computer-based assessment tools provide entirely new possibilities than questionnaires to capture children's experiences of symptoms and problems from the child's own perspective, even before reading age. Using such instruments for assessments of children's symptoms could provide new ways for understanding and communicating with children. Such interactive tools that children can use on their own are also promising as this may convey a more “true” reflection of children's experiences than those obtained indirectly through adults or instruments that are adapted from adult versions. However, how interactive instruments compare with other assessment methods has not yet been studied.
      Our review also has some limitations, primarily related to the motivation for this review: to lay the groundwork for developing SISOM, an interactive elicitation and communication tool for clinical application that can help children with cancer report their symptoms and problems from their own perspective and provide them with a “voice.” Therefore, we focused on identifying the breadth and depth of physical, psychosocial, and behavioral symptoms, and problems children with cancer can experience, the language and concepts they use to communicate their symptoms, and how these are experienced from the children's perspective. Our approach was that “anything goes;” if a symptom was reported in the literature, it was a candidate for inclusion on the list of symptoms. Therefore, we did not summarize the frequency of reported symptoms nor did we assess the quality of research studies, or the validity or reliability of instruments used to elicit symptoms. The focus was on summarizing knowledge on the type of symptoms, not to summarize the state of the art in symptom research. This would have required a different kind of review.
      Identifying symptoms and problems in the literature is of course not sufficient and only the first step in developing a new valid and reliable instrument. The methods we used to select symptoms and symptom terms for inclusion in SISOM and how we evaluated that children were able to understand the terms and graphical representations we use in the application are described elsewhere.
      • Ruland C.M.
      • Starren J.
      • Vatne T.M.
      Participatory design with children in the development of a support system for patient-centered care in pediatric oncology.
      To establish SISOM's validity and reliability requires another line of methodological and clinical research that is currently ongoing, but is beyond the scope of this literature review. However, this review provides an important basis for a better understanding of the complexity of symptoms and problems in children with cancer and the development of instruments that can catch the breadth and depth of children's symptom experiences. This may ultimately contribute to improve patient–provider communication and patient care.

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