Pediatrics ASSESSING AND MANAGING SYMPTOMS AND CO- MORBIDITIES In Children with Cancer Melody Brown Hellsten DNP,RN, PPCNP-BC, CHPPN Texas Children’s Hospital No One Fights Alone: Texas Children’s Hospital Cancer Nursing Conference

Objectives 1) Identify 5 common symptoms and co-morbidities 2) Evaluate available assessment tools for patient reported outcomes 3) Discuss pharmacologic and non-pharmacologic management strategies for symptoms and co- morbidities

Signs and Symptoms in Disease Signs- alterations perceived by the observer Symptoms – functional changes Alert individuals to potential health abnormalities Individual characteristics affect reaction/interpretation of symptoms Produce an emotional response Increased awareness, worry, dread

Symptom Experience Model 2003 Armstrong Symptoms Experience: A Concept Analysis

Symptom Management Model Watch for stacking of sedating medications Dodd and others, 2001

Symptom Fast Facts Symptom frequency and severity vary by disease and treatment regimens. Distress is generally increased at diagnosis and lessens over time Mood disturbances and sadness tend to persist through out treatment and into survivorship Children with prolonged cancer experience due to progressive and terminal illness report highest levels of distress Parent and child beliefs and expectations, level of symptom control and parental preparation influence level of symptom distress

Symptom Distress A combination of physical discomfort, mental anguish or suffering resulting from changes in sensations, function or appearance and the meaning that a person places on the symptom or illness experience (Hinds, Quargnenti & Wentz, 1992)

Symptom Burden in Cancer Lack of energy, pain, lack of appetite, nausea, drowsiness, worry/sadness Parents and children tend rate symptoms similarly Most frequently endorsed not always most distressing Less common symptoms were often rated more severe and distressing Higher severity associated with lower health related QOL Heden, 2013, Dupuis, 2012, Miller, 2011, Prichard, 2010, Woodgate, 2003, Collins, 2000, 2002

Symptom Management - Parents Families employ numerous pharmacologic and non-pharmacologic strategies to provide symptom relief for their children Parent intuition, knowledge, experience; home management; flexibility in medication management; expertise in condition/management over time Worry and distress about uncontrolled symptoms creates a sense of helplessness that leads to seeking medical attention Parents value advice from providers who understand the disease and their child

PAIN/SYMPTOM MANAGEMENT

Challenges in Symptom Assessment and Management Child/Family beliefs & expectations Numerous care providers ambulatory care; inpatient care; community based care Wide range of disease management options Pharmacological Technological Supportive Multidimensional/Inter-related nature of distress

Multidimensional Distress Child Family Physical Emotional Social Spiritual

Multidimensional Distress Cancer Sickle Cell Physical Pain; Dyspnea; Fatigue Emotional Coping; Sadness; Worry Social Isolation; withdrawal Spiritual Mortality; Faith; Hope

Inter-related Distress Child Disease Toxicity Symptoms Side Effects

Inter-related Distress child Leukemia Pain, fatigue Nausea, vomiting, Hepato- toxicity

Assessment Use a standardized patient/parent assessment tool when possible Provides consistency in assessment Allows for evaluation of symptom management Symptom tools vs QOL tools Tools for research vs clinical use Symptom Screening - MSAS 7-12, (Collins 2000, 2002) 7-12 measures 8 common symptoms, measures up to 30 symptoms, Global Distress Scale – 10 items Obtains presence of symptom, frequency, severity, distress

Assessment Understand pathophysiology, treatment, progression of disease Hunt – Three forms of knowing (disease, patient, science) Comprehensive history & exam Elicit patient report as much as possible, parent report second best OK to help kids with descriptors Helps to discern appropriate treatment Child reports ‘stomach hurts’ ?Nausea, reflux, organomegaly When, where, how long, better/worse, what do you do for it…. Pertinent diagnostic evaluations Symptom management plan Determine child and family’s priority symptoms Clarify goal of intervention from family perspective Thinking outside the box

Symptom Management Anticipatory Guidance Majority of parents prefer partnership, want information about what to expect, but ultimately feel responsible for decisions about treatment and symptom management Encourage child and parent to discuss symptoms,their belief about symptoms and what they are doing at home to manage discomfort Most symptoms will have more than one potential intervention Align interventions with child/family goal for the symptom or problem Difficult symptom management decisions Surgery/Radiation Balancing disease directed therapy and comfort in adv. disease Technology

Pain in Pediatric H/O Sources of Pain Disease Diagnosis Treatment Relapse/Progression EOL Procedures BMA/LP Port access IV/Finger pokes

Key Concepts Multidimensional Experience Acute v Chronic v Acute on Chronic Tolerance Tachyphylaxis Physical Dependence Addiction

Types of Pain Nociceptive Pain (normal processing of pain) Somatic Bone, joints, connective tissue Achy, throbbing Well localized Visceral Organs, soft tissue Aching, cramping Localized, diffuse Neuropathic Pain (abnormal processing of pain) Centrally mediated Allodynia, hyperalgesia, dysthesias, hyperpathia Deafferentation pain Phantom limb, SCI Sympathetic pain Complex regional pain syndrome s/p limb salvage Peripherally mediated Polyneuropathies - chemo Mononeuropathies - compression Sharp, shooting, electric Requires adjuvant medications 2012 ELNEC Pediatric Palliative Care – Module 6 Pain Management

Pain Transmission Nociceptive transmitters Serotonin, bradykinin, histanime, PGE, sP 2012 ELNEC Pediatric Palliative Care – Module 6 Pain Management Ascending Modulation

Descending Pain Modulation 2012 ELNEC Pediatric Palliative Care – Module 6 Pain Management

Role of Receptors in Pain Mu – analgesia, euphoria, constipation, physiological dependence; respiratory depression Delta/Kappa – spinal analgesia N-methyl-D-aspartate (NMDA) - tolerance, neuropathic pain, hyperalgesia, central sensitization Increased transmission of nociceptive messages through release of by glutamate, substance P, calcitonin

Pain and the Brain Limbic System Emotion, motivation, fight/flight, pleasure Abuse/addiction, somatization, catastrophizing Neocortex Stores memory of pain experiences, recognizes type/causes of pain Neuroplasticity Ability of nervous system to change its structure and function Chronic pain as a maladaptive form of neuroplasticity Multimodal Pain Management Balanced analgesia Cognitive-Behavioral approaches

Multidimensional Pain Assessment Self report/parent report Intensity Quality Pattern Aggravating / alleviating factors Medication history Meaning

Pain – Self Report Faces Scales Visual-Analog l l 0 10 no pain worst pain 0-10 Verbal Report Scale 0 = no pain, 10=worst pain ever Wong Baker, 1998

Multivariate Tools – Self Report Initial Pain Assessment Tool Brief Pain Inventory Neuropathy Pain Scale Pain EDU.org Measures of quality and intensity of neuropathic pain Adolescent Pediatric Pain Tool (Savedra et al., 1993) Good for ages 8 and up, chronic and acute pain

Pain – Infant/Non Verbal Proxy Revised FLACC pain tool (Voepel-Lewis et al 2002) 5 domains, 0-2pts per domain Original scale for infant assessment Revised scale adds behavioral cues characteristic of NI children, parents able to add individual behaviors Good reliability, validity

Pain Management Pharmacology Opioids NSAIDS Adjuvants Non-Pharmacologic Distraction Nurse/Child Life Parents Mind/Body techniques Hypnosis, Guided Imagery, Accupressure,

Pain Management AYA widely metastatic Ewing’s Sarcoma, fractures, non-mobile. IV hydromorphone PCA with demand, escalated to 10 IV mg/day Adjuvants – gabapentin Psychology working with distraction techniques, PT/OT Chemotherapy/XRT Transitioned to oral long acting agents (methadone) with PRN immediate release (morphine) Disease progression/Hospice – con’t Methadone, gabapentin, reinitiated PCA hydromorphone demand, palliative chemotherapy

Pain Management – EOL considerations Patients with solid tumors more likely to experience complex pain syndromes Routes/Titration Adjust based on ability to take oral meds Preferences Parent Education Importance of pain management Mechanisms of pain, medications and supportive interventions

Fatigue Fatigue in Children with Cancer (Hockenberry, 2003) Children (7-12) – profound sense of being physically tired, or having difficulty with body movements Adolescents (13-18) – changing state of exhaustion that could include physical, mental, and ‘emotional tiredness’. Sleep difficulty/fatigue most commonly reported symptom (refs) Assessment Tools Childhood Fatigue Scale (Hockenberry et al 1998) Adolescent Fatigue Scale (Hinds et al 2007, 2010) PROMIS Fatigue Scale (NIH)

Sleep-related disturbances AYA with cancer Olson (2014) Systematic Review 41 articles met review criteria – most published after 2000 Leukemia (32 articles – 457 pts), Brain Tumors (21 articles – 239 pts) Majority of articles reported on adolescents receiving therapy Sleep disorders reported Difficulty initiating sleep Fragmented night time sleep Disordered breathing Excessive Daytime Sleepiness Parasomnias

Sleep Disorders in Children with Cancer Rosen & Brand 2011 Case review of 70 children with cancer in a pediatric sleep center CNS Tumors (48), Leukemia/blood disorders (18), Other solid tumor (4) Studies PSG (53), PSG + multiple sleep latency test (36), Actigraphy x 2-4 weeks (7) Findings Excessive Daytime Sleepiness most prevalent – 60% of group, 80% CNS 1/3 of patients with EDS had OSA /CSA as etiology Symptoms started after cancer treatment Treated with stimulants with good results over a number of years Insomnia (17 pts) Most common in leukemia and other blood disorders Children <10 – behavioral conditioning by parents Adolescents – associated with HD corticosteroids – treated with sedative hypnotics associated with pain – improved with adequate pain control

Childhood, Parent Fatigue Scale

Fatigue Scale - Adolescents Hinds 2007

Fatigue Scale - Adolescents Hinds, 2007

Fatigue Contributing Factors Anemia Unrelieved pain and/or SE of analgesics Unrelieved n/v and/or SE of antiemetic regimens Sleep disturbance Frequent/prolonged hospitalizations Loss of daily routines Decreased activity levels Boredom Depression Assessment frequency, severity, distress Nature of fatigue Sleep habits Daily routine What helps/what makes it worse Effect on functional ability Medication review – look for stacking of sedating meds, steroids

Fatigue – Management Pharmacologic Manage unrelieved causal symptoms Minimize sedating meds when possible Methylphenidate Adult studies generally not better than placebo (Sharp, 2013) No studies of use during treatment in childhood cancer (Sharp, 2013) Rosen (2011) case review reported success with stimulants in pts referred to sleep center Used primarily in EOL symptom management adds to anorexia Hypnotics – consider referral to sleep specialist if available Melatonin – naturally occurring substance, can have SE’s, can be used in younger children Zolpidem (Ambien) - >12 yo, aim is short term treatment, habit forming, SE’s – dizziness, daytime drowsiness, sleep walking/driving (rare) Eszopiclone (Lunesta) – similar issues as zolpidem

Fatigue Exercise Tomlinson and others (2014) Effect of exercise on cancer related fatigue Systematic Review with Meta-Analysis (72 RCTs – 1 pediatric) Exercise had a moderate effect in reducing fatigue compared with controls Improved depression and sleep disturbance Type of exercise was did not significantly influence effect on fatigue, sleep disturbance or depression Effect was larger in studies published after 2009 Non-pharmacologic Energy sparing Hydration Socialization Sleep hygiene

Nausea/Vomiting Treatment Related Chemotherapy Induced Nausea/Vomiting (CINV) Constipation Obstruction Anxiety Anticipatory (anxiety related) Acute Delayed

Assessment Tools Nausea generally more distressing than vomiting Assessment Frequency, severity, distress Dietary recall Foods tolerated, not tolerated Close monitoring of weight, nutritional status BARF *Baxter Retching Faces Scale (Baxter, 2011) Pediatric Nausea Assessment Tool (Dupuis, 2006)

CINV Prophylaxis Practice – COG Patel (2016) Two surveys developed 94 Cancer Control and Supportive Care individuals in COG institutions Asked if institution had standardized approach to practice and focused on anti-emetic choices 54 Pharmacists at COG sites where CCL RI indicated a standardized approach to CINV prophylaxis Focused on antiemetic dosing Findings 78% indicated that their institution had standardized approach to CINV prophylaxis Anti-emetic choice varied widely among respondents Results from 36 COG institutions with CINV standardized prophylaxis demonstrated significant antiemetic dosing variability Key deviations from CPGs Antiemetic choice when corticosteroids contraindicated Dexamethasone dosing Aprepitant use in children < 12 yrs Aprepitant use in presence of known or suspected drug interaction

COG endorsed CINV Management Guidelines (Dupuis and others, 2014) (Multinational Association of Supportive Care in Cancer (MASCC), 2011)

COG endorsed CINV Management Guidelines

Loss of Appetite/Nutrition Anorexia/Cachexia is a common symptom in children with cancer Alterations in taste and smell due to chemotherapy and/or radiation affect appetite and interest in food Malnutrition can be present at diagnosis most commonly in solid tumors and metastatic disease Causes of malnutrition are multifactorial interplay of iatrogenic consequences of disease/treatment, energy and substrate metabolism, and hormonal/inflammatory disturbances. Gaynor & Sullivan 2015; Cohen 2012, 2014

Risk Stratification - Malnutrition Gaynor & Sullivan 2015

Pediatric Functional Assessment of Anorexia Cachexia Therapy

Loss of Appetite/Nutrition - Management Supportive interventions Small frequent meals, favorite foods Attentive management of CINV, pain, other symptoms of CA High calorie shakes, smoothies Dietary consultation Pharmacological interventions Megesterol recent RCT placebo controlled study demonstrated benefit in increasing BMI over controls, however all MA participants (13) experienced undetectable AM cortisol and 4 experienced adrenal suppression (Cuvelier and others 2014) Periactin Enteral/Parenteral Nutrition Pros Cons

Anxiety/Depression Myers and others (2014) found that in children with ALL (age yrs) in the first year of treatment, scores for anxiety, depression, aggression and hyperactivity were similar to population norms, however more children scored in the ‘at risk category’ for depression in the first year, and anxiety for the first 3 mos. Unhealthy family function and Hispanic ethnicity was associated with anxiety Poor physical functioning, unmarried parents, and less reliance on social support was associated with depression

Anxiety/Depression Substantial inconsistency exists in screening and treatment of anxiety and depression in children and AYA with cancer Anxiety and Depression are seen as normal responses to cancer diagnosis and treatment Procedural, needle and disease related pain is a common source of anxiety Depression has been correlated with treatment non- adherence Lauer, 2015

Anxiety/Depression Assessment General mood and demeanor Pre-cancer diagnosis functioning, mood, behavior Family dynamics, communication style Open Closed Mutual Pretense (Elephant in the Room) Access to peers, friends, social activities Sudden changes in affect, behavior Symptom distress and management

PROMIS Pediatric Anxiety Scale

PROMIS Pediatric Depression Scale

Anxiety/Depression - Management Acknowledge feelings in supportive way Don’t cheerlead Supportive listening Identify social events, activities Referral to Psychology for therapeutic treatment Psychiatry referral if medication is warranted In a survey of Pedi Oncologist prescribing of SSRIs – 71% of respondents prescribed SSRIs, 28% reported monitoring patients on SSRIs and only 9% assessed for suicidality (Phipps and others, 2012)

Symptom Management at EOL Symptoms common during treatment continue to need management at EOL Identify symptoms of most concern to child and family and manage aggressively Assess patient/family goals of care, preferences for location of care, life goals Ethical Issues Fluids, Nutrition Technology Escalation of medications, Principle of Double Effect

Summary Children with cancer experience varying degrees of symptom burden throughout their disease process Anticipating, assessing and managing symptoms on a regular basis is imperative Develop symptom management plans with parents/children based on symptoms most distressful to them Clarify goals of care, child/parent hopes and potential for symptom management interventions to achieve their goals

References Collins JJ, Byrnes ME, Dunkel IJ, et al. The Measurement of Symptoms in Children with Cancer. Journal of pain and symptom management. 2000;19(5): Collins JJ, Devine TD, Dick GS, et al. The Measurement of Symptoms in Young Children With Cancer: The Validation of the Memorial Symptom Assessment Scale in Children Aged 7–12. Journal of pain and symptom management. 2002;23(1): Miller E, Jacob E, Hockenberry MJ. Nausea, Pain, Fatigue, and Multiple Symptoms in Hospitalized Children With Cancer. Oncology Nursing Forum. 2011;38(5):E Hockenberry MJ, Hooke MC, Gregurich M, McCarthy K, Sambuco G, Krull K. Symptom clusters in children and adolescents receiving cisplatin, doxorubicin, or ifosfamide. Oncology Nursing Forum. 2010;37(1):E Baggott CR. An evaluation of the factors that affect the health-related quality of life of children following myelosuppressive chemotherapy. Supportive care in cancer. 2011;19(3): Pritchard M, Burghen EA, Gattuso JS, et al. Factors that distinguish symptoms of most concern to parents from other symptoms of dying children. Journal of pain and symptom management. Apr 2010;39(4): Fakhry H, Goldenberg M, Sayer G, et al. Health-Related Quality of Life in Childhood Cancer. Journal of developmental and behavioral pediatrics : JDBP. July/August 2013;34(6): Woodgate RL, Degner LF. Expectations and beliefs about children's cancer symptoms: perspectives of children with cancer and their families. Oncology Nursing Forum. 2003;30(3): Woodgate RL, Degner LF, Yanofsky R. A different perspective to approaching cancer symptoms in children. Journal of pain and symptom management. 2003;26(3): Baggott C, Cooper BA, Marina N, Matthay KK, Miaskowski C. Symptom cluster analyses based on symptom occurrence and severity ratings among pediatric oncology patients during myelosuppressive chemotherapy. Cancer nursing. Jan-Feb 2012;35(1):19-28 Hockenberry MJ. Sickness behavior clustering in children with cancer. Journal of Pediatric Oncology Nursing. 2011;28(5):263

References Savedra MC. Assessment of postoperation pain in children and adolescents using the adolescent pediatric pain tool. Nursing research (New York). 1993;42(1):5-9. Breau LM, McGrath PJ, Camfield CS, Finley GA. Psychometric properties of the non- communicating children's pain checklist-revised. PAIN. 2002;99(1–2): Hunt A, Goldman A, Seers K, Crichton N, Moffat V, Oulton K. Clinical validation of the Paediatric Pain Profile. Developmental Medicine & Child Neurology. 2004;46(1):9-18. Voepel-Lewis T, Merkel S, Tait AR, Trzcinka A, Malviya S. The reliability and validity of the Face, Legs, Activity, Cry, Consolability observational tool as a measure of pain in children with cognitive impairment. Anesthesia and analgesia. Nov 2002;95(5): , table of contents. Solodiuk J, Curley MAQ. Pain assessment in nonverbal children with severe cognitive impairments: the individualized numeric rating scale (INRS). Journal of pediatric nursing. 2003;18(4): Tomlinson D. Initial development of the Symptom Screening in Pediatrics Tool (SSPedi). Supportive care in cancer. 2014;22(1): Hinds PS, Hockenberry M, Tong X, et al. Validity and Reliability of a New Instrument to Measure Cancer-Related Fatigue in Adolescents. Journal of pain and symptom management. 2007;34(6):

References Baxter, A. L. (2011). "Development and validation of a pictorial nausea rating scale for children." Pediatrics (Evanston) 127(6): e1542-e1549 Cohen, J. J. (2014). "Taste and smell dysfunction in childhood cancer survivors." Appetite 75: Cuvelier, G. D. (2014). "A randomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy." Pediatric blood & cancer 61(4): Dupuis, L. L. (2006). "Development and validation of the pediatric nausea assessment tool for use in children receiving antineoplastic agents." Pharmacotherapy 26(9): Dupuis, L. L. (2014). "Guideline for the prevention and treatment of anticipatory nausea and vomiting due to chemotherapy in pediatric cancer patients." Pediatric blood & cancer 61(8): Gaynor, E. P. T. and P. B. Sullivan (2015). "Nutritional status and nutritional management in children with cancer." Archives of Disease in Childhood 100(12): Hockenberry, M. J. M. J. (2003). "Three instruments to assess fatigue in children with cancer: the child, parent and staff perspectives." Journal of pain and symptom management 25(4):

References Lai, J.S. (2005). "Anorexia/cachexia-related quality of life for children with cancer." Cancer 104(7): Lauer, A. L. (2015). "Treatment of Anxiety and Depression in Adolescents and Young Adults With Cancer." Journal of Pediatric Oncology Nursing 32(5): Myers, R. M., L. Balsamo, et al. (2014). "A Prospective Study of Anxiety, Depression, and Behavioral Changes in the First Year after Diagnosis of Childhood Acute Lymphoblastic Leukemia: A Report from the Children’s Oncology Group." Cancer 120(9): Olson, K. (2014). "Sleep-related disturbances among adolescents with cancer: a systematic review." Sleep Medicine 15(5): Patel, P. P. (2016). "Chemotherapy-Induced Nausea and Vomiting Prophylaxis: Practice Within the Children's Oncology Group." Pediatric blood & cancer 63(5): Rosen, G. G. (2011). "Sleep in children with cancer: case review of 70 children evaluated in a comprehensive pediatric sleep center." Supportive care in cancer 19(7): Sharp, V., F. Finlay, et al. (2013). "Question 1Is methylphenidate a useful treatment for cancer-related fatigue in children?" Archives of Disease in Childhood 98(1): Tomlinson, D. D. (2014). "Effect of exercise on cancer-related fatigue: a meta-analysis." American journal of physical medicine & rehabilitation 93(8):

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