Chemo Fog: What it is and what can we do about it

Transcription

1 Chemo Fog: What it is and what can we do about it Lori Bernstein, Ph.D., C.Psych. Dept of Psychosocial Oncology & Palliative Care & Cancer Survivorship Program Health, Wellness, and Cancer Survivorship Centre University Health Network, Princess Margaret Hospital Dept of Psychiatry, University of Toronto October 19, 2012 Canadian Association of General Practitioners in Oncology Calgary, Alberta

2 Disclosures I have no financial affiliations or financial conflicts of interests to disclose.

3 Learning Objectives To familiarize you with: Effects of chemotherapy on cognition Effects of radiation treatment on cognition Effects of patient-related factors on cognition Interventions/treatments Role of the GPO and patient in managing it

4 Definition Recent term (chemo-brain; chemo-fog), loosely defined as: Cognitive dysfunction (decline, impairment, disturbance) that accompanies or follows chemotherapy treatment for cancer. It was first described by breast cancer patients.

5 Self-report assessment of cognition Perceived cognitive dysfunction is a symptom experienced by patients who have had chemotherapy Symptoms are highly prevalent while on treatment (up to 85%) Breast cancer patient advocacy and support groups regularly discuss these symptoms Extending into other cancer types Impacts return-to-work success, QoL, social relationships

6 Self-reported Cognitive Problems in Daily Life after Adjuvant Chemotherapy (CMF) and Surgery Had CMF* (39 patients) Had Surgery (34 patients) Reported Concentration Problem 31 % 6 % Reported Memory Problem 21 % 3 % Reported Language Problem 8 % 3 % Cyclophosphamide, methotrexate, fluorouracil Schagen, et al. Cancer 1999

7 Chemotherapy and objective neurocognitive function

8 Objective Assessment of Cognition Objective cognitive testing (with or without imaging) is one way we quantify cognitive ability compared to normative data It is used as an outcome variable in clinical trials Can compare different groups at a single point in time (cross sectional); or Follow same groups over time and compare performance (longitudinal)

9 Objective assessment of cognitive function and chemotherapy Mean memory recall scores from the MMSE (top) and the HVLT (bottom) preand postinfusion of a mitotic inhibitor. Meyers & Wefel, JCO, 2003

10 Findings Types of cognitive domains affected: Often: Attention, concentration Short term memory (verbal and visual material) Word finding Sometimes: Spatial memory Processing speed Seldom: Logic, reasoning, problem solving Knowledge Visual spatial perception

11 Findings More chemo => increased risk (Schagen et al Neurooncol 2001) Cognitive dysfunction most severe during active treatment or while other symptoms present Improvements occur up to 2 years after treatment, but not always to pre-treatment Chemotherapy versus cranial radiation Subset of patients (~25%) show cognitive dysfunction prior to chemotherapy Cognitive dysfunction long term for subset of patients (e.g., 20 yrs post chemo - Koppelmans et al 2012 J Clin Oncol)

12 Neuropsychological test example: Working Memory

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14 N-Back Working Memory Task 1-Back (Easy Task): Report the letter that you saw 1 before (right before) what is on the screen.

15 N-Back Working Memory Task 2-Back (Harder Task): Report the letter that you saw 2 before what is on the screen.

16 3-Back Working Memory Task 3-back (very difficult): Report the letter that you saw 3 before what is on the screen.

17 This is just one example of a behavioral task testing performance, in this case of working memory Often, patients report cognitive decline, but on testing, they perform well Why might this be?

18 Twin Study Performed while in an Magnetic Resonance Imaging scanner, and you can record brain activity (via blood flow) while the person is doing the task.

19 Neuroimaging: Twin study Identical twin sisters. One had cancer and chemotherapy, and the other did not. 2 yrs post chemo. Working memory task Functional magnetic resonance imaging (fmri) This study is unique because the individuals are as identical as possible, other than the history of breast cancer

20 Functional magnetic resonance images of 60-year-old identical twins during a working memory task with incrementally increasing levels of difficulty (left to right) Ferguson, R. J. et al. J Clin Oncol; 25: Copyright American Society of Clinical Oncology

21 Functional magnetic resonance images of 60-year-old identical twins during a working memory task with incrementally increasing levels of difficulty (left to right) Ferguson, R. J. et al. J Clin Oncol; 25: Copyright American Society of Clinical Oncology

22 Twin study Chemo sister had more activation in more regions for same level of performance One implication is that cancer patient s brain has to work harder in order to do as well, even on the easy task Possible explanation for mental fatigue that patients often report

23 Cranial radiation and neurocognitive function

24 Time Course of Radiation Injury DNA of the cell damaged immediately Biologic expression of the injury: cell death, when cells attempt to divide delayed hours-days-years timing depends on cell kinetics

25 Radiation: acute effects nausea, vomiting epithelial tissues (skin, mucosa, hair loss) somnolence (up to 1 year post tx)

26 Radiation: late effects Progressive, delayed onset (1-10 years) vasculature white matter cortical atrophy endocrine dysfunction second tumors neurocognitive decline

27 Neurocognitive late effects information processing speed (thinking speed and motor speed) memory attention

28 Neurocognitive late effects Extent of decline related to: Diagnosis brain tumor patients have poorest outcomes Treatment type, dose, fractionation Age at treatment very young and elderly most vulnerable

29 Neurocognitive Late Effects: Age Matters Adults: cognitive decline, loss of previously acquired skills (e.g., dementia) Children: failure to acquire skills at the same rate as same age peers Young children (<5 yrs) most vulnerable Altered developmental trajectory Progressive falling away from peer group Academic, vocational, psychosocial implications

30 Radiation late effects in childhood Brain injured children grow into their deficit As demands change, deficits become evident

31 Raw Score Relation between age, raw score, and IQ Chronological Age

32 Case Study Paul, age 27 Early developmental milestones WNL Medulloblastoma, age 5 Surgery Craniospinal radiation 36 Gy + 18 Gy boost to posterior fossa Chemotherapy

33 Case Study (Paul) Physical Late Effects Age 11: hypothyroidism Age 14: 2 shunt revisions Age 19: progressive hearing loss Age 24: left frontal meningioma Age 27: meningioma recurred, postoperative seizures MRI documents cerebral atrophy, lacunes in the basal ganglia and thalamus, vascular lesions in the temporal lobe

34 STANDARD SCORE Case Study (Paul): Neurocognitive Late Effects Verbal IQ Performance IQ yrs 14 yrs 16 yrs 27 yrs

35 Percentile Neurocognitive late effects: brain tumor survivors VIQ P IQ WM I P SI Reading Fluency Trails A Trails B Recall, immediate Recall, delayed

36 Index Score Neurocognitive late effects: leukemia survivors < 5 years > 6 years Attention Reasoning/Calculation Memory Spatial Reaction Time Treated with chemo and whole brain RT (Test: Micro-Cog)

37 Head and Neck Another population worth examining: Can receive chemotherapy (cisplatin) Also receive radiotherapy close to brain (but is it close enough and/or of sufficient dose to have impact?) Examined the RT dose dependence to area of the brain known to be important to learning new information (medial temporal lobe).

38 Memory and Temporal Lobe RT Gan, Bernstein, Brown, et al. (2011) International Journal of Radiation Oncology, Biology, Physics.

39 CNS-directed radiation late effects: summary physical, neurocognitive, psychosocial age at treatment and dose can alter outcomes dramatically other treatments can affect outcomes too

40 Patient-related factors affecting cognition (with or without cancer) Physical (pain, anemia, hormonal, endocrine, age) Psychological (anxiety, depression, distress ) Fatigue Sleep disturbance Medication (for pain, insomnia, anxiety, or cancer itself e.g., Thalidomide for MM) Cognitive reserve (IQ, edu) Co-morbid illnesses History of brain injury/concussion

41 To review Cranial RT cog profile: delayed & degenerative/progressive Chemo cog profile: immediate and stable/ improving Mood and/or meds can mimic/exacerbate problems People with cancer can have other things going on There is no DSM diagnostic criteria for cancer-related cognitive dysfunction (NOS) Subjective and objective cognition appear to measure different phenomena Cancer-related cognitive dysfunction more inclusive term than chemo-fog or chemo-brain Etiology is multifactorial; different for different people

42 Some disease, treatment, and pt factors associated with cognitive dysfunction in cancer Other Treatment Hormone Status Genetics; Comorbidities Behaviors

43 What can GPOs do

44 Case Study: Mrs. D. Age 60, native English speaker Education: B.A.; Occupation: investment advisor Breast Cancer diagnosis June 2008 Non smoker; 2 drinks/wk On meds for high blood pressure & cholesterol On anti-hormonal treatment for estrogenreceptor positive breast cancer Seeing psychiatrist for depression, fear of recurrence, but not on any mood meds Mother had stroke; Father - Alzheimer s disease in his early 90s

45 Case Mrs. D: Self-reported Cognitive Profile: I was very smart Change (decline) learning new information retrieving recent & old info distracted, can t maintain multi-tasking speed of completing tasks (rechecking) mentally tires easily more emotional, overwhelmed when many things need to be done Less change visual memory (faces, pictures, places) language comprehension (written and spoken) visual perception, imagery logic, problem solving good, although it can take longer

46 Case: Neuropsychological Testing Strengths (High Average-Superior) Intelligence Language Memory retention (both verbal and visual) Visual perception & organization Weaknesses (Average Range) Encoding new information Variable speed of processing (avg-superior) Executive functioning (staying on task, inhibiting dominant response)

47 Case: Differential diagnosis No cognitive impairments in any domain, but still consider evidence for Cancer-related cognitive dysfunction Depression Dementia (AD/vascular) Other things need to be ruled out first: Thyroid, B12, brain mets, anemia

48 Case: Differential diagnosis Cancer-related cognitive dysfunction: encoding, attention, speed, multitasking Depression: can cause variability in retrieval, speed Dementia (AD/vascular): no evidence of this (retention, semantic fluency, wordfinding, visual spatial, organization approach, learning with repetition all intact) Blood work for thyroid, anemia, B12 Imaging for brain mets, stroke Other: fatigue, pain, sleep, medications Family member interview- no change over past year, patient stressed, back at work full time, & hard on herself

49 In general, what should GPOs do Ask questions: When did you first begin experiencing these symptoms? Have your symptoms been continuous or occasional? How do your symptoms affect your everyday life? What, if anything, seems to improve your symptoms? What, if anything, appears to worsen your symptoms? Try to speak with family member and ask them same questions about the patient

50 What can GPOs do From the medical side: Rule out other causes (e.g., stroke, dementia, thyroid, anemia, nutrition deficiencies) Usual diagnostic tools- brain MR, blood work, including formal neuropsych assessment if possible Referral to other services, e.g., neurology, geriatrician (mild cognitive impairment), psychiatry, counseling for distress Treat serious insomnia (but no benzodiazapines), & sleep apnea aggressively Montreal Cognitive Assessment, MoCA (vs MMSE) if no neuropsychology services available

51 What can GPOs do to help patients From the supportive care side: Listen for red flags, inconsistent with typical chemo-brain (worsening post treatment, not associated with other symptoms, family members notice more than patient) No magic pill

52 What else can help patients Behaviors to increase self-efficacy: Increased knowledge: Provide written information about managing expectations, explaining and normalizing symptoms (e.g., pamphlets, websites, books on chemo-brain and memory in general) Pt noticing patterns or contexts that improve or worsen symptoms Learning strategies to minimize impact of cognitive difficulties, self-management emphasis, in group or individual setting On-line information and social networking groups for remote communities

53 Interventions Under Investigation Methylphenidate - ADHD Modafinil - fatigue Alzheimer s disease meds (eg., Donepezil) SSRIs (mood, anti-inflammatory, neuroprotective) Benefits of exercise Cognitive re-training, psycho-educational programs to teach behaviors known to be associated with improved objective and selfreported cognitive performance Stress management Animal models

54 Resources for Patients Your Brain After Chemo: A Practical Guide to Lifting the Fog and Getting Back Your Focus Dan Silverman (2010) ChemoBrain: How Cancer Therapies Can Affect Your Mind Ellen Clegg (2009) Cancer-Related Cognitive Dysfunction Pamphlet (brought copies, and I can copies also) and lists some websites

55 Acknowledgements PMH Health Wellness and Cancer Survivorship Program (ELLICSR, PMH Foundation) Canadian Breast Cancer Research Alliance Canadian Breast Cancer Foundation CIHR Many colleagues at PMH, including: Kim Edelstein Norma D Agostino Pamela Catton Gary Rodin Ian Tannock Kattleya Tirona

56 Thank you!