K!N4E4 Midterm 2 Flashcards
What are the goals of pretreatment (prehabilitation)?
reduce side effects/complications, hasten recovery, qualify for treatment, delay/prevent treatment (treat disease), improve treatment efficacy
What are the goals of treatment (tolerance/efficacy)?
prevent/manage side effects and complications, complete treatment, treat disease, make treatment more effective, and hasten recovery
What is the duration of
RT?
CT?
HT?
IT?
RT=5-6 weeks
CT=4-6 months
HT=years
IT=years
What are the goals of survivorship (rehab/recovery)(prevention/promotion)?
recover from acute side effects (including deconditioning), prevent/manage long term side effects, lower disease risk (including recurrence), improve survival and general health promotion
What are the goals of end of life (palliation)?
symptom management (pain, constipation, poor appetite, psychosocial distress), maintain functional independence, improve quality of life, slow disease progression, and improve survival
How many cancer patients die from disease?
50%
What are 8 disease variables?
Type of Cancer
Subtype of Cancer
Disease Stage
Tumor Grade
Tumor Biomarkers
Time since diagnosis
Treatment Response
Disease Outcomes
What is type of cancer?
Major Cancer sites such as breast, lung, colorectal, lymphoma
What is subtype of cancer?
Lymphoma subtypes include diffuse large B cell, follicular, and mantle cell
What is disease stage?
Extent and spread of the cancer, usually ranging from stage 1 to stage 4
What is tumor grade?
Indicator of the abnormality and aggressiveness of the cancer
What is tumor biomarkers?
Estrogen receptor status, progesterone receptor status, HER2 status
What is time since diagnosis?
Common cut points are 2, 5 and 10 years.
What is treatment response?
Disease can progress, stabilize, or show a partial or complete response
What is disease outcomes?
Recurrence-free survival, progression-free survival, second primary cancers, deaths from treatment toxicity, cancer-specific survival, and overall survival
What are the 8 treatment variables?
Surgery
Radiation Therapy
Chemotherapy
Endocrine Therapy (hormone therapy)
Biologic therapy (immunotherapy)
Stem cell transplant (bone marrow transplant)
Multimodal therapy
Average relative dose intensity
What is surgery as a treatment variable?
type, location, and extent (partial vs radical nephrectomy)
What is radiation therapy as a treatment variable?
ionizing radiation of varying types, field locations, dosing, and schedules
What is chemotherapy as a treatment variable?
cytotoxic drugs of various types, administration, and scheduling
What is endocrine therapy (hormone therapy) as a treatment variable?
Hormone treatments (aromatase inhibitors)
What is biologic therapy (immunotherapy)?
uses the body’s immune system to fight cancer (herceptin)
What is stem cell transplant (bone marrow) as a treatment variable?
used to restore the stem cells when the bone marrow has been destroyed by disease, chemo, or radiation
What is multimodal therapy as a treatment variable?
combination and sequencing of different treatments
What is average relative dose intensity?
percentage of the planned chemotherapy dose received
What are the four propositions of the field of physical activity and cancer survivorship.
1: Cancer variables may be outcomes of PA
2: Cancer variables may be moderators of PA outcomes
3: Cancer variables may be determinants of PA
4: Cancer variables may be moderators of PA determinants
What does cancer variables may be outcomes of PA mean?
- PA may influence treatment decisions, completion rates, and efficacy (response)
- PA may influence disease transformations, progression, recurrence, and survival
- Cancer outcomes of PA may be intermediate outcomes for other outcomes
- fear of cancer recurrence is a major issue
What are the 4 cancer outcomes by phase?
pretreatment: progression, treatment eligibility, completion, and efficacy/response
treatment: completion, efficacy/response
survivorship: recurrence, survival
palliative: progression, survival
What does Cancer Variables may be moderators of PA Outcomes mean??
may alter typical observed exercise response
health-related fitness, psychosocial outcomes, QoL outcomes, cancer outcomes, and mechanisms
may negate or amplify “standard” effects.
any CV may moderate any exercise outcome
may also influence what PA motives are promoted
What does Cancer variables may be determinants of PA mean?
- may influence adherence and participation
- CV’s may impact any aspect of PA (type, volume, intensity, progression, pattern, context).
- may influence any social cognitive mediators of PA (attitude, control, support, intention)
What does Cancer variables may be moderators of PA determinants mean?
- demographic, medical, environmental, social cognitive
- any CV may moderate any PA correlate
- may influence which determinants are targeted.
- may alter effectiveness of PA behavior change interventions (who, what, when, where)
What is the basic proposition of EX oncology?
if cancer variables are not outcomes of PA, if they do not moderate other outcomes of PA, if they are not determinants of PA, or if they do not moderate other determinants of PA, then the case for the field of EX oncology is weak (we would apply exercise research from other populations without concern for CV)
What is “PICOS” for Exercise Oncology?
Population: disease and treatment variables
Intervention: any exercise prescription
Comparison: standard of care in cancer
Outcome: relevant to cancer patients
Study designs: RCTs where feasible
What are the 3 current settings for rehabilitations?
- pending treatments (time from decision until treatment) time is usually fairly short
- possible treatments (not “fit” for treatment) not very common (lung/major surgery)
- active surveillance (decision is not to treat right away) prostate/breast
What are the specific goals of pre-treatment?
reduce side effects/complications
hasten recovery after treatment
make treatment more effective
qualify for treatment (if “unfit” for treatment)
delay/prevent treatment (treat disease) if patient is on active surveillance
What has good evidence from the overall results for pre-treatment?
feasibility in some settings
↑ physical fitness and physical functioning
↑ some psychosocial outcomes and QoL
What has limited evidence form the overall results for pre-treatment?
surgical complications
length of hospital stay
time to adjuvant therapy
treatment/disease outcomes (preclinical/animal studies)
What are 3 key mecanisms in direct exercise effects on cancer?
- cell growth regulators
- immune system components
- inflammation
What are the 3 major findings from “High Shear Stresses under Exercise Condition Destroy Circulating Tumor Cells in a Microfluidic System?
- High shear stress of 60 dynes/cm2 achievable during intensive exercise killed more CTCs than low shear stress of 15 dynes/cm2 present in human arteries
- High shear stress caused necrosis in over 90% of CTCs within the first 4h circulation. The CTCs that survived the first 4h underwent apoptosis 16-24h post-circulation incubation
- Prolonged high shear stress reduced viability of highly metastatic and drug resistant breast cancer cells. Intensive exercise may be good strategy for generating high shear stress to destroy CTCs and prevent metastasis
What does EX during cancer treatment improve/manage?
physical fitness and physical functioning
body composition (muscle loss, fat gain)
some symptoms (fatigue, pain, sleep, depression)
some aspects of QoL (physical and functional)
For the results for EX during treatment what is there preliminary evidence for?
Improved:
chemotherapy completion rate,
treatment response and cancer outcomes
What are 5 mechanisms of improved treatment efficacy?
↑ angiogenesis and intratumoral vascularization
↑ intratumoral blood perfusion
↓ intratumoral hypoxia
↑ intratumoral immune cell infiltration
↑ delivery of other blood elements/products
What were the results of the “Fluidic shear stress increases the anti-cancer effects of ROS-generating drugs in circulating tumor cells” study?
Fluidic SS significantly increased the potency of the ROS-generating drugs doxorubicin (DOX) and cisplatin but had little effect on the non-ROS-generating drugs Taxol and etoposide
- basically shear stress makes some drugs more effective
What does the HELP trial stand for?
Healthy Exercise for Lymphoma Patients
What was the HELP trial?
RCT comparing AET to UC in 122 lymphoma patients receiving chemotherapy or off treatments
12 weeks supervised exercise training
primary endpoint TOI-An
secondary endpoints of HRF, PROs, medical
What is a key takeaway from the HELP trial?
A healthy dose of exercise is good medicine, even for lymphoma patients receiving chemotherapy
What was the EXERT trial?
Exercise during and after neoadjuvant rectal cancer treatment
What was the major finding of the EXERT trial?
Patients with rectal cancer who exercise while recieving radiation therapy more likely to have tumors disappear
What was the START trial?
Supervised Trial of Aerobic versus Resistance Training
RCT examining AET versus RET versus UC in 242 BC patients on chemotherapy.
What are the 5 steps of Rectal Cancer Treatment with timelines?
Chemoradiation (5-6weeks)
Break (6-8 weeks)
Surgery
Break (4-12weeks)
Chemo (4-4.5 months)
For the START trial? Did taxane or non-taxane have great resistance training response?
Non-taxane has better increase in strength
How does the stage of disease effect muscle mass changes in START trial?
Later stages of disease has larger improvements in muscle mass changes (both RT atnd AT)
What effects did the START trial have on relative dose intensity? (RDI)
resistance training had a statistically significant relative dose intensity compared to the control group (~90% completion)
What are the 5 steps of the recommended process for targeted exercise prescription for cancer patients?
- patient assessment
- determine health issues
- identify patient capacity and intervention suitability
- exercise prescription
- reassessment and modification
What are considerations for patients with anemia?
- shorter duration aerobic
- lower intensity
What are considerations for patients with thrombocytopenia?
- avoid exercise with a risk of falls or blunt forces
- water based activity is good
What are considerations for patients with neutropenia?
- avoid high intensity
- encourage hand washing
- avoid crowded locations
What are considerations for patients with sarcopenia?
- increased resistance training to maintain muscle mass
What are the goals of posttreatment?
recover from acute side effects (including deconditioning), prevent/manage long term side effects and complications, general health promotion, treat disease (progression/recurrence)
What does exercise after treatment improve/manage?
similar outcomes during treatment but stronger effects,
larger and more rapid improvements in fitness and QoL,
some biomarkers related to cancer/disease
What is precision medicine?
attempt to address substantial heterogeneity in patient disease and response to therapy
“tailoring of medical treatments to the individual characteristics of each patient”
“medical care to optimize therapeutic benefit for particular groups of patients, using genetic or molecular profiling” (subgroups)
What is the primary goal of precision medicine?
give an intervention to patients who will benefit and not give it to patients who will not benefit (or be harmed)
What is the secondary goal of precision medicine?
avoid the side effects and costs of giving the intervention to patients who will not benefit (or will be harmed)
What is the main difference between public health and precision medicine?
public health focuses on the population level
precision medicine focuses on an individual level
Why is precision medicine and exercise needed?
substantial variability in response to exercise interventions
What is precision medicine trying to understand?
not about understanding biological factors that are mechanisms (mediators) but biological factors that predict response (moderators)
What are you trying to identify with precision medicine?
genetic or molecular subgroups of patients whose cancer outcomes are benefitted (or harmed) by specific exercise prescriptions
- if subgroups could be identified, likely patients would be highly motivated to perform the targeted exercise prescription
What are the exercise recommendation highlights from the American Society of Clinical Oncology?
Oncology providers should recommend aerobic and resistance exercise during active treatment with curative intent to mitigate side effects of cancer treatment.
-reduce fatigue
-preserve cardiorespiratory fitness and strength
-improve QoL
-reduce anxiety and depression
-have low risk of adverse events
What are the 5 cancer specific exercise factors?
type and subtype of cancer
stage of disease
phase of the cancer continuum/trajectory
type of treatments
nature and severity of side effects
What are the 5 general exercise principles?
avoid inactivity; sedentary behavior is bad
some exercise is better than none.
more exercise is better (dose-response).
start easy and progress slowly.
exercise must be individualized based on patient function, side effects, preferences, and goals
For exercise in cancer patients, what is the most compelling efficacy outcome?
cancer outcomes (if supported by evidence)
cancer-specific symptoms/side effects
general health-related fitness outcomes
For exercise in cancer patients, what are the most important feasibility / safety issues?
surgical limitations/complications
RT side effects
chemotherapy/drug side effects
What is the 2 step process for exercise prescription?
Step 1: Develop EX prescription based on efficacy
- cancer outcomes, symptom management
Step 2: Modify EX prescription based on safety/feasibility
- driven by symptoms/side effects/toxicities
What are the 4 exercise prescription components?
type or mode of activity
total weekly amount or volume
“fractionation” (frequency, intensity, duration)
context (physical and social environment)
What is the generic recommended exercise guidelines for patients?
150 minutes/week of mod intensity aerobic EX.
75 minutes/week of vig intensity aerobic EX.
or equivalent combination ex. 50 mod + 50 vig).
2-3 days/week of strength exercises of major muscle groups using 8-12 repetitions; 3 days of balance
What is the primary dose reduction strategy?
intensity
Does exercise context matter?
- social context important for optimizing psychosocial health
- EX should engage the mind and spirit, not just the body
What are 7 Safety (risks) of EX in Cancer Patients?
low exercise capacity and decreased strength
low blood counts (myelosuppression)
poor balance and coordination (ataxia)
peripheral neuropathy
increased fatigue
decreased cognitive status
bone metastases
What are 5 potential adverse effects of exercise during or after treatment?
- exacerbation of symptoms (pain, fatigue, nausea, dyspnea)
- immunosuppression
- falls
- bone fracture
- lymphoedema
What are the 3 variables of survivors meeting the PA guidelines?
- time since diagnosis
- disease status
- disease stage
What was the only statistically significant variable between cancer/medical variables and exercise behaviour?
Major cancer type
What was different about the CARE trial?
it was objective exercise data compared to most other ones were self-report
What 2 variables were statistically significant in the CARE trial?
Length of chemo protocol:
- shorter chemo, better adherence to exercise programs
FEC-D:
REC-D is difficult to adhere to
What 2 types of cancer are associated with Affective Attitudes?
Breast, Prostate
NOT colorectal
