Cancer Survivorship Flashcards
Survivorship Issues
- Cancer
- Recurrence of primary cancer
- Secondary Malignancies
- Sexual and Reproductive Health
- Menopausal symptoms
- Sexual dysfunction
- Infertility
- Neurologic
- Cognitive problems
- Neuropathy
- Organ dysfunction
- Cardiac (anthracyclines & trastuzumab)
- Pulmonary (bleomycin)
- Renal (cisplatin)
- Bone Loss
- Mental Health
- Fatigue
- Insomnia
- Depression/anxiety
Cancer Survival Definitions
net survival
cancer survivor
- Net Survival:
- “The survival probability that would be observed in the hypothetical situation
where the cancer of interest is the only possible cause of death” (CCS,
Canadian Cancer Statistics, 2019) - “Cancer Survivor”:
- “An individual is considered a cancer survivor from the time of diagnosis,
through the balance of his or her life” (NIH, National Coalition for Cancer
Survivors, NCCN 2020) - May be living with cancer or free of cancer
- Not meant to be a label.
- NOTE: some patients do not like or identify with the term “survivor”.
Cancer Survival
* Cancer screening & treatment has vastly improved over the past 40 years
- Adult cancers (age 15-99)
- 5 year net survival is 63% (2019 CCS data)
- Prostate cancer – 93%
- Breast cancer – 88%
- Colo-rectal cancer – 65%
- Number of people with a cancer cure experience or cancer as a chronic illness is
growing - Childhood cancers (cancer under the age of 15)
- Overall 5 year survival rate for childhood cancer – 84% (2019 CCS data)
- 5 year survival is highest for Hodgkin lymphoma, retinoblastoma, nephroblastoma, gonadal germ cell tumours
(>95%) - 5 year survival is lower for AML (64%), bone tumours (70%), soft tissue sarcoma (71%)
- Many have a long life ahead!
Cancer Treatment
- Chemotherapy
- Narrow therapeutic window
- Dose limiting toxicity (DLT)
- Kills rapidly dividing cells
- Hormonal Manipulation therapies
- Menopause
- Pharmacologic/Chemical castration
- Targeted therapies
- Chronic treatment
- Radiation
- Consider possible damage to surrounding tissues
- Surgery
- Consider impacts of mastectomy, oophorectomy, colon resection, orchiectomy,
trachelectomy, brain surgery, head and neck surgery
Effects of Cancer and its Treatment
Physical
* Secondary Cancer
* Organ Damage
* Physiologic changes
from treatment
Psychosocial
* Psychologic distress
* Mental health
* Financial burden
* Developmental Issues
Short Term Effects
* Temporary and improve with
time
Long Term Effects
* Progressive
* Permanent
Late effects
* Manifest months to years later
* Example:
secondary malignancy
Chemotherapy Induced Neurotoxicity
- Can be peripheral, autonomic, and/or central neurotoxicity
- Symptoms:
- Sensory symptoms:
- Numbness, tingling, neuropathic pain, increased sensitivity to hot/cold, decreased vibration
and pinprick sensitivity - Motor symptoms:
- Hyporeflexia, weakness, muscle cramps
- Autonomic symptoms:
- Dizziness, hearing loss, constipation
- Long term considerations:
- Peripheral Neuropathy
- Movement disorders, changes in gate/posture, risk of falls
- Estimated that 30% of cancer survivors fall every year
- Evaluations for tinnitus and hearing loss (eg cisplatin)
Anticancer Drugs of Concern
Platinums Taxanes Vinca
Alkaloids IMIDs Proteasome
inhibitor
Ab-Drug
Conjugate
see slide 11
CIPN
Distribution
Glove-Stocking
Duration
Typically ~ 3 months after stopping
treatment
Can persist up to a year or longer with
some medications (IMIDs, brentuximab)
Platinum toxicity can progress for several
months and lead to permanent damage
Taxanes/Vincas duration up to 5-7 years
Risk Factors
Prior chemotherapy
Diabetes
Folate/Vit B12 deficiencies
Smoking history
Decreased creatinine clearance
CIPN Treatment
- Prevention – exercise??
- Goals of pharmacotherapy
- reduction in pain by at least 30%
- Improved function, mood, sleep
- Minimize adverse effects
- Therapeutic options:
- Duloxetine – First line, only agent shown in a RCT to be effective for CIPN
- Other agents where efficacy has been established in other forms of
neuropathic pain can be used as adjunct or if duloxetine ineffective or not
tolerated: - Gabapentin, pregabalin
- TCAs (amitriptyline, nortriptyline, desipramine, or imipramine)
Chemo Brain (aka Brain Fog)\
presentation, Mech, duration
Presentation
↓ in memory
Word-finding difficulty
Difficulty concentrating
↑ time to complete tasks
Mechanism
DNA damage & oxidative stress from cytotoxics
Also seen in targeted agents
Prevalence and Duration
46% prevalence of perceived cognitive
dysfunction in cancer survivors
May go away at end of treatment
In ~ 1/3 patients, may persist for 5-10 years
Chemotherapy related Cognitive Dysfunction
management
- No effective brief screening tool has been identified
- Mini-mental state examination (MMSE) lacks adequate sensitivity for the more subtle decline
in cognitive performance commonly seen in survivors - Management is mostly supportive
- Validation of symptom experience
- Keep in mind the implications to compliance with medications
- Provide strategies for forgetfulness
- Social support and understanding from friends/family is important
- Lifestyle: routine physical activity, limiting use of alcohol, stress management, relaxation
- Consider meditation, yoga, cognitive training (brain games)
- Consider the additive impact of brain radiation, brain cancer/metastases, brain
surgery
Mental Health
- Dealing with fear
- Can have constant and intrusive thoughts (disease, control, independence, dying)
- Managing anger
- Disease, delays, obstacles in health care system
- Guilt
- Cause of illness, impact on family, hereditary component
- Stress
- diagnosis, finances, loss of work, away from school
- Identity and Self Image
- Cancer stigma, changes in appearance
- Pain
- Clinical Mental Health Diagnosis
- Depression, Anxiety, Adjustment Disorder, PTSD
- Cancer survivors use medication for anxiety and depression at a rate about twice that of the general population
Depression and
Anxiety
The RR for depression was highest in those studies
that included patients less than 2 years since
diagnosis (p<0.0001)
The RR for anxiety was highest for patients
diagnosed with cancer more than 10 years
previously (p<0.001)
the pink column is people who were diagnosed with cancer less than 2 years ago. The blue is 2 t0 10 years, and the green is greater than 10 years. So when we look at depression.
we see this relative risk of like 2.2 to have depression.
If you were less than 2 years from your diagnosis,
where we’re looking at anxiety
greater than 10 years, that’s where the highest bar is here. I the anxiety. Is it going to come back.
Treatment depression/anxiety
- Supportive Services
- Psychologists
- Social Workers
- Support Groups
- Counselling
- Pharmacotherapy
- Options:
- SNRIs (consider if concomitant pain
or hot flashes) - SSRIs (watch for drug interactions,
example with tamoxifen) - Appropriate monitoring
- Appropriate education
- May take 2-6 weeks for SSRIs or
SNRIs to take effect
Cancer Treatment Induced Infertility
- Can impact ALL people of parenting or pre-parenting age
- Impaired spermatogenesis
- Reduced ovarian reserve
- Should be discussed BEFORE initiating therapy if possible
- Allows informed decision making for family planning and/or fertility preservation
- All interested and ambivalent patients should be referred to reproductive specialist
as early as possible before treatment. - Should be discussed DURING follow up
- Address timing and safety of potential pregnancy
- Proactively addressing infertility is associated with lower regret and
improved quality of life
Treatment Related Factors
Surgery
Infertility
Altered sexual function
Altered body image
Examples
Prostate surgery
Testicular surgery
Hysterectomy
Oopherectomy
Vulvectomy
Mastectomy
Radiation
Vascular or nerve damage
Temporary or permanent
Women
Vaginal atrophy
Painful intercourse
Ovarian failure
Men
Decreased testosterone
Testicular aplasia
Ejaculatory pain
Chemotherapy
Genital sensory neuropathy
Loss of ovarian or testicular function
Temporary or permanent
Premature menopausal symptoms
Hormonal Therapy
↓ production or action of
estrogen or testosterone
Menopausal symptoms
Decreased libido
Masculinization of women
Emasculation of men
Tamoxifen
Aromatase inhibitors
Bicalutamide, enzalutamide
GnRH agonists
alkylating agents, platinum agents, hormonal agents
induced fertility
Alkylating Agents
Damages gonadal tissue
Often measured as “cyclophosphamide equivalent dose” (CED)
Infertility impact is dose related
Cyclophosphamide
Ifosphamide
Procarbazine
Busulfan
Carmustine
Dacarbazine
Platinum Agents
Damages gonadal tissue
Believed to be associated with infertility but
evidence is controversial in women but more conclusive for me.
Cisplatin
Carboplatin
Hormonal Agents
May cause treatment related amenorrhea
Can be a long term therapy
May be teratogenic
Tamoxifen
Fertility – Male Sex at Birth
- Example – TB is a male with testicular cancer
- Remember testicular cancer is very curable and is usually unilateral
- Treatment can include unilateral orchiectomy and chemotherapy (containing
cisplatin) - Consider differences in fertility for
- Surgery alone or surgery + chemo
- If cryopreserved sperm available
Fertility Preservation – Male Sex at Birth
- Sperm Banking (semen cryopreservation)
- Testicular shielding (gonadal shielding)
- Protective cover placed on the body to shield testicles from scatter radiation
- Testicular sperm extraction
- If cannot produce a semen sample
- Collected through a medical procedure
- Testicular tissue freezing
- Experimental
- For boys that have not gone through puberty and at high risk of infertility
- Hormonal gonadoprotection
- NOT effective (ASCO guidelines)
You can have gonadal shielding, so they there’s a way that they can place kind of a protective cover over the the testicles during radiation.
If the person is really young and they can’t do a regular sperm banking, they can actually collect seamen through a needle aspirate
- there’s an experimental procedure of testicular tissue freezing again for boys who haven’t gone through puberty yet.
the different hormonal type treatments for for preserving gonadal function. They they’re not effective here.
Fertility – Female Sex at Birth
- Amenorrhea is a frequently reported outcome in the literature
- Imperfect predictor of fertility
- Maintenance of spontaneous menses can still occur in those with decreased
ovarian reserve. - Anti-Mullerian Hormone (AMH) is more strongly correlated with
antral follicle count over other lab markers - Pretreatment baseline
- Assessing ovarian reserve
- Assessing who may benefit from fertility preservation services
- Women may be counselled to avoid conception for up to 2 years after
treatment complete - Example: JR, a female with Hodgkin lymphoma
- Remember that HL is a very curable cancer that is more common in young
(<40) or older (>60) people. - Treatment related amenorrhea in HL can be affected by age, systemic therapy,
exposure to pelvic radiation. - Consider differences in fertility impact for:
- Large lymphoma mass is in the pelvic region requiring radiation
- Higher stage disease requiring escBEACOPP vs ABVD
- EscBEACOPP is more intense and contains cyclophosphamide and procarbazine
- ABVD contains dacarbazine
- Age of treatment (age 16 vs age 38)
Fertility Preservation – Female Sex at Birth
- Oocyte cryopreservation (egg freezing)
- Embryo banking/cryopreservation
- Eggs are fertilized with sperm and then frozen
- Ovarian shielding
- Protective cover placed on outside of the body to shield ovaries from scatter radiation
- Ovarian tissue freezing
- Experimental procedure
- For girls who haven’t gone through puberty (and don’t have mature eggs)
- Ovarian transposition (oophorpexy)
- Surgical repositioning of the ovaries away from radiation field
- Gonadotropin-releasing hormone agonist (GnRHa)
- Example goserelin
ASCO
Recommendations on
Ovarian Suppression
with GnRH Agonists
All but one trial have shown statistically nonsignificant results. Trials are mostly in breast
cancer patients.
There is conflicting evidence to recommend GnRHa and
other means of ovarian suppression for fertility
preservation.
When proven fertility preservation methods such as oocyte,
embryo, or ovarian tissue cryopreservation are not feasible,
and in the setting of young women with breast cancer,
GnRHa may be offered to patients in the hope of reducing
the likelihood of chemotherapy-induced ovarian
insufficiency.
However, GnRHa should not be used in place of proven
fertility preservation methods
Risk of Another Cancer
- Primary Cancer Recurrence or Relapse
- Long term follow up based on guidelines
- Diagnostic imaging
- Laboratory Tests
- Physical Exam
- Secondary Malignancy Screening
- Cancer survivors have a higher risk of a new cancer (secondary malignancy)
- Exposure to treatments that can increase cancer risk
- Cause of the first cancer may also increase risk for another cancer
- Example BRCA1 mutation can increase the risk of breast cancer and ovarian cancer
Chemotherapy Implicated in Secondary Malignancies
see slide 34
Populations at High Risk of Developing Secondary Malignancies
Breast Cancer Patients
Acute Myeloid Leukemia
Cyclophosphamide + Doxorubicin as part
of breast cancer treatment regimen
Contralateral Breast Cancer
Radiation to breast
Genetic predisposition
Dormant nature of disease
Endometrial Cancer
Tamoxifen use increases risk
Testicular Cancer Patients
Acute Myeloid Leukemia
Testicular treatment regimens:
BEP (q 21 days up to 4 cycles)
Bleomycin 30 units on Day 1
Etoposide 100 mg/m2 on Days 1-5
Cisplatin 20 mg/m2 on Days 1-5
Regimens with etoposide > 2 g/m2 were
associated with a significantly higher risk of
developing a secondary leukemia
Populations at High Risk of Developing Secondary Malignancies
pt 2
Lymphoma Patients
Acute Myeloid Leukemia, Solid Cancers
Hodgkin Lymphoma: ABVD
* Doxorubicin, bleomycin, vincristine,
dacarbazine
Non-Hodgkin Lymphoma: R-CHOP
Ritxumab, cyclophosphamide,
doxorubicin, vincristine, prednisone
Some patients may require radiation
therapy and/or autologous stem cell
transplant
Altered immune function due to disease
Pediatric Patients
Acute Myeloid Leukemia
Childhood cancer regimens include agents
like cyclophosphamide, etoposide &
anthracyclines
Usually occurs within 10 years of treatment
Solid Tumors (breast, bone, skin, thyroid)
Occur in areas of radiation
Risk may increase over time
Genetic Predisposition of Childhood Cancers
Retinoblastoma (eye cancer)
Wilm’s tumour (rare kidney cancer)
Screening for 2ndary malig?
Breast As per population guidelines
Exception: Patients who have received
radiation to chest or axilla –
mammograms begin 8 years after
radiation (but no earlier than age 25 and
no later than age 40)
Colorectal As per population guidelines
Cervical As per population guidelines
Oral Annual Exam
Skin Annual Exam
(Monthly self exam)
Prevention for 2ndary malig?
Smoking Smoking cessation counselling
Avoid chewing tobacco
Avoid second hand smoke
Alcohol ↑ risk of mouth, throat, esophagus
cancers
↑ risk of breast cancer
Diet High fat diet ↑ risk of colon cancer
↑ fiber and cruciferous vegetables
Nitrites can ↑ risk of stomach &
esophagus cancer
Sun
Exposure
Counsel on sunscreen use with SPF15
Vaccines HPV: cervical, H&N cancer
Hep B : lymphoma and HCC
Physical
Fitness loss and deconditioning during treatment
* Aerobic and resistance training programs after treatment
* Improves CV fitness, strength, body composition
* Positive impact on energy level and emotional well-being
* Improved quality of life
- Exercise and Cancer Prevention
- Physical activity is linked to decreased cancer incidence, recurrence and increased survival time (in
certain tumour types) - Possible link between inactivity/sendentary lifestyle with higher mortality (cohort study of nonmetastatic colorectal cancer patients)
- Growing body of evidence that physical activity improves CIPN, chemo induced fatigue,
myalgias/arthralgias from hormonal therapies for breast cancer - Risk of exercise associated adverse events?
- Consider those with established peripheral neuropathy, poor bone health, pulmonary issues, cardiac
issues, those at risk of falls
Mouth Care and Oral Health
- Head and neck radiation can lead to chronic mouth problems
- Mucositis (short term)
- Damage to salivary glands (long term)
- Swallowing disorders (can be long term)
- Taste/smell disorders (con be short or long term)
- Damage to salivary
glands can lead to dry mouth, severe tooth decay - Dental visits very important
- Fluoride treatments
- Artificial Saliva
- Nutritional Considerations for swallowing or taste disorders
