Strategies of Cancer Treatment & Prevention (Pence) Flashcards
1
Q
Approaches to local tx of cancer:
A
- surgery
- radiation
- ablation (cryosurgery, radiofrequency)
(tx can be combined, ex: surgery and/or ablation OR sugery + radiation)
2
Q
Approaches to systemic cancer tx:
A
- chemotherapy (cytotoxic, hormone, biologic)
3
Q
Things to consider when pursuing local therapy:
A
- can you remove all of the cancer
- are there limited options for systemic therapy
- if cure cannot be achieved, could treatment palliate
4
Q
What are the common cancers tx w/ local therapy?
A
- sarcomas
- non-melanoma skin cancer
- in situ carcinomas
5
Q
What is the timeline of tx in terms of adjuvant therapy?
A
(optimal therapy requires multiple tx modalities)
- surgery first provides “cytoreduction”
- after surgery: radiation and systemic therapy (often chemo)
6
Q
What is the timeline of tx in terms of neoadjuvant therapy?
A
(usually applied to large tumors)
- surgery is not as effective initially d/t size of tumor
1. cytoreduction provided first (chemo/rads)
2. surgery for gross reduction after initial cytoreduction
3. after surgery, more adjuvant therapy (chemo/rads)
7
Q
What is the sequential order of cancer therapies and what is their specific purpose?
A
- neoadjuvant: reduce primary tumor size, eliminate cancer cells that spread to other locations
- primary: gross elimination of tumor
- adjuvant: eliminate remaining cancer cells
8
Q
When is surgery not indicated for cancer tx?
A
- metastatic dz removes advantage of surgery
- leukemia/lymphoma
- systemic therapy is so effective that surgery is unnecessary
9
Q
What are the 3 most common types of radiation therapy?
A
- external beam radiation (intensity modulated radiotherapy (IMRT))
- brachytherapy
- systemic radionucleotides
10
Q
- type of radiation therapy
- linear accelerator delivers direct radiation beams to affected sites
A
external beam radiation
11
Q
- subtype of external beam radiation
- takes a 3D image of patient and mass
- reduces amount of radiation exposure to patients and healthy tissue
- used in instances where the tumor is wrapped around important structures (ex: aorta)
A
intensity modulated radiotherapy (IMRT)
12
Q
- subtype of external beam radiation
- commonly used in primary brain tumors
- image of the brain is generated and the vectors of radiation are mapped out to spare healthy tissue within the brain
A
cyberknife
13
Q
- type of radiation therapy
- very localized high-dose therapy delivered continuously for a prolonged time through implanted devices
- most commonly used in prostate cancer
- in prostate cancer, a needle is inserted into the prostate where radioactive seeds are implanted
A
brachytherapy
14
Q
- type of radiation therapy
- radioactive substance is injested, these molecules are absorbed through digestive tract to bloodstream, the part of the body that is targeted will absorb the molecules, the radiation destroys cancer and normal cells
- most commonly used in thyroid cancer (radioactive iodine, aka I^131, for thyroid cancer and non-cancerous dz’s of thyroid)
*people undergoing this therapy have to be isolated for ~4 days b/c they are radioactive, their body fluids also have to be disposed of properly d/t their radioactive nature*
A
systemic radionucleotides
15
Q
When should radiation therapy be used in cancer?
A
- part of adjuvant therapy
- part of neoadjuvant therapy
- when surgery is contraindicated (patient of advanced age w/ prostate cancer)
- to palliate: spinal metastasis to prevent cord compression/alleviate neurologic sx, ENT carcinoma to prevent suffocation, pelvic sidewall to prevent pain
16
Q
What are the different types of systemic cancer therapies?
A
- conventional: cytotoxic chemotherapy (does not discriminate between healthy and malignant cells)
- targeted agents: hormonal, biologics (tumor mediated, immuno-regulatory mediated, Ab conjugates)
17
Q
What is the importance of considering the therapeutic index and therapeutic window in conventional systemic cancer tx?
A
- the higher the therapeutic index (TD50/ED50), the better the drug (this means the drug has a high toxic dose and low effective dose)
- cytotoxic chemotherapies (the conventional systemic cancer tx) generally have low therapeutic indexes, meaning there will almost always be adverse side effects
- the main goal is to kill as many cancer cells while sparing healthy cells, this is why chemo is given in cycles and days to allow normal cells time to recover
- it is important to know what side effects (even on what days) may occur to ensure proper management of sx and any prior/post tx diagnostics that may need to be obtained
18
Q
What are the types and indications of targeted systemic cancer therapies?
A
- hormone: is tumor dependent on hormone stimulation (i.e. breast, prostate), look at receptor status and inhibit
- growth factors: is tumor dependent on growth factors (i.e. epidermal growth factor, vascular endothelial growth factor), look at receptor status and inhibit
- antigens: are there antigens that can be targeted (i.e. CD20 for B-cell lymphomas), use recombinant Abs (Rituximab)
- immune checkpoints: is PD-1 or CTLA on tumor cells diminishing our tumor immunity, use immune checkpoint inhibitors
19
Q
- a type of systemic cancer therapy
- T-cells (autologous or allogenic) are manipulated ex vivo (often by exposure to a virus) to express a binding domain for a tumor-associated antigen (customized) w/ a transmembrane domain and an intracellular signaling domain that intensifies the immune attack against tumor cells
- not readily available as tx currently, only been approved for ALL
- causes cytokine release syndrome (CRS) that occurs in 80%: causes high fever, flu-like sx, and even death in some cases (CRS can be tx w/ Toluzimab)
A
CAR-T therapy
(chimeric antigen receptor therapy)
20
Q
What are the indications for and types of stem cell transplantation?
A
- indications: therapy that involves ablation of the bone marrow (hematopoietic neoplasms, advanced solid tumors needing high dose cytotoxic chemotherapy)
- types: allogeneic (someone else), syngeneic (identical twin), autologous (from oneself)
21
Q
5 considerations to an effective cancer screening test
A
- easy to administer
- economic
- actionable
- sensitive
- widely available
22
Q
General difference between A/B grading and C grading for USPSTF grading:
A
- grade A and B are generally recommended
- grade C you need to informed consent from patient
23
Q
- 5th leading cause of cancer death amongst women in US
- 14,000 deaths/year
- >95% of these deaths occur in women >45 y/o
- ~20% of this cancer is dx at early stage (not good)
A
ovarian cancer
24
Q
Screening tools for ovarian cancer:
A
- physical exam
- CA-125
- transvaginal ultrasound (TVUS)
- multimodal (CA-125, TVUS)
- none of the above are considered effective screening tools (Grade D USPSTF), meaning services have no benefit and/or harms may outweigh benefits
- gray area, high risk women: FMHx of ovarian cancer or hereditary cancer syndromes (BRCA, Lynch syndrome), individualized screening plan, heightened urgency for sx, distal fallopian tubes removed
25
How beneficial is physical exam in ovarian cancer screening?
- no data suggests pelvic exams are useful in screening in avg risk women
- large ovarian masses are easiest to detect w/ pelvic exam which typically indicates advanced dz
- lack of evidence to support use as screening tool
26
How beneficial is CA-125 marker in ovarian cancer screening?
- not specific for malignant ovarian tumors (even to degree needed for screening test)
- not all ovarian cancers are CA-125 positive
- by the time CA-125 is positive, many tumors are beyond cure
- use of CA-125 shows no improvement in mortality (PLCO trial)
27
How beneficial is TVUS in ovarian cancer screening?
- shows no improvement in mortality, during screening, and 6 years after
- observer dependent: success in dx cancer depends on ability to obtain a clear image
- only good at detecting advanced dz
28
How beneficial is multimodal tools in ovarian cancer screening?
(CA-125/TVUS)
- shows no improvement in mortality
- 9.6% false positive rate, leading to unneeded surgical intervention and harm (PLCO trial)
29
- leading cause of cancer among men in US
- 26% of total cancer diagnosed among men
- 11-12% risk of men being dx in their lifetime
- 2.5% risk of dying from this cancer
- median age for death is 80 y/o
prostate cancer
30
Screening tools for prostate cancer:
- prostate specific antigen (PSA)
- digital rectal exam (DRE): falling out of favor, forget about DRE (low sensitivity and specificity)
31
How beneficial is PSA in prostate cancer screening?
- high false positive rate
- serum testing increases in many benign and inflammatory conditions (prostatitis), also milking the prostate (DRE) can increase PSA
- for age 55-59 screening w/ PSA (PLCO trial): prevented 1.3/1000 men screened over 13 years, prevented 3 cases/1000 men of metastatic prostate cancer, ~2/3 men underwent bx for elevated PSA that did not have prostate cancer (aka this is doing more harm than good)
32
Considerations and USPSTF grading when screening men w/ PSA:
- PSA for men 55-69 y/o: informed decision making, weigh benefits/risks, very small potential benefit, sizeable risk of exposing pt to potential harm (false positives, overdx, overtx), **grade C recommendation**
- PSA for men \>70 y/o: **grade D recommendation**
33
- ~40 years ago this cancer was leading cause of death of cancer death for women in US
- screening techniques and introduction of HPV vax has resulted in substantial decline in incidence of this cancer (~70%)
- decrease in new cancers/year by 22% from 1999 to 2018
cervical cancer
34
Screening tools for cervical cancer:
- pap smear
- HPV testing
- co-testing (pap and HPV)
35
Guidelines for pap smear screening:
- cytology
- excellent at detecting pre-malignant and malignant cells
- start at **age 21** (almost unanimous across guidelines (ACS says 25)), and then repeat every 3 years
- stop at **age 65**, unanimous across guidelines
- for 30-64 age group, guidelines are not as clear, in general: pap alone = q3 years; pap+HPV = q5 years (f/u will be more frequent for positive tests)
- **USPSTF recommendations**: \<21 y/o grade D (not rec), 21-29 years grade A, 30-65 years grade A, \>65 years grade D
36
How beneficial is pap smear and HPV in cervical cancer screening/prevention?
- pap smear is effective screening: very important b/c cervical cancer is hard to tx
- pap smears are excellent at identifying pre-cancerous lesions that can be tx w/ local excision and cryoablation (**before invasive cancer even arises**)
- HPV vax: reduction in pre-cancerous conditions caused by HPV strains covered by the vax
37
38
Only screening tool for endometrial cancer:
**counsel women at menopause to report any _vaginal bleeding_**
(this is our only screening tool)
39
- most common type of non-skin cancer in women
- 2nd leading cause of cancer death for women behind lung cancer
breast cancer
40
Screening tools for breast cancer:
- clinical breast exam (not suggested for routine screening in resource rich setting)
- self breast exam (not suggested for routine screening in resource rich setting)
- **mammography** (reduces mortality): current guidelines are to start screening at 50 to 74 and complete once every 2 years, however there is a recent shift to start screening at 60, **informed decision making w/ pt is key**
- MMG USPSTF recommendations: 40-49 y/o grade C, 50-74 y/o grade B
\*management of breast cancer screening varies from year to year and recommending body\*
41
How to perform self breast exam:
- allows early familiarity w/ subtle changes to breast tissue, can be started at early age, frequency of every month
- check the axilla, look for skin changes, avoid checking prior to/during menstrual cycles, find a system that helps you remember to do it
42
Guidelines for breast cancer genetic testing and preventative tx:
- BRCA-1 and BRCA-2 genetic testing: need genetic counseling, recommended w/ extensive FMHx of breast/ovarian cancer (multiple relatives, relatives dx at young age, male relatives) OR personal dx before age 45
- BRCA positive: **prophylactic surgery** as in double mastectomy (either prophylactically or in unilateral breast cancer) and bilateral salpingo-oophorectomy; **chemoprevention medication** (hormone therapy), **increased screening self exam**
43
- third leading cause of cancer death for men and women in US
- est 52,980 people will die from this cancer in 2021
- most freq dx between ages of 65-74 y/o
- 10% of cases are dx in patient's \<50 y/o
colon cancer
44
Screening tests for colon cancer:
- high-sensitivity guaiac-based fecal occult blood test (annual): requires dietary restriction, 3 stool samples, not as sensitive as other stool based tests
- fecal immunochemical test (annual): single stool sample
- fecal DNA test (every 1-3 years): most sensitive stool based test, requires entire bowel movement, higher false positive rate
- CT colonography (every 5 years): requires bowel prep, can find extracolonic pathology, doesn't require sedation
- **colonoscopy** (every 10 years): most invasive, requires sedation, requires bowel prep, can perform bx during procedure, less frequent screening
- **colon cancer screening USPSTF recommendation**s: 45-49 y/o grade B, 50-75 y/o grade A, 45 y/o (ACS rec), **informed desicion making w/ pt is key**
**\*all of these tests, if positive, will need to be followed by a colonoscopy\***
45
- leading cause of non-skin cancer in US
- \>200,000 people are dx every year
- ~150,000 deaths/year
- prevention = smoking cessation
lung cancer
46
Screening tools for lung cancer:
- **low-dose CT annually**: age 50-80 y/o w/ 20-pack-year hx of smoking OR actively smoking, OR, those who only quit smoking in past 15 years
- USPSTF **grade B recommendation**
47
Screening/USPSTF grade and prevention cheat sheet:
\*note under cervical cancer screening HPV testing should be included\*
