Quiz 1 (wk 1-2) Flashcards Preview

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Flashcards in Quiz 1 (wk 1-2) Deck (73):
1

SURGERY:
• Diagnosis/staging:

o Requires Biopsy:
o Pathologist report = formal/definitive dx!
 Needle (Not dangerous, don’t spread cancer-mb local)
• Metastasis is genetic, not mechanical
 Complete resection

2

SURGERY:
• Curative:

o Surgery- only if local
o Disease-free, must have surgical Margins around tissue are needed

3

SURGERY:
• Palliative:

o Not really used in metastatic Cancer
o Mostly to resolve obstructions
o Debulking surgery- Sarcomas- slow growing cancer & pain relief

4

SURGERY:
• Preventive:

o High risk populations- (bc gene sequencing)
o Prophylactic surgeries: (Meet w/counselor)
 Mastectomy (“BRCA”)
 Familial adenomatous polyposis carriers
o Gynecological Ca. = better w/Cancer specialist surgeon
o Pathologist report = formal/definitive dx!
o Hysterectomy/stomach surgeries = Bowel obstructions

5

SURGERY: *Radiation: (50% of pts get it)
o Fractionation:
• External beam:

Fractionation: total radiation exposure dose into smaller daily doses
 Maximizes therapeutic effect
 Minimizes effect on normal tissue (side effects)

• External beam- m/c

6

SURGERY: *Radiation: (50% of pts get it)
Fractionation: total radiation exposure dose into smaller daily doses

• Brachytherapy-

Brachytherapy- Seed implants
o Prostate cancer (liver, lung = experimental)

7

SURGERY: *Radiation: (50% of pts get it)
Fractionation: total radiation exposure dose into smaller daily doses.

• Gamma knife

• Gamma knife- Brain & CNS
o High dose, more targeted delivery methods
o fewer sessions

8

SURGERY: *Radiation: (50% of pts get it)

Goals:
 Local dz:
 Metastatic dz:
 BIGGEST REASON: After surgery

 Local dz
 Metastatic dz= palliative sx’s
• Bone pain
• Shrinking inoperative brain tumor
• Opening urinary or respiratory tract
 BIGGEST REASON: After surgery= “clean up” the area to prevent local recurrence.

9

Chemotherapy: (Round may be a single or multiple tx’s over multiple days)

• Systemic tx for Metastatic Ca
(Medical Oncologist needed)

o Included local w/high potential to spread
o Disrupt cell division
 Rapidly dividing cells most prone to damage
• Rapidly dividing cancers respond the best.

10

Chemotherapy: (Round may be a single or multiple tx’s over multiple days)

• Adjuvant therapy:
• Neo-adjuvant therapy

 Adjuvant therapy: Giving chemo after surgery
 Neo-adjuvant therapy: Chemo b4 surgery

11

Chemotherapy: (Round may be a single or multiple tx’s over multiple days)

• Adjuvant therapy: EX: Node positive Breast Ca.
 Large scale clinical trials?

o EX: Node positive Breast Ca.
 4 cycles of (AC) + 4 cycles of taxol after
• AC – Adriamycin
 Regimen based on large scale clinical trials = chance slowly.

12

Chemotherapy: (Round may be a single or multiple tx’s over multiple days)

•Metastatic dz: Protocol used until evidence of progression
 Regimen Continue until???

Regimen Continue until tumor marker scan shows tumor is growing not shrinking.

13

Chemotherapy: (Round may be a single or multiple tx’s over multiple days)

 Progression: 2nd line therapy or 3rd?

 Progression: 2nd line therapy or 3rd w/ diff. agents (Not any more unless special case)
• Transition to supportive/palliative care program

14

Chemotherapy: (Round may be a single or multiple tx’s over multiple days)

• Hormone therapies: 1st line
Used for what?

o Breast & prostate

 Block synthesis of hormones
 Work in CNS (Cause Chemometapause)
 receptive level
• given as adjuvant therapy (Breast- 5yrs)
• or tx for metastatic dz (Until progression)

15

• Biological therapies: Less immediately toxic
o Side Effects:
o Large proteins:
o Promise/pessimism:

o Side Effects: Idiosyncratic to specific agent
o Large proteins: Affect immunity and cell cycling
o Promise/pessimism: Have not being as effective in controlling dz, can get better.
 Less toxic
 More tolerable to pts

16

• Biological therapies: Categories?

Categories:
 Cytokines (interferon):
 Monoclonal antibodies (Ab):
 Checkpoint inhibitors (ib):
 Tyrosine kinase inhibitors:

17

Assessing the quality of a screening program
• Asymptomatic pop. (Less prevalent c/d = more false positives)

o Dz has to prevalent in pop
o Effectively tx when caught early (Change course if caught early)
o Resource availability (Ex: Not colon CA bc not enough surgeons)

18

Assessing the quality of a screening program
• Criteria:

o Sensitive & Specific (Good positive & negative predictive values)
o Nothing is perfect but 80-90% is good
o Test = Inexpensive & safe (Colonoscopy – better screening – ppl don’t like)

19

Assessing the quality of a screening program
• Problems:

o Pts over-estimate efficacy
o Dr’s don’t want to miss dx
o Efficacy
o Financial incentives

20

Assessing the quality of a screening program
o Efficacy

(Hard to assess – biases creep in – Ex: Prostate CA-
 Overrated benefits d/t biases
 Over diagnosis- Inflate screening efficacy stats
 Breast Ca.- 5 yr survival better, but high mortality rates (Confuse data)

21

Assessing the quality of a screening program
o Financial incentives

Early detection (screenings) & tx = $$$
 $$$ = Diff. recommendations b/t ACS vs USPSTF (More scientific)
• Ex: PSA screening
• USPSTF= No PSA or DRE screening (Recommend against them)

22

Assessing the quality of a screening program
• Breast Ca: BRCA used based on PENN II Model (Has 2 have strong family hx)

o Only screen pts w/high on risk calculator
o Bi-annial mammogram (50-74yo)
 <50yo- Questionable value
 >75yo- No value
• ACS added= women life expectancy <10yrs = NO SCREENING/ poor prognosis

23

Assessing the quality of a screening program

Breast CA screening:
o Self-breast exam
o Mammograms

Self-breast exam => NO BENEFIT
o Not enough evidence:
 Non-Mammogram screenings (Ultrasounds/MRI’s/thermogram)
 Efficacy of Reg. medical breast exams
o Mammograms may stop soon->Harm #’s close to tx #’s

24

Assessing the quality of a screening program

• PSA screening:

*USPSTF “D-rating”- against screening.
*ACS w/ informed consent

25

Assessing the quality of a screening program

• Colon Ca. Screening:

(50-75yo), 75-84yo–> not beneficial, >85yo-not recommended
o Fecal occult blood- (Annual)
o Sigmoidoscopy-Q 5 yrs
o Colonoscopy- Q 10yrs
 Not enough info–virtual colonoscopy & fecal DNA testing are equivalent ACS recommended, not USPSTF
 Aspirin- Not a chemo-preventive agent (D-rating)

26

Assessing the quality of a screening program

• Lung CA. Screening

In 2013- USPSTF & ACS recommended routine screenings
o Annual Low dose CT rec:
 >30 pack yrs, 55-80yo, smoked in last 15 yrs
 discontinued w/health limits resection (Healthy ppl enough)

27

Assessing the quality of a screening program:

• Cervical Ca screening

Most efficacious of all – HPV
o 18-65yo = Cytology (PAP) every 3 yrs
 30-65yo every 5 yrs w/ Combo PAP & HPV screen
 >65- no screening in Low risk
o Post-hysterectomy (w/cervical removal)
 Screen only: CIN 2, 3 or cervical CA. hx

28

Assessing the quality of a screening program:

• NO SCREENINGS: Insufficient or not enough evidence

o Skin (>40 all),
o testicular,
o ovarian,
o bladder
o pancreatic CA. (UW trying)

29

Chemo Basics:

Chemotherapy is any chemical you use as medicine. (Cytotoxic meds in Cancer)

• Goal???

• Goal- balance tx w/in therapeutic window of efficacy & tolerability.

Chemotherapy is any chemical you use as medicine. (Cytotoxic meds in Cancer)

30

Cytotoxic meds in Cancer:

• Mechanism:

o Disrupt nucleic acids
o Inhibit RNA/DNA production
o Disrupt cell cycle (Spindle)

31

Cytotoxic meds in Cancer:

• Each round:

o Fractional cell kill(Slower cell division = less responsive, faster = more responsive)
o Combo agents maximize cell kill
o Acute & cumulative toxicity/dose over time

32

Cytotoxic meds in Cancer:

• Regimen determination:

o Single agent- Single MOA
o Multi agents-
 Metastatic- 1-2 agents
 Usually after surgery
 many MOA’s to maximize tx efficacy
 SE’s: Dose limiting problem

33

Cytotoxic meds in Cancer:

• Time used:
o Metastatic:

 Until evidence of progression (Dz is growing)
 Until adverse effects become intolerable
 Adjuvant setting (Already had surgery- chemo cleans up dz):
• Tx is predetermined # of rounds
• Ex: Breast Ca = 8 rounds after surgery
• Lymphoma- Chop plus retoxine
 Choice:
• Predetermined by site or it’s standard

34

Cytotoxic meds in Cancer:
• Time used:
o Metastatic:

 Adjuvant setting (Already had surgery- chemo cleans up dz):
*Tx determination?

 Choice:

• Tx is predetermined # of rounds
• Ex: Breast Ca = 8 rounds after surgery
• Lymphoma- Chop plus retoxine

 Choice:
• Predetermined by site or it’s standard

35

o CR-Complete response:

No evidence of dz by scans or W/up

36

o PR-Partial response:

50% or greater reduction to initial tumor size

37

o Response rate:

CR + PR as proportion of # tx’d- (% of tx pts)

38

o Stable:

<25% change since last scan in either direction

39

o Progression Free survival (Common outcome measure)

(Key metric)

How a chemo regimen will change mortality metric (6-12 mo)?

 Ave. time to progression of dz in grp.
 How long does it take for dz to start to grow

40

o Absolute risk reduction:

 Dz recurrence % rate w/tx or without tx
 #/100 who benefit from post op tx w/ reduced recurrence risk
• lowest in ppl who have least recurrence risk w/o tx (Highest risk of recurrence benefit the most of chemo therapy)
 # in NNT (Number needed to treat)

41

o Relative risk reduction:

 Dx recurrence %w/tx divided by % w/o tx.

42

Day of treatment concerns:

• Steroids (sleep issues),
• Anti-nausea (Constipation)

43

Day 1-3 (early SE’s)
• Acute SE’s

o Nausea, vomiting, diarrhea, dehydration

44

Hematologic Nadir

“Hematologic CURVE” – Low point of the curve

Day 14: (Related to CELL DIVISION)

45

Day 14: (Related to CELL DIVISION)

• Cumulative SE’s worse screenings

o Fatigue,
o mouth sores,
o thrombocytopenia (Blood count changes),
o low immune function

46

Setting Goals: • Adjuvant setting: Reduce disease recurrence rate, some CURED (Metastatic Rare)

o Chemo can be curative even in advanced or metastatic stage! (3)

 Testicular
 Lymphomas (Aggressive)
 Leukemias

47

Setting Goals:
Adjuvant setting: Reduce disease recurrence rate, some CURED (Metastatic Rare)

o Most = Palliative (Improves survival, NOT curative)

 70-80% of pts tx’d palliative believe it to be curative. (Even when told otherwise)
 Can make a big difference in the quality of life. (Pain reduction)

48

Setting Goals:

Drug resistance: (Why most Cancers are not curative)
• Resistance

• Resistance- When effective drug dose is higher than Maximal tolerated dose.

49

Drug resistance: (Why most Cancers are not curative)

o Similar to Antibiotic resistance

o Similar to Antibiotic resistance
 Risk increases over duration of tx
 Resistance to one = resistance to others

50

Drug resistance: (Why most Cancers are not curative)

o You can choose STANDARD resistant mechanisms:

 Upregulation of P-glycoprotein efflux pump
 MDR: Multi-drug resistance protein (Efflux or sequestration pump)
 Upregulation of glutathione production (supplemental antioxidants problems)
 Breakdown of apoptosis process (via P53 mutation common w/drug resistance)

51

Drug resistance: (Why most Cancers are not curative)

• Dose intensification: (Bone marrow transplant)

o Wipe out white blood cells (WBC) bc so strong
o Must repopulate WBC
 Allogeneic transplant: Bone marrow or peripheral blood progenitors

 Used in: Blood Cancers
• Relapse or tx-refractory lymphomas
• Multiple myeloma
• Acute leukemia
• No longer used in Breast CANCER

52

Drug resistance: (Why most Cancers are not curative)

• Dose intensification: (Bone marrow transplant)
 Used in: Blood Cancers

• Relapse or tx-refractory lymphomas
• Multiple myeloma
• Acute leukemia
• No longer used in Breast CANCER

53

Alkylating Agents: Oldest = nitrogen mustard gas derivative

• Widely used in which Cancers? 3

• Binds DNA = Stops G1 – S cell cycle

o White cells cancers
o Breast
o Brain

54

Alkylating Agents: Oldest = nitrogen mustard gas derivative

• Resistance:

o Through enhanced DNA repair enzymes
o Increased Glutathione production

55

Alkylating Agents: Oldest = nitrogen mustard gas derivative

Examples:

• Cyclophosphamide
• Temozolomide
• Melaphalan
• Ifosphamide

56

Alkylating Agents: Oldest = nitrogen mustard gas derivative

o Toxicities:

 Alopecia
 Nausea
 Vomiting
 Marrow suppression

57

Antitumor Antibiotics:

• Most frequently used?
o Breast, Blood, Sarcomas

 Mechanism???:

• Anthracyclines: Most frequently used
o Breast, Blood, Sarcomas

58

Antitumor Antibiotics: Breast, Blood, Sarcomas
• Anthracyclines: Most frequently used

 Mechanism???:

Topoisomerase 2 (II) disruption
• Leads DNA strands to break

59

Antitumor Antibiotics: Anthracyclines: Most frequently used

 Resistance: Multi drug resistance protein efflux pump (-rubicin)

• Adramycin (Doxorubicin)
• Epirubicin

60

Antitumor Antibiotics: Anthracyclines: Most frequently used

 Side effects:

M/b yrs post tx (No standard preventative tx)
• Alopecia
• Mucositis
• Myelosuppression
• Cardiotoxicity (Cumulative & dose limiting)

61

Antitumor Antibiotics: Anthracyclines: Most frequently used;

• Anti-metabolites: Methotrexate (inhibits folate pathway)– 1st successful tx in pediatric tx

o Disrupt folate pathways?

 Inhibits folate binding to dihydrofolate reductase
 Folic acid tx: detrimental to leukemia in kids

• Methotrexate (inhibits folate pathway)– 1st successful tx in pediatric tx.
• Prevent folic acid in replication of RNA & DNA
• Tx followed w/”Leukovorin”

62

• Anti-metabolites: Methotrexate (inhibits folate pathway)– 1st successful tx in pediatric tx.

 Used in:

• Breast CA, GI Cancer, Blood d/o’s, Sarcomas & kids w/leukemia get maintenance therapy for up to a year.

63

Methotrexate (inhibits folate pathway)– 1st successful tx in pediatric tx.

 Adverse affects:

• NSAIDS may impair clearance
o Myelosuppresion (Why it's good for Blood Cancers)
o Mucositis
o Nephrotoxicity (kidney toxicity)

64

• Anti-metabolites:
5 FU (Fluorouracil) & Derivatives:

• Thymidylate synthase inhibitor
o Interferes w/remethylation of folate
o Synthesis of the nucleoside thymidine (DNA & RNA Replication)

65

Anti-metabolites:

• 5 FU (Fluorouracil) IV is Administered with???

Leukovorin (folic acid antagonist) = enhances effects

66

5 FU (Fluorouracil) IV is Administered w/Leukovorin (folic acid antagonist) = enhances effects
• Cancers given to???

• Cancers given to:
o Every GI CANCER regiments
o Breast, head and Neck CA

67

5 FU (Fluorouracil)

• Side effects:

o Hand/foot s/d- Neuropathic pain, Vasodilation (Beefy red skin & skin peeling)

o Myelosuppresion
o Stomatitis
o Mucositis
o Diarrhea

68

Platinum drugs (1st line):
• DNA binding = cross links that impair cell division
• (-Platin) – Stay in system for yrs after tx

Side Effects???:
*Cisplatin
*Carboplatin
*Oxaliplatin

o Cisplatin (Worse SE’s)
o Carboplatin (thrombocytopenia worse)
o Oxaliplatin (Neuropathy worse)

69

Platinum drugs (1st line):

• Used across tumor/cancer types:
• Side Effects

o Ovarian, Lung, GI Cancers

SE's:
o Nausea, vomiting, neuropathy, nephrotoxicity, myelosuppression, Ototoxicity

70

Anti-Microtubule agents (Plant based compounds): Disrupts M phase cell division
• Classes (2nd & 3rd choice):

o Taxanes (X): (Taxol, Taxotere & Abrezane)

Cancers???
Side effects???

(Taxol, Taxotere & Abrezane)
 Breast, ovarian, lung

SE's: Neuropathy, fatigue, neutropenia, hypersensitivity, fluid retention

71

Anti-Microtubule agents (Plant based compounds): Disrupts M phase cell division

o Vincas (-ine): (Navelbine, Vincristine, Vinblastine)
Cancers???
Side effects???

 Blood Cancers (late line breast CA)
 SE: neutropenia, Neuropathy & Constipation

72

Biological/Targeted agents: (Bioengineered)

Cancers?
Pathway?

• Alone only in Melanomas
• Colorectal CA.- Angiogenesis inhibitors (-ib)- (Avastin/ bevacizumad)
o Block new blood vessel formation via VEGF

• Proteins (large) aimed to target specific pathways

73

Biological/Targeted agents: (Bioengineered)

• Monoclonal antibodies (-ab):

o Rituxan: Lymphomas
o Herceptin: Breast Ca