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Exam 2 Flashcards

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1
Q

Types of Skin Cancer

A
  1. Basal Cell Skin (BCS) cancer
  2. Squamous cell skin (SCS) cancer
  3. Melanoma: most metastasis-prone type
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2
Q

Risk factors for skin cancer

A
  1. Ultraviolet (UV) light exposure
  2. Moles
  3. Fair skin, freckling, light hair
  4. Familial hx of melanoma
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3
Q

Melanoma diagnosis: ABCDE

A
  • Asymmetry: one side is different from the other
  • Border: irregular, notched, blurred
  • Color: mixed
  • Diameter: larger than 6 mm
  • Evolve: mole evolves over time
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4
Q

Melanoma staging: I ~ V

A
  1. Confined to the epidermis; “in situ”
  2. Invasion of the papillary dermis
  3. Filling of the papillary dermis but not extending to the reticular dermis
  4. Invasion of the reticular dermis
  5. Invasion of the deep, SQ tissue
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5
Q

Familial vs Sporadic melanoma

A
  • Familial: germline mutation of CDKN2A, CDK4) encoding for p16INK4A and p14ARF
  • Sporadic: random acquired mutations in p16INK4A
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6
Q

Targeted therapy:
- Most common mutation
- Regimens

A
  • Target cancer’s specific protein(s) that contributes to the growth and survival of cells
  • Most common BRAF mutation: V600E → vemurafenib, dabrafenib
  • Targeted MEK inhibitor → trametinib
  • BRAF + MEK = standard of care for melanoma
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7
Q

Immunotherapy: checkpoint targets, (+), (-)

A
  • Immune checkpoints: PD-1/-L1 axis, CTLA-4
  • (+): pts own immune system to destroy cancer cells, memory against cancer specific antigens result in more durable response, improve efficacy when used in combination
  • (-): autoimmune disease, resistance, heterogenous response
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8
Q

Systemic therapy: Immune Checkpoint Inhibitors (ICIs)
- MoA
- Formulation
- Drug - target

A
  • Block target protein “checkpoints” to turn on an immune response
  • IV formulation
  • Ipilimumab - CTLA-4
  • Pembrolizumab, Nivolumab - PD-1
  • Atezolizumab - PD-L1
  • Relatlimab - LAG-3
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9
Q

Systemic therapy: BRAF/MEK inhibitor targeted therapy
- Why given together?
- Formulation
- BRAF + MEK drugs

A
  1. Prolong time to resistance
  2. Improve toxicity profile
  3. Increase overall efficacy
    - Oral formulation
    - Dabrafenib + Trametinib
    - Vemurafenib + Cobimetinib
    - Encorafenib + Binimetinib
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10
Q

Treatment by stage (Localized)
- Stage 0 in situ or 1A
- Stage IB or II

A
  • Wide excision
  • Wide excision +/- sentinel node biopsy
  • Early stage = surgical resection
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11
Q

Adjuvant tx for resected Stage III melanoma
- Stage IIIA (sentinel node +), IIIB/C/D (SN+)
- Adjuvant treatment

A
  • Nodal basin ultrasound surveillance or complete lymph node dissection + systemic therapy or observation based on risk of recurrence
  • Nivolumab: Stage IIIB/C
  • Pembrolizumab: Stage IIIA w/ sentinel lymph node (SLN) metastasis >1 mm or stage IIIB/C
  • Dabrafenib+Trametinib: pts w/ BRAF V600 activating mutations; stage IIIA with SNL mets >1 mm or stage IIIB/C
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12
Q

Treatment by stage: Unresectable
- Stage III (satellite/ in-transit lesions)

A

Intralesional injections, local ablation, topical imiquimod

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13
Q

What is Talimogene laherparepvec (T-VEC)?
- Indication
- MoA
- Administration
- Dosing (Max dose per visit)
- AEs
- Monitor/Precautions

A
  • Oncolytic virus based on HSV-1
  • Unresectable stage III melanoma with in-transit or satellite lesions
  • Selectively infects, replicates inside, destroys cancer cells
  • Intralesional injection
  • Inject from largest to smallest; max = 4 mL
  • Chills, fatigue, fever, injection site pain, N, flu-like
  • Viral transmission risk
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14
Q

Treatment by stage: Metastatic Melanoma First-line therapy (systemic)
- Combination ICI
- Monotherapy ICI
- BRAF V600-activating mutations

A

Combination ICI (preferred)
- Nivolumab + ipilimumab/relatlimab
Monotherapy ICI
- Pembrolizumab
- Nivolumab
BRAF V600-activating Mutations
- Dabrafenib + trametinib
- Vemurafenib + Cobimetinib
- Encorafenib + binimetinib

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15
Q

ICI vs BRAF/MEK as 1st line for pts w/ BRAF V600-activating mutations
- Rapidly growing, symptomatic
- Slow growing, asymptomatic

A
  • Start with BRAF/MEK, faster onset
  • Start with ICI due to increased overall survival
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16
Q

Risk factors associated with VTE in cancer patients: Patient-/Treatment-/Tumor-related

A
  • Age, comorbidities, immobilization (hospitalization), previous VTE, hereditary thrombophilia
  • Chemo, hormonal, RBC transfusions & erythropoiesis-stimulating agents, surgery, radiation, central venous catheters
  • Tumor type (VH: gastric pancreas, brain, H: lung, hematologic, gynecologic, renal, bladder), advanced stage, localized tumor compression
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17
Q

Prevention of VTE in Inpatient

A

Enoxaparin, Dalteparin, Fondaparinux, Heparin

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18
Q

Prevention of VTE in Outpatient (Ambulatory): Criteria, Recommended agents, Duration

A
  • Cancer patients, high-risk (Khorana score 2), receiving/starting chemotherapy
  • DOACs: apixaban, rivaroxaban
  • LMWH: enoxaparin, dalteparin
  • <6 months
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19
Q

Initial treatment of VTE

A

Enoxaparin, Dalteparin, Rivaroxaban, Apixaban

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20
Q

Maintenance treatment of VTE: agents & duration

A
  • Enoxaparin, Dalteparin, Rivaroxaban, Apixaban, Edoxaban
  • Duration >3 months
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21
Q

Risk factors for extravasation: Infusion procedure-/Patient-/Drug-related

A
  • Peripheral > central access
  • Small & fragile veins, multiple previous venipunctures, obesity, conditions with an altered or impaired circulation, communication difficulties or young children
  • Overall vesicant properties of the drug
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22
Q

Vesicants Chemotherapeutic drugs (ABC MTV)

A

Anthracyclines, Bendamustine, Cisplatin, Mitoxantrone, Taxanes, Vinca alkaloids

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23
Q

Prevention of extravasation

A
  1. Education and training of HCP
  2. Ensure appropriate vascular access
  3. Selection of appropriate cannula and needle
  4. Patient education
  5. Development of local institutional guideline for prevention and management of extravasation
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24
Q

Management of anthracyclines, alkylating agents: Localize & Neutralize by ___

A
  • Localize by applying cold compresses for 20 mins QID for 1-2 days
  • Neutralize by using specific antidotes
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25
Management of vinca alkaloids, taxanes: Disperse & Dilute by ___
- Disperse by applying warm compresses for 20 mins QID for 1-2 days - Dilute by administering agents that increase absorption of extravasated drugs
26
Antidote Dexrazoxane: Indication, MoA, Dose, Warning
- Tx of extravasation of anthracyclines, prevent anthracycline-induced cardiomyopathy - Reversibly inhibit topoisomerase II - Begin ASAP but within 6 hrs - Withhold cooling compresses at least 15 mins before and during infusion
27
Antidote Dimethyl Sulfoxide (DMSO): Indication, MoA, Dose, Warning
- Tx extravasation of anthracyclines, mitoxantrone, cisplatin (alternative) - Free-radical scavenging properties, can speed up the removal of extravasated drugs from tissues - Topically, begin within 10 mins, do not cover
28
Dexrazoxane & DMSO can be used concomitantly: True or False
False; should **not** be used concomitantly
29
Antidote Hyaluronidase: Indication, MoA, Dose
- Tx extravasation of vinca alkaloids & taxanes - Degrade hyaluronic acid in the extracellular matrix, modifying the permeability of the connective tissue, increases the dispersion and absorption of extravasated drugs - IV if needle/cannula still in place - SQ in a clockwise manner if removed
30
Antidote Sodium Thiosulfate: Indication, MoA, Dose
- Tx extravasation of cisplatin, bendamustine - Create alkaline-rich site, to which alkylating agents have an affinity, thereby neutralize - Bendamustine: SQ - Cisplatin IV, SQ
31
Risk factors of mucositis: Patient vs Treatment specific
- Smoking/tobacco use, poor baseline oral hygiene, younger age, female, pretreatment nutritional status - Head/neck cancers, combined chemo & radiation, treatment duration, dose of therapy
32
Grading of oral mucositis: CTCAE Grade 1-5
1. Asymptomatic or mild symptoms; indication not indicated 2. Moderate pain or ulcer that does not interfere with oral intake; modified diet indicated 3. Severe pain; interfering with oral intake 4. Life-threatening; urgent intervention indicated 5. Death
33
Grading of oral mucositis: WHO Grade 0-4
0: None 1: Soreness/ erythema 2: Erythema/ ulcers/ can eat solids 3: Ulcers/ requires liquid diet 4: Alimentation not possible
34
Mucositis Prevention: basic oral care
- Brush teeth with soft toothbrush at least **BID** - Floss teeth at least once daily - Rinse mouth **four times daily** with bland mouth rinse (sodium bicarbonate, normal saline, or tap water)
35
Mucositis Prevention: cryotherapy
- Application of ice or cold substance (popsicles, ice cream) to mouth immediately before, during, and after administration of chemotherapy - Vasoconstriction of the blood vessels leading to reduced BF, and lower a local [ ] of chemo - Evidence is limited; melphalan, 5-FU (bolus)
36
Mucositis Prevention: L-glutamine
- AA associated w/ cell proliferation and survival - MoA: decrease cell death of mucosal tissue - Limited data
37
Mucositis Prevention: Palifermin
- MoA: recombinant keratinocyte GF that directly stimulates proliferation of epithelial cells - Indication: autologous hematopoietic stem cell transplant where WHO grade 3 - Warnings: administration w/i 24 hrs may increase mucositis, potential for stimulation of tumor growth - AEs: edema, skin rash
38
Mucositis Treatment: “Magic” Mouthwash ingredients, MoA, AEs
- Diphenhydramine + aluminum OH + lidocaine +/- nystatin - Antihistamine: reduces histamine release/inflammation - Antacid: coats the mouth and increase pH - Local anesthetic (lidocaine): provide pain relief/numbing - Nystatin: prevention/tx of oral thrush caused by Candida sp - AEs: taste disturbances, burning/tingling sensation in mouth
39
Mucositis Treatment: sucralfate MoA, D/I
- MoA: create coating on the mucosa that can help create a protective barrier - X decrease mucositis, but decrease bacterial colonization - D/I: separate meds by 1 hr before or 2 hrs after
40
Mucositis Types of pain
1. Visceral: Nociceptors in thoracic, pelvic, abdominal (internal organs) 2. Somatic: Arises from nociceptors in skin/ soft tissue, muscle 3. Neuropathic: Direct damage to somatosensory neurons 4. Psychological pain: Trauma of past procedures, prognosis, understanding of pain
41
(M) 5 A’s of pain management
1. **Analgesia**: minimize pain perception 2. **Activities**: optimize QoL and activities of daily living (ADL) 3. **AEs**: minimize both SEs of analgesic & uncontrolled pain 4. **Aberrant drug taking**: use lowest dosages, assess safety of pain management and follow up when dosages are increased/ reduced 5. **Affect**: patients’ mood/ perception of QoL
42
(M) Opioid therapy: MoA, Use, AEs
- Bind to opioid receptors in CNS, inhibiting ascending pain pathway to alter the perception to pain - **Moderate to severe** pain not related to an oncologic emergencies (spinal cord compression) - Constipation
43
(M) Opioid Naive patients
- Start & titrate short acting agents Q3-4H PRN - If multiple doses of SA opioid needed per day, consider addition of long acting opioid
44
(M) Short-acting opioids
Oxycodone IR, Hydrocodone w/ APAP, Hydromorphone, Morphine IR
45
(M) Long-acting opioids
Oxycodone ER, Methadone, Fentanyl transdermal patches
46
(M) Opioid Tolerant patients
- Pts already taking SAO: titrate doses up PRN to achieve analgesia (30-100%) - If multiple doses of SAO needed per day, consider addition of LAO
47
(M) Acute Pain Crisis first line tx
Hospitalization or inpatient hospice, PCA
48
What is Patient-controlled analgesic (PCA)?
- Programmable IV infusion device that allows the pt/caregiver to administer their own pain relief while “capping” the max amount of opioids at safe determined dosages - Basal: continuous infusion of opioid provided at set dosage to the pt each hr - Bolus: delivered when button is pressed by pt. Device programmed w/ predetermined max bolus doses allowed per hr (=“lock-out”)
49
Risk factors of colorectal cancer: Modifiable
Obesity/ high BMI, Low physical activity, Alcohol consumption, Smoking, High consumption of meat and processed foods, Low intake of fruits and vegetables
50
Risk factors of colorectal cancer: Non-Modifiable
Male, Age >50 yrs, Family hx, Genetic predisposition, Adenomatous polyps, Inflammatory bowel disease (IBD), DM
51
(CC) Screening recommendations for general populations vs high-risk
General: Colonoscopy every 10 yrs (Start 45 yo) High-risk: Lynch syndrome, Peutz-Jeghers syndrome Colonoscopy more frequently
52
(CC) FOLFOX
- Folinic acid (leucovorin) - Fluorouracil - Oxaliplatin
53
(CC) CapeOX
- Capecitabine - Oxaliplatin
54
(CC) FOLFoxIRI
- Folinic acid (leucovorin) - Fluorouracil - Oxaliplatin - Irinotecan
55
(CC) FOLFIRI
- Folinic acid (leucovorin) - Fluorouracil - Irinotecan
56
(CC) First-line treatment: Stage I Goal, First-line
- Cure - Surgical excision of primary tumor and removal of regional lymph nodes - Adjuvant chemo not recommended
57
(CC) First-line treatment: Stage II (Low Risk) Goal, First-line
- Cure - Surgery, observation - Adjuvant chemo can be considered but rarely
58
(CC) First-line treatment: Stage II (High Risk) Goal, First-line
- Cure - Surgery → 5-FU or Capecitabine or FOLFOX or CAPEOX - Adjuvant chemo can be considered if: poorly differentiated histology, lymphovascular invasion, perineural invasion, bowel obstruction, localized perforation, close/indeterminate or positive margins, <12 lymph nodes surgically examined
59
(CC) First-line treatment: Stage III (Low Risk) Goal, First-line
- Cure - Surgery → CAPEOX (3 months) or FOLFOX (3-6 months) - Adjuvant chemo recommended for all patients
60
(CC) First-line treatment: Stage III (High Risk) Goal, First-line
- Cure - Surgery → CAPEOX (3-6 months) or FOLFOX (3-6 months) - Adjuvant chemo recommended for all patients
61
(CC) First-line treatment: Stage IV Goal, First-line
- Palliative - (FOLFOX or CAPEOX or FOLFIRI or FOLFOXIRI) +/- bevacizumab - KRAS/NRAS/BRAF WT and left-sided tumors only: 1) FOLFOX + (cetuximab or panitumumab) 2) FOLFIRI + (cetuximab or panitumumab) - dMMR/MSI-H only: 1) Nivolumab +/- ipilimumab 2) pembrolizumab
62
(CC) Fluorouracil (5-FU): formuation, PK, AEs
- Pyrimidine analog (antimetabolite) - Infusional - Metabolized to form active metabolites → interfere with DNA/RNA synthesis: F-UMP, F-dUMP - Very short t ½ → used in combination w/ leucovorin - Eliminated via dihydropyridine dehydrogenase (DPD) - AEs: **hand-foot syndrome**
63
(CC) Capecitabine: absorption, AE
- Prodrug of 5-FU - Absorbed in the intestines - AEs: **hand-foot syndrome**
64
(CC) Oxaliplatin
- Platinum compound (alkylating agent) - DNA cross-links → inhibit DNA replication and transcription → cell death - AEs: cold sensitivity, neuropathy
65
(CC) Irinotecan
- Active metabolite (SN-38) bind reversibly to topoisomerase I-DNA complex, preventing religation of the cleaved DNA strand and cell lysis - AE: diarrhea - Early: atropine/ Late: loperamide - UGT1A1 deficiency (*28) leads to worse SEs
66
(CC) Anti-angiogenesis agents
- **Bevacizumab**, ziv-aflibercept, ramucirumab - Targets vascular endothelial GF (VEGF) - AEs: hemorrhage, wound healing complications, HTN, arterial thromboembolism
67
(CC) Immune checkpoint inhibitors
- PD-1 inhibitor: nivolumab, pembrolizumab - CTLA-4 inhibitor: ipilimumab - Enhances T-cell activation and proliferation - AEs: **immune-mediated organ toxicities**
68
(CC) EGFR pathway inhibitors
Cetuximab, panitumumab - Competitively inhibits epidermal GF (EGF) by binding to EGF receptor (EGFR) - AEs: **skin rashes/toxicities** Encorafenib: BRAF V600E mutation - ATP inhibitor that suppresses tumor growth through the MAPK/ERK pathway - AEs: **skin reactions**
69
(CC) Antibody-Drug conjugates
- **Fam-trastuzumab deruxtecan**: HER2 amplified - Humanized IgG1 monoclonal Ab, a cleavable linker, and a topoisomerase inhibitor → upon internalization, linker is cleaved to release the topoisomerase inhibitor → targeted DNA damage & cell death
70
Etiology/Risk factors of prostate cancer (**High Risk**)
- Family History - Race: African American > Caucasian > Asian - Genetic: tumor suppressor genes (BRCA1/2), proto-oncogenes (TP53, BRCA, BCR-ABL, HER2) - Age: median diagnosed age 67 - Diet: high-meat and high-fat diets - **African American, men with first degree relative diagnosed with prostate cancer at age <65 yo**
71
(PC) Screening recommendations
- Digital Rectal Exam (DRE) - Prostate Specific Antigen (PSA): >3 ng/mL requires further evaluation - Shared decision making process: MD & patient
72
(PC) Grading: Gleason Score Calculation, Low vs intermediate vs high
- Most common grade + second most common grade - Low: 6 - Intermediate: 7 - High: 8
73
(PC) Treatment is determined by ___ (2)
Risk stratification & Life expectancy
74
(PC) Very low risk treatment: Long vs Short life expectancy
- >=20 yrs: active surveillance, radiation, radical prostatectomy +/- pelvic lymph node dissection - 10-20 yrs: active surveillance - <10 yrs: observation
75
(PC) Low risk treatment: Long vs Short life expectancy
- >=10 yrs: active surveillance, radiation, radical prostatectomy +/- pelvic lymph node dissection - <10 yrs: observation
76
(PC) Intermediate risk treatment: Long vs Short life expectancy
- >=10 yrs: radical prostatectomy +/- pelvic lymph node dissection, radiation +/- androgen deprivation therapy (ADT; 4-6 months) or brachytherapy alone - <10 yrs: observation, radiation +/- androgen deprivation therapy (ADT; 4-6 months) or brachytherapy alone
77
(PC) High & Very High risk treatment: Long vs Short life expectancy
- >5 yrs or symptomatic: radiation + ADT (2-3 yrs), radiation + brachytherapy +/- ADT (2-3 yrs), radical prostatectomy + pelvic lymph node dissection - =<5 yrs and asymptomatic: observation, ADT, radiation
78
(PC) Observation: Goal, Preferred patients, Monitoring, (+) / (-)
- Avoid non-curative treatment - Very low to intermediate risk disease and <10 yr LE - PSA, DRE, symptoms no more than every 6 months - Avoid possible AEs & maintain QoL - Risk of progression of disease, increased pt anxiety
79
(PC) Active surveillance: Goal, Preferred patients, Monitoring, (+) / (-)
- Expectation to deliver curative therapy if the cancer progresses - Very low/low risk disease and LE >=20 yrs - PSA at least every 6 months, DRE & biopsy at least every 12 months - Avoid possible AEs & maintain QoL - Missed opportunity for cure, tx delay, increased pt anxiety
80
(PC) What is Androgen Deprivation Therapy (ADT)?
- Goal: inhibit testosterone production - Orchiectomy: surgical removal of testes - Hypothalamic-pituitary-gonadal axis: LHRH agonist: (-) feedback, LHRH antagonist --> Goal: testosterone <50 ng/dL
81
(PC) LHRH agonists MoA, agents, AEs
- Stimulate pituitary gland to produce LH & FSH → initial surge in testosterone - Goserelin, leuprolide, triptorelin, histrelin - AEs: **tumor flare**, osteoporosis, CV events
82
(PC) What is tumor flare? Prevention?
- Worsen symptoms: ureteral obstruction or urinary retention, spinal cord compression, increased bone pain - Castrate level: <50 ng/dL - Use in combination with antiandrogens (ex., bicalutamide, flutamide, nilutamide)
83
(PC) LHRH antagonists MoA, agent, AEs
- Reversibly binds to GnRHR on the pituitary gland and inhibits production of testosterone - Degarelix - **No tumor flare**
84
(PC) What is castration resistance?
- Serum testosterone <50 ng/dL - Occurs w/i 2-4 yrs on ADT therapy on ALL patients
85
(PC) Antiandrogens for non-metastatic: second generation agents & toxicities
- **Apalutamide**: seizures, QTc prolongation, avoid in thyroid dysfunction - **Enzalutamide**: seizures, CV effects - **Darolutamide**: must be taken w/ food, least DDI (does not penetrate BBB → no seizure)
86
(PC) Metastatic CRPC 1st line treatment: Asymptomatic Bone-only vs Visceral
- B-O: abiraterone, docetaxel, enzalutamide, sipuleucel-T - V: abiraterone, docetaxel, enzalutamide
87
(PC) Metastatic CRPC 1st line treatment: Symptomatic Bone-only vs Visceral
- B-O: docetaxel, radium-223 - V: docetaxel
88
(PC) Abiraterone: MoA, Dose in combination with ___, Administration with or w/o food, Warnings
- Selectively & irreversibly inhibits CYP17 → halts the formation of testosterone precursors - In combination w/ prednisone BID - Without food - Mineralocorticoid excess (HTN, hypokalemia, fluid retention)
89
(PC) Docetaxel: MoA, Warnings, SEs
- Taxane; promote assembly of microtubules, inhibit depolymerization of tubulin & stabilizes microtubules in the cell → inhibit DNA, RNA, protein synthesis - Neutropenia, fluid retention, hypersensitivity - Neuropathy
90
(PC) Cabazitaxel: MoA, Warnings, SE, Use
- Taxane; same as docetaxel - Hypersensitivity reaction - Neuropathy - Post docetaxel
91
(PC) Sipuleucel-T: MoA, SEs, Use
- Immunotherapy; stimulate immune response against prostatic acid phosphatase (PAP) - Acute infusion reactions - Asymptomatic bone-only disease
92
(PC) Radium-223: MoA, SEs, Use
- Mimics calcium to form complexes with bone mineral → alpha emitting isotope induces double strand DNA breaks - Peripheral edema, nausea - Symptomatic bone metastases w/ no know visceral metastases
93
(PC) Poly ADP-Ribose Polymerase (PARP) Inhibitors: agents, SEs, dose in combination with ___, use
- Olaparib, rucaparib - Nausea (moderate emetogenic potential) - Should be given in combination w/ ADT - Indicated in the metastatic castration resistant only
94
(PC) Lutetium-177-PSMA-617: Indication, Administration, AEs
- Metastatic CRPC, PSMA+ - Renal/hepatic toxicity - Administer pre-medications for N prior to infusion
95
(PC) Pembrolizumab: MoA, Indication
- PD-1 inhibitor; prevents activation of T cell - Metastatic CRPC
96
Risk factors of cervical cancer
1. Early age of sexual debut 2. Having multiple sexual partners or a high-risk sexual partner 3. Immunosuppression: organ transplant, immunodeficiency disorders (HIV) 4. History of sexually-transmitted infection 5. History of HPV-related vulvar or vaginal dysplasia 6. Non-adherence to screening programs 7. Tobacco smoking
97
(Cerv) Primary prevention: Vaccination schedule
- HPV vaccine recommended for all adolescents at age 11-12 - 2-dose series: 2nd dose 6-12 months after the first dose - 3-dose series (Age 15-26): 2nd dose 1-2 months after the first dose, 3rd dose 6 months after the first dose
98
(Cerv) Screening recommendations
- Women 21-29: every 3 yrs with cervical cytology alone - 30-65: every 3 yrs with cervical cytology alone, every 5 yrs with high-risk HPV testing alone, every 5 yrs with hrHPV testing in combination with cytology - 3 consecutive negative cytology results or 2 consecutive negative co-testing results within 10 yrs is recommended before stopping screening - Most recent test occurring within 5 yrs
99
(Cerv) Management of early stage/localized: IA1, IA2, IB1, IB2
Surgery +/- radiation
100
(Cerv) Management of locally advanced: IB3, II, III, IVA
- Chemoradiation = chemo + radiation - Common regimen: Pelvic External Beam Radiation (EBRT) + concurrent platinum-containing chemo → brachytherapy - Typically weekly cisplatin (carboplatin)
101
(Cerv) Cisplatin: toxicities, supportive care, monitoring
- Toxicities: severe N/V, peripheral sensory neuropathy, ototoxicity, electrolyte disturbances - Supportive care: antiemetics, hydration pre/post - Monitoring: electrolytes (K, Mg, Ca, Na)
102
(Cerv) Management of metastatic: IVB local vs systemic (PD-L1(+) vs (-))
- Local treatment: surgery +/- radiation - Systemic treatment: chemotherapy (main) - PD-L1(+): pembrolizumab + cisplatin or carboplatin + paclitaxel +/- bevacizumab - PD-L1(-): cisplatin or carboplatin + paclitaxel + bevacizumab - Incurable; palliative
103
(Cerv) Management of recurrent
- Local/regional: chemoradiation +/- surgery if applicable, chemotherapy Distant: - If new metastatic, approach as first-time - Second line for stage IVB: Pembrolizumab for PD-L1(+) or MSI-H/dMMR+ tumors / Tisotumab vedotin, cemiplimab
104
Risk factors of Lung Cancer
1. Environmental respiratory carcinogens: asbestos, arsenic, benzene 2. Genetics: first-degree relative w/ lung cancer 3. COPD 4. Asthma 5. Smoking tobacco
105
(LC) Screening target populations
Must meet all the following criteria 1. Adults 50-80 yrs 2. 20 pack-year smoking history 3. Currently smoke or have quit w/i the past 15 yrs
106
(LC) Screening recommendation
- Annual screening w/ low-dose computed tomography (CT) - Should continue until the person has not smoked for 15 yrs or develops a health condition that limits life expectancy or the ability/willingness to have curative lung surgery
107
(LC) Treatment of stages I-III Non Small Cell Lung Cancer (NSCLC): Resectable
- Surgery → adjuvant chemo +/- radiation → atezolizumab, pembrolizumab or osimertinib - Atezolizumab for 1 yr if PD-L1 >1% (If both EGFR+ and PD-L1+ give osimertinib) - Pembrolizumab for 1 yr regardless of PD-L1 - Osimertinib for 3 yrs if EGFR+
108
(LC) Treatment of stages I-III Non Small Cell Lung Cancer (NSCLC): Unresectable
- Mostly stage III - Chemoradiation → **durvalumab** (PD-L1 inhibitor) maintenance for 12 months
109
(LC) Preferred Chemotherapy in stages I-III NSCLC: Platinum Doublet nonsquamous vs squamous
- Nonsquamous: cisplatin + pemetrexed - Squamous: cisplatin + gemcitabine or docetaxel
110
(LC) Pemetrexed: MoA, Uses, Toxicities, D/I, Supportive care
- Antifolate; inhibit dihydrofolate reductase (DHFR) - Non-squamous NSCLC - Cutaneous reactions - NSAIDs, nephrotoxic drugs - Dexamethasone for 3 days beginning the day before tx (derm tox risk ), folic acid for 7 days pre through 21 days post, vitamin B12 for 7 days pre then every 3 cycles
111
(LC) EGFR mutation(+) stage IV NSCLC treatment
Most common mutations found in lung cancer **Osimertinib**
112
(LC) ALK rearrangement(+) stage IV NSCLC treatment
Alectinib, Lorlatinib, Brigatinib
113
(LC) ROS1 rearrangement(+) stage IV NSCLC treatment
Entrectinib, Crizotinib
114
(LC) BRAF V600E mutation(+) stage IV NSCLC treatment
- Dabrafenib + trametinib - Encorafenib + binimetinib
115
(LC) NTRK gene fusion (+) stage IV NSCLC treatment
Larotrectinib, Entrectinib
116
(LC) MET Exon 14 skipping mutation (+) stage IV NSCLC treatment
Capmatinib, Tepotinib
117
(LC) RET rearrangement (+) stage IV NSCLC treatment
Selpercatinib, Pralsetinib
118
(LC) PD-L1 checkpoint inhibitors stage IV NSCLC treatment: Indication, agents
- Tumor is too advanced to be surgically resectable - CTLA-4 mAb: Ipilimumab - anti-PD-1 mAb: Nivolumab, Pembrolizumab, cemiplimab-rwlc - Human anti-PD-L1 mAb: Atezolizumab, durvalumab
119
(LC) Immune-mediated AEs (irAEs) with checkpoint inhibitors
- Enterocolitis, hepatitis, dermatitis, neuropathy, endocrinopathy - **Permanently d/c and initiate systemic high-dose corticosteroid** therapy for severe immune-mediated reactions - Evaluate clinical chemistries of liver function, ACTH level, thyroid function tests at baseline and before each dose
120
(LC) Preferred first-line treatments for immune sensitive stage IV NSCLC (Nonsquamous): PD-L1 50% vs 1-49%
PD-L1 50% - Pembrolizumab + carboplatin/cisplatin + pemetrexed - Pembrolizumab - Atezolizumab - Cemiplimab PD-L1 1-49% - Pembrolizumab + carboplatin/cisplatin + pemetrexed
121
(LC) Preferred first-line treatments for immune sensitive stage IV NSCLC (Squamous): PD-L1 50% vs 1-49%
PD-L1 50% - Pembrolizumab + carboplatin + paclitaxel/albumin-bound paclitaxel - Pembrolizumab - Atezolizumab - Cemiplimab PD-L1 1-49% - Pembrolizumab + carboplatin + paclitaxel/albumin-bound paclitaxel
122
(LC) Preferred first-line treatments for PD-L1 <1% stage IV NSCLC (Nonsquamous): Performance score 0-1 vs 2
- PS 0-1: Pembrolizumab + carboplatin/cisplatin + pemetrexed - PS 2: Carboplatin + pemetrexed
123
(LC) Preferred first-line treatments for PD-L1 <1% stage IV NSCLC (Squamous): Performance score 0-1 vs 2
- PS 0-1: Pembrolizumab + carboplatin + paclitaxel/albumin-bound paclitaxel - PS 2: Carboplatin + albumin-bound paclitaxel/gemcitabine/paclitaxel
124
(LC) Maintenance therapy for stage IV NSCLC
- Initial tx of immunochemo given for 4-6 cycles - Pembrolizumab +/- pemetrexed - Atezolizumab +/- bevacizumab - Should continue for 2 yrs if no progression
125
(LC) Staging of small cell lung cancer (SCLC): Limited vs Extensive
- Limited: tumor in a single hemithorax and fits in a single radiation port - Extensive: anything beyond limited
126
(LC) Treatment of limited stage SCLC: Goal, Regimens
- Goal: cure - Cisplatin + Etoposide
127
(LC) Treatment of extensive stage SCLC: Goal, Regimens
- Goal: palliation - Chemo + immuno → maintenance immuno - Carboplatin + etoposide + atezolizumab x4 cycles → atezolizumab maintenance - Carboplatin + etoposide + durvalumab x4 cycles → durvalumab maintenance - Cisplatin + etoposide + durvalumab x4 cycles → durvalumab maintenance
128
(St) Cells that bind to MHC II
CD4 T
129
(St) Cells that express MHC II
APCs: activated B cells, dendritic cells, macrophages
130
(St) Cells that bind to MHC I
CD8 T cells and NK cells
131
(St) Cells that express MHC I
All nucleated cells including APCs and tumor cells
132
(St) CD4 “helper” T cell activation and polarization requires 3 DC-derived signals
1. Antigen specific: TCR (T cell) binds to MHC II-associated TAA on APC 2. Co-stimulatory: CD28 binds to B7 (CD80) on APC 3. Polarizing: IFN-gamma & IL-12 promote Th1; IL-10 promotes Th2 development
133
(St) CD8 “cytotoxic” T cell activation assisted by Th-1 cells via 3 signals
1. TCR binds to MHC I/antigen 2. CD28 binds to B7 3. Secretion of IL-2 by CD4 T cell --> CD8 T cell survival & memory T cells
134
(St) Activated CD8 T cells differentiate into cytotoxic T lymphocytes (CTLs) & destroy target cells expressing antigen bound to ___
MHC I
135
(St) B cell recognizes antigen through membrane-bound ___ and ___
IgM and IgD
136
(St) B cell activation most often requires Th2 cell: 3 signals
1. Crosslinking of surface Ig by antigen 2. CD40 binds to CD40L and Th2 secretes IL-4 3. secretion of IFN-gamma, IL-4, IL-10, IL-21
137
(St) Activated B cells differentiate into plasma cells, secrete circulating ___ and ___; three roles
- IgM and IgG 1. Complement 2. Opsonization and phagocytosis 3. Antibody-dependent cellular cytotoxicity (ADCC)
138
(St) CAR-T cells do/do not require antigen processing and presentation by APCs
Do **NOT**
139
(St) CAR-T cell toxicities (BBW) and treatment
1. Cytokine Release Syndrome (CRS): Corticosteroids & tocilizumab 2. Encephalopathy (ICANS or CRES): Corticosteroids - REMS
140
(St) S/S of CRS
Capillary leak, HoTN, multiorgan dysfunction/failure
141
(St) Risk factors of CRS
ALL, high tumor burden, higher CAR-T cell dose
142
(St) Toclizumab: Indication, MoA, AEs, Algorithm by CRS grading (G1-3)
- Treatment of CRS - mAb targeting IL-6R - Serious infections leading to hospitalization - Grade 1: X - Grade 2: only when >50 or comorbidities - Grade 3, 4: YES
143
(St) CTLA-4 is expressed by ___, which competes with ___ for binding to ___
Activated CD8 T cells (CTLs); CD28; B7 on DC
144
(St) PD-1 is expressed by ___
T(regs), CTLs, activated B cells, activated NK cells
145
(St) PD-L1 is expressed by ___
Tumor cells
146
(St) Managing immune-related AEs (irAEs) with checkpoint inhibitors: Thyroid
- Hypothyroidism > Hyper - Levothyroxine
147
(St) Clinical S/S of Type I IgE-mediated Hypersensitivity
Urticaria, Angioedema
148
(St) Risk factors for Type I hypersensitivity
1. IV administration 2. Multiple previous cycles of the drug 3. Prior infusion rxn to another drug in the same class 4. Hx of multiple drug allergies or atopy
149
(St) Type I IgE-mediated Hypersensitivity vs SIRs
- Type I: IRRs w/ any feature of mast cell/basophil degranulation (angioedema, urticaria) --> Grade 3-5 (Severe) - SIRs: no urticaria or angioedema --> Grade 1-5
150
(St) NCI CTCAE Grade 1, 2, 3 algorithm
- G1: Infusion not stopped, tx not needed - G2: Therapy or infusion temporarily stopped but responds promptly to symptomatic tx, prophylactic med for supportive care (benadryl, corticosteroid) - G3: Prolonged even after tx, recurrence of symptoms, hospitalization required
151
(St) IgE-mediated (Type I) infusion rxn: Platinum agents
- Premedication not routinely administered - Most common after: 1) Initial course completed, followed by relapse & re-treatment, 2) At least six cycles of continuous treatment - Skin testing(+) → refer to specialist for desensitization - Carboplatin, cisplatin, oxaliplatin
152
(St) Carboplatin infusion rxn incidence is higher in children with ___
Brain tumors
153
(St) IgE-mediated (Type I) infusion rxn: Asparaginase
- Skin testing not useful - Premed not recommended - More common IV > IM - Severe rxn to peg-asparaginase → switch to Erwinaze
154
(St) IgE-mediated (Type I) infusion rxn: Etoposide
- Low incidence - Emulsifying agent in IV preparation (polysorbate 80) thought to be the cause - Neither skin testing or premed recommended
155
(St) Non-IgE-mediated infusion rxn: Taxanes - mostly occurs ___, premed, skin testing
- 90% occur during first or second drug infusion - Premed: 1. Paclitaxel: dexamethasone 12 & 6 H prior + diphenhydramine & famotidine 30 mins prior 2. Docetaxel: dexamethasone for 3 consecutive days, starting 24 hrs prior - Skin testing recommended prior to each subsequent dose --> (+): refer (-): premed & rechallenge at slower rate
156
(St) Emulsifying agents in: paclitaxel vs docetaxel & etoposide
Cremophor EL vs polysorbate-80
157
(St) Monoclonal antibodies (mAb): Type I-like more commons with ___ (3)
Rituximab, trastuzumab, cetuximab
158
(St) Monoclonal antibodies (mAb): CRS more common with ___
Rituximab
159
(St) Monoclonal antibodies (mAb): premedication
- APAP + diphenhydramine 30 mins before first and second infusions - Famotidine 30 mins prior

Oncology (4 decks)

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