ther exam

Oncology

How do we determine the Absolute Neutrophil Count (ANC)?

ANC = (WBC) x [(% Segs + %Bands)/100]

An ANC of _____ indicates increased risk of infection from exposure.

500 - 1000

An ANC of ____ indicates increased risk of infection from host organism.

< 500

As the ANC decreases, infection risk ____.

increases

What is the nadir?

lowest ANC after chemo

What is febrile neutropenia?

Fever: single temp of 101F or greater OR 100.4F or greater orally over 1 hour period
Neutropenia: neutrophils < 500 OR neutrophils < 1000 and a predicted decline to 500 or less over the next 48 hours

___ may be the only indication of severe infection in neutropenic patients.

Fever

What are the major risk factors for developing febrile neutropenia?

1. type of malignancy (hematologic at greatest risk)
2. type of chemo regimen
3. prior myelosuppressive therapy

What agents are recommended for antibacterial prophylaxis of febrile neutropenia?

ciprofloxacin or levofloxacin

What agents are recommended for anti fungal and antiviral prophylaxis of febrile neutropenia?

fluconazole or acyclovir

When are Myeloid Growth Factors recommended for primary prevention of febrile neutropenia?

treatment regimen risk of febrile neutropenia > 20%

When are Myeloid Growth Factors recommended for secondary prevention of febrile neutropenia?

history of febrile neutropenia episode

What is the most common etiology of febrile neutropenia?

bacterial (specifically mostly Gram positive staph epi)

A MASCC Risk Index score of ____ indicates a patient has high risk febrile neutropenia.

< 21

What is recommended for low-risk treatment of febrile neutropenia?

1. PO ciprofloxacin + Augmentin
2. PO moxifloxacin

Do not use oral low-risk febrile neutropenia treatment regimen if patient received prior...

quinolone prophylaxis

What is recommended for high-risk treatment of febrile neutropenia?

inpatient IV antimicrobial(s)
1. cefepime
2. imipenem/cilastatin or meropenem
3. Zosyn

When would we recommend adding additional gram positive coverage (usually vancomycin) to high-risk treatment of febrile neutropenia?

if the patient is clinically unstable, positive culture for gram + bacteria, SSTI, etc

What is the recommendation for addition of myeloid growth factors in high-risk treatment of febrile neutropenia?

If patient received prophylactic pegfilgrastim, no further GCSF needed. If patient is already taking daily prophylactic filgrastim, continue.

When is it recommended to discontinue high-risk treatment of febrile neutropenia?

until ANC > 500 and afebrile (and no infection was identified)

What should we monitor daily during high-risk treatment of febrile neutropenia?

1. response to therapy (symptoms & cultures)
2. ANC
3. fever

What are the laboratory hallmarks of Tumor Lysis Syndrome (TLS)?

HYPERuricemia, HYPERkalemia, HYPERphosphatemia, HYPOcalcemia

Which cancers are at high risk of Tumor Lysis Syndrome (TLS)?

1. Burkitt's Lymphoma
2. AML, CLL, ALL with larger disease burden (WBC > 100k, high LDH, etc)

Which cancers are at low risk of Tumor Lysis Syndrome (TLS)?

most solid tumors (breast, prostate, lung, colon)

What is the most important method of prevention of Tumor Lysis Syndrome?

hydration

What is recommended for the prevention of Tumor Lysis Syndrome in low risk patients?

oral hydration

What is recommended for the prevention of Tumor Lysis Syndrome in intermediate risk patients?

IV hydration (NS) and allopurinol

What is recommended for the prevention of Tumor Lysis Syndrome in high risk patients?

IV hydration (NS) and rasburicase (may use allopurinol after rasburicase is given)

What is the preferred dose of rasburicase (Elitek) in prevention of Tumor Lysis Syndrome?

fixed dose of 3-6 mg x 1 dose (may repeat if needed)

Treatment of vesicant extravasation caused by _____ requires the use of cold compresses.

anthracyclines

Treatment of vesicant extravasation caused by ____ requires the use of warm compresses.

vinca alkaloids

What is recommended for the treatment of Malignant Spinal Cord Compression?

1. dexamethasone
2. surgical decompression & stabilisation
3. radiation

What is a symptom of Malignant Spinal Cord Compression that can be masked due to it being a side effect of many chemotherapy regimens?

numbness

Supportive Care

What is acute CINV?

n/v within 24 hours of dose (peak 5-6 hours)

What is delayed CINV?

n/v that occurs 1-7 days after dose

What agents are known for causing delayed CINV?

cisplatin, carboplatin, cyclophosphamide, and doxorubicin

What is anticipatory CINV?

n/v with prior cycle leads to n/v before next dose of chemotherapy is given (conditioned reflex)

What is breakthrough CINV?

n/v that occurs despite appropriate prophylactic antiemetic therapy

What is refractory CINV?

n/v during subsequent cycles after the occurrence of breakthrough n/v in prior cycles

What is the biggest risk factor for CINV?

drug emetogenicity

Which agents are considered high emetic risk chemotherapy (> 90% incidence of emesis)?

1. AC combination (anthracycline + cyclophosphamide)
2. cisplatin
3. carboplatin AUC 4 or greater
4. ifosfamide 2 g/m2 or greater per dose

True or False? Patients who do not have the ability to swallow can be prescribed ondansetron oral film or ODT for nausea/vomiting.

False (must be swallowed after dissolving in mouth)

What are the adverse effects of 5-HT3 antagonists?

headache, constipation, and QT prolongation (except palonosetron and TD/SQ granisetron)

Which 5-HT3 antagonist has the longest half life?

Palonosetron (40 hours)

Are 5-HT3 antagonists better for prevention of acute CINV, delayed CINV, or both?

acute CINV

Which NK-1 antagonist does not have a drug interaction with dexamethasone?

rolapitant

What is the maximum concomitant dexamethasone dose with NK-1 antagonists?

12 mg (due to drug interactions)

Which NK-1 antagonist requires a dose on Day 2?

oral aprepitant (Emend)

NK-1 antagonists must be given in combination with...

dexamethasone + 5-HT3 inhibitor

Dexamethasone is superior to 5-HT3 antagonists for ____ CINV.

delayed

When are phenothiazines useful for CINV?

low emetogenic chemo & breakthrough n/v

Which phenothiazines are recommended for CINV?

prochlorperazine & promethazine

Prochlorperazine is (more/less) sedating than promethazine.

less

When is olanzapine (Zyprexa) effective for CINV?

acute, delayed, and breakthrough n/v

What is a major adverse effect of olanzapine (Zyprexa)?

sedation

When is lorazepam used for CINV?

anticipatory n/v and breakthrough n/v with anxiety component

When is haloperidol used for CINV?

breakthrough

When is metoclopramide used for CINV?

low emetogenic chemo and breakthrough n/v

What is the basic recommendation for prevention of acute CINV?

premedication given 30-60 minutes prior to administration of chemotherapy (Day 1)

What is the basic recommendation for prevention of delayed CINV?

schedule corticosteroid, 5-HT3 antagonist, and/or olanzapine for 2-3 days after chemotherapy + acute prophylaxis on day 1

What is recommended for prophylaxis of CINV with high emetogenic chemo?

triplet or quad prophylaxis on day 1 + delayed n/v prophylaxis

What is recommended for prophylaxis of CINV with moderate emetogenic chemo?

doublet prophylaxis on day 1 + delayed n/v prophylaxis

What is recommended for prophylaxis of CINV with low risk emetogenic chemo?

monotherapy on day 1

What is recommended for prophylaxis of CINV with minimal risk emetogenic chemo?

no prophylaxis required (PRN)

Which 5-HT3 antagonists are recommended for prophylaxis of CINV? Do they need to be given on all days of multi-day therapy?

Any 5-HT3 antagonist can be used, but if palonosetron, Sustol, or Sancuso are given on day 1, no further 5-HT3 antagonist is needed due to their long half-lives

Which agents are recommended for monotherapy prophylaxis of CINV?

dexamethasone, 5-HT3 antagonist, prochlorperazine, or metoclopramide

What are the recommendations to preventing anticipatory CINV?

1. prevent by optimizing CINV prophylaxis
2. avoid strong smells that may precipitate symptoms
3. premedicate before coming to the clinic with lorazepam
4. non-pharm (behavioral therapy, etc)

When is it recommended to give lorazepam for anticipatory CINV?

1-2 hours before scheduled infusion/coming to the clinic

What is recommended for the treatment of breakthrough CINV?

add scheduled antiemetic(s) from a class not used in prophylactic regimen

Which agents are NOT used for breakthrough n/v?

NK-1 antagonists or long-acting agents (palonosetron, Sancuso, Sustol)

What is recommended for HSCT patients receiving TBI/high dose chemo conditioning regimens to prevent oral mucositis?

palifermin

What is suggested for head & neck cancer patients receiving chemo radiation (CT-RT) to prevent oral mucositis?

oral glutamine

What is recommended for prevention of mucositis in HSCT patients receiving melphalan conditioning regimens and other patients receiving bolus 5-FU?

oral cryotherapy

What appetite stimulants could be considered to treat anorexia and cachexia in cancer patients?

1. megestrol acetate
2. dexamethasone
3. mirtazapine
4. olanzapine

Malignant Hematology

What is the difference between Acute Lymphocytic Leukemia (ALL) and Acute Myeloid Leukemia (AML)?

ALL is major subtypes (B-Cell ALL and T-Cell ALL). AML is multiple subtypes.

Which type of acute leukemia typically affects younger patients?

ALL

Which type of acute leukemia typically affects older patients?

AML

What are the major goals of therapy in ALL/AML treatment?

1. achieve rapid complete remission
2. maintain complete remission
3. minimize toxicity

_____ is the disappearance of all physical and bone marrow evidence of leukemia (normal cellularity with less than 5% blasts), with restoration of normal hematopoiesis.

Complete Remission (CR)

Treatment of which type of acute leukemia includes routine CNS prophylaxis with intrathecal chemotherapy?

ALL

Which acute leukemia treatment regimen is more complex, ALL or AML?

ALL

HSCT is reserved for high risk patients receiving ALL or AML treatment. Do these patients receive autologous, allogeneic, or both?

allogeneic

What is the first step in acute leukemia treatment? What is the goal of that first step?

Induction Chemo - goal is to induce CR

True or False? Do not use preservative-containing solutions/drugs for intrathecal chemotherapy.

True

What is a major adverse effect of high dose cytarabine (> 1000mg/m2)? How do we prevent this?

ocular toxicity (corneal toxicity & hemorrhagic conjunctivitis) prevented with steroid eye drops

True or False? Ocular toxicity caused by high dose cytarabine is irreversible.

False (it is reversible)

What is the typical first line agent for treatment of CML?

imatinib (BCR-ABL tyrosine kinase inhibitor)

If a patient with CML does not respond to first line therapy or their disease progresses, what is the recommended next step?

use mutation profile to guide treatment

What is a major adverse effect for all BCR-ABL tyrosine kinase inhibitors?

myelosuppression

What is a major adverse effect of imatinib (Gleevec)?

fluid retention/edema

What is a major adverse effect of dasatinib (Sprycel)?

pleural/pericardial effusions

What is a major adverse effect of nilotinib (Tasigna)?

QT prolongation (BBW)

What are the major adverse effects of ponatinib (Iclusig)?

arterial thrombosis, hepatotoxicity, VTE (BBW) and heart failure

What are the preferred first line regimens for treatment of CLL?

1. acalabrutinib +/- obinutuzumab
2. venetoclax +/- obinutuzumab
3. zanubrutinib

What are the preferred second line and subsequent regimens for treatment of CLL?

1. acalabrutinib
2. zanubrutinib
3. venetoclax +/- rituximab

What can occur in patients with CLL after initiation of venetoclax, irbutinib, and acalabrutinib?

transient lymphocytosis

Which agent to treatment CLL may require hospital admission for therapy initiation in patients at high risk for tumor lysis syndrome?

venetoclax

What is the prototype chemotherapy regimen for classical Hodgkin Lymphoma (HL)?

ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)

Which classification of B cell NHL is not curable with chemo?

Indolent (follicular and marginal zone)

Which classification of B cell NHL is potentially curable with chemo?

Aggressive (mantle cell and DLBCL) and Very Aggressive (Burkitt and Lymphoblastic lymphoma)

If left untreated, patients with Indolent B cell NHL can live for ____.

years

If left untreated, patients with Aggressive B cell NHL can live for _____.

months

If left untreated, patients with Very Aggressive B cell NHL can live for _____.

weeks

What are the B symptoms associated with lymphoma?

weight loss, fever, night sweats

Can patients with NHL receive autologous HSCT, allogeneic HSCT, both, or neither?

autologous HSCT

What is the first line treatment regimen for DLBCL?

R-CHOP with or without radiation

What agents are in the R-CHOP regimen?

1. rituximab
2. cyclophosphamide (Cytoxan)
3. doxorubicin (hydroxydaunomycin; Adriamycin)
4. vincristine (Oncovin)
5. prednisone

What are 2 major adverse effects (BBW) of rituximab?

infusion reactions with first dose and Hepatitis B virus reactions

When do rituximab infusion reactions typically occur?

during first infusion

What is recommended to prevent rituximab infusion reactions?

premedication of antihistamine and acetaminophen +/- steroid

What should we screen patients for before giving rituximab or other anti-CD20 monoclonal antibodies?

Hepatitis B

What is recommended in patients receiving rituximab or other anti-CD20 monoclonal antibodies who also test positive/reactive for HBV?

prophylaxis with entecavir (continue for at least 12 months after completion of therapy)

Which type of anthracycline cardiotoxicity is irreversible?

chronic/delayed

What effects are seen with chronic/delayed anthracycline cardiotoxicity?

left ventricular dysfunction and congestive heart failure

What is 1 major proposed mechanism of chronic/delayed anthracycline cardiotoxicity?

mitochondrial iron accumulation

What do we monitor in patients receiving anthracyclines (doxorubicin, daunorubicin, etc)?

lifetime cumulative dose & LVEF

What are some cardioprotective strategies for patients receiving anthracyclines?

1. limit lifetime cumulative dose
2. prolong infusion rate
3. use cardioprotectant - dexrazoxane (Zinecard)
4. use liposomal formulation

Which cardioprotectant is recommended to give with anthracyclines? When do we give it?

dexrazoxane (Zinecard) after 300 mg/m2 of doxorubicin has been given and infused immediately before doxorubicin

What are some late effects of cancer treatment?

effects on fertility, second malignancies, cardiotoxicity, avascular necrosis, pulmonary fibrosis, hearing loss, endocrine dysfunction, cataracts

Hematopoietic Stem Cell Transplant (HSCT)

What are the steps in the stem cell transplant process?

1. Evaluation
2. Mobilization
3. Collection
4. Conditioning
5. Transplant
6. Engraftment

What are the top indications for Autologous Stem Cell Transplant?

1. multiple myeloma
2. Hodgkin lymphoma
3. Non-Hodgkin lymphoma

What are the top indications for Allogeneic Stem Cell Transplant?

1. Acute myeloid leukemia
2. Acute lymphocytic leukemia
3. Myelodysplastic Syndrome

What is the source of cells for Autologous SCT?

patient's own cells

What is the source of cells for Allogeneic SCT?

donor cells

Which requires conditioning, Autologous or Allogeneic SCT?

both

Which requires HLA matching, Autologous or Allogeneic SCT?

Allogeneic

Which has a risk of serious complications, Autologous or Allogeneic SCT?

both

Which has a risk of GvHD, Autologous or Allogeneic SCT?

Allogeneic

Which is often given outpatient, Autologous or Allogeneic SCT?

Autologous

Which has a higher risk of relapse, Autologous or Allogeneic SCT?

Autologous

Which has higher morbidity/mortality, Autologous or Allogeneic SCT?

Allogeneic

Breast Cancer

Name the 3 risk factors for breast cancer.

endocrine, genetic, lifestyle

Describe the endogenous estrogen exposure the increases the relative risk of developing breast cancer.

1. early menarche (< 12 y/o)
2. late menopause (55+ y/o)
3. nulliparity
4. late age at first birth (> 30 y/o)

True or False? Exogenous estrogen should be used for cancer prevention.

False (Estrogen/progesterone may increase the risk for breast cancer)

What is the recommendation for screening patients for breast cancer who are at average risk according to the USPSTF?

- Age 40-49: decision to start biennial mammogram is individualized
- Age 50-74: biennial mammogram
- Age 75+: insufficient evidence for mammogram

What is the recommendation for screening patients for breast cancer who are at average risk according to the NCCN?

For ages 40+, counsel on breast awareness and do mammogram and CBE annually.

What is the recommendation for screening patients for breast cancer who are at increased risk according to the NCCN?

1. Counsel on breast awareness
2. Clinical breast exam every 6-12 months
3. Mammogram annually (30-40 y/o)
4. Breast MRI annually (25-40 y/o)

What does "triple negative" mean?

ER, PR, and HER2 negative

Name the SERMs used for breast cancer therapy.

1. tamoxifen (Nolvadex/Soltamox)
2. raloxifene (Evista)
3. toremifene (Fareston)

Which SERM is indicated for risk reduction only?

raloxifene (Evista)

Which SERM is indicated for metastatic breast cancer only?

toremifene (Fareston)

Name the aromatase inhibitors used for breast cancer therapy.

1. anastrozole (Arimidex)
2. letrozole (Femara)
3. exemestane (Aromasin)

Which hormonal therapy agent is given IM?

fulvestrant (Faslodex)

What are the indications for tamoxifen?

1. pre & postmenopausal HR+ (any stage)
2. prevention in pre & postmenopausal high risk women & women with DCIS

Tamoxifen should be avoided with which drugs?

1. fluoxetine (Prozac)
2. paroxetine (Paxil)
3. bupropion (Wellbutrin)
4. duloxetine (Cymbalta)

Tamoxifen is okay to use with which drugs?

1. escitalopram (Lexapro)
2. venlafaxine (Effexor)
3. desvenlafaxine (Pristiq)
4. mirtazapine (Remeron)

What are the indications for aromatase inhibitors?

postmenopausal HR+ (all stages)

What are the off-label indications for aromatase inhibitors?

1. prevention in post menopause
2. treatment in pre menopause HR+ in combo with ovarian suppression/ablation

Which agents are used off-label in premenopausal women with HR+ breast cancer in combination with ovarian suppression/ablation?

aromatase inhibitors

Name the 2 major anti-HER2 agents.

trastuzumab (Herceptin) & pertuzumab (Perjeta)

What is the major adverse effect of trastuzumab (Herceptin)?

decreased LVEF and heart failure

What should we monitor in patients on trastuzumab (Herceptin)?

LVEF at baseline and during treatment

How is trastuzumab (Herceptin and biosimilars) administered?

IV infusion over 30 minutes every 1-3 weeks (90-min loading dose required)

How is trastuzumab (Herceptin Hylecta) administered?

SQ over 2-5 minutes every 3 weeks (loading dose not required)

Pertuzumab (Perjeta) should always be given with...

trastuzumab (Herceptin)

Name the available CDK 4/6 inhibitors.

1. abemaciclib (Verzenio)
2. palbociclib (Ibrance)
3. ribociclib (Kisqali)

What are CDK 4/6 inhibitors used for in breast cancer therapy?

metastatic, HR(+), HER2(-) breast cancer

Which CDK 4/6 inhibitor is used for adjuvant treatment of breast cancer?

abemaciclib

CDK 4/6 inhibitors should always be used in combination with...

hormonal therapy (tamoxifen, aromatase inhibitor, or fulvestrant)

What is a major adverse effect of abemaciclib? What is recommended to treat this?

diarrhea - co-prescribe loperamide at first sign of diarrhea

What are the pharmacologic options for prevention of breast cancer in premenopausal women?

tamoxifen

What are the pharmacologic options for prevention of breast cancer in postmenopausal women?

tamoxifen, raloxifene, aromatase inhibitors

At what age can we use pharmacologic options to prevent breast cancer?

35+ years old only

What is recommended as adjuvant hormonal therapy in premenopausal women?

1. tamoxifen +/- ovarian suppression/ablation
2. aromatase inhibitor + ovarian suppression/ablation

What is recommended as adjuvant hormonal therapy in postmenopausal women?

tamoxifen or aromatase inhibitor

What is recommended for treatment of metastatic HER2- disease?

hormonal therapy (add CDK inhibitor) or chemotherapy (if symptomatic metastatic disease)

What is recommended for treatment of metastatic HER2+ disease?

1. chemotherapy + anti-HER2 therapy
2. if HR+: use hormonal therapy in combo or sequenced with chemo/HER2 therapy

What is recommended for treatment of metastatic triple negative disease?

1. chemotherapy
2. if PD-L1 positive: pembrolizumab + chemo
3. sacituzumab govitecan

Prostate Cancer

What is the primary driver of prostate cancer?

androgens

What is castration-resistant prostate cancer?

In later stages of disease, prostate cancer cells can survive and proliferate without androgen signaling. There is disease progression with serum testosterone < 50 ng/dL.

True or False? Finasteride/dutasteride is recommended as a chemoprevention strategy of prostate cancer.

False (There is no universally recommended chemoprevention strategy. Finasteride/dutasteride is controversial.)

What is the preferred screening method for prostate cancer? At what age do the guidelines recommend against screening?

serum PSA; >70 years old

Name 2 factors that affect PSA.

5a-reductase inhibitors & saw palmetto

What are the 2 types of prostate cancer?

Castration-Resistant Prostate Cancer (CRPC) and Castration-Sensitive Prostate Cancer (CSPC)

What drug class is always given for metastatic prostate cancer?

LHRH agonist/antagonist

What is the goal of Androgen Deprivation Therapy (ADT)?

Induce castrate levels of testosterone (< 50 ng/dL one month after therapy initiation)

What are the pharmacologic options for ADT?

1. LHRH agonists
2. LHRH antagonists
3. antiandrogens

Name the LHRH Receptor Agonists used for prostate cancer.

1. goserelin (Zoladex)
2. leuprolide (Eligard; Lutron Depot)
3. triptorelin (Trelstar)
4. histrelin (Vantas)

Name the LHRH Receptor Antagonists used for prostate cancer.

1. degarelix (Firmagon)
2. relugolix (Orgovyx)

Which LHRH Receptor Antagonist is available SQ?

degarelix (Firmagon)

Which LHRH Receptor Antagonist is available PO?

relugolix (Orgovyx)

Which achieves castration faster - LHRH Receptor Agonists or Antagonists?

LHRH Receptor Antagonists (7 days or less)

What is the most common adverse effect of orchiectomy and LHRH agonists/antagonists?

hot flashes

What supplementation should all patients receive while receiving ADT?

calcium/vitamin D (due to decreased bone mineral density with fractures)

Name the 1st Generation Antiandrogens used for prostate cancer.

1. bicalutamide (Casodex)
2. flutamide (Eulexin)
3. nilutamide (Nilandron)

What agents are given with LHRH agonists to prevent tumor flare in metastatic disease or in long-term combination with LHRH agonists/antagonists?

1st Generation Antiandrogens

Which 1st generation antiandrogen is most often used due to having less adverse effects?

bicalutamide (Casodex)

Name the 2nd generation antiandrogens used for prostate cancer.

1. apalutamide (Erleada)
2. enzalutamide (Xtandi)
3. darolutamide (Nubeqa)

True or False? Antiandrogens can NOT be used as monotherapy to treat prostate cancer.

True (given with LHRH agonist/antagonist)

Which 2nd generation antiandrogen has less CNS effects and less drug interactions?

darolutamide (Nubeqa)

Which antiandrogens can cause CNS effects such as seizures?

2nd generation

Which agent should always be used in addition to ADT?

abiraterone acetate (Zytiga, Yonsa)

Which brand of abiraterone acetate should be given with low-dose prednisone?

Zytiga

Which brand of abiraterone acetate should be given with low-dose methylprednisolone?

Yonsa

Which brand of abiraterone acetate is given on an empty stomach?

Zytiga

Which brand of abiraterone acetate is given without regard to food?

Yonsa

Why is abiraterone acetate (Zytiga, Yonsa) given with steroids?

reduce risk for mineralocorticoid excess and adrenal insufficiency

Which chemotherapy agents are reserved for men with metastatic prostate cancer?

docetaxel (Taxotere) and cabazitaxel (Jevtana)

What is recommended to prevent fluid retention and hypersensitivity reactions with docetaxel (Taxotere)?

dexamethasone pre and/or post dose

Which patients require supportive therapy for bone metastases?

CRPC patients with bone mets

What are the supportive therapy options for bone metastases?

IV zoledronic acid, SQ denosumab (Xgeva)

Which supportive therapy for bone metastases requires dose adjustments for renal dysfunction?

zoledronic acid (contraindicated if CrCl < 30)

What supplementation is required with zoledronic acid and denosumab?

calcium/vitamin D

Colorectal Cancer (CRC)

What is the gold standard for CRC screening?

colonoscopy

Which CRC screening method requires sedation & complete bowel prep?

colonoscopy

Which CRC screening method does not require sedation and has a less extensive bowel prep?

flexible sigmoidoscopy

Which CRC screening method is noninvasive and does not require bowel prep or sedation?

stool-based fecal occult blood test (FOBT)

Which CRC screening method is a newer technology that detects markers of malignancy shed by polyps or adenocarcinomas?

stool-based DNA test

What is the average risk screening frequency of a colonoscopy?

10 years

What is the average risk screening frequency of a flexible sigmoidoscopy?

5-10 years

What is the average risk screening frequency of a stool-based fecal occult blood test (FOBT)?

1 year

What is the average risk screening frequency of a stool-based DNA test?

1-3 years (appropriate screening interval still not clear)

At what age is a patient considered average risk for CRC?

45 years old

What factors put a patient at increased risk of CRC?

1. personal history of adenoma (polyps), IBD, and/or cystic fibrosis
2. family history of CRC

What factors put a patient at high risk of CRC?

genetic syndromes (HNPCC, FAP, etc)

What screening method is used for patients at increased and high risk of CRC?

colonoscopy

Which cancer is typically not treated with radiation, colon or rectal?

colon

What is the recommended treatment for Stage I Colon Cancer?

surgery

What is the recommended treatment for Stage II Colon Cancer?

Surgery then adjuvant chemo if high risk

What is the recommended treatment for Stage III Colon Cancer?

Surgery then adjuvant chemo x 3-6 months (FOLFOX or CapeOx)

What is the recommended treatment for Stage IV Colon Cancer?

chemotherapy and/or targeted therapy until progression

What is the 1st line treatment of metastatic colon cancer?

(FOLFOX or FOLFIRI) +/- biologic agent (EGFR inhibitor or VEGF inhibitor)

What is the 1st line treatment of metastatic colon cancer if the tumor is MSI-H/dMMR?

pembrolizumab monotherapy

What is the recommended treatment for Stage I Rectal Cancer?

Surgery

What is the recommended treatment for Stage II and Stage III Rectal Cancer?

neoadjuvant chemotherapy + radiation then surgery +/- adjuvant chemo (depending on what neoadjuvant was given)

What is the recommended treatment for Stage IV Rectal Cancer?

(FOLFOX or FOLFIRI) +/- biologic agent (EGFR inhibitor or VEGF inhibitor)
[or pembrolizumab monotherapy if tumor is MSI-H/dMMR]

What is FOLFOX?

fluorouracil (5-FU) + leucovorin + oxaliplatin

What is FOLFIRI?

fluorouracil (5-FU) + leucovorin + irinotecan

What happens when leucovorin is given with 5-FU?

increases efficacy of 5-FU

What happens when leucovorin is given with high-dose methotrexate?

reverses action of methotrexate

What EGFR inhibitors are used for CRC?

cetuximab & panitumumab

What should we check for in patients with CRC before giving an EGFR inhibitor?

RAS mutations — wild-type RAS means it is EGFR inhibitor sensitive

What VEGF inhibitors are used for CRC?

bevacizumab, ramucirumab, ziv-aflibercept, regorafenib

Do EGFR inhibitors, VEGF inhibitors, or both require mutation testing?

EGFR inhibitors

What is the most common adverse effect of VEGF inhibitors?

hypertension

A patient should be checked for DPD deficiency before using which agent? Why?

5-FU - can cause severe, life-threatening toxicity

Patients should be checked for UGT1A1 mutations before using which agent? Why?

irinotecan - higher risk of severe neutropenia & diarrhea

Which phase of irinotecan-induced diarrhea has a dose-limiting toxicity?

delayed phase

What is the recommended treatment of acute phase irinotecan-induced diarrhea?

atropine

What is the recommended treatment of delayed phase irinotecan-induced diarrhea?

loperamide + supportive care

What drug must be co-prescribed with irinotecan?

loperamide

What is the dose-limiting toxicity of oxaliplatin?

peripheral neuropathy

What is recommended to prevent acute toxicity oxaliplatin-induced peripheral neuropathy?

avoid cold liquids/food

What is recommended to prevent chronic toxicity oxaliplatin-induced peripheral neuropathy?

stop-and-go approach (omit oxaliplatin after ~6 doses and resume later)

What is the recommended treatment of acute oxaliplatin-induced neurotoxicity?

prolong infusion time

What is the recommended treatment options of acute oxaliplatin-induced neurotoxicity?

1. dose reduction
2. d/c
3. duloxetine

What is the recommended prevention for the papulopustular rash caused by EGFR inhibitors?

1. skin care (moisturizer, sunscreen)
2. topical low-potency steroid
3. oral doxycycline or minocycline

What is the recommended treatment of the papulopustular rash caused by EGFR inhibitors?

1. topical/oral steroid
2. topical clindamycin/oral tetracycline

When should patients begin screening for CRC if diagnosed with IBD?

start 8 years after diagnosis

When should patients begin screening for CRC if they have a family history of CRC?

start at 40 years old at the latest

When should patients begin screening for CRC if they are at high risk?

start as early as 10 years old and check frequently

Lung Cancer

Which type of lung cancer is most common?

non-small cell lung cancer (NSCLC)

Which type of lung cancer is faster growing?

small cell lung cancer (SCLC)

Which type of lung cancer is moderately sensitive to radiation & has low sensitivity to conventional chemotherapy?

non-small cell lung cancer (NSCLC)

Which type of lung cancer is highly sensitive to conventional chemotherapy/radiation, but the responses do not last?

small cell lung cancer (SCLC)

Name the 3 pathologies of NSCLC.

1. adenocarcinoma
2. squamous cell carcinoma
3. large cell carcinoma

Which type of lung cancer has a higher incidence in smokers?

small cell lung cancer (SCLC)

Which type of lung cancer has actionable molecular alterations?

non-small cell lung cancer (NSCLC)

Which pathology of NSCLC is more common smokers?

squamous cell carcinoma

Which pathology of NSCLC is more common in non-smokers?

adenocarcinoma

An annual low dose CT scan to screen for lung cancer is recommended in patients who meet what criteria?

1. age 50-80
2. > 20 pack year history
3. current smokers OR quit within 15 years

Which stage(s) of NSCLC have a goal of curative intent?

Stage I - III

Which stage(s) of NSCLC have a goal of palliative intent?

Stage IV

What is Limited SCLC and what is the goal of therapy?

Limited SCLC means that the disease is confined to 1 radiation field. The goal is curative intent, but it is rarely curative.

What is Extensive SCLC and what is the goal of therapy?

Extensive SCLC means that the disease has spread to more than 1 radiation field. The goal is palliative intent.

What is the treatment of choice for Stage I, II, and III (resectable) NSCLC?

surgery

What is the recommended chemotherapy for Stage I, II, and III (resectable) NSCLC?

neoadjuvant or adjuvant therapy — platinum-based doublet +/- nivolumab + (osimertinib if EGFR+) or (atezolizumab if PD-L1+)

What is the recommended treatment for Stage III (unresectable) NSCLC?

platinum-based doublet + radiation followed by durvalumab x 1 year
(possible surgery for resection later on if possible)

What is the recommended treatment for Stage IV NSCLC?

systemic therapy with chemotherapy, checkpoint inhibitor, and/or targeted therapy

Which type of lung cancer can be treated with targeted therapy?

NSCLC

For metastatic NSCLC disease, what therapy is preferred in patients with PD-L1 greater than or equal to 50%?

checkpoint inhibitor monotherapy

What are the major adverse effects of cisplatin?

ototoxicity, nephrotoxicity, nausea/vomiting

What are the major adverse effects of carboplatin?

myelosuppression

What are the major adverse effects of oxaliplatin?

peripheral neuropathy

What are some major risk factors for cisplatin-induced nephrotoxicity?

1. concomitant nephrotoxins (avoid NSAIDs)
2. lack of adequate hydration

What is recommended to prevent cisplatin-induced nephrotoxicity?

hydration & avoiding nephrotoxic drugs

What is recommended to give before and after cisplatin to prevent nephrotoxicity?

pre-cisplatin: normal saline IV
post-cisplatin: maintain adequate PO fluid intake or additional IV fluids

What is the recommended treatment for cisplatin-induced nephrotoxicity?

d/c cisplatin and give supportive care (IV fluids, electrolyte management, etc)

Pemetrexed (Alimta) is only effective for which type of lung cancer?

non-squamous NSCLC

What is recommended to prevent hematologic and GI toxicities caused by pemetrexed (Alimta)?

folic acid & vitamin B12

What is recommended to prevent skin rash caused by pemetrexed (Alimta)?

dexamethasone

What is recommended 1st line for the treatment of Limited Stage SCLC?

cisplatin + etoposide with concurrent radiation

What is recommended 1st line for the treatment of Extensive Stage SCLC?

(carboplatin or cisplatin) + etoposide

Which agents are not recommended in the treatment of squamous NSCLC?

pemetrexed & bevacizumab

Intro to Oncology

What are the 4 steps of carcinogensis? Describe them.

1. Initiation - exposure to carcinogen
2. Promotion - growth of mutated cells
3. Conversion - mutated cell becomes cancerous
4. Progression - tumor invasion into local tissues; distant metastases

Which step of carcinogenesis is reversible?

promotion

What are the goals of curative intent?

long term remission & no recurrence

What are the goals of palliative intent?

improve symptoms, quality of life, & overall survival

Neoadjuvant therapy & adjuvant therapy apply to ______ tumors.

solid

_______ therapy is given BEFORE definitive treatment (usually surgery).

Neoadjuvant

______ therapy is given AFTER definitive treatment (usually surgery).

Adjuvant

Induction therapy, consolidation therapy, and maintenance therapy mainly apply to ________.

hematologic malignancies

The goal of _____ therapy is to induce remission with no visible evidence of cancer and is given first.

Induction

_____ therapy is started after induction and is used to eradicate any remaining cancer cells that are not visible.

Consolidation

_____ therapy is used to prevent recurrence.

Maintenance

_____ approximates tumor cell proliferation vs time.

Tumor Growth Model

_____ is the proportion of actively dividing cells.

growth fraction

_____ is the amount of time it takes for one cell or a group of cells to divide or double in size.

doubling time

______ is a certain percentage of cancer cells, not number, will be killed with each course of chemotherapy.

Cell Kill Hypothesis

During the early phase of tumor growth, most cancer cells are actively dividing showing a ______ growth fraction and a _____ doubling time.

high; short

As cancer grows, growth fraction is ______ and doubling time is ______ as cancer outgrows blood/nutrient supply.

lower; longer

Solid Organ Transplant – Dr. White

Which immune system is the first line of defense?

innate

Which immune system is able to develop a highly specific response and is referred to as "immune memory"?

adaptive

What are the 2 major arms of the adaptive immune system?

Humoral & Cell-Mediated

What cells make up the adaptive immune system?

B cells and T cells

Which HLA genes are responsible for cell-mediated transplant rejection?

Class I HLA genes (HLA-A, HLA-B, HLA-C)

Which HLA genes are responsible for antibody mediated transplant rejection?

Class II HLA genes (HLA-DP, HLA-DQ, HLA-DR)

What are the 3 signals requires for T cell activation?

1. Antigen presentation (with MHC)
2. co-stimulation signal (CD 80/86)
3. interaction of IL-2 with IL-2 receptor

Which immunoglobulin is responsible for long-term immunity?

IgG

Which immunoglobulin is the first antibody secreted post antigen exposure?

IgM

Which immunosuppressive agents are used for induction?

1. basiliximab
2. thymoglobulin
3. alemtuzumab

Which immunosuppressive agents are used for maintenance?

1. calcineurin inhibitors
2. antimetabolites
3. steroids

Which immunosuppressive agents are depleting?

1. thyroglobulin
2. alemtuzumab (Campath)

What is the MOA of thymoglobulin?

anti-CD3

How long do the immunosuppressive effects of thymoglobulin last?

3-4 weeks

What premedications should be given with thymoglobulin? Why?

acetaminophen 325-1000mg, diphenhydramine 50mg, methylprednisolone given to minimize cytokine release symptoms

What is a major adverse effect of thymoglobulin?

cytokine release syndrome

What lab(s) do we monitor to determine efficacy of thymoglobulin?

absolute lymphocyte count (ALC) goal of < 50

What lab(s) do we monitor to determine toxicity of thymoglobulin?

WBC & platelet count

What is the MOA of alemtuzumab (Campath)?

monoclonal antibody against CD52

Due to its half-life of 12 days, what effect do we see with alemtuzumab (Campath)?

prolonged lymphopenia

What are the adverse effects of alemtuzumab (Campath)? What is recommended to prevent or treat these adverse effects?

1. Infusion Reactions: premedicate with apap, Benadryl, methylprednisolone
2. Neutropenia: Tx with filgrastim
3. Anemia: Tx with erythropoietin
4. Thrombocytopenia: Tx with transfusion

What is the MOA of basiliximab (Simulect)?

IL-2 receptor antagonist

Which immunosuppressive agents are non-depleting?

basiliximab (Simulect)

What is the duration of blockade for basiliximab (Simulect)?

30-45 days

Which induction immunosuppressive agent does not require premedication?

basiliximab (no cytokine release syndrome)

What is the MOA of methylprednisolone?

down regulate cytokine gene expression leading to decreased T cell proliferation; decreased antigen presentation

What is the MOA of tacrolimus & cyclosporine?

Calcineurin Inhibitors - inhibit calcineurin, IL-2 synthesis inhibited, T cell proliferation inhibited

Name the calcineurin inhibitors used in SOT.

tacrolimus & cyclosporine

How are tacrolimus & cyclosporine dosed?

dosed based on levels

What is the major adverse effect of tacrolimus & cyclosporine?

nephrotoxicity

What major drug interaction do we worry about with calcineurin inhibitors and mTOR inhibitors?

CYP 3A4 (They are metabolized by CYP 3A4 so inhibitors will increase their concentration and inducers will decrease their concentration)

Name the major 3A4 inhibitors.

1. clarithromycin
2. erythromycin
3. azole antifungals
4. diltiazem, verapamil
5. grapefruit juice

Name the major 3A4 inducers.

1. rifampin
2. phenytoin
3. carbamazepine
4. St. John's Wort

Which antimetabolites are used for SOT?

mycophenolic acid & azathioprine

How are antimetabolites doses adjusted in SOT?

dose adjustments based on side effects

What is the MOA of antimetabolites?

inhibit cell cycle proliferation

What are the adverse effects of mycophenolate?

GI upset, leukopenia, anemia, thrombocytopenia

Which antimetabolite is teratogenic and cannot be used during pregnancy?

mycophenolate

What are the adverse effects of azathioprine?

leukopenia, anemia, thrombocytopenia, pancreatitis, hepatotoxicity, squamous skin cell carcinoma

What are the major drug interactions with antimetabolites?

1. azathioprine + allopurinol
2. mycophenolate + birth control

Which steroid is typically used for maintenance immunosuppression in SOT?

low-dose prednisone

Which mTOR inhibitors are used for maintenance immunosuppression in SOT?

sirolimus & everolimus

How are mTOR inhibitors dosed in SOT?

based on levels

What is the MOA of mTOR inhibitors (sirolimus, everolimus)?

regulates synthesis of proteins necessary for cell cycle progression from G1 to S phase, blocks IL-2 signal transduction which ultimately regulates cell growth & proliferation

What is the BBW with mTOR inhibitors?

increased risk of hepatic artery thrombosis in first 30 days post transplant (do NOT use in liver transplants within first month)

Which agents should not be used within the first month of liver transplant due to BBW of hepatic clotting?

mTOR inhibitors

What are some adverse effects of mTOR inhibitors?

thrombocytopenia, anemia, proteinuria, hyperlipidemia, decreased wound healing

Belatacept can only be used in _____ patients.

Epstein-Barr virus (EBV) positive

What is the MOA of belatacept?

costimulation blocker (Signal 2)

What are the BBW of belatacept?

post-transplant lymphomas (PTLD), malignancies, and other infections

Which immunosuppressive agent has a BBW of PTLD, malignancies, and other infections?

belatacept

Which antisuppressive agent can only be used in EBV positive patients?

belatacept

What are the pros to using Calcineurin Inhibitors?

potent immunosuppressive agents

What are the cons to using Calcineurin Inhibitors?

nephrotoxicity, neurotoxicity, PTDM, hypertension

What are the pros to using antimetabolites?

potent immunosuppressive agents, no nephrotoxicity, no drug levels to monitor

What are the cons to using antimetabolites?

GI upset & bone marrow suppression

What are the pros to using steroids?

potent immunosuppressive agents, no nephrotoxicity, no drug levels to monitor

What are the cons to using steroids?

hypertension, edema, hyperglycemia

What are the pros to using mTOR inhibitors?

some evidence to suggest decreased HCC recurrence, no nephrotoxicity

What are the cons to using mTOR inhibitors?

bone marrow suppression, hepatic artery thrombosis, impaired wound healing, proteinuria

What are the pros to using belatacept?

infusions in clinic every 4 weeks, no nephrotoxicity

What are the cons to using belatacept?

infusions in clinic every 4 weeks, increased rejection, newer agent with less data, can't use in EBV(-) patients

What is the recommended treatment of Acute Cellular Rejection?

IV methylprednisolone (or thymoglobulin if steroid resistant)

What are the treatment options for Antibody Mediated Rejection (AMR)?

1. plasmapheresis
2. IVIG
3. rituximab
4. bortezomib

What is the drug of choice and recommended duration to prevent PJP in SOT patients?

Bactrim x 6-12 months

What are the alternative agents for PJP prevention in SOT patients that have a sulfa allergy?

dapsone, atovaquone, pentamidine

SOT patients should be checked for G6PD deficiency before starting ____ to prevent or treat PJP.

dapsone

What is the drug of choice for the treatment of PJP in SOT patients?

Bactrim (can add prednisone if severe)

What are the alternative agents for the treatment of PJP in SOT patients?

atovaquone, dapsone

What is the most important infection occurring in transplant recipients?

cytomegalovirus (CMV)

What viral status indicates high risk for CMV?

(+/-)

What viral status indicates intermediate risk for CMV?

(+/+) or (-/+): recipient is already positive

What viral status indicates low risk for CMV?

(-/-)

What is the difference between CMV Viremia and CMV Disease?

Viremia is evidence of infection only and Disease is evidence of infection plus symptoms

What is the recommended treatment for CMV?

1. IV ganciclovir
2. PO valganciclovir

Which agent is preferred for the treatment of CMV Viremia?

PO valganciclovir

What is the recommended agent and duration of therapy after the CMV PCR is 0?

valganciclovir x 3 months

What should we monitor in patients taking ganciclovir or valganciclovir for prevention/treatment of CMV?

1. PCR weekly until 0
2. renal function (adjust dose)

What is recommended for fungal prophylaxis in SOT patients?

prevent oral candidiasis with nystatin or clotrimazole