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Critical Care/Hematology/Oncology > Week 5 > Flashcards

Week 5 Flashcards

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1
Q

overviews of oncologic emergency categories

A

metabolic
*hypercalcemia of malignancy
*tumor lysis syndrome

hematologic
*febrile neutropenia

structureal
*spinal cord compression

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2
Q

Oncologic Emergency type

tumor lysis syndrome

Patho:

Clinical Presentation:

Risk factors:

Dx and workup:

Prevention:

Mgt/treatment plan:

A

Patho: occurs when large number of cancer cells die ithin a short period of time. cell contents are released into the blood. including dna, phosphate, potassium,-> leads to production of uric acid-> deposit in kidneys

Clinical Presentation:
Hyperkalemia (ecg abnomalities, cardiac arrest)
hypruricmemia(aki, crystal nephropathy)
hyperphosphatemia(ak, gi upset, ams)
hypocalcemia (ams, seizures, tetany)

Risk factors:
Cancer related: high proliferative, tumor bulk, circulating tumor cells, sensitivity to chemo
pt specific: elevated UA, nephropathy, hydration sttaus, hypotension, acidic uring, HF

Dx and workup:
lab TLS: >/2 or more of metabolic abnormalities w.in 3 days before or 7 days after initial trt.
*hyperkalemia>6
*hyperuricemia>8
hyperphosphatemia>4.5
*hypocalcemia</7
or 25% increase or decrease(calcium) from baseline

clinical tls: lab tls SS +
*aki
*seizures
*cardiac arrythmias

Prevention:
*hold causative agents
*hydration, avoid sodium bicarb

Mgt:

high risk: hydration, rasburicase, allopurinol
intermediate risk: hydration, allopurinol, consider rasburicase
low risk: observation, normal hydration, monitoring

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3
Q

mgt of TLS

allopurinol

moa:
indication:
dosing:
consideration:

A

mgt of TLS

allopurinol

moa: decreased formation of uric cid formation
indication: pt at risk for devloping tls. initiate 24 hrs before chemo
dosing: 300 mg po daily
consideration:
ddi
renal function
severe hypersensitivity

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4
Q

mgt of TLS

rasburicase

moa:
indication:
dosing:
consideration:

A

mgt of TLS

moa: reduce uric acif levels, wont inhibit uric acid formation

indication:preexsiting hyperuricemia

dosing: 1.5 mg or 3 mg

consideration:
leave blood samples on ice. heat can break down uric acid een more. put sample on ice,

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5
Q

refractory tls to rasburicase

A

use dialysis

rare

refractory volume overload, oligouria, and anuria

persistent hyperkalemia or hyperuricemia

hyperphosphatemia induced hypocalcemia

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6
Q

trt of hyperkalemia in tls

A

hydration- diuretics to optimize urine output

caclium chloride-stabilizes cardiac cell membrane

regular insulin: drives K intracellularly

sodium bicarb: drive K+ intracelularly by increasing ph

sodium polystyrene: promotes gi excretion of K

dialysis: removes K+ thorugh blood filtration

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7
Q

trt of hyperphosphatemia

A

first line: hydration

lmit dietary phosphate to 800-1000 mg/day

phophate binders: calcium acetate, calcium cabronate, aluminum hydroxide, lanthanum, sevelamer

last line dialysis

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8
Q

trt of hypocalcemia

A

resolves w. resolution of hyperphosphatemia

only trt symptomatic hyperphosphatemia to avoid overcorrection

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9
Q

Oncologic Emergency type

febrile neutropenia

Patho:

Clinical Presentation:

Risk factors:

Dx and workup:

Prevention:

Mgt/treatment plan:

A

Oncologic Emergency type

fever: single temp >38.3 OR temp>38C for over 1 hour AND ANC<500 or ANC<1000 and expected to drop to <500 in 48hrs

*often first and osmetimes only sign an immunocompromised pt has developed an infection

Patho:

Clinical Presentation:

Risk factors:

Dx and workup:
Low: anticipated <7 days
ntermediate: anticipated 7-10 days
high neutropenia >10 days

hx and physical, labs (cbc, renal function tests, lfts, electrolytes, microbe culture

Prevention:
low risk: none
intermediate: consider bacterial, funcal . use viral
high risk: use bacterial, consider fungal, and use viral

Mgt/treatment plan:

antimicrobials: levofloxcin and ciprofloxacin

pneumoccal: penecillin vk

antifungal: floconazole, posaconazole, voriconazole, micafungin, caspofungin

pneumocystisis: bactrim

viral: acyclovir

csf: Pegfilgastrim, filgastrim

Risk assessmen score: MASCC score
*high risk: <21
low risk>/21

low risk: outpt mgt-> oral abx

high risk pt: inpt mgt. broad spectrum iv abx

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10
Q

oral options for outpt management of febrile neutropenia

A

ciprofloxacin +augmentin

levofloxacin

moxifloxcain

ciprofloxacin +clindamycin

oraloptions not appropriate for pts on fluoro quinolones at time of diagnosis
pts w. N/V

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11
Q

in pt management of febrile neutropenia

A

iv therapy

monotherapy w. broad spectrum anti pseudamonal abx

cefepime
pip tazo
meropenem
imipenem
ceftazidime

double gram-coverage can be condisrd

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12
Q

mrsa coverage in febrile neutropenia

A

not covered unless specific indicaion

ex; catheter related infections
ssti
pneumonia
mucositis

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13
Q

fungal coverage in febrile neutropenia

A

fungal coverage added later on in course of febrile neutropenia..

only add if have + fungal markers (beta d glucan..) positive fungal cultures, doesnt respond to initial therapy in 4-7 days

trt: fluconazole, voriconazole, itraconazole, isavuconazole, posaconazole, liposomal amphotericin b

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14
Q

duration of treatment for fbrile neutropenia

A

unidentified infection
*continue untik
**anc >500
and afebrile >/2 days

identified infection:
ssti 7-14 days
blood stream infction: Gram-, 10-14 days: gram+ 7-14 days
bacterial sinusitis:7-14 days
bacterial pneumonia: 7-14 days
fungal (candida=2 weeks: mold=12 weeks)

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15
Q

Oncologic Emergency type

hypercalcemia of malignancy

Patho:

Clinical Presentation:

Risk factors:

Dx and workup:

Prevention:

Mgt/treatment plan:

A

Oncologic Emergency type

Patho:
humoral hypercalcemia: mediated by systemic secretion of PTH hormone. 80% of all cases

osteolytic hypercalcemia: increase osteoclastic bone resorption

vitamin d secreting lymphoma

ectopic hyperparathyoidism<1% cases

Clinical Presentation:
mild hypercalcemia: corrcted calcium
neurologic lethargy, confusion, irratibility, muscle weakness, etc.

Risk factors:

Dx and workup:

Prevention:

Mgt/treatment plan:
symptomatic hypercalcemia is an oncologic emergency
primary goal: treat underlying malignancy

hold medicines that can potentially worsen hypercalcemia

  1. HYDRATION: saline +/- furosemide (increase calciuresis)

primary therapies: iv biphosphonates, rank-l inhibitors

secondary therapies: calcitonin, glucocorticoids

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16
Q

biphosphonates

A

agents: zolendreic acid
pamidronate

inhibt bone resorption

takes up to 7-days to see effects

AE:!! flu like symptoms (pppx w. tylenol)!!, fevers arthralgias , neohrotoxicity,

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17
Q

denosumab

A

rank-l inhibitor reduce osteoclast acitivity

efficacy: 9-10 days

used in hyprcalcemia refractory to biphosphonates. use in pts w.evere renal impairment

toxicity: severe hypocalcemia, hypophosphatemia

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18
Q

calcitonin

A

inhibits bone resportion

can cause tachyphylaxis

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19
Q

other agents for hypercalcemia of malignancy

A

glucocorticoids: inhibits osteoclastic bone resoprtin by decreasing cytokines:

calcimemmetics (cinacalcet: effective for PTH carcinoma or primary/secondary hyperparathyroididm

dialysis: severe hypercalcemia due to renal insufficiency
*unable to hydrate pt

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20
Q

forms of lung cancer

A

2 forms of lung cancer

Non small cel85%) cmall cell(15%
Non small cell
*squamous (30) *non squamous70%)

Nonsquamous (
a)large cell (10%)
b)adenocarcinoma

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21
Q

clinical presentation of lung cancer

A

Clinical presentation of lung cancer
*pulmonary symptoms: cough dyspnea, chest pain or disocmfort, w. Or w.o hemoptysis
Extrapullmonary: fatigue, weightloss, anorexia

Paraneoplastic syndromes: hypercalcemia and siadh

disseminated disease can cause additional symptoms

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22
Q

most effective prevention in lung cancer

A

Most efective prevention in lung cancer:
*avoid tobacco
*maintain healthy diet high in fruits and vegetables
*offer screening to high risk individuals

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23
Q

general treatment goals for NSCLC

A

Treatment goals for NSCLC
*stage 1-11: cure
Stage III-Iv: prolongation of survival

Treatment goals for SCLC
Limited stage: cure
Extensive stage: prolongation of survival

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24
Q

local NSCLC (stage 1-2) trt

A

Stage 1:curgery
Stage 2:
Surgery followed by adjuvant therapy
Platinum based chemo regimen for 4 cycles
Osimertinib (EGFR+) for up to 3 years
Atezolizumab (PD-L1>/1%)
Neoadjuvant (therapy b4 surgery to shrink tumor down to increase chances of complete tumor removal
Radiation therapy
Reserved for pts who cant get surgery

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25
local advanced stage nsclc (stage 3 tretment
Local advanced stage NSCLC (stage3) treatment Stage 3a Neoadjuvant chemo+/-nivolimumab Adjuvant osimertinib (EGFR+) OR atezolizumab (PDL1>/1%) Concurrent chemoradiotherapy for non surgical candidates Stage 3b-3c Considered unresectable disease Concurrent chemo radiaion Immunotherapy to increase progression free and overall survival
26
neoadjuvant regimens for nsclc
Neoadjuvant regimens for nsclc Cisplatin or carboplatin incombo w. Other agents that are non platinum agents *** pemetrexid only for nonsquamous histology only
27
cisplatn vs carboplatin
Cisplatin Myelosupression n/v Diarrhea constipation Oral mucosisitis Alopecia Nephrotoxicity (hypokalemia, hypomagnesemia) Ototoxicity Peripheral neuropathy Carboplatin Thrombocytopenia Less n/v than cisplatin diarrhea/ constipation Oral mucositis Alopecia nephrotox(less than cisplatin) Ototoxicity (less than cisplatin Peripheral neuropathy (less than cisplatin) Calvert equation: equation used to determine n dosing carboplatin based on pt renal function. Reduced risk of toxicities that we cant do w. Cisplatin
28
cisplatin equation
Total dose= AUCX(CRcL+25)
29
advanced nsclc stage 4 or relapsed trt
Advances nsclc: stave 4 or relapsed disease trt If pt has targeted genetic mutation Mutation in any: EGFR, ALK, ROS1,BRAF NTRK, RET, MET Kinase inhibitor targeted to mutation PDL1+>/50% pd1/pdl1inhibitor+/-chemo pdl1<1 Pdl1 inhibitor + chemo
30
advanced nsclc trt EGFR inhibitors in nsclc
growth factor receptor inhibitors Egfr mutations most prevalent in adenocarcinomas and non smokers Agent examples First (Erlotinib, gefitinib, afatinib Second gen: (dacomitinib Third: osimertinib FIRST LINEEE!! Significantly improved PFS and os CAPERED TO FIRST GEN AGENTS, AND IMPROVED CNS ACTIVITY, BETTER TOLERABILITY
31
EGFR inhibitor AE
EGFR INHIBITOR AE: Class adverse effects Skin rash Dry skin Nail toxicity Diarrhea conjunctivitis SPECIFIC drug side effects Osimertinib Cyp3a4 substrate No ph dependent absorption Myelosupression Dose reduction for severe renal impairment
32
advanced nsclc trt alk inhibitors
ALK INHIBITORS Less common than egfr mutations Seocnd and third gen superior improvement in outcomes First gen: crizotinib, certinib, Second gen: alectinib, brigatinib Third gen: lorlatinib
33
advanced nsclc trt alk inhibitor agent pearls
Brigatinib Ddi: cyp3a4 substrate Ph dependent absorption: no AE: insterital lung disease/pneumonitis, myalgia, htn Alectinib Ddi: cyp3a4 substrate Ph dependent absorption: no AE: constipation, myalgias, lft elevation, anemias Lorlatinib Ddi: cyp3a4 Ph dependent absorption: AE: depression, anxiety, has good cns penetration, weight increase
34
advanced nsclc trt KRAS inhibiots
More common mutation sthat smoke cigarrettes Pts with this have poor disease prognosis Indicated for nsclc and kras g12c mutation after recepit of one therpay
35
advanced nsclc trt kras inhibitor agent pearls
Sotorasinib Ddi:cyp3a4 substrate Ph dependent absorption:YES. Avoid ppis h2ra AE: Adagrasib Ddi: Ph dependent absorption: NONE AE: renal impairment, qtc prolongation,
36
advanced nsclc trt agents if pdl1 expression >50%
PDL1 expression level of >/50% or higher TReatments Single agent immunotherapy Pembrolizumab Atezolizumab Cemiplimab
37
advanced nsclc trt pdl1 1-49%
PDL1 1-49%(BASICALLY MODERATE -low EXPRESSION) Cisplatin or carpo +paclitaxel +permbrolizumab (squamous) Cis or carb+ pemetrexed +pembrolizumab (non squamous) Cis or carb +paclitaxel + nivolimumab Etc.
38
advanced nsclc trt 2nd line trt
No previous checkpoint inhibitor: pembrolizumab, nivolumab, atezolizumab Previous checkpoint inhibitor: docetaxel+ramucirumab(preffered over single agent), ramurcirumab +pembrolizumab, docetaxel, pemetrexed
39
immunothwrapy for nsclc patho
Immunotherapy for nsclc patho Pd1l1: inhibits t cel killing of tumor cell-blocking allowst cell tumor killing Ctla4: binding inhibits t cell acitivation: blocking potentiates t cell activation and killing
40
advanced nsclc trt immunotherapy AE
Immunotherapy related side effects in nsclc Onst: w.in first few weks to months after initiation but can occur anytime Combing bdl1/ctla4 increases side effects Different grades of AE Grade1:continue immunotherapy Grade 2: hold immunotherapy and consider admin prednisone gradde3>: hold immunotherapy and give prednisone (or equiv) Pred: 0.5-2mg/kg/day 5-7 days Steroid refractory: mycophenolate, infliximab
41
advanced nsclc trt VEGF inhibitors
VASCULAR ENDOTHELIAL GROWTH FACORS (VEGF) Cancer cells form new blood cells, which increase nutrient flow and permit growth and metastasis VEG F inhibitors Nsclc specific agents: bevacizumab, ramucirumab AE: HTN, thromboembolic events, major bleeds Avoid in pts w, squamous histology (bevacizumab), recent hemoptysis, on tpx anticoagulation for new onset vte, recent surgical procedure.
42
chemo for lung cancer
Taxanes Nsclc specific agents: paclitaxel, docetaxel Moa: inhibits mitosis AE: myelosupression, ALOPECIA, PERIPHERAL NEUROPATHY(dose limiting ae), hypersensitivity (premdicate to prevent), peripheral edema (docetaxel Pemetrexed Moa: inhibits DHFR. inhibit folate synthesis, causing cell death Ci: severe renal dysfunction (crcl<45), NSAIDS decrease clearance AE: dose limiting (myelosupression, skin rashes)
43
SCLC overview
Rapidly diving malignancy. 60-70% extensive disease stage Poor prognosis Trt of choice is chemo +/- radiation
44
SCLC trt first line and second line
Sclc treatment First line Platinum agents +/- other agents Cisplatin+etoposide Carboplatin+etoposide Carbo+epot+atezolizumab (extensive only) Carbo+epot+durvulomab (extensive only) Second line Topetecan Lurbinectedin Clinical trial
45
sclc trt agent pearls
Etoposide: Moa: topoisomerase inhibitor Dose limiting AE: myelosupression Topotecan Topoisomeras I inhibitor Renal dosage adjustment Myelosupression (neutropenia Lurbinectedin Moa: alkynates dna Pk: cyp3a4 substrate Fatigue, hepatic enzyme, extravasation, nausea
46
what is lymphoma
What is it Cancers of the lymphoid lineage Low incidence global Two major divisions Hodkins Non hodgekins *Can either be bcell, t-cell, or nk cell *Also classified as Indolent Aggressive Very aggressive
47
mechanism of lymphomas
Mechanisms of infectious disease on causing l ymphomas : lymphocyte transforming viruses disrupt cell actiivty.
48
types of lymphona
TYpes of Lymphoma B cell nhl T cell/nk NHL HL all divided up further into indolent, agressive, or very aggressive
49
SS lymphadenoma
SS of lymphoma Ymphadenoma “B symptoms” Fevers Night sweats Weight loss Usually advanced disease
50
diffuse large b cell lymphoma overview
Diffuse Large B-CELL lymphoma (DLBCL) Most common heme malignancy in usa Germinal center bcl vs activator center b cell Gcb has greater survival than ABC 40% of pts w. Adverse cytogenetics will experience failure (not all inclusive)
51
prognosis of dlbcl
Prognosis of dlbcl Best response to therapy: adherence of drug at specific dose Anthracyclines are most impotant drugs (doxorubicine) Fitness test Who can fail? AGE>60 STAGEIII-IV ecog>2 (performance status … poorer activity) LDH>UNL
52
trt for dlbcl
GOLD STANDARD FOR DLBCL R-CHOP R: rituxumab on day 0 C:Cyclophosphamide on day 1 H: Doxorubicin on day 1 O: vincristine on day 1 P: prednisone Given q21 days for usually 6 days
53
trt of dlcbl rituxumab
Rituxumab Moa: mAb binds to CD20*** Increased OS by 15% when added to chop Ae: TLS HOLD first cycle if tls risk is high Infusino reactions, gi perforation, decrease efficacy of vaccines Pearls: infusion directions, tls, hold if disease in gi tract
54
trt of dlbcl cyclophosphamide
Cyclophosphamide pearls Alopecia High NV risk Hemmorhagic cystitis/fluids
55
trt of dlbcl doxorubicin
Doxorubicin pearls Lifetime dose cap 450 mg/m2 Baseline ECHO due to nonreversible HF Nv and mucositis
56
trt of dlbcl vincristine
Vincristine pearls Neuropathy (NO VINES IN SPINE) Neuropathy in sensory (taste, smell, touch)
57
trt of dlbcl prednisone
Prednisone pearls Hyperglycemia Steroid induced psychoses Insomnia
58
trt od dlbcl CHOP supportive care
Chop supportive care Emetic risk high Antiemetics Febrile neutropenia Pegfilgastrim and filgastrim Viral reactivation (ritxumab) Give ppx antiviral for pts who have had hbv Tls Aggressive hydration Allopurinol Hold rituxumab?
59
otions for pts w. poor lvef
Options for pts with poor lvef Rceop R-cepp RCDOP RGCVP R-DA-EPOCH
60
alternative therapy for RCHOP
Alternative for RCHOP (new therapy) Pola-R-CHP Add polatuzumab, remove vincristine PGS improved Acts similarly to vincristine
61
DA-R-EPOCH
DA-R-EPOCH Preferred over rchop in certain settings duble/tripple hit lymphoma Primarymediastinal lymphoma Hiv associated dlbcl
62
relapsed/refracctory dlbcl
Relapsed /refractory disease Auto transplant Definitive cure in second line Giving stem cells back after taking them and purifying them. High dose chemo given to prior to overcome resistance CAR T-CELL Definitive cur in second line T cells flagged w. Anti cd19 antibodies (found on lymphomas) AE: cytokine release syndrome, neurotoxiciy Very well response rate Palliation Use other moa therapies
63
follicular lymphoma
Follicular lymphoma(FL) Indolent lymphoma Rarely cured Drugs work less Indications fo treatment Cytopenias Consider grade, FLIPI score Infections Symptomatic disease End organ function Bulky disease Change in aggressiveness diseas First line trt of follicular lymphoma considerations Obinutuzumab c rituxumab Improves PFS Infusion reactions Rituxumab maintenance BR v RCHOP Relapsed refractory FL Rule out transformation into DLBCL DONT REPEAT SIMILAR REGIMENS 3RD LINE Mosenutuzumab Engaged cd3 t cells AE: cytokine release syndrome Complete response rate: 60%
64
hodgekins lymphoma overview
Hodgekins Lymphoma B cell lymphoma arising from germinal center Highly curable Divided into 2 categories Classical hodgkins lymphoma (cHL) CD20 NEG, CD30+ Nodular lymphocyte-predominant hodgkins lymphoma(NLPHL) Cd20 +, cd30 - Main risk factors Epstein barr virus HIV Patho of HL CHL do not express traditional b cell markers (ex!!! Substitute CD30) Very inflammatory cancer; a lot of pro inflammatory markers
65
NLPHL TRT
NLPHL TRT CD20+ cd30- RITUXUMAB + any chemo regimens Classical HL TRT ABVD ADRIAMYCIN BLEOMYCIN VINBLATINE DACARBAZINE Pulmonary fibrosis Infertility Avoid in pulmonary function issues at baseline AFTER 2 CYCLES, DO PET SCAN. If refractory-> escalate to BEACOPP If responsive, can remove bleomycin, to make AVD Due to creation of free radicals, can cause pulmonary fibrosis, higher risk when given w. G-CSF (filgastrim and pegfilgrastim Brentuximab antiCD30 Side effects: neuropathathy AAVD Useful in some pts High rates of neutropenia and neuropathy Relapsed disease Use different agent

Critical Care/Hematology/Oncology (4 decks)

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