HYU Onc - Kidney Flashcards

1
Q

Renal Mass Staging: T1a, T1b

A

T1a: < or = 4 cm
T1b: < or = 7 cm

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2
Q

Renal Mass Staging: T2a, T2b

A

T2a: < or = 10 cm
T2b: >10 cm

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3
Q

Renal Mass Staging: T3a

A

T3a: renal vein, pelvicalyceal, perirenal/renal sinus fat within Gerota

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4
Q

Renal Mass Staging: T3b

A

IVC below diaphragm

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5
Q

Renal Mass Staging: T3c

A

VC above diaphragm

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6
Q

Renal Mass Staging: T4

A

Outside of Gerota or involving adrenal

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7
Q

Stage I

A

T1N0M0

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8
Q

Stage II

A

T2N0M0

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9
Q

Stage III

A

T3N0-1M0
T1-2N1M0

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10
Q

Stage IV

A

M1

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11
Q

Postoperative Risk Stratification

A

Low Risk: pT1 and Grade 1-2

Intermediate Risk: pT1 and Grade 3-4, or pT2 and any G

High Risk: pT3 and any G

Very High Risk: pT4 or pN1, sarcomatoid, rhabdoid, macroscopic R1

*Note, positive final margin should increase risk category by one level and increase clinical vigilance

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12
Q

Evaluation of renal mass:
- Imaging?
- Labs?
- CKD?

A

Get multi-phase cross sectional imaging (enhancing = greater that 20 HU)
Consider MRI if suspicion for IVC thrombus
Get CT chest for advanced tumors

If malignancy suspected –> CBC, UA, CMP, chest imaging

Solid or Bosniak 3/4 mass: Use GFR to assign CKD stage I-V
- (90+, 60+, 30+, 15+, <15 or Dialysis)

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13
Q

When to consult nephrology?

A

Consider for eGFR <45, expected postop GFR <30, proteinuria, DM with CKD

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14
Q

When to consult Med Onc?

A

Concerned for potential clinical mets
Incomplete resection

Consider adjuvant treatment for High Risk (T3 and G) or locally advanced, fully resected cancers

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15
Q

When to consult genetics?

A

Recommend for age 46 or less, multifocal/bilateral renal masses, whenever the personal/family history suggests a familial renal neoplastic syndrome

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16
Q

When to perform Renal Mass Biopsy (RMB)?

A

Consider if suspicious for hematologic/metastatic/inflammatory/infectious mass

For solid mass, multiple cores&raquo_space; FNA

PPV ~100%, NPV ~60%, Nondiagnostic ~15%

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17
Q

Partial Nephrectomy:
- When do you prioritize this?
- When do you consider it?
- Surgical considerations?

A

Prioritize PNx: cT1a (when Tx is indicated), cases with solitary kidney, bilateral tumors, familial RCC, multifocal, severe CKD

Consider PNx: young patients, multifocal masses, increased risk for future CKD (HTN, DM, urolithiasis, morbid obesity)

Surgical considerations: minimize warm ischemia time, prioritize negative margins, consider enucleation if familial RCC, multifocal or severe CKD

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18
Q

When is radical nephrectomy preferred over partial nephrectomy?

A

Radical only preferred over partial if:
1. High tumor complexity and pNx would be difficult even in experienced hands
2. No preexisting CKD or proteinuria
3. Normal contralateral kidney and new baseline GFR likely to be >45

Consider radical when oncologic potential is suggested by tumor size, RMB, and/or imaging characteristics

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19
Q

When is Thermal Ablation appropriate? How to follow up?

A

Consider for cT1a <3cm AFTER renal mass biopsy
Radio and cryo are options
Counsel slightly worse outcomes (i.e. local recurrence rates)
Can repeat ablation as needed

Obtain pre and post contrast abdominal imaging within 6 months of ablation, then follow IR postop protocol

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20
Q

When to consider active surveillance? Triggers for intervention?

A

Consider especially for <2cm, repeat imaging in 3-6 months
Consider RMB for mass with solid component
Individualize surveillance based on growth rate and shared decision making (SDM)

Potential triggers for intervention in healthier patients?
- Growth to >3cm
- >5mm/year of growth

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21
Q

Follow-up labs post-op?

A

Cr, UA, eGFR –> refer to nephrology PRN

Consider other labs as needed and if advanced disease expected (CBC, LDH, LFTs, Alk Phos, Ca++)

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22
Q

Abdominal imaging after nephrectomy and partial nephrectomy?

Chest imaging?

A

CT w/ and w/o contrast or MRI for 5 years
Consider switching LR and IR patients to alternating cross sectional imaging and abdominal US

SDM for further imaging after 5 years

LR: yearly for 5 years
IR + TA: 6, 12, 24, 36, 48, 60 (q6m for a year)
HR: 6, 12, 18, 24, 30, 36, 48, 60 (q6m for 3 years)
VHR: 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 (every 3 months for a year, then every 6 months to 3 years, then yearly)

Chest imaging: CXR for LR+IR, CT for HR and VHR
SDM after 5 years

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23
Q

What to do when renal artery vasospasm during hilar dissection?

A

Reduced perfusion
Pale kidney

  1. Reduce insufflation pressure
  2. Apply topical papaverine (opium alkaloid antispasmodic vasodilator) to renal hilar vessels
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24
Q

When to consider when using argon gas laparoscopically?

A

Argon beam will increase abdominal pressure due to addition of argon gas
- Important to vent abdomen via a port to relieve pressure

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25
Interaortocaval nodes only drain the right kidney
They drain the left kidney with advanced disease
26
Incidence of local recurrence after nephrectomy? What does this mean for 5 year survival?
Incidence 2.9% Poor prognosis: 5 year survival 30% Synchronous mets at the time of recurrence are an independent predictor of poor prognosis
27
Hand-assisted lap compared to straight lap? What does this mean for donor nephrectomies?
Hand-assisted lap has higher rates of wound complications (infections and hernias) In setting of donor nephrectomy, warm ischemia time of donor kidney is reduced because specimen can be quickly removed via hand-port. Other outcomes are similar to straight lap.
28
Acute bleed following ligation/division of left renal hilum
Think about disruption of a lumbar vein, because this inserted into the renal vein posteriorly
29
Workflow for urine leak after partial nephrectomy
Start with perc drain placement if drain not already present If leak persists, make sure drain isn't directly on leak site, and take off of suction Place urethral catheter and do RPG + ureteral stent If unable to place stent, place PCN
30
Severe, persistent back pain resistant to pain meds after renal surgery
Consider rhabdomyolysis (if pain contralateral to side of surgery, check CK) Pancreatic injury (if pain is on left following left-sided renal surgery, check amylase and lipase)
31
Proposed criteria for cytoreductive nephrectomy
Ability to resect >75% of the tumor No brain mets (need to be treated with radiation or surgery prior to cNx) Adequate pulmonary and cardiac reserve ECOG performance status of 0-1 (0=Fully active, able to carry on all pre-disease performance without restriction 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work) Predominantly clear-cell histology Disease has not progressed through systemic therapy (sunitinib)
32
Vaccinations s/p splenectomy
Indicated due to risk of severe infection with encapsulated bacteria SHiN - Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis
33
New lesion with early enhancement and prompt washout at prior tumor site after partial nephrectomy
Get US with doppler to determine pseudoaneurysm vs. recurrence
34
RCC tumor thrombus levels
0 = renal vein 1 = <2cm into IVC 2 = >2cm into IVC but still below hepatic veins 3 = above hepatic veins but below diaphragm 4 = above diaphragm 3 and 4 may need bypass during sugrery
35
"Persistent central enhancement"
Tumor recurrence after cryoablation
36
Ways to optimize (lap) renal cryoablation
Real-time intraop US to monitor progression of cryo lesion Cryoprobe tip at deepest margin of tumor Target temperature below -40C Extend the cryo lesion ~1cm beyond the margin of the tumor Active double freeze-thaw cycle
37
Small renal mass(es) are identified in conjunction with widespread LAD outside of typical LN drainage zones
Suspect renal involvement of lymphoma Perc LN biopsy to determine Tx plan
38
Renal tumor with high signal on T1 on MRI
Fat in lesion Think AML Think a/w tuberous sclerosis AML = benign tumor of perivascular epithelioid cell origin
39
MRI sequence most likely to confirm AML
T2 with fat suppression On CT, suspect AML if negative HU (fat) are mentioned Angioembolization often effective, particularly in setting of acute bleed If massive, will need nephrectomy
40
Drug that can be used to shrink AMLs
Everolimus (Afinitor) Tumor growth typically resumes when treatment is discontinued Can watch AMLs when small, can cause problems if >4 cm
41
Benign tumor in 20yo with elevated peripheral renin
Juxtaglomerular tumor Tumor secretes renin patients typically <20yo Cured with surgery
42
Rare, extremely aggressive tumor associated with sickle cell trait
Renal medullary carcinoma - Arises from collecting duct <100 cases ever Mean survival <6 months 75% on right side Central/infiltrative, not amenable to partial Does not typically respond to chemo/immunotherapies
43
Treatment for metastatic renal medullary carcinoma
Carboplatin + paclitaxel is first line (not upfront surgical resection) Gemcitabine + adriamycin is 2nd line
44
Collecting duct RCC
More aggressive --> younger age of presentation Resistant to standard chemos for RCC, but sometimes responsive to gemcitabine and cisplatin chemos (behave more like UCC)
45
Renal pseudotumor
Column of Bertin Focal cortical hyperplasia Best established with DMSA scan
46
How to follow patients with oncocytoma or indeterminate histology on renal mass biopsy
Follow with same imaging protocols used for untreated low risk renal cancers due to risk of substantial growth and risk of inaccurate biopsy results
47
How to distinguish between oncocytoma and RCC?
Technetium-sestamibi nuclear scanning - oncocytoma will have high radiotracer uptake - RCC will have low radiotracer uptake
48
Preferred regimens for relapse or stage IV metastatic CCRCC (favorable and poor/intermediate risk)
Pembrolizumab + axitinib - Keynote-426 Nivolumab + cabozantinib - CheckMate-9ER Pembrolizumab + lenvatinib - CLEAR Cabozantinib monotherapy (CABOSUN) is a preferred option for poor/intermediate risk
49
Metastatic RCC sites with worst to best prognosis
Brain, liver, bone, LNs, lung, adrenal
50
What labs do you need to monitor Sunitinib with/for?
Associated with hypothyroidism - get thyroid labs
51
Renovascular fistulae treatment - If asymptomatic due to biopsy? - If asymptomatic due to RCC? - What symptoms do they cause when symptomatic? - Cirsoid AV fistula?
- If asymptomatic due to biopsy? 70% will close spontaneously, observe - If asymptomatic due to RCC? Nephrectomy - What symptoms do they cause when symptomatic? HTN, hematuria, high output heart failure. Treat with embo, ligation, partial or complete nephrectomy - Cirsoid AV fistula? Cirsoid means to resemble a varix. These are too complex for angioembolization. Treatment of choice is nephrectomy.
52
Von Hippel Lindau - Inheritance pattern? - Manifestations? - Gene associated? - Gene location? - Leading cause of death in VHL?
- Inheritance pattern? AD - Manifestations? Hemangioblastomas of retina, cerebellum, medulla (~70%, get brain/spine MRI when diagnosed), cavernous hemangiomas in skin, mucosa and organs, pancreatic masses. About half will develop multiple bilateral RCCs and other tumors associated with deletion of the tumor suppressor gene VHL on 3p - Gene associated? (VHL (tumor suppressor gene)) - Gene location? Short arm of 3p25 - Leading cause of death in VHL? Kidney cancer Ipsilateral cysts should be removed at time of partial nephrectomy (when a solid mass is >3 cm) because they can harbor carcinoma
53
Medication that is FDA approved for treatment of VHL-associated RCC? Mechanism?
Belzutifan (HIF-2a inhibitor) Common side effects include anemia (from reduced epo), and fatugue When VHL (a TSG) is deleted, causes constitutive expression of HIF (a transcription factor), which activated angiogenic growth factors (like VEGF, EPO)
54
Hereditary syndrome with type 1 papillary RCC? - Gene? - Location of gene?
Hereditary papillary renal cell carcinoma RAre cMet codes for RTK protein --> papillary RCCs only, no extra-renal findings
55
Hereditary syndrome with type 2 papillary RCC? Gene? Location of gene?
Hereditary leiomyomatosis RCC (HLRCC) FH gene codes for fumarate hydratase (TSG) --> painful leiomyomas (cutaneous, uterine) + papillary RCC --> bad disease, patients may die young --> start annual screening with contrasted MRI at age 8 Surveillance of tumors not recommended, take them out 1q42
56
Birt-Hogg-Dube - Gene? - Gene location? - Tumor type? - Manifestations?
Gene - BHD1 On 17p11 Mutated gene codes for folliculin --> painless fibrofolliculomas (benign) Bilateral RCCs (chromophobe RCC or oncocytomas) Lung cysts, risk of pneumothorax
57
Tuberous Sclerosis - Inheritance pattern? - Manifestations?
- AD Facial lesions (adenoma sebaceum) Hypopigmented "ash leaf spots" on skin Cortical and retinal hamartomas Seizures/epilepsy Mental retardation Renal cysts Renal AMLs Cardiac rhabdomyomas Increased incidence of astrocytomas Incomplete penetrance, variable presentation
58
Lynch syndrome - Where are mutations? - What organs most likely to get cancer?
= Hereditary Non-polyposis Colorectal Cancer - Genes MLH1, MSH2/6, PMS2 - Colorectal, endometrial, digestive, ovarian, upper tract cancers
59
Cowden Syndrome
PTEN hamartoma syndrome PTEN = phosphatase and tensin homolog mutations --> hamartomas Endometrial and kidney cancers
60
Li-Fraumeni Syndrome
Tumor suppressor p53 mutation Breast cancer, osteosarcoma, soft tissue sarcoma, leukemia, lymphoma
61
Neurofibromatosis
Caused by oncogene mutation in MF1 (csome 17) or NF2 (csome 22) Classically manifests with cafe au lait spots
62
MEN 2A
Gain of function in RET proto-oncogene Medullary thyroid cancer, parathyroid hyperplasia, pheochromocytoma
63
MEN 2B
Gain of function in RET proto-oncogene Medullary thyroid cancer, pheochromocytoma, marfanoid body habitus, mucosal neuroma
64
RCC Screening?
Renal US for ESRD patients after 3 years of dialysis HLRCC patients at age 8 VHL patients at age 16
65
Favorable molecular markers for survival in RCC
Absent vimentin, absent p53, High CAIX
66
Bosniak 1 Classification
Simple cyst, imperceptible wall, no work-up indicated 0% chance of malignancy
67
Bosniak 2
Minimally complex A few thin, <1 mm septations or thin calcifications Non-enhancing high-attenuation (due to proteinaceous or hemorrhagic contents) Risk of malignancy ~0%
68
Bosniak 2F
Minimally complex Increased number of septa Minimally thickened with nodular or thick calcifications May be perceived but not measurable enhancement of a hairline smooth thin septa Hyperdense cyst >3cm in diameter, mostly intrarenal No enhancement Requiring follow-up - US or CT around 6 months Cancer risk 5-10%
69
Bosniak 3
Indeterminate, thick, nodular, multiple septa or wall with measurable enhancement, hyperdense on CT Tx: partial nephrectomy or ablation in poor surgical candidates ~50% risk of cancer
70
Bosniak 4
Clearly malignant Solid mass with large cystic or necrotic component Treatment: partial or radical nephrectomy ~100% risk of cancer
71
Lit: localized RCC in VHL
Belzutifan for localized RCC in VHL HIF-2a inhibition can shrink small RCCs in VHL
72
Lit: Radical Nx with or without LND
EORTC Completely LND NOT needed during radical nephrectomy for N0M0 RCC - OS, PFS, time to progression and complications rates didn't differ
73
Lit: EORTC partial vs radical nephrectomy and renal function
Partial nephrectomy is better than radical nephrectomy for preserving renal function... duh Similar for OS, median follow-up 9.3 years
74
Lit: Cytoreductive nephrectomy and interferon SWOG 8949 2001
cytoreductive nephrectomy and interferon improved median OS by 3 months (11 vs. 8) over interferon alone
75
Lit: EORTC cytoreductive nephrectomy trial 2001
Cytoreductive nephrectomy + interferon improves median OS by 10 months (17 vs. 7) over interferon alone A combined analysis for SWOG and WORTC studies similarly revealed a survival benefit with cNx (13.6 vs. 7.8 months)
76
Lit: CARMENA 2018 (cNx)
cNx + sunitinib has WORSE median OS than sunitinib alone (!)
77
Lit: SURTIME 2018 (cNx)
Sunitinib + delayed cNx (when indicated) has better OS than upfront cNx
78
Lit: (not) ASSURE(d) 2016 Adjuvant systemic therapy after rNx
Adjuvant targeted therapy (sunitinib or sorafenib) does not improve disease free survival (DFS) over placebo Stopped early due to side effects with no evidence of improved DFS with either therapy Non-metastatic patients
79
Lit: S-TRAC 2016 Adjuvant systemic therapy after rNx
Adjuvant sunitinib improves median DFS by one year over placebo (no OS benefit) RCT Locoregional high risk RCC patients
80
Lit: KEYNOTE-564 2021 Adjuvant systemic therapy after rNx
Adjuvant pembro improves DFS s/p rNx for high-risk RCC RCT OS data immature, but seems to favor pembro group at 24 months
81
Lit: Global ARCC - Temsirolimus, Interferon-a or both? 2007 Advanced RCC
Temsirolimus identified as best choice for poor-prognosis RCC RCT Temsirolimus - mTOR inhibitor IFN - activates inflammatory and immune responses
82
Lit: Sunitinib vs. IFN-a for mRCC? 2007 Advanced RCC
Sunitinib > IFN-a for mRCC PFS and objective response rate better RCT Sunitinib - TKI --> VEGF and PDGFR IFN - activates inflammatory and immune responses
83
Lit: TARGET 2007 Advanced RCC
Sorafenib > placebo for mRCC s/p 1 prior systemic therapy RCT Sorafenib - TKI --> VEGF, PDGFR and RAF kinase - Significant SE profile includes rare cardiac ischemia
84
Lit: RECORD-1 2008 Advanced RCC
mccRCC patients who fail sunitinib should get Everolimus RCT everolimus --> mTOR inhibitor PFS was improved in the everolimus group compared to placebo
85
Lit: COMPARZ 2013 Advanced RCC
Pazopanib is non-inferior to sunitinib for m-ccRCC and has superior safety profile Pazopanib --> TKI - VEGF, PDGFR, fibroblast growth factor receptor (FGFR), and c-kit RCT Median PFS and OS were similar and non-inferior to sunitinib
86
Lit: METEOR 2015 Advanced RCC
Cabozantinib has better PFS than everolimus for RCC with progression through a VEGFR-targeted treatment Median PFS and rate or progression or death favored cabozantinib
87
Lit: CheckMate 025 2015 Advanced RCC
Nivolumab has better OS than everolimus for advanced RCC s/p 1-2 anti-angiogenic Txs (sunitinib) RCT
88
Lit: CABOSUN 2017 Advanced RCC
Cabozantinib extends PFS vs. sunitinib in poor/intermediate risk met ccRCC RCT Previously untreated patients
89
Lit: CheckMate 214 2018 Advanced RCC
Nivolumab + ipilimumab has better 18 month OS than sunitinib for poor and intermediate risk patients with untreated advanced RCC (with clear cell component) RCT Previously untreated Ipilimumab = monoclonal Ab to CTLA-4 --> inhibits T-cell suppression
90
Lit: IMmotion151 2019 Advanced RCC
Atezolizumab + bevacizumab > sunitinib for PD-L1+ mRCC patients RCT Patients with mRCC (cc or sarcomatoid) Atezolizumab = igG4l mAb to PD-L1 Bevacizumab = mAb that inhibits VEGF-A to block angiogenesis
91
Lit: KEYNOTE 426 2019 Advanced RCC
Pembro + axitinib has increased 1-yr OS over sunitinib REGARDLESS of PD-L1 status Pembrolizumab = IgG4k mAb to PD-1 Axitinib = TKI --> VEGFR, c-kit, PDGFR
92
Lit: TIVO-3 2020 Advanced RCC
Tivozanib has better PFS than sorafenib in mRCC s/p multiple prior systemic Tx RCT Tivozanib = potent and selective TKI --> VEGF Sorafenib = TKI --> VEGF, RAF kinase, PDGFR
93
Lit: CheckMate 9ER 2021 Advanced RCC
Cabozantinib + nivolumab has better OS than sunitinib for previously untreated advanced or mRCC RCT Cabozantinib = TKI --> VEGF, MET, TAm Nivolumab = IgG4 mAb to PD-1 --> inhibits T cell suppression Cabo/nivo patients have increase QoL
94
Lit: CLEAR 2021 Advanced RCC
(Lenvatinib + pembrolizumab) > (lenvatinib + temsirolimus) > sunitinib for PFS in previously untreated, advanced RCC Pembrolizumab = IgG4k mAb to PD-1 Lenvatinib = TKI--> VEGF, FGFR, PDGFR
95
Sunitinib mechanism
TKI --> VEGF + PDGFR Decreases tumor angiogenesis and growth
96
Sunitinib side effects
Myelosuppression, nephrotoxicity, hepatotoxicity, diarrhea, fatigue, nausea, stomatitis, vomiting, HTN, HTN, Hand-Foot Sx, rash
97
Sorafenib mechanism
TKI --> VEGF + PDGFR + RAF kinase Decreases tumor angiogenesis and growth
98
Sorafenib side effects
Cardiac ischemia or infarction (3%), lymphopenia, hepatotoxicity, diarrhea, fatigue, nausea, anorexia, vomiting, HTN, rash
99
Tivozanib mechanism
TKI --> VEGF Decreases tumor angiogenesis and growth
100
Tivozanib side effects
HTN, fatigue, diarrhea, rash, hoarse voice
101
Cabozantinib mechanism
TKI --> VEGF + MET + TAM Decreases tumor angiogenesis and growth
102
Cabozantinib side effects
GI perforation and fistula HTN Fatigue Diarrhea Rash Seizures Jaw osteonecrosis Anorexia HA Dizziness
103
Nivolumab mechanism
IgG4 mAb to PD-1 Decreases T-cell suppression Increases T-cells killing cancer cells
104
Nivolumab side effects
Immune-mediated inflammation, hypothyroidism or hyperthyroidism, pancreatitis with Type I DM, colitis, rash, peripheral edema, neuropathy
105
Ipilimumab mechanism
IgG1-mAb to CTLA-4 Decreases T-cell suppression Increases T-cells killing cancer cells
106
Ipilimumab side effects
Colitis Diarrhea Fever Stomach pain Bloating Difficulty breathing
107
Atezolizumab mechanism
IgG4-mAb to PD-L1 Decreases T-cell suppression Increases T-cells killing cancer cells
108
Atezolizumab side effects
Fatigue Anorexia Nausea UTI
109
Bevacizumab mechanism
IgG1-mAb to VEGF Decreased tumor angiogenesis Increased apoptosis
110
Bevacizumab side effects
HTN Rash Nose bleeds Infection
111
Lenvatinib mechanism
TKI --> VEGF + FGFR + PDGFR Decreased tumor angiogenesis Increased apoptosis
112
Lenvatinib side effects
HTN Diarrhea Fatigue Anorexia Hypotension Thrombocytopenia
113
Pembrolizumab mechanism
IgG4-mAb to PD-1 Decreased T-cell suppression Increased T-cells killing cancer cells (Same mechanism as nivolumab?)
114
Pembrolizumab side effects
Immune-mediated inflammation Hypo- or hyperthyroidism Pancreatitis with Type 1 DM Colitis Rash Fatigue Diarrhea Nausea
115
Axitinib mechanism
TKI --> VEGF, PDGFR, c-kit Decreases tumor angiogenesis and growth
116
Axitinib side effects
Diarrhea HTN Fatigue Anorexia Nausea Dysphonia Hand-foot sxs Weight loss Vomiting Constipation
117
Pazopanib mechanism
TKI --> VEGF, PDGFR, FGFR, c-kit Decreased tumor angiogenesis and growth
118
Pazopanib side effects
Nausea Vomiting Diarrhea HTN Anorexia Rash Hair Loss Fatigue
119
Temsirolimus mechanism
mTOR inhibitor Decreased protein synthesis Decreased tumor survival and growth
120
Temsirolimus side effects
Fatigue Rash Mucositis Myelosuppression Hyperglycemia
121
Everolimus mechanism
mTOR inhibitor Decreased protein synthesis Decreased tumor survival and growth
122
Everolimus side effects
Fatigue Rash Diarrhea Stomatitis Infections Myelosuppression Hyperglycemia