Renal cell carcinoma

Renal Cell Carcinoma

Renal Cell Carcinoma Part 1

What are the first- and second- line therapies for non-clear cell metastatic kidney cancer ?

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First line VEGFi
Second line mTORi

Renal Cell Carcinoma Part 1
Renal cell carcinoma

What are the non-clear cell kidney cancer subtypes ?

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Chromophobe, collecting duct RCC, medullary, translocation, papillary

Renal cell carcinoma
Renal cell carcinoma

What is the treatment modality for medullary metastatic kidney cance ?

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Cytotoxic chemotherapy

Renal cell carcinoma
Renal cell carcinoma

What is the first-line therapy for non-clear cell metastatic kidney cancer?

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VEGF inhibitors

Renal cell carcinoma
Renal cell carcinoma

How can you increase the overall response rate of axitinib?

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Increase the dose

Renal cell carcinoma
Renal cell carcinoma

What are the poor prognostic features of newly diagnosed metastatic renal cell carcinoma ?

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Elevated LDH, anemia, hypercalcemia, poor performance status

Renal cell carcinoma
Renal cell carcinoma

What is the therapeutic treatment for angiolipomas and tuberous sclerosis?

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mTOR inhibitor

Renal cell carcinoma
Renal cell carcinoma

What tumors does TSCL predispose patients to?

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Clear-cell kidney cancer, angiolipoma, pulmonary lymphangiomatosis, subcutaneous ependymal giant
cell astrocytoma, retinal hamartoma

Renal cell carcinoma
Renal cell carcinoma

What gene/protein change is seen with Birt-Hogg-Dube syndrome?

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FLCN gene
Protein folliculin

Renal cell carcinoma
Renal cell carcinoma

Which chromosome deletion is seen with Birt-Hogg-Dube syndrome?

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17p

Renal cell carcinoma
Renal cell carcinoma

What is the name of the paraneoplastic syndrome and kidney cancer that causes liver enzyme
elevations?

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Stauffer syndrome, elevation in AST and ALT with no liver involvement

Renal cell carcinoma
Renal cell carcinoma

What is the most common paraneoplastic syndrome in kidney cancer?

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Anemia

Renal cell carcinoma
Renal cell carcinoma

What signs and symptoms in men should prompt a concern for kidney cancer ?

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Left scrotal varicocele that won’t be evacuated upon being recumbent

Renal cell carcinoma
Renal cell carcinoma

What complications can IVC involvement lead to in metastatic kidney cancer?

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Budd-Chiari syndrome, pulmonary embolism

Renal cell carcinoma
Renal cell carcinoma

What are the size cut-offs for T1, T2, T3, T4 RCC?

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T1 less than 7 cm
T2 7 to 10 cm
T3 invasion locally excluding Gerota’s fascia and adrenal gland
T4 invasion into Gerota’s fascia and adrenal gland

Renal cell carcinoma
Renal cell carcinoma

When is the role of radiation in metastatic kidney cancer ?

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Painful bone metastases, painful tumor burden, brain metastases

Renal cell carcinoma
Renal cell carcinoma

Which chromosome in von Hippel-Lindau is involved for renal cell carcinoma?

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3p

Renal cell carcinoma
Renal cell carcinoma

Which protein is mutated in papillary kidney cancer?

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MET

Renal cell carcinoma
Renal cell carcinoma

What is the role of surgery for metastatic kidney cancer?

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If greater than or equal to 75% of tumor can be debulked then should be considered

Renal cell carcinoma
Renal cell carcinoma

Which chemotherapy agents have some activity in metastatic kidney cancer?

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Gemcitabine and capecitabine

Renal cell carcinoma
Renal cell carcinoma

Which 2 proteins are upstream of mTOR?

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AKT and PI3K

Renal cell carcinoma
Renal cell carcinoma

What was the comparator arm in CHecKMATE-025 clinical trial for nivolumab in advanced RCC?

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Everolimus

Renal cell carcinoma
Renal cell carcinoma

Which tyrosine kinase inhibitors are approved for first line treatment in metastatic kidney cancer?

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cabozantinib, sorafenib, sunitinib, pazopanib, lenvatinib, axitinib + PDL1

Renal cell carcinoma
Renal cell carcinoma

What is the first question to ask when determining first-line therapy for metastatic kidney cancer?

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Candidate for immunotherapy

Renal cell carcinoma
Renal cell carcinoma

Which cytogenetic change is seen in greater than 90% of clear cell carcinoma?

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3p loss

Renal cell carcinoma
Renal cell carcinoma

Which viral infection increases the risk for RCC?

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Hepatitis C

Renal cell carcinoma
Renal cell carcinoma

Which renal cell carcinomas are sickle cell anemia patients predisposed to?

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Medullary RCC

Renal cell carcinoma
Renal cell carcinoma

What incidental kidney finding on imaging predisposes ESRD patients to RCC?

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Cystic Kidney Disease

Renal cell carcinoma
Renal cell carcinoma

What are the known risk factors for kidney cancer?

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White ethnicity, male, smoking, hypertension, obesity, cystic kidney disease

Renal cell carcinoma
Renal cell carcinoma

What are the top 2 different histologies for all cancers of the kidney?

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Clear-cell 90%, transitional cell 10%

Renal cell carcinoma
Renal cell carcinoma

What rheumatologic autoimmune disease can occur as a secondary paraneoplastic syndrome in
metastatic kidney cancer ?

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Polymyalgia rheumatica

Renal cell carcinoma
Renal cell carcinoma

What percentage of patients will be upstaged after surgery in renal cell carcinoma?

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10%

Renal cell carcinoma
Renal cell carcinoma

What complete blood count change can occur with kidney cancer?

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Anemia or erythrocytosis as well as thrombocytosis

Renal cell carcinoma
Renal Cell Carcinoma Part 2

What defines T4 disease in renal cell carcinoma?

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Invasion into Gerota’s fascia and ipsilateral adrenal gland invasion

Renal Cell Carcinoma Part 2
Renal cell carcinoma

What defines T3 disease in renal cell carcinoma ?

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Invasion into veins, arteries, perinephric tissue, but no adrenal gland invasion

Renal cell carcinoma
Renal cell carcinoma

What constitutes stage III renal cell carcinoma ?

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Ann T3 any N1

Renal cell carcinoma
Renal cell carcinoma

What is medullary carcinoma of the kidney?

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Variant of collecting duct associated with sickle cell trait

Renal cell carcinoma
Renal cell carcinoma

Which chromosomal translocation variant is seen in renal cell carcinoma?

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Xp11.2

Renal cell carcinoma
Renal cell carcinoma

Which tyrosine kinase inhibitor has the highest overall response rate is first-line treatment?

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Axitinib is Area under the curve can be maintained at >300 ng-hour/mL, otherwise cabozantinib

Renal cell carcinoma
Renal cell carcinoma

What is lenvatinib approved in combination with?

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Everolimus

Renal cell carcinoma
Renal cell carcinoma

What is the second line therapy for non-clear cell RCC?

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Everolimus

Renal cell carcinoma
Renal cell carcinoma

What is a feared complication of tenserolimus?

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Pneumonitis

Renal cell carcinoma
Renal cell carcinoma

When should Everolimus be considered for metastatic kidney cancer?

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Third or fourth line, consider in combination with lenvatinb

Renal cell carcinoma
Renal cell carcinoma

What does sorafenib inhibit?

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VEGF, PDGFR, FLT3, FGFR, C-RAF, BRAF

Renal cell carcinoma
Renal cell carcinoma

What does axitinib inhibit?

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VEEGF 1, 2, 3

Renal cell carcinoma
Renal cell carcinoma

What dose Linvatinib need to be combined with in stage IV kidney cancer?

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Everolimus

Renal cell carcinoma
Renal cell carcinoma

What side effect with Axitinib is a marker of a good response?

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Elevated diastolic blood pressure

Renal cell carcinoma
Renal cell carcinoma

What other cell surface receptor proteins does sunitnib target besides VEGFR?

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cKIT and PDGFR

Renal cell carcinoma
Renal cell carcinoma

Which 2 pathways are upregulated with von Hippel-Lindau Lindau mutated renal cell carcinoma?

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MTOR
VEGFR

Renal cell carcinoma
Renal cell carcinoma

What other tyrosine kinase inhibitor is cabozantinb superior to?

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Sunitinb

Renal cell carcinoma
Renal cell carcinoma

What is the treatment schedule for sunitinib ?

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4 weeks on 2 weeks off

Renal cell carcinoma
Renal cell carcinoma

Which proteins does cabozantinib target besides VEGFR?

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MET and AXL

Renal cell carcinoma
Renal cell carcinoma

Is pazopanib or sunitinb better tolerated?

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pazopanib

Renal cell carcinoma
Renal cell carcinoma

What is the #1 cause of pazopanib discontinuation?

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Elevated liver enzymes

Renal cell carcinoma
Renal cell carcinoma

Which protein down regulates the mTOR pathway?

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PT EN

Renal cell carcinoma
Renal cell carcinoma

Which syndrome causes chromophobe renal cell carcinoma?

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Birt-Hogg-Dube syndrome

Renal cell carcinoma
Renal cell carcinoma

What else does Birt-Hogg-Dube syndrome predispose patients to besides RCC?

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Pulmonary blebs

Renal cell carcinoma
Renal cell carcinoma

What cancers can develop with von Hippel-Lindau?

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Central nervous system hemangioblastoma, clear cell kidney cancer, PNET, pheochromocytoma, retinal
hemangioblastoma

Renal cell carcinoma
Renal cell carcinoma

How can you manage grade 1 pneumonitis secondary to mTOR inhibitor that are not symptomatic?

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Continue with therapy

Renal cell carcinoma
Renal cell carcinoma

What is the maximum number of metastases that can be resected in metastatic kidney cancer?

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3

Renal cell carcinoma
Renal cell carcinoma

Which soluble growth factor binds the MET receptor?

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Hepatocytes growth factor receptor

Renal cell carcinoma
Renal cell carcinoma

Which family of medications can be used for papillary renal cell carcinoma?

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mTORi and VEGFi

Renal cell carcinoma
Renal cell carcinoma

What is the CK7 and CK20 staining pattern for clear cell kidney cancer ?

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CK 7 negative, CK 20 negative

Renal cell carcinoma
Renal cell carcinoma

Which VEGF targeting agent can you combine with interferon for advanced kidney cancer?

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Bevacizumab

Renal cell carcinoma
Renal cell carcinoma

How many times the upper limit of normal of LFTS should prompt discontinuation of pazopanib?

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8 times the upper limit of normal

Renal cell carcinoma
Renal cell carcinoma

When would you consider radiofrequency ablation or cryoablation for kidney cancer versus partial or
radical nephrectomy?

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Only if the patient is not a surgical candidate

Renal cell carcinoma
Renal cell carcinoma

What is the size cut off for partial versus radical nephrectomy?

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7 cm

Renal cell carcinoma
Renal cell carcinoma

What is interleukin-2 dose for metastatic kidney cancer?

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720,000 international units per kilogram

Renal cell carcinoma
Renal cell carcinoma

Which enzyme will increase the likelihood of a response to high-dose interleukin-2?

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Carbonic Anhydrase X

Renal cell carcinoma
Renal cell carcinoma

Which categories of therapeutics are active for metastatic RCC?

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PDL 1, CTLA4, high-dose interleukin, interferon, VEGF targeting antibodies and inhibitors, mTOR
targeting agents

Renal cell carcinoma
Renal cell carcinoma

Which 3 conditions predisposed to bilateral renal cell carcinoma?

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Von Hippel-Lindau, tuberous sclerosis, papillary RCC

Renal cell carcinoma
Renal cell carcinoma

Which stages of kidney cancer can be cured with surgery?

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Stage I, 2, 3, 4

Renal cell carcinoma
Renal cell carcinoma

What is unique about collecting duct RCC treatment?

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Notable response to chemotherapy

Renal cell carcinoma
Renal Cell Carcinoma Part 3

What were the results of the COMPARZ trial for RCC ?

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Pazopanib and sunitinib have similar efficacy in advanced RCC as first line therapy but QOL is higher with pazopanib

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What did the COMPARZ trial assess in advanced RCC ?

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Sunitinib versus pazopanib for first line use in advanced RCC

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Is there phase 1, 2, and or 3 data to support the use of regorafenib in advanced RCC ?

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Phase II

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What is the most common grade 3/4 AE seen with regorafenib in RCC patients ?

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Hand-foot syndrome

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Does the addition of lenvatinib to everolimus improve OS in second line advanced RCC ?

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No

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Has an OS ever been demonstrated with single agent sunitinib in advanced RCC ?

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Yes, A618-1034 trial

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Which metabolic side effects are common with tenserolimus ?

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Hyperglycemia and hyperlipidemia

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Has an OS advantage ben demonstrated with cabozantinib in the first line setting in advanced RCC ?

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Yes, CABOSUN trial

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What did the CABOSUN trial assess for advanced RCC ?

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Cabozantinib in the first line setting for intermediate and poor risk RCC in the first line setting

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Is there randomized phase 3 data showing an improvement in OS with bevacizumab single agent for advanced RCC ?

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No

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What was the comparator in the METEOR trial for advanced RCC assessing cabozantinib ?

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Everolimus

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Has an OS advantage ben demonstrated with cabozantinib in the second line setting in advanced RCC ?

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Yes, METEOR trial

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Does the addition of everolimus to lenvatinib improve OS in second line advanced RCC ?

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No

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Has everolimus ever shown a statistically significant improvement in PFS or OS in metastatic RCC ?

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Only, PFS, second and later line, RECORD-1 trial

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Which ethnic subset of patients had the best ORR and OS outcomes in the CheckMate -025 trial using nivolumab in RCC ?

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Japanese

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What comparator was used in the CheckMAte-025 trial in advanced RCC using nivolumab ?

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Everolimus

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Has an OS advantage ben demonstrated in second and later line use of nivolumab for advanced RCC ?

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Yes, CheckMate-025 trial

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Is there an OS advantage to pazopanib monotherapy in advanced RCC ?

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No, VEG105192 trial

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What was discovered about prior TKI progressors from the AXIS trial for RCC ?

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Those with less than a median DOR to first line sunitinib did better wrt OS on either sorafenib or axitinib

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What did the AXIS trial assess in RCC ?

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Axitinib versus sorafenib in second and later line RCC

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What did the JAVELIN Renal 101 trial assess in RCC ?

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Avelumab + axitinib versus sunitinib in first line advanced RCC

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Has an OS advantage been demonstrated with Pembrolizumab + axitinib in the first line setting versus sunitinib ?

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Yes , KEYNOTE-426

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What did the KEYNOTE-426 trial assess in advanced RCC ?

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Pembrolizumab + axitinib in the first line versus sunitinib

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Were there more grade 3/4 AE with cabazantinib or sunitinib in CABOSUN ?

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Cabozantinib, 68%

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What was cabozantinib compared to in CABOSUN for RCC ?

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Sunitinib

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Which subset of patients derive the most benefit from ipi+nivo based off the CheckMate-214 trial ?

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Intermediate and poor risk

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What was the most common grade 3/4 AE seen with first line ipi+nivo in RCC in CheckMate-214 ?

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Elevated lipase, 10%

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

In the CheckMate – 214 trial, did the ipi+nivo arm or the sunitinib arm have more grade 3/4 AE for RCC ?

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Sunitinib, 17% with hypertension

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

Has a PFS and / or OS been demonstrated with first line ipi+nivo in advanced RCC ?

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Yes, CheckMate-214 trial

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma Part 3

What did the CheckMate-214 trial use as a comparator for first line ipi+nivo in advanced RCC ?

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Sunitinib

Renal Cell Carcinoma Part 3
Renal Cell Carcinoma

What are the disadvantages to a partial versus full nephrectomy in early stage RCC?

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increased risk of overall postoperative complications, postoperative hemorrhagic complications, and urinary fistula

Renal Cell Carcinoma
Renal Cell Carcinoma

Is a 2w/1w cycle inferior to 4w/2w cycle for sunitinib in RCC ?

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No, similar outcomes supported by meta-analyses

Renal Cell Carcinoma
Renal Cell Carcinoma

What is a more tolerable schedule for sunitinib in RCC than 4w/2w cycle ?

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2/1

Renal Cell Carcinoma
Renal Cell Carcinoma

What exam feature is predictive of poorer OS in metastatic RCC?

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Sarcopenia

Renal Cell Carcinoma
Renal Cell Carcinoma

Which variables are independent risk factors in the development of brain metastases in RCC at diagnosis ?

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Tumor size > 7cm and increasing patient age

Renal Cell Carcinoma
Renal Cell Carcinoma

Does a high pre-op neutrophil to lymphocyte ratio predict improved overall survival ?

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Yes, for tumors smaller than 5cm

Renal Cell Carcinoma
Renal cell carcinoma

What is recommended first-line therapy for papillary renal cell carcinoma?

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Sunitinib

Renal cell carcinoma
Renal cell carcinoma

Which non-clear cell kidney cancer subtypes should be offered chemotherapy ?

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Collecting duct tumors

Renal cell carcinoma
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