Neuroendocrine tumors

Question 1

What is the tx for well differentiated Grade 1/2 tumors of the GI tract for locally advanced or metastatic disease?

Answer 1

Everolimus (Cat 1 for non-functional tumors), Octreotide LAR or Lanreotide, Lu 177 Dotatate for progressive tumors on SSA (Cat 1 for mid-gut tumors)

Question 2

If a patient has locally advanced and metastatic disease that is asymptomatic and low tumor burden what do you do?

Answer 2

You just observe as these tumors can be very slow growing and b/c of this you won’t have to treat for quite some time for some patients.

Question 3

What are typically indications to treat these tumors (more so for locally advanced and metastatic disease)?

Answer 3

If they are functional and causing symptoms generally you treat. If they have a high tumor burden and widely metastatic you treat.

Question 4

With SSAs such as Lanreotide and Octreotide what does NCCN say you can do for those that experience progressive disease?

Answer 4

For those tumors that are SSTR+ you increase the dose to above label to see if you can get a response

Question 5

For tumors of the GI tract NCCN lists that you can use chemo/RT using a 5-FU regimen for locally advanced unresectable disease. It says not to use for small bowel mesenteric disease

Question 6

What are the tx options for lung/thymus locally advanced disease that is low grade and significant tumor burden or disease progression or symptomatic or intermediate grade?

Answer 6

Remember the tumor burden must be high. You can use Everolimus (Cat 1 for non-functional tumors) or you can use Octreotide/Lanreotide

Question 7

Besides the first line options used for lung/thymus tumors what are additional options NCCN recommends?

Answer 7

Carbo/Cisplatin w/Etoposide, TMZ +/-Capecitabine (only for intermediate grade/atypical tumors w/high Ki-67). You obviously have the option of Lu 177 if SSTR+ and they progress on SSAs.

Question 8

What are your first line options for pancreatic neuroendocrine tumors?

Answer 8

Octreotide/Lanreotide, Everolimus (Cat 1 for progressive disease), Sunitinib (37.5mg daily), Lu 177 for progression on SSA, TMZ+Capecitabine (esp for high tumor burden/symptoms and desire to shrink the tumor)

Question 9

What chemo can you use for bulky, locally advanced, highly symptomatic pancreatic tumors?

Answer 9

FOLFOX or CAPEOX

Question 10

What medication is indicated in VHL germline mutation and pancreatic tumors?

Answer 10

Belzutifan

Question 11

It says for pancreatic tumors you can also consider using SSAs for tumors that are SSTR neg

Question 12

Remember that you have the option of using RT+/-concurrent chemo in pancreatic tumors that are locally advanced and unresectable

Question 13

If a patient experiences disease progression for any neuroendocrine tumor on Octreotide/Lanreotide what should be done if the tumor is non-functional or functional?

Answer 13

Non-functional-discontinue the drug
Functional-continue the drug as it can be combined with other agents.

Question 14

For well differentiated tumors that are also grade 3 one thing to pay close attention to here is the Ki67 score and the full extent of the tumor. Within this category tumors can be behave quite differently. What mitotic rate corresponds to each grade?

Answer 14

<2 mitoses-G1
2-20 mitoses-G2
>20 mitoses-G3

Question 15

For well differentiated tumors that are Grade 3 and have good tumor biology (i.e. low Ki67) what are the treatment options?

Answer 15

So the key concept here is that given that it is a grade 3 tumor you can use chemo here as front line tx: Carbo/Cisplatin w/Etoposide, FOLFOX/CAPEOX, TMZ+/-Capecitabine. Everolimus is an option. Sunitinib-pancreas only. Additionally you have your other hormone directed options that you use for G 1/2 tumors. Pembro-MSI-H/dMMR, TMB-H

Question 16

It says you can consider RT+/-concurrent chemo for well differentiated Grade 3 tumors that are locally advanced unresectable

Question 17

What are the tx options for poorly differentiated neuroendocrine tumors outside the lung?

Answer 17

Straight chemo: Caro/Cisplatin w/Etoposide, FOLFIRI, FOLFOX. It says you give these agents w/resectable dx and you can give it concurrently or sequentially w/RT for unresectable tumors. TMZ +/-Capecitabine.

Question 18

Remember that targeted therapy is an option for metastatic poorly differentiated tumors using IO Pembro and Ipi/Nivo in addition to BRAF and NTRK and RET fusion med.

Answer 18

Pembro-MSI-H, d-MMR, TMB-H
Ipi/Nivo-Cat2B progressive disease only
NTRK: Entrecrinib, Repotrectinib, Larotrectinib
RET-Selpercatinib
BRAF: Drabafenib/Trametinib

Question 19

What is the tx of locally advanced/unresectable adrenal tumors? Remember these are neuroendocrine tumors!

Answer 19

Carbo/Etoposide+/-Doxorubicin+/-mitotate
Can exchange Carbo w/Cisplatin. Can do mitotane alone (more so for hormone than anti-tumor) and Pembro+/-Mitotane.

Question 20

What is the tx for locally advanced or metastatic pheochromocytoma?

Answer 20

HSA iobenguane I 131(needs positive scan for this), clinical trial, Sunitinib 37.5mg daily, chemo (CVS or TMZ), Lu-177, or Octreotide or Lanreotide