Neuroendocrine Tumor Chemotherapy - PowerPoint Presentation

Slide1

Neuroendocrine Tumor Chemotherapy

Dr. Ali

Okhovatian

. M.D

.

Active Member of American Society of Clinical Oncology

Nov 14, 2018

Slide2

Histologic Classification of NET

NET are generally

subclassified

by site of origin , stage, and histologic characteristics.

Tumor differentiation and grade often correlate with mitotic count and Ki-67 proliferation index.

Increased mitotic rate and high Ki-67 index are associated with a more aggressive clinical course and worse prognosis.

Slide3

Histologic Classification of NET,

Cont

In some cases, however, tumors may not fall clearly into one category. For example, a morphologically well-differentiated NET with a low mitotic index may have a Ki-67 index that falls into the high-grade category.

A key recommendation is that tumor differentiation, mitotic rate, and Ki-67 index should all be included in the pathology report.

Slide4

Histologic Classification of NET , Con

The classification of lung and thymus carcinoids varies from that of

gastroenteropancreatic

NET in some classification systems, and in particular does not include Ki-67 and includes the assessment of necrosis.

In NET unlike other malignancies, primary tumor size and depth of invasion had little bearing on survival in early-stage disease.

Slide5

Histologic Classification of NET, con

Presence of lymph node and distant metastases have the strongest effect on survival.

In addition to information on histologic classification and stage, the margin status , and the presence of vascular or

perineural

invasion may also have prognostic significance.

Slide6

Histologic C

lassification of NET ,

con

Whether or not tumors are associated with symptoms of hormone

hypersecretion

(“functioning” or “ non-functioning”) is, in general, a part of the clinical rather than histologic diagnosis. Thus , functional status is usually not included in the pathology report. However, If a specific clinical situation suggests that correlation with histologic evidence of peptide hormone may be helpful, then biochemical or IHC may be performed.

Slide7

Management of

Locoregional

NET

Resection is the primary treatment approach for most localized carcinoid tumors.

Although symptoms of hormone

hypersecretion

are more common in metastatic disease, with

locoregional

disease with this symptoms, we can use

octreotide

or

lanreotide

.

Slide8

Thymic NET

Localized or

locoregional

disease are generally treated with surgical resection without adjuvant therapy if negative margin.

There is limited data on the utility of radiation with or without chemotherapy for

unresectable

disease or positive margins.

Slide9

Thymic NET,

con

RT is considered category 3 for low-grade (atypical) tumors.

In intermediate grade tumor(atypical) , RT with or without

cisplatin

or carboplatin and

etoposide

is more generally recommended, because they have greater efficacy in tumors with higher mitotic and proliferative index.

Slide10

Bronchopulmonary NET

Surgery including lobectomy or other anatomic resection, and

mediastinal

node dissection or sampling is

recommnded

for stage I,II, and IIIA. If surgery is feasible and disease in stage I,II, or low-grade IIIA, patients may be monitored with surveillance. If stage IIIA is intermediate grade, adjuvant therapy using chemotherapy with or without RT may be considered.

Slide11

Bronchopulmonary NET,

con

There is limited data on the efficacy of

chemoradiation

for

unresectable

stage IIIA or IIIB.

If surgical resection is not medically feasible , or if there are positive margins following resection for patients with low-grade, or if patients have low-grade stage IIIB, then RT with or without chemotherapy is considered by some panel( category 3).

Slide12

Bronchopulmonary

NET,

con

If stage IIIA or IIIB are intermediate grade, RT with or without chemotherapy is generally recommended.

Slide13

Appendiceal NET

A small proportion of these tumors may also contain evidence of adenocarcinoma (

ie

, “

adenocarcinoid

” or “ goblet cell carcinoid”). These should be managed according to

colon cancer.

Slide14

Evaluation of

Locoregional

/distant Metastatic GI,

Bronchopulmonary

, and

Thymic

NET

Poorly differentiated

bronchopulmonary

or

thymic

tumors may have less avidity for 68

Ga

-

dotatate

PET/CT, therefore FDG-PET/CT may be considered for NETs that are poorly differentiated or have atypical histology.

Slide15

Management of

Locoregional

Unresectable

/Metastatic GI NET

Patients with metastatic NET and carcinoid syndrome should be treated with

octreotide

or

lanreotide

. The long-acting release (LAR) formulation of

octreotide

, 20-30 mg IM every 4

wk

, is commonly used for chronic symptom management. But therapeutic levels are not achieved for 7-14 days, so short-acting

octreotide

( 150- 250 mcg SC 3 times daily) can be added for rapid relief of symptoms.

Slide16

Management of Locoregional

Unresectable

/Metastatic GI

NET,

con

Lanreotide

has similar mechanism of action as

octreotide

. Several studies have shown it to be effective at controlling symptoms in patients with carcinoid tumors,

gastrinomas

, or

VIPomas

.

Slide17

Management of Locoregional

Unresectable

/Metastatic GI

NET,con

If carcinoid tumor is poorly controlled,

telotristat

, small

molcule

trytophan

hydoxylase

(TPH) inhibitor, which decreases urinary 5-HIAA levels and the frequency of bowel movement, should be considered. It was approved by the FDA in February 2017 and recommended for persistent diarrhea.

Slide18

Resection of Metastatic disease

In some cases, limited hepatic metastases or other sites of disease can undergo complete resection of primary tumor and metastases with curative intent.

Noncurative

debulking

surgery can also be considered in select cases, especially if the patient is symptomatic either from tumor bulk or hormone production.

Slide19

Resection of Metastatic disease,

con

Resection of the primary site in the setting of

unresectable

metastases is generally not indicated if the primary site remains asymptomatic and is relatively stable.

Slide20

Hepatic-directed Therapies for Metastatic NET of GI tract

For patients with

unresectable

, hepatic-predominant, progressive disease, may be considered, mainly for palliative goals of extending life and relieving hormonal symptoms ( RFA or

cryoablation

, hepatic arterial embolization

or chemoembolization).

Slide21

Therapy for Advanced GI NET

Everolimus

( an inhibitor of

mTOR

) can be considered for progressive metastatic GI carcinoids. It can be given with

octreotide

LAR. Adverse events include: stomatitis, fatigue, rash, and diarrhea.

Slide22

Therapy for Advanced

Bronchopulmonary

or

Thymic

NET

Patients with advanced intermediate-grade should generally be initiated on systemic therapy. Options include;

octreotide

or

lanreotide

,

everolimus

,

temozolamide

. Carboplatin or

cisplatin

and

etoposide

is generally considered for tumors on the higher end of atypical category with respect to Ki-67 and grade. These drugs may be given with or without

octreotide

.

Slide23

Therapy for

Locoregional

resectable

Pancreatic

NET

For

Insulinoma

, first stabilizing glucose levels with diet and/or

diazoxide

. Also we can use

everolimus

in this scenario.

For

Glucagonoma

,

hypercoagulable

state reported in 10% to 33%, so perioperative anticoagulation can be considered, because of increased risk of pulmonary emboli.

Slide24

Therapy for

Locoregional

/ Metastatic Pancreatic NET

Unfortunately, most patients who present with pancreatic NET have

unresectable

disease. For patients who are asymptomatic and have low tumor burden and stable disease, observation can be considered, with marker assessment and

abdominopelvic

CT or MRI every 3 to 12 months until clinically significant progression occurs.

Slide25

Therapy for Locoregional

/ Metastatic Pancreatic

NET,

con

For symptomatic patients with

unresectable

disease, those who initially present with clinically significant tumor burden, or those with clinically significant disease progression, options include:

octreotide

or

lanreotide

; if disease continue to progress:

everolimus

or

sunitinib

, or treatment with cytotoxic chemotherapy.

Slide26

Therapy for Locoregional

/ Metastatic Pancreatic

NET,con

The molecularly targeted agents

everolimus

and

sunitinib

have been confirmed to have antitumor activity and to improve PFS in patients with advanced pancreatic NET.

Streptozocin

is FDA-approved for use in patients with advanced pancreatic NET.

Temozolamide

has activity at least comparable to

streptozocin

in Pancreatic NET.

Slide27

Therapy for

Nonmetastatic

Adrenal Carcinoma

Adjuvant therapy may be considered if the patient is at high risk for local recurrence based on positive margins, ruptured capsule, large size, or high grade. Adjuvant RT to the tumor bed can be considered in these cases, particularly if concern exists regarding tumor spillage or close margins after surgery.

Slide28

Therapy for Metastatic Adrenal Carcinoma

Resection may be considered if greater than 90% of the tumor and metastases can be removed. Otherwise, systemic therapy should be initiated.

Choices of systemic therapy are

mitotane

monotherapy

or various combinations of

cisplatin

, carboplatin,

etoposide

,

streptozocin

, and

mitotane

.

Slide29

Therapy for Metastatic Adrenal

Carcinoma,

con

Pembrolizumab

( an

Ig

G4

isotype

antibody) should be considered in mismatch repair- deficient (

dMMR

) or microsatellite instability – high (MSI-H)

unresectable

/metastatic adrenocortical tumors that have progressed following prior treatment and have no satisfactory alternative treatment options.

Slide30

Therapy for

Pheochromocytoma

/

Paraganglioma

For locally

unresectable

tumors, RT can be considered, with

cytoreductive

resection, when possible. Alternatively, if tumors are positive on MIBG scan with

dosimetry

, treatment with iodine-131- MIBG therapy is recommended.

Slide31

Therapy for Pheochromocytoma

/

Paraganglioma,

con

When distant metastases are present,

cytoreductive

resection is also recommended when possible, and medical therapy should be continued for secreting tumors. Other options for

unresectable

/ metastatic include: 1) systemic chemotherapy (CVD or

temozolamide

), 2) iodine-131-MIBG therapy, or 3) palliative RT for bone metastases.

Slide32

High grade or Poorly differentiated NET/ Large or Small cell carcinoma

Most

extrapulmonary

poorly differentiated NET are aggressive and require treatment similar to small cell lung cancer.

For

resectable

tumors, surgical resection and chemotherapy with or without RT are advised. Alternatively, definitive

chemoradiation

can be considered.

Slide33

High grade or Poorly differentiated NET/ Large or Small cell

carcinoma

,con

For

unresectable

locoregional

disease, RT in combination with chemotherapy is recommended.

If metastatic tumors are present, chemotherapy alone is recommended (

cisplatin

or carboplatin with

etoposide

).

Slide34

Thank you for your attention