Tailoring Treatment for You

1
Tailoring Treatment for You

• Run Yu, MD, PhD
• Director
• Carcinoid and NET Center
• Cedars-Sinai Medical Center

2
Outline

• Introduction
• Treatment options
• Is this treatment right for you?
• Questions and answers

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Neuroendocrine cells
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Nature of carcinoid

• Most such tumors are slow-growing
• It is challenging to predict individual tumor
  behavior by doctors
• The best clues are
• 1) Organ of origin
• 2) Clinical presentation
• 3) Tumor pathology
• Some tumors secrete hormones such as serotonin

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Tumor classification

• By locations
• Foregut lungs, esophagus, stomach, duodenum (1st
  part of small bowel)
• Midgut jejunum, ileum, appendix, ascending colon
• Hindgut transverse colon, descending colon,
  rectum

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Tumor classification

• By pathology
• Well-differentiated endocrine tumors low grade
  of malignancy
• Well-differentiated endocrine carcinomas more
  aggressive with metastases
• Poorly-differentiated endocrine carcinomas high
  grade of malignancy

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Clinical presentation

• Rare disease. Incidence 1-2/100,000/yr
• Carcinoid syndromes
• Flushing, diarrhea, asthma-like attacks,
  right-side heart disease
• Local tumor mass effects or metastasis
• Incidental finding

8
Diagnosis

• Delay in diagnosis is common
• Reason is that symptoms are not unique
• Think of it and test for it!

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Biochemical tests

• Serotonin, 5-HIAA for carcinoid syndrome
• Also CGA, NSE, PP, hCG, CEA
• Important for diagnosis and follow-up as tumor
  markers

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Imaging for GI NETs

• Upper and lower GI EGD colonoscopy, Barium
  studies
• Jejunum and ileum challenging
• Barium small-bowel series, enteroclysis,
• Endoscopy double-balloon enteroscopy, capsule
  study, push enteroscopy
• CT/MRI
• Octreotide scan
• PET

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Prognosis

• Site appendix, rectum better than stomach, small
  intestine, and colon
• Size lt1 cm better than gt2 cm
• Metastasis better without it
• Ki-67 the lower, the better
• Carcinoid syndrome better without it
• CGA, 5-HIAA the lower, the better

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Basic facts on treatments

• Most carcinoids are slow-growing
• Surgeries are getting safer and safer
• No perfect clinical trials have been done to
  compare treatment approaches
• Many retrospective studies and expert opinions
• Several guidelines are available from scholarly
  societies

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Aggressive approaches

• Become a trend in academic centers
• Appear to be superior to wait and see in theory
  and by experience
• Basic assumption patients benefit from reduction
  of tumor burden
• Remove primary and metastatic tumor as much as
  possible
• Team effort to choose a comprehensive plan

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Surgery

• Only way for cure
• Also for debulking or symptom relief
• Outcome is generally good but surgeon- and
  center-dependent
• Make sure your surgeon knows what she/hes doing
• Surgery has intrinsic operative risks
• Patient selection is key

15
Somatostatin analog

• Octreotide and sandostatin
• Great medications
• Best in controlling diarrhea
• Also reduces tumor size
• Very few side effects gall stones, mild diabetes
• I give it to all patients with active carcinoid
• The issue is cost and insurance coverage

16
Interferon alpha

• Works
• Effects are similar to somatostatin analogs
• The problem is side effects
• Not used as often
• Have uses in patients who do not respond to
  somatostatin analogs

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Chemotherapy

• Reserved for fast-growing and metastatic
  carcinoid
• Usually not very effective
• A lot of side effects

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Chemoembolization

• Great for liver metastasis
• Best for tumors limited to one lobe of liver
• Some patients have severe side effects

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SIR-Spheres

• Radioactive Yttrium 90 microspheres
• Cause internal radiation to liver tumors
• Can still do chemoembolization after Sir-spheres
  but not vice versa.

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Radiation

• External beam radiation for metastasis to bone,
  brain, or spinal cord

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Experimental treatments

• Internal targeted radiation
• 111In-DTPA-pentetreotide
• 90Y-DOTA-octreotide
• 177Lutetium-DOTA-Octreotate
• Rad001
• An oral medication
• May work for carcinoid
• Cedars is currently running this trial by Dr.
  Wolin

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Which treatment is right for ME?

• Team approach
• Safely remove as much tumor as possible by
  surgery
• Sandostatin for all patients with active disease
• Regional therapy for liver metastasis
  SIR-sphere, chemoembolization
• Interferon alpha for patients not responding to
  sandostatin

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An example

• Jenny (not her real name) is a 45-year-old mother
  of 3 lovely children. At 39, she had hysterectomy
  secondary to fibroids. She has symptoms of small
  bowel obstruction and was sent to emergency room.
• In the ER, small bowel obstruction is confirmed
  and is thought to be caused by the surgical
  adhesion from hysterectomy.

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Jennys story continued

• Abdominal surgery is done to remove the adhesion.
• During surgery, besides the adhesion, a terminal
  ileum tumor and lymph nodes are found, and by
  inspection, several liver metastases are noted.
• The small bowel tumor and lymph nodes are
  resected. Liver biopsy is done
• Pathology shows carcinoid.

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What should Jenny do

• Biochemical markers mildly elevated
• Imaging liver metastasis
• Treatment will depend.

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CNET at Cedars

• Carcinoid and Neuroendocrine Tumor Center
• Dr. Yu, Director, endocrinology
• Drs. Colquhoun and Nissen, surgery
• Dr. Wolin, oncology
• Drs. Lo and Sadda, gastroenterology
• Drs. Dhall, pathology
• Drs. Waxman and D'Agnolo, nuclear medicine
• Dr. Wachsman, diagnostic radiology
• Dr. Friedman, interventional radiology
• And other expert physicians for carcinoid and
  neuroendocrine tumors.

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Questions

• All questions from patients are great questions
  by definition.