To introduce the Interdisciplinary Neuroendocrine care team model at London Health Sciences Centre/London Regional Cancer Program

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2 To introduce the Interdisciplinary Neuroendocrine care team model at London Health Sciences Centre/London Regional Cancer Program To highlight the decision making process, treatment recommendations and referral process for patients diagnosed with neuroendocrine tumor To increase the understanding of treatment options available in London

3 Dr. W. Kocha, Medical Oncologist Dr. R. Reid, Nuclear Medicine Dr. D. Gray, General Surgeon Dr. D. Quan, Hepatobillary Surgeon Dr. J. Elliott, Interventional Radiologist Dr. A. Mujoomdar, Interventional Radiologist Dr. B. Dias, Cardiologist Dr. M. Lock, Radiation Oncologist

4 Dr. C. Howlett, Pathologist Dr. S. Van Uum, Endocrinologist St. Joseph s Hospital Catherine Bond-Mills, Pharmacist James Mulligan, Registered Dietician Heather Shaddick, Social Worker Helen Battler, Spiritual Care Specialist Rosemary Davidson, Primary Nurse

5 Dr. Kocha, Medical Oncologist Specialist on antineoplastic therapy. Utilizes targeted therapies, clinical trials, somatostatin analogs that best treat neuroendocrine tumours. Also a hematologist therefore familiar with hematological abnormalities that can result from therapies. Dr. Reid, Nuclear Medicine Expertise evaluating isotope scans, obtaining/administration of radiopharmaceutical therapy. I 131 MIBG, In111 Octreotide and Lutetium 177 Octreotate. Samarium offered for wide spread bone metastases. Dr. Gray, General Surgeon Recommends surgery which can span the spectrum of complete resection to debulking of tumour to preventing life threatening complications from tumour invasion.

6 Dr. Quan, Hepatobillary Surgeon Specialty ranges from liver transplant, resection or debulking of liver tumours. Debulking if able to remove 80% of metastatic liver disease. Extremely important for patients who have functional tumours. Dr. Elliott & Dr. Mujoomdar, Interventional Radiologists Expertise in performing embolizations/rfa procedures for metastatic liver tumors. Perform liver biopsies, angiograms, place billary stents, nephrostomy tubes. Evaluate patients to determine who would benefit from embolizations or RFA procedures. Dr. Dias, Cardiologist Evaluates echocardiograms to determine the intervention/treatment of carcinoid related heart disease. Provides surgeons with cardiac risk factor and patients ability to undergo general anesthetic.

7 Dr. Lock, Radiation Oncologist Expertise in the application of external beam radiation therapy for metastatic bone lesions and will treat metastatic liver tumours if applicable. Dr. Howlett, Pathologist Reports and reviews pathologies of neuroendocrine tumours. Determines the Ki-67% and # of mitosis/high powered field which differentiates the low to high grade NET s. Pathology directs treatment. Dr. VanUum, Endocrinologist Expertise in the management of hormone imbalances that accompany many of the MEN I/II NET s and pnet s. Prescribes, adjusts medication required for thyroid abnormalities, diabetes, pituitary tumors.

8 Catherine Bond-Mills, Pharmacist Collaborates with inpatient pharmacy. Referral point for patients who require assistance for medication coverage, patient assistant programs. Reinforces education on oral chemotherapy, targeted therapies. Supportive Care Team James Mulligan, Registered Dietician Heather Shaddick, Social Worker Helen Battler, Spiritual Care Specialist Rosemary Davidson, Primary Nurse Collaborates with MDT members, coordinates treatment, procedures, referrals, admissions. Provide patient education re: treatment options & recommendation. Develops education material. Provides emotional support. Contact point for patients and health care professionals in Canada.

9 Intake clerk/secretary from any MDT physicians accepts referral. Information required per MDT Guidelines: Operative note/pathology with Ki-67 & #of mitoses/hpf Radiology/Nuclear Medicine scans done within 6 weeks of referral to LRCP/LHSC Lab values, 24 hour urinary 5-HIAA or urinary catecholamines Clinical notes, previous chemotherapy, radiation therapy, targeted therapies, embolizations, somatostatin analogue therapy

10 WORKING TOGETHER Core group of physicians on the Neuroendocrine Team discuss all new patients referred to LRCP or LHSC at the multidisciplinary tumour board rounds At MDT rounds, treatment options and plan of care is the focus The goal of the team is to enhance the quality of life for each patient by sharing their expertise in the management/recommendations of NET s

11 PATIENTS OUTSIDE THE LIN: It is important to maintain contact with your local team We WANT TO SHARE your care! Tumour board note/letter is dictated with recommendations to the referring physician. The letter requests the referring physician review the MDT recommendations with their patient If surgery is an option, patients often prefer this be preformed close to home rather than in London If radioisotope therapy offered, treatment must be in London BUT care is shared with referring oncologist If chemotherapy is the recommendation, this can be done at the local cancer centre

12 WORKING TOGETHER PATIENTS INSIDE THE LIN: Intake clerk schedules patient for a consultation with Dr. Kocha and Dr. Reid. Treatment recommendations discussed and referral made to appropriated MDT physician Surgery..Referral to Dr. Gray or Dr. Quan Radioisotope therapy..referral to Dr. Reid/Dr. Kocha Chemotherapy..Referral to Dr. Kocha External beam radiation therapy..referral to Dr. Lock

13 LET S TALK ABOUT NEUROENDOCRINE TUMOURS

14 NEUROENDOCRINE TUMOURS NET s are derived from cells of the nervous & endocrine system. NET cells are located in the endocrine glands, adrenals, pancreas, thyroid, pituitary Can start at the respiratory system and end at the rectum. NET cells also found in the ovaries and testes Total of 24 types of NET s

15 FUNCTIONING NET S Most common functioning NET s are Carcinoids (50% in the GI tract). Pheochromocytoma & Paraganglioma are functional tumours Four common functional pnet s, each named after the hormone they secrete Symptoms of hormone production can make a person very ill. This can lead to early diagnosis which results in resection Most common hormone secreted is serotonin, this causes carcinoid syndrome

16 TUMOURS & THEIR HORMONES TUMOUR HORMONE SYNDROME Carcinoid Serotonin, histamine, bradykinin, kallikrein, etc Flushing, diarrhea, cramps, wheezing, palpitations, Rt. heart changes, heart failure Insulinoma Insulin Hypoglycemia, very high insulin levels, low glucose levels Glucogonoma Glucagon High glucagon levels, diarrhea, weight loss, thromboembolic disease, rash necrolytic migratory erythema VIPoma Vasoactive intestinal peptide Profuse watery diarrhea, hypokalemia, hypochlorhydria, anemia, dehydration

17 TUMOURS & THEIR HORMONES TUMOUR HORMONE SYNDROME Gastrinoma Gastrin Recurrent multiple peptic ulcers, diarrhea, hyperacidity, abdominal pain Pheochromocytoma Paraganglioma Epinephrine & Norepinephrine Medullary thyroid Calcitonin Hypertension, tachycardia, palpitations, sweats, pallor, nausea, feelings of impending death Hypocalcemia, osteoporosis

18 NON-FUNCTIONING NET s May be found incidentally at surgery, can be large but due to lack of hormone production the individual does not feel ill Presenting symptom may be intermittent SBO due to mesenteric fibrosis 25 to 50% of carcinoid tumours are non-functioning 33 to 50% of pnet s are non-functioning Carcinoid or pnet s can evolve into a functioning tumour

19 PATHOLOGY... SO IMPORTANT

20 Dr. Howlett, the pathologist on the NET team, reviews pathology at tumour board rounds. If incomplete, he will request the actual slides be sent to him for review. Ki-67 is regarded as a prognostic factor for survival and directs treatment. NET s are divided into low, intermediate and high grade classifications. Grade determines treatment/prognosis Low and intermediate grade tumours are well differentiated and have a more favourable prognosis (G1 and G2 disease) High grade tumours are poorly differentiated, more aggressive and have a less favourable prognosis (G3 disease)

21 Tumours that demonstrate a significant increase in growth on imaging need to be biopsied and pathology reviewed It is not uncommon for tumours to transform and develop more aggressive features on pathology WHO classification if NET s was updated 2010 Criteria based on: proliferative activity(how fast the cells grow) tumour pathology, well or poorly differentiated tumour size and involved nodes metastases

22 TREATMENT OPTIONS

23 SURGERY.. EVEN IF METASTATIC! Dr. Gray and Dr. Quan evaluate the role of surgery at MDT rounds RESECT the primary tumour = CURE RESECT or debulk liver tumours if able to remove 80% REDUCE tumour size. Debulking can improve overall survival (NET S are usually slow growing), reduce symptoms from hormone producing NET s, and improve efficacy of radiopharmaceutical therapy REDUCE symptoms caused by tumour. Mesenteric fibrotic changes caused by primary tumours in the GI tract can lead to partial or complete bowel obstruction. Resection or bypass surgery will reduce or eliminate this complication

24 RADIOPHARACEUTICAL THERAPY Dr. Reid, Nuclear Medicine physician secures all three isotopes, In 111 Octreotide, I 131 MIBG and Lutetuim 177 Octreotate. He administers the isotope in the patients room. All isotopes are requested by special access therefore follow up is ongoing even after completion of therapy. In 111 Octreotide and I 131 MIBG scan are required at LHSC to determine avidity to the isotope. In 111 Octreotide and/or I 131 MIBG therapy is offered pending avidity. Often carcinoid and pheochromocytoma have avidity for both isotopes. pnet s are only avid for In 111 Octreotide Lutetium 177 therapy. Tumour must be octreotide avid. Highest energy isotope given in Canada

25 IN 111 OCTREOTIDE THERAPY In 111 Octreotide therapy planned q 6 weeks x 3 Admit 3 days to a private room. Body secretions radioactive (esp. urine) 5FU or Xeloda given 7 days before and 7 days after each isotope therapy. Four hours post isotope Epirubicin & Carboplatin are administered. Chemotherapy acts as a radiosensitizer. Weekly blood work at local lab while on therapy and x 8 weeks after final therapy. CT/MRI 3-4 months after last Octreotide therapy Pending response, maintenance therapy q 6 months x 2 years. Goal to achieve tumour stability

26 I -131 MIBG THERAPY MIBG therapy planned q 9 weeks x 3 based on blood work values Admit 5 days to a private room. Body secretions urine, stool and blood are radioactive 5FU or Xeloda given 7 days before and for 7 days after each isotope therapy. Four hours post isotope Epirubicin & Carboplatin are administered. Chemotherapy acts as a radiosensitizer. Thyrosafe (Potassium Iodide) x 10 days to protect the thyroid. Weekly blood work at local lab while on therapy and x 8 weeks after final therapy. CT/MRI 3-4 months after last MIBG therapy. Pending response maintenance therapy q 6 months x 2 years. Goal to achieve tumour stability

27 ALTERNATING ISOTOPE THERAPY Offered if avidity for both In 111 Octreotide and I 131 MIBG. Receive 2 treatments of each isotope Chemotherapy is administered with each isotope therapy MIBG - 9 week recovery Octreotide - 6 week recovery MIBG - 9week recovery then final treatment with Octreotide Weekly blood work at local lab while on therapy and x 8 weeks after final therapy CT/MRI 3-4 months after last therapy. Pending response maintenance therapy q 6 months x 2 years. Goal to achieve tumour stability

28 LUTETIUM 177 OCTREOTATE If avid for Octreotide, total of 3 therapies q 10 to 16 weeks CT scan, Octreotide and Renal scan including GFR pre L-177 tx Admit 3 days to a private room. Body secretions urine, stool and blood radioactive Chemotherapy not administer with Lutetium, higher radiation Weekly blood work at local lab while on therapy and x 8 weeks after final therapy CT/MRI 3-4 months after final therapy. Regular follow up appointments to monitor tumour response

29 TRANSARTERIAL CHEMOEMBOLIZATION TACE is preformed by Dr. Mujoomdar or Dr. Elliott Interventional Radiologists Localized palliative therapy for liver only metastases from neuroendocrine tumours. There can be no disease outside the liver for this therapy Most tumours receive blood supply from the hepatic artery, embolization interrupts this blood supply, thus delays tumour growth Contraindicated if portal vein occlusion, dilated billiary ducts, previous Whipple s procedure, ascites

30 TRANSARTERIAL CHEMOEMBOLIZATION A thin catheter is thread up into the tumour by the physician. The catheter entry point is the groin In London doxorubicin and cisplatin powder are mixed with lipiodol and injected into the tumour. Chemotherapy increases tumour necrosis Review of 122 patients treated with TACE, 82% had tumour regression and 92% reported improvement of symptoms TACE can be done to reduce tumour volume prior to radioisotope therapy. Less tumour volume=more concentrated isotope therapy

31 COURSE IN HOSPITAL IV antibiotics, foley catheter and pain pump started pre embolization Post embolization oral antibiotics for 10 days. Ondansetron, decadron while in hospital( 3 day admission) Common side effects are bloating, decreased appetite and increased fatigue that can last x 4-6 weeks Functional tumours Sandostatin 60 mg IM 14 days prior to embolization Sandostatin 500 mcg. s/c 1 hr pre embolization If carcinoid syndrome during procedure Sandostatin IV

32 TREATMENTS AVAILABLE AT YOUR LOCAL CANCER CENTRE

33 TREATMENTS AVAILABLE AT YOUR LOCAL CANCER CENTRE CHEMOTHERPAY G3 Disease: Etoposide/Cisplatinum 5Flurouracil infusion x 14 days/dacarbazine infusion for last 5 days of the cycle Streptozocin/Adriamycin or 5FU (only for pnet s) Asses response after every 2 cycles, treat to maximum response G2 Disease: Same chemotherapy as for G3 disease, image after every 2 cycles and treat to maximum response. Your Oncologist then can advise Dr. Kocha of response. Next step is to perform the In 111 Octreotide and/or MIBG scan, if avid offer appropriate isotope therapy

34 SOMATOSTATIN ANALOGUES (SSA s) Bind to somatostatin receptors to decrease production of hormones. Serotonin from carcinoids, insulin, glucogon, gastrin and vasoactive polypeptide(vip) from pancreatic neuroendocrine tumours. Recommend as primary treatment for symptomatic NET s and asymptomatic NET s with progressive disease to stabilize tumour. Evidence of tumour stability in 35-70% of patients on LAR (PROMID trial) TARGETED THERAPIES Interfere and block various pathways that are needed for cancer cells to grow. They can prevent the formation of blood vessels, cut off the blood and oxygen supply to the cells. End result, inhibits tumour growth

35 The complexities of a Neuroendocrine tumour require the collaboration of a TEAM of health care professionals The MDT at LRCP/LHSC are committed to provide the very best care, management and follow up for this unique patient population Our team strives to educate Health Care Professionals across Canada about the complexities of NET s and treatment options available in London It is the collaboration and dedication of this team that will offer you the most current treatment options and best quality of life

36 YOUR QUESTIONS PLEASE

37 THANK YOU FOR YOUR TIME