1 / 44

Week 6 Case Presentation

Week 6 Case Presentation. Neuroendocrine Malignancy. Introduction.

idola-barry
Download Presentation

Week 6 Case Presentation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Week 6 Case Presentation • Neuroendocrine Malignancy

  2. Introduction • JR, 51 F previously working at Marketing division in Monash Uni, presented for r/v prior to her monthly Zometa (Zoledronic Acid) infusions for metastatic bronchial carcinoid tumour which was diagnosed in Mar 2010 following worsening non-productive cough and dyspnoea, and 20kg LOW. No significant past medical or family history of cancer was noted, and JR is a life-long non-smoker and has NKDA. She is currently well and ambulating, but experiences moderate fatigue limiting her ADLs (ECOG performance status 2)

  3. HOPC • Feb 2010 • Worsening non-productive cough over a few months associated with LOW of 20kg over 4 mths, worsening dyspnoea and LOA. • Nil chest pain, haemoptysis, fever / flushing, NS, chills/shakes, lumps felt, change in bowel or urinary habits • Sought medical assistance in Feb 2010 • CT scan arranged - highly vascularised lesion in the left lower lobe.

  4. PMHx • AC joint dissection in 2012 • IVF x 4C in 2004 • GORD • Sinusitis • NKDA • Nil regular meds previously

  5. FHx • No significant history of cancer in the family

  6. Social Hx • Avid cook, ensures well-balanced meals • Good social support • Nil financial issues, on private insurance

  7. Plan • Referred for bronchoscopy • Histopathology consistent with a bronchial carcinoid tumour • Urinary 5-HIAA : 110 H • HRCT scan - highly vascularised, non-spiculated mass in the left lower lobe. 4.4 x 3.2 x 5 cm. 2 small left posteroinferior • Dx: Bronchial carcinoid tumour AJCC Stage I/B (T2 N1 M0) • Referred to surgeon for VATS minimally invasive thorascopically assisted left lower lobectomy • Nuclear medicine octreotide study - Normal • Refer to Medonc for further management • commence on Somatulin (Lanreotide) 120mg

  8. F/up • Urinary 5-HIAA • 13/2/11 : 186; 11/8/11: 372H • Chromogranin A increased • 25/10/12 : 121 ; 9/5/13 : 158

  9. Mets • 18 Jun 2012 • P/W worsening (L) hip pain during routine r/v • XR showed radiolucent area in (L) acetabular region • whole body bone scan performed subsequently - mets to (L) hip • Repeat urinary 5-HIAA and chromagranin - both elevated • Plan : • RT + Commence on Zometa + continue on Somatulin

  10. Mets • 15 Feb 2013 • c/o tenderness over skull and (L) shoulder • CT brain, skull, chest - multiple liver mets • Plan • Liver Biopsy - consistent with mets from bronchial carcinoid tumour • LFTs - normal • Refer for IV radionuclide therapy @ Peter Macallum- require PET octreoscan • Mets in liver • pagetic changes detected in left clavicle and ilium

  11. Mets • FDG PET/CT & GaTate Functional Imaging performed • Ki-67 <5% • low somatostatin expression at sites of disease in abdomen and pelvis - more de-differentiated disease • ineligible for IV radionuclide therapy - recommend commencement of IV ChemoRx • Recommend cessation of Somatulin due to low somatostatin expression

  12. Chemotherapy • Commenced of 6C CBDCA / Etoposide • Experienced recurrent anaemia requiring multiple transfusions post-chemo, profound fatigue, anorexia, n/v, cancer-related pain and multiple episodes of neutropaenia requiring admissions • Developed depression - commence on mirtazapine; referral to psycho-oncologist • ChemoRx was poorly tolerated - only 5C were completed • MRI showed stable disease as of 27/8/13 • Commence of monthly Zometa (Zoledronic Acid)

  13. CEA levels

  14. Current issues • Moderate fatigue - unable to work but ADLs remain relatively good • Social isolation • Residual (L) shoulder pain - commence on Lyrica (pregabalin) • Depression - mirtazapine 60mg • Poor appetite - commence on dexamethasone 4mg for motivation / energy / appetite

  15. Current Medications • Lyrica 75mg - neuropathic pain • Magmin 500mg • Avanza 60mg - depression • Dexamethasone 4mg • Durogesic patch 25mcg/h • Endone 5mg • Seretide Accuhaler • Zometa

  16. Neuroendocrine Tumours

  17. Introduction • neoplasms that arise from the cells of the endocrine and nervous system • Classification : well-differentiated, low grade malignancy, high grade malignancy • Types • GEP-NETs - 2/3 of all GEP-NETs carcinoid, 1/3 PNET • Lung (SCLC, carcinoid, LCNEC) • Pituitary, Thymus, Parathyroid, Thyroid, EPSCC, adrenal, phaeochromocytomas, peripheral nervous system, breast, GU tract

  18. Introduction • Expresses unique syndromes & biochemical markers • Steroids - usually by adrenal cortex / gonads • Peptide hormones & catecholamines • APUD - 5HT, NA/Adr, Histamines, Kinins • Peptide hormones • GI hormones • MEN syndrome

  19. MEN Syndromes • MEN1 [TSG @ 11q13] • pituitary tumours + pancreatic islet cell tumours + parathyroid tumours • MEN 2 [ret oncogene @ 10q11] • MEN2A - medullary CA of thyroid + Bilateral phaeochromocytoma + parathyroid hyperplasia / adenoma • MEN 2B - medullary CA of thyroid + bilateral phaeochromocytoma + multiple mucosal ganglioneuromas • Cushing syndrome may develop as a consequence of ectopic ACTH production

  20. Carcinoid Tumours • <1% of all tumours • may be in association with MEN1 • Primary tumour usually an APUD - small, commonly located in the small intestine but may also be found in stomach / colorectal / lung / ovary • Mets • liver mets are common; may result in liver failure with replacement of functional liver tissue with tumour • bone mets are usually osteoblastic • desmoplastic response - mesenteric fibrosis causing bowel obstruction

  21. Carcinoid tumours • 30-50% of tumours are hormonally-active - carcinoid syndrome • Rare without liver mets [unless ovarian] • usually associated with malignancy • may exhibit niacin deficiencies, acromegaly, Cushing’s syndrome, peptic ulcerations, serum calcium abnormalities

  22. Carcinoid tumours • Symptoms • Endocrinologically inactive • Cough, haemoptysis, pulmonary infections, chest pain, pain from direct compression of the liver from mets • Endocrinologically-active • Hormonal : flushing, diarrhoea, hypotension, light-headedness, bronchospasm, HF, abdominal cramping, peripheral oedema, heart palpitations • Ex: HF, Hepatomegaly, cushing’s syndrome, acromegaly, chronic skin changes • precipitants : emotional stress, alcohol, exercise, eating, vigorous palpation of liver with mets

  23. Investigations • Bloods • 24h Urine 5-HIAA (>9mg/24h) • Chromogranin A • Imaging

  24. Anaesthesia • increased risk of flushing, bronchospasm and hypotension during surgery • minimise use of adrenergics and hypotensives [morphine, curare] • pre-op : octreotide 100mg SC tds 2/52 prior • peri-op : octreotide IV 50mcg/h prior to anaesthesia, increase if hypotensive • post-op : taper over 1/52

  25. Management • Symptomatic • Localised • Metastatic • Palliative

  26. Symptomatic Mx • Somatostatin analogs • decrease production of 5-HIAA • ameliorate symptoms in 90% of patients • tumouristatic with increase in PFS • Octreotide is able to induce an earlier reduction in IGF-1 levels and more marked reduction in GH levels cf. lanreotide • However, lanreotide dosing schedule does not require induction with daily octreotide (Short-acting) 14d prior to starting on octreotide LAR • recommend octreotide for ST pre-surgical treatment • recommend lanreotide for chronic therapy to boost compliance

  27. Symptomatic Mx • IFNα • better efficacy than somatostatin analogs • more acceptable SE profile

  28. Symptomatic Mx • Hypotension - mediated by kinins, PG, catecholamines • Avoid β-adrenergics; α-adrenergics & vasoconstrictive agents are preferred [methaoxamine / angiotensin] • +/- corticosteroids for hypotension prevention • Flushing -mediated kinins & histamines • Prochloperazine, phenoxybenazmine, prednisone, benadryl + tagament, methyldopa • Avoid MAO-I

  29. Symptom management • Bronchospasm - mediated by histamine : aminophylline • Diarrhoea - mediated by serotonin : imodium, lomotil, zofran, cyproheptadine • Bowel obstruction - NGT + IV therapy • Pellagra - daily niacin • Right Ventricular failure - avoid valve replacement. manage with diuretics, refer

  30. Localised disease • Surgery remains the mainstay of treatment for cure and increase in overall survival with debulking • Partial Hepatectomy may be performed if liver mets are confined to an area of the liver

  31. Chemotherapy • In general NETS do not show high degree of sensitivity to chemotherapy • low mitotic rates • presence of high levels of bcl-2 • increased expression of multi-drug resistance gene • Response rate <30% • Applicable situations include • aggressive disease • high proliferation rates • aggressive pancreatic NETS - chemosensitive with RR ~40-70%

  32. Metastatic Disease • Pancreatic NET • Typical : Streptozocin-based chemotherapy, Everolimus, Sunitinib • Everolimus + octreotide LAR showed a 5mth delay in tumour progression c.f. octreotide alone • Atypical - As with GI-NET

  33. Streptozocin • Single agent chemotherapy has insignificant RR <10% • STZ has shown to have a better survival outcome for unresectable pancreatic NETS • In combination with 5FU / Adriamycin, RR increased drastically • STZ + FU : RR 45% • STZ + Doxorubicin : RR 69%, PFS 20mths (vs. 6.9) , oS 2.2 yrs (vs. 1.4); more drug-related toxicitiies

  34. Metstatic Disease • GI-NET • cisplatin + etoposide • more signficant nausea, neurotoxicity and nephrotoxicity • carboplatin + etoposide • more significant haematological toxicities • used for patients with poor renal function

  35. Cisplatin + Etoposide • 67% of patients with poorly differentiated NETS achieved overall regression of the tumour • median survival of 19mths • No significant benefit seen in well-differentiated tumours • Carboplatin often substituted in place of cisplatin due to nephrotoxicity

  36. Metastatic Disease • High response rate to cisplatin + etoposide for patients with high grade NET of colon and rectum • Marginal anti-tumor activitiy and relatively severe toxicity for hepatobiliary or pancreatic poorly differentiated neuroendocrine carcinoma

  37. Metastatic Disease • IV Radionuclide therapy • Lutetium-177 Octreotate radiopeptide therapy • Patient selection • sufficient uptake of 111In-Octreotide or 68Ga-labelled somatostatin analogues • disseminated, hitopathologically proven relatively well-differentiated NET • Ki67 score <10% • unresectable disease

  38. Metastatic Disease • IV Radionuclide therapy • more effective as an early stage disease progression • chemotherapy is not a pre-requisite for radiopeptide therapy • cease LAR octreotide 6/52 prior to increase receptivity to radiopeptide therapy. short-acting octreotide may be used for symptomatic control in patients with debilitating symptoms

  39. Metastatic Disease • Hepatic artery chemoembolization

  40. Metastatic Disease • IV Radionuclide Therapy • 4 cycles with intervals of 6-8 weeks • response determined at 6/12 post-completion • metabolic response - comparative 177Lu-octreotate timor uptake on 24h scintiscancs post-therapy administration • objective response - CT/MRI studies @ 3-6mth intervals • biochemical response - serial chromograinin A titre, + urinary 5-HIAA levels • Symptomatic response • AE

  41. Palliative • Hepatic Artery embolisation • palliate endocrine symptoms / pain • regression of symptoms in 4/12 in 60% of patients • tumour shrinkage up to 80% • SE: pyrexia, nausea, LFT abnormalities • improved duration of response when used in conduction with chemotherapy

  42. Palliative • RT • carcinoids are relatively radio resistant - not a means of cure • mainly used for palliate e.g. bone mets

  43. Future • Bevacizumab • carcinoids tend to be highly vascularised • shown a rapid and sustained decrease in tumour blood flow with disease stabilisation / partial response achieved when used in conjunction with octreotide [c.f. IFNα + octreotide] • need ongoing trials prior to approval

  44. References • [1] Ducreux m, Baudin E, Schlumberger M. Treatment strategy of neuroendocrine tumours (review). Revue du Practicin. 2002 Feb 1; 52(3):290-6. • [2] Rougier P, Mitry E. Chemotherapy in the treatment of neuroendocrine malignant tumours (review). Digestion. 2000; 62 Suppl 1:73-8. • [3] Kosmidis PA. Treatment of carcinoid of the lung. Current Opinion in Oncology. 2004 Mar; 16(2):146-9. • [4] Strosberg JR, Nasir A, Hodul P, Kwols L. Biology and treatment of metastatic gastrointestinal neuroendocrine tumours. Gastrointestinal Cancer Research. 2007 Dec 14; 2(3):113-125. • [5] Basu Bristi, Sirohi Bhawna, Corrie P. Systemic therapy for neuroendocrine tumors of gastroenteropancreatic origin. Endocrine-related cancer. 2010; 17:75-90. • [6] National Cancer Institute. Treatment for advanced carcinoid tumours [Internet]. USA: Yao J; 2008 [updated 2008 Jun 24; cited 2014 Mar 4]. Available from : http://www.cancer.gov/clinicaltrials/featured/trials/swog-s0518 • [7] National Cancer Institute. MD anderson study find everolimus prolongs progression-free survival for patients with neuroendocrine tumours [Internet]. USA: NCI Cancer Center News; 2011 [updated 2011 Nov 30; cited 2014 Mar 4]. Available from : http://www.cancer.gov/newscenter/cancerresearchnews/2011/MDAndersonEverolimusStudy • [8] Demirkan BH, Eriksson b. Systemic treatment of neuroendocrine tumours with hepatic metastases (Review). Turkish Journal of Gastroenterology. 2012; 23(5) : 427-37. • [9] Razzore P, Colao A, Baldelli R, Gaia D, Marzullo P, Ferretti E et al. Comparison of six months therapy with octreotide versus lanreotide in acromegalic patients: a retrospective study. Clinical Endocrinology. 1999 Aug; 51(2):159-164. • [10] Clinical Oncological Society of Australia. Guidelines for the diagnosis and management of gastroenteropancreatic neuroendocrine tumours (GEP NETs) [Internet]. Australia: COSA; 2010 [updated Nov 2010; cited 2014 Mar 4]. Available from: http://wiki.cancer.org.au/australia/COSA:NETs_guidelines/Radionuclide_Therapy • [11] Casciato DA, Territo MC, editors. Manual of clinical oncology. 7th ed. Philadelphia, USA: Lippincott Williams & Wilkins. 2012. Chapter 15, Endocrine Neoplasm.; p. 408-414.

More Related