Transcript Week 6 Case Presentation - Oncology Clinics Victoria

Week 6 Case
Presentation
Neuroendocrine Malignancy
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)
HOPC
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Feb 2010
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Worsening non-productive cough over a few months
associated with LOW of 20kg over 4 mths, worsening
dyspnoea and LOA.
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Nil chest pain, haemoptysis, fever / flushing, NS,
chills/shakes, lumps felt, change in bowel or urinary
habits
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Sought medical assistance in Feb 2010
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CT scan arranged - highly vascularised lesion in the left
lower lobe.
PMHx
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AC joint dissection in 2012
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IVF x 4C in 2004
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GORD
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Sinusitis
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NKDA
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Nil regular meds previously
FHx
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No significant history of cancer in the family
Social Hx
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Avid cook, ensures well-balanced meals
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Good social support
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Nil financial issues, on private insurance
Plan
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Referred for bronchoscopy
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Histopathology consistent with a bronchial carcinoid tumour
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Urinary 5-HIAA : 110 H
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HRCT scan - highly vascularised, non-spiculated mass in the left lower lobe. 4.4 x 3.2 x
5 cm. 2 small left posteroinferior
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Dx: Bronchial carcinoid tumour AJCC Stage I/B (T2 N1 M0)
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Referred to surgeon for VATS minimally invasive thorascopically assisted left lower
lobectomy
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Nuclear medicine octreotide study - Normal
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Refer to Medonc for further management
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commence on Somatulin (Lanreotide) 120mg
F/up
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Urinary 5-HIAA
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13/2/11 : 186; 11/8/11: 372H
Chromogranin A increased
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25/10/12 : 121 ; 9/5/13 : 158
Mets
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18 Jun 2012
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P/W worsening (L) hip pain during routine r/v
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XR showed radiolucent area in (L) acetabular region
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whole body bone scan performed subsequently - mets to (L) hip
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Repeat urinary 5-HIAA and chromagranin - both elevated
Plan :
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RT + Commence on Zometa + continue on Somatulin
Mets
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15 Feb 2013
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c/o tenderness over skull and (L) shoulder
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CT brain, skull, chest - multiple liver mets
Plan
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Liver Biopsy - consistent with mets from bronchial carcinoid tumour
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LFTs - normal
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Refer for IV radionuclide therapy @ Peter Macallum- require PET octreoscan
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Mets in liver
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pagetic changes detected in left clavicle and ilium
Mets
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FDG PET/CT & GaTate Functional Imaging performed
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Ki-67 <5%
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low somatostatin expression at sites of disease in
abdomen and pelvis - more de-differentiated disease
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ineligible for IV radionuclide therapy - recommend
commencement of IV ChemoRx
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Recommend cessation of Somatulin due to low
somatostatin expression
Chemotherapy
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Commenced of 6C CBDCA / Etoposide
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Experienced recurrent anaemia requiring multiple transfusions postchemo, profound fatigue, anorexia, n/v, cancer-related pain and
multiple episodes of neutropaenia requiring admissions
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Developed depression - commence on mirtazapine; referral to
psycho-oncologist
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ChemoRx was poorly tolerated - only 5C were completed
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MRI showed stable disease as of 27/8/13
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Commence of monthly Zometa (Zoledronic Acid)
CEA levels
Current issues
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Moderate fatigue - unable to work but ADLs remain
relatively good
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Social isolation
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Residual (L) shoulder pain - commence on Lyrica
(pregabalin)
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Depression - mirtazapine 60mg
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Poor appetite - commence on dexamethasone 4mg for
motivation / energy / appetite
Current Medications
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Lyrica 75mg - neuropathic pain
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Magmin 500mg
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Avanza 60mg - depression
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Dexamethasone 4mg
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Durogesic patch 25mcg/h
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Endone 5mg
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Seretide Accuhaler
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Zometa
Neuroendocrine
Tumours
Introduction
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neoplasms that arise from the cells of the endocrine and nervous
system
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Classification : well-differentiated, low grade malignancy, high grade
malignancy
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Types
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GEP-NETs - 2/3 of all GEP-NETs carcinoid, 1/3 PNET
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Lung (SCLC, carcinoid, LCNEC)
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Pituitary, Thymus, Parathyroid, Thyroid, EPSCC, adrenal,
phaeochromocytomas, peripheral nervous system, breast, GU tract
Introduction
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Expresses unique syndromes & biochemical markers
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Steroids - usually by adrenal cortex / gonads
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Peptide hormones & catecholamines
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APUD - 5HT, NA/Adr, Histamines, Kinins
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Peptide hormones
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GI hormones
MEN syndrome
MEN Syndromes
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MEN1 [TSG @ 11q13]
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pituitary tumours + pancreatic islet cell tumours + parathyroid
tumours
MEN 2 [ret oncogene @ 10q11]
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MEN2A - medullary CA of thyroid + Bilateral phaeochromocytoma +
parathyroid hyperplasia / adenoma
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MEN 2B - medullary CA of thyroid + bilateral phaeochromocytoma +
multiple mucosal ganglioneuromas
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Cushing syndrome may develop as a consequence of ectopic ACTH
production
Carcinoid Tumours
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<1% of all tumours
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may be in association with MEN1
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Primary tumour usually an APUD - small, commonly located in the
small intestine but may also be found in stomach / colorectal / lung /
ovary
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Mets
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liver mets are common; may result in liver failure with replacement
of functional liver tissue with tumour
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bone mets are usually osteoblastic
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desmoplastic response - mesenteric fibrosis causing bowel
obstruction
Carcinoid tumours
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30-50% of tumours are hormonally-active carcinoid syndrome
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Rare without liver mets [unless ovarian]
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usually associated with malignancy
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may exhibit niacin deficiencies, acromegaly,
Cushing’s syndrome, peptic ulcerations, serum
calcium abnormalities
Carcinoid tumours
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Symptoms
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Endocrinologically inactive
•
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Cough, haemoptysis, pulmonary infections, chest pain, pain from direct
compression of the liver from mets
Endocrinologically-active
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Hormonal : flushing, diarrhoea, hypotension, light-headedness, bronchospasm, HF,
abdominal cramping, peripheral oedema, heart palpitations
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Ex: HF, Hepatomegaly, cushing’s syndrome, acromegaly, chronic skin changes
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precipitants : emotional stress, alcohol, exercise, eating, vigorous palpation of liver
with mets
Investigations
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Bloods
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24h Urine 5-HIAA (>9mg/24h)
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Chromogranin A
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Imaging
Anaesthesia
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increased risk of flushing, bronchospasm and
hypotension during surgery
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minimise use of adrenergics and hypotensives
[morphine, curare]
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pre-op : octreotide 100mg SC tds 2/52 prior
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peri-op : octreotide IV 50mcg/h prior to anaesthesia,
increase if hypotensive
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post-op : taper over 1/52
Management
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Symptomatic
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Localised
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Metastatic
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Palliative
Symptomatic Mx
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Somatostatin analogs
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decrease production of 5-HIAA
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ameliorate symptoms in 90% of patients
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tumouristatic with increase in PFS
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Octreotide is able to induce an earlier reduction in IGF-1 levels and more marked
reduction in GH levels cf. lanreotide
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However, lanreotide dosing schedule does not require induction with daily octreotide
(Short-acting) 14d prior to starting on octreotide LAR
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recommend octreotide for ST pre-surgical treatment
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recommend lanreotide for chronic therapy to boost compliance
Symptomatic Mx
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IFNα
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better efficacy than somatostatin analogs
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more acceptable SE profile
Symptomatic Mx
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Hypotension - mediated by kinins, PG, catecholamines
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Avoid β-adrenergics; α-adrenergics & vasoconstrictive
agents are preferred [methaoxamine / angiotensin]
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+/- corticosteroids for hypotension prevention
Flushing -mediated kinins & histamines
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Prochloperazine, phenoxybenazmine, prednisone,
benadryl + tagament, methyldopa
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Avoid MAO-I
Symptom management
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Bronchospasm - mediated by histamine : aminophylline
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Diarrhoea - mediated by serotonin : imodium, lomotil,
zofran, cyproheptadine
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Bowel obstruction - NGT + IV therapy
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Pellagra - daily niacin
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Right Ventricular failure - avoid valve replacement.
manage with diuretics, refer
Localised disease
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Surgery remains the mainstay of treatment for
cure and increase in overall survival with
debulking
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Partial Hepatectomy may be performed if liver
mets are confined to an area of the liver
Chemotherapy
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In general NETS do not show high degree of sensitivity to chemotherapy
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low mitotic rates
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presence of high levels of bcl-2
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increased expression of multi-drug resistance gene
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Response rate <30%
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Applicable situations include
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aggressive disease
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high proliferation rates
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aggressive pancreatic NETS - chemosensitive with RR ~40-70%
Metastatic Disease
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Pancreatic NET
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Typical : Streptozocin-based chemotherapy,
Everolimus, Sunitinib
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Everolimus + octreotide LAR showed a 5mth
delay in tumour progression c.f. octreotide
alone
Atypical - As with GI-NET
Streptozocin
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Single agent chemotherapy has insignificant RR <10%
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STZ has shown to have a better survival outcome for
unresectable pancreatic NETS
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In combination with 5FU / Adriamycin, RR increased
drastically
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STZ + FU : RR 45%
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STZ + Doxorubicin : RR 69%, PFS 20mths (vs. 6.9) ,
oS 2.2 yrs (vs. 1.4); more drug-related toxicitiies
Metstatic Disease
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GI-NET
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cisplatin + etoposide
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more signficant nausea, neurotoxicity and
nephrotoxicity
carboplatin + etoposide
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more significant haematological toxicities
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used for patients with poor renal function
Cisplatin + Etoposide
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67% of patients with poorly differentiated NETS
achieved overall regression of the tumour
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median survival of 19mths
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No significant benefit seen in well-differentiated
tumours
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Carboplatin often substituted in place of cisplatin
due to nephrotoxicity
Metastatic Disease
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High response rate to cisplatin + etoposide for
patients with high grade NET of colon and rectum
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Marginal anti-tumor activitiy and relatively severe
toxicity for hepatobiliary or pancreatic poorly
differentiated neuroendocrine carcinoma
Metastatic Disease
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IV Radionuclide therapy
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Lutetium-177 Octreotate radiopeptide therapy
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Patient selection
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sufficient uptake of 111In-Octreotide or 68Ga-labelled somatostatin
analogues
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disseminated, hitopathologically proven relatively welldifferentiated NET
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Ki67 score <10%
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unresectable disease
Metastatic Disease
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IV Radionuclide therapy
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more effective as an early stage disease progression
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chemotherapy is not a pre-requisite for radiopeptide
therapy
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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
Metastatic Disease
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Hepatic artery chemoembolization
Metastatic Disease
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IV Radionuclide Therapy
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4 cycles with intervals of 6-8 weeks
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response determined at 6/12 post-completion
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metabolic response - comparative 177Lu-octreotate timor uptake on 24h
scintiscancs post-therapy administration
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objective response - CT/MRI studies @ 3-6mth intervals
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biochemical response - serial chromograinin A titre, + urinary 5-HIAA levels
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Symptomatic response
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AE
Palliative
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Hepatic Artery embolisation
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palliate endocrine symptoms / pain
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regression of symptoms in 4/12 in 60% of patients
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tumour shrinkage up to 80%
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SE: pyrexia, nausea, LFT abnormalities
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improved duration of response when used in
conduction with chemotherapy
Palliative
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RT
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carcinoids are relatively radio resistant - not a
means of cure
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mainly used for palliate e.g. bone mets
Future
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Bevacizumab
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carcinoids tend to be highly vascularised
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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]
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need ongoing trials prior to approval
References
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[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.
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[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.
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[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.
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[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
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[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.