Pancreatic%20Neuroendocrine%20Neoplasm%20(pNEN)%20case

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Pancreatic Neuroendocrine Neoplasm (pNEN) case

• Case Presentation
• Dr. Chatzellis Eleftherios MDIntern in
  Endocrinology

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Case History - 2001

• 58 year old male patient
• 2001 abdominal pain
• CT scan 5cm tumor pancreatic tail
• Multiple focal lesions in the liver
• FNAB (liver lesion) ? Well Differentiated NEN
• grade 2 (ki67 4)
• CgA 5,2 nmol/l (lt4), other markers negative
• No secretory symptoms (non-functioning pNEN)
• SRS (Octreoscan) avid uptake (Krenning score
  3) in both primary pNEN and liver metastases

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Case History
HE stain
ki67
Chromogranin A
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Case History 2001-2005

• Sweden (Uppsala) ? Suggested surgery to reduce
  tumor burden and local complications
• Patient refused
• Chemotherapy (Streptozotocin 5-FU)
  Somatostatin analogues (SSAs)
• 1 year later (2002) DISEASE PROGRESSION (PD)
• Addition of pegylated INF-a
• Chemotherapy was discontinued after 2,5 years
  (mild renal impairment)
• 2002-2005 STABLE DISEASE (SD)
• CgA 10,5 nmol/l (lt4)

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Case History 2006-2008

• 2006 Hypercalcemia occurred for the first time
• Ca 11,8 mg/dl (8,5 - 10,1)
• P 1,98 mg/dl (2,5 - 4,5)
• PTH 2,54 pg/ml (10 - 65)
• PTHrP 84 pmol/l (lt2)
• CgA 45 nmol/l (lt4)
• Imaging DISEASE PROGRESSION (PD)
• Increased SSAs dosage peg-INFa
• Normalization Ca
• 2006-2008 STABLE DISEASE (SD) - Biochemical
  control

Humoral Malignancy-associated Hypercalcemia (PTHrP
- related)
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Case History 2008-2009

• 2008 peg-INFa discontinued (depression)
• 2008 Hypercalcemia (12,9 mg/dl)
• DISEASE PROGRESSION (PD)
• 2008-2009 177Lu-DOTATATE x5 cycles (25.6 GBq)
• Increased SSAs dosage
• Addition of pasireotide 1200µg bid
• ?Ca 10,7 mg/dl, CgA115 nmol/l, PTHrP140
  pmol/l
• 2009 DISEASE PROGRESSION (PD)
• biochemical relapse (Ca 11,8 mg/dl)

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Case History 2009-2010

• Temozolomide Capecitabine (CAP-TEM)
• 2009-2010 STABLE DISEASE (SD)
• Biochemical control of Ca required additional
  treatment
• SOM230 and SSAs
• Forced Diuresis
• Prednisolone 40mg/d
• Biphosphonates (i.v. zolendronate 4mg monthly)
• Cinacalcet 90mg/d
• SIDE-EFFECTS Proximal myopathy - muscle atrophy,
  patient immobilization (wheel chair), severe
  Diabetes Mellitus (100 IU insulin/d)

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Case History 2010

• Tumor burden reduction (cytoreduction) necessary
• Biochemical control (Ca)
• Reduce treatment side-effects
• OPTIONS
• Surgery Patient still denied
• PRRT Already performed (GFR, marrow toxicity)
• RF Ablation Not applicable due to large liver
  lesions
• Embolization (TAE/TACE)
• Pre-embolization evaluation Portal vein
  thrombosis
• Selective approach (embolization of small
  branches of hepatic artery)

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Case History - TAE
Post-embolization
Pre-embolization
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Post-embolization status
Case History - TAE

• TMZ Capecitabine
• SSAs
• Pasireotide 1200mcg/d
• Prednisolone 40 mg/d
• Zolendronate 4mg/m
• Insulin treatment

• TMZ Capecitabine
• SSAs at ½ dosage
• X
• Prednisolone 8 mg/d
• X
• X

• Ca 10,2 mg/dl
• CgA 50 nmol/l
• PTHrP 38 pmol/l

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Case History 2010

• 6 months after TAE
• Ca 13,2 mg/dl
• DISEASE PROGRESSION (PD)
• Painful lump on left thigh

T2
T1
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Case History 2010
Bone scintigraphy Tc 99m
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Case History 2010

• BONE METASTASES vs BENIGN LESION
• Bone Biopsy ? Brown tumor (in the context of
  prolonged PTHrP action on bone)
• New liver lesion biopsy ? ki67 4, IHC () for
  PTHrP

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Case History 2010-2012

• Temozolomide (200mg/m2 Days 1-5 q4w)
  Bevacizumab (10 mg/kg q2w) Everolimus (10mg/d)
• SSAs
• Ca 8,8 mg/dl
• Temozolomide and Bevacizumab D/C after 6 months
  due to thrombocytopenia
• 2010-2012 STABLE DISEASE (SD)

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Case History 2012-2014

• 2012 DISEASE PROGRESSION (PD)
• Ca9,34 mg/dl, PTHrP 50 pmol/l
• Sunitinib 37,5 mg/d SSAs
• 6 months later Ca 6,5 mg/dl !!!
• 2012-2014 STABLE DISEASE (SD)

April 2014 Patient deceased (hepatic
encephalopathy - malnutrition)
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Pegylated INFa
Pasireotide
BEV-TEM
STZ 5FU
Everolimus
Sunitinib
PRRT
CAP-TEM
SSAs
Embolization

Ca
CgA
PTHrP
2006
2006
2009
2009
2009
2010
2012
2012
2014
2005
2001
2008
2010
2010
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Case synopsis

• WD pNEN grade 2 Stage IV (liver metastases)
• Change of functional status during disease course
• Rare PTHrP secretion (paraneoplastic syndrome)
• Even more rare brown tumor due to PTHrP
• Employment of several treatment agents/modalities
  to achieve both tumoral and biochemical control
• Importance of cytoreductive interventions and
  novel molecular targeted therapies in controlling
  secretory symptoms/syndrome
• Long survival despite metastatic disease at
  presentation (application of different
  therapeutic modalities)

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Improving Survival of NET patients
James Yao, ENETS 2014
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