An Institutional Approach to
Neuroendocrine Carcinoma
Mark Bloomston, M.D.
Associate Professor of Surgery
Division of Surg...
• No disclosures
“Definitions”
• Islet cell carcinoma – NEC of pancreas
– Nonfunctioning, insulinoma, gastrinoma,
glucagonoma, VIPoma
• Car...
Carcinoid
• Is a true cancer
• ~12,000 new cases per year
• Slow growing
• Long-term survival common, even with
metastatic...
Carcinoid Symptoms
• Primary tumor
– Pain, bowel obstruction, jaundice
• Metastases
– Non-hormonal: Pain, fatigue, weight ...
Metastatic Carcinoid
• Liver most common distant organ
– Can result in liver dysfunction
• Often results in symptoms
• Oft...
Management of Liver Metastases
• Local Therapies
– Surgical resection
– Ablation
• Regional Therapies
– Chemoembolization
– Bland embolization
– Selectiv...
Chemoembolization
• a.k.a. Transarterial Chemoembo (TACE)
• a.k.a. Hepatic Artery Chemoembo (HACE)
• Done in radiology sui...
TACE
• Pros
– Can treat multiple tumors at once
– Low complication and mortality rates
– Minimally invasive
• Cons
– Diffi...
J Gastrointest Surg 2007;11:264-71
• Retrospective review of 122 patients
– 1992 – 2004
• All patients considered “inopera...
TACE – OSU Experience
• Retrospective review of 122 patients
– 1992 – 2004
• All patients considered inoperable
• Indicati...
TACE – OSU Experience
• Whole liver favored (75%)
• Complications 23%
• Mortality 5%
• CT response = 82%
– Median TTP = 19...
Overall Survival
• Median – 33.3 m
• 2-year – 58%
• 5-year – 28%
• 10-year – 8%
J Gastrointest Surg 2007;11:264-71
TACE – Current Practice
• Rarely do whole liver
• TACE team established
• Early discharge
• Close follow-up
• Multidiscipl...
Surgical Resection
• Only potential cure
• Cytoreduction or debulking
– Requires removal of at least 90% of tumor
– Effect...
Cytoreductive Hepatectomy
Author Year N Therapy Results
Chamberlain et al 2000 85 Medical vs HAE vs
Hepatectomy
Improved O...
Osborne et al. Ann Surg Oncol 2006
Survival Advantage after Transarterial
Chemoembolization for Operable
Metastatic Carcinoid Reflects Tumor
Biology Rather t...
Hypothesis
• Following TACE, patients with disease
amenable to cytoreductive hepatectomy
would have better:
• Tumor respon...
Methods
• TACE was undertaken in 200 consecutive
patients with NET metastases to the liver
– 98 had pre-TACE imaging avail...
Methods
• Pre-TACE imaging re-assessed for
operability
Potentially Resectable (N=28) Inoperable (N=70)
Results
Potentially resectable Inoperable P
Primary resected 20 (71%) 27 (38%) <0.05
Carcinoid Syndrome 26 (92%) 51 (73%) ...
Results
• No difference between groups for:
– Complications (10%)
– Mortality (3%)
– Length of Stay (5 days ± 3.6)
Overall Survival
Potentially
Resectable
Inoperable
Median 62 months 21 months
2-yr 89% 46%
5-yr 53% 19%
Progression Free Survival
Potentially
Resectable
Inoperable
Median 22 months 13 months
2-yr 50% 27%
5-yr 9% 8%
Response Potentially Resectable Inoperable P
Radiographic 21/28 (75%) 56/64 (87%) 0.21
Median Duration 86 weeks 75 weeks 0...
Conclusions
• Liver metastases from NET amenable to
cytoreductive hepatectomy represent better
tumor biology
• TACE does n...
Management of the Metastatic
Neuroendocrine Primary
Background
• Primary often occult
• Resection of primary may be morbid
• Improved outcome reported with removal
of primary
J Gastrointest Surg 2006;10:1361
J Gastrointest Surg 2006;10:1361
Mortality: R2 > R0/1 (21% vs. 2%, p=0.009)
Conclusions
• Long-term survival possible with complete
resection of neuroendocrine tumors of the
pancreas
– 5 year surviv...
Expectant Management of the
Asymptomatic Primary is Safe in
Patients Undergoing
Chemoembolization for Metastatic
Neuroendo...
Purpose
• To determine the fate of asymptomatic
primary neuroendocrine tumors not
resected in patients undergoing TACE
Referred for TACE
N=197
Primary gone
N=97
Primary intact
N=100
Asymptomatic primary
N=93
Symptomatic primary
N=7
Developed...
Results
• Only 4% of primaries became
symptomatic during f/u (median 35.6m)
• No deaths due to primaries or removal
Overall Survival
• Primary resected in 89 evaluable patients
– 57 with symptoms
– 42 without symptoms
Conclusions
• Asymptomatic primaries rarely require removal
in patients undergoing TACE
• Delayed removal of primary does ...
Institutional Approach
• Where should consultation be sought?
– High volume center with experience in NEC
• Who should man...
Institutional Approach
• Should primary be removed?
– If symptomatic or threatening
– Not mandatory
• Treatment for liver ...
NET Clinic
• Medical Oncology
– Manisha Shah
– Tanios Bekaii-Saab
– Jeffrey Rose
• Surgical Oncology
– E. Christopher Elli...
Regional Therapy for Metastatic Neuroendocrine Carcinoma
Regional Therapy for Metastatic Neuroendocrine Carcinoma
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Regional Therapy for Metastatic Neuroendocrine Carcinoma

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Regional Therapy for Metastatic Neuroendocrine Carcinoma

  1. 1. An Institutional Approach to Neuroendocrine Carcinoma Mark Bloomston, M.D. Associate Professor of Surgery Division of Surgical Oncology The Ohio State University
  2. 2. • No disclosures
  3. 3. “Definitions” • Islet cell carcinoma – NEC of pancreas – Nonfunctioning, insulinoma, gastrinoma, glucagonoma, VIPoma • Carcinoid – well differentiated NEC • Atypical carcinoid – moderately diff NEC • Small cell carcinoma – poorly diff NEC
  4. 4. Carcinoid • Is a true cancer • ~12,000 new cases per year • Slow growing • Long-term survival common, even with metastatic disease • Management of symptoms is paramount
  5. 5. Carcinoid Symptoms • Primary tumor – Pain, bowel obstruction, jaundice • Metastases – Non-hormonal: Pain, fatigue, weight loss – Hormonal: carcinoid syndrome, valve disease
  6. 6. Metastatic Carcinoid • Liver most common distant organ – Can result in liver dysfunction • Often results in symptoms • Often incurable • Long-term survival still possible
  7. 7. Management of Liver Metastases
  8. 8. • Local Therapies – Surgical resection – Ablation • Regional Therapies – Chemoembolization – Bland embolization – Selective internal radiotherapy • Systemic Therapies – Chemotherapy
  9. 9. Chemoembolization • a.k.a. Transarterial Chemoembo (TACE) • a.k.a. Hepatic Artery Chemoembo (HACE) • Done in radiology suite • Cocktail of chemo, oil, contrast – Mitomycin C, cisplatin, doxorubicin • Embolization particles
  10. 10. TACE • Pros – Can treat multiple tumors at once – Low complication and mortality rates – Minimally invasive • Cons – Difficult recovery – Unpredictable drug distribution – Makes future surgery difficult
  11. 11. J Gastrointest Surg 2007;11:264-71 • Retrospective review of 122 patients – 1992 – 2004 • All patients considered “inoperable” • Indications: – Liver tumor progression – Poorly controlled symptoms – Large tumor burden in liver
  12. 12. TACE – OSU Experience • Retrospective review of 122 patients – 1992 – 2004 • All patients considered inoperable • Indications: – Liver tumor progression – Poorly controlled symptoms – Large tumor burden in liver Bloomston et al., J Gastrointest Surg 2007,11(3)
  13. 13. TACE – OSU Experience • Whole liver favored (75%) • Complications 23% • Mortality 5% • CT response = 82% – Median TTP = 19 months • Serologic response (pancreastatin) = 80% – Median TTP = 7 months • Symptom response = 92% – Median TTP = 13 months Bloomston et al., J Gastrointest Surg 2007,11(3)
  14. 14. Overall Survival • Median – 33.3 m • 2-year – 58% • 5-year – 28% • 10-year – 8% J Gastrointest Surg 2007;11:264-71
  15. 15. TACE – Current Practice • Rarely do whole liver • TACE team established • Early discharge • Close follow-up • Multidisciplinary planning
  16. 16. Surgical Resection • Only potential cure • Cytoreduction or debulking – Requires removal of at least 90% of tumor – Effective palliation in nearly 90% – Durable palliation of nearly 2 years – May improve survival • Up to 80% of liver can be removed in healthy patients
  17. 17. Cytoreductive Hepatectomy Author Year N Therapy Results Chamberlain et al 2000 85 Medical vs HAE vs Hepatectomy Improved OS with hepatectomy Yao et al 2001 36 TACE vs Hepatectomy Improved OS with hepatectomy Osborne et al 2006 120 TACE vs Hepatectomy Improved OS and symptom control with hepatectomy Gomez et al 2007 18 Surgical resection Prolonged symptom control and OS
  18. 18. Osborne et al. Ann Surg Oncol 2006
  19. 19. Survival Advantage after Transarterial Chemoembolization for Operable Metastatic Carcinoid Reflects Tumor Biology Rather than Efficacy Arrese D, Feria-Arias E, Hatzaras I, Guy G, Khabiri H, Schmidt C, Shah M, Bloomston M The Ohio State University Columbus, Ohio Presented at ACS Clinical Congress 2010
  20. 20. Hypothesis • Following TACE, patients with disease amenable to cytoreductive hepatectomy would have better: • Tumor response • Symptom control • Overall Survival
  21. 21. Methods • TACE was undertaken in 200 consecutive patients with NET metastases to the liver – 98 had pre-TACE imaging available for review • Indications for TACE: – poor symptom control – liver tumor progression – large tumor burden
  22. 22. Methods • Pre-TACE imaging re-assessed for operability Potentially Resectable (N=28) Inoperable (N=70)
  23. 23. Results Potentially resectable Inoperable P Primary resected 20 (71%) 27 (38%) <0.05 Carcinoid Syndrome 26 (92%) 51 (73%) 0.03 Mean pre-TACE pancreastatin 5,186 pg/mL (Range 84-35,700) 10,158 pg/mL Range (96-48,200) 0.06 Mean # of liver segments involved 4.45 ± 1.68 7.14 ± 0.98 <0.05 Proportion of liver involved 16% Range (5-60) 41 % Range (5-95) <0.05
  24. 24. Results • No difference between groups for: – Complications (10%) – Mortality (3%) – Length of Stay (5 days ± 3.6)
  25. 25. Overall Survival Potentially Resectable Inoperable Median 62 months 21 months 2-yr 89% 46% 5-yr 53% 19%
  26. 26. Progression Free Survival Potentially Resectable Inoperable Median 22 months 13 months 2-yr 50% 27% 5-yr 9% 8%
  27. 27. Response Potentially Resectable Inoperable P Radiographic 21/28 (75%) 56/64 (87%) 0.21 Median Duration 86 weeks 75 weeks 0.09 Symptom 19/26 (73%) 41/51 (80%) 0.5 Median Duration 13.6 weeks 12.2 weeks 0.82 Biochemical 22/25 (88%) 53/56 (94%) 1 Median Duration 20 weeks 14.2 weeks 0.81 Response to TACE
  28. 28. Conclusions • Liver metastases from NET amenable to cytoreductive hepatectomy represent better tumor biology • TACE does not result in superior outcomes in these favorable patients • We support a multi-institutional trial comparing outcomes in TACE vs. surgical cytoreduction
  29. 29. Management of the Metastatic Neuroendocrine Primary
  30. 30. Background • Primary often occult • Resection of primary may be morbid • Improved outcome reported with removal of primary
  31. 31. J Gastrointest Surg 2006;10:1361
  32. 32. J Gastrointest Surg 2006;10:1361 Mortality: R2 > R0/1 (21% vs. 2%, p=0.009)
  33. 33. Conclusions • Long-term survival possible with complete resection of neuroendocrine tumors of the pancreas – 5 year survival 74% with R0 resection • Palliative/debulking pancreatectomy requires extensive resection resulting in substantial morbidity and mortality – Should be approached cautiously J Gastrointest Surg 2006;10:1361
  34. 34. Expectant Management of the Asymptomatic Primary is Safe in Patients Undergoing Chemoembolization for Metastatic Neuroendocrine Carcinoma Tassone, Patrick; Arrese, David; Klemanski, Dori; Shah, Manisha; Schmidt, Carl; Abdel-Misih, Sherif; and Bloomston, Mark Submitted to Society of Surgical Oncology 2011 Cancer Symposium
  35. 35. Purpose • To determine the fate of asymptomatic primary neuroendocrine tumors not resected in patients undergoing TACE
  36. 36. Referred for TACE N=197 Primary gone N=97 Primary intact N=100 Asymptomatic primary N=93 Symptomatic primary N=7 Developed Symptoms N=4 (4%) No Symptoms Developed Median f/u 35.6m N=89 (96%) Primary Resected after TACE N=6 (6%)
  37. 37. Results • Only 4% of primaries became symptomatic during f/u (median 35.6m) • No deaths due to primaries or removal
  38. 38. Overall Survival • Primary resected in 89 evaluable patients – 57 with symptoms – 42 without symptoms
  39. 39. Conclusions • Asymptomatic primaries rarely require removal in patients undergoing TACE • Delayed removal of primary does not increase morbidity or mortality • Removal of asymptomatic primary does not improve survival compared to waiting for symptoms to occur
  40. 40. Institutional Approach • Where should consultation be sought? – High volume center with experience in NEC • Who should manage treatment? – Multidisciplinary team led by an experienced clinician with knowledge of treatment options and clinical trials
  41. 41. Institutional Approach • Should primary be removed? – If symptomatic or threatening – Not mandatory • Treatment for liver mets? – Sandostatin a must for symptoms – Surgery, if possible and benefit > risk – Clinical trial, when available – TACE as regional therapy of choice
  42. 42. NET Clinic • Medical Oncology – Manisha Shah – Tanios Bekaii-Saab – Jeffrey Rose • Surgical Oncology – E. Christopher Ellison – Peter Muscarella – Edward Martin – Mark Bloomston – Carl Schmidt – Sherif Abdel-Misih • Radiation Oncology – Nina Mayr – Ben Moeller • Interventional Oncology – Gregory Guy – Hooman Khabiri – Ali Rikabi – Jamal Al-Taani • Nurses and Nurse Practitioners – Dori Klemanski – Daria Arbogast – Linda Vaders – Lisa Binzel – Lisa Parks – Meghan Routt – Gail Davidson (Liver Tx Coordinator) – Marianne Bunch – Elizabeth Delaney (CNS) – 7th Floor James Nursing • Data Management – John Wilson – Maria-Teresa (“MT”) Ramirez – James Irwin NETclinic@osumc.edu
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