regional therapy for metastatic neuroendocrine carcinoma
TRANSCRIPT
An Institutional Approach to Neuroendocrine Carcinoma
Mark Bloomston, M.D.
Associate Professor of Surgery
Division of Surgical Oncology
The Ohio State University
• No disclosures
“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
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
Carcinoid Symptoms
• Primary tumor– Pain, bowel obstruction, jaundice
• Metastases– Non-hormonal: Pain, fatigue, weight loss– Hormonal: carcinoid syndrome, valve disease
Metastatic Carcinoid
• Liver most common distant organ– Can result in liver dysfunction
• Often results in symptoms• Often incurable• Long-term survival still possible
Management of Liver Metastases
• Local Therapies– Surgical resection– Ablation
• Regional Therapies– Chemoembolization– Bland embolization– Selective internal radiotherapy
• Systemic Therapies– Chemotherapy
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
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
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
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)
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)
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• Multidisciplinary planning
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
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
Osborne et al. Ann Surg Oncol 2006
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
Hypothesis
• Following TACE, patients with disease amenable to cytoreductive hepatectomy would have better:
• Tumor response• Symptom control • Overall Survival
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
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%) 0.03
Mean pre-TACE pancreastatin
5,186 pg/mL(Range 84-35,700)
10,158 pg/mLRange (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
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 SurvivalPotentially 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 0.09
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
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
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 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
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
Purpose
• To determine the fate of asymptomatic primary neuroendocrine tumors not resected in patients undergoing TACE
Referred for TACEN=197
Primary goneN=97
Primary intactN=100
Asymptomatic primaryN=93
Symptomatic primaryN=7
Developed SymptomsN=4 (4%)
No Symptoms DevelopedMedian f/u 35.6m
N=89 (96%)
Primary Resected after TACEN=6 (6%)
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 not increase morbidity or mortality
• Removal of asymptomatic primary does not improve survival compared to waiting for symptoms to occur
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
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
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