Innovations in Pancreatic Cancer: A Reason to Hope
1. Innovations in Pancreatic Cancer:
Reason to Hope
A. James Moser, M.D. FACS.
Director, Institute for Hepatobiliary and Pancreatic Surgery
Beth Israel Deaconess Medical Center
Visiting Associate Professor of Surgery
Harvard Medical School
2. We Share Your Mission
โข Imagine a Future without Pancreatic Cancer!
โ Raise Awareness Today
โข Early diagnosis and prevention
โ Hope for Tomorrow
โข Dedicated team of cancer specialists
โข โLivingโ with pancreatic cancer
โ Change in the FUTURE
โข Clinical trials
โข Outreach and Fundraising for a โcureโ
โข Laboratory research
3. Focus on the Imminent:
Modern Total Pancreatectomy
โข 62 yo man; recurring abdominal pain
โข chronic pancreatitis; PRSS1 gene mutation
โข Predicted 25% lifetime risk of PDA
โข PanIN3; Back at work three weeks postop
4. Rising Incidence of Pancreatic Cancer
โข Geographic risk of
pancreatic cancer
โ Rising in Cape Cod and
New England
โ Falling in Western PA and
West Virginia
โข Aging population
โข Obesity
โข Genetic risk factors
โข Smoking
5. โข By 2030:
โ 2nd cause of cancer death
โ 1.4-1.8% incr. per year
โข Possible Factors
โ Obesity
โ Caucasian
6. Pancreatic Cancer Statistics
โข 4th most common cause of cancer death
โ 34,000 new cases every year
โ โSilentโ disease
โข Vague abdominal pain or unexplained weight loss
โข New-onset diabetes (one in 332 new patients)
โข Smoking (two-fold increased risk)
โข Family history of cancer (two-fold in 1st degree relatives)
โข When the tumor is found:
โ 15% of patients have operable cancer (stage 1/2)
โ 25-30% have advanced pancreatic cancer (stage 3)
โ 55% cancer has spread (metastatic, stage 4)
7. Extent of Disease at Diagnosis
Improvements in diagnostic imaging?
Shaib et al, Aliment Pharmacol Ther 24, 87-94, 2006
8. Issues for the Pancreatic Cancer Patient
โข Can you treat my cancer?
โข Can you relieve my symptoms?
โ Nutrition: Fatigue/ loss of appetite
โ Pain
โ Jaundice: Bile duct blocked
โ Nausea and vomiting
โข Narrowing of outlet from stomach
โข โNo one to watch over meโ
โ Physician specialization
โ Regionalization of care
โข The Internet has no librarian
10. โWhy do you need to go to medical
school when you have the Internet?โ
His Expectation
โข PubMed citations for pancreatic cancer:
โ 2592 clinical trial reports
โข 1530 chemotherapy trials
โข 1134 surgery citations
โข 165 chemoradiation trials
โข โDonโt be afraid to see what you see.โ
Ronald Reagan
11. Regionalized Care for Pancreatic Cancer?
Sener et al, J Am Coll Surg 1999; 189: 1-7.
12. BIDMC Pancreatic Cancer Center
Vision
The state of the art for
pancreatic cancer is a
clinical trial.
14. Evolution of Personalized Medicine
โข 19th century
โ โThe practice of medicine is an artโฆโ William Osler
โข 20th century
โ RCTs to delineate outcome variables
โข NSABP โs triumph over radical mastectomy
โข 21st century: art replaced by science
โ The tumor target: the 6th vital sign
โ Oncotype DX
โข Stage I/II node negative ER(+) breast cancer
โข Recurrence risk based on gene expression profiling
15. The Future of Pancreatic Cancer
โข Combine new treatments to
โ Kill cancer cells around the main tumor
and in the liver
โ Optimize patient selection for surgery
โ Maximize survival
โข Maximize quality of life after surgery
โข Immunotherapy
โข Novel Chemotherapy after surgery
16. BIDMC Pancreatic Cancer
Specialty Care Center
617-667-PANC (7262)
โข Multidisciplinary Clinical Care โข Clinical Research
โ Specialized expertise โ Pancreatic Cancer Registry
โข Pancreatic surgery โข Database
โข Gastroenterology โ Clinical Trials
โข Medical oncology โข New drugs
โข Radiation oncology โข Immunotherapy
โข Chronic pain โข Cyberknife
โข Cancer genetics โข New stents
โข Nutrition/ Alternative Medicine โข Molecular diagnosis
Social Work
17. Staging, Diagnosis, and Treatment
โข Stage the disease
โ Stage I/II: surgery is possible
โ Stage III: too advanced for surgery
โ Stage IV: metastatic
โข Stage-specific therapy
โ Stage I/II: surgery, systemic therapy, radiation
โ Stage III: systemic therapy, radiation, ?surgery
โ Stage IV: systemic therapy
18. Allaying Fear of Chemotherapy
โข Stage 4; Gemzar/Xeloda
โข How will chemo make me feel?
โข Less burden with time
โข Reduced coping effort
19. Better Quality of Life
โข Stage 4 pancreatic cancer
โข Gemzar/Xeloda
โ Reduced pain
โ Improved mood
20. Chemotherapy That Works
โข FOLFIRINOX vs. Gemcitabine (2011)
โ Stage 4 pancreatic cancer
โ Significantly improved:
โข response rate
โข disease control (63%-79% of patients)
โข Better quality of life at 6 months
โ 75% improvement in overall survival
21. Stereotactic Radiosurgery (Cyberknife)
โข Highly-conformal XRT
with real-time imaging
โข Gold fiducials for targeting
โข Breath-tracker software
โข 36 Gy, 3 fractions
โข Multiple studies
โ All pts had local control
โ Distant mets as first site of
progression
23. Leave No Cancer Behind
Portal vein NOT involved Portal vein involved
24.
25. No Substitute for Experience
Makary et al, Pancreaticoduodenectomy in the very elderly, JOGS 2006.
26. Case Presentation:
โข 70 y/o woman with painless jaundice
โข CT showed 2x3 cm ill defined mass in head
of pancreas
โข EUS confirms mass
โข Biopsy revealed adenocarcinoma
โข ERCP showed obstruction of bile duct
โข Surgery first vs. clinical trial
29. Case Presentation
โข Robot-assisted minimally-invasive
pancreaticoduodenectomy (Whipple operation)
โข Uneventful recovery discharged home on POD 10
eating a regular diet.
โข Final pathology revealed 2 cm adenocarcinoma,
negative margins and no lymph node involvement
โข Received adjuvant chemotherapy on a clinical trial
31. Worse Cancer = Even Bigger
Operation
Portal vein involved
32. Preoperative Therapy for PAC
โข Goals of neoadjuvant multimodality therapy:
โ reduce risk of positive margin
โ Sterilize regional lymph nodes
โ Treat systemic disease
โข Candidates for neoadjuvant therapy
โ Resectable (new indication)
โ Locally-advanced disease
โข invasion of SM-PV confluence, mesenteric arteries
โข local lymphadenopathy
โข Published: 5-FU, gemcitabine, paclitaxel, + XRT
33. BIDMC Pancreatic Cancer Center
Mission
โข Combine new treatments to:
โ Improve survival
โ Optimize patient selection for surgery
โข Chemotherapy and radiation before surgery
โ Surgical patients with โresectableโ pancreatic cancer
โ Reduce recurrences in the liver
โ Chemotherapy/Cyberknife for advanced cancers
โข Novel radiotherapy: Stereotactic radiosurgery
โข Immunotherapy and new agents for metastatic disease
34. Does Radical Surgery Improve Outcome?
โข โRegionalโ pancreatectomy to clear SMA margin
โ increased morbidity and mortality (Fortner)
โ No patients with positive margins survive 5 years
โข Extended lymphadenectomy does NOT improve
survival
โข EQUIVALENT results after portal vein resection
โข tumor interface with PV/SMV
โข Location, not biology?
35. What We Do
โข Multidisciplinary evaluation by expert team
โข BIDMC Pancreatic Cancer Specialty Care Center
โ Multidisciplinary Pancreatic Cancer Conference
โข Helical pancreas mass protocol CT
โข Endoscopic Ultrasound (EUS)
โข Encourage neoadjuvant therapy on protocol
โข Staging laparoscopy
โ Inspect peritoneal surfaces; UTZ for suspicious hepatic lesions
โข Portal vein resection: Yes
โข En bloc resection of adjacent organs: Probably
โข Adjuvant chemotherapy: Yes
36. Staging, Diagnosis, and
Treatment
โข Stage the disease
โ Stage I/II: surgery is possible (resectable)
โข Tumor diameter
โข Presence of lymph nodes
โ Stage III: too advanced for surgery
โข Mesenteric vascular involvement
โข โBorderlineโ resectable vs. locally-advanced
โ Stage IV: metastatic
โข Stage-specific therapy
โ Stage I/II: surgery, systemic therapy,
?radiation
โ Stage III: systemic therapy, radiation,
37. Lessons from Radical Surgery
โข Locally and regionally aggressive disease at diagnosis
โข Resection improves survival in a subset of patients
โ No validated models to determine who will/will
not benefit
โ nodal, retroperitoneal margin status and PV
invasion difficult to evaluate with certainty
โข Time to focus on tumor biology, not location
โ sterilize locoregional nodes and peripancreatic
tissue
38. Evolution of Personalized Medicine
โข 19th century
โ โThe practice of medicine is an artโฆโ William Osler
โข 20th century
โ RCTs to delineate outcome variables
โข NSABP โs triumph over radical mastectomy
โข 21st century: art replaced by science
โ The tumor target: the 6th vital sign
โ Oncotype DX
โข Stage I/II node negative ER(+) breast cancer
โข Recurrence risk based on gene expression profiling
39. Personalized Medicine for PAC
โข Continuous quality improvement
โ Minimizing perioperative morbidity
โ Maximize adjuvant therapy
โข Individualize surgical decision-making
โ Beyond the โone-size-fits-allโ approach
โ Genetic predictors of aggressive biology
โข Tumor genetics accessible preoperatively
โ Identifying responders prior to surgery
โข Rational target selection for chemotherapy
โ Tailor the treatment to the tumor
40. Neoadjuvant Design Elements
โข Analysis of treated tumor
โ Science leads the way
โข Potential clinical benefits
โ reduce risk of positive margin
โ Sterilize regional lymph nodes
โ Early treatment of systemic disease
โข Candidates for neoadjuvant therapy
โ Resectable (new indication)
โ Locally-advanced disease
โข invasion of SM-PV confluence, mesenteric arteries
โข local lymphadenopathy (Stage 2B)
โข Published: gemcitabine, cisplation, paclitaxel, etc
42. Perception Trumps Reality
!
Bilimoria K, National Failure to Operate on Early Stage Pancreatic Cancer, Ann Surg 2007 Aug
43. Why Minimally-Invasive Surgery?
โข Potential benefits
โ Improved quality of life
โ Increased patient acceptance
โ Earlier/more frequent adjuvant chemotherapy
โ Better cancer outcomes?
โข Foreseeable risks
โ Oncologic compromises
โข Margin negative rate/ nodal harvest
โ Preventable technical harm
โข Conversion events
โข Fear of Cost differential
44. Minimally-Invasive Pancreatic Surgery
โข Worldโs largest experience: 250 cases to date
โข Tumors in the pancreatic neck, body, tail
โ Benign and malignant lesions
โ Distal and extended distal pancreatectomy
โข With/without splenectomy
โ Enucleation for islet cell tumors
โข Pancreatic head lesions
โ Enucleation
โ Robotic pancreatoduodenectomy (Whipple)
45. This is the Futureโฆ
But Not Yet
Fancy
molecular
stuff
46. Minimally-Invasive Pancreatic Oncology
1. Recreate open techniques
2. Maximize margin negative
outcomes
3. Minimize conversions
4. Eliminate selection bias
Validated prediction rule
Bao et al, HPB 2009
47. Perception Trumps Reality
!
Bilimoria K, National Failure to Operate on Early Stage Pancreatic Cancer, Ann Surg 2007 Aug
48. This is the Futureโฆ
But Not Yet
Fancy
molecular
stuff
49. Minimally-Invasive Pancreatic Oncology
1. Recreate open techniques
2. Maximize margin negative
outcomes
3. Minimize conversions
4. Eliminate selection bias
Validated prediction rule
Bao et al, HPB 2009
50. Minimally-Invasive Surgery for PDC
โข Retrospective, 9 centers, 2000-2008
โ 212 distal panc for PDC, 23 laparoscopic
โ 3:1 matched comparison to historical controls
โ Minimally-invasive patients heavier
โข Pathology
โ No differences in margin status or nodal harvest
โข Minimally-invasive group
โ Reduced hospitalization (2 days)
โ Reduced blood loss
Kooby et al J Am Coll Surg 2010; 210(5)
51. Minimally-Invasive vs. Open
โข Retrospective, UPMC, 2002-2010
โ 62 distal pancreatectomies for PDC (34 open, 28 MIS)
โ Intention to treat methodology/Propensity score analysis
โข Control imbalances between the groups
โ No selection bias evident
โข Demographics, comorbid conditions, imaging factors
โข Short-term outcomes: reduced EBL and LOS
โ 5 laparoscopic conversions to ODP
โ Complication rates same
โ Cancer outcomes identical
52. โข Robotic procedure superior
โ Greater risk of PDC in robot group (43% vs. 19%)
โ No robotic conversions to open surgery
โข 0% robotic vs. 16% laparoscopic, p<0.05
โ Retrieved more lymph nodes (19 vs. 9, p<0.05)
โ Reduced risk of a positive surgical margin
โข 0% robotic vs. 36% laparoscopic (p<0.05)
โข Effect of conversion on outcome
โ Incision; longer hospitalization (2 days); blood loss
Data presented as either mean SD, median (IQR), or n (%)
53. Robotic Pancreatoduodenectomy
โข Two experienced surgeons
โข Surgeon console
โ Stereoscopic vision
โ Fine motor and foot control
โ Tremor dampening
โข Patient console
โ Three articulated arms
โ Camera
โข Seven laparoscopic ports
55. Technical Feasibility
Ann Surg Oncol
DOI 10.1245/s10434-011-2045-0
ORI GI NA L A RT I CL E โ PA N CREA T I C T UM ORS
Outcomes After Robot-Assisted Pancr eaticoduodenectomy
for Per iampullar y L esions
F
Her ber t J. Zeh1,2, Amer H. Zur eikat 1, Aar on Secr est 1, M ustapha Dauoudi 1, David Bar tlett 1, and A. James M oser 1,2
1
Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA; 2Division of HPB
OO
Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA
Ann Surg Oncol
DOI 10.1245/s10434-011-2045-0
ABSTRACT robot-assisted approach holds promise. Larger, more 40
ORI GI NA L A RTI CL E โ theoretical advantages that
Backgr ound. There are manyPA NCREA TI C TUM ORS mature multi-institutional cohorts will be needed to explore 41
a minimally invasive approach to the pancreaticoduoden- potential bene๏ฌts over open and laparoscopic techniques. 42
56. Outcomes of 100 Robotic-Assisted PD
Characteristic Mean/ Frequency
Age, year, mean ยฑ SD 67.7ยฑ12.7
Female sex, n (%) 47 (47%)
Body mass index, mean ยฑ SD 27.3ยฑ 5.7
CCI Age Unadjusted 1 (1-3) (Median/ IQR)
CCI Age Adjusted 4 (2-5) (Median/ IQR)
Prior abdominal surgery, n (%) 51 (51%)
ASA score, n (%)
I 0(0%)
II 33 (33%)
III 62 (62%)
IV 5 (5%)
Pre-op CA 19-9 40.7 (16-225)
(Median/IQR)
ASA American Society of Anesthesiologists