peritoneal surgery and intraperitoneal chemotherapy | mesothelioma applied research foundation
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Peritoneal Surgery and Intraperitoneal Chemotherapy, presented by Garrett Nash, MD of Memorial Sloan-Kettering at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.orgTRANSCRIPT
Cytoreductive Surgery and Intraperitoneal Chemotherapy
Garrett Nash MD, MPH Assistant Attending Surgeon
Memorial Sloan-Kettering Cancer Center September 28th, 2012
Peritoneal Mesothelioma
About me
• Training in Colorectal Surgery and Surgical Oncology
• Peritoneal based diseases
–Appendix Cancer
–Metastatic Colorectal Cancer
–Peritoneal Mesothelioma
Peritoneal Mesothelioma
Peritoneal Mesothelioma
• What is the disease?
• What are the surgical options?
• What are the outcomes after surgery?
Peritoneal Mesothelioma
Peritoneal Mesothelioma
• 2nd most common site of mesothelioma is the peritoneum
– 10-30% of cases of mesothelioma
– 300-400/cases in U.S. year
Peritoneal Mesothelioma
Background • Causes
– Asbestos exposure
– Simian virus-40
– Radiation
– Chronic inflammation of the peritoneum
• Presentation – Increased abdominal girth
– Ascites (fluid in the abdomen)
– Abdominal pain
– Weight loss
Peritoneal Mesothelioma
Treatment Options
• “Traditional”
– Chemotherapy (doxorubicin and cisplatin)
– Radiation
– Drainage of abdominal fluid to alleviate pressure (palliative paracentesis)
– Surgical excision of some of the tumor to alleviate intestinal blockage (palliative debulking)
Peritoneal Mesothelioma
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
Surgical Options
• Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (IPC)
– Surgical cytoreduction to eliminate visible disease by destroying tumor (burning/peeling/wiping) or removing organs
– Delivery of chemotherapy directly to the peritoneal surfaces to eliminate microscopic disease
Peritoneal Mesothelioma
Intraperitoneal Chemotherapy
• EPIC – Early Postoperative Intraperitoneal Chemotherapy
– Taxol/5FU
• HIPEC – Hyperthermic (heated) Intraperitoneal Chemotherapy
– Cisplatin/Doxorubicin/Mitomycin C
Peritoneal Mesothelioma
Management of Ovarian Cancer
Gynecologic Oncology Group. N Engl J Med. 2006.5;354:34-43.
415 patients with peritoneal metastasis were randomized 1. Intraperitoneal chemotherapy (post operative) 2. Intravenous chemotherapy after cytoreductive surgery
Peritoneal Mesothelioma
Verwaal. J Clin Oncol. 2003;21(20):3737-43.
Management of Colorectal Cancer
Peritoneal Mesothelioma
105 patients with peritoneal metastasis were randomized 1. Intravenous chemotherapy 2. Cytoreductive surgery + intraperitoneal chemo + intravenous
chemo
CRS + IPC + IVC
IVC
• Review of cytoreductive surgery and IPC
• 7 non randomized studies
• 240 patients
Peritoneal Mesothelioma
Inclusion Criteria
• Histological diagnosis of diffuse malignant peritoneal mesothelioma (DMPM)
• Patients undergoing cytoreductive surgery (CRS) + intraperitoneal chemo (IPC)
Exclusion Criteria
• Surgical debulking without IPC
• Studies that mix in other cancer types
Peritoneal Mesothelioma
Annals of Oncology 18:827-834, 2007
Survival after CRS with IPC
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
Survival after CRS with IPC
• Range of average survival by study: 3-7 years
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
• Average length of operation 6-10 hours
• Average hospital length of stay 16 days
• Surgical complication rate 25-40%
• Hematological toxicity 8-26%
• Perioperative mortality 0-8%
Complications and Mortality after Cytoreductive Surgery and IPC
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
How can we predict prognosis?
• No widely accepted staging system for peritoneal mesothelioma
• No information on National Cancer Institute website (cancer.gov)
Peritoneal Mesothelioma
• 8 institutions prospective collected data
• 294 patients treated with cytoreductive surgery and intraperitoneal chemotherapy
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
• Primary objective: Formulate a staging system through identification of prognostic factors.
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Patient Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Pathology/Surgery Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Classification of Peritoneal Mesothelioma
• 3 histological subtypes
– Epithelial
– Sarcomatoid
– Mixed/biphasic
Peritoneal Mesothelioma
Epithelial
Sarcomatoid
Pathology/Surgery Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Peritoneal cancer index (PCI)
• During surgery • Tumor distribution (13 abdominal pelvic regions) •Tumor nodule size (0-3 points)
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Pathology/Surgery Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
TNM staging system
• Most common system used for staging cancer
• T stage – size or depth of tumor (1-4)
• N stage – presence of lymph nodes with cancer (0-2)
• M stage – presence of metastasis to organs (0- 1)
Peritoneal Mesothelioma
TNM staging system
• Most common system used for staging cancer • T stage – size or depth of tumor (1-4)
• N stage – presence of lymph nodes with cancer (0-2)
• M stage – presence of metastasis to organs (0- 1)
• For colon cancer
• Stage I = T1/2, N0, M0
• Stage II = T3/4, N0, M0
• Stage III = N1/2, M0
• Stage IV = M1
Peritoneal Mesothelioma
Survival Stratified by T Stage Based on PCI
• T1 = PCI 1-10
• T2 = PCI 11-20
• T3 = PCI 21-30
• T4 = PCI 30-39
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Peritoneal Mesothelioma
Survival Stratified by Nodal Stage
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Survival Stratified by M stage
• M1 = extraabdominal disease (e.g. chest/skin)
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Overall survival stratified by TNM staging system
52 patients
Peritoneal Mesothelioma
T1 N0 M0
T2-3 N0 M0
T4 or N1 or M1
166 patients
76 patients
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Combining TNM Stage with Histology and Optimal Surgery
HR CI
Sarcomatoid vs. epitheloid 5.5 2.9-10.5
Incomplete vs. complete CRS 2.0 1.2-3.2
Stage II vs. I 3.3 1.2-9.4
Stage III vs. I 5.9 2.1-17.2
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Summary
• Appears to stratify patients for prognosis
–Patients who do poorly
• High volume disease
• Extra-abdominal disease
• Non-epitheloid histology
–Patients who do ‘well’
• Low volume disease
• Node negative
– Selected patients undergoing CRS
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Conclusions
• Surgery offers good long term outcomes for selected patients with favorable tumors
• Surgery is high risk
• We need comparative studies that demonstrate how much surgery and intraperitoneal chemotherapy may benefit patients
Peritoneal Mesothelioma
Thank You
• Mesothelioma Applied Research Foundation and Lee Krug, MD
Peritoneal Mesothelioma
Thank You
• Mesothelioma Applied Research Foundation and Lee Krug, MD
• My medical oncology collaborator, Andrea Cercek, MD
Peritoneal Mesothelioma
Thank You
• Mesothelioma Applied Research Foundation and Lee Krug, MD
• My medical oncology collaborator, Andrea Cercek, MD
• The patients who allow us to study their tumors
Peritoneal Mesothelioma