peritoneal surgery and intraperitoneal chemotherapy | mesothelioma applied research foundation

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