Como selecionar os pacientes para peritonectomia e quimio-

hipertermia

SHIGEKI KUSAMURA MD PhD

Ss Tumori Peritoneali

Peritoneum is the 2deg most common site of disease progression after the

liver

Synchronous Peritoneal Metastasis 43 ndash 51

Metachronous Peritoneal Metastasis 42- 60

Poor prognosis if treated by systemic chemotherapy only

Less responsive to systemic chemotherapy than hematogenous metastasis

Peritoneal metastases from colorectal cancer

Br J Surg 2012 Int J Cancer 2011 Br J Surg 2002 Int J Clin

Oncol 2014

Br J Surg 2012 Eur J Surg Oncol Br J Surg 2002 Ann Surg

2006

BA biological agents (Cetuximab Bevacizumab)

Peritoneal metastasis Treated by systemic chemotherapy

Baratti Kusamura Deraco et al Crit Rev Oncol Hematol 2016

PM-CRC -gtsignificantly shorter OS than those with other isolated sites of metastases

In patients with several sites of metastasis poor OS is a function of both increased ndeg of metastatic sites and PM

Isolated PM 163 months

Peritonectomy

Multivisceral resections

Intraperitoneal chemotherapyHyperthermia

HIPEC Microscopic clearance

Macroscopic

clearance

Locoregional therapy

PM CRC

Peritoneal metastases from colo-rectal cancer

Operability

Age PS Comorbidity

Resectability

Mesentery Small Bowel Distant

metastasis

Benefits Risks

Multidisciplinary team

lsquoDecision is more important than Incisionrsquo

Brendan Moran

Proficiency

86 PCIlt20

Median OS 301 months

5 yr OS 27

5 yr DFS 10

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

Peritoneum is the 2deg most common site of disease progression after the

liver

Synchronous Peritoneal Metastasis 43 ndash 51

Metachronous Peritoneal Metastasis 42- 60

Poor prognosis if treated by systemic chemotherapy only

Less responsive to systemic chemotherapy than hematogenous metastasis

Peritoneal metastases from colorectal cancer

Br J Surg 2012 Int J Cancer 2011 Br J Surg 2002 Int J Clin

Oncol 2014

Br J Surg 2012 Eur J Surg Oncol Br J Surg 2002 Ann Surg

2006

BA biological agents (Cetuximab Bevacizumab)

Peritoneal metastasis Treated by systemic chemotherapy

Baratti Kusamura Deraco et al Crit Rev Oncol Hematol 2016

PM-CRC -gtsignificantly shorter OS than those with other isolated sites of metastases

In patients with several sites of metastasis poor OS is a function of both increased ndeg of metastatic sites and PM

Isolated PM 163 months

Peritonectomy

Multivisceral resections

Intraperitoneal chemotherapyHyperthermia

HIPEC Microscopic clearance

Macroscopic

clearance

Locoregional therapy

PM CRC

Peritoneal metastases from colo-rectal cancer

Operability

Age PS Comorbidity

Resectability

Mesentery Small Bowel Distant

metastasis

Benefits Risks

Multidisciplinary team

lsquoDecision is more important than Incisionrsquo

Brendan Moran

Proficiency

86 PCIlt20

Median OS 301 months

5 yr OS 27

5 yr DFS 10

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

BA biological agents (Cetuximab Bevacizumab)

Peritoneal metastasis Treated by systemic chemotherapy

Baratti Kusamura Deraco et al Crit Rev Oncol Hematol 2016

PM-CRC -gtsignificantly shorter OS than those with other isolated sites of metastases

In patients with several sites of metastasis poor OS is a function of both increased ndeg of metastatic sites and PM

Isolated PM 163 months

Peritonectomy

Multivisceral resections

Intraperitoneal chemotherapyHyperthermia

HIPEC Microscopic clearance

Macroscopic

clearance

Locoregional therapy

PM CRC

Peritoneal metastases from colo-rectal cancer

Operability

Age PS Comorbidity

Resectability

Mesentery Small Bowel Distant

metastasis

Benefits Risks

Multidisciplinary team

lsquoDecision is more important than Incisionrsquo

Brendan Moran

Proficiency

86 PCIlt20

Median OS 301 months

5 yr OS 27

5 yr DFS 10

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

PM-CRC -gtsignificantly shorter OS than those with other isolated sites of metastases

In patients with several sites of metastasis poor OS is a function of both increased ndeg of metastatic sites and PM

Isolated PM 163 months

Peritonectomy

Multivisceral resections

Intraperitoneal chemotherapyHyperthermia

HIPEC Microscopic clearance

Macroscopic

clearance

Locoregional therapy

PM CRC

Peritoneal metastases from colo-rectal cancer

Operability

Age PS Comorbidity

Resectability

Mesentery Small Bowel Distant

metastasis

Benefits Risks

Multidisciplinary team

lsquoDecision is more important than Incisionrsquo

Brendan Moran

Proficiency

86 PCIlt20

Median OS 301 months

5 yr OS 27

5 yr DFS 10

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

Peritonectomy

Multivisceral resections

Intraperitoneal chemotherapyHyperthermia

HIPEC Microscopic clearance

Macroscopic

clearance

Locoregional therapy

PM CRC

Peritoneal metastases from colo-rectal cancer

Operability

Age PS Comorbidity

Resectability

Mesentery Small Bowel Distant

metastasis

Benefits Risks

Multidisciplinary team

lsquoDecision is more important than Incisionrsquo

Brendan Moran

Proficiency

86 PCIlt20

Median OS 301 months

5 yr OS 27

5 yr DFS 10

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

PM CRC

Peritoneal metastases from colo-rectal cancer

Operability

Age PS Comorbidity

Resectability

Mesentery Small Bowel Distant

metastasis

Benefits Risks

Multidisciplinary team

lsquoDecision is more important than Incisionrsquo

Brendan Moran

Proficiency

86 PCIlt20

Median OS 301 months

5 yr OS 27

5 yr DFS 10

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

86 PCIlt20

Median OS 301 months

5 yr OS 27

5 yr DFS 10

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

CC-Score as a Prognostic Indicators of Survival

Median OS cc01 33 months

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

PCI as a Prognostic Indicator of Survival

PCI 5 year OS ()

0-6 44

7-12 22

13-19 29

gt19 7

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

Median OS 35 mts

Median OS 14 mts

Conclusion In the presence of other

relative contraindications SRCC should

refrain a surgeon from performing CRS

and HIPEC

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with

curative treatment of colorectal liver metastases an updated systematic review

El-Nakeep S Rashad N Oweira H Schmidt J Helbling D Giryes A Petrausch U Mehrabi A Decker M

Abdel-Rahman O

77 full-text papers assessed and 6 papers were finally included

Median OS 6-49 months

Five-year OS 18-28

Three-year OS 22-42

Survival was lower in patients with liver metastases and peritoneal metastasis (PM) than those with

PM alone in the majority of studies

Expert Rev Gastroenterol Hepatol 2017

Single prognostic factor vs predictive model

Peritoneal Cancer index

Histological subtype

Completeness of

cytoreductionCompleteness of

cytoreduction

RISK PREDICTION MODEL

Mediana OS 86 37 20

13

COMPASS risk prediction

model

C-INDEX 062

R2 008

PSDSS

C-INDEX 072

R2 019

COMPASS

0 12 24 36 48 60

Months from surgery

10

05

00

Sur

viva

l pro

babi

lity

Right colon n=41 median 193 m

Left colon n=55 median 388 m

P=0024

Genes statu

s

right left P value

KRAS wt

mut

12 (13)

29 (41)

34 (35)

21 (22)

0003

NRAS wt

mut

2

29

3

37

1000

BRAF wt

mut

4

29

1

41

0163

PIK3C

A

wt

mut

4

14

3

20

0679

n=41 n=55

Baratti Kusamura Perrone Deraco

2018 XII Int Symp on Regional Cancer

Therapies JacksonvilleUSA

Primary tumor side amp gene mutations in PM-CRC

Mediana OS 86 37 20

13

COMPASS risk prediction

model

C-INDEX 062

R2 008

PSDSS

C-INDEX 072

R2 019

COMPASS

0 12 24 36 48 60

Months from surgery

10

05

00

Sur

viva

l pro

babi

lity

Right colon n=41 median 193 m

Left colon n=55 median 388 m

P=0024

Genes statu

s

right left P value

KRAS wt

mut

12 (13)

29 (41)

34 (35)

21 (22)

0003

NRAS wt

mut

2

29

3

37

1000

BRAF wt

mut

4

29

1

41

0163

PIK3C

A

wt

mut

4

14

3

20

0679

n=41 n=55

Baratti Kusamura Perrone Deraco

2018 XII Int Symp on Regional Cancer

Therapies JacksonvilleUSA

Primary tumor side amp gene mutations in PM-CRC

COMPASS risk prediction

model

C-INDEX 062

R2 008

PSDSS

C-INDEX 072

R2 019

COMPASS

0 12 24 36 48 60

Months from surgery

10

05

00

Sur

viva

l pro

babi

lity

Right colon n=41 median 193 m

Left colon n=55 median 388 m

P=0024

Genes statu

s

right left P value

KRAS wt

mut

12 (13)

29 (41)

34 (35)

21 (22)

0003

NRAS wt

mut

2

29

3

37

1000

BRAF wt

mut

4

29

1

41

0163

PIK3C

A

wt

mut

4

14

3

20

0679

n=41 n=55

Baratti Kusamura Perrone Deraco

2018 XII Int Symp on Regional Cancer

Therapies JacksonvilleUSA

Primary tumor side amp gene mutations in PM-CRC

C-INDEX 062

R2 008

PSDSS

C-INDEX 072

R2 019

COMPASS

0 12 24 36 48 60

Months from surgery

10

05

00

Sur

viva

l pro

babi

lity

Right colon n=41 median 193 m

Left colon n=55 median 388 m

P=0024

Genes statu

s

right left P value

KRAS wt

mut

12 (13)

29 (41)

34 (35)

21 (22)

0003

NRAS wt

mut

2

29

3

37

1000

BRAF wt

mut

4

29

1

41

0163

PIK3C

A

wt

mut

4

14

3

20

0679

n=41 n=55

Baratti Kusamura Perrone Deraco

2018 XII Int Symp on Regional Cancer

Therapies JacksonvilleUSA

Primary tumor side amp gene mutations in PM-CRC

0 12 24 36 48 60

Months from surgery

10

05

00

Sur

viva

l pro

babi

lity

Right colon n=41 median 193 m

Left colon n=55 median 388 m

P=0024

Genes statu

s

right left P value

KRAS wt

mut

12 (13)

29 (41)

34 (35)

21 (22)

0003

NRAS wt

mut

2

29

3

37

1000

BRAF wt

mut

4

29

1

41

0163

PIK3C

A

wt

mut

4

14

3

20

0679

n=41 n=55

Baratti Kusamura Perrone Deraco

2018 XII Int Symp on Regional Cancer

Therapies JacksonvilleUSA

Primary tumor side amp gene mutations in PM-CRC

HRadj 95 CI P value

BRAF mutations (vs wt) 239 223-462 0009

Primary site (right vs left) 055 035-087 0010

PCI (gt9 vs le9) 178 115- 277 0010

CCR (2 vs 1 vs 0) 238 105-540 0039

Stage IV primary tumor 042 026-067 0001

Primary tumor side amp gene mutations in PM-CRC

Baratti Kusamura Perrone Deraco

2018 XII Int Symp on Regional Cancer

Therapies JacksonvilleUSA

32 studies on CRS and HIPEC for PM-CRC

Major morbidity rates 176 ndash 524

- weighted average 326

Mortality 0-81

- weighted average 29

N= 211

Severe morbidity 251

Breaking points

Milan 141

Bentivoglio 126

Breaking points

Milan 158

Bentivoglio 134

Breaking points

Milan 144

Bentivoglio 60

7 years

Kusamura et al Annals of Surgery 2011 JSO 2012

Learning curve for cytoreductive surgery and hyperthermic

intraperitoneal chemotherapy in peritoneal surface

malignancies analysis of two centres

Comparative trials

Author Patients

(n)

Treatment Median

survival

P value

Vic Verwaal 54

51

CRS + HIPEC (MMC) + 5FULV

5FULV

223

126

0032

Matheme 18

18

CRS + SPIC (5FUFA)

5FUFA or 5FULV+ methoan

320

140

001

Elias 48

48

CRS + HIPEC (OXL) + sCT

FOLFOXFOLFIRI + BA

627

239

lt005

Franko 38

67

CRS + HIPEC (MMC) + sCT

FOLFOXFOLFIRI + BA

347

168

lt0001

Esquivel 609

275

CRS + HIPEC (various) plusmn sCT

Syst CT (various)

410

100

NA

BA biological agents (Cetuximab Bevacizumab)

JCO 2003 Br J Surg 2004 JCO 2009 Cancer 2010 Ann Surg Oncol 2014

PRODIGE 7

Phase III RCT role of HIPEC after CCR01 for PM from CRC

Better survival

Complications

Lead time bias vs treatment effect

Prophylo CHIP

Second look Italian trial

Colopec

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

32 studies on CRS and HIPEC for PM-CRC

Major morbidity rates 176 ndash 524

- weighted average 326

Mortality 0-81

- weighted average 29

N= 211

Severe morbidity 251

Breaking points

Milan 141

Bentivoglio 126

Breaking points

Milan 158

Bentivoglio 134

Breaking points

Milan 144

Bentivoglio 60

7 years

Kusamura et al Annals of Surgery 2011 JSO 2012

Learning curve for cytoreductive surgery and hyperthermic

intraperitoneal chemotherapy in peritoneal surface

malignancies analysis of two centres

Comparative trials

Author Patients

(n)

Treatment Median

survival

P value

Vic Verwaal 54

51

CRS + HIPEC (MMC) + 5FULV

5FULV

223

126

0032

Matheme 18

18

CRS + SPIC (5FUFA)

5FUFA or 5FULV+ methoan

320

140

001

Elias 48

48

CRS + HIPEC (OXL) + sCT

FOLFOXFOLFIRI + BA

627

239

lt005

Franko 38

67

CRS + HIPEC (MMC) + sCT

FOLFOXFOLFIRI + BA

347

168

lt0001

Esquivel 609

275

CRS + HIPEC (various) plusmn sCT

Syst CT (various)

410

100

NA

BA biological agents (Cetuximab Bevacizumab)

JCO 2003 Br J Surg 2004 JCO 2009 Cancer 2010 Ann Surg Oncol 2014

PRODIGE 7

Phase III RCT role of HIPEC after CCR01 for PM from CRC

Better survival

Complications

Lead time bias vs treatment effect

Prophylo CHIP

Second look Italian trial

Colopec

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

N= 211

Severe morbidity 251

Breaking points

Milan 141

Bentivoglio 126

Breaking points

Milan 158

Bentivoglio 134

Breaking points

Milan 144

Bentivoglio 60

7 years

Kusamura et al Annals of Surgery 2011 JSO 2012

Learning curve for cytoreductive surgery and hyperthermic

intraperitoneal chemotherapy in peritoneal surface

malignancies analysis of two centres

Comparative trials

Author Patients

(n)

Treatment Median

survival

P value

Vic Verwaal 54

51

CRS + HIPEC (MMC) + 5FULV

5FULV

223

126

0032

Matheme 18

18

CRS + SPIC (5FUFA)

5FUFA or 5FULV+ methoan

320

140

001

Elias 48

48

CRS + HIPEC (OXL) + sCT

FOLFOXFOLFIRI + BA

627

239

lt005

Franko 38

67

CRS + HIPEC (MMC) + sCT

FOLFOXFOLFIRI + BA

347

168

lt0001

Esquivel 609

275

CRS + HIPEC (various) plusmn sCT

Syst CT (various)

410

100

NA

BA biological agents (Cetuximab Bevacizumab)

JCO 2003 Br J Surg 2004 JCO 2009 Cancer 2010 Ann Surg Oncol 2014

PRODIGE 7

Phase III RCT role of HIPEC after CCR01 for PM from CRC

Better survival

Complications

Lead time bias vs treatment effect

Prophylo CHIP

Second look Italian trial

Colopec

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

Breaking points

Milan 141

Bentivoglio 126

Breaking points

Milan 158

Bentivoglio 134

Breaking points

Milan 144

Bentivoglio 60

7 years

Kusamura et al Annals of Surgery 2011 JSO 2012

Learning curve for cytoreductive surgery and hyperthermic

intraperitoneal chemotherapy in peritoneal surface

malignancies analysis of two centres

Comparative trials

Author Patients

(n)

Treatment Median

survival

P value

Vic Verwaal 54

51

CRS + HIPEC (MMC) + 5FULV

5FULV

223

126

0032

Matheme 18

18

CRS + SPIC (5FUFA)

5FUFA or 5FULV+ methoan

320

140

001

Elias 48

48

CRS + HIPEC (OXL) + sCT

FOLFOXFOLFIRI + BA

627

239

lt005

Franko 38

67

CRS + HIPEC (MMC) + sCT

FOLFOXFOLFIRI + BA

347

168

lt0001

Esquivel 609

275

CRS + HIPEC (various) plusmn sCT

Syst CT (various)

410

100

NA

BA biological agents (Cetuximab Bevacizumab)

JCO 2003 Br J Surg 2004 JCO 2009 Cancer 2010 Ann Surg Oncol 2014

PRODIGE 7

Phase III RCT role of HIPEC after CCR01 for PM from CRC

Better survival

Complications

Lead time bias vs treatment effect

Prophylo CHIP

Second look Italian trial

Colopec

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

Comparative trials

Author Patients

(n)

Treatment Median

survival

P value

Vic Verwaal 54

51

CRS + HIPEC (MMC) + 5FULV

5FULV

223

126

0032

Matheme 18

18

CRS + SPIC (5FUFA)

5FUFA or 5FULV+ methoan

320

140

001

Elias 48

48

CRS + HIPEC (OXL) + sCT

FOLFOXFOLFIRI + BA

627

239

lt005

Franko 38

67

CRS + HIPEC (MMC) + sCT

FOLFOXFOLFIRI + BA

347

168

lt0001

Esquivel 609

275

CRS + HIPEC (various) plusmn sCT

Syst CT (various)

410

100

NA

BA biological agents (Cetuximab Bevacizumab)

JCO 2003 Br J Surg 2004 JCO 2009 Cancer 2010 Ann Surg Oncol 2014

PRODIGE 7

Phase III RCT role of HIPEC after CCR01 for PM from CRC

Better survival

Complications

Lead time bias vs treatment effect

Prophylo CHIP

Second look Italian trial

Colopec

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

PRODIGE 7

Phase III RCT role of HIPEC after CCR01 for PM from CRC

Better survival

Complications

Lead time bias vs treatment effect

Prophylo CHIP

Second look Italian trial

Colopec

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

Better survival

Complications

Lead time bias vs treatment effect

Prophylo CHIP

Second look Italian trial

Colopec

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

The panel recognizes the need for RCT that will address the risks and benefits associated with each of these modalities

Cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment for patients with PM-CRC

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions

bull Peritoneal recurrence is a predominant cause of treatment

failure in CRC patients

bull CRSHIPEC offers a chance of improved survival in

established PM

bull Right side-gt worse

bull The lsquoearlier the betterrsquo police is appealing but still

experimental

bull Confirmation in a phase-III trial is warranted

Conclusions