Beruflich Dokumente
Kultur Dokumente
2058
PR AC T IC E
GUIDELINE
KEY WORDS
Peritoneal surface malignancy, pseudomyxoma peritonei, carcinomatosis, colorectal cancer, appendiceal
cancer, hyperthermic intraperitoneal chemotherapy,
cytoreductive surgery, peritoneal metastasis
1. INTRODUCTION
A peritoneal surface malignancy ( psm) is a cancer
arising from or spreading to the peritoneal surfaces.
It can be a primary disease arising from the peritoneum (such as malignant peritoneal mesothelioma) or
a secondary disease (such as metastasis originating
from a primary malignant neoplasm). Primary psm is
rare; the most frequent forms are primary peritoneal
Current OncologyVolume 22, Number 2, April 2015
mesothelioma and serous carcinoma of the peritoneum. Secondary psm is by far the most frequent. Its
origin is often cancers of the gastrointestinal tract,
but it can frequently arise from ovarian cancer and
breast cancer (mostly the lobular subtype). However,
many cancers can metastasize to the peritoneum17.
Surgical treatment of psm is recent810. Before
1989, cures were anecdotal, and median survival
was 9 months. Now, long-term survival is possible
in 25%85% of patients1,2,46,8,11,12, depending on
patient and disease characteristics8,1320. Despite that
success, a lack of agreement on many issues (drug,
dose, duration) means that many questions remain,
and few randomized controlled trials have provided
comparative evidence.
In selected cases, optimal treatment of psm consists of a combination of cytoreductive surgery (crs)
and hyperthermic intraperitoneal chemotherapy
(hipec). This complex procedure requires a dedicated
multidisciplinary team. Unfortunately, worldwide,
philosophic and fundamental differences exist about
issues ranging from patient selection to treatment approaches. Consequently, no accepted standard of care
for the provision of this treatment has been developed.
A primary concern in the medical community
regarding psm treatment by crs plus hipec is the
paucity of phaseiii studies to support this modern
therapeutic approach. The lack of studies is, in part,
a result of the strong personal biases found among
surgeons providing psm care, the rapid increase in the
number of centres offering this multimodal approach,
and the relatively small number of patients at risk.
Well-selected psm patients can clearly be treated
with crs and hipec. However, in the absence of a large
body of level1 evidence, Canadian surgical and medical oncologists should offer psm patients a thoughtful,
carefully integrated approach founded in surgical and
biologic principles and supported by the available evidence. To that end, it is strongly recommended that all
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2. METHODS
Before these guidelines were written, the literature in PubMed was searched using the key words
peritoneal carcinomatosis, PC, intraperitoneal
chemotherapy, HIPEC, colorectal neoplasms
(or cancers), colonic neoplasms (or cancers),
rectal neoplasms (or cancers), pseudomyxoma
peritonei, debulking, and chemohyperthermia.
Descriptive studies and clinical trials (phaseii and
iii) published between 1990 and 2013 were retained.
As additional sources of information, published
guidelines from national and international organizations were obtained:
table i
University
Surgeon
MaisonneuveRosemont Hospital
Montreal
Calgary
Pierre Duba
Lucas Sideris
Walley Templea
Lloyd Mack
Rami Younana
Carman Giacomantonioa
Erika Haasea
Andrea McCarta
Anand Govindarajan
Tsafrir Vanounoua
Pamela Hebbarda
Yarrow McConnella
Montreal
Dalhousie
Alberta
Toronto
Montreal
Manitoba
British Columbia
Status
Open
Open
Open
Open
Open
Open
Pending
Pending
Open
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table ii
Questions addressed during the Canadian HIPEC Collaborative Group consensus process
Q1
Q2
Q3
Q4
Q5
Q6
Q7
Q8
Q9
Q10
Q11
Q12
Q13
Q14
Q15
Q16
Q17
Eligibility when a synchronous primary tumour accompanies low-grade disseminated peritoneal adenomucinosis (dpam) or
intermediate-grade peritoneal mucinous carcinomatosis ( pmca-i)
Q18
Q19
Eligibility when a synchronous primary tumour accompanies grade1 or 2I adenocarcinoma from the appendix
Q20
Eligibility in the case of a peritoneal surface malignancy ( psm) arising less than 6 months after surgery for a primary adenocarcinoma grade1 or 2 from colorectal origin
Q21
Eligibility in the case of synchronous psm and a primary adenocarcinoma grade1 or 2 from colorectal origin
Q22
Eligibility in the case of pmca or grade3 adenocarcinomas originating from the appendix
Q23
Q24
Q25
Q26
Q27
Eligibility in the presence of extra-regional lymph node invasion in the case of dpam or pmca-i
Q28
Q29
Eligibility when in the presence of extra-peritoneal invasion in the case of dpam or pmca-i
Q30
Eligibility in the presence of extra-regional lymph node invasion in the case of a psm originating from a grade1 or 2 appendiceal
adenocarcinoma
Q31
Eligibility in the presence of liver invasion in the case of a psm originating from a grade1 or 2 appendiceal adenocarcinoma
Q32
Eligibility in the presence of extra-peritoneal invasion in the case of a psm originating from a grade1 or 2 appendiceal adenocarcinoma
Q33
Eligibility in the presence of extra-regional lymph node invasion in the case of a psm originating from a grade1 or 2 colorectal
adenocarcinoma
Q34
Eligibility in the presence of liver invasion in the case of a psm originating from a grade1 or 2 colorectal adenocarcinoma
Q35
Eligibility in the presence of extra-peritoneal invasion in the case of a psm originating from a grade1 or 2 colorectal adenocarcinoma
Q36
Q37
Eligibility when the pci score exceeds 20 in the case of psm originating from a grade1 or 2 appendiceal adenocarcinoma
Q38
Eligibility when the pci score exceeds 20 in the case of a psm originating from a grade1 or 2 colorectal adenocarcinoma
Q39
Q40
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DUB et al.
table iii
Level of
consensus
Level of
evidence
Applicability
Vote of agreement
Status of recommendation
or ii
>70%
ii
or iii
50%70%
ii, iv,
<50%
Not
applicable
chicg=
or v
Not applicable
3. CENTRES
4. TEAMS
3.1 Resources
To create viable Canadian guidelines, a census of
the resources available across Canada was taken. All
centres have access to computed tomography imaging and modern diagnostic equipment, but access to
positron-emission tomography imaging is limited in
some areas. Most teams have dedicated intraperitoneal perfusion equipment, but some use a modified
extracorporeal circulation machine dedicated to
cardiac surgery (an important difference, because
perfusion temperature is limited to 41C with the
latter machine). Finally, drug access is not the same
across Canada: The choice of chemotherapeutic and
dose is limited by some authorities. Oxaliplatin is
used for hipec at some sites in Canada; mitomycinC
is currently available at all sites.
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5. PATIENT SELECTION
Patient selection (Tableiv) can be divided into patientrelated criteria and disease-related criteria. Essentially,
a patient must be fit enough to undergo a high-risk
procedure, and the disease must demonstrate biologic
behaviour that is potentially curable by a combination
of crs and hipec7,2634. On occasion, palliative hipec
for intractable ascites can be considered35.
table iv
performance status
0
1
2
Patient age
65 Years
6674 Years
75 Years
Body mass index
35
40
Histologic gradeb
Classical i or ii
Classical iii
dpam / lamn/pmca-i
Classical iii or pmca
Interval from primary tumour
to peritoneal carcinomatosis
Any
6 Months
Synchronous or <6 months
Extraperitoneal diseasec
Present
Peritoneal carcinomatosis index
Any
20
>20
Predicted score for
completeness
of cytoreduction
0
1
2
3
Eligibility by origin
(level of consensus)
Colorectal
Appendiceal
Yes (a)
No (c)a
No (a)
Yes (a)
Yes (b)
No (c)a
Yes (a)
No (c)a
No (b)a
Yes (a)
No (c)a
No (b)a
Yes (a)
No (b)a
Yes (a)
No (b)a
Yes (a)
No (b)a
Yes (a)
ecog
Yes (a)
No (b)a
Yes (a)
Yes (a)
No (c)a
No (a)
No (a)
Yes (b)
Yes (a)
No (b)
Yes (a)
No (b)
No (a)
Yes (a)
Yes (a)
No (c)c
No (a)
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table v Terminology
Criterion
Peritoneal carcinomatosis index
( pci)32
Definition
The pci index describes the extent of carcinomatosis before surgery. The abdomen
is divided into 13 sections. Each section is assigned a score from 0 to 3:
0 = No tumour
1 = Tumour < 5mm
2 = Tumour 5mm5cm
3 = Tumour > 5cm
The sum of the scores for the 13 sections yields a total score out of 39.
total colonoscopy;
computed tomography imaging of chest, abdomen,
and pelvis30,46,47;
positron-emission tomographycomputed tomography imaging (if available in cases of nonmucinous disease)47;
confirmation of disease (that is, pathology review,
tissue biopsy, or progression on imaging); and
other appropriate examinations, including laparoscopy as judged necessary by the investigator48.
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6. SURGICAL CONSIDERATIONS
Cytoreductive surgery is divided into 3 phases:
6.2 CRS
Cytoreduction should be planned according to the
area at risk of incomplete resection60. The area of
the abdomen at highest risk of incomplete resection
should be addressed first, because it serves as an
indicatorthat is, the procedure should be stopped
if the resection is not possible28,61,62 (locb).
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6.3 HIPEC
Delivery of hipec can be performed using an open or
a closed technique65. Both techniques are performed
across the country and are considered safe. The
highest risk for chemotherapy exposure is during
clean-up, which is the same for both procedures.
Whichever technique is chosen, the dose, the duration, and the temperature of perfusion should not be
modified (locb).
7. OUTCOMES
Overall survival varies from 20% to 90% at 5
years70,72,7579. It is influenced26,29,31,32,55,78 by origin
of the psm, histology, pci score, patient comorbidities (performance status, body mass index, health
problems), cancer-related symptoms, and surgical
morbidity and mortality79,80.
Good prognostic factors include appendiceal origin,
dpam and low-grade tumours, a low pci score, and a patient who is asymptomatic and has no comorbidities11.
Evaluation of outcomes is needed for the future
development and funding of hipec programs81. To
assess outcomes, all Canadian patients should be
included in a prospective database, ideally with
matched tissues (normal and cancerous).
Outcomes that should be measured include complications79,80, overall survival2,11,28,44,57,62,69,8285,
disease-free survival, quality of life86,87, and costeffectiveness88.
8. RESEARCH
The priority of the chicg research program is to maintain a national prospective database and matchedtissue tumour bank. All Canadian psm patients should
be included in a database, either locally or nationally,
and have tumour, normal tissue, and blood stored in
a local tumour bank, if available.
9. ACCESSIBILITY
9.1 Statistics
As published by the Canadian Cancer Society89,
23,900 new colorectal cancer cases were expected in
2013, and up to 10% (n= 2390) would be expected to
have peritoneal carcinomatosis. Of the latter group,
Current OncologyVolume 22, Number 2, April 2015
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table vi
Drug
Dose
Duration
(minutes)
Intra-abdominal
temperature (C)
300mg/m 2
400mg (fixed dose)
460mg/m 2
30
60
30
4043
4043
4043
5-Fluorouracil (400450mg/m 2)
plus leucovorin (20mg/m 2)
given 3060 minutes
before the oxaliplatin
1030mg/m 2
3040mg (fixed dose)
1mg/kg (70mg maximum)
6090
6090
6090
4043
4043
4043
None
None
None
Oxaliplatin
Mitomycin C
9.2 Accessibility
After the chicg census, it was estimated that the
existing Canadian teams can treat 200250 new patients annuallya number that doesnt come close to
matching the number of predicted new cases. Ideally,
a national coordinating centre should be created to
improve accessibility (Q16).
10. SUMMARY
Given the increasing evidence that selected patients
with psm can benefit from an aggressive surgical approach combined with hipec, the guidelines presented
here are intended to provide the physicians who treat
these patients with the necessary tools to do so. The
key messages to take from these guidelines are the
importance of a multidisciplinary team approach,
the need for strict patient selection, early referral to
a centre with expertise in the surgical management
of psm, and close collaboration between medical and
surgical oncologists to devise a treatment plan. It will
be important to standardize the approach to these
patients so that the benefits of crs and hipec can be
realized across the country and so that all eligible
patients have the opportunity to receive treatment.
11. ACKNOWLEDGMENTS
The authors are indebted to Mr.Barry D. Stein and
Ms.Filomena ServidioItaliano of the Colorectal
Cancer Association of Canada, who spearheaded the
formation of the chicg and the writing of these guidelines. Financial support for meetings was provided
by the Colorectal Cancer Association of Canada with
sponsorship from SanofiAventis, Amgen, Pfizer,
and Belmont Instruments.
Current OncologyVolume 22, Number 2, April 2015
13. REFERENCES
1. Schellinx ME, von Meyerfeldt MF, Sugarbaker PH. Peritoneal
carcinomatosis from adenocarcinoma of the colon. Cancer
Treat Res 1996;81:24760.
2. Sugarbaker PH, Schellinx ME, Chang D, Koslowe P, Meyerfeldt M. Peritoneal carcinomatosis from adenocarcinoma of
the colon. World J Surg 1996;20:58591.
3. Jacquet P, VidalJove J, Zhu B, Sugarbaker P. Peritoneal
carcinomatosis from gastrointestinal malignancy: natural
history and new prospects for management. Acta Chir Belg
1994;94:1917.
4. Elias D, Raynard B, Farkhondeh F, et al. Peritoneal carcinomatosis of colorectal origin. Gastroenterol Clin Biol
2006;30:12004.
5. Macri A, Saladino E, Bartolo V, et al. Peritoneal carcinomatosis of colorectal origin. World J Gastrointest Oncol
2010;2:98101.
6. Elias D, Goere D. Peritoneal carcinomatosis of colorectal
origin: recent advances and future evolution toward a curative
treatment. Recent Results Cancer Res 2007;169:11522.
7. Elias D, Dub P, Blot F, et al. Peritoneal carcinomatosis
treatment with curative intent: the Institut GustaveRoussy
experience. Eur J Surg Oncol 1997;23:31721.
8. Sugarbaker PH. Surgical treatment of peritoneal carcinomatosis: 1988 Du Pont lecture. Can J Surg 1989;32:16470.
9. Pocard M, Boige V. Cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy for peritoneal colorectal carcinomatosis: a newly validated standard whose contribution
remains to be assessed [French]. Bull Cancer 2005;92:1514.
10. Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and longterm outcome data of patients with pseudomyxoma peritonei
from appendiceal origin treated by a strategy of cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy. J
Clin Oncol 2012;30:244956.
11. Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren
H. 8-Year follow-up of randomized trial: cytoreduction and
hyperthermic intraperitoneal chemotherapy versus systemic
e108 Copyright 2015 Multimed Inc. Following publication in Current Oncology, the full text of each article is available immediately and archived in PubMed Central (PMC).
DUB et al.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
e109
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
e110 Copyright 2015 Multimed Inc. Following publication in Current Oncology, the full text of each article is available immediately and archived in PubMed Central (PMC).
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73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
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Mission Objectives
Structure
The chicg coordinating committee (chicg-cc) comprises one representative from each accredited Canadian team, plus one representative of the business
committee. The chicg-cc is responsible for scientific
and strategic planning, and coordinates subcommittees on accessibility; data and tissue banking;
standardization and guidelines review; basic and
preclinical research; phasei, ii, and iii trials; technology
evaluation; and quality control and audit.
e112 Copyright 2015 Multimed Inc. Following publication in Current Oncology, the full text of each article is available immediately and archived in PubMed Central (PMC).