Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is emerging as a new standard treatment for peritoneal surface malignancies. Traditionally, peritoneal carcinomatosis was considered incurable and treated only with palliative chemotherapy. However, CRS-HIPEC aims to remove all visible tumor deposits surgically and then uses heated chemotherapy in the abdominal cavity to target any remaining microscopic disease. Studies show CRS-HIPEC provides significantly longer survival times compared to intravenous chemotherapy alone, with median overall survivals of 16-36 months. Experts indicate CRS-HIPEC should now be considered the standard of care for select patients with peritoneal metastases from conditions like ovarian
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Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies
1. Cytoreductive Surgery plus
HIPEC:
NEW STANDARD for Treating
Peritoneal Surface Malignancies
Mary Ondinee M. Igot, MD, MSCM, FPCP, FPSO,
FPSMO
Medical Oncologist / Neuro – Oncologist
2. Outline
• Peritoneal Metastases
• Cytoreductive Surgery plus Hyperthermic
Intraperitoneal Chemotherapy (CRS-HIPEC) for
Peritoneal Metastases
• Fundamentals
• Technical Requirements
• Chemotherapy Used
• The Right Patient
3. Peritoneal Metastases
• Peritoneal dissemination from gastrointestinal and
gynecological malignancies is common.
• Traditionally, it has been regarded as an end-stage
disease which was only amenable to palliation and
systemic chemotherapy.
• Poor literature on effective treatments because they
are often excluded from clinical trials because they
have “non-measurable disease.”
4. Peritoneal Metastases
• NIHILISTIC ATTITUDE toward this condition.
• Second most common cause of death after liver metastases
• Prone to frequent hospitalizations because of recurrent
obstruction and intraabdominal infections
• Virtually incurable
• AVERAGE LIFE EXPECTANCY: 6 months
• With best systemic chemotherapy,
• MEDIAN OVERALL SURVIVAL: 20 months
• MEDIAN DISEASE FREE SURVIVAL: 10 months
5. Cytoreductive Surgery (CRS) =
Peritonectomy + Organ Resection
• 1930s, attempting to remove all visible deposits was
reported for ovarian cancers and eventually was
accepted as a treatment with survival benefit.
• Attempts have been done in various non-gynecologic
malignancies.
6. “It is what the surgeon does not see
that kills the patient.”
• Paul Sugarbaker
• Peritoneal metastases should
not be equated with
generalized disease.
• Involvement of the peritoneal
surfaces may occur in the
absence of hematogeneous
metastases or it may
represent the dominant clinical
picture.
• Peritoneal metastases =
Locoregional disease
The Sugarbaker
Technique
7. Strong Rationale for Locoregional
Treatment
• Treatment of macroscopic
disease
• Cytoreductive surgery
• Peritonectomy procedures
• Treatment of microscopic
disease
• Heated intraperitoneal
chemotherapy
• Treatment of systemic
disease
• IV chemotherapy
9. Principles and Rationale behind HIPEC
• “Plasma – Peritoneal Barrier”
• Targets microscopic disease that cannot be completely
eradicated by surgery.
• Provides pharmacokinetic advantage of attaining high
local concentrations of chemotherapeutic agents, 12-15x
the maximum tolerated plasma concentration
• Median peak peritoneal concentration 1,116x that of the
normal plasma level of chemotherapy can be achieved.
• High temperature increases drug penetration and provides a
synergistic effect with intraperitoneal chemotherapy.
• Effect of IP chemotherapy on tumour cells also enhanced
because adhesions have not been formed.
• Mitomycin C, oxaliplatin, etc.
14. Predictors for Success
• Cancer deposits in 6 or
more regions of the
abdomen HIGH
TUMOR LOAD
• Completeness of
cytoreduction (R0, R1,
R2)
• Number of resections
and anastomoses
15. N = 2298
Average operating time: 9.5 hours
80% had complete tumor removal
Average hospital stay: 21 days
Post-operative mortality: 2%
Major morbidity: 24%
16.
17. 9 comparative studies and 28 studies
Primary and/or recurrent ovarian cancer
Primary Recurrent
DFS (months) 19.2 17.8
OS (months) 16.1 35.8
Morbidity (%) 31.3 26.2
Mortality (%) 1.8 1.8
18.
19. Present Indications
• Pseudomyxoma peritoneii or jelly belly
• Appendiceal adenocarcinoma
• Peritoneal mesothelioma
• Colorectal cancer with peritoneal metastases
• Ovarian cancer with peritoneal metastases
• Gastric cancer with peritoneal metastases
20. The Eligible Patient
• Patient-Related Criteria
• Good performance status
• No major comorbidities
• BMI > 35 is a relative contraindication
• Physiologic age is considered
• Patients less than 65 yrs are good candidates
• If more than 65 yrs, carefully selected
• Patient must be motivated and must understand and accept the
risks of the procedure
21. • Disease-Related Criteria
• Primary cancer: Ovarian, CRC, primary peritoneal,
mesothelioma considered as part of standard care already
• Others: gastric, sarcoma, etc…
• Histology: Signet ring, poorly differentiated/undifferentiated
The Eligible Patient
22. • Absolute Contraindications:
• Extra-abdominal disease
• Extensive intra-abdominal disease
• Cancer of unknown primary
The Eligible Patient
23. Why should I refer my patient?
• It more than doubles the survival.
• Just last year, it has already been incorporated in the
NCCN 2017 First Quarter Guidelines.
24.
25.
26. Why should I refer my patient?
• It more than doubles the survival.
• Just this year, it has already been incorporated in the
NCCN 2017 First Quarter Guidelines.
• Now a standard treatment. Offer to avoid legal
complications.
27.
28. “They thought I was overly aggressive.
Turned out, I was right all along.”
-Dr Paul Sugarbaker