Role of HIPEC in Ovary

1. HIPEC : IS IT STANDARD OF CARE
IN CA OVARY?
Dr Priyanka Malekar
DNB surgical oncology, 2nd year
01/11/18

2. Definition of HIPEC
( hyperthermic intraperitoneal chemotherapy)
• Heated chemotherapy is circulated in peritoneal cavity at a fixed flow rate of
30-120 mints, maintaining an intra-abdominal temperature of 42-43 degree C
• Principle: intraoperatively affect tumor cell kill by process of diffusion of
chemotherapeutic drugs into residual tumor cell deposits after the CRS, using
heat to potentiate their cytotoxicity.
• Critical residual tumor size <2.5 mm, above which HIPEC is not effective

3. Mechanism of action
• Impairment of DNA repair mechanism: increases sensitivity to
chemotherapy
• Induces apoptosis
• Activates heat shock proteins: serves as receptor for natural killer cells,
inhibits angiogenesis, denaturation of proteins: increases cytotoxicity.

4. Prognostic indicators :
• Peritoneal carcinomatosis index ( PCI- Sugarbaker’s)
• Completeness of cytoreduction score.
• Histologic tumor grade
……….select patient for HIPEC

5. PCI…

6. Completeness of cytoreduction
• To classify completeness of cytoreduction
• CC- 0: no visible peritoneal seeding exist
• CC-1: tumor nodule persisting after cytoreduction are <2.5 mm: it can be
dealt with IP chemotherapy
• CC-2: residual tumor between 2.5 mm to 2.5 cm
• CC-3: residual tumor > 2.5 cm or confluence of unresectable tumor nodules
at any site within the abdomen and pelvis.

7. Indications of CRS + HIPEC…
• Ca ovary:
1. Platinum sensitive recurrence if
complete cytoreduction is possible
2. Platinum resistant disease if first
surgery was incomplete and a
complete CRS is possible
3. Platinum resistant disease If there is
response to chemotherapy and the
disease is resectable
• Prognostic factors:
• PCI 10-12
• CC-0/1 resections

8. Contraindications:
• Poor performance status
• PCI >12
• Multiple extraabdominal metastasis or massive suprarenal retroperitoneal
lymph nodes
• Involvement of pancreas head, bladder trigone, porta hepatis
• Extensive bowel resection

10. Role of HIPEC in colorectal cancers:
Already established

11. Intraperitoneal chemotherapy

13. NEJM 2006)

15. GOG 252

20. NEJM JANUARY 2018…

21. Background…
• Addition of HIPEC to interval CRS would improve outcomes among patients who also
receive NACT for stage III epithelial ovarian , fallopian and peritoneal carcinoma.
• Methods:
Multicentre open label phase III trial
n= 245 , stable disease after 3 cycles of carb+pacli with or without HIPEC
Randomization at the time of surgery
post HIPEC 3 more cycles pacli + carbo
Primary end point : recurrence free survival; secondary end point: OS

22. Eligibility criteria..
• Newly diagnosed stage III referred for NACT because of extensive disease
or surgery incompletely performed ( > 1 cm residual disease).
• HIPEC protocol:
Pt assigned at time of surgery 1:1 ratio, to undergo CRS with or without
HIPEC
8 hospitals involved.

23. Process of HIPEC
• Abdomen filled with heated saline at 40 degrees C,
• Cisplatin 100 mg /m2 and 1 litre/ mint ( IP)
• HIPEC 120 mins including 90 mins perfusion period.
• Post op patients received 3 cycles of carboplatin + paclitaxel
• Follow up : CA 125 every 3 monthly, CT scan every 6 monthly

24. Result: April 2007 to April 2016, n=245

26. Efficacy:
• Median follow up : 4.7 yrs
• Total number of deaths 137/245 ( 56%)
• Event of disease recurrence or death 209/245( 85%)
• 110/123 pts ( 89%) in surgery alone group
• 99 /122 pts ( 81%) in Sx + HIPEC

27. • Median recurrence free survival : HIPEC 14.2 months, surgery group 10.7
months ( Difference 3.5 months)
• Probability of recurrence free survival at 3 years:
8 % Sx alone group versus 17 % in Sx + HIEC group
• Median OS:
Sx alone group 33.9 months versus 45 .1 months in Sx + HIPEC group

29. Discussion..
• Previous trials have shown that 6 cycles of IP + IV versus IV CHT alone showed
survival advantage of 16 months.
• Disadvantage of IP:
Poor tolerance to post op IV therapy
Increase in side effects: neuro and nephrotoxicity
Increased catheter related complications in IP group
• HIPEC is std of care in colorectal cancer
• This is first randomized trial to show survival benefit in ovarian cancer

30. Discussion…
• Addition of HIPEC to CRS resulted in longer median RFS ( 3.5 months) &
longer median OS by 11.8 months than surgery alone
• This effect was seen across all prespecified stratification factors
• All patients received NACT followed by Adjuvant CHT after Sx
• Incidence of complications were similar in both groups excep incidence of
colostomy or ileostomy after bowel resection , 72% (21/29 pts) versus 43%
(13/30 pts)

32. Drawbacks of study
• Randomization took place at the time of surgery in cases in which complete
CRS was anticipated…randomization should have been done at the time of
entry of the pt to the trial and should be blinded
• Duration of surgery: Sx + HIPEC : 338 min, Surg alone: 192 mints
………….DIFFICULT to BELIEVE…!!!!!

33. • Post op day in ICU average stay: 1 day..!!!!!!!!!!
• Long term toxicity : neuro and nephropathy
• Definition of primary end point was rise of CA 125 only , if clinical
symptom was the end point then RFS would have increased more
(thought process…..do we treat asymptomatic rise of CA 125…???)

34. • Median RFS was longer in HIPEC group versus Sx alone group by 3.5 months but
the median OS was 12 months longer in HIPEC group than Sx group.
( longer OS due to adjuvant CHT in HIPEC group …???)
• Similar differences were also seen in GOG 172 trial ( diff between RFS and OS was
5.5 months & 15.9 months respectively for the IP therapy group)

35. Conclusion…
• In woman with FIGO III ovarian cancer CRS + HIPEC resulted in longer
survival than CRS alone but further confirmatory trials are needed to
establish HIPEC as a std of care
• HIPEC should be used only in the context of clinical trial even after
complete CRS.

36. • THANK YOU…