Efficacy of hyperthermic intraperitoneal chemotherapy in patients with epithelial ovarian cancer: a meta-analysis

Figures & data

Figure 1. Flow diagram of study selection.

Table 1. The characteristics of the included studies.

Author	RCT	Patient’s number	Median age (years)	Primary or recurrent	Median OS (months)	Median PFS (months)	NOS score	Median follow-up (months)	Morbidity (p-value)	Mortality (%)
CRS + HIPEC vs CRS
van Driel et al. [1]	Yes	122/123	61/63	P	45.7/33.9	14.2/10.7	3^#	56.4	0.76	/
Mendivil et al. [30]	No	69/69	59.8/62.9*	P	33.8/33.6*	25.1/20*	8	36/44	≤Grade 2	/
Wu et al. [29]	No	48/48	46.6/45.8*	P	/	26/18	7	30	>0.05	/
Baiocchi et al. [31]	No	29/50	51.6/58.4	R	58.3/59.3	15.8/18.6	7	56.7/40.5	0.015	0/4
Vernaccini et al. [28]	No	9/5	/	R	/	/	6	/	/	/
Spiliotis et al. [32]	Yes	60/60	58.3/58.1*	R	26.7/13.4*	/	3^#	/	/	/
Cascales-Campos [33]	No	32/22	54/55	R	/	/	8	18/29	0.453	0/0
Le Brun [34]	No	23/19	>55^$	R	/	/	8	24/32*	/	0/0
Cascales-Campos et al. [35]	No	52/35	57/57	P	/	39.1/26.7*	7	/	/	/
Konigsrainer et al. [36]	No	62/28	56/54	R	35/14	/	7	19	0.254	0/0
Fagotti et al. [37]	No	30/13	51/55	R	/	26/15	7	45/36	/	0/0
Warschkow [38]	No	21/90	58.9/65.0*	Both	/	/	8	29.4/38.3*	0.985	0/11
Kim [39]	No	19/24	48/49	P	NR/51	NR/18.5	8	80.2*	HIPEC safer	0/0
Munoz-Casares et al. [40]	No	14/12	54/54*	R	/	48/24*	7	/	NS	0/0
Gori et al. [41]	No	29/19	55.5/57.0*	P	64.4/46.4	/	9	/	NS	/
Ryu et al. [42]	No	57/60	46.1/47.7*	P	NR/72	48.7/19.8	8	46.7/46.0*	NS	/
CRS + HIPEC vs Chemotherapy
Safra et al. [43]	No	27/84	54.3/54.3*	R	/	15/6	7	/	No toxicity related to HIPEC	0/0

* : mean; $: the number of patients >55 years: HIPEC group, 16 of 23 patients, control group, 13 of 19 patients; #: Jadad score.

/: not available; P: primary; R: recurrent; NR: not reach; NS: not significant.

Figure 2. Forest plots showing the effect of HIPEC on survival of EOC. (A) The effect of HIPEC on OS of EOC. (B) The effect of HIPEC on PFS of EOC.

Table 2. The effect of HIPEC on each year OS/PFS rate of EOC and subgroup analysis according to primary or recurrent EOC.

OS/PFS	Study (n)	Statistics for each study			Heterogeneity
		OR	95% CI	p-Value	I² (%)	p-Value
OS of all
1-Year	14	2.82	1.54–5.18	0.001	21.3	0.228
2-Year	13	2.67	1.83–3.91	0.000	14.0	0.303
3-Year	12	3.02	1.82–4.99	0.000	57.5	0.007
4-Year	11	2.33	1.50–3.63	0.000	49.0	0.033
5-Year	10	2.48	1.71–3.61	0.000	31.4	0.158
PFS of all
1-Year	10	1.87	1.23–2.82	0.003	41.7	0.079
2-Year	10	2.79	1.91–4.07	0.000	38.1	0.105
3-Year	10	2.52	1.78–3.57	0.000	17.9	0.279
4-Year	10	3.12	1.84–5.30	0.000	52.6	0.025
5-Year	8	2.19	1.45–3.31	0.000	0.0	0.695
OS of primary EOC
1-Year	5	1.78	0.86–3.68	0.120	0.0	0.864
2-Year	5	2.11	1.33–3.35	0.001	0.0	0.811
3-Year	5	1.99	1.37–2.88	0.000	0.0	0.467
4-Year	5	1.99	1.15–3.44	0.013	48.2	0.103
5-Year	5	2.14	1.50–3.06	0.000	1.4	0.399
PFS of primary EOC
1-Year	6	2.11	1.49–2.98	0.000	0.0	0.701
2-Year	6	3.01	2.16–4.19	0.000	0.0	0.542
3-Year	6	2.56	1.66–3.94	0.000	33.2	0.187
4-Year	6	3.28	1.59–6.76	0.001	68.1	0.008
5-Year	4	2.10	1.30–3.40	0.003	0.0	0.729
OS of recurrent EOC
1-Year	8	3.17	1.16–8.66	0.025	45.1	0.091
2-Year	7	3.36	1.56–7.26	0.002	46.0	0.085
3-Year	6	4.32	1.59–11.73	0.004	67.3	0.009
4-Year	5	2.55	1.06–6.17	0.037	57.9	0.050
5-Year	4	2.75	1.09–6.91	0.031	56.5	0.075
PFS of recurrent EOC
1-Year	4	1.46	0.50–4.28	0.495	73.1	0.011
2-Year	4	2.48	0.88–7.04	0.087	68.3	0.024
3-Year	4	2.57	1.25–5.25	0.010	13.6	0.324
4-Year	4	2.70	1.26–5.78	0.011	9.4	0.346
5-Year	4	2.59	1.08–6.21	0.033	10.2	0.342

Figure 3. Forest plots showing the effect of HIPEC on survival of EOC after subgroup analysis. (A) The effect of HIPEC on OS of EOC according to different study design. (B) The effect of HIPEC on PFS of EOC according to different study design. (C) The effect of HIPEC on OS of EOC according to primary or recurrent EOC. (D) The effect of HIPEC on PFS of EOC according to primary or recurrent EOC.

Figure 4. Funnel plots and Egger’s linear regression test for publication bias of the studies. (A) Publication bias evaluation of the studies about OS. (B) Publication bias evaluation of the studies about PFS.

Table 3. The 14 ongoing randomized controlled HIPEC trials.

Clinical Trials.gov identifier	Condition	Intervention		HIPEC regimen	Status
		Experimental group	Control group
NCT03373058	Advanced-stage primary	CRS + HIPEC + chemotherapy	CRS + chemotherapy	Paclitaxel 175 mg/m² or Cisplatin 75 mg/m², 90 min, 43 °C	Not yet recruiting
NCT02124421	Stage III–IV primary	CRS + HIPEC + IV	CRS + IV/IP	Carboplatin, 90 min	Recruiting
NCT01091636	Primary	CRS + HIPEC + IV	CRS + IV	Cisplatin 75 mg/m², 90 min, 41.5 °C	Unknown
NCT03188432	Stage IIIC–IV primary	IV + CRS + HIPEC	IV + CRS + IP	Carboplatin, 120 min	Recruiting
NCT03275194	Stage IIIC–IV primary	NAC + CRS + HIPEC	NAC + CRS	Cisplatin and Doxorubicin	Recruiting
NCT03180177	Advanced-stage primary	NAC + CRS + HIPEC +  chemotherapy	NAC + CRS +  chemotherapy	Paclitaxel 175 mg/m² or Cisplatin 75 mg/m², 90 min, 43 °C	Not yet recruiting
NCT01628380	Stage IIIC primary	NAC + CRS + HIPEC	NAC + CRS	Cisplatin 100 mg/m² and Paclitaxel 175 mg/m², 90 min, 42 °C	Recruiting
NCT01767675	Platinum-sensitive recurrent	CRS + HIPEC + chemotherapy	CRS + chemotherapy	Carboplatin	Recruiting
NCT01539785	Platinum-sensitive recurrent	CRS + HIPEC	CRS	Cisplatin 75 mg/m², 60 min, 41.5 °C	Recruiting
NCT01376752	Platinum-sensitive recurrent	CRS + HIPEC	CRS	Cisplatin 75 mg/m²	Recruiting
NCT02681432	Stage II–IV primary and recurrent	CRS + HIPEC	CRS	Paclitaxel 175 mg/m², 60 min, 42–43 °C	Recruiting
NCT03371693	Advanced and platinum- sensitive recurrent	CRS + HIPEC + IV	CRS + IV	Lobaplatin 30 mg/m², 60 min, 43 °C ± 0.5 °C	Active, not recruiting
NCT02328716	Primary and platinum- sensitive recurrent	CRS + HIPEC	CRS	Cisplatin 75 mg/m²	Recruiting
NCT02567253	Stage III primary and recurrent	CRS + HIPEC + chemotherapy	CRS + IP +  chemotherapy	Cisplatin 75 mg/m² or Cisplatin 100 mg/m², 90 min, 41 °C	Recruiting

IV: intravenous chemotherapy.

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