Comparison of open and closed hyperthermic intraperitoneal chemotherapy: Results from the United States hyperthermic intraperitoneal chemotherapy collaborative

Table 1 Comparison of clinicopathologic and perioperative variables by hyperthermic intraperitoneal chemotherapy technique

				Open	Closed	P value
				n = 372	n = 1440
				n (%)	n (%)
Female gender				165 (44.4)	616 (42.8)	0.58
Mean age (SD)				52.7 (12.4)	54.6 (12.4)	0.02
Race						< 0.01
	White			350 (94.1)	1140 (79.2)
	Black			16 (4.3)	83 (5.8)
	Asian			2 (0.5)	79 (5.5)
	Latino			0 (0)	71 (4.9)
	Other			4 (1.1)	50 (3.5)
	Missing			0 (0)	17 (1.2)
Mean BMI (SD)				28.4 (6.6)	27.9 (6.6)	0.22
Previous CRS						< 0.01
	0			328 (88.1)	1088 (75.6)
	1			38 (10.2)	298 (20.7)
	2+			5 (1.3)	51 (3.5)
	Missing			1 (0.3)	3 (0.2)
Mean preoperative albumin (SD)				4.0 (0.5)	4.1 (0.5)	0.17
Histology						< 0.01
		Appendiceal		311 (83.6)	870 (60.4)
		Colorectal		42 (11.3)	376 (26.1)
		Mesothelioma		9 (2.4)	142 (9.9)
		Other		10 (2.7)	52 (3.6)
Tumor differentiation (appendiceal and colorectal)						< 0.01
	Well			214 (60.6)	647 (51.9)
	Moderate or poor			105 (29.8)	511 (41.0)
	Missing			34 (9.6)	88 (7.1)
ASA grade						< 0.01
	1 / 2			26 (7.0)	249 (17.3)
	3 / 4			346 (93.0)	1024 (71.1)
	Missing			0 (0)	167 (11.6)
Mean PCI (SD)				10.8 (14.7)	14.7 (8.7)	< 0.01
Neoadjuvant chemotherapy						0.47
			Yes	129 (34.7)	508 (35.3)
			No	239 (64.3)	925 (64.2)
			Missing	4 (1.1)	7 (0.5)
Mean operative time (h) (SD)				6.7 (2.1)	8.5 (2.7)	< 0.01
Mean estimated blood loss (cc) (SD)				491 (931)	444 (560)	0.37
IP chemotherapy						0.05
	Mitomycin-C			352 (94.6)	1299 (90.2)
	Cisplatin			14 (3.8)	90 (6.3)
	Other			6 (1.6)	51 (3.5)
Median MMC dose (mg) (IQR)				54 (40-60)	40 (33-40)	< 0.01
Median cisplatin dose (mg) (IQR)				75 (58-110)	138 (86-250)	< 0.01
Target temperature 40-43 ˚C				362 (97.3)	1415 (98.3)	0.25
Mean HIPEC duration (min) (SD)				87 (10)	89 (8)	0.14
CCR						< 0.01
	CC 0/1			316 (84.9)	1263 (87.7)
	CC 2/3			53 (14.2)	74 (5.1)
	Missing			3 (0.8)	103 (7.2)
Median LOS (IQR)				9 (8-13)	10 (8-13)	0.50
Complications						0.27
	Grade 0-II			306 (82.3)	1146 (79.6)
	Grade III-V			66 (17.7)	294 (20.4)
90-d readmission						< 0.01
	Yes			47 (12.6)	341 (23.7)
	No			321 (86.3)	1089 (75.6)
	Missing			4 (1.1)	10 (0.7)
Re-operation				32 (8.6)	131 (9.1)	0.59
Median days in ICU (IQR)				2 (2-3)	1 (0-3)	< 0.01
90-d mortality				14 (3.8)	25 (1.7)	0.03
Adjuvant chemotherapy						< 0.01
			Yes	47 (12.6)	341 (23.7)
			No	323 (86.8)	1095 (76.0)
			Missing	2 (0.5)	4 (0.3)

HIPEC: Hyperthermic intraperitoneal chemotherapy; SD: Standard deviation; BMI: Body mass index; CRS: Cytoreductive surgery; ASA: American Society of Anesthesiology; PCI: Peritoneal carcinomatosis index; IP: Intraperitoneal; CCR: Completeness of cytoreduction; LOS: Length of stay; IQR: Interquartile range; ICU: Intensive care unit.

Table 2 Multivariable analysis for overall survival based on histology

Factor		OS entire cohort			OS appendiceal cohort			OS colorectal cohort
		HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value
Age	< 65	Reference			Reference			Reference
	≥ 65	1.07	0.79-1.45	0.65	1.21	0.80-1.81	0.37	0.87	0.54-1.39	0.57
Previous CRS	No	Reference			Reference			Reference
	Yes	1.22	0.91-1.64	0.18	1.51	1.01-2.24	0.04	1.10	0.69-1.73	0.68
Histology	Appendiceal	Reference
	Colorectal	2.75	1.99-3.78	< 0.01
Differentiation	Well	Reference			Reference			Reference
	Mod / poor	3.22	2.28-4.55	< 0.01	3.92	2.63-5.82	< 0.01	1.55	0.79-3.06	0.20
ASA	1-2	Reference			Reference			Reference
	3-4	1.98	1.17-3.32	0.01	1.83	0.94-3.56	0.07	2.01	0.84-4.79	0.11
PCI	< 20	Reference			Reference			Reference
	≥ 20	1.86	1.34-2.57	< 0.01	1.86	1.21-2.88	< 0.01	1.94	1.17-3.21	0.01
PIC dose	Low dose	Reference			Reference			Reference
	High dose	1.35	0.91-2.02	0.13	1.16	0.67-2.01	0.58	1.49	0.65-3.42	0.33
CCR	0-1	Reference			Reference			Reference
	2-3	2.33	1.49-3.63	< 0.01	2.15	1.28-3.61	< 0.01	5.74	1.99-16.56	< 0.01
Complications	0 – II	Reference			Reference			Reference
	III – V	1.61	1.20-2.14	< 0.01	1.23	0.81-1.86	0.31	1.96	1.26-3.05	< 0.01
Adjuvant chemo	No	Reference			Reference			Reference
	Yes	1.16	0.86-1.56	0.31	1.33	0.87-2.05	0.18	0.98	0.65-1.48	0.94
PIC method	Open	Reference			Reference			Reference
	Closed	0.75	0.51-1.10	0.14	0.78	0.48-1.25	0.31	0.67	0.29-1.53	0.34

OS: Overall survival; HR: Hazards ratio; ASA: American Society of Anesthesiology; CRS: Cytoreductive surgery; HIPEC: Hyperthermic intraperitoneal chemotherapy; PCI: Peritoneal carcinomatosis index; CC: Completeness of cytoreduction.

Table 3 Multivariable analysis for recurrence-free survival based on histology

Factor		RFS entire cohort			RFS appendiceal cohort			RFS colorectal cohort
		HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value
Age	< 65	Reference			Reference			Reference
	≥ 65	1.00	0.78-1.26	0.99	0.95	0.69-1.29	0.75	1.03	0.70-1.50	0.87
Previous CRS	No	Reference			Reference			Reference
	Yes	1.27	1.01-1.59	0.04	1.35	1.01-1.81	0.04	1.17	0.80-1.70	0.39
Histology	Appendiceal	Reference
	Colorectal	2.20	1.72-2.82	< 0.01
Differentiation	Well	Reference			Reference			Reference
	Mod / Poor	1.77	1.37-2.29	< 0.01	1.89	1.41-2.55	< 0.01	0.91	0.54-1.52	0.73
ASA	1-2	Reference			Reference			Reference
	3-4	1.56	1.12-2.18	0.01	1.82	1.20-2.77	< 0.01	1.23	0.69-2.21	0.46
PCI	< 20	Reference			Reference			Reference
	≥ 20	1.59	1.24-2.02	< 0.01	1.78	1.33-2.39	< 0.01	1.27	0.80-2.03	0.31
PIC dose	Low dose	Reference			Reference			Reference
	High dose	1.06	0.71-1.59	0.74	0.87	0.53-1.41	0.58	1.32	0.66-2.63	0.42
CCR	0-1	Reference			Reference			Reference
	2-3	1.90	1.02-3.55	0.04	2.35	1.17-4.72	0.02	1.04	0.25-4.27	0.95
Complications	0 – II	Reference			Reference			Reference
	III – V	1.23	0.96-1.56	0.09	1.20	0.87-1.65	0.24	1.10	0.74-1.64	0.62
Adjuvant chemo	No	Reference			Reference			Reference
	Yes	1.46	1.16-1.84	< 0.01	2.23	0.63-3.05	< 0.01	0.92	0.66-1.28	0.62
PIC method	Open	Reference			Reference			Reference
	Closed	1.39	1.00-1.93	0.05	1.13	0.77-1.66	0.52	1.75	0.93-3.29	0.08

HR: Hazards ratio; ASA: American Society of Anesthesiology; CRS: Cytoreductive surgery; HIPEC: Hyperthermic intraperitoneal chemotherapy; PCI: Peritoneal carcinomatosis index; CC: Completeness of cytoreduction.