Advances in the management of peritoneal mesothelioma

Table 1 Selected studies examining overall survival with cytoreduction and hyperthermic intraperitoneal chemotherapy

Ref.	Year	Era	Sample No.	Age	Gender (female)	HIPEC Agents	Histological Subtype or Grade	Follow-up	Median survival	1 yr	2 yr	3 yr	5 yr	7 yr	10 yr
Park et al[33]	1999	1993-1998	18	47	28%	CDDP	9 E, 3 mixed 1 MMF 1 cystic 4 Unk	19	NR		80
Loggie et al[112]	2001		12	511	8%	MMC	Not stated	45.2	34.2	60	60	50	33	33
Feldman et al[48]	2003	1993-2002	49	47	43%	CDDP	26 E, 4 S 16 TP 1 adenomatoid	28.3	92	86	77	59	59
Costamagna et al[61]	2003	1995-2003	24			CDDP + DOXO, single agent MMC or DOXO			40	78	70	70	52
Brigand et al[6]	2006	1989-2004	15	53.6	29%	CDDP + MMC	12 E, 2 B 1 MC	46.7	35.6	69.3	57.7	43.3	28.9
Elias et al[60]	2007	1996-2005	26	461	46%	oxaliplatin + irinotecan, single agent oxaliplatin or DOXO	13 E, 1 B 11 TP, 1 MC	55	100	88	83	68	63
Gómez Portilla et al[113]	2007	1998-2005	7	501	43%	CDDP + DOXO, single agent MMC or oxaliplatin	5 E, 2 B	11	NR	43	43	43	43
Hesdorffer et al[55]	2008	1997-2000	27	531	26%	CDDP + MMC	23 E, 4 S		70			67%
Passot et al[114]	2008	1989-2006	22			CDDP + MMC	16 E, 3 B 3 MC	47	36.9	69	62	52	31
Chua et al[115]	2009	1997-2008	20	55.71	30%	CDDP + DOXO	16 E, 1 B, 2 S 1 MC	18.1	29.5	78.2		46.3
Blackham et al[49]	2010	1993-2008	34	54.91	32%	CDDP or MMC	29 E, 4 B 1 Unk	72	40.8	61		56	17
Kluger et al[54]	2010	1997-2004	47	491	36%	CDDP + MMC	43 E, 4 B	54	54.9	80.9		61.7	48.9
Cao et al[46]	2012	1989-2009	294	50	46%	CDDP + DOXO2	259 E, 27 B/S 8 Unk	25	67	83	62	52
Alexander et al[47]	2013	1992-2010	211	52	60%	CDDP or MMC	113 High, 54 Low 44 Unk		38.4				41		26
Schaub et al[59]	2013	1994-2010	104	50.9	39%	CDDP	90 E, 14B/S	49.4	52			58	46
Wong et al[52]	2013	2004-2012	26	64	38%	CDDP	15 E, 3 B 1 MMF 3 WD, 1 cystic 3 Unk		41.2
NMDeraco et al[37]	2003	1995-2002	19	491	53%	CDDP + MMC or DOXO	13 E, 1 S, 1 mixed 2WD, 2MC	27	NR			69
NMDeraco et al[39]	2003		28		61%								70
NMDeraco et al[38]	2003		61	511	49%	CDDP + MMC or DOXO		20					54
NMDeraco et al[40]	2006	1995-2005	49	521		CDDP + DOXO or MMC	43 E, 6 B	20.31					57
NMDeraco et al[50]	2013	1995-2011	116	54.41	48%	CDDP + DOXO or MMC	105 E, 11 B/S	32.91					49
NMBaratti et al[20]	2007	1997-2005	60	53.5	60%		43 E, 6 B 5 MC, 6 P	23					53.7
NMBaratti et al[36]	2007	1995-2006	12	38	100%	CDDP + DOXO	4 MC, 8 WD	27	NR				90
NMBaratti et al[35]	2010	1996-2008	83	54	55%	CDDP + MMC or DOXO	72 E, 10 B, 1 S	52	44				49.5		45.5
NMBaratti et al[34]	2013	1996-2012	108	56.5	46%	CDDP + DOXO or MMC	93 E, 14 B, 1 S	48.8	63.2				52.4		44.6
WCYan et al[45]	2006		100	501	40%	CDDP + DOXO	86 E, 7 B/S 7 Unk	48	52	78		55	46	39
WCYan et al[44]	2007	1989-2005	70	471	43%	CDDP + DOXO	65 E, 5 B	35	59	82	67	57	49
WCYan et al[41]	2007	1989-2005	62	471	45%	CDDP + DOXO	57 E, 5 B	37	79	84		58	50
WCYan et al[42]	2009	1989-2009	401	501	44%	CDDP + DOXO2 or MMC, single agent CDDP or MMC	318 E, 48 B/S 35 Unk	33	53	81		60	47
WCYan et al[43]	2011	1989-2009	294	501	46%	CDDP + DOXO2	259 E, 27 B/S 8 Unk	24	67	83	62	52

¹Mean values are indicated with an asterisk. Follow-up and survival are reported in months;

²Most common chemotherapy agent reported. The principal centers including the National Cancer Institute of Milan and the Washington Cancer Center are noted with superscripts NM and WC, respectively. NR: Not reached; CDDP: Cisplatin; MMC: Mitomycin or Mitomycin C; DOXO: Doxorubicin; E: Epithelial or epithelioid subtype; B: Biphasic; S: Sarcomatoid or sarcomatous; B/S: Biphasic or sarcomatoid; MMF: Malignant or epithelial with mucinous features; MC: Benign multicystic; TP: Tubillopapillary; P: Papillary or mixed papillary; WD: Well-differentiated; Unk: Unknown or not specified.

Table 2 Prognostic factors in cytoreduction and hyperthermic intraperitoneal chemotherapy procedures

Ref.	Year	Sample No.	Prognostic factors overall survival (multivariate only)
Deraco et al[38]	2003	61	Completeness of cytoreduction
Feldman et al[48]	2003	49	1No prior debulking, deep invasion, age > 60, residual disease > 1 cm
Nonaka et al[51]	2005	35	Completeness of cytoreduction, low mitotic count, lower nuclear grade
Deraco et al[40]	2006	49	Completeness of cytoreduction, low mitotic count/50 HPF
Yan et al[45]	2006	100	No lymph node metastasis, female gender, epithelial type, adequate cytoreduction
Baratti et al[20]	2007	60	1High-grade histology, WHO performance status > 0, Inadequate cytoreduction
Yan et al[41]	2007	62	Mesothelioma nuclear size
Yan et al[42]	2009	401	Epithelial subtype, absence of lymph node metastasis, completeness of cytoreduction 0/1, HIPEC
Baratti et al[35]	2010	83	Pathologically negative lymph nodes, epithelial subtype, mitotic count ≤ 5/50 HPF, Completeness of cytoreduction
Kluger et al[54]	2010	47	1Biphasic histological subtype
Yan et al[43]	2011	294	1Biphasic/sarcomatoid subtype, completeness of cytoreduction score of 2/3, proposed TNM Stage II or III
Cao et al[46]	2012	294	Female gender, TNM staging
Baratti et al[53]	2012	60	Complete parietal peritonectomy, complete cytoreduction, negative lymph nodes, Epithelial histology, low MIB-1 index
Alexander et al[47]	2013	211	Age < 60 yr, R0-1 vs R2-3, low histologic grade, use of cisplatin vs mitomycin-C
Baratti et al[34]	2013	108	Epithelial histology, histologically negative lymph nodes, Ki-67 < 10%
Deraco et al[50]	2013	116	Histological subtype, completeness of cytoreduction, absence of morbidity 3-5 grade
Schaub et al[59]	2013	104	Histological subtype, pre-CRS PCI, preoperative serum CA-125
Wong et al[52]	2013	29	Lower peritoneal carcinoma index, completeness of cytoreduction
Pillai et al[58]	2013	33	Presence of nuclear estrogen receptor beta

¹Variables that have negatively impacted overall survival.

Table 3 Morbidity, peri-operative mortality, and length of stay associated cytoreduction with hyperthermic intraperitoneal chemotherapy

Ref.	Year	Sample No.	Complication rate	Peri-operative mortality	Re-operation	Abdominal	Cardiac/pulmonary	Sepsis	Wound Infection	Other infection	Renal	Vascular	Hematologic	Other	LOS
Park et al[33]	1999	18	24%		1	1	1	1	2	1				1
Feldman et al[48]	2003	49	25%	0	2	4	5	2	3	1	1			2
Costamagna et al[61]	2003	24	26%	11
Brigand et al[6]	2006	15	40%	0	0					0	0			0	16.3
Elias et al[60]	2007	26	54%	4	4	1	1			4	1	3	2	2	281
Gomez et al[113]	2007	7	71%												41.51
Hesdorffer et al[55]	2008	27	30%	0		2	1			1		1		3
Passot et al[114]	2008	22	47%	0
Chua et al[115]	2009	20	65%	1		2	5	2			1		1	3	16.51
Yano et al[62]	2009	17	41%	5.8			2			2		1		3
Kluger et al[54]	2010	47	34%	2	1	3	9	2	2	9	2	1		1	161
Cao et al[46]	2012	294	33%	2		50	38				26		15		231
Alexander et al[47]	2013	211	30%	2.3	20	20	25		9			6	8	11	11
Wong et al[52]	2013	29	65%	4	1	4	1		6		2		10	4	9
Deraco et al[37]	2003	19	25%	0		3				1	1			3	321
Deraco et al[39]	2003	28	14%	0
Deraco et al[38]	2003	61	23%	0		7
Deraco et al[40]	2006	49	15%G3			9	2	4		5	4		3	5	241
Deraco et al[50]	2013	116	41%G3	2.6											25
Baratti et al[36]	2007	12	8%G3	0	1	1
Baratti et al[116]	2008	5	20%G3	0	1	1
Baratti et al[35]	2010	83	28%G3	2.4
Baratti et al[117]	2010	12	8%G3	0											18
Baratti et al[53]	2012	60	28%G3	0	7	8	4	3	1		7	2	5	1
Baratti et al[34]	2013	108	39%	1.9		14	10	6			10		7
Yan et al[45]	2006	100	36%G3	5		6	8	7		11		5	8	10	221
Yan [44]	2007	70	41%G3	3	4	3	4	3		2		4	5	3	231
Yan et al[42]	2009	401	46%G3	2		74	57				39		25		221

¹Mean values. Cells with the superscript G3 represent grade 3 or above complications. Abdominal complications include perforation, abscess formation, dehiscence, and fistula. "Other" complications include neurological and musculoskeletal complaints, emesis, and dehydration. Numerical values represent cases or patient number unless otherwise stated.